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P16882

- GHR_MOUSE

UniProt

P16882 - GHR_MOUSE

Protein

Growth hormone receptor

Gene

Ghr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 147 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      Previous versions | rss
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    Functioni

    Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to, and activates the JAK2/STAT5 pathway By similarity.By similarity
    The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei354 – 3541Required for endocytosis and down-regulationBy similarity

    GO - Molecular functioni

    1. growth hormone receptor activity Source: MGI
    2. peptide hormone binding Source: MGI
    3. protein binding Source: BHF-UCL

    GO - Biological processi

    1. 2-oxoglutarate metabolic process Source: BHF-UCL
    2. allantoin metabolic process Source: BHF-UCL
    3. citrate metabolic process Source: BHF-UCL
    4. creatine metabolic process Source: BHF-UCL
    5. creatinine metabolic process Source: BHF-UCL
    6. cytokine-mediated signaling pathway Source: GOC
    7. endocytosis Source: UniProtKB-KW
    8. fatty acid metabolic process Source: BHF-UCL
    9. growth hormone receptor signaling pathway Source: BHF-UCL
    10. isoleucine metabolic process Source: BHF-UCL
    11. oxaloacetate metabolic process Source: BHF-UCL
    12. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
    13. regulation of multicellular organism growth Source: BHF-UCL
    14. succinate metabolic process Source: BHF-UCL
    15. taurine metabolic process Source: BHF-UCL
    16. valine metabolic process Source: BHF-UCL

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Endocytosis

    Enzyme and pathway databases

    ReactomeiREACT_198561. Prolactin receptor signaling.
    REACT_198614. Growth hormone receptor signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Growth hormone receptor
    Short name:
    GH receptor
    Alternative name(s):
    Somatotropin receptor
    Cleaved into the following chain:
    Growth hormone-binding protein
    Short name:
    GH-binding protein
    Short name:
    GHBP
    Alternative name(s):
    Serum-binding protein
    Gene namesi
    Name:Ghr
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:95708. Ghr.

    Subcellular locationi

    Cell membrane; Single-pass type I membrane protein
    Note: On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway.By similarity
    Chain Growth hormone-binding protein : Secreted By similarity
    Note: Complexed to a substantial fraction of circulating GH.By similarity

    GO - Cellular componenti

    1. extracellular region Source: Reactome
    2. extrinsic component of membrane Source: MGI
    3. integral component of membrane Source: UniProtKB-KW
    4. nucleus Source: MGI
    5. plasma membrane Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 24241 PublicationAdd
    BLAST
    Chaini25 – 650626Growth hormone receptorPRO_0000010961Add
    BLAST
    Chaini25 – 264240Growth hormone-binding proteinBy similarityPRO_0000010962Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi56 ↔ 66By similarity
    Disulfide bondi109 ↔ 120By similarity
    Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi134 ↔ 148By similarity
    Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.By similarity
    On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization By similarity.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP16882.
    PRIDEiP16882.

    PTM databases

    PhosphoSiteiP16882.

    Expressioni

    Tissue specificityi

    Expressed in all tissues tested including, liver, heart, adipose tissue, mammary gland, testes, ovary, brain, kidney and muscle. Highest levels in liver.

    Developmental stagei

    During gestation, both hepatic and serum expression begins at day 9. Levels increased 8-fold in liver and 30-fold in serum by late gestation. Levels of isoform 1 and isoform 2 similarly begin at day 9 with isoform 1 expression reaching maximum levels by day 13, isoform 2 levels continue to increase until the end of pregnancy.1 Publication

    Gene expression databases

    ArrayExpressiP16882.
    BgeeiP16882.
    CleanExiMM_GHR.
    GenevestigatoriP16882.

    Interactioni

    Subunit structurei

    On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation.By similarity

    Protein-protein interaction databases

    DIPiDIP-441N.
    IntActiP16882. 4 interactions.
    MINTiMINT-2738349.

