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Description:
Myosin VI a molecular motor involved in intracellular vesicle and organelle transport, is the only Myosin motor that binds to the pointed end of Actin. This unique Myosin has only one light chain in the lever-arm domain and has highly irregular stepping with a wide range of step sizes, unlike that of other characterised Myosins. It associates with Clathrin-coated vesicles and disabled 2, indicating a role for Myosin VI in endocytosis. Mouse Myosin VI is expressed within the sensory hair cells of the cochlea. Human Myosin VI is mapped to the centromeric region of chromosome 6, a region that shows syntenic homology with the corresponding mouse chromosome 9 region, where the Snell's Waltzer mutation is located. The behavioural effects of the mouse Snell's Waltzer mutation are lack of responsiveness to sound, hyperactivity, head tossing and circling, due to the disorganization and fusing of stereocilia bundles within the inner ear. Defects of Myosin VI cause autosomal dominant nonsyndromic sensori-neural deafness in humans. Human Myosin VI is expressed in fetal cochlea and brain, as well as in adult brain.
Description:
CCT2 is one of eight largely unrelated subunit proteins found in a protein chaperone complex known as the chaperonin-containing TCP-1 (CCT) or TRiC complex. The CCT complex is an abundanct cytoslic component that is credited with helping newly synthesized polypeptides adopt the correct conformation (1). Proteins that fold and assemble with the help of CCT include the cytoskeletal proteins actin and tubulin as well as up to 15% of newly synthesized eukaryotic proteins (2). CCT2 is the β-subunit of the chaperone complex and is one of several CCT proteins that exhibit increased expression in response to stress. This implies that the CCT complex helps cells recover from protein damage by assisting in protein folding and assembly (3). CCT subunit levels also change throughout the cell cycle, with lower proteins levels (and reduced chaperone activity) found during induced cell cycle arrest during at M phase (4). Each CCT subunit is thought to perform a specific function during protein folding and assembly (5); CCT2 exhibits both actin and tubulin binding activities (6,3) but the exact molecular function on this subunit remains uncertain.
Description:
Chromosome 9 consists of about 145 million bases and 4% of the human genome and encodes nearly 900 genes. Considered to play a role in gender determination, deletion of the distal portion of 9p can lead to development of male to female sex reversal, the phenotype of a female with a male X,Y genotype. Hereditary hemorrhagic telangiectasia, which is characterised by harmful vascular defects, is associated with the chromosome 9 gene encoding endoglin protein, ENG. Familial dysautonomia is also associated with chromosome 9 though through the gene IKBKAP. Notably, chromosome 9 encompasses the largest interferon family gene cluster. Chromosome 9 is partnered with chromosome 22 in the translocation leading to the aberrant production of BCR-ABL fusion protein often found in leukemias. The C9orf57 gene product has been provisionally designated C9orf57 pending further characterisation.
Description:
Cell adhesion molecules influence cell growth, differentiation, embryogenesis, immune response and cancer metastasis by networking information from the extracellular matrix to the cell. Sidekick-1 (SDK1) is a 2,213 amino acid single-pass membrane protein that functions as a cell adhesion molecule by guiding axonal terminals to specific synapses in developing neurons. Existing as three alternatively spliced isoforms, Sidekick-1 is expressed in retinal neurons and contains thirteen fibronectin type-III domains and six Ig-like C2-type (immunoglobulin-like) domains. Sidekick-1 expression is upregulated in glomeruli of patients with HIV-associated nephropathy, where it leads to podocyte dysfunction. The gene encoding Sidekick-1 maps to human chromosome 7p22.2 and murine chromosome 5 G2.
Description:
Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.
Description:
Cell adhesion molecules influence cell growth, differentiation, embryogenesis, immune response and cancer metastasis by networking information from the extracellular matrix to the cell. Sidekick-1 (SDK1) is a 2,213 amino acid single-pass membrane protein that functions as a cell adhesion molecule by guiding axonal terminals to specific synapses in developing neurons. Existing as three alternatively spliced isoforms, Sidekick-1 is expressed in retinal neurons and contains thirteen fibronectin type-III domains and six Ig-like C2-type (immunoglobulin-like) domains. Sidekick-1 expression is upregulated in glomeruli of patients with HIV-associated nephropathy, where it leads to podocyte dysfunction. The gene encoding Sidekick-1 maps to human chromosome 7p22.2 and murine chromosome 5 G2.
Description:
Made up of nearly 146 million bases, chromosome 8 encodes about 800 genes. Translocation of portions of chromosome 8 with amplifications of the c-Myc gene are found in some leukaemias and lymphomas, and typically associated with a poor prognosis. Portions of chromosome 8 have been linked to schizophrenia and bipolar disorder. Trisomy 8, also known as Warkany syndrome 2, most often results in early miscarriage but is occasionally seen in a mosaic form in surviving patients who suffer to a varying degree from a number of symptoms including retarded mental and motor development, and certain facial and developmental defects. WRN is a DNA helicase encoded by chromosome 8 and shown defective in those with the early aging disorder Werner syndrome. Chromosome 8 is also associated with Pfeiffer syndrome, congenital hypothyroidism and Waardenburg syndrome. The C8orf45 gene product has been provisionally designated C8orf45 pending further characterisation.
Description:
Made up of nearly 146 million bases, chromosome 8 encodes about 800 genes. Translocation of portions of chromosome 8 with amplifications of the c-Myc gene are found in some leukemias and lymphomas, and typically associated with a poor prognosis. Portions of chromosome 8 have been linked to schizophrenia and bipolar disorder. Trisomy 8, also known as Warkany syndrome 2, most often results in early miscarriage but is occasionally seen in a mosaic form in surviving patients who suffer to a varying degree from a number of symptoms including retarded mental and motor development, and certain facial and developmental defects. WRN is a DNA helicase encoded by chromosome 8 and shown defective in those with the early aging disorder Werner syndrome. Chromosome 8 is also associated with Pfeiffer syndrome, congenital hypothyroidism and Waardenburg syndrome. The C8orf44 gene product has been provisionally designated C8orf44 pending further characterisation.
Description:
FunctionMay promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining.
Description:
Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors.
Description:
Made up of nearly 146 million bases, chromosome 8 encodes about 800 genes. Translocation of portions of chromosome 8 with amplifications of the c-Myc gene are found in some leukemias and lymphomas, and typically associated with a poor prognosis. Portions of chromosome 8 have been linked to schizophrenia and bipolar disorder. Trisomy 8, also known as Warkany syndrome 2, most often results in early miscarriage but is occasionally seen in a mosaic form in surviving patients who suffer to a varying degree from a number of symptoms including retarded mental and motor development, and certain facial and developmental defects. WRN is a DNA helicase encoded by chromosome 8 and shown defective in those with the early aging disorder Werner syndrome. Chromosome 8 is also associated with Pfeiffer syndrome, congenital hypothyroidism and Waardenburg syndrome. The C8orf44 gene product has been provisionally designated C8orf44 pending further characterisation.
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