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Protein

Growth hormone receptor

Gene

Ghr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to, and activates the JAK2/STAT5 pathway.
The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei346 – 3461Required for endocytosis and down-regulation

GO - Molecular functioni

  • growth hormone receptor activity Source: RGD
  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: RGD
  • SH2 domain binding Source: RGD

GO - Biological processi

  • activation of JAK2 kinase activity Source: BHF-UCL
  • activation of Janus kinase activity Source: RGD
  • activation of MAPK activity Source: BHF-UCL
  • cartilage development involved in endochondral bone morphogenesis Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • endocytosis Source: UniProtKB-KW
  • growth hormone receptor signaling pathway Source: BHF-UCL
  • hormone-mediated signaling pathway Source: RGD
  • JAK-STAT cascade Source: BHF-UCL
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • negative regulation of neuron death Source: RGD
  • positive regulation of cell differentiation Source: RGD
  • positive regulation of JAK-STAT cascade Source: RGD
  • response to cytokine Source: RGD
  • response to food Source: RGD
  • response to glucocorticoid Source: RGD
  • response to hormone Source: RGD
  • response to interleukin-1 Source: RGD
  • response to morphine Source: RGD
  • response to peptide hormone Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Endocytosis

Enzyme and pathway databases

ReactomeiR-RNO-1170546. Prolactin receptor signaling.
R-RNO-982772. Growth hormone receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth hormone receptor
Short name:
GH receptor
Alternative name(s):
Somatotropin receptor
Cleaved into the following chain:
Growth hormone-binding protein
Short name:
GH-binding protein
Short name:
GHBP
Alternative name(s):
Serum-binding protein
Gene namesi
Name:Ghr
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi2687. Ghr.

Subcellular locationi

Isoform 2 :
  • Secreted
  • Membrane

  • Note: Mainly secreted. In adipose tissue, isoform 2 is mostly membrane associated.
Growth hormone-binding protein :
  • Secreted By similarity

  • Note: Complexed to a substantial fraction of circulating GH.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 265247ExtracellularSequence analysisAdd
BLAST
Transmembranei266 – 28924HelicalSequence analysisAdd
BLAST
Topological domaini290 – 638349CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: RGD
  • extracellular space Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • mitochondrion Source: RGD
  • neuronal cell body Source: RGD
  • nucleus Source: RGD
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi346 – 3461F → A: No internalization nor down-regulation. No effect on transcriptional signaling. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence analysisAdd
BLAST
Chaini19 – 638620Growth hormone receptorPRO_0000010969Add
BLAST
Chaini19 – 256238Growth hormone-binding proteinBy similarityPRO_0000010970Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi56 ↔ 66By similarity
Disulfide bondi101 ↔ 112By similarity
Glycosylationi115 – 1151N-linked (GlcNAc...)Sequence analysis
Disulfide bondi126 ↔ 140By similarity
Glycosylationi156 – 1561N-linked (GlcNAc...)Sequence analysis
Glycosylationi161 – 1611N-linked (GlcNAc...)Sequence analysis
Glycosylationi200 – 2001N-linked (GlcNAc...)Sequence analysis
Modified residuei342 – 3421PhosphoserineBy similarity

Post-translational modificationi

On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2. Phosphorylation on either (or all of) Tyr-534, Tyr-566 and/or Tyr-627 is required for STAT5 activation. Phosphorylation on Tyr-333 would seem necessary for JAK2 activation.2 Publications
On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP16310.
PRIDEiP16310.

PTM databases

iPTMnetiP16310.
PhosphoSiteiP16310.

Expressioni

Tissue specificityi

Highest expression in liver. Also expressed in heart, kidney and muscle.

Developmental stagei

Expression is low at birth. Increases to adult levels after 5 weeks.

Gene expression databases

BgeeiENSRNOG00000015654.
ExpressionAtlasiP16310. baseline and differential.
GenevisibleiP16310. RN.

Interactioni

Subunit structurei

On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation.

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: RGD
  • SH2 domain binding Source: RGD

Protein-protein interaction databases

BioGridi247275. 1 interaction.
DIPiDIP-63N.
IntActiP16310. 1 interaction.
MINTiMINT-4588405.
STRINGi10116.ENSRNOP00000044119.

