Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Growth hormone receptor

Gene

Ghr

Organism
Mus musculus (Mouse)
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
Sitei354 – 3541Required for endocytosis and down-regulationBy similarity

GO - Molecular functioni

  1. growth factor binding Source: MGI
  2. growth hormone receptor activity Source: MGI
  3. peptide hormone binding Source: MGI
  4. protein homodimerization activity Source: MGI

GO - Biological processi

  1. 2-oxoglutarate metabolic process Source: BHF-UCL
  2. allantoin metabolic process Source: BHF-UCL
  3. cellular response to hormone stimulus Source: MGI
  4. citrate metabolic process Source: BHF-UCL
  5. creatine metabolic process Source: BHF-UCL
  6. creatinine metabolic process Source: BHF-UCL
  7. cytokine-mediated signaling pathway Source: GOC
  8. endocytosis Source: UniProtKB-KW
  9. fatty acid metabolic process Source: BHF-UCL
  10. growth hormone receptor signaling pathway Source: BHF-UCL
  11. insulin-like growth factor receptor signaling pathway Source: MGI
  12. isoleucine metabolic process Source: BHF-UCL
  13. multicellular organismal metabolic process Source: MGI
  14. oxaloacetate metabolic process Source: BHF-UCL
  15. positive regulation of multicellular organism growth Source: MGI
  16. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  17. regulation of multicellular organism growth Source: BHF-UCL
  18. response to estradiol Source: MGI
  19. succinate metabolic process Source: BHF-UCL
  20. taurine metabolic process Source: BHF-UCL
  21. valine metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Endocytosis

Enzyme and pathway databases

ReactomeiREACT_289947. Prolactin receptor signaling.
REACT_317434. Growth hormone receptor signaling.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:95708. Ghr.

Subcellular locationi

  1. Cell membrane; Single-pass type I membrane protein

  2. Note: On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway.By similarity
Chain Growth hormone-binding protein :
  1. Secreted By similarity

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 273249ExtracellularSequence AnalysisAdd
BLAST
Transmembranei274 – 29724HelicalSequence AnalysisAdd
BLAST
Topological domaini298 – 650353CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: MGI
  2. extracellular region Source: Reactome
  3. extracellular space Source: MGI
  4. extrinsic component of membrane Source: MGI
  5. growth hormone receptor complex Source: MGI
  6. integral component of membrane Source: MGI
  7. integral component of plasma membrane Source: MGI
  8. nucleus Source: MGI
  9. plasma membrane Source: MGI
  10. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24241 PublicationAdd
BLAST
Chaini25 – 650626Growth hormone receptorPRO_0000010961Add
BLAST
Chaini25 – 264240Growth hormone-binding proteinBy similarityPRO_0000010962Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi56 ↔ 66By similarity
Disulfide bondi109 ↔ 120By similarity
Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi134 ↔ 148By similarity
Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence Analysis
Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence Analysis
Modified residuei350 – 3501PhosphoserineBy 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

MaxQBiP16882.
PaxDbiP16882.
PRIDEiP16882.

PTM databases

PhosphoSiteiP16882.

Expressioni

Tissue specificityi

Expressed in all tissues tested including, liver, heart, adipose tissue, mammary gland, testes, ovary, brain, kidney and muscle. Highest levels in liver.

Developmental stagei

During gestation, both hepatic and serum expression begins at day 9. Levels increased 8-fold in liver and 30-fold in serum by late gestation. Levels of isoform 1 and isoform 2 similarly begin at day 9 with isoform 1 expression reaching maximum levels by day 13, isoform 2 levels continue to increase until the end of pregnancy.1 Publication

Gene expression databases

BgeeiP16882.
CleanExiMM_GHR.
ExpressionAtlasiP16882. baseline and differential.
GenevestigatoriP16882.

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-441N.
IntActiP16882. 4 interactions.
MINTiMINT-2738349.

Structurei

3D structure databases

ProteinModelPortaliP16882.
SMRiP16882. Positions 50-260.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini159 – 262104Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni303 – 39088Required for JAK2 bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi248 – 2525WSXWS motif
Motifi306 – 3149Box 1 motif
Motifi349 – 35810UbE 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

eggNOGiNOG45313.
GeneTreeiENSGT00530000063112.
HOVERGENiHBG005836.
InParanoidiP16882.
KOiK05080.
OrthoDBiEOG79W94T.
PhylomeDBiP16882.

