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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei345 – 3451Required for ubiquitin-dependent internalization and down-regulationBy similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi332 – 3321Y → F: No effect. 1 Publication
Mutagenesisi337 – 3371Y → F: No effect. 1 Publication
Mutagenesisi390 – 3901Y → F: No effect. 1 Publication
Mutagenesisi487 – 4871Y → F: No effect. 1 Publication
Mutagenesisi534 – 5341Y → F: Loss of transcriptional signaling; when associated with F-566 or F-627. 1 Publication
Mutagenesisi566 – 5661Y → F: Loss of transcriptional signaling. when associated with F-534 or F-627. 1 Publication
Mutagenesisi595 – 5951Y → F: Loss of transcriptional signaling. 1 Publication
Mutagenesisi627 – 6271Y → F: Loss of transcriptional signaling. when associated with F-534 or F-566. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Chaini19 – 638620Growth hormone receptorPRO_0000010965Add
BLAST
Chaini19 – 256238Growth hormone-binding proteinBy similarityPRO_0000010966Add
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

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.

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.
SMRiP19756. 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
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.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

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.
SMRiP19756. Positions 50-255.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-650N.
STRINGi9823.ENSSSCP00000017873.

Proteomic databases

PaxDbiP19756.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

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

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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Landrace X Yorkshire.
    Tissue: Liver.
  2. "Identification of tyrosine residues in the intracellular domain of the growth hormone receptor required for transcriptional signaling and Stat5 activation."
    Hansen L.H., Wang X., Kopchick J.J., Bouchelouche P., Nielsen J.H., Galsgaard E.D., Billestrup N.
    J. Biol. Chem. 271:12669-12673(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, STAT5 ACTIVATION, MUTAGENESIS OF TYR-332; TYR-337; TYR-390; TYR-487; TYR-534; TYR-566; TYR-595 AND TYR-627.

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 11, 2015
This is version 128 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.