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P16882 (GHR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth hormone receptor

Short name=GH receptor
Alternative name(s):
Somatotropin receptor

Cleaved into the following chain:

  1. Growth hormone-binding protein
    Short name=GH-binding protein
    Short name=GHBP
    Alternative name(s):
    Serum-binding protein
Gene names
Name:Ghr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length650 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.

Subunit structure

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.

Subcellular location

Cell membrane; Single-pass type I membrane protein. Note: On growth hormone binding, GHR is ubiquitinated, internalized, down-regulated and transported into a degradative or non-degradative pathway By similarity.

Isoform 2: Secreted.

Growth hormone-binding protein: Secreted By similarity. Note: Complexed to a substantial fraction of circulating GH By similarity.

Tissue specificity

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

Developmental stage

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. Ref.9

Domain

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.

Post-translational modification

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.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 1 subfamily.

Contains 1 fibronectin type-III domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process2-oxoglutarate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

allantoin metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

citrate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

creatine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

creatinine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 6303755. Source: GOC

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

growth hormone receptor signaling pathway

Inferred from direct assay PubMed 8702683. Source: BHF-UCL

isoleucine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

oxaloacetate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 8702683. Source: BHF-UCL

regulation of multicellular organism growth

Inferred from direct assay PubMed 18648510. Source: BHF-UCL

succinate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

taurine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

valine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extrinsic component of membrane

Inferred from direct assay PubMed 11834450. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay PubMed 9144201. Source: MGI

plasma membrane

Inferred from direct assay PubMed 9144201. Source: MGI

   Molecular_functiongrowth hormone receptor activity

Inferred from direct assay PubMed 6303755. Source: MGI

peptide hormone binding

Inferred from physical interaction PubMed 10556780. Source: MGI

protein binding

Inferred from physical interaction PubMed 8702683. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16882-1)

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.
Isoform 2 (identifier: P16882-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.8
Chain25 – 650626Growth hormone receptor
PRO_0000010961
Chain25 – 264240Growth hormone-binding protein By similarity
PRO_0000010962

Regions

Topological domain25 – 273249Extracellular Potential
Transmembrane274 – 29724Helical; Potential
Topological domain298 – 650353Cytoplasmic Potential
Domain159 – 262104Fibronectin type-III
Region303 – 39088Required for JAK2 binding By similarity
Motif248 – 2525WSXWS motif
Motif306 – 3149Box 1 motif
Motif349 – 35810UbE motif

Sites

Site3541Required for endocytosis and down-regulation By similarity

Amino acid modifications

Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation1691N-linked (GlcNAc...) Potential
Glycosylation2081N-linked (GlcNAc...) Potential
Disulfide bond56 ↔ 66 By similarity
Disulfide bond109 ↔ 120 By similarity
Disulfide bond134 ↔ 148 By similarity

Natural variations

Alternative sequence271 – 29727DIQFP…VVIFS → GTKSNSQHPHQEIDNHLYHQ LQRIRHP in isoform 2.
VSP_001716
Alternative sequence298 – 650353Missing in isoform 2.
VSP_001717

Experimental info

Sequence conflict251T → A AA sequence Ref.8
Sequence conflict1621G → A in AAK62802. Ref.5
Sequence conflict2401S → F in AAA69000. Ref.2
Sequence conflict3251E → G in AAD32556. Ref.3
Sequence conflict4231R → A in AAD32556. Ref.3
Sequence conflict4231R → A in AAH75720. Ref.4
Sequence conflict4231R → A in AAP33018. Ref.7
Sequence conflict5101D → V in AAH75720. Ref.4
Sequence conflict5101D → V in AAP33018. Ref.7
Sequence conflict5591R → P in AAH75720. Ref.4
Sequence conflict5591R → P in AAP33018. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (HMW GHR) [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 95653380CAF0B931

FASTA65072,783
        10         20         30         40         50         60 
MDLCQVFLTL ALAVTSSTFS GSEATPATLG KASPVLQRIN PSLGTSSSGK PRFTKCRSPE 

        70         80         90        100        110        120 
LETFSCYWTE GDNPDLKTPG SIQLYYAKRE SQRQAARIAH EWTQEWKECP DYVSAGKNSC 

