GHR_HUMAN
ID GHR_HUMAN Reviewed; 638 AA.
AC P10912; Q9HCX2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Growth hormone receptor;
DE Short=GH receptor;
DE AltName: Full=Somatotropin receptor;
DE Contains:
DE RecName: Full=Growth hormone-binding protein;
DE Short=GH-binding protein;
DE Short=GHBP;
DE AltName: Full=Serum-binding protein;
DE Flags: Precursor;
GN Name=GHR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2825030; DOI=10.1038/330537a0;
RA Leung D.W., Spencer S.A., Cachianes G., Hammonds R.G., Collins C.,
RA Henzel W.J., Barnard R., Waters M.J., Wood W.I.;
RT "Growth hormone receptor and serum binding protein: purification, cloning
RT and expression.";
RL Nature 330:537-543(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT LEU-544.
RX PubMed=2813379; DOI=10.1073/pnas.86.20.8083;
RA Godowski P.J., Leung D.W., Meacham L.R., Galgani J.P., Hellmiss R.,
RA Keret R., Rotwein P.S., Parks J.S., Laron Z., Wood W.I.;
RT "Characterization of the human growth hormone receptor gene and
RT demonstration of a partial gene deletion in two patients with Laron-type
RT dwarfism.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8083-8087(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
RX PubMed=1569971; DOI=10.1210/mend.6.2.1569971;
RA Urbanek M., MacLeod J.N., Cooke N.E., Liebhaber S.A.;
RT "Expression of a human growth hormone (hGH) receptor isoform is predicted
RT by tissue-specific alternative splicing of exon 3 of the hGH receptor gene
RT transcript.";
RL Mol. Endocrinol. 6:279-287(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=8855247; DOI=10.1073/pnas.93.20.10723;
RA Dastot F., Sobrier M.-L., Duquesnoy P., Duriez B., Goossens M., Amselem S.;
RT "Alternatively spliced forms in the cytoplasmic domain of the human growth
RT hormone (GH) receptor regulate its ability to generate a soluble GH-binding
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10723-10728(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=9360546; DOI=10.1210/jcem.82.11.4358;
RA Amit T., Bergman T., Dastot F., Youdim M.B.H., Amselem S., Hochberg Z.;
RT "A membrane-fixed, truncated isoform of the human growth hormone
RT receptor.";
RL J. Clin. Endocrinol. Metab. 82:3813-3817(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Liver;
RX PubMed=9058373; DOI=10.1210/mend.11.3.9901;
RA Ross R.J., Esposito N., Shen X.Y., Von Laue S., Chew S.L., Dobson P.R.,
RA Postel-Vinay M.-C., Finidori J.;
RT "A short isoform of the human growth hormone receptor functions as a
RT dominant negative inhibitor of the full-length receptor and generates large
RT amounts of binding protein.";
RL Mol. Endocrinol. 11:265-273(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 263-336.
RA Orlovsky I.V., Borovikova I.E., Rubtsov P.M.;
RT "Comparing of nucleotide sequences of alternatively spliced region of
RT mammalian growth hormone receptor genes.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP CHARACTERIZATION (ISOFORM 4).
RX PubMed=8360189; DOI=10.1016/s0021-9258(17)46730-5;
RA Urbanek M., Russell J.E., Cooke N.E., Liebhaber S.A.;
RT "Functional characterization of the alternatively spliced, placental human
RT growth hormone receptor.";
RL J. Biol. Chem. 268:19025-19032(1993).
RN [9]
RP MOLECULAR MECHANISM OF PRODUCTION (ISOFORM 4).
RX PubMed=10764769; DOI=10.1074/jbc.m001615200;
RA Pantel J., Machinis K., Sobrier M.-L., Duquesnoy P., Goossens M.,
RA Amselem S.;
RT "Species-specific alternative splice mimicry at the growth hormone receptor
RT locus revealed by the lineage of retroelements during primate evolution.";
RL J. Biol. Chem. 275:18664-18669(2000).
RN [10]
RP DISULFIDE BONDS.
