Adiponectin precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q15848 (ADIPO_HUMAN)

Last modified January 19, 2010. Version 106. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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
    Adipose most abundant gene transcript 1 protein
      Short name=apM-1
    Gelatin-binding protein

Gene names

Name:	ADIPOQ
Synonyms:	ACDC, ACRP30, APM1, GBP28

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	244 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.9
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.10 Ref.11
Subcellular location	Secreted.
Tissue specificity	Synthesized exclusively by adipocytes and secreted into plasma.
Domain	The C1q domain is commonly called the globular domain.
Post-translational modification	Hydroxylated Lys-33 was not identified in Ref.11, probably due to poor representation of the N-terminal peptide in mass fingerprinting. 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 By similarity. Ref.11 O-linked glycans consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Not N-glycosylated. Ref.11
Polymorphism	Genetic variations in ADIPOQ influence the variance in adiponectin serum levels and define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556].
Involvement in disease	Defects in ADIPOQ are the cause of adiponectin deficiency (ADPND) [MIM:612556]. ADPND results in very low concentrations of plasma adiponectin. Ref.12 Genetic variations in ADIPOQ are associated with non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.
Pharmaceutical use	Adiponectin might be used in the treatment of diabetes type 2 and insulin resistance.
Miscellaneous	Variants Arg-84 and Ser-90 show impaired formation of HMW complexes whereas variants Cys-112 and Thr-164 show impaired secretion of adiponectin in any form. 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 By similarity. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation are significantly decreased as compared with healthy controls.
Sequence similarities	Contains 1 C1q domain. Contains 1 collagen-like domain.

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Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Collagen Repeat Signal
Molecular function	Hormone
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	Complete proteome Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Inferred from sequence or structural similarity. Source: UniProtKB generation of precursor metabolites and energy Ref.2 Traceable author statement. Source: ProtInc glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB glucose metabolic process Inferred from sequence or structural similarity. Source: UniProtKB low-density lipoprotein particle clearance Inferred from direct assay. Source: UniProtKB negative regulation of I-kappaB kinase/NF-kappaB cascade Ref.8 Inferred from direct assay. Source: UniProtKB negative regulation of fat cell differentiation Inferred from direct assay. Source: UniProtKB negative regulation of gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of granulocyte differentiation Ref.7 Inferred from direct assay. Source: UniProtKB negative regulation of heterotypic cell-cell adhesion Inferred from direct assay. Source: UniProtKB negative regulation of inflammatory response Non-traceable author statement. Source: UniProtKB negative regulation of low-density lipoprotein receptor biosynthetic process Inferred from direct assay. Source: UniProtKB negative regulation of macrophage derived foam cell differentiation Inferred from direct assay. Source: UniProtKB negative regulation of macrophage differentiation Ref.7 Inferred from direct assay. Source: UniProtKB negative regulation of phagocytosis Ref.7 Inferred from direct assay. Source: UniProtKB negative regulation of tumor necrosis factor production Ref.7 Inferred from direct assay. Source: UniProtKB negative regulation of tumor necrosis factor-mediated signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of cholesterol efflux Inferred from direct assay. Source: UniProtKB positive regulation of fatty acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glucose import Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of myeloid cell apoptosis Ref.7 Inferred from direct assay. Source: UniProtKB positive regulation of protein kinase A signaling cascade Ref.8 Inferred from direct assay. Source: UniProtKB response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to tumor necrosis factor Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	cytokine activity Non-traceable author statement. Source: UniProtKB eukaryotic cell surface binding Ref.8 Inferred from direct assay. Source: UniProtKB hormone activity Inferred from direct assay. Source: UniProtKB protein homodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

