"Bioss"

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ADAMTS proteases are secreted enzymes containing a prometalloprotease domain of the reprolysin type. The ADAMTS proteases function in processing of procollagens and von Willebrand factor as well as catabolism of aggrecan, versican and brevican. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration.A member of the metalloproteinase family containing disintegrin like domains (ADAMs), the function of ADAMTS8 is still poorly understood. ADAMTS8 contains the canonical HExxHxxxxxH zinc metalloproteinase motif, and has been shown to be proteolytically active on a range of substrates. ADAMTS8 is inhibited by the endogenous MMP inhibitors, TIMP1, 2, 3 and 4, but most efficiently by TIMP3. In addition to the metalloprotease domain, ADAMTS8 has a propeptide domain, a Prohormone Convertase (PC, furin) cleavage site, a cysteine rich domain and thrombospondin 1 like domains.

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Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors. This gene encodes the type 1 receptor which is thought to mediate the major cardiovascular effects of angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least five transcript variants have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants. [provided by RefSeq].

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C1orf103

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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.

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Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.

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FGF22 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The mouse homolog of this gene was found to be preferentially expressed in the inner root sheath of the hair follicle, which suggested a role in hair development.Fibroblast Growth Factor-22 stimulates the proliferation and activation of cells that express FGF receptor.

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APPBP1 is a member of the ubiquitin-activating E1 family. In fetal tissues APPBP1 is widely expressed and in adult tissues it is expressed throughout the brain. APPBP1 is a cell membrane associated protein and functions as the regulatory subunit in a heterodimer with UBA3. The APPBP1/UBA3 complex binds to and activates NEDD8, a ubiquitin-like protein involved in signal transduction, cell proliferation and development. This suggests that APPBP1 affects a variety of cellular functions. In addition, APPBP1 is essential for cell cycle progression through the S/M checkpoint. More specifically, it inhibits the entry into S phase and promotes entry into M phase.

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Transcription factors, OTX1 and OTX2, are two murine homologs of the Drosophila orthodenticle (OTD), show a limited amino acid sequence divergence. OTX1 and OTX2 play an important role during early and later events required for proper brain development in that they are involved in the processes of induction, specification and regionalization of the brain. OTX1 is involved in corticogenesis, sensory organ development and pituitary functions, while OTX2 is necessary earlier in development, for the correct anterior neural plate specification and organization of the primitive streak. OTX2 is also required in the early specification of the neuroectoderm, which is destined to become the fore-midbrain, and both OTX1 and OTX2 co-operate in patterning the developing brain through a dosage-dependent mechanism. A molecular mechanism depending on a precise threshold of OTX proteins is necessary for the correct positioning of the isthmic region and for anterior brain patterning. The genes which encode OTX1 and OTX2 map to human chromosomes 2p13 and 14q21-q22, respectively.

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Estrogen and progesterone receptor are members of a family of transcription factors that are regulated by the binding of their cognate ligands. The interaction of hormone-bound estrogen receptors with estrogen responsive elements(EREs) alters transcription of ERE-containing genes. The carboxy terminal region of the estrgen receptor contains the ligand binding domain, the amino terminus serves as the transactivation domain, and the DNA binding domain is centrally located. Two forms of estrogen receptor have been identified, ER Alpha and ER Beta. ER Alpha and ER Beta have been shown to be differentially activated by various ligands. The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (hPR-A and hPR-B), which arise from alternative splicing. In most cells, hPR-B functions as a transcriptional activator of progesterone-responsive gene, whereas hPR-A function as a transcriptional inhibitor of all steroid hormone receptors.

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Nudel is important for normal cortical development. It is invovled in microtubule organization, nuclear translocation, and neuronal positioning in concert with various other factors (including Lis1, Pafah1b1, Pahfah1b2, dynein, dynorphin A and cdk5). Western blot analysis of mouse tissues shows abundant expression of Nudel in brain and testis, and much lower expression in heart, liver, kidney, and skeletal muscle. In fractionated rat brain, Nudel and Lis1 are both found in fractions enriched for postsynaptic density proteins. Immunostaining of embryonic day 18 mouse brain sections revealed staining of migrating neurons and thalamocortical axons of the intermediate zone of the developing cerebral cortex, as well as several other developing brain regions. The deduced protein contains 345 amino acids and has a calculated molecular mass of 38.4 kDa. It has a coiled coil motif (residues 19 to 201), followed by several potential phosphorylation sites for casein kinase II, protein kinase C or CDK5. Nudel shares about 50% identity with mouse and human NUDE proteins.