    Structurei

    3D structure databases

    ProteinModelPortaliP16882.
    SMRiP16882. Positions 50-260.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini25 – 273249ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini298 – 650353CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei274 – 29724HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini159 – 262104Fibronectin type-IIIPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni303 – 39088Required for JAK2 bindingBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi248 – 2525WSXWS motif
    Motifi306 – 3149Box 1 motif
    Motifi349 – 35810UbE motif

    Domaini

    The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
    The box 1 motif is required for JAK interaction and/or activation.
    The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).
    The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.By similarity

    Sequence similaritiesi

    Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG45313.
    GeneTreeiENSGT00530000063112.
    HOVERGENiHBG005836.
    InParanoidiP16882.
    KOiK05080.
    OrthoDBiEOG79W94T.
    PhylomeDBiP16882.

    Family and domain databases

    Gene3Di2.60.40.10. 2 hits.
    InterProiIPR003961. Fibronectin_type3.
    IPR025871. GHBP.
    IPR015152. Growth/epo_recpt_lig-bind.
    IPR013783. Ig-like_fold.
    IPR003528. Long_hematopoietin_rcpt_CS.
    [Graphical view]
    PfamiPF09067. EpoR_lig-bind. 1 hit.
    PF12772. GHBP. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 2 hits.
    PROSITEiPS50853. FN3. 1 hit.
    PS01352. HEMATOPO_REC_L_F1. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P16882-1) [UniParc]FASTAAdd to Basket

    Also known as: HMW GHR

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDLCQVFLTL ALAVTSSTFS GSEATPATLG KASPVLQRIN PSLGTSSSGK    50
    PRFTKCRSPE LETFSCYWTE GDNPDLKTPG SIQLYYAKRE SQRQAARIAH 100
    EWTQEWKECP DYVSAGKNSC YFNSSYTSIW IPYCIKLTTN GDLLDQKCFT 150
    VDEIVQPDPP IGLNWTLLNI SLTGIRGDIQ VSWQPPPNAD VLKGWIILEY 200
    EIQYKEVNES KWKVMGPIWL TYCPVYSLRM DKEHEVRVRS RQRSFEKYSE 250
    FSEVLRVIFP QTNILEACEE DIQFPWFLII IFGIFGVAVM LFVVIFSKQQ 300
    RIKMLILPPV PVPKIKGIDP DLLKEGKLEE VNTILGIHDN YKPDFYNDDS 350
    WVEFIELDID EADVDEKTEG SDTDRLLSND HEKSAGILGA KDDDSGRTSC 400
    YDPDILDTDF HTSDMCDGTL KFRQSQKLNM EADLLCLDQK NLKNLPYDAS 450
    LGSLHPSITQ TVEENKPQPL LSSETEATHQ LASTPMSNPT SLANIDFYAQ 500
    VSDITPAGGD VLSPGQKIKA GIAQGNTQRE VATPCQENYS MNSAYFCESD 550
    AKKCIAVARR MEATSCIKPS FNQEDIYITT ESLTTTAQMS ETADIAPDAE 600
    MSVPDYTTVH TVQSPRGLIL NATALPLPDK KNFPSSCGYV STDQLNKIMQ 650
    Length:650
    Mass (Da):72,783
    Last modified:August 1, 1990 - v1
    Checksum:i95653380CAF0B931
    GO
    Isoform 2 (identifier: P16882-2) [UniParc]FASTAAdd to Basket

    Also known as: LMW GHR, GHBP

    The sequence of this isoform differs from the canonical sequence as follows:
         271-297: DIQFPWFLIIIFGIFGVAVMLFVVIFS → GTKSNSQHPHQEIDNHLYHQLQRIRHP
         298-650: Missing.

