ID ADIPO_HUMAN Reviewed; 244 AA. AC Q15848; Q58EX9; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 02-SEP-2026, entry version 233. DE RecName: Full=Adiponectin; DE AltName: Full=30 kDa adipocyte complement-related protein; DE AltName: Full=Adipocyte complement-related 30 kDa protein; DE Short=ACRP30; DE AltName: Full=Adipocyte, C1q and collagen domain-containing protein; DE AltName: Full=Adipose most abundant gene transcript 1 protein {ECO:0000303|PubMed:8619847}; DE Short=apM-1 {ECO:0000303|PubMed:10403784}; DE AltName: Full=Gelatin-binding protein; DE Flags: Precursor; GN Name=ADIPOQ; GN Synonyms=ACDC, ACRP30, APM1, GBP28 {ECO:0000303|PubMed:10095105, GN ECO:0000303|PubMed:8947845}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Adipose tissue; RX PubMed=8619847; DOI=10.1006/bbrc.1996.0587; RA Maeda K., Okubo K., Shimomura I., Funahashi T., Matsuzawa Y., Matsubara K.; RT "cDNA cloning and expression of a novel adipose specific collagen-like RT factor, apM1 (AdiPose Most abundant Gene transcript 1)."; RL Biochem. Biophys. Res. Commun. 221:286-289(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10095105; DOI=10.1016/s0378-1119(99)00041-4; RA Saito K., Tobe T., Minoshima S., Asakawa S., Sumiya J., Yoda M., Nakano Y., RA Shimizu N., Tomita M.; RT "Organization of the gene for gelatin-binding protein (GBP28)."; RL Gene 229:67-73(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10403784; DOI=10.1006/bbrc.1999.0865; RA Schaeffler A., Orso E., Palitzsch K.D., Buechler C., Drobnik W., Fuerst A., RA Schoelmerich J., Schmitz G.; RT "The human apM-1, an adipocyte-specific gene linked to the family of TNF's RT and to genes expressed in activated T cells, is mapped to chromosome RT 1q21.3-q23, a susceptibility locus identified for familial combined RT hyperlipidemia (FCH)."; RL Biochem. Biophys. Res. Commun. 260:416-425(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROTEIN SEQUENCE OF 19-33. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [6] RP PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8947845; DOI=10.1093/oxfordjournals.jbchem.a021483; RA Nakano Y., Tobe T., Choi-Miura N.H., Mazda T., Tomita M.; RT "Isolation and characterization of GBP28, a novel gelatin-binding protein RT purified from human plasma."; RL J. Biochem. 120:803-812(1996). RN [7] RP CHARACTERIZATION. RX PubMed=10961870; DOI=10.1182/blood.v96.5.1723; RA Yokota T., Oritani K., Takahashi I., Ishikawa J., Matsuyama A., Ouchi N., RA Kihara S., Funahashi T., Tenner A.J., Tomiyama Y., Matsuzawa Y.; RT "Adiponectin, a new member of the family of soluble defense collagens, RT negatively regulates the growth of myelomonocytic progenitors and the RT functions of macrophages."; RL Blood 96:1723-1732(2000). RN [8] RP FUNCTION. RX PubMed=10982546; DOI=10.1161/01.cir.102.11.1296; RA Ouchi N., Kihara S., Arita Y., Okamoto Y., Maeda K., Kuriyama H., Hotta K., RA Nishida M., Takahashi M., Muraguchi M., Ohmoto Y., Nakamura T., RA Yamashita S., Funahashi T., Matsuzawa Y.; RT "Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF- RT kappaB signaling through a cAMP-dependent pathway."; RL Circulation 102:1296-1301(2000). RN [9] RP SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF CYS-36, AND CHARACTERIZATION OF RP VARIANTS ARG-84; SER-90; CYS-112 AND THR-164. RX PubMed=12878598; DOI=10.1074/jbc.m300365200; RA Waki H., Yamauchi T., Kamon J., Ito Y., Uchida S., Kita S., Hara K., RA Hada Y., Vasseur F., Froguel P., Kimura S., Nagai R., Kadowaki T.; RT "Impaired multimerization of human adiponectin mutants associated with RT diabetes. Molecular structure and multimer formation of adiponectin."; RL J. Biol. Chem. 278:40352-40363(2003). RN [10] RP SUBUNIT, HYDROXYLATION AT PRO-44; PRO-47; PRO-53; LYS-65; LYS-68; PRO-71; RP PRO-76; LYS-77; PRO-91; PRO-95 AND LYS-101, GLYCOSYLATION AT LYS-65; RP LYS-68; LYS-77 AND LYS-101, DISULFIDE BOND, LACK OF HYDROXYLATION AT RP PRO-62; PRO-86 AND PRO-104, LACK OF GLYCOSYLATION AT ASN-230, MUTAGENESIS RP OF LYS-33; CYS-36; LYS-65; LYS-68; LYS-77 AND LYS-101, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=16497731; DOI=10.1210/me.2005-0390; RA Richards A.A., Stephens T., Charlton H.K., Jones A., Macdonald G.A., RA Prins J.B., Whitehead J.P.; RT "Adiponectin multimerization is dependent on conserved lysines in the RT collagenous domain: evidence for regulation of multimerization by RT alterations in posttranslational modifications."; RL Mol. Endocrinol. 