RX PubMed=2406245; DOI=10.1016/s0021-9258(19)39741-8;
RA Fuh G., Mulkerrin M.G., Bass S., McFarland N., Brochier M., Bourrel J.H.,
RA Light D.R., Wells J.A.;
RT "The human growth hormone receptor. Secretion from Escherichia coli and
RT disulfide bonding pattern of the extracellular binding domain.";
RL J. Biol. Chem. 265:3111-3115(1990).
RN [11]
RP SITE CRITICAL TO PROTEOLYSIS, AND MUTAGENESIS OF GLU-260; GLU-261 AND
RP ASP-262.
RX PubMed=11785980; DOI=10.1006/bbrc.2001.6261;
RA Conte F., Salles J.P., Raynal P., Fernandez L., Molinas C., Tauber M.,
RA Bieth E.;
RT "Identification of a region critical for proteolysis of the human growth
RT hormone receptor.";
RL Biochem. Biophys. Res. Commun. 290:851-857(2002).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 19-254 IN COMPLEX WITH GROWTH
RP HORMONE.
RX PubMed=1549776; DOI=10.1126/science.1549776;
RA de Vos A.M., Ultsch M., Kossiakoff A.A.;
RT "Human growth hormone and extracellular domain of its receptor: crystal
RT structure of the complex.";
RL Science 255:306-312(1992).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-256 IN COMPLEX WITH GROWTH
RP HORMONE.
RX PubMed=8943276; DOI=10.1074/jbc.271.50.32197;
RA Sundstroem M., Lundqvist T., Roedin J., Giebel L.B., Milligan D.,
RA Norstedt G.;
RT "Crystal structure of an antagonist mutant of human growth hormone, G120R,
RT in complex with its receptor at 2.9-A resolution.";
RL J. Biol. Chem. 271:32197-32203(1996).
RN [15]
RP VARIANT LARS SER-114.
RX PubMed=2779634; DOI=10.1056/nejm198910123211501;
RA Amselem S., Duquesnoy P., Attree O., Novelli G., Bousnina S.,
RA Postel-Vinay M.-C., Goossens M.;
RT "Laron dwarfism and mutations of the growth hormone-receptor gene.";
RL N. Engl. J. Med. 321:989-995(1989).
RN [16]
RP VARIANT PHE-440.
RX PubMed=8421103; DOI=10.1210/jcem.76.1.8421103;
RA Kou K., Lajara R., Rotwein P.;
RT "Amino acid substitutions in the intracellular part of the growth hormone
RT receptor in a patient with the Laron syndrome.";
RL J. Clin. Endocrinol. Metab. 76:54-59(1993).
RN [17]
RP VARIANTS LARS LYS-89; GLN-149; ASP-162; CYS-179 AND GLY-229.
RX PubMed=8504296; DOI=10.1093/hmg/2.4.355;
RA Amselem S., Duquesnoy P., Duriez B., Dastot F., Sobrier M.-L., Valleix S.,
RA Goossens M.;
RT "Spectrum of growth hormone receptor mutations and associated haplotypes in
RT Laron syndrome.";
RL Hum. Mol. Genet. 2:355-359(1993).
RN [18]
RP CHARACTERIZATION OF VARIANT LARS SER-114.
RX PubMed=8450064; DOI=10.1172/jci116304;
RA Edery M., Rozakis-Adcock M., Goujon L., Finidori J., Levi-Meyrueis C.,
RA Paly J., Djiane J., Postel-Vinay M.-C., Kelly P.A.;
RT "Lack of hormone binding in COS-7 cells expressing a mutated growth hormone
RT receptor found in Laron dwarfism.";
RL J. Clin. Invest. 91:838-844(1993).
RN [19]
RP VARIANT LARS HIS-170.
RX PubMed=8137822; DOI=10.1002/j.1460-2075.1994.tb06392.x;
RA Duquesnoy P., Sobrier M.-L., Duriez B., Dastot F., Buchanan C.R.,
RA Savage M.O., Preece M.A., Craescu C.T., Blouquit Y., Goossens M.,
RA Amselem S.;
RT "A single amino acid substitution in the exoplasmic domain of the human
RT growth hormone (GH) receptor confers familial GH resistance (Laron
RT syndrome) with positive GH-binding activity by abolishing receptor
RT homodimerization.";
RL EMBO J. 13:1386-1395(1994).
RN [20]
RP VARIANTS GHIP LYS-62 AND CYS-179, AND VARIANTS HIS-229 AND ASP-242.
RX PubMed=7565946; DOI=10.1056/nejm199510263331701;
RA Goddard A.D., Covello R., Luoh S.-M., Clackson T., Attie K.M.,
RA Gesundheit N., Rundle A.C., Wells J.A., Carlsson L.M.S.;
RT "Mutations of the growth hormone receptor in children with idiopathic short
RT stature.";
RL N. Engl. J. Med. 333:1093-1098(1995).
RN [21]
RP VARIANTS LARS SER-56; LEU-58 AND ARG-68.
RX PubMed=9024232; DOI=10.1210/jcem.82.2.3725;
RA Sobrier M.-L., Dastot F., Duquesnoy P., Kandemir N., Yordam N.,
RA Goossens M., Amselem S.;
RT "Nine novel growth hormone receptor gene mutations in patients with Laron
RT syndrome.";
RL J. Clin. Endocrinol. Metab. 82:435-437(1997).
RN [22]
RP VARIANT LARS GLN-149, AND CHARACTERIZATION OF VARIANT LARS GLN-149.
RX PubMed=9661642; DOI=10.1210/jcem.83.7.4954;
RA Walker J.L., Crock P.A., Behncken S.N., Rowlinson S.W., Nicholson L.M.,
RA Boulton T.J.C., Waters M.J.;
RT "A novel mutation affecting the interdomain link region of the growth
RT hormone receptor in a Vietnamese girl, and response to long-term treatment
RT with recombinant human insulin-like growth factor-I and luteinizing
RT hormone-releasing hormone analogue.";
RL J. Clin. Endocrinol. Metab. 83:2554-2561(1998).
RN [23]
RP VARIANT ILE-162.
RX PubMed=9814495; DOI=10.1210/jcem.83.11.5238;
RA Sanchez J.E., Perera E., Baumbach L., Cleveland W.W.;
RT "Growth hormone receptor mutations in children with idiopathic short
RT stature.";
RL J. Clin. Endocrinol. Metab. 83:4079-4083(1998).
RN [24]
RP VARIANTS LARS HIS-170; THR-171; PRO-172 AND GLY-173, AND CHARACTERIZATION
RP OF VARIANTS LARS THR-171; PRO-172 AND GLY-173.
RX PubMed=9851797; DOI=10.1210/jcem.83.12.5357;
RA Wojcik J., Berg M.A., Esposito N., Geffner M.E., Sakati N., Reiter E.O.,
RA Dower S., Francke U., Postel-Vinay M.-C., Finidori J.;
RT "Four contiguous amino acid substitutions, identified in patients with
RT Laron syndrome, differently affect the binding affinity and intracellular
RT trafficking of the growth hormone receptor.";
RL J. Clin. Endocrinol. Metab. 83:4481-4489(1998).
RN [25]
RP VARIANTS HIS-179; HIS-229; PHE-440; THR-495; LEU-544 AND THR-579.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [26]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [27]
RP VARIANTS LARS CYS-226 AND ASN-262.
RX PubMed=10870033; DOI=10.1530/eje.0.1430071;
RA Enberg B., Luthman H., Segnestam K., Ritzen E.M., Sundstroem M.,
RA Norstedt G.;
RT "Characterisation of novel missense mutations in the GH receptor gene
RT causing severe growth retardation.";
RL Eur. J. Endocrinol. 143:71-76(2000).
RN [28]
RP VARIANT LEU-544.