    Show »
    Length:297
    Mass (Da):34,105
    Checksum:i667F5F80088482A4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti25 – 251T → A AA sequence (PubMed:3398846)Curated
    Sequence conflicti162 – 1621G → A in AAK62802. (PubMed:7894338)Curated
    Sequence conflicti240 – 2401S → F in AAA69000. (PubMed:7988474)Curated
    Sequence conflicti325 – 3251E → G in AAD32556. (PubMed:10425445)Curated
    Sequence conflicti423 – 4231R → A in AAD32556. (PubMed:10425445)Curated
    Sequence conflicti423 – 4231R → A in AAH75720. (PubMed:15489334)Curated
    Sequence conflicti423 – 4231R → A in AAP33018. 1 PublicationCurated
    Sequence conflicti510 – 5101D → V in AAH75720. (PubMed:15489334)Curated
    Sequence conflicti510 – 5101D → V in AAP33018. 1 PublicationCurated
    Sequence conflicti559 – 5591R → P in AAH75720. (PubMed:15489334)Curated
    Sequence conflicti559 – 5591R → P in AAP33018. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei271 – 29727DIQFP…VVIFS → GTKSNSQHPHQEIDNHLYHQ LQRIRHP in isoform 2. 2 PublicationsVSP_001716Add
    BLAST
    Alternative sequencei298 – 650353Missing in isoform 2. 2 PublicationsVSP_001717Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M33324 mRNA. Translation: AAA37690.1. Sequence problems.
    M31680 mRNA. Translation: AAA37689.1. Sequence problems.
    U15012, U15011, U15013 Genomic DNA. Translation: AAA69000.1.
    AF120489
    , AF120481, AF120482, AF120483, AF120484, AF120485, AF120486, AF120487, AF120488 Genomic DNA. Translation: AAD32556.1.
    AF120487
    , AF120481, AF120482, AF120483, AF120484, AF120485, AF120486 Genomic DNA. Translation: AAD32555.1.
    BC024375 mRNA. Translation: AAH24375.1.
    BC075720 mRNA. Translation: AAH75720.1.
    U49266, U49268, U43933 Genomic DNA. Translation: AAK62802.1.
    U49267 Genomic DNA. Translation: AAK62803.1.
    AY271378 Genomic DNA. Translation: AAP33018.1.
    CCDSiCCDS27358.1. [P16882-1]
    CCDS37024.1. [P16882-2]
    PIRiI48363.
    S33608.
    RefSeqiNP_001041643.1. NM_001048178.2. [P16882-2]
    NP_001273299.1. NM_001286370.1.
    NP_034414.2. NM_010284.3.
    XP_006520026.1. XM_006519963.1.
    XP_006520027.1. XM_006519964.1.
    XP_006520028.1. XM_006519965.1.
    XP_006520029.1. XM_006519966.1.
    UniGeneiMm.3986.

    Genome annotation databases

    EnsembliENSMUST00000110697; ENSMUSP00000106325; ENSMUSG00000055737. [P16882-2]
    ENSMUST00000110698; ENSMUSP00000106326; ENSMUSG00000055737. [P16882-2]
    GeneIDi14600.
    KEGGimmu:14600.
    UCSCiuc007vcd.1. mouse. [P16882-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M33324 mRNA. Translation: AAA37690.1 . Sequence problems.
    M31680 mRNA. Translation: AAA37689.1 . Sequence problems.
    U15012 , U15011 , U15013 Genomic DNA. Translation: AAA69000.1 .
    AF120489
    , AF120481 , AF120482 , AF120483 , AF120484 , AF120485 , AF120486 , AF120487 , AF120488 Genomic DNA. Translation: AAD32556.1 .
    AF120487
    , AF120481 , AF120482 , AF120483 , AF120484 , AF120485 , AF120486 Genomic DNA. Translation: AAD32555.1 .
    BC024375 mRNA. Translation: AAH24375.1 .
    BC075720 mRNA. Translation: AAH75720.1 .
    U49266 , U49268 , U43933 Genomic DNA. Translation: AAK62802.1 .
    U49267 Genomic DNA. Translation: AAK62803.1 .
    AY271378 Genomic DNA. Translation: AAP33018.1 .
    CCDSi CCDS27358.1. [P16882-1 ]
    CCDS37024.1. [P16882-2 ]
    PIRi I48363.
    S33608.
    RefSeqi NP_001041643.1. NM_001048178.2. [P16882-2 ]
    NP_001273299.1. NM_001286370.1.
    NP_034414.2. NM_010284.3.
    XP_006520026.1. XM_006519963.1.
    XP_006520027.1. XM_006519964.1.
    XP_006520028.1. XM_006519965.1.
    XP_006520029.1. XM_006519966.1.
    UniGenei Mm.3986.