Ref.5

Chain

19 – 244

226

Adiponectin

PRO_0000003543

Regions

Domain

42 – 107

Collagen-like

Domain

108 – 244

137

C1q

Sites

Site

Not hydroxylated

Site

Not hydroxylated

Site

104

Not hydroxylated

Site

230

Not glycosylated

Amino acid modifications

Modified residue

5-hydroxylysine Probable

Modified residue

4-hydroxyproline Ref.11

Modified residue

4-hydroxyproline Ref.11

Modified residue

4-hydroxyproline Ref.11

Modified residue

5-hydroxylysine Ref.11

Modified residue

5-hydroxylysine Ref.11

Modified residue

4-hydroxyproline; partial Ref.11

Modified residue

4-hydroxyproline; partial Ref.11

Modified residue

5-hydroxylysine Ref.11

Modified residue

4-hydroxyproline Ref.11

Modified residue

4-hydroxyproline; partial Ref.11

Modified residue

101

5-hydroxylysine Ref.11

Glycosylation

O-linked (Gal...); partial Ref.11

Glycosylation

O-linked (Gal...); partial Ref.11

Glycosylation

O-linked (Gal...); partial Ref.11

Glycosylation

101

O-linked (Gal...); partial Ref.11

Disulfide bond

Interchain; in form MMW and form HMW Ref.10 Ref.11

Natural variations

Natural variant

G → R Does not form high molecular weight multimers. Ref.10 Ref.13 Ref.16

VAR_013273

Natural variant

G → S Does not form high molecular weight multimers. Ref.10 Ref.16

VAR_027395

Natural variant

111

Y → H: dbSNP rs17366743. Ref.16

VAR_027396

Natural variant

112

R → C in ADPND; does not assemble into trimers resulting in impaired secretion from the cell. Ref.10 Ref.12 Ref.15

VAR_013274

Natural variant

117

V → M

VAR_013275

Natural variant

164

I → T Associated with low plasma adiponectin concentration and diabetes mellitus type 2; does not assemble into trimers resulting in impaired secretion from the cell. Ref.10 Ref.13 Ref.15

VAR_013276

Natural variant

221

R → S

VAR_013277

Natural variant

241

H → P

VAR_013278

Experimental info

Mutagenesis

K → R: No effect on formation of HMW multimers. Ref.11

Mutagenesis

C → S: Impaired formation of MMW and HMW multimers. Ref.10 Ref.11

Mutagenesis

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

Mutagenesis

K → R: Impaired formation of HMW multimers; when associated with R-65. Ref.11

Mutagenesis

K → R: Impaired formation of HMW multimers; when associated with R-101. Ref.11

Mutagenesis

101

K → R: Impaired formation of HMW multimers; when associated with R-77. Ref.11

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Sequences

Sequence

Length

Mass (Da)

Tools

Q15848-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 64D8C6C1204B1018
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FASTA

244

26,414

        10         20         30         40         50         60 
MLLLGAVLLL LALPGHDQET TTQGPGVLLP LPKGACTGWM AGIPGHPGHN GAPGRDGRDG 

        70         80         90        100        110        120 
TPGEKGEKGD PGLIGPKGDI GETGVPGAEG PRGFPGIQGR KGEPGEGAYV YRSAFSVGLE 

       130        140        150        160        170        180 
TYVTIPNMPI RFTKIFYNQQ NHYDGSTGKF HCNIPGLYYF AYHITVYMKD VKVSLFKKDK 

       190        200        210        220        230        240 
AMLFTYDQYQ ENNVDQASGS VLLHLEVGDQ VWLQVYGEGE RNGLYADNDN DSTFTGFLLY 