20:1673-1687(2006). RN [11] RP GLYCOSYLATION AT THR-21 AND THR-22, SUBUNIT, IDENTIFICATION BY MASS RP SPECTROMETRY, AND MUTAGENESIS OF THR-20; THR-21 AND THR-22. RX PubMed=19855092; DOI=10.1210/me.2009-0133; RA Richards A.A., Colgrave M.L., Zhang J., Webster J., Simpson F., Preston E., RA Wilks D., Hoehn K.L., Stephenson M., Macdonald G.A., Prins J.B., RA Cooney G.J., Xu A., Whitehead J.P.; RT "Sialic acid modification of adiponectin is not required for RT multimerization or secretion but determines half-life in circulation."; RL Mol. Endocrinol. 24:229-239(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P., RA Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 104-244, AND SUBUNIT. RX PubMed=22449980; DOI=10.1016/j.febslet.2012.02.024; RA Min X., Lemon B., Tang J., Liu Q., Zhang R., Walker N., Li Y., Wang Z.; RT "Crystal structure of a single-chain trimer of human adiponectin globular RT domain."; RL FEBS Lett. 586:912-917(2012). RN [14] RP VARIANT ADPOD CYS-112, AND POLYMORPHISM. RX PubMed=10918532; DOI=10.1038/sj.ijo.0801244; RA Takahashi M., Arita Y., Yamagata K., Matsukawa Y., Okutomi K., Horie M., RA Shimomura I., Hotta K., Kuriyama H., Kihara S., Nakamura T., Yamashita S., RA Funahashi T., Matsuzawa Y.; RT "Genomic structure and mutations in adipose-specific gene, adiponectin."; RL Int. J. Obes. Relat. Metab. Disord. 24:861-868(2000). RN [15] RP VARIANTS ARG-84; MET-117; THR-164; SER-221 AND PRO-241, AND INVOLVEMENT IN RP ADPOD. RX PubMed=11812766; DOI=10.2337/diabetes.51.2.536; RA Hara K., Boutin P., Mori Y., Tobe K., Dina C., Yasuda K., Yamauchi T., RA Otabe S., Okada T., Eto K., Kadowaki H., Hagura R., Akanuma Y., Yazaki Y., RA Nagai R., Taniyama M., Matsubara K., Yoda M., Nakano Y., Kimura S., RA Tomita M., Kimura S., Ito C., Froguel P., Kadowaki T.; RT "Genetic variation in the gene encoding adiponectin is associated with an RT increased risk of type 2 diabetes in the Japanese population."; RL Diabetes 51:536-540(2002). RN [16] RP ERRATUM OF PUBMED:11812766. RA Hara K., Boutin P., Mori Y., Tobe K., Dina C., Yasuda K., Yamauchi T., RA Otabe S., Okada T., Eto K., Kadowaki H., Hagura R., Akanuma Y., Yazaki Y., RA Nagai R., Taniyama M., Matsubara K., Yoda M., Nakano Y., Kimura S., RA Tomita M., Kimura S., Ito C., Froguel P., Kadowaki T.; RL Diabetes 51:1294-1294(2002). RN [17] RP VARIANTS SER-221 AND PRO-241, POLYMORPHISM, AND VARIANTS ADPOD CYS-112 AND RP THR-164. RX PubMed=12086969; DOI=10.2337/diabetes.51.7.2325; RA Kondo H., Shimomura I., Matsukawa Y., Kumada M., Takahashi M., Matsuda M., RA Ouchi N., Kihara S., Kawamoto T., Sumitsuji S., Funahashi T., Matsuzawa Y.; RT "Association of adiponectin mutation with type 2 diabetes: a candidate gene RT for the insulin resistance syndrome."; RL Diabetes 51:2325-2328(2002). RN [18] RP VARIANTS ARG-84; SER-90 AND HIS-111. RX PubMed=12354786; DOI=10.1093/hmg/11.21.2607; RA Vasseur F., Helbecque N., Dina C., Lobbens S., Delannoy V., Gaget S., RA Boutin P., Vaxillaire M., Lepretre F., Dupont S., Hara K., Clement K., RA Bihain B., Kadowaki T., Froguel P.; RT "Single-nucleotide polymorphism haplotypes in the both proximal promoter RT and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone RT levels and contribute to the genetic risk for type 2 diabetes in French RT Caucasians."; RL Hum. Mol. Genet. 