ID:ADIPO_HUMAN DESCRIPTION: RecName: Full=Adiponectin; AltName: Full=30 kDa adipocyte complement-related protein; AltName: Full=Adipocyte complement-related 30 kDa protein; Short=ACRP30; AltName: Full=Adipocyte, C1q and collagen domain-containing protein; AltName: Full=Adipose most abundant gene transcript 1 protein; Short=apM-1; AltName: Full=Gelatin-binding protein; Flags: Precursor; FUNCTION: Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW. SUBUNIT: Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly may rely aditionally on lysine hydroxylation and glycosylation. LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9A via the C1q domain (heterotrimeric complex) (By similarity). SUBCELLULAR LOCATION: Secreted. TISSUE SPECIFICITY: Synthesized exclusively by adipocytes and secreted into plasma. DOMAIN: The C1q domain is commonly called the globular domain. PTM: Hydroxylated Lys-33 was not identified in PubMed:16497731, probably due to poor representation of the N-terminal peptide in mass fingerprinting. PTM: HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagene-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin- sensitizing activity of adiponectin in hepatocytes (By similarity). PTM: O-glycosylated. Not N-glycosylated. O-linked glycans on hydroxylysines consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Sialylated to varying degrees depending on tissue. Thr-22 appears to be the major site of sialylation. Higher sialylation found in SGBS adipocytes than in HEK fibroblasts. Sialylation is not required neither for heterodimerization nor for secretion. Not sialylated on the glycosylated hydroxylysines. Desialylated forms are rapidly cleared from the circulation. POLYMORPHISM: Genetic variations in ADIPOQ influence the variance in adiponectin serum levels and define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556]. DISEASE: Defects in ADIPOQ are the cause of adiponectin deficiency (ADPND) [MIM:612556]. ADPND results in very low concentrations of plasma adiponectin. DISEASE: Genetic variations in ADIPOQ are associated with non- insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. PHARMACEUTICAL: Adiponectin might be used in the treatment of diabetes type 2 and insulin resistance. MISCELLANEOUS: Variants Arg-84 and Ser-90 show impaired formation of HMW complexes whereas variants Cys-112 and Thr-164 show impaired secretion of adiponectin in any form. MISCELLANEOUS: HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW- complex secretion (By similarity). In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation are significantly decreased as compared with healthy controls. SIMILARITY: Contains 1 C1q domain. SIMILARITY: Contains 1 collagen-like domain. WEB RESOURCE: Name=Wikipedia; Note=Adiponectin entry; URL="http://en.wikipedia.org/wiki/Adiponectin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15848
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001666 response to hypoxia GO:0001934 positive regulation of protein phosphorylation GO:0006006 glucose metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006635 fatty acid beta-oxidation GO:0007584 response to nutrient GO:0007623 circadian rhythm GO:0009744 response to sucrose GO:0009749 response to glucose GO:0009967 positive regulation of signal transduction GO:0010469 regulation of receptor activity GO:0010642 negative regulation of platelet-derived growth factor receptor signaling pathway GO:0010739 positive regulation of protein kinase A signaling GO:0010745 negative regulation of macrophage derived foam cell differentiation GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway GO:0010875 positive regulation of cholesterol efflux GO:0010906 regulation of glucose metabolic process GO:0014823 response to activity GO:0019395 fatty acid oxidation GO:0030336 negative regulation of cell migration GO:0030853 negative regulation of granulocyte differentiation GO:0031667 response to nutrient levels GO:0031953 negative regulation of protein autophosphorylation GO:0032270 positive regulation of cellular protein metabolic process GO:0032720 negative regulation of tumor necrosis factor production GO:0032757 positive regulation of interleukin-8 production GO:0032869 cellular response to insulin stimulus GO:0033034 positive regulation of myeloid cell apoptotic process GO:0034115 negative regulation of heterotypic cell-cell adhesion GO:0034383 low-density lipoprotein particle clearance GO:0034612 response to tumor necrosis factor GO:0035690 cellular response to drug GO:0042304 regulation of fatty acid biosynthetic process GO:0042493 response to drug GO:0042593 glucose homeostasis GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043407 negative regulation of MAP kinase activity GO:0045471 response to ethanol GO:0045599 negative regulation of fat cell differentiation GO:0045650 negative regulation of macrophage differentiation GO:0045715 negative regulation of low-density lipoprotein particle receptor biosynthetic process GO:0045721 negative regulation of gluconeogenesis GO:0045776 negative regulation of blood pressure GO:0045860 positive regulation of protein kinase activity GO:0045892 negative regulation of transcription, DNA-templated GO:0045923 positive regulation of fatty acid metabolic process GO:0046326 positive regulation of glucose import GO:0046888 negative regulation of hormone secretion GO:0050728 negative regulation of inflammatory response GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050765 negative regulation of phagocytosis GO:0050805 negative regulation of synaptic transmission GO:0050873 brown fat cell differentiation GO:0051260 protein homooligomerization GO:0051384 response to glucocorticoid GO:0070208 protein heterotrimerization GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0070543 response to linoleic acid GO:0070994 detection of oxidative stress GO:0071320 cellular response to cAMP GO:0071639 positive regulation of monocyte chemotactic protein-1 production GO:0071872 cellular response to epinephrine stimulus GO:0072659 protein localization to plasma membrane GO:0090317 negative regulation of intracellular protein transport GO:1900121 negative regulation of receptor binding GO:1904706 negative regulation of vascular smooth muscle cell proliferation GO:1904753 negative regulation of vascular associated smooth muscle cell migration GO:2000279 negative regulation of DNA biosynthetic process GO:2000467 positive regulation of glycogen (starch) synthase activity GO:2000478 positive regulation of metanephric glomerular visceral epithelial cell development GO:2000481 positive regulation of cAMP-dependent protein kinase activity GO:2000534 positive regulation of renal albumin absorption GO:2000584 negative regulation of platelet-derived growth factor receptor-alpha signaling pathway GO:2000590 negative regulation of metanephric mesenchymal cell migration