HDTN

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1)." Maeda K., Okubo K., Shimomura I., Funahashi T., Matsuzawa Y., Matsubara K. Biochem. Biophys. Res. Commun. 221:286-289(1996) [PubMed: 8619847] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adipose tissue.
[2]	"Organization of the gene for gelatin-binding protein (GBP28)." Saito K., Tobe T., Minoshima S., Asakawa S., Sumiya J., Yoda M., Nakano Y., Shimizu N., Tomita M. Gene 229:67-73(1999) [PubMed: 10095105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The human apM-1, an adipocyte-specific gene linked to the family of TNF's and to genes expressed in activated T cells, is mapped to chromosome 1q21.3-q23, a susceptibility locus identified for familial combined hyperlipidemia (FCH)." Schaeffler A., Orso E., Palitzsch K.D., Buechler C., Drobnik W., Fuerst A., Schoelmerich J., Schmitz G. Biochem. Biophys. Res. Commun. 260:416-425(1999) [PubMed: 10403784] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-33.
[6]	"Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma." Nakano Y., Tobe T., Choi-Miura N.H., Mazda T., Tomita M. J. Biochem. 120:803-812(1996) [PubMed: 8947845] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN SEQUENCE.
[7]	"Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages." Yokota T., Oritani K., Takahashi I., Ishikawa J., Matsuyama A., Ouchi N., Kihara S., Funahashi T., Tenner A.J., Tomiyama Y., Matsuzawa Y. Blood 96:1723-1732(2000) [PubMed: 10961870] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway." Ouchi N., Kihara S., Arita Y., Okamoto Y., Maeda K., Kuriyama H., Hotta K., Nishida M., Takahashi M., Muraguchi M., Ohmoto Y., Nakamura T., Yamashita S., Funahashi T., Matsuzawa Y. Circulation 102:1296-1301(2000) [PubMed: 10982546] [Abstract] Cited for: CHARACTERIZATION.
[9]	"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. Kadowaki T. Nat. Med. 7:941-946(2001) [PubMed: 11479627] [Abstract] Cited for: FUNCTION.
[10]	"Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin." Waki H., Yamauchi T., Kamon J., Ito Y., Uchida S., Kita S., Hara K., Hada Y., Vasseur F., Froguel P., Kimura S., Nagai R., Kadowaki T. J. Biol. Chem. 278:40352-40363(2003) [PubMed: 12878598] [Abstract] Cited for: SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF CYS-36, CHARACTERIZATION OF VARIANTS ARG-84; SER-90; CYS-112 AND THR-164.
[11]	"Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications." Richards A.A., Stephens T., Charlton H.K., Jones A., Macdonald G.A., Prins J.B., Whitehead J.P. Mol. Endocrinol. 20:1673-1687(2006) [PubMed: 16497731] [Abstract] Cited for: SUBUNIT, HYDROXYLATION AT PRO-44; PRO-47; PRO-53; LYS-65; LYS-68; PRO-71; PRO-76; LYS-77; PRO-91; PRO-95 AND LYS-101, GLYCOSYLATION AT LYS-65; LYS-68; LYS-77 AND LYS-101, DISULFIDE BOND, LACK OF HYDROXYLATION AT PRO-62; PRO-86 AND PRO-104, LACK OF GLYCOSYLATION AT ASN-230, MUTAGENESIS OF LYS-33; CYS-36; LYS-65; LYS-68; LYS-77 AND LYS-101, MASS SPECTROMETRY.
[12]	"Genomic structure and mutations in adipose-specific gene, adiponectin." Takahashi M., Arita Y., Yamagata K., Matsukawa Y., Okutomi K., Horie M., Shimomura I., Hotta K., Kuriyama H., Kihara S., Nakamura T., Yamashita S., Funahashi T., Matsuzawa Y. Int. J. Obes. Relat. Metab. Disord. 24:861-868(2000) [PubMed: 10918532] [Abstract] Cited for: VARIANT ADPND CYS-112.
[13]	"Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population." Hara K., Boutin P., Mori Y., Tobe K., Dina C., Yasuda K., Yamauchi T., Otabe S., Okada T., Eto K., Kadowaki H., Hagura R., Akanuma Y., Yazaki Y., Nagai R., Taniyama M., Matsubara K., Yoda M. Kadowaki T. Diabetes 51:536-540(2002) [PubMed: 11812766] [Abstract] Cited for: VARIANTS ARG-84; MET-117; THR-164; SER-221 AND PRO-241.
[14]	Erratum Hara K., Boutin P., Mori Y., Tobe K., Dina C., Yasuda K., Yamauchi T., Otabe S., Okada T., Eto K., Kadowaki H., Hagura R., Akanuma Y., Yazaki Y., Nagai R., Taniyama M., Matsubara K., Yoda M. Kadowaki T. Diabetes 51:1294-1294(2002)
[15]	"Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome." Kondo H., Shimomura I., Matsukawa Y., Kumada M., Takahashi M., Matsuda M., Ouchi N., Kihara S., Kawamoto T., Sumitsuji S., Funahashi T., Matsuzawa Y. Diabetes 51:2325-2328(2002) [PubMed: 12086969] [Abstract] Cited for: VARIANTS CYS-112; THR-164; SER-221 AND PRO-241, ASSOCIATION WITH LOW PLASMA ADIPONECTIN CONCENTRATION AND DIABETES MELLITUS TYPE 2.
[16]	"Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians." Vasseur F., Helbecque N., Dina C., Lobbens S., Delannoy V., Gaget S., Boutin P., Vaxillaire M., Lepretre F., Dupont S., Hara K., Clement K., Bihain B., Kadowaki T., Froguel P. Hum. Mol. Genet. 11:2607-2614(2002) [PubMed: 12354786] [Abstract] Cited for: VARIANTS ARG-84; SER-90 AND HIS-111.
+	Additional computationally mapped references.