11:2607-2614(2002). RN [19] RP INVOLVEMENT IN ADPOD. RX PubMed=35869090; DOI=10.1038/s41525-022-00314-z; RA Simeone C.A., Wilkerson J.L., Poss A.M., Banks J.A., Varre J.V., RA Guevara J.L., Hernandez E.J., Gorsi B., Atkinson D.L., Turapov T., RA Frodsham S.G., Morales J.C.F., O'Neil K., Moore B., Yandell M., RA Summers S.A., Krolewski A.S., Holland W.L., Pezzolesi M.G.; RT "A dominant negative ADIPOQ mutation in a diabetic family with renal RT disease, hypoadiponectinemia, and hyperceramidemia."; RL NPJ Genom. Med. 7:43-43(2022). CC -!- FUNCTION: Important adipokine involved in the control of fat metabolism CC and insulin sensitivity upon binding to its receptors ADIPOR1 or CC ADIPOR2, with direct anti-diabetic effect. Also has anti-atherogenic CC and anti-inflammatory activities (By similarity). Stimulates AMPK CC phosphorylation and activation in the liver and the skeletal muscle, CC enhancing glucose utilization and fatty-acid combustion (By CC similarity). Antagonizes TNF by negatively regulating its expression in CC various tissues such as liver and macrophages, and also by CC counteracting its effects. Inhibits endothelial NF-kappa-B signaling CC through a cAMP-dependent pathway (PubMed:10982546). May play a role in CC cell growth, angiogenesis and tissue remodeling by binding and CC sequestering various growth factors with distinct binding affinities, CC depending on the type of complex, LMW, MMW or HMW (By similarity). CC {ECO:0000250|UniProtKB:Q60994, ECO:0000269|PubMed:10982546}. CC -!- ACTIVITY REGULATION: Polymerization and secretion of adiponectin is CC inhibited by succination of cysteine residues by the Krebs cycle CC intermediate fumarate, which leads to S-(2-succinyl)cysteine residues. CC {ECO:0000250|UniProtKB:Q60994}. CC -!- SUBUNIT: Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The CC trimers (low molecular weight complexes / LMW) are assembled via non- CC covalent interactions of the collagen-like domains in a triple helix CC and hydrophobic interactions within the globular C1q domain. Several CC trimers can associate to form disulfide-linked hexamers (middle CC molecular weight complexes / MMW) and larger complexes (higher CC molecular weight / HMW). The HMW-complex assembly is also modulated by CC the degree of lysine hydroxylation and glycosylation. LMW, MMW and HMW CC complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW CC complex binds to FGF2. Interacts with CTRP9 via the C1q domain CC (heterotrimeric complex). {ECO:0000250|UniProtKB:Q60994}. CC -!- INTERACTION: CC Q15848; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-10827839, EBI-19125216; CC Q15848; Q13520: AQP6; NbExp=3; IntAct=EBI-10827839, EBI-13059134; CC Q15848; P07307-3: ASGR2; NbExp=3; IntAct=EBI-10827839, EBI-12808270; CC Q15848; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-10827839, EBI-747430; CC Q15848; Q13323: BIK; NbExp=3; IntAct=EBI-10827839, EBI-700794; CC Q15848; O60238: BNIP3L; NbExp=3; IntAct=EBI-10827839, EBI-849893; CC Q15848; Q8WZ55: BSND; NbExp=3; IntAct=EBI-10827839, EBI-7996695; CC Q15848; Q6UXG8-3: BTNL9; NbExp=3; IntAct=EBI-10827839, EBI-17953245; CC Q15848; P49069: CAMLG; NbExp=3; IntAct=EBI-10827839, EBI-1748958; CC Q15848; Q8WV48: CCDC107; NbExp=3; IntAct=EBI-10827839, EBI-947033; CC Q15848; Q8TD46-4: CD200R1; NbExp=3; IntAct=EBI-10827839, EBI-12824513; CC Q15848; P11912: CD79A; NbExp=3; IntAct=EBI-10827839, EBI-7797864; CC Q15848; O95484: CLDN9; NbExp=3; IntAct=EBI-10827839, EBI-18341636; CC Q15848; Q8IUN9: CLEC10A; NbExp=3; IntAct=EBI-10827839, EBI-2873246; CC Q15848; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-10827839, EBI-11749983; CC Q15848; P34972: CNR2; NbExp=3; IntAct=EBI-10827839, EBI-2835940; CC Q15848; O75208: COQ9; NbExp=3; IntAct=EBI-10827839, EBI-724524; CC Q15848; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-10827839, EBI-18013275; CC Q15848; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-10827839, EBI-6942903; CC Q15848; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-10827839, EBI-2680384; CC