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Eph receptor A2 is the receptor for members of the ephrin-A family. It binds to ephrin-A1, -A3, -A4 and -A5. Eph receptor A3 is also a receptor for members of the ephrin-A family. It binds to ephrin-A2, -A3, -A4 and -A5 and is thought to play a role in lymphoid function. Eph receptor A4 is a receptor for members of the ephrin-A family. It binds to ephrin-A1, -A4 and -A5. It binds more poorly to ephrin-A2 and -A3. It may play a role in a signal transduction process involved in hindbrain pattern formation.

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Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation.

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The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.

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Apoptosis, or programmed cell death, occurs during normal cellular differentiation and development of multicellular organisms. Apoptosis is induced by certain cytokines including TNF and Fas ligand of the TNF family through their death domain containing receptors, TNFR1 and Fas. Cell death signals are transduced by death domain (DD) containing adapter molecules and members of the ICE/CED3 protease family. A novel DD containing molecule was recently cloned from mouse, human and monkey and designated Daxx. Daxx is a death domain containing important intermediate in the Fas mediated apoptosis. Daxx binds specifically to the Fas death domain and enhances Fas induced apoptosis and activates the Jun N terminal kinase (JNK) pathway. It is widely expressed in fetal and adult human and mouse tissue, indicating its important function in Fas signaling pathways.

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The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eucaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and thus may be involved in controlling the timing of mitosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors.

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DR1, also known as NC2∫ (negative cofactor 2 subunit ∫), is a TFIID (TATA box-binding protein)-associated protein. DR1 localizes to the nucleus and contains an N-terminal histone fold motif, a TFIID-binding domain and an alanine and glutamine rich region. Via its histone fold motif, DR1 forms a heterodimer with NC2å (DRAP1) to comprise the conserved eukaryotic complex, NC2 (negative cofactor 2). The NC2 complex can both positively and negatively regulate transcription by RNA Pol II. More specifically, NC2 acts as a repressor of TATA-dependent transcription and acts as an activator for DPE-dependent transcription. NC2 represses RNA Pol II transcription by binding to TFIID and inhibiting association of the transcription factors TFIIA and TFIIB. NC2 activity is regulated by phosphorylation. Both subunits, NC2å and DR1, are phosphorylated in vivo.

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Making up nearly 6% of the human genome, chromosome 6 contains around 1,200 genes within 170 million base pairs of sequence. Deletion of a portion of the q arm of chromosome 6 is associated with early onset intestinal cancer, suggesting the presence of a cancer susceptibility locus. Porphyria cutanea tarda is associated with chromosome 6 through the HFE gene which, when mutated, predisposes an individual to developing this porphyria. Notably, the PARK2 gene, which is associated with Parkinson's disease, and the genes encoding the major histocompatiblity complex proteins, which are key molecular components of the immune system and determine predisposition to rheumatic diseases, are also located on chromosome 6. Stickler syndrome, 21-hydroxylase deficiency and maple syrup urine disease are also associated with genes on chromosome 6. A bipolar disorder susceptibility locus has been identified on the q arm of chromosome 6.

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Teneurin-3, also known as Ten-3, TNM3 or ODZ3, is a 2,699 amino acid single-pass type II membrane protein that contains 25 YD repeats, 8 EGF-like domains, 5 NHL repeats and one teneurin N-terminal domain. Localized to the membrane and expressed in brain, testis and ovary, Teneurin-3 exists as a disulfide-liked homodimer that is thought to function as a cellular signal transducer. Additionally, Teneurin-3 may participate in eye-specific patterning in the visual pathway and is required for aligned binocular vision. The gene encoding Teneurin-3 maps to chromosome 4. Representing approximately 6% of the human genome, chromosome 4 contains nearly 900 genes, one of which is the Huntingtin gene, which is found to encode an expanded glutamine tract in cases of Huntington's disease. FGFR-3 is also encoded on chromosome 4 and has been associated with thanatophoric dwarfism, achondroplasia, Muenke syndrome and bladder cancer. Chromosome 4 is also tied to Ellis-van Creveld syndrome, methylmalonic acidemia and polycystic kidney disease.

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This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The protein encoded by this gene is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified.

