Reviewed, UniProtKB/Swiss-Prot Q15848 (ADIPO_HUMAN)

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
    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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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.

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.
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.
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. O-linked glycans consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Not N-glycosylated.
Involvement in disease	Defects in ADIPOQ are the cause of adiponectin deficiency [MIM:605441]. The result is a very low concentration of plasma adiponectin. Decreased adiponectin plasma levels are associated with obesity insulin resistance, and diabetes type 2.
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.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation Obesity
Domain	Collagen Repeat Signal
Molecular function	Hormone
PTM	Glycoprotein Hydroxylation
Technical term	Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	generation of precursor metabolites and energy Ref.2 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 18	18
	Chain	19 – 244	226	Adiponectin
Regions
	Domain	42 – 107	66	Collagen-like
	Domain	108 – 244	137	C1q
Sites
	Site	62	1	Not hydroxylated
	Site	86	1	Not hydroxylated
	Site	104	1	Not hydroxylated
	Site	230	1	Not glycosylated
Amino acid modifications
	Modified residue	33	1	5-hydroxylysine Probable
	Modified residue	44	1	4-hydroxyproline
	Modified residue	47	1	4-hydroxyproline
	Modified residue	53	1	4-hydroxyproline
	Modified residue	65	1	5-hydroxylysine
	Modified residue	68	1	5-hydroxylysine
	Modified residue	71	1	4-hydroxyproline; partial
	Modified residue	76	1	4-hydroxyproline; partial
	Modified residue	77	1	5-hydroxylysine
	Modified residue	91	1	4-hydroxyproline
	Modified residue	95	1	4-hydroxyproline; partial
	Modified residue	101	1	5-hydroxylysine
	Glycosylation	65	1	O-linked (Gal...); partial
	Glycosylation	68	1	O-linked (Gal...); partial
	Glycosylation	77	1	O-linked (Gal...); partial
	Glycosylation	101	1	O-linked (Gal...); partial
	Disulfide bond	36		Interchain; in form MMW and form HMW
Natural variations
	Natural variant	84	1	G → R
	Natural variant	90	1	G → S
	Natural variant	111	1	Y → H: dbSNP rs17366743.
	Natural variant	112	1	R → C in adiponectin deficiency.
	Natural variant	117	1	V → M
	Natural variant	164	1	I → T
	Natural variant	221	1	R → S
	Natural variant	241	1	H → P
Experimental info
	Mutagenesis	33	1	K → R: No effect on formation of HMW multimers
	Mutagenesis	36	1	C → S: Impaired formation of MMW and HMW multimers
	Mutagenesis	65	1	K → R: Impaired formation of HMW multimers; when associated with R-68
	Mutagenesis	68	1	K → R: Impaired formation of HMW multimers; when associated with R-65
	Mutagenesis	77	1	K → R: Impaired formation of HMW multimers; when associated with R-101
	Mutagenesis	101	1	K → R: Impaired formation of HMW multimers; when associated with R-77

Sequences

	Sequence		Length	Mass (Da)
	Q15848-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 64D8C6C1204B1018	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

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. , 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.
[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.
[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, ABSENCE OF HYDROXYLATION AT PRO-62; PRO-86 AND PRO-104, ABSENCE 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 ADIPONECTIN DEFICIENCY 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. , Nakano Y., Kimura S., Tomita M., Kimura S., Ito C., Froguel P., 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]	"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.

Web resources

Wikipedia

Adiponectin entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
PIR	JC4708.
RefSeq	NP_004788.1.
UniGene	Hs.80485
3D structure databases
HSSP	HSSP built from PDB template 1C28 based on UniProtKB Q60994.
SMR	Q15848. Positions 108-244.
ModBase	Search...
Proteomic databases
PeptideAtlas	Q15848.
Genome annotation databases
Ensembl	ENSG00000181092. Homo sapiens. [Contig view]
GeneID	9370.
KEGG	hsa:9370.
Organism-specific databases
H-InvDB	HIX0020222.
HGNC	HGNC:13633. ADIPOQ.
MIM	605441. gene+phenotype.
PharmGKB	PA134933118.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q15848.
HOVERGEN	Q15848.
Gene expression databases
ArrayExpress	Q15848.
CleanEx	HS_ADIPOQ.
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.
ProDom	PD000007. Clg_helix. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00110. C1Q. 1 hit. [Graphical view]
PROSITE	PS50871. C1Q. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
LinkHub	Q15848.
SOURCE	Search...
ProtoNet	Search...

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:	July 22, 2008
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)