Q15848; P30040: ERP29; NbExp=3; IntAct=EBI-10827839, EBI-946830; CC Q15848; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-10827839, EBI-18304435; CC Q15848; P49327: FASN; NbExp=3; IntAct=EBI-10827839, EBI-356658; CC Q15848; P12314: FCGR1A; NbExp=3; IntAct=EBI-10827839, EBI-2869867; CC Q15848; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-10827839, EBI-3918971; CC Q15848; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-10827839, EBI-12142257; CC Q15848; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-10827839, EBI-13345167; CC Q15848; O15529: GPR42; NbExp=3; IntAct=EBI-10827839, EBI-18076404; CC Q15848; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-10827839, EBI-1052304; CC Q15848; P42858: HTT; NbExp=9; IntAct=EBI-10827839, EBI-466029; CC Q15848; P38484: IFNGR2; NbExp=3; IntAct=EBI-10827839, EBI-3905457; CC Q15848; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-10827839, EBI-749265; CC Q15848; O95279: KCNK5; NbExp=3; IntAct=EBI-10827839, EBI-3934936; CC Q15848; P23276: KEL; NbExp=3; IntAct=EBI-10827839, EBI-746662; CC Q15848; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-10827839, EBI-11956541; CC Q15848; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-10827839, EBI-373355; CC Q15848; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-10827839, EBI-2858252; CC Q15848; Q6IN84: MRM1; NbExp=3; IntAct=EBI-10827839, EBI-5454865; CC Q15848; Q96HJ5: MS4A3; NbExp=3; IntAct=EBI-10827839, EBI-12806656; CC Q15848; P15941-11: MUC1; NbExp=3; IntAct=EBI-10827839, EBI-17263240; CC Q15848; O14524-2: NEMP1; NbExp=3; IntAct=EBI-10827839, EBI-10969203; CC Q15848; O00623: PEX12; NbExp=3; IntAct=EBI-10827839, EBI-594836; CC Q15848; Q8NFJ6: PROKR2; NbExp=3; IntAct=EBI-10827839, EBI-12902928; CC Q15848; P15151: PVR; NbExp=3; IntAct=EBI-10827839, EBI-3919694; CC Q15848; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-10827839, EBI-17247926; CC Q15848; O43765: SGTA; NbExp=7; IntAct=EBI-10827839, EBI-347996; CC Q15848; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-10827839, EBI-744081; CC Q15848; Q96PQ1: SIGLEC12; NbExp=3; IntAct=EBI-10827839, EBI-17640454; CC Q15848; A1A5C7-2: SLC22A23; NbExp=3; IntAct=EBI-10827839, EBI-12081840; CC Q15848; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-10827839, EBI-17295964; CC Q15848; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-10827839, EBI-13389236; CC Q15848; Q96A49: SYAP1; NbExp=3; IntAct=EBI-10827839, EBI-10770179; CC Q15848; Q8N205-2: SYNE4; NbExp=6; IntAct=EBI-10827839, EBI-12099160; CC Q15848; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-10827839, EBI-11724423; CC Q15848; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-10827839, EBI-10982110; CC Q15848; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-10827839, EBI-11722971; CC Q15848; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-10827839, EBI-12345267; CC Q15848; O43557: TNFSF14; NbExp=3; IntAct=EBI-10827839, EBI-524131; CC Q15848; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-10827839, EBI-17716262; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8947845}. CC -!- TISSUE SPECIFICITY: Synthesized exclusively by adipocytes and secreted CC into plasma. {ECO:0000269|PubMed:8947845}. CC -!- DOMAIN: The C1q domain is commonly called the globular domain. CC -!- PTM: HMW complexes are more extensively glycosylated than smaller CC oligomers. Hydroxylation and glycosylation of the lysine residues CC within the collagen-like domain of adiponectin seem to be critically CC involved in regulating the formation and/or secretion of HMW complexes CC and consequently contribute to the insulin-sensitizing activity of CC adiponectin in hepatocytes. {ECO:0000250|UniProtKB:Q60994}. CC -!