Antibodies for cancer research

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue.Tissue specificity: Highly expressed in placenta. Low expression in small intestine, liver and colon.

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue.Tissue specificity: Highly expressed in placenta. Low expression in small intestine, liver and colon.

ABL2(ARG, Abelson-related gene) is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins includes the tyrosine kinase domains and extends amino-terminal to include the SH2 and SH3 domains. ABL2 is expressed in both normal and tumor cells. The ABL2 gene product is expressed as two variants bearing different amino termini, both approximately 12-kb in length. c-Abl shows both cytoplasmic and nuclear localization，c-Abl is involved in two different chromosomal translocations present in human leukemias, which generate Bcr-Abl and TEL-Abl.

Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing.

AFP (alpha-fetoprotein), a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatoma or teratoma. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly.

Akt2 (also designated protein kinase B beta or v-akt murine thymoma viral oncogene homolog 2 ), with 481-amino acid protein (about 53kDa), belongs to the AKT serine/threonine protein kinase family, which also includes Akt1 and Akt3. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. Among the members of AKT family, Akt2 is associated with the development of human cancers. Akt2 inhibits cisplatin-induced JNK/p38 and Bax activation through phosphorylation of ASK1 and thus, plays an important role in chemoresistance. Further, Akt2 plays a specific role in muscle differentiation.

Akt3 (also designated protein kinase B gamma or v-akt murine thymoma viral oncogene homolog 3)，with 479-amino acid protein (about 53kDa), belongs to the AKT serine/threonine protein kinase family, which also includes Akt1 and Akt2. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake.Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. Identifying Akt3 as a selective target in melanoma cells also provides new therapeutic opportunities for patients in the advanced stages of this disease.

Akt3 (also designated protein kinase B gamma or v-akt murine thymoma viral oncogene homolog 3)，with 479-amino acid protein (about 53kDa), belongs to the AKT serine/threonine protein kinase family, which also includes Akt1 and Akt2. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake.Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. Identifying Akt3 as a selective target in melanoma cells also provides new therapeutic opportunities for patients in the advanced stages of this disease.

The poly Q polymorphism in (amplified in breast cancer) gene is usually assessed by fragment length analysis which does not reveal the actual sequence variation. The purpose of this study is to investigate the sequence variation of poly Q encoding region in breast cancer cell lines at single molecule level, and to determine if the sequence variation is related to AIB1 gene amplification.

The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet.

ALDH1A1 is an aldehyde dehydrogenase able to oxidize a wide variety of aliphatic aldehydes (retinaldehyde, acetaldehyde, etc.) to the corresponding carboxylic acids (retinoic acid, acetic acid, etc.). ALDH1A1 (also known as RALDH1, ALDH1, or AHD2) is highly expressed in the dorsal retina, ventral midbrain (dopaminergic neurons), and hematopoietic stem cells. ALDH1A1 is involved in retinoic acid (RA) synthesis during vertebrate embryogenesis. ALDH1A1 is first detected at E9.0-E10.5 in cranial tissues (ventral mesencephalon, dorsal retina, thymic primordia, optic vesicles) and in the mesonephros. ALDH1A1 is also of interest in Parkinson’s Disease (PD) being expressed in the the A9 dopaminergic (DA) neuronal group projecting to the dorsal striatum; this is the most vulnerable site in PD (Chung et al, 2005). ALDH1A1 protein is a known mesencephalic dopaminergic marker. ALDH1A1 is a cytosolic enzyme that preferentially oxidizes retinaldehyde to retinoic acid .ALDH1A1 is expressed in the epithelium of many organs, including brain, liver, testis, eye lens and cornea .ALDH1A1 is highly expressed in brain dopaminergic neurons, where it produces the retinoic acid required for their differentiation and development .The retinoic acid produced by ALDH1A1 is also important for the differentiation of hematopoietic stem cells.

The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet.

AMACR (alpha-methylacyl-CoA racemase) has been recently described as prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. Expression of AMACR protein is found in prostatic adenocarcinoma but not in benign prostatic tissue. It stains premalignant lesions of prostate: high-grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia. AMACR can be used as a positive marker for PIN. Defects in AMACR are the cause of congenital bile acid synthesis defect type 4 (CBAS4); also known as cholestasis, intrahepatic, with defective conversion of trihydroxycoprostanic acid to cholic acid or trihydroxycoprostanic acid in bile. Clinical features include neonatal jaundice, intrahepatic cholestasis, bile duct deficiency and absence of cholic acid from bile.

The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor which is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor. The main function of the androgen receptor is as a DNA binding transcription factor which regulates gene expression; however, the androgen receptor has other functions as well. Androgen regulated genes are critical for the development and maintenance of the male sexual phenotype.

Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. Human aminopeptidase N is a receptor for one strain of human coronavirus that is an important cause of upper respiratory tract infections. Defects in this gene appear to be a cause of various types of leukemia or lymphoma.

The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder.Tissue specificity: Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.

Aurora A plays a role in cell cycle regulation during anaphase and/or telophase, in relation to the function of the centrosome/spindle pole region during chromosome segregation. Aurora A plays a key role during tumor development and progression and is overexpressed in many human cancers including breast, ovarian and colorectal. Aurora A is viewed as a potential target for anticancer drug treatment.Tissue specificity: Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines.

This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.

This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.

This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma.Tissue specificity: Expressed in a variety of tissues.

Beclin-1 participates in the regulation of autophagy and has an important role in development, tumorigenesis, and neurodegeneration. Tissue specificity: Ubiquitous.

This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Component of the Polycomb group (PcG) multiprotein PRC1 complex, a complex required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A ‘Lys-119’, rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of RNF2/RING2.

BRAF: v-raf murine sarcoma viral oncogene homolog B1, also known as BRAF1; RAFB1; B-RAF1; FLJ95109. Entrez Protein NP_004324. It is the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway. B-Raf contains three consensus Akt phosphorylationsites (Ser364, Ser428, and Thr439). B-Raf is a key regulatory molecule of the mitogen-activated protein kinase kinase (MEK), it has a long amino-terminal region,the region is essential for homo-dimerization of B-Raf and hetero-dimerization of B-Raf and c-Raf at the plasma membrane, followed by phosphorylation of Thr118 in the amino-terminal B-Raf-specific region. Notably, in calcium ionophore-stimulated HeLa cells, B-Raf could propagate signals to MEK under the basal level of GTP-Ras. Expression of Raf-B is highly restricted with highestlevels in the cerebrum and testes and defects in braf are involved in a wide range of cancers. The BRAF gene mutation is frequently detected in papillary thyroid carcinoma,melanocytic nevi, primary cutaneous melanomas and colorectal cancers.

