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Protein

Growth hormone receptor

Gene

GHR

Organism
Oryctolagus cuniculus (Rabbit)
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 (By similarity).By similarity
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)DescriptionActionsGraphical viewLength
Sitei345Required for endocytosis and down-regulation1

GO - Molecular functioni

  • cytokine receptor activity Source: InterPro
  • peptide hormone binding Source: BHF-UCL
  • proline-rich region binding Source: BHF-UCL

GO - Biological processi

  • endocytosis Source: UniProtKB-KW
  • growth hormone receptor signaling pathway Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Endocytosis

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

Growth hormone-binding protein :
  • Secreted

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 264ExtracellularSequence analysisAdd BLAST246
Transmembranei265 – 288HelicalSequence analysisAdd BLAST24
Topological domaini289 – 638CytoplasmicSequence analysisAdd BLAST350

GO - Cellular componenti

  • endosome lumen Source: Reactome
  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: BHF-UCL
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi338N → A: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi339D → A: Slightly impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi340D → A: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi341S → A: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi341S → L or T: Slightly impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi342W → A: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi342W → L: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi343V → A: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi343V → G: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi344E → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication1
Mutagenesisi344E → D: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi345F → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication1
Mutagenesisi345F → L or V: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi345F → Y: No effect on GHR-mediated GH internalization. No effect on ubiquitination. 1 Publication1
Mutagenesisi346I → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication1
Mutagenesisi346I → F: Slightly impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi346I → L: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi347E → A or D: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi348L → A or V: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi349D → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication1
Mutagenesisi349D → E: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi349D → N: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi350I → A: Impaired GHR-mediated GH internalization. 1 Publication1
Mutagenesisi351D → A: No effect on GHR-mediated GH internalization. 1 Publication1
Mutagenesisi352D → A: No effect on GHR-mediated GH internalization. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Add BLAST18
ChainiPRO_000001096719 – 638Growth hormone receptorAdd BLAST620
ChainiPRO_000001096819 – 256Growth hormone-binding proteinAdd BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi56 ↔ 66By similarity
Disulfide bondi101 ↔ 112By similarity
Glycosylationi115N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi126 ↔ 140By similarity
Glycosylationi156N-linked (GlcNAc...)Sequence analysis1
Glycosylationi161N-linked (GlcNAc...)Sequence analysis1
Glycosylationi200N-linked (GlcNAc...)Sequence analysis1
Modified residuei341PhosphoserineBy similarity1

Post-translational modificationi

The soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. Shedding is inhibited by growth hormone (GH) binding to the receptor probably due to a conformational change in GHR rendering the receptor inaccessible to ADAM17.1 Publication
On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.By similarity
On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

PTM databases

iPTMnetiP19941.

Miscellaneous databases

PMAP-CutDBP19941.

Interactioni

Subunit structurei

On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain (By similarity). Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation (By similarity). Interacts with ADAM17.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Stat5aP422303EBI-7526279,EBI-617434From a different organism.
Stat5bP422326EBI-7526279,EBI-617454From a different organism.

GO - Molecular functioni

  • proline-rich region binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi1172345. 4 interactors.
DIPiDIP-313N.
IntActiP19941. 4 interactors.
MINTiMINT-1535520.
STRINGi9986.ENSOCUP00000007343.

Structurei

3D structure databases

ProteinModelPortaliP19941.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini151 – 254Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni260 – 262Required for ADAM17-mediated proteolysis3
Regioni294 – 379Required for JAK2 bindingBy similarityAdd BLAST86

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi240 – 244WSXWS motif5
Motifi297 – 305Box 1 motif9
Motifi340 – 349UbE motif10

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP19941.
KOiK05080.

Family and domain databases

CDDicd00063. FN3. 1 hit.
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.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P19941-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLWQLLLTV ALAGSSDAFS GSEATPATLG RASESVQRVH PGLGTNSSGK
60 70 80 90 100
PKFTKCRSPE LETFSCHWTD GVHHGLKSPG SVQLFYIRRN TQEWTQEWKE
110 120 130 140 150
CPDYVSAGEN SCYFNSSYTS IWIPYCIKLT NNGGMVDQKC FSVEEIVQPD
160 170 180 190 200
PPIGLNWTLL NVSLTGIHAD IQVRWEPPPN ADVQKGWIVL EYELQYKEVN
210 220 230 240 250
ETQWKMMDPV LSTSVPVYSL RLDKEYEVRV RSRQRSSEKY GEFSEVLYVT
260 270 280 290 300
LPQMSPFTCE EDFRFPWFLI IIFGIFGLTV MLFVFIFSKQ QRIKMLILPP
310 320 330 340 350
VPVPKIKGID PDLLKEGKLE EVNTILAIQD SYKPEFYNDD SWVEFIELDI
360 370 380 390 400
DDPDEKTEGS DTDRLLSNSH QKSLSVLAAK DDDSGRTSCY EPDILENDFN
410 420 430 440 450
ASDGCDGNSE VAQPQRLKGE ADLLCLDQKN QNNSPYHDVS PAAQQPEVVL
460 470 480 490 500
AEEDKPRPLL TGEIESTLQA APSQLSNPNS LANIDFYAQV SDITPAGSVV
510 520 530 540 550
LSPGQKNKAG NSQCDAHPEV VSLCQTNFIM DNAYFCEADA KKCIAVAPHV
560 570 580 590 600
DVESRVEPSF NQEDIYITTE SLTTTAERSG TAEDAPGSEM PVPDYTSIHL
610 620 630
VQSPQGLVLN AATLPLPDKE FLSSCGYVST DQLNKILP
Length:638
Mass (Da):71,077
Last modified:February 1, 1991 - v1
Checksum:iE05CCE1D7294624C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015252 mRNA. Translation: AAB67613.1.
PIRiS08544. B28176.
RefSeqiNP_001076105.1. NM_001082636.1.
UniGeneiOcu.2168.

Genome annotation databases

GeneIDi100009325.
KEGGiocu:100009325.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015252 mRNA. Translation: AAB67613.1.
PIRiS08544. B28176.
RefSeqiNP_001076105.1. NM_001082636.1.
UniGeneiOcu.2168.

3D structure databases

ProteinModelPortaliP19941.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172345. 4 interactors.
DIPiDIP-313N.
IntActiP19941. 4 interactors.
MINTiMINT-1535520.
STRINGi9986.ENSOCUP00000007343.

PTM databases

iPTMnetiP19941.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009325.
KEGGiocu:100009325.

Organism-specific databases

CTDi2690.

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP19941.
KOiK05080.

Miscellaneous databases

PMAP-CutDBP19941.

Family and domain databases

CDDicd00063. FN3. 1 hit.
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.
PF00041. fn3. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 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_RABIT
AccessioniPrimary (citable) accession number: P19941
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: November 30, 2016
This is version 132 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, Direct protein sequencing, 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.