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.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16882-1) [UniParc]FASTAAdd to basket

Also known as: HMW GHR

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDLCQVFLTL ALAVTSSTFS GSEATPATLG KASPVLQRIN PSLGTSSSGK
60 70 80 90 100
PRFTKCRSPE LETFSCYWTE GDNPDLKTPG SIQLYYAKRE SQRQAARIAH
110 120 130 140 150
EWTQEWKECP DYVSAGKNSC YFNSSYTSIW IPYCIKLTTN GDLLDQKCFT
160 170 180 190 200
VDEIVQPDPP IGLNWTLLNI SLTGIRGDIQ VSWQPPPNAD VLKGWIILEY
210 220 230 240 250
EIQYKEVNES KWKVMGPIWL TYCPVYSLRM DKEHEVRVRS RQRSFEKYSE
260 270 280 290 300
FSEVLRVIFP QTNILEACEE DIQFPWFLII IFGIFGVAVM LFVVIFSKQQ
310 320 330 340 350
RIKMLILPPV PVPKIKGIDP DLLKEGKLEE VNTILGIHDN YKPDFYNDDS
360 370 380 390 400
WVEFIELDID EADVDEKTEG SDTDRLLSND HEKSAGILGA KDDDSGRTSC
410 420 430 440 450
YDPDILDTDF HTSDMCDGTL KFRQSQKLNM EADLLCLDQK NLKNLPYDAS
460 470 480 490 500
LGSLHPSITQ TVEENKPQPL LSSETEATHQ LASTPMSNPT SLANIDFYAQ
510 520 530 540 550
VSDITPAGGD VLSPGQKIKA GIAQGNTQRE VATPCQENYS MNSAYFCESD
560 570 580 590 600
AKKCIAVARR MEATSCIKPS FNQEDIYITT ESLTTTAQMS ETADIAPDAE
610 620 630 640 650
MSVPDYTTVH TVQSPRGLIL NATALPLPDK KNFPSSCGYV STDQLNKIMQ
Length:650
Mass (Da):72,783
Last modified:August 1, 1990 - v1
Checksum:i95653380CAF0B931
GO
Isoform 2 (identifier: P16882-2) [UniParc]FASTAAdd to basket

Also known as: LMW GHR, GHBP

The sequence of this isoform differs from the canonical sequence as follows:
     271-297: DIQFPWFLIIIFGIFGVAVMLFVVIFS → GTKSNSQHPHQEIDNHLYHQLQRIRHP
     298-650: Missing.

Show »
Length:297
Mass (Da):34,105
Checksum:i667F5F80088482A4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251T → A AA sequence (PubMed:3398846).Curated
Sequence conflicti162 – 1621G → A in AAK62802 (PubMed:7894338).Curated
Sequence conflicti240 – 2401S → F in AAA69000 (PubMed:7988474).Curated
Sequence conflicti325 – 3251E → G in AAD32556 (PubMed:10425445).Curated
Sequence conflicti423 – 4231R → A in AAD32556 (PubMed:10425445).Curated
Sequence conflicti423 – 4231R → A in AAH75720 (PubMed:15489334).Curated
Sequence conflicti423 – 4231R → A in AAP33018 (Ref. 7) Curated
Sequence conflicti510 – 5101D → V in AAH75720 (PubMed:15489334).Curated
Sequence conflicti510 – 5101D → V in AAP33018 (Ref. 7) Curated
Sequence conflicti559 – 5591R → P in AAH75720 (PubMed:15489334).Curated
Sequence conflicti559 – 5591R → P in AAP33018 (Ref. 7) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei271 – 29727DIQFP…VVIFS → GTKSNSQHPHQEIDNHLYHQ LQRIRHP in isoform 2. 2 PublicationsVSP_001716Add
BLAST
Alternative sequencei298 – 650353Missing in isoform 2. 2 PublicationsVSP_001717Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33324 mRNA. Translation: AAA37690.1. Sequence problems.
M31680 mRNA. Translation: AAA37689.1. Sequence problems.
U15012, U15011, U15013 Genomic DNA. Translation: AAA69000.1.
AF120489
, AF120481, AF120482, AF120483, AF120484, AF120485, AF120486, AF120487, AF120488 Genomic DNA. Translation: AAD32556.1.
AF120487
, AF120481, AF120482, AF120483, AF120484, AF120485, AF120486 Genomic DNA. Translation: AAD32555.1.
BC024375 mRNA. Translation: AAH24375.1.
BC075720 mRNA. Translation: AAH75720.1.
U49266, U49268, U43933 Genomic DNA. Translation: AAK62802.1.
U49267 Genomic DNA. Translation: AAK62803.1.
AY271378 Genomic DNA. Translation: AAP33018.1.
CCDSiCCDS27358.1. [P16882-1]
CCDS37024.1. [P16882-2]
PIRiI48363.
S33608.
RefSeqiNP_001041643.1. NM_001048178.2. [P16882-2]
NP_001273299.1. NM_001286370.1.
NP_034414.2. NM_010284.3.
XP_006520026.1. XM_006519963.2.
XP_006520028.1. XM_006519965.2.
UniGeneiMm.3986.

