Reviewed, UniProtKB/Swiss-Prot O00253 (AGRP_HUMAN)

Names and originHide

Protein names

Recommended name:
Agouti-related protein

Gene names

Name:	AGRP
Synonyms:	AGRT, ART

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

Protein attributesHide

Sequence length	132 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)Hide

Function	Plays a role in weight homeostasis. May play a role in the regulation of melanocortin receptors within the hypothalamus and adrenal gland, and therefore in the central control of feeding.
Subcellular location	Secreted By similarity.
Tissue specificity	Expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with a lower level of expression occurring in testis, lung, and kidney.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Involvement in disease	Defects in AGRP may be a cause of autosomal dominant obesity [MIM:601665].
Sequence similarities	Contains 1 agouti domain.

OntologiesHide

Keywords
Cellular component	Secreted
Disease	Disease mutation Obesity
Domain	Knottin Signal
PTM	Disulfide bond
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	hormone-mediated signaling pathway Inferred from electronic annotation. Source: InterPro neuropeptide signaling pathway Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	neuropeptide hormone activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)Hide

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 132

112

Agouti-related protein

PRO_0000001034

Regions

Domain

87 – 129

43

Agouti

Amino acid modifications

Disulfide bond

87 ↔ 102

Ref.7

Disulfide bond

94 ↔ 108

Ref.7

Disulfide bond

101 ↔ 119

Ref.7

Disulfide bond

105 ↔ 129

Ref.7

Disulfide bond

110 ↔ 117

Ref.7

Natural variations

Natural variant

67

1

A → T in obesity; late onset. [dbSNP:rs5030980] Ref.3 Ref.10

VAR_015385

Experimental info

Sequence conflict

6

1

V → L in AAB68621. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

132

Helix Strand Turn

Details...

Beta strand

95 – 97

3

Beta strand

101 – 103

3

Beta strand

107 – 115

9

Beta strand

117 – 120

4

Beta strand

125 – 127

3

SequencesHide

	Sequence		Length	Mass (Da)
	O00253-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 1CCBE112C3EB10F5	FASTA	132	14,440
	10 20 30 40 50 60 MLTAAVLSCA LLLALPATRG AQMGLAPMEG IRRPDQALLP ELPGLGLRAP LKKTTAEQAE 70 80 90 100 110 120 EDLLQEAQAL AEVLDLQDRE PRSSRRCVRL HESCLGQQVP CCDPCATCYC RFFNAFCYCR 130 KLGTAMNPCS RT

ReferencesHide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice." Shutter J.R., Graham M., Kinsey A.C., Scully S., Luethy R., Stark K.L. Genes Dev. 11:593-602(1997) [PubMed: 9119224] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein." Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., Barsh G.S. Science 278:135-138(1997) [PubMed: 9311920] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal gland.
[3]	"The gene structure and minimal promoter of the human agouti related protein." Brown A.M., Mayfield D.K., Volaufova J., Argyropoulos G. Gene 277:231-238(2001) [PubMed: 11602360] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-67.
[4]	"Association between an agouti-related protein gene polymorphism and anorexia nervosa." Vink T., Hinney A., van Elburg A.A., van Goozen S.H., Sandkuijl L.A., Sinke R.J., Herpertz-Dahlmann B.M., Hebebrand J., Remschmidt H., van Engeland H., Adan R.A. Mol. Psychiatry 6:325-328(2001) [PubMed: 11326303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	SeattleSNPs variation discovery resource Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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].
[7]	"Determination of disulfide structure in agouti-related protein (AGRP) by stepwise reduction and alkylation." Bures E.J., Hui J.O., Young Y., Chow D.T., Katta V., Rohde M.F., Zeni L., Rosenfeld R.D., Stark K.L., Haniu M. Biochemistry 37:12172-12177(1998) [PubMed: 9724530] [Abstract] Cited for: DISULFIDE BONDS.
[8]	"NMR structure of a minimized human agouti related protein prepared by total chemical synthesis." Bolin K.A., Anderson D.J., Trulson J.A., Thompson D.A., Wilken J., Kent S.B.H., Gantz I., Millhauser G.L. FEBS Lett. 451:125-131(1999) [PubMed: 10371151] [Abstract] Cited for: STRUCTURE BY NMR OF 87-132.
[9]	"Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity." Jackson P.J., McNulty J.C., Yang Y.K., Thompson D.A., Chai B., Gantz I., Barsh G.S., Millhauser G.L. Biochemistry 41:7565-7572(2002) [PubMed: 12056887] [Abstract] Cited for: STRUCTURE BY NMR OF 87-120.
[10]	"A polymorphism in the human agouti-related protein is associated with late-onset obesity." Argyropoulos G., Rankinen T., Neufeld D.R., Rice T., Province M.A., Leon A.S., Skinner J.S., Wilmore J.H., Rao D.C., Bouchard C. J. Clin. Endocrinol. Metab. 87:4198-4202(2002) [PubMed: 12213871] [Abstract] Cited for: VARIANT THR-67.
+	Additional computationally mapped references.

Web resourcesHide

SeattleSNPs

Cross-referencesHide

Sequence databases

EMBL
GenBank
DDBJ

U88063 mRNA. Translation: AAB52240.1.
U89485 mRNA. Translation: AAB68621.1.
AF314194 Genomic DNA. Translation: AAL09457.1.
AF281309 Genomic DNA. Translation: AAK96256.1.
DQ374394 Genomic DNA. Translation: ABC88473.1.
BC110443 mRNA. Translation: AAI10444.1.

IPI

IPI00010869.

RefSeq

NP_001129.1.

UniGene

Hs.104633

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HYK	NMR	-	A	87-132	[»]
1MR0	NMR	-	A	87-120	[»]
2IQV	model	-	B	87-132	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

O00253.

Proteomic databases

PRIDE

O00253.

Genome annotation databases

Ensembl

ENST00000290953; ENSP00000290953; ENSG00000159723; Homo sapiens. [Genome view]
ENST00000393941; ENSP00000377515; ENSG00000159723; Homo sapiens. [Genome view]

GeneID

181.

KEGG

hsa:181.

UCSC

uc002etg.1. human.

Organism-specific databases

CTD

181.

GeneCards

GC16M066073.

HGNC

HGNC:330. AGRP.

MIM

601665. phenotype.
602311. gene.

PharmGKB

PA24627.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20473.

HOGENOM

HBG126983.

HOVERGEN

HBG050467.

InParanoid

O00253.

OMA

QGAQMGL.

OrthoDB

EOG9S4S23.

PhylomeDB

O00253.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_3_pathway. Syndecan-3-mediated signaling events.

Gene expression databases

ArrayExpress

O00253.

Bgee

O00253.

CleanEx

HS_AGRP.

Genevestigator

O00253.

GermOnline

ENSG00000159723. Homo sapiens.

Family and domain databases

InterPro

IPR007733. Agouti.
[Graphical view]

Gene3D

G3DSA:4.10.760.10. Agouti. 1 hit.

PANTHER

PTHR16551. Agouti. 1 hit.

Pfam

PF05039. Agouti. 1 hit.
[Graphical view]

SMART

SM00792. Agouti. 1 hit.
[Graphical view]

SUPFAM

SSF57055. Agouti. 1 hit.

PROSITE

PS60024. AGOUTI_1. 1 hit.
PS51150. AGOUTI_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

738.

SOURCE

Search...

Entry informationHide

Entry name

AGRP_HUMAN

Accession

Primary (citable) accession number: O00253
Secondary accession number(s): O15459, Q2TBD9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	July 13, 2010
This is version 96 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.