ADIPO_HUMAN
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 03-AUG-2022, entry version 214.
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;
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 CHARACTERIZATION.
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 FUNCTION.
RX PubMed=11479627; DOI=10.1038/90984;
RA Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y.,
RA Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y.,
RA Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M.,
RA Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P.,
RA Kadowaki T.;
RT "The fat-derived hormone adiponectin reverses insulin resistance associated
RT with both lipoatrophy and obesity.";
RL Nat. Med. 7:941-946(2001).
RN [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
RP VARIANT ADPND CYS-112.
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 [16]
RP VARIANTS ARG-84; MET-117; THR-164; SER-221 AND PRO-241.
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 [17]
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 [18]
RP VARIANTS CYS-112; THR-164; SER-221 AND PRO-241, AND ASSOCIATION WITH LOW
RP PLASMA ADIPONECTIN CONCENTRATION AND DIABETES MELLITUS TYPE 2.
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 [19]
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).
CC -!- FUNCTION: Important adipokine involved in the control of fat metabolism
CC and insulin sensitivity, with direct anti-diabetic, anti-atherogenic
CC and anti-inflammatory activities. Stimulates AMPK phosphorylation and
CC activation in the liver and the skeletal muscle, enhancing glucose
CC utilization and fatty-acid combustion. Antagonizes TNF-alpha by
CC negatively regulating its expression in various tissues such as liver
CC and macrophages, and also by counteracting its effects. Inhibits
CC endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May
CC play a role in cell growth, angiogenesis and tissue remodeling by
CC binding and sequestering various growth factors with distinct binding
CC affinities, depending on the type of complex, LMW, MMW or HMW.
CC {ECO:0000269|PubMed:11479627}.
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 -!- DISEASE: Adiponectin deficiency (ADPND) [MIM:612556]: A condition that
CC results in very low concentrations of plasma adiponectin.
CC {ECO:0000269|PubMed:10918532}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC 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";
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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_001177800.1.
DR RefSeq; NP_004788.1; NM_004797.3.
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 PDBsum; 4DOU; -.
DR PDBsum; 6U66; -.
DR PDBsum; 6U6N; -.
DR AlphaFoldDB; Q15848; -.
DR SMR; Q15848; -.
DR BioGRID; 114771; 102.
DR CORUM; Q15848; -.
DR IntAct; Q15848; 61.
DR STRING; 9606.ENSP00000389814; -.
DR TCDB; 8.A.94.1.1; the adiponectin (adiponectin) family.
DR GlyGen; Q15848; 6 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 EPD; Q15848; -.
DR jPOST; Q15848; -.
DR MassIVE; Q15848; -.
DR PaxDb; Q15848; -.
DR PeptideAtlas; Q15848; -.
DR PRIDE; Q15848; -.
DR ProteomicsDB; 60791; -.
DR ABCD; Q15848; 5 sequenced antibodies.
DR Antibodypedia; 19310; 1898 antibodies from 49 providers.
DR DNASU; 9370; -.
DR Ensembl; ENST00000320741.7; ENSP00000320709.2; ENSG00000181092.10.
DR Ensembl; ENST00000444204.2; ENSP00000389814.2; ENSG00000181092.10.
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 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; 125853; phenotype.
DR MIM; 605441; gene.
DR MIM; 612556; phenotype.
DR neXtProt; NX_Q15848; -.
DR OpenTargets; ENSG00000181092; -.
DR PharmGKB; PA134933118; -.
DR VEuPathDB; HostDB:ENSG00000181092; -.
DR eggNOG; ENOG502QRY3; Eukaryota.
DR GeneTree; ENSGT00940000159828; -.
DR HOGENOM; CLU_001074_0_2_1; -.
DR InParanoid; Q15848; -.
DR OMA; DSTFMGF; -.
DR OrthoDB; 1258047at2759; -.
DR PhylomeDB; Q15848; -.
DR TreeFam; TF329591; -.
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 SignaLink; Q15848; -.
DR SIGNOR; Q15848; -.
DR BioGRID-ORCS; 9370; 6 hits in 1070 CRISPR screens.
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 tissues.
DR ExpressionAtlas; Q15848; baseline and differential.
DR Genevisible; Q15848; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; NAS:BHF-UCL.
DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; TAS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0033691; F:sialic acid binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IEA:Ensembl.
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:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0070994; P:detection of oxidative stress; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
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:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IDA:UniProtKB.
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:0046888; P:negative regulation of hormone secretion; IEA:Ensembl.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0090317; P:negative regulation of intracellular protein transport; IDA:UniProtKB.
DR GO; GO:1905598; P:negative regulation of low-density lipoprotein receptor activity; IDA:BHF-UCL.
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:0031953; P:negative regulation of protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:1900121; P:negative regulation of receptor binding; IDA:UniProtKB.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IDA: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:0045923; P:positive regulation of fatty acid metabolic process; ISS:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:2000467; P:positive regulation of glycogen (starch) synthase activity; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0110113; P:positive regulation of lipid transporter activity; IDA:ARUK-UCL.
DR GO; GO:2000478; P:positive regulation of metanephric podocyte development; ISS:UniProtKB.
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:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IDA:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
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:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IDA:UniProtKB.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; ISS:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0070543; P:response to linoleic acid; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009744; P:response to sucrose; IEA:Ensembl.
DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR028572; Adiponectin.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR PANTHER; PTHR15427:SF20; PTHR15427:SF20; 1.
DR Pfam; PF00386; C1q; 1.
DR Pfam; PF01391; Collagen; 1.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
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; Reference proteome; 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 58..72
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 ADPND; 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 (associated with low plasma adiponectin
FT concentration and diabetes mellitus type 2; does not
FT assemble into trimers resulting in impaired secretion from
FT the cell; 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..147
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
