GHR_COLLI
ID GHR_COLLI Reviewed; 611 AA.
AC Q90375;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 106.
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 Columba livia (Rock dove).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Columbiformes; Columbidae; Columba.
OX NCBI_TaxID=8932;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Cheng C.H.K., Shaw P.C., Tsim K.W.K., Lau K.F.;
RT "Molecular cloning of the entire coding sequence of pigeon growth hormone
RT receptor cDNA by PCR techniques.";
RL Submitted (JAN-1996) 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.
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 -!- 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; U20353; AAA84745.1; -; mRNA.
DR AlphaFoldDB; Q90375; -.
DR SMR; Q90375; -.
DR STRING; 8932.XP_005514612.1; -.
DR eggNOG; KOG3555; Eukaryota.
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; 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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Endocytosis; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..611
FT /note="Growth hormone receptor"
FT /id="PRO_0000010945"
FT CHAIN 21..?
FT /note="Growth hormone-binding protein"
FT /id="PRO_0000010946"
FT TOPO_DOM 21..240
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265..611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 125..228
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 270..355
FT /note="Required for JAK2 binding"
FT /evidence="ECO:0000250"
FT REGION 411..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 214..218
FT /note="WSXWS motif"
FT MOTIF 273..281
FT /note="Box 1 motif"
FT MOTIF 316..325
FT /note="UbE motif"
FT COMPBIAS 411..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 321
FT /note="Required for endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT CARBOHYD 16
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..44
FT /evidence="ECO:0000250"
FT DISULFID 75..86
FT /evidence="ECO:0000250"
FT DISULFID 100..114
FT /evidence="ECO:0000250"
SQ SEQUENCE 611 AA; 68851 MW; C48750BF9EE4EBDA CRC64;
MDLRHLLLTL VLVCANDSLS ASDDVLRLPQ ISKCRSPELE TFSCYWTDGN FYNLSAPGTI
QLLYMKRNDE DWKECPDYIT AGENSCYFNT SYTSIWIPYC VKLVNKDEVF DEKCFSVDEI
VLPDPPVHLN WTLLNTSQTG IHGDIQVRWD PPPTADVQKG WITLEYELQY KEVNETKWKE
LEPRLSTMVP LYSLKIGRDY EIRVRSRQRT SEKFGEFSEI LYVSFSQAGI EFVHCAEEIE
FPWFLVVIFG ACGLAVTVIL ILLSKQSRLK MLIFPPVPVP KIKGIDPDLL KKGKLDEVNS
ILASHDNYKT QLYNDDLWVE FIELDIEDPD EKNRVSDTDR LLSEDHLKSH SCLGAKDDDS
GRASCCEPDI PETDFSASDT CDAISDIDQF KKVTEKEEDL LCLGRKDNDE SLPSLANTDT
QQPRMSTRPE NSQPWPPFAD SIDAASPSAH NQLSNQNSLR NTDFYAQVSD ITPAGSVVLS
PGQKSKVARA RCEFCTEQNF TLDNAYFCEA DVKKCIAVIS HEEDEPRVQA QICNEDTYFT
TESLTTTGIS LGASTAETPS PEVPVPDYTS IHIVHSPQGL VLNATALPVP DKEFNMSCGY
VSTDQLNKIM P