    3D structure databases

    ProteinModelPortali P16882.
    SMRi P16882. Positions 50-260.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-441N.
    IntActi P16882. 4 interactions.
    MINTi MINT-2738349.

    PTM databases

    PhosphoSitei P16882.

    Proteomic databases

    PaxDbi P16882.
    PRIDEi P16882.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000110697 ; ENSMUSP00000106325 ; ENSMUSG00000055737 . [P16882-2 ]
    ENSMUST00000110698 ; ENSMUSP00000106326 ; ENSMUSG00000055737 . [P16882-2 ]
    GeneIDi 14600.
    KEGGi mmu:14600.
    UCSCi uc007vcd.1. mouse. [P16882-2 ]

    Organism-specific databases

    CTDi 2690.
    MGIi MGI:95708. Ghr.

    Phylogenomic databases

    eggNOGi NOG45313.
    GeneTreei ENSGT00530000063112.
    HOVERGENi HBG005836.
    InParanoidi P16882.
    KOi K05080.
    OrthoDBi EOG79W94T.
    PhylomeDBi P16882.

    Enzyme and pathway databases

    Reactomei REACT_198561. Prolactin receptor signaling.
    REACT_198614. Growth hormone receptor signaling.

    Miscellaneous databases

    ChiTaRSi GHR. mouse.
    NextBioi 286368.
    PROi P16882.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P16882.
    Bgeei P16882.
    CleanExi MM_GHR.
    Genevestigatori P16882.

    Family and domain databases

    Gene3Di 2.60.40.10. 2 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR025871. GHBP.
    IPR015152. Growth/epo_recpt_lig-bind.
    IPR013783. Ig-like_fold.
    IPR003528. Long_hematopoietin_rcpt_CS.
    [Graphical view ]
    Pfami PF09067. EpoR_lig-bind. 1 hit.
    PF12772. GHBP. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 2 hits.
    PROSITEi PS50853. FN3. 1 hit.
    PS01352. HEMATOPO_REC_L_F1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains."
      Smith W.C., Kuniyoshi J., Talamantes F.
      Mol. Endocrinol. 3:984-990(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    2. "Mouse growth hormone receptor/binding protein and growth hormone receptor transcripts are produced from a single gene by alternative splicing."
      Edens A., Southard J.N., Talamantes F.
      Endocrinology 135:2802-2805(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE OF 156-300 (ISOFORM 1).
      Strain: DBA/2J and Swiss Webster.
    3. "Structure and expression of the mouse growth hormone receptor/growth hormone binding protein gene."
      Moffat J.G., Edens A., Talamantes F.
      J. Mol. Endocrinol. 23:33-44(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
      Strain: DBA/2J and Swiss Webster.
    4. "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] (ISOFORMS 1 AND 2).
      Tissue: Kidney.
    5. "An exon encoding the mouse growth hormone binding protein (mGHBP) carboxy terminus is located between exon 7 and 8 of the mouse growth hormone receptor gene."
      Zhou Y., He L., Kopchick J.J.
      Receptor 4:223-227(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 47-88 AND 156-650 (ISOFORM 1).
      Strain: C57BL/6.
    6. Zhou Y., He L., Kopchick J.J.
      Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    7. "Mouse growth hormone receptor cytoplasmic exons 9 and 10 genomic clone with flanking intronic sequence."
      Rowland J.E., Waters M.J.
      Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-650 (ISOFORM 1).
      Strain: 129/SvJ.
    8. "Isolation of two molecular weight variants of the mouse growth hormone receptor."
      Smith W.C., Colosi P., Talamantes F.
      Mol. Endocrinol. 2:108-116(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 25-41.
    9. "Structure and regulation of expression of the mouse GH receptor."
      Talamantes F., Ortiz R.
      J. Endocrinol. 175:55-59(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiGHR_MOUSE
    AccessioniPrimary (citable) accession number: P16882
    Secondary accession number(s): P16590
    , Q61653, Q6DI66, Q80W86, Q8R1M5, Q920Z3, Q9R264
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: August 1, 1990
    Last modified: October 1, 2014
    This is version 147 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3