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Protein

Amphiregulin

Gene

AREG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109321-MONOMER.
ReactomeiR-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
SignaLinkiP15514.
SIGNORiP15514.

Names & Taxonomyi

Protein namesi
Recommended name:
Amphiregulin1 Publication
Short name:
AR1 Publication
Alternative name(s):
Colorectum cell-derived growth factor1 Publication
Short name:
CRDGF1 Publication
Gene namesi
Name:AREGImported
Synonyms:AREGBImported, SDGFImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:651. AREG.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei199 – 221HelicalSequence analysisAdd BLAST23

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi374.
OpenTargetsiENSG00000109321.
PharmGKBiPA162376851.

Chemistry databases

ChEMBLiCHEMBL3731.

Polymorphism and mutation databases

BioMutaiAREG.
DMDMi113754.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000000747320 – 100Add BLAST81
ChainiPRO_0000007474101 – 187AmphiregulinAdd BLAST87
PropeptideiPRO_0000007475188 – 252Add BLAST65

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi30N-linked (GlcNAc...)Sequence analysis1
Glycosylationi113N-linked (GlcNAc...)Sequence analysis1
Glycosylationi119N-linked (GlcNAc...)1
Disulfide bondi146 ↔ 159PROSITE-ProRule annotation1 Publication
Disulfide bondi154 ↔ 170PROSITE-ProRule annotation1 Publication
Disulfide bondi172 ↔ 181PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP15514.
PaxDbiP15514.
PeptideAtlasiP15514.
PRIDEiP15514.

PTM databases

iPTMnetiP15514.
PhosphoSitePlusiP15514.

Miscellaneous databases

PMAP-CutDBP15514.

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000109321.
CleanExiHS_AREG.
ExpressionAtlasiP15514. baseline and differential.
GenevisibleiP15514. HS.

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106869. 11 interactors.
DIPiDIP-5766N.
IntActiP15514. 8 interactors.
MINTiMINT-105624.
STRINGi9606.ENSP00000370227.

Chemistry databases

BindingDBiP15514.

Structurei

Secondary structure

1252
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni145 – 149Combined sources5
Helixi150 – 152Combined sources3
Beta strandi155 – 162Combined sources8
Turni163 – 166Combined sources4
Beta strandi167 – 171Combined sources5
Beta strandi178 – 180Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RNLNMR-A142-184[»]
ProteinModelPortaliP15514.
SMRiP15514.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15514.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini142 – 182EGF-likePROSITE-ProRule annotationAdd BLAST41

Sequence similaritiesi

Belongs to the amphiregulin family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXZG. Eukaryota.
ENOG4112CXY. LUCA.
GeneTreeiENSGT00530000063708.
HOGENOMiHOG000034038.
HOVERGENiHBG060279.
InParanoidiP15514.
KOiK09782.
OMAiCKCHQDY.
PhylomeDBiP15514.
TreeFamiTF332773.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
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

        10         20         30         40         50
MRAPLLPPAP VVLSLLILGS GHYAAGLDLN DTYSGKREPF SGDHSADGFE
60 70 80 90 100
VTSRSEMSSG SEISPVSEMP SSSEPSSGAD YDYSEEYDNE PQIPGYIVDD
110 120 130 140 150
SVRVEQVVKP PQNKTESENT SDKPKRKKKG GKNGKNRRNR KKKNPCNAEF
160 170 180 190 200
QNFCIHGECK YIEHLEAVTC KCQQEYFGER CGEKSMKTHS MIDSSLSKIA
210 220 230 240 250
LAAIAAFMSA VILTAVAVIT VQLRRQYVRK YEGEAEERKK LRQENGNVHA

IA
Length:252
Mass (Da):27,895
Last modified:February 1, 1991 - v2
Checksum:i68C1FA6BCD4D2BED
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01891880D → V.1 PublicationCorresponds to variant rs373527160dbSNPEnsembl.1
Natural variantiVAR_01891981Y → C.1 PublicationCorresponds to variant rs28364979dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
AC021180 Genomic DNA. No translation available.
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

EnsembliENST00000395748; ENSP00000379097; ENSG00000109321.
GeneIDi374.
KEGGihsa:374.
UCSCiuc032tme.2. human.

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:
EMBLi
GenBanki
DDBJi
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.
AC021180 Genomic DNA. No translation available.
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RNLNMR-A142-184[»]
ProteinModelPortaliP15514.
SMRiP15514.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106869. 11 interactors.
DIPiDIP-5766N.
IntActiP15514. 8 interactors.
MINTiMINT-105624.
STRINGi9606.ENSP00000370227.

Chemistry databases

BindingDBiP15514.
ChEMBLiCHEMBL3731.

PTM databases

iPTMnetiP15514.
PhosphoSitePlusiP15514.

Polymorphism and mutation databases

BioMutaiAREG.
DMDMi113754.

Proteomic databases

EPDiP15514.
PaxDbiP15514.
PeptideAtlasiP15514.
PRIDEiP15514.

Protocols and materials databases

DNASUi374.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395748; ENSP00000379097; ENSG00000109321.
GeneIDi374.
KEGGihsa:374.
UCSCiuc032tme.2. human.

Organism-specific databases

CTDi374.
DisGeNETi374.
GeneCardsiAREG.
HGNCiHGNC:651. AREG.
HPAiCAB023519.
HPA008720.
MIMi104640. gene.
neXtProtiNX_P15514.
OpenTargetsiENSG00000109321.
PharmGKBiPA162376851.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IXZG. Eukaryota.
ENOG4112CXY. LUCA.
GeneTreeiENSGT00530000063708.
HOGENOMiHOG000034038.
HOVERGENiHBG060279.
InParanoidiP15514.
KOiK09782.
OMAiCKCHQDY.
PhylomeDBiP15514.
TreeFamiTF332773.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109321-MONOMER.
ReactomeiR-HSA-204005. COPII (Coat Protein 2) Mediated Vesicle Transport.
R-HSA-5694530. Cargo concentration in the ER.
SignaLinkiP15514.
SIGNORiP15514.

Miscellaneous databases

EvolutionaryTraceiP15514.
GeneWikiiAmphiregulin.
GenomeRNAii374.
PMAP-CutDBP15514.
PROiP15514.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109321.
CleanExiHS_AREG.
ExpressionAtlasiP15514. baseline and differential.
GenevisibleiP15514. HS.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 161 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.