BRAF: v-raf murine sarcoma viral oncogene homolog B1, also known as BRAF1; RAFB1; B-RAF1; FLJ95109. Entrez Protein NP_004324. It is the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway. B-Raf contains three consensus Akt phosphorylationsites (Ser364, Ser428, and Thr439). B-Raf is a key regulatory molecule of the mitogen-activated protein kinase kinase (MEK), it has a long amino-terminal region,the region is essential for homo-dimerization of B-Raf and hetero-dimerization of B-Raf and c-Raf at the plasma membrane, followed by phosphorylation of Thr118 in the amino-terminal B-Raf-specific region. Notably, in calcium ionophore-stimulated HeLa cells, B-Raf could propagate signals to MEK under the basal level of GTP-Ras. Expression of Raf-B is highly restricted with highestlevels in the cerebrum and testes and defects in braf are involved in a wide range of cancers. The BRAF gene mutation is frequently detected in papillary thyroid carcinoma,melanocytic nevi, primary cutaneous melanomas and colorectal cancers.

This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified.

The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.

The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.

CA IX is a transmembrane protein and the only tumor-associated carbonic anhydrase isoenzyme known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Tissue specificity: Expressed primarily in carcinoma cells lines. Expression is restricted to very few normal tissues and the most abundant expression is found in the epithelial cells of gastric mucosa.

The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript, that is expressed predominantly during G2/M phase. The different transcripts result from the use of alternate transcription initiation sites. (provided by RefSeq) It has higher expression in tumor tissues .

During each cell cycle cyclins undergo periodic accumulation and destruction. As key regulators of the cell cycle the cyclins control important transitions by acting as regulatory subunits of the Cdks. Early in the G1 phase of the cell cycle, cyclin D1 induction is followed by cyclin E induction. This sequential progression is marked early on in G1 by the activation of Cdk4 and in mid to late G1 by the activation of Cdk2 and the hyperphosphorylation of pRB. The final transition into S phase is thought to be dependent on the increased expression and association of cyclin E and Cdk2. In a recent study, Cyclin D1 regulates cellular metabolism, fat cell differentiation and cellular migration. Cyclin D1 is also involved in development and cancer. Cyclin D1 has also been linked to the development and progression of several cancers including breast, bladder, esophagus, and lung.

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene.

This gene encodes a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Tetraspanins are cell surface glycoproteins with four transmembrane domains that form multimeric complexes with other cell surface proteins. The encoded protein functions in many cellular processes including differentiation, adhesion, and signal transduction, and expression of this gene plays a critical role in the suppression of cancer cell motility and metastasis.

In lymphoid tissue, UCHM1 reacts with monocyte-like cells, such as in the red pulp of the spleen and in the subcapsular region of thymus. Strong reactivity is found on vascular endothelium in lymph nodes and liver, weak reactivity in thymus, spleen and tonsil, and no reactivity in lung, brain, skin and kidney. CD14 is a receptor for the LPS binding protein, and may be involved in the clearance of pathogens from the blood. CD14 (UCHM1) is reactive with cell lines U937 (histiocytic lymphoma), THP1-0 (probably monocytic) and 15% of HL60 (weakly, a promyelocytic cell line), but not with K562 (erythroleukemia cell line) or other B or T cell lines.

This gene encodes a sialoglycoprotein that is expressed on mature granulocytes and in many B cells. The encoded protein is anchored via a glycosyl phosphatidylinositol (GPI) link to the cell surface.

CD31, also known as platelet endothelial cell adhesion molecule 1 (PECAM1), is a type I integral membrane glycoprotein and a member of the immunoglobulin superfamily of cell surface receptors.It is constitutively expressed on the surface of endothelial cells, and concentrated at the junction between them. The antibody reacts with the murine form of the Platelet-Endothelial Cell Adhesion Molecule. The reactivity of the antibody is restricted to the isoform of the molecule that is selectively expressed by endothelial cells.The antigen is predominantly present at the lateral borders of endothelial cells as described for human PECAM-1.It is also weakly expressed on many peripheral lymphoid cells and platelets.CD31 has been used to measure angiogenesis in association with tumor recurrence. Other studies have also indicated that CD31 and CD34 can be used as markers for myeloid progenitor cells and recognize different subsets of myeloid leukemia infiltrates (granular sarcomas).

CD34 is a transmembrane glycoprotein with a molecular mass of approximately 110 kD that is selectively expressed on human hematopoietic progenitor cells, endothelial cells and some fibroblasts. It could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. CD34 is highly expressed on hematopoietic progenitors, as well as on endothelial cells. CD34 has been used to measure angiogenesis, which reportedly predicts tumor recurrence.

CD34 is a transmembrane glycoprotein with a molecular mass of approximately 110 kD that is selectively expressed on human hematopoietic progenitor cells, endothelial cells and some fibroblasts. It could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. CD34 is highly expressed on hematopoietic progenitors, as well as on endothelial cells. CD34 has been used to measure angiogenesis, which reportedly predicts tumor recurrence.

The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein’s activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein’s activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene.

CD44, also known as IN, LHRMIC4, CDW44, HCELL. It is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.

CD44, also known as IN, LHRMIC4, CDW44, HCELL. It is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.

The protein CD80 (Cluster of Differentiation 80) is a molecule found on activated B cells and monocytes which provides a costimulatory signal necessary for T cell activation and survival. It is also known as B7.1. Its principal mode of action is by binding to CD28. Along with CD86, these molecules provide the necessary stimuli to prime T cells against antigens presented by antigen-presenting cells. CD80 and CD86 also bind to CTLA-4, a cell surface molecule expressed on activated T cells. Interactions between CD80 or CD86 with CTLA-4 decrease the response of T cells. Mouse research by scientists at Emory University showed that estrogen-related bone loss is linked to recently discovered pathways involving various proteins, such as CD80 and other functions. In a nutshell, reactive oxygen stimulates dendritic cells, which activate other immune cells to up-regulate production of CD80, the molecule co-responsible for T cell activation. “When this pathway is activated, it leads to increased T cell TNF production and ultimately to bone loss.” In turn, T cells produce a protein, Tumor Necrosis Factor, which increases the formation of osteoclasts in rodents and humans. Osteoclasts cause minerals to be released from the bone, so that calcium is taken into the bloodstream to be used for other functions of the body. Osteoclast differentiation is inhibited by osteoprotegerin; Estrogen stimulates osteoprotegerin production.

