ID   GHR_MOUSE               Reviewed;         650 AA.
AC   P16882; P16590; Q61653; Q6DI66; Q80W86; Q8R1M5; Q920Z3; Q9R264;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   27-MAR-2024, entry version 205.
DE   RecName: Full=Growth hormone receptor;
DE            Short=GH receptor;
DE   AltName: Full=Somatotropin receptor;
DE   Contains:
DE     RecName: Full=Growth hormone-binding protein;
DE              Short=GH-binding protein;
DE              Short=GHBP;
DE     AltName: Full=Serum-binding protein;
DE   Flags: Precursor;
GN   Name=Ghr;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=2739661; DOI=10.1210/mend-3-6-984;
RA   Smith W.C., Kuniyoshi J., Talamantes F.;
RT   "Mouse serum growth hormone (GH) binding protein has GH receptor
RT   extracellular and substituted transmembrane domains.";
RL   Mol. Endocrinol. 3:984-990(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE OF
RP   156-300 (ISOFORM 1).
RC   STRAIN=DBA/2J, and Swiss Webster;
RX   PubMed=7988474; DOI=10.1210/endo.135.6.7988474;
RA   Edens A., Southard J.N., Talamantes F.;
RT   "Mouse growth hormone receptor/binding protein and growth hormone receptor
RT   transcripts are produced from a single gene by alternative splicing.";
RL   Endocrinology 135:2802-2805(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RC   STRAIN=DBA/2J, and Swiss Webster;
RX   PubMed=10425445; DOI=10.1677/jme.0.0230033;
RA   Moffat J.G., Edens A., Talamantes F.;
RT   "Structure and expression of the mouse growth hormone receptor/growth
RT   hormone binding protein gene.";
RL   J. Mol. Endocrinol. 23:33-44(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 47-88 AND 156-650 (ISOFORM 1).
RC   STRAIN=C57BL/6J;
RX   PubMed=7894338;
RA   Zhou Y., He L., Kopchick J.J.;
RT   "An exon encoding the mouse growth hormone binding protein (mGHBP) carboxy
RT   terminus is located between exon 7 and 8 of the mouse growth hormone
RT   receptor gene.";
RL   Receptor 4:223-227(1994).
RN   [6]
RP   SEQUENCE REVISION.
RA   Zhou Y., He L., Kopchick J.J.;
RL   Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-650 (ISOFORM 1).
RC   STRAIN=129/SvJ;
RA   Rowland J.E., Waters M.J.;
RT   "Mouse growth hormone receptor cytoplasmic exons 9 and 10 genomic clone
RT   with flanking intronic sequence.";
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   PROTEIN SEQUENCE OF 25-41.
RX   PubMed=3398846; DOI=10.1210/mend-2-2-108;
RA   Smith W.C., Colosi P., Talamantes F.;
RT   "Isolation of two molecular weight variants of the mouse growth hormone
RT   receptor.";
RL   Mol. Endocrinol. 2:108-116(1988).
RN   [9]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=12379490; DOI=10.1677/joe.0.1750055;
RA   Talamantes F., Ortiz R.;
RT   "Structure and regulation of expression of the mouse GH receptor.";
RL   J. Endocrinol. 175:55-59(2002).
CC   -!- FUNCTION: Receptor for pituitary gland growth hormone involved in
CC       regulating postnatal body growth. On ligand binding, couples to, and
CC       activates the JAK2/STAT5 pathway (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: The soluble form (GHBP) acts as a reservoir of growth hormone
CC       in plasma and may be a modulator/inhibitor of GH signaling.
CC   -!- SUBUNIT: On growth hormone (GH) binding, forms homodimers and binds
CC       JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2
CC       activation, binding to CIS and SOCS2 inhibits STAT5 activation.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein. Note=On growth hormone binding, GHR is ubiquitinated,
CC       internalized, down-regulated and transported into a degradative or non-
CC       degradative pathway. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Growth hormone-binding protein]: Secreted
CC       {ECO:0000250}. Note=Complexed to a substantial fraction of circulating
CC       GH. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=HMW GHR;
CC         IsoId=P16882-1; Sequence=Displayed;
CC       Name=2; Synonyms=LMW GHR, GHBP;
CC         IsoId=P16882-2; Sequence=VSP_001716, VSP_001717;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues tested including, liver,
CC       heart, adipose tissue, mammary gland, testes, ovary, brain, kidney and
CC       muscle. Highest levels in liver.
CC   -!- DEVELOPMENTAL STAGE: During gestation, both hepatic and serum
CC       expression begins at day 9. Levels increased 8-fold in liver and 30-
CC       fold in serum by late gestation. Levels of isoform 1 and isoform 2
CC       similarly begin at day 9 with isoform 1 expression reaching maximum
CC       levels by day 13, isoform 2 levels continue to increase until the end
CC       of pregnancy. {ECO:0000269|PubMed:12379490}.
CC   -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC       folding and thereby efficient intracellular transport and cell-surface
CC       receptor binding.
CC   -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC       activation.
CC   -!- DOMAIN: The extracellular domain is the ligand-binding domain
CC       representing the growth hormone-binding protein (GHBP).