- PTM: O-glycosylated. Not N-glycosylated. O-linked glycans on CC hydroxylysines consist of Glc-Gal disaccharides bound to the oxygen CC atom of post-translationally added hydroxyl groups. Sialylated to CC varying degrees depending on tissue. Thr-22 appears to be the major CC site of sialylation. Higher sialylation found in SGBS adipocytes than CC in HEK fibroblasts. Sialylation is not required neither for CC heterodimerization nor for secretion. Not sialylated on the CC glycosylated hydroxylysines. Desialylated forms are rapidly cleared CC from the circulation. {ECO:0000269|PubMed:16497731, CC ECO:0000269|PubMed:19855092}. CC -!- PTM: Succination of Cys-36 by the Krebs cycle intermediate fumarate, CC which leads to S-(2-succinyl)cysteine residues, inhibits polymerization CC and secretion of adiponectin. Adiponectin is a major target for CC succination in both adipocytes and adipose tissue of diabetic mammals. CC It was proposed that succination of proteins is a biomarker of CC mitochondrial stress and accumulation of Krebs cycle intermediates in CC adipose tissue in diabetes and that succination of adiponectin may CC contribute to the decrease in plasma adiponectin in diabetes. CC {ECO:0000250|UniProtKB:Q60994}. CC -!- POLYMORPHISM: Genetic variations in ADIPOQ influence the variance in CC adiponectin serum levels and define the adiponectin serum levels CC quantitative trait locus 1 (ADIPQTL1) [MIM:612556]. CC {ECO:0000269|PubMed:10918532, ECO:0000269|PubMed:12086969}. CC -!- DISEASE: Adiponectin deficiency (ADPOD) [MIM:612556]: An autosomal CC dominant condition characterized by very low concentrations of plasma CC adiponectin. Levels of adiponectin are decreased in obesity and may CC contribute to a chronic state of inflammation that leads to insulin CC resistance, type 2 diabetes, coronary artery disease, myocardial CC infarction, non-alcoholic steatohepatitis, and kidney disease. CC {ECO:0000269|PubMed:10918532, ECO:0000269|PubMed:11812766, CC ECO:0000269|PubMed:12086969}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Adiponectin might be used in the treatment of diabetes CC type 2 and insulin resistance. CC -!- MISCELLANEOUS: Variants Arg-84 and Ser-90 show impaired formation of CC HMW complexes whereas variants Cys-112 and Thr-164 show impaired CC secretion of adiponectin in any form. CC -!- MISCELLANEOUS: HMW-complex blood contents are higher in females than in CC males, are increased in males by castration and decreased again upon CC subsequent testosterone treatment, which blocks HMW-complex secretion CC (By similarity). In type 2 diabetic patients, both the ratios of HMW to CC total adiponectin and the degree of adiponectin glycosylation are CC significantly decreased as compared with healthy controls. CC {ECO:0000250}. CC -!- CAUTION: The expected hydroxylation of Lys-33 was not identified, CC probably due to poor representation of the N-terminal peptide in mass CC fingerprinting. {ECO:0000269|PubMed:16497731}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Adiponectin entry; CC URL="https://en.wikipedia.org/wiki/Adiponectin"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D45371; BAA08227.1; -; mRNA. DR EMBL; AB012165; BAA86716.1; -; Genomic_DNA. DR EMBL; AJ131460; CAB52413.1; -; Genomic_DNA. DR EMBL; AJ131461; CAB52413.1; JOINED; Genomic_DNA. DR EMBL; BC054496; AAH54496.1; -; mRNA. DR EMBL; BC096308; AAH96308.1; -; mRNA. DR EMBL; BC096309; AAH96309.1; -; mRNA. DR EMBL; BC096310; AAH96310.1; -; mRNA. DR EMBL; BC096311; AAH96311.1; -; mRNA. DR CCDS; CCDS3284.1; -. DR PIR; JC4708; JC4708. DR RefSeq; NP_001171271.1; NM_001177800.2. DR RefSeq; NP_004788.1; NM_004797.4. DR PDB; 4DOU; X-ray; 2.00 A; A=104-244. DR PDB; 6U66; X-ray; 0.99 A; A/B/C=107-244. DR PDB; 6U6N; X-ray; 2.15 A; C=108-244. DR AlphaFoldDB; Q15848; -. DR SMR; Q15848; -. DR BioGRID; 114771; 104. DR CORUM; Q15848; -. DR FunCoup; Q15848; 249. DR IntAct; Q15848; 129. DR NDEx; IQUERY-CP-ADIPOQ; 12 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000389814; -. DR TCDB; 8.A.94.1.1; the adiponectin (adiponectin) family. DR GlyCosmos; Q15848; 6 sites, 2 glycans. DR GlyGen; Q15848; 7 sites, 