This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined.

This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds TGFB1 and TGFB3 with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia.

This gene encodes a pentaspan transmembrane glycoprotein. The protein localizes to membrane protrusions and is often expressed on adult stem cells, where it is thought to function in maintaining stem cell properties by suppressing differentiation. Mutations in this gene have been shown to result in retinitis pigmentosa and Stargardt disease. Expression of this gene is also associated with several types of cancer. This gene is expressed from at least five alternative promoters that are expressed in a tissue-dependent manner. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. The encoded protein is also a member of the immunoglobulin superfamily. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene.

This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.

The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons.

This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.

Costimulatory B7 molecules (e.g., B7-1, or CD80; MIM 112203) signal through CD28 (MIM 186760) family molecules such as CD28, CTLA4 (MIM 123890), and ICOS (MIM 604558). May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling.

The cell division control protein cdc2, also known as cyclin-dependent kinase 1 (Cdk1) or p34/cdk1, plays a key role in the control of the eukaryotic cell cycle, where it is required for entry into S-phase and mitosis. Cdc2 exists as a complex with both cyclin A and cyclin B. The best characterized of these associations is the Cdc2 p34 cyclin B complex, which is required for the G2 to M phase transition. Activation of Cdc2 is controlled at several steps including cyclin binding and phosphorylation of threonine 161. However, the critical regulatory step in activating cdc2 during progression into mitosis appears to be dephosphorylation of Tyr15 and Tyr14. Phosphorylation at Tyr15 and inhibition of Cdc2 is carried out by WEE1 and MIK protein kinases while Tyr15 dephosphorylation and activation of Cdc2 is carried out by the cdc25 phosphatase. The isoform CDC2deltaT is found in breast cancer tissues. Furthermore, cdc2/Cdk1 is a key mediator of neuronal cell death in brain development and degeneration.

The cell division control protein cdc2, also known as cyclin-dependent kinase 1 (Cdk1) or p34/cdk1, plays a key role in the control of the eukaryotic cell cycle, where it is required for entry into S-phase and mitosis. Cdc2 exists as a complex with both cyclin A and cyclin B. The best characterized of these associations is the Cdc2 p34 cyclin B complex, which is required for the G2 to M phase transition. Activation of Cdc2 is controlled at several steps including cyclin binding and phosphorylation of threonine 161. However, the critical regulatory step in activating cdc2 during progression into mitosis appears to be dephosphorylation of Tyr15 and Tyr14. Phosphorylation at Tyr15 and inhibition of Cdc2 is carried out by WEE1 and MIK protein kinases while Tyr15 dephosphorylation and activation of Cdc2 is carried out by the cdc25 phosphatase. The isoform CDC2deltaT is found in breast cancer tissues. Furthermore, cdc2/Cdk1 is a key mediator of neuronal cell death in brain development and degeneration.

E-Cadherin is a 120 kDa transmembrane glycoprotein that is localized in the adherens junctions of epithelial cells. There, it interacts with the cytoskeleton through the associated cytoplasmic catenin proteins. In addition to being a calcium-dependent adhesion molecule, E-Cadherin is also a critical regulator of epithelial junction formation. Its association with catenins is necessary for cell-cell adhesion. These E-cadherin/catenin complexes associate with corical actin bundles at both the zonula adherens and the lateral adhesion plaques. Tyrosine phosphorylation can disrupt these complexes, leading to changes in cell adhesion properties. E-Cadherin expression is often down-regulated in highly invasive, poorly differentiated carcinomas. Increased expression of E-Cadherin in these cells reduces invasiveness. Thus, loss of expression or function of E-Cadherin appears to be an important step in tumorigenic progression.Tissue specificity: Non-neural epithelial tissues.

E-Cadherin is a 120 kDa transmembrane glycoprotein that is localized in the adherens junctions of epithelial cells. There, it interacts with the cytoskeleton through the associated cytoplasmic catenin proteins. In addition to being a calcium-dependent adhesion molecule, E-Cadherin is also a critical regulator of epithelial junction formation. Its association with catenins is necessary for cell-cell adhesion. These E-cadherin/catenin complexes associate with corical actin bundles at both the zonula adherens and the lateral adhesion plaques. Tyrosine phosphorylation can disrupt these complexes, leading to changes in cell adhesion properties. E-Cadherin expression is often down-regulated in highly invasive, poorly differentiated carcinomas. Increased expression of E-Cadherin in these cells reduces invasiveness. Thus, loss of expression or function of E-Cadherin appears to be an important step in tumorigenic progression.Tissue specificity: Non-neural epithelial tissues.

p27 KIP 1 is a cell cycle regulatory mitotic inhibitor of cdk activity. p27 KIP 1 is a candidate tumor suppressor gene, and has been proposed to function as a possible mediator of TGF beta induced G1 arrest. p27 KIP 1 is up regulated in response to antimitogenic stimuli. The increased protein expression of p27 results in cellular arrest by binding to cyclin/Cdk complexes such as cyclin D1/Cdk4. Decreased levels of p27Kip1, mainly due to proteosomal degradation, are found in various epithelial tumors originating from lung, breast, colon, ovary, esophagus, thyroid and prostate.Tissue specificity: Expressed in all tissues tested. Highest levels in skeletal muscle, lowest in liver and kidney.

The protein encoded by this gene is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene.Tissue specificity: Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. High levels are seen in the placenta while low levels are seen in the liver.

This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene.

Carcino Embryonic Antigen (CEA) is synthesised during development in the fetal gut, and is re-expressed in increased amounts in intestinal carcinomas and several other tumors. Antibodies to CEA are useful in identifying the origin of various metastatic adenocarcinomas and in distinguishing pulmonary adenocarcinomas (60 to 70% are CEA+) from pleural mesotheliomas (rarely or weakly CEA+). The carcinoembryonic antigen (CEA) is a member of a large family of glycoproteins and a useful tumor marker for adenocarcinoma. Tissue specificity: Found in adenocarcinomas of endodermally derived digestive system epithelium and fetal colon.

Carcino Embryonic Antigen (CEA) is synthesised during development in the fetal gut, and is re-expressed in increased amounts in intestinal carcinomas and several other tumors. Antibodies to CEA are useful in identifying the origin of various metastatic adenocarcinomas and in distinguishing pulmonary adenocarcinomas (60 to 70% are CEA+) from pleural mesotheliomas (rarely or weakly CEA+). The carcinoembryonic antigen (CEA) is a member of a large family of glycoproteins and a useful tumor marker for adenocarcinoma. Tissue specificity: Found in adenocarcinomas of endodermally derived digestive system epithelium and fetal colon.