Genome annotation databases

EnsembliENSMUST00000110697; ENSMUSP00000106325; ENSMUSG00000055737. [P16882-2]
ENSMUST00000110698; ENSMUSP00000106326; ENSMUSG00000055737. [P16882-2]
GeneIDi14600.
KEGGimmu:14600.
UCSCiuc007vcd.1. mouse. [P16882-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33324 mRNA. Translation: AAA37690.1. Sequence problems.
M31680 mRNA. Translation: AAA37689.1. Sequence problems.
U15012, U15011, U15013 Genomic DNA. Translation: AAA69000.1.
AF120489
, AF120481, AF120482, AF120483, AF120484, AF120485, AF120486, AF120487, AF120488 Genomic DNA. Translation: AAD32556.1.
AF120487
, AF120481, AF120482, AF120483, AF120484, AF120485, AF120486 Genomic DNA. Translation: AAD32555.1.
BC024375 mRNA. Translation: AAH24375.1.
BC075720 mRNA. Translation: AAH75720.1.
U49266, U49268, U43933 Genomic DNA. Translation: AAK62802.1.
U49267 Genomic DNA. Translation: AAK62803.1.
AY271378 Genomic DNA. Translation: AAP33018.1.
CCDSiCCDS27358.1. [P16882-1]
CCDS37024.1. [P16882-2]
PIRiI48363.
S33608.
RefSeqiNP_001041643.1. NM_001048178.2. [P16882-2]
NP_001273299.1. NM_001286370.1.
NP_034414.2. NM_010284.3.
XP_006520026.1. XM_006519963.2.
XP_006520028.1. XM_006519965.2.
UniGeneiMm.3986.

3D structure databases

ProteinModelPortaliP16882.
SMRiP16882. Positions 50-260.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-441N.
IntActiP16882. 4 interactions.
MINTiMINT-2738349.

PTM databases

PhosphoSiteiP16882.

Proteomic databases

MaxQBiP16882.
PaxDbiP16882.
PRIDEiP16882.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000110697; ENSMUSP00000106325; ENSMUSG00000055737. [P16882-2]
ENSMUST00000110698; ENSMUSP00000106326; ENSMUSG00000055737. [P16882-2]
GeneIDi14600.
KEGGimmu:14600.
UCSCiuc007vcd.1. mouse. [P16882-2]

Organism-specific databases

CTDi2690.
MGIiMGI:95708. Ghr.

Phylogenomic databases

eggNOGiNOG45313.
GeneTreeiENSGT00530000063112.
HOVERGENiHBG005836.
InParanoidiP16882.
KOiK05080.
OrthoDBiEOG79W94T.
PhylomeDBiP16882.

Enzyme and pathway databases

ReactomeiREACT_289947. Prolactin receptor signaling.
REACT_317434. Growth hormone receptor signaling.

Miscellaneous databases

ChiTaRSiGhr. mouse.
NextBioi286368.
PROiP16882.
SOURCEiSearch...

Gene expression databases

BgeeiP16882.
CleanExiMM_GHR.
ExpressionAtlasiP16882. baseline and differential.
GenevestigatoriP16882.

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.
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

« Hide 'large scale' publications
  1. "Mouse serum growth hormone (GH) binding protein has GH receptor extracellular and substituted transmembrane domains."
    Smith W.C., Kuniyoshi J., Talamantes F.
    Mol. Endocrinol. 3:984-990(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  2. "Mouse growth hormone receptor/binding protein and growth hormone receptor transcripts are produced from a single gene by alternative splicing."
    Edens A., Southard J.N., Talamantes F.
    Endocrinology 135:2802-2805(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE OF 156-300 (ISOFORM 1).
    Strain: DBA/2J and Swiss Webster.
  3. "Structure and expression of the mouse growth hormone receptor/growth hormone binding protein gene."
    Moffat J.G., Edens A., Talamantes F.
    J. Mol. Endocrinol. 23:33-44(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
    Strain: DBA/2J and Swiss Webster.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Kidney.
  5. "An exon encoding the mouse growth hormone binding protein (mGHBP) carboxy terminus is located between exon 7 and 8 of the mouse growth hormone receptor gene."
    Zhou Y., He L., Kopchick J.J.
    Receptor 4:223-227(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 47-88 AND 156-650 (ISOFORM 1).
    Strain: C57BL/6.
  6. Zhou Y., He L., Kopchick J.J.
    Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  7. "Mouse growth hormone receptor cytoplasmic exons 9 and 10 genomic clone with flanking intronic sequence."
    Rowland J.E., Waters M.J.
    Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-650 (ISOFORM 1).
    Strain: 129/SvJ.
  8. "Isolation of two molecular weight variants of the mouse growth hormone receptor."
    Smith W.C., Colosi P., Talamantes F.
    Mol. Endocrinol. 2:108-116(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 25-41.
  9. "Structure and regulation of expression of the mouse GH receptor."
    Talamantes F., Ortiz R.
    J. Endocrinol. 175:55-59(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiGHR_MOUSE
AccessioniPrimary (citable) accession number: P16882
Secondary accession number(s): P16590
, Q61653, Q6DI66, Q80W86, Q8R1M5, Q920Z3, Q9R264
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: April 1, 2015
This is version 153 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.