Reviewed, UniProtKB/Swiss-Prot Q60994 (ADIPO_MOUSE)

Names and origin

Protein names

Recommended name:
    Adiponectin
Alternative name(s):
    Adipocyte, C1q and collagen domain-containing protein
    30 kDa adipocyte complement-related protein
    Adipocyte complement-related 30 kDa protein
      Short name=ACRP30
    Adipocyte-specific protein AdipoQ

Gene names

Name:	Adipoq
Synonyms:	Acdc, Acrp30, Apm1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	247 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Subunit structure	Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly may rely aditionnally 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. Ref.9 Ref.10 Ref.11
Subcellular location	Secreted.
Tissue specificity	Synthesized exclusively by adipocytes and secreted into plasma.
Induction	During hormone-induced adipose differentiation and activated by insulin.
Post-translational modification	HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagene-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes. Ref.5 O-linked glycans consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Not N-glycosylated. Ref.5
Miscellaneous	HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion.
Sequence similarities	Contains 1 C1q domain. Contains 1 collagen-like domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Collagen Repeat Signal
Molecular function	Hormone
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	brown fat cell differentiation Inferred from direct assay. Source: MGI fatty acid beta-oxidation Inferred from mutant phenotype. Source: MGI glucose homeostasis Ref.7 Inferred from direct assay. Source: MGI glucose metabolic process Ref.7 Inferred from direct assay. Source: MGI negative regulation of fat cell differentiation Inferred from direct assay. Source: UniProtKB negative regulation of gluconeogenesis Ref.7 Inferred from direct assay. Source: MGI positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay. Source: MGI positive regulation of fatty acid metabolic process Inferred from mutant phenotype. Source: MGI positive regulation of glucose import Inferred from direct assay. Source: MGI protein homooligomerization Ref.1 Inferred from direct assay. Source: MGI response to glucose stimulus Inferred from direct assay. Source: MGI
Cellular component	endoplasmic reticulum Inferred from direct assay. Source: MGI extracellular space Ref.1 Ref.7 Inferred from direct assay. Source: MGI
Molecular function	hormone activity Ref.6 Ref.7 Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.5

Chain

18 – 247

230

Adiponectin

PRO_0000003544

Regions

Domain

45 – 110

66

Collagen-like

Domain

111 – 247

137

C1q

Sites

Site

79

1

Not hydroxylated

Site

98

1

Not hydroxylated

Site

107

1

Not hydroxylated

Site

233

1

Not glycosylated

Amino acid modifications

Modified residue

47

1

4-hydroxyproline By similarity

Modified residue

50

1

4-hydroxyproline By similarity

Modified residue

56

1

4-hydroxyproline By similarity

Modified residue

68

1

5-hydroxylysine Ref.5

Modified residue

71

1

5-hydroxylysine Ref.5

Modified residue

80

1

5-hydroxylysine Ref.5

Modified residue

94

1

4-hydroxyproline Ref.5

Modified residue

104

1

5-hydroxylysine Ref.5

Glycosylation

68

1

O-linked (Gal...) Ref.5

Glycosylation

71

1

O-linked (Gal...) Ref.5

Glycosylation

80

1

O-linked (Gal...) Ref.5

Glycosylation

104

1

O-linked (Gal...) Ref.5

Disulfide bond

39

Interchain By similarity

Natural variations

Natural variant

113

1

M → V

Experimental info

Mutagenesis

68

1

K → R: Impaired formation of HMW multimers; when associated with R-71; R-80 and R-104. Ref.11

Mutagenesis

71

1

K → R: Impaired formation of HMW multimers; when associated with R-68; R-80 and R-104. Ref.11

Mutagenesis

80

1

K → R: Impaired formation of HMW multimers; when associated with R-68; R-71 and R-104. Ref.11

Mutagenesis

104

1

K → R: Impaired formation of HMW multimers; when associated with R-68; R-71 and R-80. Ref.11

Sequence conflict

50

1

P → S in AAB06706. Ref.2

Sequence conflict

74

1

A → S in AAB06706. Ref.2

Sequence conflict

117

1

A → G in AAB06706. Ref.2

Sequence conflict

148

1

G → N in AAB06706. Ref.2

Sequence conflict

243

1

Y → F in AAB06706. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

247

Helix Strand Turn

Details...

