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MGP003877

UniProt Annotations

Entry Information
Gene Nameadiponectin, C1Q and collagen domain containing
Protein EntryADIPO_HUMAN
UniProt IDQ15848
SpeciesHuman
Comments
Comment typeDescription
DiseaseAdiponectin deficiency (ADPND) [MIM:612556]: A condition that results in very low concentrations of plasma adiponectin. {ECO:0000269|PubMed:10918532}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDiabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DomainThe C1q domain is commonly called the globular domain.
FunctionImportant 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. {ECO:0000269|PubMed:11479627}.
MiscellaneousHMW-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. {ECO:0000250}.
MiscellaneousVariants 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.
PharmaceuticalAdiponectin might be used in the treatment of diabetes type 2 and insulin resistance.
PolymorphismGenetic variations in ADIPOQ influence the variance in adiponectin serum levels and define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556].
PtmHMW 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). {ECO:0000250}.
PtmHydroxylated Lys-33 was not identified in PubMed:16497731, probably due to poor representation of the N-terminal peptide in mass fingerprinting. {ECO:0000269|PubMed:16497731}.
PtmO-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. {ECO:0000269|PubMed:16497731, ECO:0000269|PubMed:19855092}.
SimilarityContains 1 C1q domain. {ECO:0000255|PROSITE- ProRule:PRU00368}.
SimilarityContains 1 collagen-like domain. {ECO:0000305}.
Subcellular LocationSecreted.
SubunitHomomultimer. 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 additionally 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). {ECO:0000250}.
Tissue SpecificitySynthesized exclusively by adipocytes and secreted into plasma.
Web ResourceName=Wikipedia; Note=Adiponectin entry; URL="http://en.wikipedia.org/wiki/Adiponectin";
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