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Separase is a cysteine protease that is essential for mitotic progression by separating sister chromatids. Each cell must receive one chromatid of every chromosome, during mitosis. Cohesin plays an important role in cohering sister chromatids during the prophase through anaphase stages of mitosis, making certain that genomic information is replicated accurately. As the cellular division process continues, separase destroys cohesin by means of cleavage, allowing the chromatids to separate and divide with the cell. Separase activity is highly regulated. It not only cleaves cohesin at the onset of anaphase but also cleaves itself, promoting downregulation of separase after anaphase. Should a human cell become an aneuploid (one too many or too few chromatids), the embryo most likely will not survive. Should the embryo survive, it will most likely develop severe birth defects or later develop malignant cancers.

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SLC14A1 is one of two major mammalian urea transporters, which play a critical role in the urine-concentrating mechanism. Their abundance is regulated by vasopressin, glucocorticoids, and mineralocorticoids. These regulatory mechanisms may be important in disease states such as diabetes.

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Functions as an electroneutral and bidirectional ammonium transporter. May regulate transepithelial ammonia secretion.

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Cell cycle progression is controlled in part by a family of cyclin proteins and cyclin dependent kinases (Cdks). Cdk proteins work in concert with the cyclins to phosphorylate key substrates involved in each phase of cell cycle progression. Specifically, Cdk2 interacts with Cyclins A, B1, B3, D, or E to control cell cycle progression. The Cyclin-dependent kinase 2-interacting protein (CINP) interacts with components of the replication complex and Cdk2 and Cdc7, thereby providing a functional and physical link between Cdk2 and Cdc7 during firing of the origins of replication. However, CINP is phopshorylated by Cdc7, but not by Cdk2. CINP also interacts with ATR-interacting protein and regulates ATR-dependent signaling, resistance to replication stress and G2 checkpoint integrity.

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Cell cycle progression is controlled in part by a family of cyclin proteins and cyclin dependent kinases (Cdks). Cdk proteins work in concert with the cyclins to phosphorylate key substrates involved in each phase of cell cycle progression. Specifically, Cdk2 interacts with Cyclins A, B1, B3, D, or E to control cell cycle progression. The Cyclin-dependent kinase 2-interacting protein (CINP) interacts with components of the replication complex and Cdk2 and Cdc7, thereby providing a functional and physical link between Cdk2 and Cdc7 during firing of the origins of replication. However, CINP is phopshorylated by Cdc7, but not by Cdk2. CINP also interacts with ATR-interacting protein and regulates ATR-dependent signaling, resistance to replication stress and G2 checkpoint integrity.

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Modulates the activity of cell cycle-specific kinases. Enhances CDK1 activity. May contribute to the regulation of the cell cycle. May inhibit growth of glioma cells by promoting arrest of mitotic progression at the G2/M transition. Fibrogenic factor contributing to the pathogenesis of renal fibrosis through fibroblast activation.

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FBXO4 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It probably recognizes and binds to phosphorylated target proteins. It recognizes TERF1 and promotes its ubiquitination together with UBE2D1.

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FBXO4 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It probably recognizes and binds to phosphorylated target proteins. It recognizes TERF1 and promotes its ubiquitination together with UBE2D1.

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The protein encoded by this gene contains an acidic domain, a putative bipartite nuclear localization signal, a nuclear export signal, a leucine-isoleucine zipper, and phosphorylation motifs. In addition, the encoded protein contains Armadillo/beta-catenin-like repeats, which have been implicated in protein-protein interactions. Although the function of this protein has not been determined, the C-terminal portion of the protein has been shown to possess apoptosis-inducing activity.

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When SLTM is overexpressed it acts as a general inhibitor of transcription that eventually leads to apoptosis.

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This gene encodes a highly glycosylated transmembrane protein with a high content of threonine and serine residues in its extracellular domain, similar to a broadly defined category of proteins termed mucins. Exposure of some cell types to anti PORIMIN (pro oncosis receptor inducing membrane injury) antibody, crosslinks this protein on the cell surface and induces a type of cell death termed oncosis. Oncosis is distinct from apoptosis and is characterized by a loss of cell membrane integrity without DNA fragmentation. This gene product is proposed to function as a cell surface receptor that mediates cell death.

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Protein kinases are enzymes that transfer a phosphate group from a phosphate donor onto an acceptor amino acid in a substrate protein. By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes, classified in 8 major groups based on sequence comparison of their tyrosine (PTK) or serine/threonine (STK) kinase catalytic domains. Epidermal Growth factor receptor (EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck, brain, bladder, stomach, breast, lung, endometrium, cervix, vulva, ovary, esophagus, stomach and in squamous cell carcinoma.

