GHR_CANLF
ID GHR_CANLF Reviewed; 638 AA.
AC Q9TU69; Q29394;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 131.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RC TISSUE=Mammary gland;
RX PubMed=10579357; DOI=10.1210/endo.140.12.7189;
RA van Garderen E., van der Poel H.J.A., Swennenhuis J.F., Wissink E.H.J.,
RA Rutteman G.R., Hellmen E., Mol J.A., Schalken J.A.;
RT "Expression and molecular characterization of the growth hormone receptor
RT in canine mammary tissue and mammary tumors.";
RL Endocrinology 140:5907-5914(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 351-373.
RX PubMed=8894053; DOI=10.1007/bf02399951;
RA Venta P.J., Brouillette J.A., Yuzbasiyan-Gurkan V., Brewer G.J.;
RT "Gene-specific universal mammalian sequence-tagged sites: application to
RT the canine genome.";
RL Biochem. Genet. 34:321-341(1996).
CC -!- FUNCTION: Receptor for pituitary gland growth hormone involved in
CC regulating postnatal body growth. On ligand binding, couples to the
CC 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9TU69-1; Sequence=Displayed;
CC Name=2; Synonyms=Putative protein A;
CC IsoId=Q9TU69-2; Sequence=Not described;
CC Name=3; Synonyms=Putative protein B;
CC IsoId=Q9TU69-3; Sequence=Not described;
CC Name=4; Synonyms=Putative protein C;
CC IsoId=Q9TU69-4; Sequence=Not described;
CC Name=5; Synonyms=Putative protein D;
CC IsoId=Q9TU69-5; Sequence=Not described;
CC -!- TISSUE SPECIFICITY: Expressed in normal and tumorous mammary tissues,
CC being localized in epithelial and myoepithelial/spindle cell components
CC and in the activated fibroblasts of desmoplastic tumor stroma. Isoform
CC 1, isoform 2 and isoform 3 are found in both normal and tumorous
CC mammary tissues, isoform 1 being the predominant isoform. Isoform 1,
CC isoform 3, isoform 4 and isoform 5 are expressed in the CMT-U335 cell
CC line.
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 -!- MISCELLANEOUS: [Isoform 2]: Produced by exon 8 skipping resulting in a
CC frameshift and introduction of a stopcodon at position 12 of exon 9.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by exon 7 skipping resulting in a
CC frameshift and introduction of a stopcodon at position 619.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by the usage of alternative splice
CC donor/acceptor sites resulting in the elimination of the greater part
CC of exon 6 and the beginning of exon 7. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by the usage of alternative splice
CC donor site resulting in the elimination of a part of exon 7 and the
CC entire exon 8. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF133835; AAF07397.1; -; mRNA.
DR EMBL; L77673; AAA97423.1; -; Genomic_DNA.
DR RefSeq; NP_001003123.1; NM_001003123.1. [Q9TU69-1]
DR AlphaFoldDB; Q9TU69; -.
DR SMR; Q9TU69; -.
DR STRING; 9612.ENSCAFP00000037936; -.
DR PaxDb; Q9TU69; -.
DR GeneID; 403721; -.
DR KEGG; cfa:403721; -.
DR CTD; 2690; -.
DR eggNOG; KOG3555; Eukaryota.
DR InParanoid; Q9TU69; -.
DR OrthoDB; 346239at2759; -.
DR Proteomes; UP000002254; 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 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 SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Endocytosis;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..638
FT /note="Growth hormone receptor"
FT /id="PRO_0000010953"
FT CHAIN 19..256
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010954"
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 REGION 428..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 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"
SQ SEQUENCE 638 AA; 71041 MW; DD4AF6F48E75B840 CRC64;
MDLWQLLLTL AVAGSGSAFS GSEATPTILG SASQSLQRVN PGLGTNSSEK PKFTKCRSPE
LETFSCHWTD GVRHGLKNAG SVQLFYIRRS TQEWTQEWKE CPDYVSAGEN SCYFNSSYTS
IWIPYCIKLT SNGGTVDQKC FSVEEIVQPD PPIGLNWTLL NISLTGIHAD IQVRWEPPPN
ADVQKGWIVL KYELQYKEVN ESQWKMMDPV SATSVPVYSL RLDKEYEVRV RSRQRNSEKY
GEFSEALYVT LPQMSPFACE EDFQFPWFLI IIFGIFGLTM ILFLFIFSKQ QRIKMLILPP
VPVPKIKGID PDLLKEGKLE EVNTILAIHD NYKPEFYNDD SWVEFIELDI DDLDEKTEGS
DTDRLLSNDH EKSLNILGAK DDDSGRTSCY EPDILETDFN ASDVCDGTSE VAQPQRLKGE
VDLLCLDQKN QNNSPSTDTT PTTQQPSIIL AKENKPRPLL ISGTESTQQA AHTQLSNPSS
LANIDFYAQV SDITLAGSVV LSPGQKNKAG ISPCDMPPEV ASLCQANFIM DNAYFCEADA
KKCITVAPHV EAESRVEPSF NQEDIYITTE SLTTTAGQSG TTERAVSSEM PVPDYTSIHI
IQSPRGLVLN ATALPLPDKE FLSSCGYVST DQLNKIMP