CHK2: CHK2 checkpoint homolog (S. pombe). In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Three transcript variants encoding different isoforms have been found for this gene.

C-kit (CD117, 145kDa) functions as a tyrosine kinase receptor which becomes activated upon binding of its ligand SCF (stem-cell factor), the C-kit gene encodes the human homolog of the proto-oncogene c-kit. which was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. KIT is a type 3 transmembrane receptor for MGF (mast cell growth factor). Mutations in KIT are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism.

MECT1 (also known as MucoEpidermoid Carcinoma Translocated 1) functions as a transcriptional coactivator for CREB1, which activates transcription through both consensus and variant cAMP response element (CRE) sites. MECT1 does not appear to modulate CREB1 DNA-binding activity but enhances the interaction of CREB1 with TAF4/TAFII-130. MECT1 translocates with MAML2 (MasterMind-Like Protein 2) to yield a fusion oncogene: t(11;19) (q21;p13). This translocation occurs in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. The novel fusion product that results disrupts the Notch signaling pathway. The fusion protein consists of the N-terminus of MECT1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of MECT1 has been detected in a small number of mucoepidermoid carcinomas. Multiple isoforms have been reported for the MECT1 protein. Tissue specificity: Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart, spleen, lung, skeletal muscle, salivary gland, ovary and kidney.

CSF1, also known as MCSF, is a four-α-helicalbundle cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. This protein may be involved in development of the placenta.

Casein kinase II (CK2) is a constitutively active, ubiquitously expressed serine/threonine protein kinasethat is thought to have a regulatory function in cell proliferation, cell differentiation and apoptosis. CK2functions as a tetrameric complex consisting of two regulatory beta-subunits and two catalytic units (alphaand alpha’) in a homomeric or heteromeric conformation. Whilst the alpha- and alpha’-subunits arecatalytically identical, proteins that regulate CK2, such as cdc2 and Hsp90, preferentially bind to thealpha and not the alpha’-subunit. CK2 can phosphorylate a number of key intracellular signaling proteinsimplicated in tumor suppression (p53 and PTEN) and tumorigenesis (myc, jun, NF-kappaB). CK2 is also thoughtto influence Wnt signaling via beta-catenin phosphorylation and the PI 3-K signaling pathway via thephosphorylation of Akt.

This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression. Mutations in this gene have been associated with invasive breast cancers, prostate cancers, and Wilms’ tumors.Tissue specificity: Ubiquitous. Absent in primary spermatocytes.

This gene is overexpressed in breast cancer and squamous cell carcinomas of the head and neck. The encoded protein is localized in the cytoplasm and in areas of the cell-substratum contacts. This gene has two roles: (1) regulating the interactions between components of adherens-type junctions and (2) organizing the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells. During apoptosis, the encoded protein is degraded in a caspase-dependent manner. The aberrant regulation of this gene contributes to tumor cell invasion and metastasis. Three splice variants that encode different isoforms have been identified for this gene. (provided by RefSeq)

This gene, CYP1A1, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme’s endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15.

Biochemically, most members of the CK family fall into one of two classes, type I (acidic polypeptides) and type II (basic polypeptides). The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. Cytokeratins have been found to be useful markers of tissue differentiation which is directly applicable to the characterization of malignant tumors.

CK7 (Keratin, type II cytoskeletal 7) is a protein that in humans is encoded by the KRT7 gene. CK7 is a member of the keratin family. It is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described.

Cytokeratin 8, also known as CK8, KRT8, K8. Entrez Protein NP_002264. It is a member of the type II keratin family. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells.It typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis

The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This type I cytokeratin is paired with keratin 4 and expressed in the suprabasal layers of non-cornified stratified epithelia. Mutations in this gene and keratin 4 have been associated with the autosomal dominant disorder White Sponge Nevus. The type I cytokeratins are clustered in a region of chromosome 17q21.2. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been described.

CK17, also known as KRT17, it is the type I intermediate filament chain keratin 17. It is found in nail beds, hair follicles, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. May play a role in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial “stem cells”. May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation. Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state. Modulates the function of TNF-alpha in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway. Involved in tissue repair.

Cytokeratin 18, also known as CK18, CYK18, KRT18. It encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene.

The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This cytokeratin is a major cellular protein of mature enterocytes and goblet cells and is specifically expressed in the gastric and intestinal mucosa. The type I cytokeratin genes are clustered in a region of chromosome 17q12-q21.

DDR1: discoidin domain receptor tyrosine kinase 1. Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene is a RTK that is widely expressed in normal and transformed epithelial cells and is activated by various types of collagen. This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the Dictyostelium discoideum protein discoidin I in their extracellular domain. Its autophosphorylation is achieved by all collagens so far tested (type I to type VI). In situ studies and Northern-blot analysis showed that expression of this encoded protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, this protein is significantly over-expressed in several human tumors from breast, ovarian, esophageal, and pediatric brain. This gene is located on chromosome 6p21.3 in proximity to several HLA class I genes. Alternative splicing of this gene results in multiple transcript variants.

Dkk-3 (Dickkopf-3) is a member of the dickkopf family. It is a 350 amino acid secreted glycoprotein that is composed of an N-terminal signal peptide and two conserved cysteine-rich domains, which are separated by a 12 amino acid linker region. This secreted protein is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene.

This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein.

This gene encodes a transmembrane protein containing six epidermal growth factor repeats. The protein is involved in the differentiation of several cell types, including adipocytes; it is also thought to be a tumor suppressor. It is one of several imprinted genes located in a region of on chr 14q32. Certain mutations in this imprinted region can cause phenotypes similar to maternal and paternal uniparental disomy of chromosome 14 (UPD14). This gene is expressed from the paternal allele. A polymorphism within this gene has been associated with child and adolescent obesity. The mode of inheritance for this polymorphism is polar overdominance; this non-Mendelian inheritance pattern was first described in sheep with the callipyge phenotype, which is characterized by muscle hypertrophy and decreased fat mass.

The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis.

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppresor gene.

Endothelial nitric-oxide synthase (eNOS), also known as NOS3, it is an important enzyme in the cardiovascular system. It is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm.

EP300: E1A binding protein p300. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer.

E7 transforming protein (Human papillomavirus type 16).

E7 transforming protein (Human papillomavirus type 16).

