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P15514 (AREG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length252 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.12

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

S100A4P264474EBI-953674,EBI-717058

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 10081
PRO_0000007473
Chain101 – 18787Amphiregulin
PRO_0000007474
Propeptide188 – 25265
PRO_0000007475

Regions

Transmembrane199 – 22123Helical; Potential
Domain142 – 18241EGF-like

Amino acid modifications

Glycosylation301N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential
Glycosylation1191N-linked (GlcNAc...)
Disulfide bond146 ↔ 159 Ref.13
Disulfide bond154 ↔ 170 Ref.13
Disulfide bond172 ↔ 181 Ref.13

Natural variations

Natural variant801D → V. Ref.2
VAR_018918
Natural variant811Y → C. Ref.2
VAR_018919

Secondary structure

.......... 252
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P15514 [UniParc].

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

FASTA25227,895
        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' 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]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"Clarification of the C-terminal proteolytic processing site of human Amphiregulin."
Levano K.S., Kenny P.A.
FEBS Lett. 586:3500-3502(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 188-194, CLEAVAGE SITE.
[11]"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.
[12]"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.
[13]"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, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30704 mRNA. Translation: AAA51781.1.
M30702 expand/collapse EMBL AC list , M30698, M30699, M30700, M30701 Genomic DNA. Translation: AAA51773.1.
AY442340 Genomic DNA. Translation: AAR05438.1.
BT019866 mRNA. Translation: AAV38669.1.
CH471057 Genomic DNA. Translation: EAX05710.1.
BC009799 mRNA. Translation: AAH09799.1.
BC146953 mRNA. Translation: AAI46954.1.
BC146967 mRNA. Translation: AAI46968.1.
CCDSCCDS3565.1.
PIRA34702.
RefSeqNP_001648.1. NM_001657.3.
UniGeneHs.270833.
Hs.645475.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RNLNMR-A142-184[»]
ProteinModelPortalP15514.
SMRP15514. Positions 142-184.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106869. 4 interactions.
DIPDIP-5766N.
IntActP15514. 5 interactions.
MINTMINT-105624.
STRING9606.ENSP00000264487.

Chemistry

BindingDBP15514.
ChEMBLCHEMBL3731.

PTM databases

PhosphoSiteP15514.

Polymorphism databases

DMDM113754.

Proteomic databases

MaxQBP15514.
PaxDbP15514.
PeptideAtlasP15514.
PRIDEP15514.

Protocols and materials databases

DNASU374.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264487; ENSP00000264487; ENSG00000109321.
ENST00000380846; ENSP00000370227; ENSG00000205595.
ENST00000395748; ENSP00000379097; ENSG00000109321.
GeneID374.
KEGGhsa:374.
hsa:727738.
UCSCuc021xpc.1. human.

Organism-specific databases

CTD374.
GeneCardsGC04P075300.
GC04P075480.
HGNCHGNC:651. AREG.
HGNC:34509. AREGB.
HPACAB023519.
HPA008720.
MIM104640. gene.
neXtProtNX_P15514.
PharmGKBPA162376851.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41450.
HOGENOMHOG000034038.
HOVERGENHBG060279.
InParanoidP15514.
KOK09782.
OMAMLRRIAI.
OrthoDBEOG7XDBH6.
PhylomeDBP15514.
TreeFamTF332773.

Enzyme and pathway databases

SignaLinkP15514.

Gene expression databases

BgeeP15514.
CleanExHS_AREG.
GenevestigatorP15514.

Family and domain databases

InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERPTHR10740. PTHR10740. 1 hit.
SMARTSM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP15514.
GeneWikiAmphiregulin.
NextBio1565.
PMAP-CutDBP15514.
PROP15514.
SOURCESearch...

Entry information

Entry nameAREG_HUMAN
AccessionPrimary (citable) accession number: P15514
Secondary accession number(s): Q5U026
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

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