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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei345 – 3451Required for endocytosis and down-regulation

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 264246ExtracellularSequence analysisAdd
BLAST
Transmembranei265 – 28824HelicalSequence analysisAdd
BLAST
Topological domaini289 – 638350CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi338 – 3381N → A: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi339 – 3391D → A: Slightly impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi340 – 3401D → A: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi341 – 3411S → A: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi341 – 3411S → L or T: Slightly impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi342 – 3421W → A: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi342 – 3421W → L: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi343 – 3431V → A: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi343 – 3431V → G: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi344 – 3441E → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication
Mutagenesisi344 – 3441E → D: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi345 – 3451F → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication
Mutagenesisi345 – 3451F → L or V: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi345 – 3451F → Y: No effect on GHR-mediated GH internalization. No effect on ubiquitination. 1 Publication
Mutagenesisi346 – 3461I → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication
Mutagenesisi346 – 3461I → F: Slightly impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi346 – 3461I → L: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi347 – 3471E → A or D: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi348 – 3481L → A or V: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi349 – 3491D → A: Impaired GHR-mediated GH internalization. Greatly reduced ubiquitination. 1 Publication
Mutagenesisi349 – 3491D → E: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi349 – 3491D → N: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi350 – 3501I → A: Impaired GHR-mediated GH internalization. 1 Publication
Mutagenesisi351 – 3511D → A: No effect on GHR-mediated GH internalization. 1 Publication
Mutagenesisi352 – 3521D → A: No effect on GHR-mediated GH internalization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Chaini19 – 638620Growth hormone receptorPRO_0000010967Add
BLAST
Chaini19 – 256238Growth hormone-binding proteinPRO_0000010968Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...)Sequence analysis
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 residuei341 – 3411PhosphoserineBy similarity

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 interactions.
DIPiDIP-313N.
IntActiP19941. 4 interactions.
MINTiMINT-1535520.
STRINGi9986.ENSOCUP00000007343.

Structurei

3D structure databases

ProteinModelPortaliP19941.
SMRiP19941. Positions 50-255.
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
Regioni260 – 2623Required for ADAM17-mediated proteolysis
Regioni294 – 37986Required for JAK2 bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi240 – 2445WSXWS motif
Motifi297 – 3059Box 1 motif
Motifi340 – 34910UbE motif

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

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.
SMRiP19941. Positions 50-255.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172345. 4 interactions.
DIPiDIP-313N.
IntActiP19941. 4 interactions.
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

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: June 8, 2016
This is version 130 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.