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Protein kinases are enzymes that transfer a phosphate group from a phosphate donor onto an acceptor amino acid in a substrate protein. By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. The protein kinase family is one of the largest families of proteins in eukaryotes, classified in 8 major groups based on sequence comparison of their tyrosine (PTK) or serine/threonine (STK) kinase catalytic domains. Epidermal Growth factor receptor (EGFR) is the prototype member of the type 1 receptor tyrosine kinases. EGFR overexpression in tumors indicates poor prognosis and is observed in tumors of the head and neck, brain, bladder, stomach, breast, lung, endometrium, cervix, vulva, ovary, esophagus, stomach and in squamous cell carcinoma.

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Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity.

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The RING-type zinc finger motif is present in a number of viral and eukaryotic proteins and is made of a conserved cysteine-rich domain that is able to bind two zinc atoms. Proteins that contain this conserved domain are generally involved in the ubiquitination pathway of protein degradation. RNF113B (ring finger protein 113B), also referred to as zinc finger protein 183-like 1, RNF161, MGC26599, bA10G5.1 or ZNF183L1, is a 322 amino acid protein containing one C3H1-type zinc finger and one RING-type zinc finger. The gene encoding RNF113B maps to human chromosome 13, which houses over 400 genes, such as BRCA2 and RB1, and comprises nearly 4% of the human genome. Trisomy 13, also known as Patau syndrome, is deadly and the few who survive past one year suffer from permanent neurologic defects, difficulty eating and vulnerability to serious respiratory infections.

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The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008].

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The PDE4A8 is a testis germ cell-specific PDE4A variant. There are two PDE4A variants identified in rat testis (PDE4A8 and an un-characterized 76 kDa PDE4A protein). Spermatogenesis is accompanied by expression of a varied repertoire of PDE4 enzymes at different stages of cell differentiation that presumably perform specialized functions. Confocal microscopic examination revealed the presence of PDE4A8 in primary and secondary spermatids but not in mature spermatozoa. PDE4A8 inhibition results in increased apoptosis of the germ cells accompanied with reduction in the number of mature spermatozoa.

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The PDE4A8 is a testis germ cell-specific PDE4A variant. There are two PDE4A variants identified in rat testis (PDE4A8 and an un-characterized 76 kDa PDE4A protein). Spermatogenesis is accompanied by expression of a varied repertoire of PDE4 enzymes at different stages of cell differentiation that presumably perform specialized functions. Confocal microscopic examination revealed the presence of PDE4A8 in primary and secondary spermatids but not in mature spermatozoa. PDE4A8 inhibition results in increased apoptosis of the germ cells accompanied with reduction in the number of mature spermatozoa.

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C17orf53 is a 647 amino acid protein that is encoded by a gene mapping to human chromosome 17. Chromosome 17 makes up over 2.5% of the human genome with about 81 million bases encoding over 1,200 genes. Two key tumor suppressor genes are associated with chromosome 17, namely, p53 and BRCA1. Tumor suppressor p53 is necessary for maintenance of cellular genetic integrity by moderating cell fate through DNA repair versus cell death. Malfunction or loss of p53 expression is associated with malignant cell growth and Li-Fraumeni syndrome. Like p53, BRCA1 is directly involved in DNA repair, specifically it is recognized as a genetic determinant of early onset breast cancer and predisposition to cancers of the ovary, colon, prostate gland and fallopian tubes. Chromosome 17 is also linked to neurofibromatosis, a condition characterized by neural and epidermal lesions, and dysregulated Schwann cell growth. Alexander disease, Birt-Hogg-Dube syndrome and Canavan disease are also associated with chromosome 17.

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C17orf57 is a 973 amino acid protein that is encoded by a gene mapping to human chromosome 17. Chromosome 17 makes up over 2.5% of the human genome with about 81 million bases encoding over 1,200 genes. Two key tumor suppressor genes are associated with chromosome 17, namely, p53 and BRCA1. Tumor suppressor p53 is necessary for maintenance of cellular genetic integrity by moderating cell fate through DNA repair versus cell death. Malfunction or loss of p53 expression is associated with malignant cell growth and Li-Fraumeni syndrome. Like p53, BRCA1 is directly involved in DNA repair, specifically it is recognized as a genetic determinant of early onset breast cancer and predisposition to cancers of the ovary, colon, prostate gland and fallopian tubes. Chromosome 17 is also linked to neurofibromatosis, a condition characterized by neural and epidermal lesions, and dysregulated Schwann cell growth. Alexander disease, Birt-Hogg-Dube syndrome and Canavan disease are also associated with chromosome 17.