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Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation.

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SH3TC2 (SH3 domain and tetratricopeptide repeats 2) is a 1,288 amino acid protein that contains one SH3 domain and eight TPR repeats. The SH3TC2 gene encodes a protein expressed in Schwann cells of peripheral nerves, and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions. The SH3TC2 protein is expressed in adult heart, testis, spinal cord, and brain as well as in fetal brain and liver. Mild mononeuropathy of the median nerve (MNMN) is caused by heterozygous mutation in the SH3TC2 gene. Also, Charcot-Marie-Tooth disease type 4C (CMT4C) is a more severe neuropathy caused by homozygous or compound heterozygous mutation in the SH3TC2 gene. Existing as four alternatively spliced isoforms and containing 18 exons, the SH3TC2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish, and maps to human chromosome 5q32.

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Hamartin, or TSC1, is a suspected tumor suppressor implicated in the disease tuberous sclerosis 1. It is a negative regulator of cell division controlling the transition from G0/G1 to S phase, and it seems to act through the phosphatidylinositol 3 kinase/Akt pathway. TSC1 interacts with tuberin m(TSC2), which is thought to be a GAP (GTPase Activating Protein) for the Rap1 and Rab5 small G Proteins. The Hamartin/Tuberin complex has been shown to inhibit mTor. Hamartin has also been shown to interact with ERM (Ezrin-Radixin-Moesin) proteins and with F-actin, suggesting a role for TSC proteins in modulation of cell adhesion and morphology.

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Human papilloma viruses (HPVs) can be classified as either high risk or low risk according to their association with cancer. HPV16 and HPV18 are the most common of the high risk group while HPV6 and HPV11 are among the low risk types. Approximately 90% of cervical cancers contain HPV DNA of the high risk types. Mutational analysis have shown that the E6 and E7 genes of the high risk HPVs are necessary and sufficient for HPV transforming function. The specific interactions of the E6 and E7 proteins with p53 and pRB, respectively, correlate with HPV high and low risk classifications. The high risk HPV E7 proteins bind to pRB with a higher affinity than do the low risk HPV proteins, and only the high risk HPV E6 proteins form detectable complexes with p53 in vitro. Human papillomaviruses (HPV) are small DNA viruses which infect epithelia of the skin and mucosa. Over 90 types have been identified and they mostly cause a variety of benign lesions such as warts and verrucae. However, some subtypes, notably types 16 and 18, 31 and 33, have been confirmed as agents which cause cervical cancer. The E6 protein is a transcriptional transactivator. Binds double-stranded DNA. This protein may be involved in the oncogenic potential of this virus (cervical neoplasia-associated virus).

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The ubiquitin (Ub) pathway involves three sequential enzymatic steps that facilitate the conjugation of Ub and Ub-like molecules to specific protein substrates. The first step requires the ATP-dependent activation of the Ub C-terminus and the assembly of multi-Ub chains by the Ub-activating enzyme known as the E1 component. The Ub chain is then conjugated to the Ub-conjugating enzyme (E2) to generate an intermediate Ub-E2 complex. The Ub-ligase (E3) then catalyzes the transfer of Ub from E2 to the appropriate protein substrate. A wide range of enzymes facilitate in the proteolytic Ub pathway, including monoclonal nonspecific suppressor factor-beta (MNSF-beta), a subunit of MNSF, which is a lymphokine product of a murine T cell hybrid-oma that restricts the production of LPS-induced immunoglobulin secreting cells in an antigen-nonspecific manner. MNSF-beta is a ubiquitin-like fusion protein consisting of the ribosomal protein S30 and a protein that shares 36% sequence identity with ubiquitin. This ubiquitin-like segment (Ubi-L) can be cleaved from MNSF-beta in the cytosol.

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Implicated in a number of cellular processes, including proliferation, differentiation, caspase-dependent and caspase-independent apoptosis, suppression of transformation (tumor suppressor), inhibition of protein phosphatase 2A, regulation of mRNA trafficking and stability in association with ELAVL1, and inhibition of acetyltransferases as part of the INHAT (inhibitor of histone acetyltransferases) complex. Plays a role in E4F1-mediated transcriptional repression.