This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. Tissue specificity: This protein is expressed in almost all epithelial cell membranes but not on mesodermal or neural cell membranes. Found on the surface of adenocarcinomas.

EPH receptor A2 (EphA2), with 976-amino acid protein (about 107 kDa), belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EphA1, EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, EphA8, EphA10, EphB1, EphB2, EphB3, EphB4 and EphB6 are Eph family receptors for Ephrin family ligands. In normal cells, EphA2 negatively regulates cell growth and invasiveness. EphA2 is overexpressed by many human cancers, and is often associated with poor prognostic features. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers.EphA2 may serve as a novel target for bladder cancer, colonic adenocarcinoma and ovarian cancer therapy.

EPH receptor B4 (EphB4), with 987-amino acid protein (about 108kDa), belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. EphB4 acts as a negative regulator of blood vessel branching and vascular network formation, switching the vascularization program from sprouting angiogenesis to circumferential vessel growth. EphB4 and its ligand ephrinB2 express in several kinds of tumor cells and correlate with tumorigenesis. EphB4 is thus a potential candidate as a predictor of disease outcome in several kinds of tumor and as target for novel therapy.

ERBB2: v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian). This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.

The C-erbB-2 (HER-2/neu) gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. Amplification or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. High levels of c-erbB-2 were associated with estrogen receptor (ER) and progesterone receptor negativity. Overexpression of the c-erbB-2 oncogene has been shown to be associated with poor prognosis in ovarian and breast cance, The level of increased Neu expression can be a predictor of disease prognosis

ERBB2: v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian). This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.

ERBB3: v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ERBB3, v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). It is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ERBB3: v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ER (estrogen receptor 1) a member of the steroid receptor superfamily, contains highly conserved DNA binding (DBD) and ligand binding domains (LBD). Through its estrogen-independent and estrogen-dependent activation domains (AF-1 and AF-2, respectively), ER regulates transcription by recruiting coactivator proteins and interacting with general transcriptional machinery. Phosphorylation provides an important mechanism to regulate ER activity. ER is phosphorylated on multiple sites. Serines 104, 106, 118 and 167 are located in the amino-terminal transcription activation function domain AF-1, and phosphorylation of these serines plays an important role in regulating ER activity. Ser118 may be the substrate of the transcription regulatory kinase cdK7. Ser167 may be phosphorylated by p90RSK and Akt. Phosphorylation of Ser167 may confer tamoxifen resistance in breast cancer patients.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

The ETS1 is a transcription factor known to regulate expression of a number of genes involved in extracellular matrix remodeling. ETS1 is absent from normal gastric epithelium but is expressed in approximately 60% of gastric carcinomas and oral squamous cell carcinomas with a significant correlation to the tumor stage.

The ETS1 is a transcription factor known to regulate expression of a number of genes involved in extracellular matrix remodeling. ETS1 is absent from normal gastric epithelium but is expressed in approximately 60% of gastric carcinomas and oral squamous cell carcinomas with a significant correlation to the tumor stage.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform.

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform.

FES (feline sarcoma oncogene) and Fer are the only two members of a unique family of cytoplasmic protein tyrosine kinases. FES and Fer contain a central Src homology-2 (SH2) domain and a carboxy-terminal tyrosine kinase catalytic domain. They are structurally distinguished from other members of cytoplasmic protein tyrosine kinase subfamilies by the presence of amino-terminal Fer/CIP4 homology and coiled-coil domains. FES was originally identified as an oncogene from avian and feline retroviruses. Human c-Fes has been implicated in myeloid, vascular endothelial and neuronal cell differentiation. FES has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Mutations may activate the FES kinase and thereby contribute to cancer. However, recent data strongly suggests that the c-FES protein-tyrosine kinase is a tumor suppressor rather than a dominant oncogene in colorectal cancer.

FES (feline sarcoma oncogene) and Fer are the only two members of a unique family of cytoplasmic protein tyrosine kinases. FES and Fer contain a central Src homology-2 (SH2) domain and a carboxy-terminal tyrosine kinase catalytic domain. They are structurally distinguished from other members of cytoplasmic protein tyrosine kinase subfamilies by the presence of amino-terminal Fer/CIP4 homology and coiled-coil domains. FES was originally identified as an oncogene from avian and feline retroviruses. Human c-Fes has been implicated in myeloid, vascular endothelial and neuronal cell differentiation. FES has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Mutations may activate the FES kinase and thereby contribute to cancer. However, recent data strongly suggests that the c-FES protein-tyrosine kinase is a tumor suppressor rather than a dominant oncogene in colorectal cancer.

FGFR4: fibroblast growth factor receptor 4. Entrez Protein NP_002002. It is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies between three alternate forms, as indicated for members 1-3. This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples, suggesting a role in breast and ovarian tumorigenesis.

This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. Tissue specificity: Placenta, lung, heart, and kidney, does not seem to be expressed in pancreas and brain. VEGFR-3 is induced in all endothelial cells (EC’s) during early embryogenesis, and its expression eventually disappears from the vascular endothelial cells of adult tissues. VEGFR-3 is constitutively expressed in the adult lymphatic endothelium. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of tumor-bearing tissues.VEGFR-3 expression in adults is largely restricted to the endothelial cells of the lymphatic system, and high endothelial venules (HEV).

The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene.

The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene.

This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms.

FoxP3 (Forkhead box protein 3), a highly conserved forkhead/winged-helix transcription factor, plays a crucial role in maintaining immune homeostasis by governing the development and function of regulatory T cells. It is constitutively expressed at high level in CD25+ CD4+ Treg cells and at low level in a CD25- CD4+ Treg cell subset. Defects in gene encoding FoxP3 protein cause the scurfy phenotype in mice, and in human the IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, X-linked syndrome), also known as X-linked autoimmunity-allergic dysregulation (XLAAD) syndrome.

GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.Tissue specificity: Expressed in cells lacking fibronectin.ABCAM:It is heavily, and specifically, expressed in astrocytes and certain other astroglia in the central nervous system, in satellite cells in peripheral ganglia, and in non myelinating Schwann cells in peripheral nerves.In addition many types of brain tumor, presumably derived from astrocytic cells, heavily express GFAP. GFAP is also found in the lens epithelium, Kupffer cells of the liver, in some cells in salivary tumors and has been reported in erythrocytes.

Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of neurological diseases. GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimer’s disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3beta are found in the brain where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transduction cascade of a large number of growth factors and cytokines. The activity of GSK is regulated by phosphorylation (Akt: Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3β, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene.