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Web resources

Wikipedia

Adiponectin entry

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Cross-references

Sequence databases
EMBL GenBank DDBJ	D45371 mRNA. Translation: BAA08227.1. AB012165 Genomic DNA. Translation: BAA86716.1. AJ131460, AJ131461 Genomic DNA. Translation: CAB52413.1. BC054496 mRNA. Translation: AAH54496.1. BC096308 mRNA. Translation: AAH96308.1. BC096309 mRNA. Translation: AAH96309.1. BC096310 mRNA. Translation: AAH96310.1. BC096311 mRNA. Translation: AAH96311.1.
IPI	IPI00020019.
PIR	JC4708.
RefSeq	NP_004788.1.
UniGene	Hs.80485
3D structure databases
SMR	Q15848. Positions 45-78, 79-105, 108-244.
ModBase	Search...
Protein-protein interaction databases
STRING	Q15848.
Proteomic databases
PeptideAtlas	Q15848.
PRIDE	Q15848.
Genome annotation databases
Ensembl	ENST00000320741; ENSP00000320709; ENSG00000181092; Homo sapiens. [Genome view] ENST00000412955; ENSP00000405611; ENSG00000181092; Homo sapiens. [Genome view] ENST00000444204; ENSP00000389814; ENSG00000181092; Homo sapiens. [Genome view]
GeneID	9370.
KEGG	hsa:9370.
UCSC	uc003fra.1. human.
Organism-specific databases
CTD	9370.
GeneCards	GC03P188044.
H-InvDB	HIX0020222.
HGNC	HGNC:13633. ADIPOQ.
HPA	CAB025475.
MIM	125853. phenotype. 605441. gene. 612556. phenotype.
PharmGKB	PA134933118.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16473.
HOGENOM	HBG444750.
HOVERGEN	Q15848.
InParanoid	Q15848.
OMA	YHITVYM.
OrthoDB	EOG91G5PK.
PhylomeDB	Q15848.
Gene expression databases
ArrayExpress	Q15848.
Bgee	Q15848.
CleanEx	HS_ADIPOQ.
Genevestigator	Q15848.
GermOnline	ENSG00000181092. Homo sapiens.
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
NextBio	35094.
SOURCE	Search...

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Entry information

Entry name

ADIPO_HUMAN

Accession

Primary (citable) accession number: Q15848
Secondary accession number(s): Q58EX9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents