GHR_CAVPO
ID GHR_CAVPO Reviewed; 628 AA.
AC Q9JI97; Q9JKG1; Q9JKT1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 111.
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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12110920;
RA Zhang X.N., Lu X.B., Zhu S.Q.;
RT "cDNA cloning of the guinea pig growth hormone receptor.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 32:81-83(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10767558; DOI=10.1016/s0378-1119(00)00053-6;
RA Adkins R.M., Vandeberg J., Li W.-H.;
RT "Molecular evolution of growth hormone and receptor in the guinea-pig, a
RT mammal unresponsive to growth hormone.";
RL Gene 246:357-363(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jullie H.A., Ymer S.I., Harrop S.A., Odorico D.M., Herington A.C.;
RT "Sequence of the guinea pig growth hormone (GH) receptor: a possible
RT explanation for the GH insensitivity of the guinea pig.";
RL Submitted (JAN-2000) 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. {ECO:0000250}.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation. {ECO:0000250}.
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 -!- MISCELLANEOUS: Guinea-pig is completely unresponsive to endogenous or
CC exogenous growth hormone. It is not clear whether the aberrant behavior
CC of its GH-GHR system can be attributed to a defect in post-receptor
CC signaling.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF247665; AAF74191.1; -; mRNA.
DR EMBL; AF238492; AAF67171.1; -; mRNA.
DR EMBL; AF227186; AAF35249.1; -; mRNA.
DR RefSeq; NP_001166177.1; NM_001172706.1.
DR AlphaFoldDB; Q9JI97; -.
DR SMR; Q9JI97; -.
DR STRING; 10141.ENSCPOP00000012923; -.
DR GeneID; 100135527; -.
DR KEGG; cpoc:100135527; -.
DR CTD; 2690; -.
DR eggNOG; KOG3555; Eukaryota.
DR InParanoid; Q9JI97; -.
DR OrthoDB; 346239at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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..628
FT /note="Growth hormone receptor"
FT /id="PRO_0000010955"
FT CHAIN 19..256
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010956"
FT TOPO_DOM 19..266
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..628
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 endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10912"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 CONFLICT 73
FT /note="H -> P (in Ref. 3; AAF35249)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="Q -> K (in Ref. 2; AAF67171)"
FT /evidence="ECO:0000305"
FT CONFLICT 165..166
FT /note="TA -> NS (in Ref. 3; AAF35249)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="I -> T (in Ref. 2; AAF67171)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="V -> I (in Ref. 2; AAF67171)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="D -> N (in Ref. 2; AAF67171)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="L -> Q (in Ref. 2; AAF67171)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 628 AA; 70355 MW; 82487BAAF86660D1 CRC64;
MDLWQLLLTL AVVGSSNAFV GREAVTVTLN RANLSLQRVN ASLETNSSGN PKFTKCRSPE
LETFSCHWTD EGHHGLKSTG FIQMFYTKRN SQEQNQEWKE CPDYVSAGEN SCYFNSSYTS
IWKPYCVKLT SNGGKVDEKC FYVEEIVQPD PPTGLNWTLM NTSATAIYGD IQVRWKPPRS
ADVKKGWIML DYELQIKQTN ETQWKMMDPV TSTSVPLYSL RLDKEYEVRI RSRLQNSDKY
GEFSEILYIT LPQSSPFTCE EEFQFPWFLI MIFGIFGLTV MLLVVMFSKQ QRIKMLILPP
VPVPKIKGVD PDLLKEGKLE EVNTILAIHD NSKPQFYNDD SWVEFIELDI DDSDEKIEGS
DTDRLLSSDH QKSLNILGAK DGDSGRTSCY EPDILEADFN ANDGTSEDVQ PDKLKEEADL
LCLDEKNQNN SPCDAPPDPQ QALVIPPEEE KPQPLLIGKT ESTNQDAPNQ ISNPISLANM
DFYAQVSDIT PAGSVVLSPG QKNKAGLSQC EAHPEANFVK DNACFFKGDA KNPDVMTPHI
EVKSHEEPSF KQEDPYITTE SLTTAAEKSG PPEQSPSSEM ALPDYTSIHI VQSPQGLILN
AAALPLPDKE FLSSCGYVST DQLNKIML