Structurei

3D structure databases

ProteinModelPortaliP16310.
SMRiP16310. Positions 50-254.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini151 – 254104Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni295 – 38086Required for JAK2 bindingAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi240 – 2445WSXWS motif
Motifi298 – 3069Box 1 motif
Motifi341 – 35010UbE motif

Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.1 Publication
The box 1 motif is required for JAK interaction and/or activation.1 Publication
The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).1 Publication
The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.1 Publication

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
GeneTreeiENSGT00530000063112.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP16310.
KOiK05080.
OMAiIDFYAQV.
OrthoDBiEOG091G03CN.
PhylomeDBiP16310.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16310-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDLWRVFLTL ALAVSSDMFP GSGATPATLG KASPVLQRIN PSLRESSSGK
60 70 80 90 100
PRFTKCRSPE LETFSCYWTE GDDHNLKVPG SIQLYYARRI AHEWTPEWKE
110 120 130 140 150
CPDYVSAGAN SCYFNSSYTS IWIPYCIKLT TNGDLLDEKC FTVDEIVQPD
160 170 180 190 200
PPIGLNWTLL NISLPGIRGD IQVSWQPPPS ADVLKGWIIL EYEIQYKEVN
210 220 230 240 250
ETKWKTMSPI WSTSVPLYSL RLDKEHEVRV RSRQRSFEKY SEFSEVLRVT
260 270 280 290 300
FPQMDTLAAC EEDFRFPWFL IIIFGIFGVA VMLFVVIFSK QQRIKMLILP
310 320 330 340 350
PVPVPKIKGI DPDLLKEGKL EEVNTILGIH DNYKPDFYND DSWVEFIELD
360 370 380 390 400
IDDADEKTEE SDTDRLLSDD QEKSAGILGA KDDDSGRTSC YDPDILDTDF
410 420 430 440 450
HTSDMCDGTS EFAQPQKLKA EADLLCLDQK NLKNSPYDAS LGSLHPSITL
460 470 480 490 500
TMEDKPQPLL GSETESTHQL PSTPMSSPVS LANIDFYAQV SDITPAGGVV
510 520 530 540 550
LSPGQKIKAG LAQGNTQLEV AAPCQENYSM NSAYFCESDA KKCIAAAPHM
560 570 580 590 600
EATTCVKPSF NQEDIYITTE SLTTTARMSE TADTAPDAEP VPDYTTVHTV
610 620 630
KSPRGLILNA TALPLPDKKK FLSSCGYVST DQLNKIMQ
Length:638
Mass (Da):71,237
Last modified:August 1, 1990 - v1
Checksum:i0D8E9AF759A21A3B
GO
Isoform 2 (identifier: P16310-2) [UniParc]FASTAAdd to basket
Also known as: Short from, GHBP

The sequence of this isoform differs from the canonical sequence as follows:
     263-279: DFRFPWFLIIIFGIFGV → GPKFNSQHPHQEIDNHL
     280-638: Missing.

Show »
Length:279
Mass (Da):31,957
Checksum:iE0704AC95DB1B7C3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei263 – 27917DFRFP…GIFGV → GPKFNSQHPHQEIDNHL in isoform 2. 1 PublicationVSP_010231Add
BLAST
Alternative sequencei280 – 638359Missing in isoform 2. 1 PublicationVSP_010232Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04811 mRNA. Translation: AAA41219.1.
S49003 mRNA. Translation: AAP13886.1.
U44722 Genomic DNA. Translation: AAC52916.1.
PIRiA32985. A33505.
B32985.
RefSeqiNP_058790.1. NM_017094.1. [P16310-1]
XP_008758976.1. XM_008760754.1. [P16310-1]
UniGeneiRn.2178.

Genome annotation databases

EnsembliENSRNOT00000046951; ENSRNOP00000044119; ENSRNOG00000015654. [P16310-1]
GeneIDi25235.
KEGGirno:25235.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04811 mRNA. Translation: AAA41219.1.
S49003 mRNA. Translation: AAP13886.1.
U44722 Genomic DNA. Translation: AAC52916.1.
PIRiA32985. A33505.
B32985.
RefSeqiNP_058790.1. NM_017094.1. [P16310-1]
XP_008758976.1. XM_008760754.1. [P16310-1]
UniGeneiRn.2178.

3D structure databases

ProteinModelPortaliP16310.
SMRiP16310. Positions 50-254.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247275. 1 interaction.
DIPiDIP-63N.
IntActiP16310. 1 interaction.
MINTiMINT-4588405.
STRINGi10116.ENSRNOP00000044119.

PTM databases

iPTMnetiP16310.
PhosphoSiteiP16310.

Proteomic databases

PaxDbiP16310.
PRIDEiP16310.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000046951; ENSRNOP00000044119; ENSRNOG00000015654. [P16310-1]
GeneIDi25235.
KEGGirno:25235.

Organism-specific databases

CTDi2690.
RGDi2687. Ghr.

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
GeneTreeiENSGT00530000063112.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP16310.
KOiK05080.
OMAiIDFYAQV.
OrthoDBiEOG091G03CN.
PhylomeDBiP16310.

Enzyme and pathway databases

ReactomeiR-RNO-1170546. Prolactin receptor signaling.
R-RNO-982772. Growth hormone receptor signaling.

Miscellaneous databases

PROiP16310.

Gene expression databases

BgeeiENSRNOG00000015654.
ExpressionAtlasiP16310. baseline and differential.
GenevisibleiP16310. RN.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR003961. FN3_dom.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGHR_RAT
AccessioniPrimary (citable) accession number: P16310
Secondary accession number(s): Q64236, Q80XW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: September 7, 2016
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.