Beta strand

117 – 121

5

Beta strand

137 – 140

4

Turn

148 – 150

3

Beta strand

159 – 172

14

Beta strand

174 – 180

7

Beta strand

183 – 190

8

Beta strand

197 – 208

12

Beta strand

213 – 218

6

Beta strand

236 – 244

9

Sequences

	Sequence		Length	Mass (Da)
	Q60994-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 137B687D873988C4	FASTA	247	26,841
	10 20 30 40 50 60 MLLLQALLFL LILPSHAEDD VTTTEELAPA LVPPPKGTCA GWMAGIPGHP GHNGTPGRDG 70 80 90 100 110 120 RDGTPGEKGE KGDAGLLGPK GETGDVGMTG AEGPRGFPGT PGRKGEPGEA AYMYRSAFSV 130 140 150 160 170 180 GLETRVTVPN VPIRFTKIFY NQQNHYDGST GKFYCNIPGL YYFSYHITVY MKDVKVSLFK 190 200 210 220 230 240 KDKAVLFTYD QYQEKNVDQA SGSVLLHLEV GDQVWLQVYG DGDHNGLYAD NVNDSTFTGF LLYHDTN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel serum protein similar to C1q, produced exclusively in adipocytes." Scherer P.E., Williams S., Fogliano M., Baldini G., Lodish H.F. J. Biol. Chem. 270:26746-26749(1995) [PubMed: 7592907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adipocyte.
[2]	"AdipoQ is a novel adipose-specific gene dysregulated in obesity." Hu E., Liang P., Spiegelman B.M. J. Biol. Chem. 271:10697-10703(1996) [PubMed: 8631877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[3]	"Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30." Das K., Lin Y., Widen E., Zhang Y., Scherer P.E. Biochem. Biophys. Res. Commun. 280:1120-1129(2001) [PubMed: 11162643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Heart.
[5]	"Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity." Wang Y., Xu A., Knight C., Xu L.Y., Cooper G.J.S. J. Biol. Chem. 277:19521-19529(2002) [PubMed: 11912203] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-25, HYDROXYLATION AT LYS-68; LYS-71; LYS-80; PRO-94 AND LYS-104, GLYCOSYLATION AT LYS-68; LYS-71; LYS-80 AND LYS-104, GLYCAN STRUCTURE, ABSENCE OF HYDROXYLATION AT PRO-79; PRO-98 AND PRO-107, ABSENCE OF GLYCOSYLATION AT ASN-233, MASS SPECTROMETRY.
[6]	"The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity." Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y., Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M. , Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P., Kadowaki T. Nat. Med. 7:941-946(2001) [PubMed: 11479627] [Abstract] Cited for: FUNCTION.
[7]	"The adipocyte-secreted protein Acrp30 enhances hepatic insulin action." Berg A.H., Combs T.P., Du X., Brownlee M., Scherer P.E. Nat. Med. 7:947-953(2001) [PubMed: 11479628] [Abstract] Cited for: FUNCTION.
[8]	"The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice." Xu A., Wang Y., Keshaw H., Xu L.Y., Lam K.S.L., Cooper G.J.S. J. Clin. Invest. 112:91-100(2003) [PubMed: 12840063] [Abstract] Cited for: FUNCTION.
[9]	"Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes." Xu A., Chan K.W., Hoo R.L.C., Wang Y., Tan K.C.B., Zhang J., Chen B., Lam M.C., Tse C., Cooper G.J.S., Lam K.S.L. J. Biol. Chem. 280:18073-18080(2005) [PubMed: 15760892] [Abstract] Cited for: SUBUNIT, FUNCTION.
[10]	"Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner." Wang Y., Lam K.S.L., Xu J.Y., Lu G., Xu L.Y., Cooper G.J.S., Xu A. J. Biol. Chem. 280:18341-18347(2005) [PubMed: 15734737] [Abstract] Cited for: SUBUNIT, FUNCTION.
[11]	"Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex." Wang Y., Lam K.S.L., Chan L., Chan K.W., Lam J.B.B., Lam M.C., Hoo R.C.L., Mak W.W.N., Cooper G.J.S., Xu A. J. Biol. Chem. 281:16391-16400(2006) [PubMed: 16621799] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF LYS-68; LYS-71; LYS-80 AND LYS-104.
[12]	"The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor." Shapiro L., Scherer P.E. Curr. Biol. 8:335-338(1998) [PubMed: 9512423] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 111-247.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U37222 mRNA. Translation: AAA80543.1.
U49915 mRNA. Translation: AAB06706.1.
AF304466 Genomic DNA. Translation: AAK13417.1.
AK003138 mRNA. Translation: BAB22597.1.

IPI

IPI00311383.

RefSeq

NP_033735.3.

UniGene

Mm.3969

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C28	X-ray	2.10	A/B/C	113-247	[»]
1C3H	X-ray	2.10	A/B/C/D/E/F	111-247	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q60994.

Proteomic databases

PRIDE

Q60994.

Genome annotation databases

Ensembl

ENSMUST00000023593; ENSMUSP00000023593; ENSMUSG00000022878; Mus musculus. [Genome view]

GeneID

11450.

KEGG

mmu:11450.

Organism-specific databases

CTD

11450.

MGI

MGI:106675. Adipoq.

Phylogenomic databases

eggNOG

roNOG04854.

HOGENOM

HBG444750.

HOVERGEN

Q60994.

InParanoid

Q60994.

Gene expression databases

ArrayExpress

Q60994.

Bgee

Q60994.

CleanEx

MM_ADIPOQ.

Genevestigator

Q60994.

GermOnline

ENSMUSG00000022878. Mus musculus.

Family and domain databases

InterPro

IPR001073. C1q.
IPR008160. Collagen.
IPR008983. Tumour_necrosis_fac-like.
[Graphical view]

Gene3D

G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.

Pfam

PF00386. C1q. 1 hit.
PF01391. Collagen. 1 hit.
[Graphical view]

PRINTS

PR00007. COMPLEMNTC1Q.

SMART

SM00110. C1Q. 1 hit.
[Graphical view]

PROSITE

PS50871. C1Q. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

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Entry information

Entry name

ADIPO_MOUSE

Accession

Primary (citable) accession number: Q60994
Secondary accession number(s): Q62400, Q9DC68

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)