CC   -!- DOMAIN: The ubiquitination-dependent endocytosis motif (UbE) is
CC       required for recruitment of the ubiquitin conjugation system on to the
CC       receptor and for its internalization. {ECO:0000250}.
CC   -!- PTM: On GH binding, phosphorylated on tyrosine residues in the
CC       cytoplasmic domain by JAK2. {ECO:0000250}.
CC   -!- PTM: On ligand binding, ubiquitinated on lysine residues in the
CC       cytoplasmic domain. This ubiquitination is not sufficient for GHR
CC       internalization (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; M33324; AAA37690.1; ALT_SEQ; mRNA.
DR   EMBL; M31680; AAA37689.1; ALT_SEQ; mRNA.
DR   EMBL; U15012; AAA69000.1; -; Genomic_DNA.
DR   EMBL; U15011; AAA69000.1; JOINED; Genomic_DNA.
DR   EMBL; U15013; AAA69000.1; JOINED; Genomic_DNA.
DR   EMBL; AF120489; AAD32556.1; -; Genomic_DNA.
DR   EMBL; AF120481; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120482; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120483; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120484; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120485; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120486; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120487; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120488; AAD32556.1; JOINED; Genomic_DNA.
DR   EMBL; AF120487; AAD32555.1; -; Genomic_DNA.
DR   EMBL; AF120481; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; AF120482; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; AF120483; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; AF120484; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; AF120485; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; AF120486; AAD32555.1; JOINED; Genomic_DNA.
DR   EMBL; BC024375; AAH24375.1; -; mRNA.
DR   EMBL; BC075720; AAH75720.1; -; mRNA.
DR   EMBL; U49266; AAK62802.1; -; Genomic_DNA.
DR   EMBL; U49268; AAK62802.1; JOINED; Genomic_DNA.
DR   EMBL; U43933; AAK62802.1; JOINED; Genomic_DNA.
DR   EMBL; U49267; AAK62803.1; -; Genomic_DNA.
DR   EMBL; AY271378; AAP33018.1; -; Genomic_DNA.
DR   CCDS; CCDS27358.1; -. [P16882-1]
DR   CCDS; CCDS37024.1; -. [P16882-2]
DR   PIR; I48363; I48363.
DR   PIR; S33608; S33608.
DR   RefSeq; NP_001041643.1; NM_001048178.2. [P16882-2]
DR   RefSeq; NP_001273299.1; NM_001286370.1.
DR   RefSeq; NP_034414.2; NM_010284.3.
DR   AlphaFoldDB; P16882; -.
DR   SMR; P16882; -.
DR   BioGRID; 199915; 2.
DR   DIP; DIP-441N; -.
DR   IntAct; P16882; 1.
DR   MINT; P16882; -.
DR   STRING; 10090.ENSMUSP00000069457; -.
DR   GlyCosmos; P16882; 4 sites, No reported glycans.
DR   GlyGen; P16882; 4 sites.
DR   iPTMnet; P16882; -.
DR   PhosphoSitePlus; P16882; -.
DR   MaxQB; P16882; -.
DR   PaxDb; 10090-ENSMUSP00000069457; -.
DR   PeptideAtlas; P16882; -.
DR   ProteomicsDB; 265743; -. [P16882-1]
DR   ProteomicsDB; 265744; -. [P16882-2]
DR   Pumba; P16882; -.
DR   Antibodypedia; 23220; 492 antibodies from 36 providers.
DR   DNASU; 14600; -.
DR   Ensembl; ENSMUST00000110697.9; ENSMUSP00000106325.3; ENSMUSG00000055737.13. [P16882-2]
DR   Ensembl; ENSMUST00000110698.9; ENSMUSP00000106326.3; ENSMUSG00000055737.13. [P16882-2]
DR   GeneID; 14600; -.
DR   KEGG; mmu:14600; -.
DR   UCSC; uc007vce.2; mouse. [P16882-2]
DR   AGR; MGI:95708; -.
DR   CTD; 2690; -.
DR   MGI; MGI:95708; Ghr.
DR   VEuPathDB; HostDB:ENSMUSG00000055737; -.
DR   eggNOG; KOG3555; Eukaryota.
DR   GeneTree; ENSGT00940000159987; -.
DR   HOGENOM; CLU_017892_1_1_1; -.
DR   InParanoid; P16882; -.
DR   OrthoDB; 5317462at2759; -.
DR   PhylomeDB; P16882; -.
DR   Reactome; R-MMU-1170546; Prolactin receptor signaling.
DR   Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR   BioGRID-ORCS; 14600; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Ghr; mouse.
DR   PRO; PR:P16882; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; P16882; Protein.
DR   Bgee; ENSMUSG00000055737; Expressed in proximal tubule and 248 other cell types or tissues.
DR   ExpressionAtlas; P16882; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0070195; C:growth hormone receptor complex; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0043235; C:receptor complex; ISO:MGI.
DR   GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR   GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR   GO; GO:0004903; F:growth hormone receptor activity; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0008289; F:lipid binding; ISO:MGI.