2 O-linked glycans (2 sites). DR iPTMnet; Q15848; -. DR PhosphoSitePlus; Q15848; -. DR BioMuta; ADIPOQ; -. DR DMDM; 2493789; -. DR CPTAC; non-CPTAC-1057; -. DR MassIVE; Q15848; -. DR PaxDb; 9606-ENSP00000389814; -. DR PeptideAtlas; Q15848; -. DR ProteomicsDB; 60791; -. DR ABCD; Q15848; 5 sequenced antibodies. DR Antibodypedia; 19310; 1922 antibodies from 51 providers. DR DNASU; 9370; -. DR Ensembl; ENST00000320741.7; ENSP00000320709.2; ENSG00000181092.11. DR Ensembl; ENST00000444204.2; ENSP00000389814.2; ENSG00000181092.11. DR Ensembl; ENST00000881747.1; ENSP00000551806.1; ENSG00000181092.11. DR Ensembl; ENST00000956685.1; ENSP00000626744.1; ENSG00000181092.11. DR GeneID; 9370; -. DR KEGG; hsa:9370; -. DR MANE-Select; ENST00000320741.7; ENSP00000320709.2; NM_004797.4; NP_004788.1. DR UCSC; uc003fra.4; human. DR AGR; HGNC:13633; -. DR ClinPGx; PA134933118; -. DR CTD; 9370; -. DR DisGeNET; 9370; -. DR GeneCards; ADIPOQ; -. DR HGNC; HGNC:13633; ADIPOQ. DR HPA; ENSG00000181092; Group enriched (adipose tissue, breast). DR MalaCards; ADIPOQ; -. DR MIM; 605441; gene. DR MIM; 612556; phenotype. DR OpenTargets; ENSG00000181092; -. DR VEuPathDB; HostDB:ENSG00000181092; -. DR eggNOG; ENOG502QRY3; Eukaryota. DR GeneTree; ENSGT00940000159828; -. DR HOGENOM; CLU_001074_0_2_1; -. DR InParanoid; Q15848; -. DR OMA; GTYYFAY; -. DR OrthoDB; 8044756at2759; -. DR PAN-GO; Q15848; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q15848; -. DR PathwayCommons; Q15848; -. DR Reactome; R-HSA-163680; AMPK inhibits chREBP transcriptional activation activity. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR SignaLink; Q15848; -. DR SIGNOR; Q15848; -. DR Agora; ENSG00000181092; -. DR BioGRID-ORCS; 9370; 7 hits in 1146 CRISPR screens. DR EvolutionaryTrace; Q15848; -. DR GeneWiki; Adiponectin; -. DR GenomeRNAi; 9370; -. DR Pharos; Q15848; Tbio. DR PRO; PR:Q15848; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q15848; protein. DR Bgee; ENSG00000181092; Expressed in synovial joint and 114 other cell types or tissues. DR ExpressionAtlas; Q15848; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0140144; C:non-collagenous component of basement membrane; TAS:GO_Central. DR GO; GO:0005125; F:cytokine activity; NAS:BHF-UCL. DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl. DR GO; GO:0033691; F:sialic acid binding; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB. DR GO; GO:0033211; P:adiponectin-activated signaling pathway; IDA:ARUK-UCL. DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:UniProtKB. DR GO; GO:0038002; P:endocrine signaling; IEA:Ensembl. DR GO; GO:0006635; P:fatty acid beta-oxidation; ISS:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; ISS:UniProtKB. DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IDA:BHF-UCL. DR GO; GO:0045776; P:negative regulation of blood pressure; IDA:UniProtKB. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IDA:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB. DR GO; GO:0060621; P:negative regulation of cholesterol import; IDA:BHF-UCL. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:BHF-UCL. DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:BHF-UCL. DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:BHF-UCL. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; IDA:BHF-UCL. DR GO; GO:0045650; P:negative regulation of macrophage differentiation; IDA:BHF-UCL. DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB. DR GO; GO:2000590; P:negative regulation of metanephric mesenchymal cell migration; ISS:UniProtKB. DR GO; GO:0050765; P:negative regulation of phagocytosis; IDA:BHF-UCL. DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:2000584; P:negative regulation of platelet-derived growth factor receptor-alpha signaling pathway; ISS:UniProtKB. DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; IDA:BHF-UCL. DR GO; GO:0050805; P:negative regulation of synaptic transmission; IDA:UniProtKB. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL. DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; IDA:UniProtKB. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0141163; P:positive regulation of cAMP/PKA signal transduction; IDA:BHF-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0046326; P:positive regulation of D-glucose import across plasma membrane; ISS:BHF-UCL. DR GO; GO:0045923; P:positive regulation of fatty acid metabolic process; ISS:BHF-UCL. DR GO; GO:2000467; P:positive regulation of glycogen (starch) synthase activity; ISS:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB. DR GO; GO:0050996; P:positive regulation of lipid catabolic process; ISS:UniProt. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IDA:UniProtKB. DR GO; GO:0033034; P:positive regulation of myeloid cell apoptotic process; IDA:BHF-UCL. DR GO; GO:2000534; P:positive regulation of renal albumin absorption; IDA:UniProtKB. DR GO; GO:0009967; P:positive regulation of signal transduction; ISS:BHF-UCL. DR GO; GO:0010906; P:regulation of glucose metabolic process; IDA:UniProtKB. DR GO; GO:0009749; P:response to glucose; ISS:BHF-UCL. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR FunFam; 2.60.120.40:FF:000001; Complement C1q B chain; 1. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR001073; C1q_dom. DR InterPro; IPR008160; Collagen. DR InterPro; IPR050392; Collagen/C1q_domain. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR15427:SF20; ADIPONECTIN; 1. DR PANTHER; PTHR15427; EMILIN ELASTIN MICROFIBRIL INTERFACE-LOCATED PROTEIN ELASTIN MICROFIBRIL INTERFACER; 1. DR Pfam; PF00386; C1q; 1. DR Pfam; PF01391; Collagen; 1. DR PRINTS; PR00007; COMPLEMNTC1Q. DR SMART; SM00110; C1Q; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS50871; C1Q; 1. DR PDBsum; 4DOU; -. DR PDBsum; 6U66; -. DR PDBsum; 6U6N; -. PE 1: Evidence at protein level; KW 3D-structure; Collagen; Diabetes mellitus; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Hormone; Hydroxylation; KW Obesity; Pharmaceutical; Proteomics identification; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:15340161, FT ECO:0000269|PubMed:8947845" FT CHAIN 19..244 FT /note="Adiponectin" FT /id="PRO_0000003543" FT DOMAIN 42..107 FT /note="Collagen-like" FT DOMAIN 108..244 FT /note="C1q" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368" FT REGION 40..101 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 55..70 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 62 FT /note="Not hydroxylated" FT /evidence="ECO:0000269|PubMed:16497731" FT SITE 86 FT /note="Not hydroxylated" FT /evidence="ECO:0000269|PubMed:16497731" FT SITE 104 FT /note="Not hydroxylated" FT /evidence="ECO:0000269|PubMed:16497731" FT SITE 230 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 33 FT /note="5-hydroxylysine" FT /evidence="ECO:0000250|UniProtKB:Q3Y5Z3" FT MOD_RES 36 FT /note="S-(2-succinyl)cysteine" FT /evidence="ECO:0000250|UniProtKB:Q60994" FT MOD_RES 44 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 47 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 53 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 65 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 68 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 71 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 76 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 77 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 91 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 95 FT /note="4-hydroxyproline; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT MOD_RES 101 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:16497731" FT CARBOHYD 21 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:19855092" FT CARBOHYD 22 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:19855092" FT CARBOHYD 65 FT /note="O-linked (Gal...) hydroxylysine; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT CARBOHYD 68 FT /note="O-linked (Gal...) hydroxylysine; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT CARBOHYD 77 FT /note="O-linked (Gal...) hydroxylysine; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT CARBOHYD 101 FT /note="O-linked (Gal...) hydroxylysine; partial" FT /evidence="ECO:0000269|PubMed:16497731" FT DISULFID 36 FT /note="Interchain; in form MMW and form HMW" FT /evidence="ECO:0000269|PubMed:12878598, FT ECO:0000269|PubMed:16497731" FT VARIANT 84 FT /note="G -> R (does not form high molecular weight FT multimers; dbSNP:rs199646033)" FT /evidence="ECO:0000269|PubMed:11812766, FT ECO:0000269|PubMed:12354786, ECO:0000269|PubMed:12878598" FT /id="VAR_013273" FT VARIANT 90 FT /note="G -> S (does not form high molecular weight FT multimers; dbSNP:rs62625753)" FT /evidence="ECO:0000269|PubMed:12354786, FT ECO:0000269|PubMed:12878598" FT /id="VAR_027395" FT VARIANT 111 FT /note="Y -> H (in dbSNP:rs17366743)" FT /evidence="ECO:0000269|PubMed:12354786" FT /id="VAR_027396" FT VARIANT 112 FT /note="R -> C (in ADPOD; does not assemble into trimers FT resulting in impaired secretion from the cell; FT dbSNP:rs121917815)" FT /evidence="ECO:0000269|PubMed:10918532, FT ECO:0000269|PubMed:12086969, ECO:0000269|PubMed:12878598" FT /id="VAR_013274" FT VARIANT 117 FT /note="V -> M (in dbSNP:rs747223144)" FT /evidence="ECO:0000269|PubMed:11812766" FT /id="VAR_013275" FT VARIANT 164 FT /note="I -> T (in ADPOD; does not assemble into trimers FT resulting in impaired secretion from the cell; FT dbSNP:rs185847354)" FT /evidence="ECO:0000269|PubMed:11812766, FT ECO:0000269|PubMed:12086969, ECO:0000269|PubMed:12878598" FT /id="VAR_013276" FT VARIANT 221 FT /note="R -> S (in dbSNP:rs138773406)" FT /evidence="ECO:0000269|PubMed:11812766, FT ECO:0000269|PubMed:12086969" FT /id="VAR_013277" FT VARIANT 241 FT /note="H -> P (in dbSNP:rs141205818)" FT /evidence="ECO:0000269|PubMed:11812766, FT ECO:0000269|PubMed:12086969" FT /id="VAR_013278" FT MUTAGEN 20 FT /note="T->A: No change in sialylated isoforms." FT /evidence="ECO:0000269|PubMed:19855092" FT MUTAGEN 21 FT /note="T->A: Some loss of sialylated isoforms." FT /evidence="ECO:0000269|PubMed:19855092" FT MUTAGEN 22 FT /note="T->A: Abolishes sialylated isoforms." FT /evidence="ECO:0000269|PubMed:19855092" FT MUTAGEN 33 FT /note="K->R: No effect on formation of HMW multimers." FT /evidence="ECO:0000269|PubMed:16497731" FT MUTAGEN 36 FT /note="C->S: Impaired formation of MMW and HMW multimers." FT /evidence="ECO:0000269|PubMed:12878598, FT ECO:0000269|PubMed:16497731" FT MUTAGEN 65 FT /note="K->R: Impaired formation of HMW multimers; when FT associated with R-68." FT /evidence="ECO:0000269|PubMed:16497731" FT MUTAGEN 68 FT /note="K->R: Impaired formation of HMW multimers; when FT associated with R-65." FT /evidence="ECO:0000269|PubMed:16497731" FT MUTAGEN 77 FT /note="K->R: Impaired formation of HMW multimers; when FT associated with R-101." FT /evidence="ECO:0000269|PubMed:16497731" FT MUTAGEN 101 FT /note="K->R: Impaired formation of HMW multimers; when FT associated with R-77." FT /evidence="ECO:0000269|PubMed:16497731" FT STRAND 114..118 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:6U6N" FT STRAND 134..137 FT /evidence="ECO:0007829|PDB:6U66" FT TURN 145..148 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 156..177 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 180..187 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 195..205 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 210..216 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:6U66" FT STRAND 233..241 FT /evidence="ECO:0007829|PDB:6U66" SQ SEQUENCE 244 AA; 26414 MW; 64D8C6C1204B1018 CRC64; MLLLGAVLLL LALPGHDQET TTQGPGVLLP LPKGACTGWM AGIPGHPGHN GAPGRDGRDG TPGEKGEKGD PGLIGPKGDI GETGVPGAEG PRGFPGIQGR KGEPGEGAYV YRSAFSVGLE TYVTIPNMPI RFTKIFYNQQ NHYDGSTGKF HCNIPGLYYF AYHITVYMKD VKVSLFKKDK AMLFTYDQYQ ENNVDQASGS VLLHLEVGDQ VWLQVYGEGE RNGLYADNDN DSTFTGFLLY HDTN //