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Protein

Growth hormone receptor

Gene

GHR

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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
Sitei341Required for endocytosis and down-regulationBy similarity1

GO - Molecular functioni

GO - Biological processi

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 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 – 260ExtracellularSequence analysisAdd BLAST242
Transmembranei261 – 284HelicalSequence analysisAdd BLAST24
Topological domaini285 – 634CytoplasmicSequence analysisAdd BLAST350

GO - Cellular componenti

  • cytosol Source: AgBase
  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: AgBase
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001095119 – 634Growth hormone receptorAdd BLAST616
ChainiPRO_000001095219 – 252Growth hormone-binding proteinBy similarityAdd BLAST234

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi56 ↔ 66By similarity
Glycosylationi73N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi97 ↔ 108By similarity
Glycosylationi111N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi122 ↔ 136By similarity
Glycosylationi152N-linked (GlcNAc...)Sequence analysis1
Glycosylationi157N-linked (GlcNAc...)Sequence analysis1
Glycosylationi196N-linked (GlcNAc...)Sequence analysis1
Modified residuei337PhosphoserineBy 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

PaxDbiO46600.
PRIDEiO46600.

Expressioni

Tissue specificityi

Highly expressed in both adult and fetal liver. Lower levels in kidney, anterior pituitary, skeletal muscle, adipose tissue and mammary gland.

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

STRINGi9913.ENSBTAP00000001758.

Structurei

3D structure databases

ProteinModelPortaliO46600.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini147 – 250Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni290 – 375Required for JAK2 bindingBy similarityAdd BLAST86

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi236 – 240WSXWS motif5
Motifi293 – 301Box 1 motif9
Motifi336 – 345UbE 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).By similarity
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.
InParanoidiO46600.
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.
PF12772. GHBP. 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.

O46600-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLWQLLLTL AVAGSSDAFS GSEATPAFLV RASQSLQILY PVLETNSSGN
60 70 80 90 100
PKFTKCRSPE LETFSCHWTD GANHSLQSPG SVQMFYIRRD IQEWKECPDY
110 120 130 140 150
VSAGENSCYF NSSYTSVWTP YCIKLTSNGG IVDHKCFSVE DIVQPDPPVG
160 170 180 190 200
LNWTLLNISL TEIHADILVK WEPPPNTDVK MGWIILEYEL HYKELNETQW
210 220 230 240 250
KMMDPLMVTS VPMYSLRLDK EYEVRVRTRQ RNTEKYGKFS EVLLITFPQM
260 270 280 290 300
NPSACEEDFQ FPWFLIIIFG ILGLAVTLYL LIFSKQQRIK MLILPPVPVP
310 320 330 340 350
KIKGIDPDLL KEGKLEEVNT ILAIHDNYKH EFYNDDSWVE FIELDIDDPD
360 370 380 390 400
EKTEGSDTDR LLSNDHEKSL NIFGAKDDDS GRTSCYEPDI LEADFHVSDM
410 420 430 440 450
CDGTSEVAQP QRLKGEADIS CLDQKNQNNS PSNDAAPASQ QPSVILVEEN
460 470 480 490 500
KPRPLLIGGT ESTHQAVHTQ LSNPSSLANI DFYAQVSDIT PAGNVVLSPG
510 520 530 540 550
QKNKTGNPQC DTHPEVVTPC QANFIVDNAY FCEVDAKKYI ALAPHVEAES
560 570 580 590 600
HVEPSFNQED IYITTESLTT TAGRSGTAEH VPSSEIPVPD YTSIHIVQSP
610 620 630
QGLVLNATAL PLPDKEFLSS CGYVSTDQLN KIMP
Length:634
Mass (Da):70,901
Last modified:May 10, 2004 - v2
Checksum:iB86920A99261BE75
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71G → V no nucleotide entry (PubMed:2289631).Curated1
Sequence conflicti279Y → F in AAU94310 (Ref. 3) Curated1
Sequence conflicti528N → T in AAU94310 (Ref. 3) Curated1
Sequence conflicti552V → I in AAC02534 (PubMed:9710756).Curated1
Sequence conflicti552V → I in AAU94310 (Ref. 3) Curated1
Sequence conflicti555S → G no nucleotide entry (PubMed:2289631).Curated1
Sequence conflicti593S → F in AAD45668 (PubMed:10376317).Curated1
Sequence conflicti600P → S in AAD45668 (PubMed:10376317).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti519P → S.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044258 mRNA. Translation: AAC02534.1.
AY748827 mRNA. Translation: AAU94310.1.
AF036297 mRNA. Translation: AAC33315.2.
AF085281 mRNA. Translation: AAD22521.1.
AF036290 mRNA. Translation: AAC33308.1.
AF036291 mRNA. Translation: AAC33309.1.
AF036292 mRNA. Translation: AAC33310.1.
AF036293 mRNA. Translation: AAC33311.1.
AF036294 mRNA. Translation: AAC33312.1.
AF036295 mRNA. Translation: AAC33313.1.
AF036296 mRNA. Translation: AAC33314.1.
AF326349 mRNA. Translation: AAK97345.1.
AF140284 Genomic DNA. Translation: AAD45668.1.
RefSeqiNP_788781.1. NM_176608.1.
UniGeneiBt.111379.
Bt.79147.

Genome annotation databases

GeneIDi280805.
KEGGibta:280805.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044258 mRNA. Translation: AAC02534.1.
AY748827 mRNA. Translation: AAU94310.1.
AF036297 mRNA. Translation: AAC33315.2.
AF085281 mRNA. Translation: AAD22521.1.
AF036290 mRNA. Translation: AAC33308.1.
AF036291 mRNA. Translation: AAC33309.1.
AF036292 mRNA. Translation: AAC33310.1.
AF036293 mRNA. Translation: AAC33311.1.
AF036294 mRNA. Translation: AAC33312.1.
AF036295 mRNA. Translation: AAC33313.1.
AF036296 mRNA. Translation: AAC33314.1.
AF326349 mRNA. Translation: AAK97345.1.
AF140284 Genomic DNA. Translation: AAD45668.1.
RefSeqiNP_788781.1. NM_176608.1.
UniGeneiBt.111379.
Bt.79147.

3D structure databases

ProteinModelPortaliO46600.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000001758.

Proteomic databases

PaxDbiO46600.
PRIDEiO46600.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi280805.
KEGGibta:280805.

Organism-specific databases

CTDi2690.

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiO46600.
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.
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_BOVIN
AccessioniPrimary (citable) accession number: O46600
Secondary accession number(s): O77538
, Q5XM78, Q9TQV9, Q9TUY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: November 30, 2016
This is version 122 of the entry and version 2 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.