Amphiregulin precursor - Homo sapiens (Human)

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P15514 (AREG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 127. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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

General annotation (Comments)

Function	Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts.
Subunit structure	The immature precursor interacts with CNIH. Ref.9
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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 12743035. Source: BHF-UCL cell proliferation Traceable author statement Ref.4. Source: ProtInc cell-cell signaling Traceable author statement Ref.4. Source: ProtInc epidermal growth factor receptor signaling pathway Inferred from direct assay PubMed 12743035. Source: BHF-UCL positive regulation of DNA replication Inferred from mutant phenotype PubMed 12743035. Source: BHF-UCL
Cellular_component	cell surface Inferred from direct assay PubMed 12743035. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 12743035. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	growth factor activity Traceable author statement Ref.4. Source: ProtInc
Complete GO annotation...

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

Helical; 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. Ref.2

VAR_018918

Natural variant

Y → C. Ref.2

VAR_018919

Secondary structure

252

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P15514 [UniParc].

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

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 101-122.
[8]	"Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells." Johnson G.R., Kannan B., Shoyab M., Stromberg K. J. Biol. Chem. 268:2924-2931(1993) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS EGFR LIGAND.
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CNIH.
[10]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_001657.2.
XP_001125684.1. XM_001125684.4.

UniGene

Hs.270833.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P15514.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5766N.

IntAct

P15514. 2 interactions.

MINT

MINT-105624.

STRING

9606.ENSP00000264487.

PTM databases

PhosphoSite

P15514.

Proteomic databases

PaxDb

P15514.

PeptideAtlas

P15514.

PRIDE

P15514.

Protocols and materials databases

DNASU

374.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264487; ENSP00000264487; ENSG00000109321.
ENST00000380846; ENSP00000370227; ENSG00000205595.
ENST00000395748; ENSP00000379097; ENSG00000109321.

GeneID

374.
727738.

KEGG

hsa:374.
hsa:727738.

UCSC

uc021xpc.1. human.

Organism-specific databases

CTD

374.
727738.

GeneCards

GC04P075300.
GC04P075480.

HGNC

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

HPA

CAB023519.
HPA008720.

MIM

104640. gene.

neXtProt

NX_P15514.

PharmGKB

PA162376851.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41450.

HOGENOM

HOG000034038.

HOVERGEN

HBG060279.

InParanoid

P15514.

K09782.

OMA

EYEGEAE.

OrthoDB

EOG4C2HC5.

PhylomeDB

P15514.

Gene expression databases

ArrayExpress

P15514.

Bgee

P15514.

CleanEx

HS_AREG.

Genevestigator

P15514.

GermOnline

ENSG00000109321. Homo sapiens.
ENSG00000205595. Homo sapiens.

Family and domain databases

InterPro

IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view]

PANTHER

PTHR10740. PTHR10740. 1 hit.

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

BindingDB

P15514.

ChEMBL

CHEMBL3731.

EvolutionaryTrace

P15514.

NextBio

1565.

PMAP-CutDB

P15514.

SOURCE

Search...

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:	May 1, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents