GHR_MOUSE
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 03-AUG-2022, entry version 196.
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 GlyGen; P16882; 4 sites.
DR iPTMnet; P16882; -.
DR PhosphoSitePlus; P16882; -.
DR MaxQB; P16882; -.
DR PaxDb; P16882; -.
DR PeptideAtlas; P16882; -.
DR PRIDE; P16882; -.
DR ProteomicsDB; 265743; -. [P16882-1]
DR ProteomicsDB; 265744; -. [P16882-2]
DR Antibodypedia; 23220; 402 antibodies from 36 providers.
DR DNASU; 14600; -.
DR Ensembl; ENSMUST00000110697; ENSMUSP00000106325; ENSMUSG00000055737. [P16882-2]
DR Ensembl; ENSMUST00000110698; ENSMUSP00000106326; ENSMUSG00000055737. [P16882-2]
DR GeneID; 14600; -.
DR KEGG; mmu:14600; -.
DR UCSC; uc007vce.2; mouse. [P16882-2]
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; 346239at2759; -.
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 73 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 245 other tissues.
DR ExpressionAtlas; P16882; baseline and differential.
DR Genevisible; P16882; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; 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:0019898; C:extrinsic component of membrane; IDA:MGI.
DR GO; GO:0070195; C:growth hormone receptor complex; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO: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:0004896; F:cytokine receptor activity; 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: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:0042976; P:activation of Janus kinase activity; 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:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; 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: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; -; 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 Pfam; PF09067; EpoR_lig-bind; 1.
DR Pfam; PF12772; GHBP; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
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