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene.

GSTP1 (glutathione-S-transferase, pi 1), also called GST3/DFN7, is a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. GSTP1 act like a tumor suppressor gene, which when inactivated leads to tumor growth, and the -class glutathione S-transferase is commonly inactivated by somatic CpGisland hypermethylation in cancers of the prostate, liver, and breast. Methylation of regulatory sequences at the GSTP1 gene locus is found in the vast majority (>90%) of prostate carcinomas and is associated with transcriptional down-regulation.

Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS1 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase (DG42) from Xenopus laevis, and a recently described murine hyaluronan synthase.

Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS2 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1.

USP7 or HAUSP is a ubiquitin specific protease or a deubiquitylating enzyme that cleaves ubiquitin from its substrates. Since ubiquitylation (polyubiquitination) is most commonly associated with the stability and degradation of cellular proteins, HAUSP acitivity generally stabilizes its substrate proteins. HAUSP is most popularly known as a direct antagonist of Mdm2, the E3 ubiquitin ligase for the tumor suppressor protein, p53.Normally, p53 levels are kept low in part due to Mdm2-mediated ubiquitylation and degradation of p53. Interestingly, in response to oncogenic insults, HAUSP can deubiquitinate p53 and protect p53 from Mdm2-mediated degradation, indicating that it may possess a tumor suppressor function for the immediate stabilization of p53 in response to stress. Another important role of HAUSP function involves the oncogenic stabilization of p53. Oncogenes such as Myc and E1A are thought to activate p53 through a p19 alternative reading frame (p19ARF, also called ARF)-dependent pathway, although some evidence suggests ARF is not essential in this process. An intriguing possibility is that HAUSP provides an alternative pathway for safeguarding the cell against oncogenic insults.

HDAC3: histone deacetylase 3, also known as HD3, RPD3, RPD3-2. Entrez Protein NC_000005. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene.

HDAC3: histone deacetylase 3, also known as HD3, RPD3, RPD3-2. Entrez Protein NC_000005. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene.

Hypoxia-inducible factor-1 (HIF1) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF1 is a heterodimer composed of an alpha subunit and a beta subunit. The beta subunit has been identified as the aryl hydrocarbon receptor nuclear translocator (ARNT). This gene encodes the alpha subunit of HIF-1. Overexpression of a natural antisense transcript (aHIF) of this gene has been shown to be associated with nonpapillary renal carcinomas. Two alternative transcripts encoding different isoforms have been identified. (provided by RefSeq) Tissue specificity: Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors.

The hexokinases utilize Mg-ATP as a phosphoryl donor to catalyze the first step of intracellular glucose metabolism, the conversion of glucose to glucose- 6-phosphate. Four hexokinase isoenzymes have been identified, including hexokinase I (HXK I), hexokinase II (HXK II), hexokinase III (HXK III) and hexokinase IV (HXK IV, also designated glucokinase or GCK). Hexokinases I-III each contain an N-terminal cluster of hydrophobic amino acids. Glucokinase lacks the N-terminal hydrophobic cluster. The hydrophobic cluster is thought to be necessary for membrane binding. This is substantiated by the finding that glucokinase has lower affinity for glucose than do the other hexokinases .Hexokinase 2 is the predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells.

The antibody MEM-147 reacts with all human classical MHC Class I molecules in native cell-surface forms (e.g. it recognizes native HLA-A2 in cytofluorometry and immunoprecipitation but not in Western blotting). MHC Class I molecules (MHC Class Ia) are expressed on the surface of all human nucleated cell types.

The antibody W6/32 recognises MHC Class I molecules (MHC Class Ia) that are expressed on the surface of all human nucleated cell types. The antibody W6/32 is a valuable reagent for analysing variations in HLA class I expression in different disease states e.g. liver disease, muscular dystrophy, inflammatory myopathy and other neuromuscular disorders. This antibody W6/32 is also suitable as a positive control for HLA tissue typing and crossmatching.

HLA-DR is a MHC Class II antigen expressed on dendritic cells, B cells, monocytes, macrophages, myeloid and erythroid precursors and some epithelial cells. MHC class II antigens are also expressed on activated T cells. Expression of MHC class II antigens is regulated by cytokines such as IFN-gamma, which also induces expression on fibroblasts, epithelial and endothelial cells. Certain HLA Class II molecules are associated with autoimmune diseases such as coeliac disease, insulin-dependent diabetes mellitus, rheumatoid arthritis and multiple sclerosis. MHC class II molecules are heterodimers of non-covalently associated a and b chains. MHC II on antigen presenting cells bind and present processed peptide antigens, which are then recognized by the T cell receptor on CD4+ cells.

HLA-DR is a MHC Class II antigen expressed on dendritic cells, B cells, monocytes, macrophages, myeloid and erythroid precursors and some epithelial cells. MHC class II antigens are also expressed on activated T cells. Expression of MHC class II antigens is regulated by cytokines such as IFN-gamma, which also induces expression on fibroblasts, epithelial and endothelial cells. Certain HLA Class II molecules are associated with autoimmune diseases such as coeliac disease, insulin-dependent diabetes mellitus, rheumatoid arthritis and multiple sclerosis. MHC class II molecules are heterodimers of non-covalently associated a and b chains. MHC II on antigen presenting cells bind and present processed peptide antigens, which are then recognized by the T cell receptor on CD4+ cells.

HLA-DR is a MHC Class II antigen expressed on dendritic cells, B cells, monocytes, macrophages, myeloid and erythroid precursors and some epithelial cells. MHC class II antigens are also expressed on activated T cells. Expression of MHC class II antigens is regulated by cytokines such as IFN-gamma, which also induces expression on fibroblasts, epithelial and endothelial cells. Certain HLA Class II molecules are associated with autoimmune diseases such as coeliac disease, insulin-dependent diabetes mellitus, rheumatoid arthritis and multiple sclerosis. MHC class II molecules are heterodimers of non-covalently associated a and b chains. MHC II on antigen presenting cells bind and present processed peptide antigens, which are then recognized by the T cell receptor on CD4+ cells.

This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5′ region overlaps the INS gene and the 3′ region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5′ UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism.Tissue specificity: Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines .IMP-3 is a marker for carcinomas and high-grade dysplastic lesions of pancreatic ductal epithelium.

IGFBP2: insulin-like growth factor binding protein 2. IGFBP2 is a member of the ISGBP family which bind various IGFs. IGFBP2 is overexpressed in a wide spectrum of other cancers, including glioma, prostate cancer, synovial sarcoma, neuroblastoma, colon cancer, adrenocortical cancer, lung cancer, Wilms’ tumor, and hepatoblastoma. The overexpression of IGFBP2 also correlates with the aggressiveness of some tumors. IGFBP2 activates the expression of matrix metalloprotease 2, which contributes to cell invasiveness.

INHA (A-inhibin subunit precursor, inhibin alpha subunit ), also called inhibin (alpha), which is located on chromosome 2q33-q36. Inhibin is a gonadal protein that preferentially suppresses the secretion of pituitary follicle-stimulating hormone (FSH). Inhibin comprises of two subunits, Inhibin A and B. Inhibin has been shown to regulate gonadal stromal cell proliferation negatively and to have tumor suppressor activity. In addition, serum levels of inhibin have been shown to reflect the size of granulosa cell tumors and can therefore be used as a marker for primary as well as recurrent disease. In addition to their role in endocrine feedback in the reproductive sytem, inhibins subserve local regulatory roles in numerous extragonadal tissues, including brain, adrenal,bone marrow, placenta, and most notably anterior pituitary. Inhibin alpha subunit gene expression is down regulated in human prostate cancer, suggesting a tumor suppressive role.

Inhibins are peptide hormones produced by the granulosa cells in female follicles and by Sertoli cells in the male seminiferous tubules. They are selectively expressed by cells of sex cord stromal derivation, and inhibit the secretion of follitropin by the pituitary gland. Inhibins are also involved in regulating diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins, as inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibin has 2 subunits (alpha and beta) that are coded by separate genes. The alpha subunit determines whether inhibin or activin will be produced. The alpha subunit remains constant, such that the various types of inhibin are defined by the beta subunit (a,b,c,d). Inhibin A is a dimer of alpha and beta A. Inhibin B is a dimer of alpha and beta B. Proteolytic processing yields a number of inhibin alpha bioactive forms: the 20/23 kDa forms consist solely of the mature alpha chain, the 26/29 kDa forms consist of the most N terminal propeptide linked through a disulfide bond to the mature alpha chain, and the 50/53 kDa forms encompass the entire proprotein. Each type can be furthermore either mono or diglycosylated, causing the mass difference.

Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene.

Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene.

ITK: IL2-inducible T-cell kinase. This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation.

This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation.

JAK3, Janus kinase 3. It is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease).

Ki67, also known as MKI67, it is the prototypic cell cycle related nuclear protein, expressed by proliferating cells in all phases of the active cell cycle (G1, S, G2 and M phase). It is absent in resting (G0) cells. Ki67 antibodies are useful in establishing the cell growing fraction in neoplasms (immunohistochemically quantified by determining the number of Ki67 positive cells among the total number of resting cells = Ki67 index). In neoplastic tissues the prognostic value is comparable to the tritiated thymidine labelling index. The correlation between low Ki67 index and histologically low grade tumours is strong. Ki67 is routinely used as a neuronal marker of cell cycling and proliferation.

Ki67: antigen identified by monoclonal antibody Ki-67. Ki67 antigen is the prototypic cell cycle related nuclear protein, expressed by proliferating cells in all phases of the active cell cycle (G1, S, G2 and M phase). It is absent in resting (G0) cells. Ki67 antibodies are useful in establishing the cell growing fraction in neoplasms (immunohistochemically quantified by determining the number of Ki67 positive cells among the total number of resting cells = Ki67 index). In neoplastic tissues the prognostic value is comparable to the tritiated thymidine labelling index. The correlation between low Ki67 index and histologically low grade tumours is strong. Ki67 is routinely used as a neuronal marker of cell cycling and proliferation.

Ki67, also known as MKI67, it is the prototypic cell cycle related nuclear protein, expressed by proliferating cells in all phases of the active cell cycle (G1, S, G2 and M phase). It is absent in resting (G0) cells. Ki67 antibodies are useful in establishing the cell growing fraction in neoplasms (immunohistochemically quantified by determining the number of Ki67 positive cells among the total number of resting cells = Ki67 index). In neoplastic tissues the prognostic value is comparable to the tritiated thymidine labelling index. The correlation between low Ki67 index and histologically low grade tumours is strong. Ki67 is routinely used as a neuronal marker of cell cycling and proliferation.

The c-Kit proto-oncogene is a member of the receptor tyrosine kinase family and, more specifically, is closely related to the platelet derived growth factor receptor (PDGFR). c-Kit, the normal cellular homolog of the HZ4-feline sarcoma virus transforming gene (v-Kit), encodes a transmembrane receptor. c-Kit regulates a variety of biological responses including chemotaxis, cell prolif- eration, apoptosis and adhesion. c-Kit is also identical with the product of the W locus in mice and, as such, is integral to the development of mast cells and hematopoiesis. The ligand for the c-Kit receptor (KL) has been identified and is encoded at the murine steel (SI) locus. Kit is the human homolog of the proto- oncogene c-Kit. Mutations in Kit are integral for tumor growth and progression in various cancers.

Kruppel-like factor 4 (gut),endothelial Kruppel-like zinc finger protein. May act as a transcriptional activator. Binds the CACCC core sequence. May be involved in the differentiation of epithelial cells and may also function in the development of the skeleton and kidney. KLF4 is highly expressed in the epithelial cells of the skin and the gastrointestinal tract.

Kruppel-like factor 4 (gut),endothelial Kruppel-like zinc finger protein. May act as a transcriptional activator. Binds the CACCC core sequence. May be involved in the differentiation of epithelial cells and may also function in the development of the skeleton and kidney. KLF4 is highly expressed in the epithelial cells of the skin and the gastrointestinal tract.

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its protein product is a protease present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms.

LAMB1: laminin, beta 1. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contain several EGF-like repeats, and domains IV and VI have a globular conformation. Laminin, beta 1 is expressed in most tissues that produce basement membranes, and is one of the 3 chains constituting laminin 1, the first laminin isolated from Engelbreth-Holm-Swarm (EHS) tumor. A sequence in the beta 1 chain that is involved in cell attachment, chemotaxis, and binding to the laminin receptor was identified and shown to have the capacity to inhibit metastasis.

Lck (lymphocyte-specific protein tyrosine kinase), with 509-amino acid protein (about 56kDa), belongs to the Src non-receptor tyrosine kinases family. By virtue of common structural motifs, the Src family is composed of nine members in vertebrates, including Src, Yes, Fgr, Frk, Fyn, Lyn, Hck, Lck and Blk. Lck is expressed predominantly in T cells and is localized to the inner surface of the plasma membrane. Lck is activated after T cell stimulation and is required for T-cell proliferation and IL-2 production. Aberrant expression or activation of Lck kinase has been reported in both lymphoid and nonlymphoid malignancies. In addition, inhibition of Lck has been a target to prevent lymphocyte activation and acute rejection.

