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Protein

Growth hormone receptor

Gene

GHR

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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 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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei345 – 3451Required for endocytosis and down-regulationBy similarity

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
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence analysisAdd
BLAST
Chaini19 – 638620Growth hormone receptorPRO_0000010953Add
BLAST
Chaini19 – 256238Growth hormone-binding proteinBy similarityPRO_0000010954Add
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

PaxDbiQ9TU69.

Expressioni

Tissue specificityi

Expressed in normal and tumorous mammary tissues, being localized in epithelial and myoepithelial/spindle cell components and in the activated fibroblasts of desmoplastic tumor stroma. Isoform 1, isoform 2 and isoform 3 are found in both normal and tumorous mammary tissues, isoform 1 being the predominant isoform. Isoform 1, isoform 3, isoform 4 and isoform 5 are expressed in the CMT-U335 cell line.

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

STRINGi9615.ENSCAFP00000037936.

Structurei

3D structure databases

ProteinModelPortaliQ9TU69.
SMRiQ9TU69. 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.
InParanoidiQ9TU69.
KOiK05080.

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]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9TU69-1) [UniParc]FASTAAdd to basket

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
MDLWQLLLTL AVAGSGSAFS GSEATPTILG SASQSLQRVN PGLGTNSSEK
60 70 80 90 100
PKFTKCRSPE LETFSCHWTD GVRHGLKNAG SVQLFYIRRS TQEWTQEWKE
110 120 130 140 150
CPDYVSAGEN SCYFNSSYTS IWIPYCIKLT SNGGTVDQKC FSVEEIVQPD
160 170 180 190 200
PPIGLNWTLL NISLTGIHAD IQVRWEPPPN ADVQKGWIVL KYELQYKEVN
210 220 230 240 250
ESQWKMMDPV SATSVPVYSL RLDKEYEVRV RSRQRNSEKY GEFSEALYVT
260 270 280 290 300
LPQMSPFACE EDFQFPWFLI IIFGIFGLTM ILFLFIFSKQ QRIKMLILPP
310 320 330 340 350
VPVPKIKGID PDLLKEGKLE EVNTILAIHD NYKPEFYNDD SWVEFIELDI
360 370 380 390 400
DDLDEKTEGS DTDRLLSNDH EKSLNILGAK DDDSGRTSCY EPDILETDFN
410 420 430 440 450
ASDVCDGTSE VAQPQRLKGE VDLLCLDQKN QNNSPSTDTT PTTQQPSIIL
460 470 480 490 500
AKENKPRPLL ISGTESTQQA AHTQLSNPSS LANIDFYAQV SDITLAGSVV
510 520 530 540 550
LSPGQKNKAG ISPCDMPPEV ASLCQANFIM DNAYFCEADA KKCITVAPHV
560 570 580 590 600
EAESRVEPSF NQEDIYITTE SLTTTAGQSG TTERAVSSEM PVPDYTSIHI
610 620 630
IQSPRGLVLN ATALPLPDKE FLSSCGYVST DQLNKIMP
Length:638
Mass (Da):71,041
Last modified:May 1, 2000 - v1
Checksum:iDD4AF6F48E75B840
GO
Isoform 2 (identifier: Q9TU69-2)

Also known as: Putative protein A

Sequence is not available
Note: Produced by exon 8 skipping resulting in a frameshift and introduction of a stopcodon at position 12 of exon 9.
Length:
Mass (Da):
Isoform 3 (identifier: Q9TU69-3)

Also known as: Putative protein B

Sequence is not available
Note: Produced by exon 7 skipping resulting in a frameshift and introduction of a stopcodon at position 619.
Length:
Mass (Da):
Isoform 4 (identifier: Q9TU69-4)

Also known as: Putative protein C

Sequence is not available
Note: Produced by the usage of alternative splice donor/acceptor sites resulting in the elimination of the greater part of exon 6 and the beginning of exon 7.
Length:
Mass (Da):
Isoform 5 (identifier: Q9TU69-5)

Also known as: Putative protein D

Sequence is not available
Note: Produced by the usage of alternative splice donor site resulting in the elimination of a part of exon 7 and the entire exon 8.
Length:
Mass (Da):

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF133835 mRNA. Translation: AAF07397.1.
L77673 Genomic DNA. Translation: AAA97423.1.
RefSeqiNP_001003123.1. NM_001003123.1. [Q9TU69-1]
UniGeneiCfa.2436.

Genome annotation databases

GeneIDi403721.
KEGGicfa:403721.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF133835 mRNA. Translation: AAF07397.1.
L77673 Genomic DNA. Translation: AAA97423.1.
RefSeqiNP_001003123.1. NM_001003123.1. [Q9TU69-1]
UniGeneiCfa.2436.

3D structure databases

ProteinModelPortaliQ9TU69.
SMRiQ9TU69. Positions 50-255.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000037936.

Proteomic databases

PaxDbiQ9TU69.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi403721.
KEGGicfa:403721.

Organism-specific databases

CTDi2690.

Phylogenomic databases

eggNOGiENOG410IFQI. Eukaryota.
ENOG410XTHJ. LUCA.
HOGENOMiHOG000015773.
HOVERGENiHBG005836.
InParanoidiQ9TU69.
KOiK05080.

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]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Expression and molecular characterization of the growth hormone receptor in canine mammary tissue and mammary tumors."
    van Garderen E., van der Poel H.J.A., Swennenhuis J.F., Wissink E.H.J., Rutteman G.R., Hellmen E., Mol J.A., Schalken J.A.
    Endocrinology 140:5907-5914(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
    Tissue: Mammary gland.
  2. "Gene-specific universal mammalian sequence-tagged sites: application to the canine genome."
    Venta P.J., Brouillette J.A., Yuzbasiyan-Gurkan V., Brewer G.J.
    Biochem. Genet. 34:321-341(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 351-373.

Entry informationi

Entry nameiGHR_CANLF
AccessioniPrimary (citable) accession number: Q9TU69
Secondary accession number(s): Q29394
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 109 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.