DR   GO; GO:0017046; F:peptide hormone binding; IPI:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR   GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR   GO; GO:0032870; P:cellular response to hormone stimulus; ISO:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0042445; P:hormone metabolic process; ISO:MGI.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISO:MGI.
DR   GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:MGI.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:MGI.
DR   GO; GO:0040014; P:regulation of multicellular organism growth; IMP:BHF-UCL.
DR   GO; GO:0032107; P:regulation of response to nutrient levels; ISO:MGI.
DR   GO; GO:0032355; P:response to estradiol; ISO:MGI.
DR   GO; GO:0019530; P:taurine metabolic process; IMP:BHF-UCL.
DR   CDD; cd00063; FN3; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR025871; GHBP.
DR   InterPro; IPR015152; Growth/epo_recpt_lig-bind.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003528; Long_hematopoietin_rcpt_CS.
DR   PANTHER; PTHR23036; CYTOKINE RECEPTOR; 1.
DR   PANTHER; PTHR23036:SF108; GROWTH HORMONE RECEPTOR; 1.
DR   Pfam; PF09067; EpoR_lig-bind; 1.
DR   Pfam; PF12772; GHBP; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 2.
DR   PROSITE; PS50853; FN3; 1.
DR   PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
DR   Genevisible; P16882; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Direct protein sequencing;
KW   Disulfide bond; Endocytosis; Glycoprotein; Membrane; Phosphoprotein;
KW   Receptor; Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:3398846"
FT   CHAIN           25..650
FT                   /note="Growth hormone receptor"
FT                   /id="PRO_0000010961"
FT   CHAIN           25..264
FT                   /note="Growth hormone-binding protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000010962"
FT   TOPO_DOM        25..273
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        274..297
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        298..650
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          159..262
FT                   /note="Fibronectin type-III"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   REGION          303..390
FT                   /note="Required for JAK2 binding"
FT                   /evidence="ECO:0000250"
FT   REGION          466..486
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           248..252
FT                   /note="WSXWS motif"
FT   MOTIF           306..314
FT                   /note="Box 1 motif"
FT   MOTIF           349..358
FT                   /note="UbE motif"
FT   SITE            354
FT                   /note="Required for endocytosis and down-regulation"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         350
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P10912"
FT   CARBOHYD        123
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        164
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        208
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        56..66
FT                   /evidence="ECO:0000250"
FT   DISULFID        109..120
FT                   /evidence="ECO:0000250"
FT   DISULFID        134..148
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         271..297
FT                   /note="DIQFPWFLIIIFGIFGVAVMLFVVIFS -> GTKSNSQHPHQEIDNHLYHQL
FT                   QRIRHP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:2739661"
FT                   /id="VSP_001716"
FT   VAR_SEQ         298..650
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:2739661"
FT                   /id="VSP_001717"
FT   CONFLICT        25
FT                   /note="T -> A (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        162
FT                   /note="G -> A (in Ref. 5; AAK62802)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        240
FT                   /note="S -> F (in Ref. 2; AAA69000)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        325
FT                   /note="E -> G (in Ref. 3; AAD32556)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        423
FT                   /note="R -> A (in Ref. 3; AAD32556, 4; AAH75720 and 7;
FT                   AAP33018)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        510
FT                   /note="D -> V (in Ref. 4; AAH75720 and 7; AAP33018)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        559
FT                   /note="R -> P (in Ref. 4; AAH75720 and 7; AAP33018)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   650 AA;  72783 MW;  95653380CAF0B931 CRC64;
     MDLCQVFLTL ALAVTSSTFS GSEATPATLG KASPVLQRIN PSLGTSSSGK PRFTKCRSPE
     LETFSCYWTE GDNPDLKTPG SIQLYYAKRE SQRQAARIAH EWTQEWKECP DYVSAGKNSC
     YFNSSYTSIW IPYCIKLTTN GDLLDQKCFT VDEIVQPDPP IGLNWTLLNI SLTGIRGDIQ
     VSWQPPPNAD VLKGWIILEY EIQYKEVNES KWKVMGPIWL TYCPVYSLRM DKEHEVRVRS
     RQRSFEKYSE FSEVLRVIFP QTNILEACEE DIQFPWFLII IFGIFGVAVM LFVVIFSKQQ
     RIKMLILPPV PVPKIKGIDP DLLKEGKLEE VNTILGIHDN YKPDFYNDDS WVEFIELDID
     EADVDEKTEG SDTDRLLSND HEKSAGILGA KDDDSGRTSC YDPDILDTDF HTSDMCDGTL
     KFRQSQKLNM EADLLCLDQK NLKNLPYDAS LGSLHPSITQ TVEENKPQPL LSSETEATHQ
     LASTPMSNPT SLANIDFYAQ VSDITPAGGD VLSPGQKIKA GIAQGNTQRE VATPCQENYS
     MNSAYFCESD AKKCIAVARR MEATSCIKPS FNQEDIYITT ESLTTTAQMS ETADIAPDAE
     MSVPDYTTVH TVQSPRGLIL NATALPLPDK KNFPSSCGYV STDQLNKIMQ
//