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Protein

Growth hormone receptor

Gene

GHR

Organism
Sus scrofa (Pig)
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)DescriptionActionsGraphical viewLength
Sitei345Required for ubiquitin-dependent internalization and down-regulationBy similarity1

GO - Molecular functioni

GO - Biological processi

  • endocytosis Source: UniProtKB-KW
  • growth hormone receptor signaling pathway Source: BHF-UCL
  • positive regulation of peptidyl-tyrosine phosphorylation 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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Growth hormone-binding protein :
  • Secreted By similarity

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

Topology

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi332Y → F: No effect. 1 Publication1
Mutagenesisi337Y → F: No effect. 1 Publication1
Mutagenesisi390Y → F: No effect. 1 Publication1
Mutagenesisi487Y → F: No effect. 1 Publication1
Mutagenesisi534Y → F: Loss of transcriptional signaling; when associated with F-566 or F-627. 1 Publication1
Mutagenesisi566Y → F: Loss of transcriptional signaling. when associated with F-534 or F-627. 1 Publication1
Mutagenesisi595Y → F: Loss of transcriptional signaling. 1 Publication1
Mutagenesisi627Y → F: Loss of transcriptional signaling. when associated with F-534 or F-566. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Add BLAST18
ChainiPRO_000001096519 – 638Growth hormone receptorAdd BLAST620
ChainiPRO_000001096619 – 256Growth hormone-binding proteinBy similarityAdd 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

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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP19756.
PRIDEiP19756.

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.By similarity

Protein-protein interaction databases

DIPiDIP-650N.
STRINGi9823.ENSSSCP00000017873.

Structurei

3D structure databases

ProteinModelPortaliP19756.
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
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.By similarity

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.
InParanoidiP19756.

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.

P19756-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLWQLLLTL AVAGSSDAFS GSEATPAVLV RASQSLQRVH PGLETNSSGK
60 70 80 90 100
PKFTKCRSPE LETFSCHWTD GVRHGLQSPG SIQLFYIRRS TQEWTQEWKE
110 120 130 140 150
CPDYVSAGEN SCYFNSSYTS IWIPYCIKLT SNGGTVDQKC FSVEEIVQPD
160 170 180 190 200
PPIGLNWTLL NISLTGIHAD IQVRWEPPPN ADVQKGWIVL EYELQYKEVN
210 220 230 240 250
ETQWKMMDPV LSTSVPVYSL RLDKEYEVRV RSRQRNSEKY GEFSEVLYVT
260 270 280 290 300
LPQMSPFACE EDFRFPWFLI IIFGIFGLTV ILFLLIFSKQ QRIKMLILPP
310 320 330 340 350
VPVPKIKGID PDLLKEGKLE EVNTILAIHD NYKHEFYSDD SWVEFIELDI
360 370 380 390 400
DDPDEKTEGS DTDRLLNNDH EKSLTILGAK EDDSGRTSCY EPDILETDFN
410 420 430 440 450
ANDVCDGTAE VAQPQRLKGE ADLLCLDQKN QNNSPSNDAA PATQQPSVIL
460 470 480 490 500
AEENKPRPLI ISGTDSTHQT AHTQLSNPSS LANIDFYAQV SDITPAGSVV
510 520 530 540 550
LSPGQKNKAG ISQCDMHLEV VSPCPANFIM DNAYFCEADA KKCIAMAPHV
560 570 580 590 600
EVESRLAPSF NQEDIYITTE SLTTTAGRSA TAECAPSSEM PVPDYTSIHI
610 620 630
VQSPQGLVLN ATALPLPDKE FLSSCGYVST DQLNKIMP
Length:638
Mass (Da):71,145
Last modified:February 1, 1991 - v1
Checksum:iBC7C66536F4DFF97
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54429 mRNA. Translation: CAA38301.1.
PIRiS12136.
UniGeneiSsc.93799.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54429 mRNA. Translation: CAA38301.1.
PIRiS12136.
UniGeneiSsc.93799.

3D structure databases

ProteinModelPortaliP19756.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-650N.
STRINGi9823.ENSSSCP00000017873.

Proteomic databases

PaxDbiP19756.
PRIDEiP19756.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiP19756.

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_PIG
AccessioniPrimary (citable) accession number: P19756
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: November 30, 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, 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.