       130        140        150        160        170        180 
YFNSSYTSIW IPYCIKLTTN GDLLDQKCFT VDEIVQPDPP IGLNWTLLNI SLTGIRGDIQ 

       190        200        210        220        230        240 
VSWQPPPNAD VLKGWIILEY EIQYKEVNES KWKVMGPIWL TYCPVYSLRM DKEHEVRVRS 

       250        260        270        280        290        300 
RQRSFEKYSE FSEVLRVIFP QTNILEACEE DIQFPWFLII IFGIFGVAVM LFVVIFSKQQ 

       310        320        330        340        350        360 
RIKMLILPPV PVPKIKGIDP DLLKEGKLEE VNTILGIHDN YKPDFYNDDS WVEFIELDID 

       370        380        390        400        410        420 
EADVDEKTEG SDTDRLLSND HEKSAGILGA KDDDSGRTSC YDPDILDTDF HTSDMCDGTL 

       430        440        450        460        470        480 
KFRQSQKLNM EADLLCLDQK NLKNLPYDAS LGSLHPSITQ TVEENKPQPL LSSETEATHQ 

       490        500        510        520        530        540 
LASTPMSNPT SLANIDFYAQ VSDITPAGGD VLSPGQKIKA GIAQGNTQRE VATPCQENYS 

       550        560        570        580        590        600 
MNSAYFCESD AKKCIAVARR MEATSCIKPS FNQEDIYITT ESLTTTAQMS ETADIAPDAE 

       610        620        630        640        650 
MSVPDYTTVH TVQSPRGLIL NATALPLPDK KNFPSSCGYV STDQLNKIMQ 

« Hide

Isoform 2 (LMW GHR) (GHBP) [UniParc].

Checksum: 667F5F80088482A4
Show »

FASTA29734,105

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M33324 mRNA. Translation: AAA37690.1. Sequence problems.
M31680 mRNA. Translation: AAA37689.1. Sequence problems.
U15012, U15011, U15013 Genomic DNA. Translation: AAA69000.1.
AF120489 expand/collapse EMBL AC list , AF120481, AF120482, AF120483, AF120484, AF120485, AF120486, AF120487, AF120488 Genomic DNA. Translation: AAD32556.1.
AF120487 expand/collapse EMBL AC list , 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.
CCDSCCDS27358.1. [P16882-1]
CCDS37024.1. [P16882-2]
PIRI48363.
S33608.
RefSeqNP_001041643.1. NM_001048178.2. [P16882-2]
NP_001273299.1. NM_001286370.1.
NP_034414.2. NM_010284.3.
XP_006520026.1. XM_006519963.1.
XP_006520027.1. XM_006519964.1.
XP_006520028.1. XM_006519965.1.
XP_006520029.1. XM_006519966.1.
UniGeneMm.3986.

3D structure databases

ProteinModelPortalP16882.
SMRP16882. Positions 50-260.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-441N.
IntActP16882. 4 interactions.
MINTMINT-2738349.

PTM databases

PhosphoSiteP16882.

Proteomic databases

PaxDbP16882.
PRIDEP16882.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000110697; ENSMUSP00000106325; ENSMUSG00000055737. [P16882-2]
ENSMUST00000110698; ENSMUSP00000106326; ENSMUSG00000055737. [P16882-2]
GeneID14600.
KEGGmmu:14600.
UCSCuc007vcd.1. mouse. [P16882-2]

Organism-specific databases

CTD2690.
MGIMGI:95708. Ghr.

Phylogenomic databases

eggNOGNOG45313.
GeneTreeENSGT00530000063112.
HOVERGENHBG005836.
InParanoidP16882.
KOK05080.
OrthoDBEOG79W94T.
PhylomeDBP16882.

Gene expression databases

ArrayExpressP16882.
BgeeP16882.
CleanExMM_GHR.
GenevestigatorP16882.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR003961. Fibronectin_type3.
IPR025871. GHBP.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamPF09067. EpoR_lig-bind. 1 hit.
PF12772. GHBP. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGHR. mouse.
NextBio286368.
PROP16882.
SOURCESearch...

Entry information

Entry nameGHR_MOUSE
AccessionPrimary (citable) accession number: P16882
Secondary accession number(s): P16590 expand/collapse secondary AC list , Q61653, Q6DI66, Q80W86, Q8R1M5, Q920Z3, Q9R264
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: July 9, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot