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P15514

- AREG_HUMAN

UniProt

P15514 - AREG_HUMAN

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Protein

Amphiregulin

Gene
AREG, SDGF
AREGB
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. growth factor activity Source: ProtInc
  2. protein binding Source: IntAct

GO - Biological processi

  1. cell-cell signaling Source: ProtInc
  2. cell proliferation Source: ProtInc
  3. epidermal growth factor receptor signaling pathway Source: BHF-UCL
  4. G-protein coupled receptor signaling pathway Source: BHF-UCL
  5. positive regulation of DNA replication Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

SignaLinkiP15514.

Names & Taxonomyi

Organism-specific databases

Protein namesi
Recommended name:
Amphiregulin
Short name:
AR
Alternative name(s):
Colorectum cell-derived growth factor
Short name:
CRDGF
Gene namesi
Name:AREG
Synonyms:SDGF
AND
Name:AREGB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4
HGNCiHGNC:651. AREG.
HGNC:34509. AREGB.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei199 – 22123Helical; Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. extracellular space Source: BHF-UCL
  3. integral component of membrane Source: UniProtKB-KW

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162376851.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919 Reviewed predictionAdd
BLAST
Propeptidei20 – 10081PRO_0000007473Add
BLAST
Chaini101 – 18787AmphiregulinPRO_0000007474Add
BLAST
Propeptidei188 – 25265PRO_0000007475Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi30 – 301N-linked (GlcNAc...) Reviewed prediction
Glycosylationi113 – 1131N-linked (GlcNAc...) Reviewed prediction
Glycosylationi119 – 1191N-linked (GlcNAc...)
Disulfide bondi146 ↔ 1591 Publication
Disulfide bondi154 ↔ 1701 Publication
Disulfide bondi172 ↔ 1811 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP15514.
PaxDbiP15514.
PeptideAtlasiP15514.
PRIDEiP15514.

PTM databases

PhosphoSiteiP15514.

Miscellaneous databases

PMAP-CutDBP15514.

Expressioni

Inductioni

By phorbol 12-myristate 13-acetate (PMA).

Gene expression databases

BgeeiP15514.
CleanExiHS_AREG.
GenevestigatoriP15514.

Organism-specific databases

HPAiCAB023519.
HPA008720.

Interactioni

Subunit structurei

The immature precursor interacts with CNIH.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
S100A4P264474EBI-953674,EBI-717058

Protein-protein interaction databases

BioGridi106869. 4 interactions.
DIPiDIP-5766N.
IntActiP15514. 5 interactions.
MINTiMINT-105624.
STRINGi9606.ENSP00000264487.

Structurei

Secondary structure

1
252
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni145 – 1495
Helixi150 – 1523
Beta strandi155 – 1628
Turni163 – 1664
Beta strandi167 – 1715
Beta strandi178 – 1803

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2RNLNMR-A142-184[»]
ProteinModelPortaliP15514.
SMRiP15514. Positions 142-184.

Miscellaneous databases

EvolutionaryTraceiP15514.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini142 – 18241EGF-likeAdd
BLAST

Sequence similaritiesi

Belongs to the amphiregulin family.
Contains 1 EGF-like domain.

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG41450.
HOGENOMiHOG000034038.
HOVERGENiHBG060279.
InParanoidiP15514.
KOiK09782.
OMAiMLRRIAI.
OrthoDBiEOG7XDBH6.
PhylomeDBiP15514.
TreeFamiTF332773.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P15514-1 [UniParc]FASTAAdd to Basket

« Hide

MRAPLLPPAP VVLSLLILGS GHYAAGLDLN DTYSGKREPF SGDHSADGFE    50
VTSRSEMSSG SEISPVSEMP SSSEPSSGAD YDYSEEYDNE PQIPGYIVDD 100
SVRVEQVVKP PQNKTESENT SDKPKRKKKG GKNGKNRRNR KKKNPCNAEF 150
QNFCIHGECK YIEHLEAVTC KCQQEYFGER CGEKSMKTHS MIDSSLSKIA 200
LAAIAAFMSA VILTAVAVIT VQLRRQYVRK YEGEAEERKK LRQENGNVHA 250
IA 252
Length:252
Mass (Da):27,895
Last modified:February 1, 1991 - v2
Checksum:i68C1FA6BCD4D2BED
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801D → V.1 Publication
VAR_018918
Natural varianti81 – 811Y → C.1 Publication
VAR_018919

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M30704 mRNA. Translation: AAA51781.1.
M30702
, 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.
CCDSiCCDS3565.1.
PIRiA34702.
RefSeqiNP_001648.1. NM_001657.3.
UniGeneiHs.270833.
Hs.645475.

Genome annotation databases

EnsembliENST00000264487; ENSP00000264487; ENSG00000109321.
ENST00000380846; ENSP00000370227; ENSG00000205595.
ENST00000395748; ENSP00000379097; ENSG00000109321.
GeneIDi374.
KEGGihsa:374.
UCSCiuc021xpc.1. human.

Polymorphism databases

DMDMi113754.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M30704 mRNA. Translation: AAA51781.1 .
M30702
, 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 .
CCDSi CCDS3565.1.
PIRi A34702.
RefSeqi NP_001648.1. NM_001657.3.
UniGenei Hs.270833.
Hs.645475.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2RNL NMR - A 142-184 [» ]
ProteinModelPortali P15514.
SMRi P15514. Positions 142-184.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106869. 4 interactions.
DIPi DIP-5766N.
IntActi P15514. 5 interactions.
MINTi MINT-105624.
STRINGi 9606.ENSP00000264487.

Chemistry

BindingDBi P15514.
ChEMBLi CHEMBL3731.

PTM databases

PhosphoSitei P15514.

Polymorphism databases

DMDMi 113754.

Proteomic databases

MaxQBi P15514.
PaxDbi P15514.
PeptideAtlasi P15514.
PRIDEi P15514.

Protocols and materials databases

DNASUi 374.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264487 ; ENSP00000264487 ; ENSG00000109321 .
ENST00000380846 ; ENSP00000370227 ; ENSG00000205595 .
ENST00000395748 ; ENSP00000379097 ; ENSG00000109321 .
GeneIDi 374.
KEGGi hsa:374.
UCSCi uc021xpc.1. human.

Organism-specific databases

CTDi 374.
GeneCardsi GC04P075300.
GC04P075480.
HGNCi HGNC:651. AREG.
HGNC:34509. AREGB.
HPAi CAB023519.
HPA008720.
MIMi 104640. gene.
neXtProti NX_P15514.
PharmGKBi PA162376851.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG41450.
HOGENOMi HOG000034038.
HOVERGENi HBG060279.
InParanoidi P15514.
KOi K09782.
OMAi MLRRIAI.
OrthoDBi EOG7XDBH6.
PhylomeDBi P15514.
TreeFami TF332773.

Enzyme and pathway databases

SignaLinki P15514.

Miscellaneous databases

EvolutionaryTracei P15514.
GeneWikii Amphiregulin.
NextBioi 1565.
PMAP-CutDB P15514.
PROi P15514.
SOURCEi Search...

Gene expression databases

Bgeei P15514.
CleanExi HS_AREG.
Genevestigatori P15514.

Family and domain databases

InterProi IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view ]
PANTHERi PTHR10740. PTHR10740. 1 hit.
SMARTi SM00181. EGF. 1 hit.
[Graphical view ]
PROSITEi PS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiAREG_HUMAN
AccessioniPrimary (citable) accession number: P15514
Secondary accession number(s): Q5U026
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1991
Last modified: September 3, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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