LGR5 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5) is a Protein Coding gene. Among its related pathways are Wnt signaling pathway (KEGG). GO annotations related to this gene include G-protein coupled receptor activity and transmembrane signaling receptor activity. An important paralog of this gene is LGR6.

LGR5 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5) is a Protein Coding gene. Among its related pathways are Wnt signaling pathway (KEGG). GO annotations related to this gene include G-protein coupled receptor activity and transmembrane signaling receptor activity. An important paralog of this gene is LGR6.

LIM domain containing preferred translocation partner in lipoma. The Zyxin family of proteins contains five members, Ajuba, LIMD1, LPP,TRIP6 and Zyxin. LPP (LIM-containing lipoma-preferred partner), a LIM domain-containing scaffolding protein contains three LIM domains at its carboxy
terminus, which are preceded by a proline-rich pre-LIM region containing a number of protein interaction domains. LPP, an 80 kDa protein, localizes to sites of cell adhesion, such as focal adhesions and cell-cell contacts,and shuttles to the nucleus where it has transcriptional activation capacity.The human LPP gene maps to chromosomal location 3q28, and preferentially
translocates to the HMGIC gene in a subclass of human benign mesenchymal tumors known as lipomas.

Mammaglobin is a gene that is expressed almost exclusively in the normal breast epithelium and human breast cancer. It is a member of the secretoglobin gene family and forms a heterodimer with lipophilin B. It has been suggested that mammaglobin may be a useful marker for breast cancer clinical research. Studies investigating the detection of mRNA by RT PCR from circulating carcinoma cells in the peripheral blood of breast cancer patients have shown that mammaglobin is a highly specific marker and correlates with several prognostic factors, such as lymph node involvement.

MAP1A and MAP1B are microtubule-associated proteins which mediate the physical interactions between microtubules and components of the cytoskeleton. MAP1A and MAP1B each consist of a heavy chain subunit and multiple light chain subunits. The protein encoded by this gene is one of the light chain subunits and can associate with either MAP1A or MAP1B. Two transcript variants encoding different isoforms have been found for this gene. The expression of variant 1 is suppressed in many tumor cell lines, suggesting that may be involved in carcinogenesis.

MAP2K4(mitogen-activated protein kinase kinase 4), which is located on chromosome 17p11.2, with 399-amino acid protein (about 45 kDa), belongs to the  family of protein kinases located upstream of the MAP kinases and responsible for their activation has been identified.  MEK-4 (also called MEK4/MKK4) activates both p38 and JNK MAP kinases.
MKK4 is a central mediator in the stress activated protein kinase signaling pathway that responds to a number of cellular and environmental stressors. By phosphorylating MAP kinases such as JNK,MKK4 can ultimately transmit stress signals to nuclear transcription factors that mediate various processes including proliferation, apoptosis, and differentiation. Its distinct biological functions have been identified for MKK4 including a role in development, hepatogenesis, and metastasis suppression.

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

MATK (megakaryocyte-associated tyrosine kinase), also known as CTK, this protein has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer.

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7.

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7.

Maternal embryonic leucine-zipper kinase (MELK) is a key regulator of survival of stemlike GBM cells in vitro. MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene.

MER (c-mer proto-oncogene tyrosine kinase) is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. MER has been identified as a tyrosine kinase potentially involved in the development of glioblastomas. It is expressed at highest levels in ovary, prostate, lung and kidney. Gas6, a growth arrest specific gene, and the related anticoagulation factor Protein S have been identified as ligands for the UFO family of receptors. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP).

Metadherin (Metastasis adhesion protein), also known as MTDH, LYsine-RIch CEACAM1 co-isolated (LYRIC), is a novel protein that localizes with the tight junction proteins ZO-1 and occludin in polarized epithelial cells. At the tight junction, it acts not as a structural component, but is rather recruited during the maturation of the tight junction complex. Metadherin is overexpressed in breast cancer tissue and breast tumor xenografts, while much lower levels are expressed in normal breast tissue. Metadherin binds to lung vasculature, one of the four common sites of breast cancer metastasis, through a C-terminal segment in the extracellular domain; blocking this lung-homing domain with antibodies or inhibiting metadherin with siRNA has been reported to inhibit breast cancer metastasis.

DNA-mismatch repair (MMR), a conserved process that involves correcting errors made during DNA synthesis, is crucial to the maintenance of genomic integrity. Lack of a functional DNA-mismatch repair pathway is a common characteristic of several different types of human cancers, either due to an MMR gene mutation or promoter-methylation gene silencing. MLH1 is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in hereditary nonpolyposis colon cancer (HNPCC). MLH1 is an integral part of the protein complex responsible for mismatch repair expressed in lymphocytes, heart, colon, breast, lung, spleen, testis, prostate, thyroid and gall bladder, and is methylated in several ovarian tumors. Loss of MLH1 protein expression is associated with a mutated phenotype, microsatellite instability and a predisposition to cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal dominant inherited cancer syndrome that signifies a high risk of colorectal and various other types of cancer, the MLH1 gene exhibits a pathogenic mutation. Inactivation of the MLH1 gene causes genome instability and predisposition to cancer. MLH1 also plays a role in meiotic recombination.

Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila). Eukaryotic RNA polymerase II mediates the synthesis of mature and functional messenger RNA. This is a multistep process, called the transcription cycle,that includes five stages: preinitiation, promoter, clearance, elongation and termination. Elongation is thought to be a critical stage for the regulation of gene expression. ELL (11-19 lysine-rich leukemia protein, also designated MEN) functions as an RNA polymerase II elongation factor that increases the rateof transcription by suppressing transient pausing by RNA polymerase II. Also, ELL is thought to regulate cellular proliferation. ELL is abundantly expressed in peripheral blood leukocytes, skeletal muscle, placenta and testis, and has lower expression in spleen, thymus, heart, brain, lung, kidney, liver and ovary.The gene encoding human ELL, which maps to chromosome 19p13.1, is one of several genes which undergo translocation with the MLL gene on chromo-some 11q23 in acute myeloid leukemia. MLL (myeloid/lymphoid leukemia,also designated ALL-1 and HRX) is a 430 kDa protein that regulates embryonal and hematopoietic development.