GHR_PIG
ID GHR_PIG Reviewed; 638 AA.
AC P19756;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 25-MAY-2022, entry version 143.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Landrace X Yorkshire; TISSUE=Liver;
RX PubMed=2243805; DOI=10.1093/nar/18.21.6451;
RA Cioffi J.A., Wang X., Kopchick J.J.;
RT "Porcine growth hormone receptor cDNA sequence.";
RL Nucleic Acids Res. 18:6451-6451(1990).
RN [2]
RP PHOSPHORYLATION, STAT5 ACTIVATION, AND MUTAGENESIS OF TYR-332; TYR-337;
RP TYR-390; TYR-487; TYR-534; TYR-566; TYR-595 AND TYR-627.
RX PubMed=8647880; DOI=10.1074/jbc.271.21.12669;
RA Hansen L.H., Wang X., Kopchick J.J., Bouchelouche P., Nielsen J.H.,
RA Galsgaard E.D., Billestrup N.;
RT "Identification of tyrosine residues in the intracellular domain of the
RT growth hormone receptor required for transcriptional signaling and Stat5
RT activation.";
RL J. Biol. Chem. 271:12669-12673(1996).
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.
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; X54429; CAA38301.1; -; mRNA.
DR PIR; S12136; S12136.
DR AlphaFoldDB; P19756; -.
DR SMR; P19756; -.
DR DIP; DIP-650N; -.
DR STRING; 9823.ENSSSCP00000017873; -.
DR PaxDb; P19756; -.
DR PRIDE; P19756; -.
DR eggNOG; KOG3555; Eukaryota.
DR InParanoid; P19756; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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 GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA: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; PF00041; fn3; 1.
DR Pfam; PF12772; GHBP; 1.
DR SMART; SM00060; FN3; 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 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 CHAIN 19..638
FT /note="Growth hormone receptor"
FT /id="PRO_0000010965"
FT CHAIN 19..256
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010966"
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..638
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 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 SITE 345
FT /note="Required for ubiquitin-dependent internalization and
FT 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"
FT MUTAGEN 332
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 337
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 390
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 487
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 534
FT /note="Y->F: Loss of transcriptional signaling; when
FT associated with F-566 or F-627."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 566
FT /note="Y->F: Loss of transcriptional signaling. when
FT associated with F-534 or F-627."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 595
FT /note="Y->F: Loss of transcriptional signaling."
FT /evidence="ECO:0000269|PubMed:8647880"
FT MUTAGEN 627
FT /note="Y->F: Loss of transcriptional signaling. when
FT associated with F-534 or F-566."
FT /evidence="ECO:0000269|PubMed:8647880"
SQ SEQUENCE 638 AA; 71145 MW; BC7C66536F4DFF97 CRC64;
MDLWQLLLTL AVAGSSDAFS GSEATPAVLV RASQSLQRVH PGLETNSSGK PKFTKCRSPE
LETFSCHWTD GVRHGLQSPG SIQLFYIRRS TQEWTQEWKE CPDYVSAGEN SCYFNSSYTS
IWIPYCIKLT SNGGTVDQKC FSVEEIVQPD PPIGLNWTLL NISLTGIHAD IQVRWEPPPN
ADVQKGWIVL EYELQYKEVN ETQWKMMDPV LSTSVPVYSL RLDKEYEVRV RSRQRNSEKY
GEFSEVLYVT LPQMSPFACE EDFRFPWFLI IIFGIFGLTV ILFLLIFSKQ QRIKMLILPP
VPVPKIKGID PDLLKEGKLE EVNTILAIHD NYKHEFYSDD SWVEFIELDI DDPDEKTEGS
DTDRLLNNDH EKSLTILGAK EDDSGRTSCY EPDILETDFN ANDVCDGTAE VAQPQRLKGE
ADLLCLDQKN QNNSPSNDAA PATQQPSVIL AEENKPRPLI ISGTDSTHQT AHTQLSNPSS
LANIDFYAQV SDITPAGSVV LSPGQKNKAG ISQCDMHLEV VSPCPANFIM DNAYFCEADA
KKCIAMAPHV EVESRLAPSF NQEDIYITTE SLTTTAGRSA TAECAPSSEM PVPDYTSIHI
VQSPQGLVLN ATALPLPDKE FLSSCGYVST DQLNKIMP
