Amphiregulin precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P15514 (AREG_HUMAN)

Last modified November 24, 2009. Version 96. 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:
    Amphiregulin
      Short name=AR
Alternative name(s):
    Colorectum cell-derived growth factor
      Short name=CRDGF

Gene names

Name:	AREG
Synonyms:	SDGF
AND
Name:	AREGB

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	252 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	Bifunctional growth-modulating glycoprotein. Inhibits growth of several human carcinoma cells in culture and stimulates proliferation of human fibroblasts and certain other tumor cells.
Subunit structure	The immature precursor interacts with CNIH. Ref.8
Subcellular location	Membrane; Single-pass membrane protein.
Induction	By phorbol 12-myristate 13-acetate (PMA).
Miscellaneous	AR is a protein containing cysteines in disulfide linkage(s) that are essential for its biological activity. AR may contain oligosaccharides and/or lipid moieties that are not obligatory for the biological activity.
Sequence similarities	Belongs to the amphiregulin family. Contains 1 EGF-like domain.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal Transmembrane
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from direct assay. Source: UniProtKB cell proliferation Ref.4 Traceable author statement. Source: ProtInc cell-cell signaling Ref.4 Traceable author statement. Source: ProtInc epidermal growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of DNA replication Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB extracellular space Ref.5 Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW growth factor activity Ref.4 Traceable author statement. Source: ProtInc
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 – 19

Potential

Propeptide

20 – 100

PRO_0000007473

Chain

101 – 184

Amphiregulin

PRO_0000007474

Propeptide

185 – 252

PRO_0000007475

Regions

Transmembrane

199 – 221

Potential

Domain

142 – 182

EGF-like

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

113

N-linked (GlcNAc...) Potential

Glycosylation

119

N-linked (GlcNAc...)

Disulfide bond

146 ↔ 159

By similarity

Disulfide bond

154 ↔ 170

By similarity

Disulfide bond

172 ↔ 181

By similarity

Natural variations

Natural variant

D → V

VAR_018918

Natural variant

Y → C

VAR_018919

Secondary structure

252

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P15514-1 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: 68C1FA6BCD4D2BED
Show »

FASTA

252

27,895

        10         20         30         40         50         60 
MRAPLLPPAP VVLSLLILGS GHYAAGLDLN DTYSGKREPF SGDHSADGFE VTSRSEMSSG 

        70         80         90        100        110        120 
SEISPVSEMP SSSEPSSGAD YDYSEEYDNE PQIPGYIVDD SVRVEQVVKP PQNKTESENT 

       130        140        150        160        170        180 
SDKPKRKKKG GKNGKNRRNR KKKNPCNAEF QNFCIHGECK YIEHLEAVTC KCQQEYFGER 

       190        200        210        220        230        240 
CGEKSMKTHS MIDSSLSKIA LAAIAAFMSA VILTAVAVIT VQLRRQYVRK YEGEAEERKK 

       250 
LRQENGNVHA IA

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity." Plowman G.D., Green J.M., McDonald V.L., Neubauer M.G., Disteche C.M., Todaro G.J., Shoyab M. Mol. Cell. Biol. 10:1969-1981(1990) [PubMed: 2325643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-80 AND CYS-81.
[3]	"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]. Tissue: Brain.
[4]	"Structure and function of human amphiregulin: a member of the epidermal growth factor family." Shoyab M., Plowman G.D., McDonald V.L., Bradley J.G., Todaro G.J. Science 243:1074-1076(1989) [PubMed: 2466334] [Abstract] Cited for: PROTEIN SEQUENCE OF 101-184.
[5]	"Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7." Shoyab M., McDonald V.L., Bradley J.G., Todaro G.J. Proc. Natl. Acad. Sci. U.S.A. 85:6528-6532(1988) [PubMed: 3413110] [Abstract] Cited for: PROTEIN SEQUENCE OF 101-131.
[6]	"A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin." Cook P.W., Mattox P.A., Keeble W.W., Pittelkow M.R., Plowman G.D., Shoyab M., Adelman J.P., Shipley G.D. Mol. Cell. Biol. 11:2547-2557(1991) [PubMed: 2017164] [Abstract] Cited for: PROTEIN SEQUENCE OF 101-126.
[7]	"Colorectum cell-derived growth factor (CRDGF) is homologous to amphiregulin, a member of the epidermal growth factor family." Culouscou J.-M., Remacle-Bonnet M., Carlton G.W., Plowman G.D., Shoyab M. Growth Factors 7:195-205(1992) [PubMed: 1333777] [Abstract] Cited for: PROTEIN SEQUENCE OF 101-122.
[8]	"Cornichon regulates transport and secretion of TGFalpha-related proteins in metazoan cells." Perez Castro C., Piscopo D., Nakagawa T., Derynck R. J. Cell Sci. 120:2454-2466(2007) [PubMed: 17607000] [Abstract] Cited for: INTERACTION WITH CNIH.
[9]	"Solution structure of the EGF-like domain from human amphiregulin." RIKEN structural genomics initiative (RSGI) Submitted (JAN-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 142-184.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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Cross-references

Sequence databases

M30704 mRNA. Translation: AAA51781.1.
M30702

M30701 Genomic DNA. Translation: AAA51773.1.
AY442340 Genomic DNA. Translation: AAR05438.1.
BC009799 mRNA. Translation: AAH09799.1.

IPI

IPI00012023.

PIR

A34702.

RefSeq

NP_001648.1.
XP_001125684.1.

UniGene

Hs.270833
Hs.645475

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RNL	NMR	-	A	142-184	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5766N.

IntAct

P15514. 1 interaction.

STRING

P15514.

Proteomic databases

PeptideAtlas

P15514.

PRIDE

P15514.

Genome annotation databases

Ensembl

ENST00000264487; ENSP00000264487; ENSG00000109321; Homo sapiens. [Genome view]
ENST00000380846; ENSP00000370227; ENSG00000205595; Homo sapiens. [Genome view]
ENST00000395748; ENSP00000379097; ENSG00000109321; Homo sapiens. [Genome view]

GeneID

374.
727738.

KEGG

hsa:374.
hsa:727738.

UCSC

uc003hif.1. human.

Organism-specific databases

CTD

374.
727738.

GeneCards

GC04P075550.
GC04P075700.

H-InvDB

HIX0004290.
HIX0057471.

HGNC

HGNC:651. AREG.
HGNC:34509. AREGB.

HPA

CAB023519.
HPA008720.

MIM

104640. gene.

PharmGKB

PA24933.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15514.

HOVERGEN

P15514.

OMA

GDHSADG

OrthoDB

EOG9H74XW

Gene expression databases

ArrayExpress

P15514.

Bgee

P15514.

CleanEx

HS_AREG.

Genevestigator

P15514.

GermOnline

ENSG00000109321. Homo sapiens.
ENSG00000205595. Homo sapiens.

Family and domain databases

InterPro

IPR006209. EGF.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR015497. EGF_rcpt_ligand.
[Graphical view]

PANTHER

PTHR10740. EGF_rcpt_ligand. 1 hit.

Pfam

PF00008. EGF. 1 hit.
[Graphical view]

SMART

SM00181. EGF. 1 hit.
[Graphical view]

PROSITE

PS00022. EGF_1. 1 hit.
PS01186. EGF_2. False negative.
PS50026. EGF_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

1565.

PMAP-CutDB

P15514.

SOURCE

Search...

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Entry information

Entry name

AREG_HUMAN

Accession

Primary (citable) accession number: P15514

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	February 1, 1991
Last modified:	November 24, 2009
This is version 96 of the entry and version 2 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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