GHR_BOSIN
ID GHR_BOSIN Reviewed; 634 AA.
AC P79108;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 25-MAY-2022, entry version 112.
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 Bos indicus (Zebu).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9915;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Gir; TISSUE=Liver;
RA Souza S.C., Wang X., Lobo R.B., Kopchick J.J.;
RT "Bovine growth hormone receptor cDNA derived from Bos taurus indicus.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
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 {ECO:0000250}.
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). {ECO:0000250}.
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; X70041; CAA49635.1; -; mRNA.
DR AlphaFoldDB; P79108; -.
DR SMR; P79108; -.
DR Proteomes; UP000515132; Genome 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; 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..634
FT /note="Growth hormone receptor"
FT /id="PRO_0000010949"
FT CHAIN 19..252
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010950"
FT TOPO_DOM 19..260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..634
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 147..250
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 290..375
FT /note="Required for JAK2 binding"
FT /evidence="ECO:0000250"
FT MOTIF 236..240
FT /note="WSXWS motif"
FT MOTIF 293..301
FT /note="Box 1 motif"
FT MOTIF 336..345
FT /note="UbE motif"
FT SITE 341
FT /note="Required for endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10912"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 56..66
FT /evidence="ECO:0000250"
FT DISULFID 97..108
FT /evidence="ECO:0000250"
FT DISULFID 122..136
FT /evidence="ECO:0000250"
SQ SEQUENCE 634 AA; 70980 MW; 91955A28296CBD2E CRC64;
MDLWQLLLTL AVAGSSDAFS GSEATPAFLV RASQSLQILY PVLETNSSGN PKFTKCRSPE
LETFSCHWTD GANHSLQSPG SVQMFYIRRD IQEWKECPDY VSAGENSCYF NSSYTSVWTP
YCIKLTSNGG IVDHKCFSVE DIVQPDPPVG LNWTLLNISL TEIHADILVK WEPPPNTDVK
MGWIILEYEL HYKELNETQW KMMDPLMVTS VPMYSLRLDK EYEVRVRTRQ RNTEKYGKFS
EVLLITFPQM NPSACEEDFQ FPWFLIIMFG ILGLAVTLFL LIFSKQQRIK MLILPPVPVP
KIKGIDPDLL KEGKLEEVNT ILAIHDNYKH EFYNDDSWVE FIELDIDDPD EKTEGSDTDR
LLSNDHEKSL NIFGAKDDDS GRTSCYEPDI LEADFHVSDM CDGTSEVAQP QRLKGEADIS
CLDQKNQNNS PSNDAAPANQ QPSVIHVEEN KPRPLLIGGT ESTHQAVHHQ LSNPSSLANI
DFYAQVSDIT PAGNVVLSPG QKNKTGNPQC DTHPEVVTSC QANFIVDNAY FCEVDAKKYI
ALAPHVEAES HVEPSFNQED IYITTESLTT TAGRSGTAEH VPSSEIPVPD YTSIHIVQSP
QGLVLNATAL PLPDKEFLSS CGYVSTDQLN KIMP
