GHR_SAIBB
ID GHR_SAIBB Reviewed; 632 AA.
AC Q95ML5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 97.
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 Saimiri boliviensis boliviensis (Bolivian squirrel monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Saimiriinae; Saimiri.
OX NCBI_TaxID=39432;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11371582; DOI=10.1093/oxfordjournals.molbev.a003895;
RA Liu J.-C., Makova K.D., Adkins R.M., Gibson S., Li W.-H.;
RT "Episodic evolution of growth hormone in primates and emergence of the
RT species specificity of human growth hormone receptor.";
RL Mol. Biol. Evol. 18:945-953(2001).
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 {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Note=On growth hormone binding, GHR is
CC ubiquitinated, internalized, down-regulated and transported into a
CC degradative or non-degradative pathway. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Growth hormone-binding protein]: Secreted
CC {ECO:0000250}. Note=Complexed to a substantial fraction of circulating
CC GH. {ECO:0000250}.
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; AF339061; AAK62288.1; -; mRNA.
DR RefSeq; NP_001289860.1; NM_001302931.1.
DR AlphaFoldDB; Q95ML5; -.
DR SMR; Q95ML5; -.
DR STRING; 39432.ENSSBOP00000019300; -.
DR GeneID; 101042350; -.
DR CTD; 2690; -.
DR Proteomes; UP000233220; Whole Genome Shotgun Assembly.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004896; F:cytokine receptor activity; IEA:InterPro.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
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; PF00041; fn3; 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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Endocytosis; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..632
FT /note="Growth hormone receptor"
FT /id="PRO_0000010971"
FT CHAIN 19..256
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010972"
FT TOPO_DOM 19..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 151..254
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 294..379
FT /note="Required for JAK2 binding"
FT /evidence="ECO:0000250"
FT REGION 356..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 240..244
FT /note="WSXWS motif"
FT MOTIF 297..305
FT /note="Box 1 motif"
FT MOTIF 340..349
FT /note="UbE motif"
FT COMPBIAS 357..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 345
FT /note="Required for endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10912"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 56..66
FT /evidence="ECO:0000250"
FT DISULFID 101..112
FT /evidence="ECO:0000250"
FT DISULFID 126..140
FT /evidence="ECO:0000250"
SQ SEQUENCE 632 AA; 70884 MW; 440E17AF6277EDA3 CRC64;
MDLWQLLLTL ALAGSSDAFS GRETTAAVLS RVSQSLLSVN PGLKTNSSKE PKFTKCRSPE
LETFSCRWTD AVHHGLKSPG PIQLFYTRRN TQEGTQEWKE CPDYVSAGEN SCYFNSSFTS
IWIPYCIKLT SNGGTVDEKC FSVDQIVQPD PPIALNWTLL NISLTGVHAD IQVRWEAPPN
ADIQKGWMVL EYELQYKEVN ETQWKMMDPI LSTSVPLYSL RVDKEYEVRV RSRQRKSENY
GEFSEVLYVK LPQMSQFTCE EDFYYPWLLI IIFGISGLTV MLFVFLFSKQ QRIKMLILPP
VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI EDPDEKTEGL
DTDRLLSSDH EKSRSNLGVK DGDSGRTSCY EPDMLETDFN ANDIHDGTSE VVQPQRLKGE
ADLLCLDQKN QNNSPYHDAC PAIHQPSVIQ AEKNKPQPLL IDGAESTHQA AHIQLSNPSS
LANIDFYAQV SDITPAGSVV LSPGQKNNGG MSQWDMHPEV VSLCQANFIM DNAYFCEADA
KKCIPVTPHI KVESHTEPSF NQEDIYITTE SLTTTARRPG TAEHVPGSEM PVPDYTSIHI
VQSPQGLILN ATALPLPDKE FLSSCGYVAQ TN
