GHR_CHICK
ID GHR_CHICK Reviewed; 608 AA.
AC Q02092; Q6LDA0;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 145.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2036984; DOI=10.1210/endo-128-6-3183;
RA Burnside J., Liou S.S., Cogburn L.A.;
RT "Molecular cloning of the chicken growth hormone receptor complementary
RT deoxyribonucleic acid: mutation of the gene in sex-linked dwarf chickens.";
RL Endocrinology 128:3183-3192(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-112.
RC TISSUE=Liver;
RX PubMed=8114754; DOI=10.1210/mend.7.11.8114754;
RA Huang N., Cogburn L.A., Agarwal S.K., Marks H.L., Burnside J.;
RT "Overexpression of a truncated growth hormone receptor in the sex-linked
RT dwarf chicken: evidence for a splice mutation.";
RL Mol. Endocrinol. 7:1391-1398(1993).
RN [3]
RP PROTEOLYTIC PROCESSING.
RX PubMed=10082631; DOI=10.1006/gcen.1998.7202;
RA Vleurick L., Kuhn E.R., Decuypere E., Burnside J., Pezet A., Edery M.;
RT "Generation of chicken growth hormone-binding proteins by proteolysis.";
RL Gen. Comp. Endocrinol. 113:283-289(1999).
RN [4]
RP INTERNALIZATION, AND JAK2 ACTIVATION.
RX PubMed=11997231; DOI=10.1016/s1096-4959(02)00037-4;
RA Kuhn E.R., Vleurick L., Edery M., Decuypere E., Darras V.M.;
RT "Internalization of the chicken growth hormone receptor complex and its
RT effect on biological functions.";
RL Comp. Biochem. Physiol. 132B:299-308(2002).
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 {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; Single-pass type I membrane
CC protein. Note=On growth hormone binding, GHR is ubiquitinated,
CC internalized, down-regulated and transported into a degradative or non-
CC degradative pathway.
CC -!- TISSUE SPECIFICITY: Broad specificity.
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.
CC -!- PTM: On GH binding, proteolytically cleaved, in vitro, to produce GHBP.
CC {ECO:0000269|PubMed:10082631}.
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 -!- PTM: Proteolytically cleaved, in vitro, to release the growth hormone-
CC binding protein (GHBP). {ECO:0000269|PubMed:10082631}.
CC -!- DISEASE: Note=Defects in GHR are a cause of sex-linked dwarf chicken. A
CC restriction fragment length polymorphism, and an aberrantly-sized
CC transcript in liver leads to a GHR with undetectable GH-binding
CC activity causing growth deficiency and other endocrine abnormalities.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; M74057; AAA48781.1; -; mRNA.
DR EMBL; S68576; AAB29983.2; -; mRNA.
DR PIR; S32823; S32823.
DR RefSeq; NP_001001293.1; NM_001001293.1.
DR AlphaFoldDB; Q02092; -.
DR SMR; Q02092; -.
DR STRING; 9031.ENSGALP00000023927; -.
DR PaxDb; Q02092; -.
DR GeneID; 408184; -.
DR KEGG; gga:408184; -.
DR CTD; 2690; -.
DR VEuPathDB; HostDB:geneid_408184; -.
DR eggNOG; KOG3555; Eukaryota.
DR InParanoid; Q02092; -.
DR OrthoDB; 346239at2759; -.
DR PhylomeDB; Q02092; -.
DR PRO; PR:Q02092; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
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: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; 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; Dwarfism; Endocytosis; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..608
FT /note="Growth hormone receptor"
FT /id="PRO_0000010943"
FT CHAIN 17..?
FT /note="Growth hormone-binding protein"
FT /id="PRO_0000010944"
FT TOPO_DOM 17..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..608
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 122..226
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 413..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 211..215
FT /note="WSXWS motif"
FT MOTIF 270..278
FT /note="Box 1 motif"
FT MOTIF 313..322
FT /note="UbE motif"
FT SITE 318
FT /note="Required for endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..44
FT /evidence="ECO:0000250"
FT DISULFID 72..83
FT /evidence="ECO:0000250"
FT DISULFID 97..111
FT /evidence="ECO:0000250"
FT CONFLICT 111..112
FT /note="CF -> KK (in Ref. 2; AAB29983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 608 AA; 68573 MW; D71AD7B6C62528DC CRC64;
MDLRHLLFTL ALVCANDSLS ASDDLLQWPQ ISKCRSPELE TFSCYWTDGK VTTSGTIQLL
YMKRSDEDWK ECPDYITAGE NSCYFNTSYT SIWIPYCVKL ANKDEVFDEK CFSVDEIVLP
DPPVHLNWTL LNTSQTGIHG DIQVRWDPPP TADVQKGWIT LEYELQYKEV NETKWKELEP
RLSTVVPLYS LKMGRDYEIR VRSRQRTSEK FGEFSEILYV SFTQAGIEFV HCAEEIEFPW
FLVVVFGVCG LAVTAILILL SKQPRLKMLI FPPVPVPKIK GIDPDLLKKG KLDEVNSILA
SHDNYKTQLY NDDLWVEFIE LDIDDSDEKN RVSDTDRLLS DDHLKSHSCL GAKDDDSGRA
SCYEPDIPET DFSASDTCDA ISDIDQFKKV TEKEEDLLCL HRKDDVEALQ SLANTDTQQP
HTSTQSESRE SWPPFADSTD SANPSVQTQL SNQNSLTNTD FYAQVSDITP AGSVVLSPGQ
KSKVGRAQCE SCTEQNFTMD NAYFCEADVK KCIAVISQEE DEPRVQEQSC NEDTYFTTES
LTTTGINLGA SMAETPSMEM PVPDYTSIHI VHSPQGLVLN ATALPVPEKE FNMSCGYVST
DQLNKIMP
