ADIPO_BOVIN
ID ADIPO_BOVIN Reviewed; 240 AA.
AC Q3Y5Z3; A5D7A8; Q95MQ4;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
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;
DE Short=apM-1;
DE Flags: Precursor;
GN Name=ADIPOQ; Synonyms=ACRP30, APM1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-26; 194-197; 203-208 AND
RP 221-228, GLYCOSYLATION, AND STRUCTURE OF CARBOHYDRATES.
RC TISSUE=Adipose tissue;
RX PubMed=11382781; DOI=10.1074/jbc.m104148200;
RA Sato C., Yasukawa Z., Honda N., Matsuda T., Kitajima K.;
RT "Identification and adipocyte differentiation-dependent expression of the
RT unique disialic acid residue in an adipose tissue-specific glycoprotein,
RT adipo Q.";
RL J. Biol. Chem. 276:28849-28856(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Morsci N.S., Schnabel R.D., Taylor J.F.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 18-26, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP HYDROXYLATION AT LYS-28; PRO-39; PRO-42; PRO-48; LYS-60; LYS-63; LYS-72;
RP PRO-86 AND LYS-96, GLYCOSYLATION AT LYS-28; LYS-60; LYS-63 AND LYS-96, LACK
RP OF HYDROXYLATION AT PRO-57; PRO-66; PRO-71; PRO-90 AND PRO-99, LACK OF
RP GLYCOSYLATION AT ASN-225, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15378692; DOI=10.1002/pmic.200400826;
RA Wang Y., Lu G., Wong W.P.S., Vliegenthart J.F.G., Gerwig G.J., Lam K.S.L.,
RA Cooper G.J.S., Xu A.;
RT "Proteomic and functional characterization of endogenous adiponectin
RT purified from fetal bovine serum.";
RL Proteomics 4:3933-3942(2004).
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 (By
CC similarity). {ECO:0000250}.
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 Q3Y5Z3; Q3Y5Z3: ADIPOQ; NbExp=2; IntAct=EBI-7264459, EBI-7264459;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:15378692}.
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. O-linked glycans on hydroxylysine residues consist
CC of Glc-Gal disaccharides bound to the oxygen atom of post-
CC translationally added hydroxyl groups (By similarity). O-linked
CC glycosylations elsewhere disialylated with the structure
CC Neu5Acalpha2->8Neu5Acalpha2->3Gal. Sialylated by alpha 2,8-
CC sialyltransferase III. Desialylated forms are rapidly cleared from the
CC circulation. Not N-glycosylated. {ECO:0000250,
CC ECO:0000269|PubMed:11382781, ECO:0000269|PubMed:15378692}.
CC -!- PTM: Succination of Cys-31 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 -!- 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 {ECO:0000250}.
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DR EMBL; AF269230; AAK58902.1; -; mRNA.
DR EMBL; DQ156120; AAZ81421.1; -; Genomic_DNA.
DR EMBL; BC140488; AAI40489.1; -; mRNA.
DR RefSeq; NP_777167.1; NM_174742.2.
DR AlphaFoldDB; Q3Y5Z3; -.
DR SMR; Q3Y5Z3; -.
DR MINT; Q3Y5Z3; -.
DR STRING; 9913.ENSBTAP00000026395; -.
DR PaxDb; Q3Y5Z3; -.
DR PeptideAtlas; Q3Y5Z3; -.
DR PRIDE; Q3Y5Z3; -.
DR GeneID; 282865; -.
DR CTD; 9370; -.
DR eggNOG; ENOG502QRY3; Eukaryota.
DR HOGENOM; CLU_001074_0_2_1; -.
DR InParanoid; Q3Y5Z3; -.
DR OrthoDB; 1258047at2759; -.
DR TreeFam; TF329591; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0071944; C:cell periphery; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:UniProtKB.
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: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; ISS:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0090317; P:negative regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; ISS:UniProtKB.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISS: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; ISS:UniProtKB.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISS:UniProtKB.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0045923; P:positive regulation of fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0110113; P:positive regulation of lipid transporter activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0033034; P:positive regulation of myeloid cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2000534; P:positive regulation of renal albumin absorption; ISS:UniProtKB.
DR GO; GO:0009967; P:positive regulation of signal transduction; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISS:UniProtKB.
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 Collagen; Direct protein sequencing; Disulfide bond; Glycoprotein; Hormone;
KW Hydroxylation; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:11382781,
FT ECO:0000269|PubMed:15378692"
FT CHAIN 18..240
FT /note="Adiponectin"
FT /id="PRO_0000236269"
FT DOMAIN 43..102
FT /note="Collagen-like"
FT DOMAIN 103..240
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 29..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..67
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 57
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT SITE 66
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT SITE 71
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT SITE 90
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT SITE 99
FT /note="Not hydroxylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT SITE 225
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 28
FT /note="5-hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 31
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q60994"
FT MOD_RES 39
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 42
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 48
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 60
FT /note="5-hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 63
FT /note="5-hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 72
FT /note="5-hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 86
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:15378692"
FT MOD_RES 96
FT /note="5-hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT CARBOHYD 28
FT /note="O-linked (Gal...) hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT CARBOHYD 60
FT /note="O-linked (Gal...) hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT CARBOHYD 63
FT /note="O-linked (Gal...) hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT CARBOHYD 72
FT /note="O-linked (Gal...) hydroxylysine"
FT /evidence="ECO:0000269|PubMed:11382781"
FT CARBOHYD 96
FT /note="O-linked (Gal...) hydroxylysine"
FT /evidence="ECO:0000269|PubMed:15378692"
FT DISULFID 31
FT /note="Interchain; in form MMW and form HMW"
FT /evidence="ECO:0000250"
FT CONFLICT 66
FT /note="P -> A (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="V -> L (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="D -> E (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 77..83
FT /note="ETGITGI -> DVGMTGA (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="S -> A (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 116..117
FT /note="RQ -> TR (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="T -> S (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="L -> Y (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="L -> M (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 171..173
FT /note="YKN -> FKK (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="L -> V (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="H -> Y (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 184..186
FT /note="FQD -> YQE (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="Y -> H (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="K -> V (in Ref. 1; AAK58902)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 240 AA; 26133 MW; 409122E49F3AF253 CRC64;
MLLQGALLLL LALPSHGEDN MEDPPLPKGA CAGWMAGIPG HPGHNGTPGR DGRDGTPGEK
GEKGDPGLVG PKGDTGETGI TGIEGPRGFP GTPGRKGEPG ESAYVYRSAF SVGLERQVTV
PNVPIRFTKI FYNQQNHYDG TTGKFLCNIP GLYYFSYHIT VYLKDVKVSL YKNDKALLFT
HDQFQDKNVD QASGSVLLYL EKGDQVWLQV YEGENHNGVY ADNVNDSTFT GFLLYHNIVE
