GHR_BOVIN
ID GHR_BOVIN Reviewed; 634 AA.
AC O46600; O77538; Q5XM78; Q9TQV9; Q9TUY7;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 25-MAY-2022, entry version 137.
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 taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Liver;
RX PubMed=2289631; DOI=10.1016/0303-7207(90)90143-v;
RA Hauser S.D., McGrath M.F., Collier R.J., Krivi G.G.;
RT "Cloning and in vivo expression of bovine growth hormone receptor mRNA.";
RL Mol. Cell. Endocrinol. 72:187-200(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Liver;
RX PubMed=9710756; DOI=10.3168/jds.s0022-0302(98)75760-1;
RA Lucy M.C., Boyd C.K., Koenigsfeld A.T., Okamura C.S.;
RT "Expression of somatotropin receptor messenger ribonucleic acid in bovine
RT tissues.";
RL J. Dairy Sci. 81:1889-1895(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou Y., Jiang H.;
RT "Functional expression of bovine growth hormone receptor.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-14.
RX PubMed=11255006; DOI=10.1016/s0378-1119(01)00356-0;
RA Jiang H., Lucy M.C.;
RT "Variants of the 5'-untranslated region of the bovine growth hormone
RT receptor mRNA: isolation, expression and effects on translational
RT efficiency.";
RL Gene 265:45-53(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 470-634, AND VARIANT SER-519.
RX PubMed=10376317; DOI=10.1046/j.1365-2052.1999.00382-9.x;
RA Ge W., Davis M.E., Hines H.C., Irvin K.M.;
RT "Polymorphism in exon 10 of the bovine GHR gene detected by PCR-DGGE.";
RL Anim. Genet. 30:167-168(1999).
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 -!- TISSUE SPECIFICITY: Highly expressed in both adult and fetal liver.
CC Lower levels in kidney, anterior pituitary, skeletal muscle, adipose
CC tissue and mammary gland.
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; AF044258; AAC02534.1; -; mRNA.
DR EMBL; AY748827; AAU94310.1; -; mRNA.
DR EMBL; AF036297; AAC33315.2; -; mRNA.
DR EMBL; AF085281; AAD22521.1; -; mRNA.
DR EMBL; AF036290; AAC33308.1; -; mRNA.
DR EMBL; AF036291; AAC33309.1; -; mRNA.
DR EMBL; AF036292; AAC33310.1; -; mRNA.
DR EMBL; AF036293; AAC33311.1; -; mRNA.
DR EMBL; AF036294; AAC33312.1; -; mRNA.
DR EMBL; AF036295; AAC33313.1; -; mRNA.
DR EMBL; AF036296; AAC33314.1; -; mRNA.
DR EMBL; AF326349; AAK97345.1; -; mRNA.
DR EMBL; AF140284; AAD45668.1; -; Genomic_DNA.
DR RefSeq; NP_788781.1; NM_176608.1.
DR AlphaFoldDB; O46600; -.
DR SMR; O46600; -.
DR STRING; 9913.ENSBTAP00000001758; -.
DR PaxDb; O46600; -.
DR PRIDE; O46600; -.
DR GeneID; 280805; -.
DR KEGG; bta:280805; -.
DR CTD; 2690; -.
DR eggNOG; KOG3555; Eukaryota.
DR InParanoid; O46600; -.
DR OrthoDB; 346239at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IDA:AgBase.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0070195; C:growth hormone receptor complex; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:AgBase.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0004903; F:growth hormone receptor activity; IBA:GO_Central.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
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_0000010951"
FT CHAIN 19..252
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010952"
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"
FT VARIANT 519
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:10376317"
FT CONFLICT 71
FT /note="G -> V (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="Y -> F (in Ref. 3; AAU94310)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="N -> T (in Ref. 3; AAU94310)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="V -> I (in Ref. 2; AAC02534 and 3; AAU94310)"
FT /evidence="ECO:0000305"
FT CONFLICT 555
FT /note="S -> G (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="S -> F (in Ref. 5; AAD45668)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="P -> S (in Ref. 5; AAD45668)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 634 AA; 70901 MW; B86920A99261BE75 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 FPWFLIIIFG ILGLAVTLYL LIFSKQQRIK MLILPPVPVP
KIKGIDPDLL KEGKLEEVNT ILAIHDNYKH EFYNDDSWVE FIELDIDDPD EKTEGSDTDR
LLSNDHEKSL NIFGAKDDDS GRTSCYEPDI LEADFHVSDM CDGTSEVAQP QRLKGEADIS
CLDQKNQNNS PSNDAAPASQ QPSVILVEEN KPRPLLIGGT ESTHQAVHTQ LSNPSSLANI
DFYAQVSDIT PAGNVVLSPG QKNKTGNPQC DTHPEVVTPC QANFIVDNAY FCEVDAKKYI
ALAPHVEAES HVEPSFNQED IYITTESLTT TAGRSGTAEH VPSSEIPVPD YTSIHIVQSP
QGLVLNATAL PLPDKEFLSS CGYVSTDQLN KIMP
