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P15514

- AREG_HUMAN

UniProt

P15514 - AREG_HUMAN

Protein

Amphiregulin

Gene

AREG

more
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (01 Feb 1991)
      Previous versions | rss
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    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

    Keywords - Molecular functioni

    Cytokine, Growth factor

    Enzyme and pathway databases

    SignaLinkiP15514.

    Names & Taxonomyi

    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

    Organism-specific databases

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

    Subcellular locationi

    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 – 1919Sequence AnalysisAdd
    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...)Sequence Analysis
    Glycosylationi113 – 1131N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi119 – 1191N-linked (GlcNAc...)
    Disulfide bondi146 ↔ 1591 PublicationPROSITE-ProRule annotation
    Disulfide bondi154 ↔ 1701 PublicationPROSITE-ProRule annotation
    Disulfide bondi172 ↔ 1811 PublicationPROSITE-ProRule annotation

    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. 6 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP15514.

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei199 – 22123HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini142 – 18241EGF-likePROSITE-ProRule annotationAdd
    BLAST

    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

    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

    EnsembliENST00000395748; 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. 6 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 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: October 1, 2014
    This is version 140 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