RX PubMed=12910492; DOI=10.1002/ajmg.a.20172;
RA Takada D., Ezura Y., Ono S., Iino Y., Katayama Y., Xin Y., Wu L.L.,
RA Larringa-Shum S., Stephenson S.H., Hunt S.C., Hopkins P.N., Emi M.;
RT "Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol
RT phenotype in familial hypercholesterolemia: intra-familial association
RT study in an eight-generation hyperlipidemic kindred.";
RL Am. J. Med. Genet. A 121:136-140(2003).
RN [29]
RP VARIANT LARS ILE-244.
RX PubMed=14678285; DOI=10.1111/j.1365-2265.2004.01930.x;
RA Jorge A.A.L., Souza S.C.A.L., Arnhold I.J.P., Mendonca B.B.;
RT "The first homozygous mutation (S226I) in the highly-conserved WSXWS-like
RT motif of the GH receptor causing Laron syndrome: suppression of GH
RT secretion by GnRH analogue therapy not restored by dihydrotestosterone
RT administration.";
RL Clin. Endocrinol. (Oxf.) 60:36-40(2004).
CC -!- FUNCTION: Receptor for pituitary gland growth hormone involved in
CC regulating postnatal body growth. On ligand binding, couples to the
CC JAK2/STAT5 pathway (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The soluble form (GHBP) acts as a reservoir of growth hormone
CC in plasma and may be a modulator/inhibitor of GH signaling.
CC -!- FUNCTION: Isoform 2 up-regulates the production of GHBP and acts as a
CC negative inhibitor of GH signaling.
CC -!- SUBUNIT: On growth hormone (GH) binding, forms homodimers and binds
CC JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2
CC activation, binding to CIS and SOCS2 inhibits STAT5 activation.
CC Interacts with ADAM17. {ECO:0000250}.
CC -!- INTERACTION:
CC P10912; Q16829: DUSP7; NbExp=2; IntAct=EBI-286316, EBI-1265847;
CC P10912; P01241: GH1; NbExp=4; IntAct=EBI-286316, EBI-1026046;
CC P10912; P10912: GHR; NbExp=4; IntAct=EBI-286316, EBI-286316;
CC P10912; P16333: NCK1; NbExp=3; IntAct=EBI-286316, EBI-389883;
CC P10912; P18031: PTPN1; NbExp=5; IntAct=EBI-286316, EBI-968788;
CC P10912; P17706: PTPN2; NbExp=8; IntAct=EBI-286316, EBI-984930;
CC P10912; P26045: PTPN3; NbExp=4; IntAct=EBI-286316, EBI-1047946;
CC P10912; P43378: PTPN9; NbExp=2; IntAct=EBI-286316, EBI-742898;
CC P10912; P23467: PTPRB; NbExp=3; IntAct=EBI-286316, EBI-1265766;
CC P10912; Q9HD43: PTPRH; NbExp=4; IntAct=EBI-286316, EBI-1267176;
CC P10912; Q12913: PTPRJ; NbExp=2; IntAct=EBI-286316, EBI-2264500;
CC P10912; Q9JLI4: Ncoa6; Xeno; NbExp=2; IntAct=EBI-286316, EBI-286271;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Note=On growth hormone binding, GHR is ubiquitinated,
CC internalized, down-regulated and transported into a degradative or non-
CC degradative pathway. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I
CC membrane protein. Note=Remains fixed to the cell membrane and is not
CC internalized.
CC -!- SUBCELLULAR LOCATION: [Growth hormone-binding protein]: Secreted.
CC Note=Complexed to a substantial fraction of circulating GH.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=GHRfl;
CC IsoId=P10912-1; Sequence=Displayed;
CC Name=2; Synonyms=GHRtr, GHR1-279;
CC IsoId=P10912-2; Sequence=VSP_010227, VSP_010228;
CC Name=3; Synonyms=GHR1-277;
CC IsoId=P10912-3; Sequence=VSP_010229, VSP_010230;
CC Name=4; Synonyms=GHRd3;
CC IsoId=P10912-4; Sequence=VSP_010225, VSP_010226;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues with high expression
CC in liver and skeletal muscle. Isoform 4 is predominantly expressed in
CC kidney, bladder, adrenal gland and brain stem. Isoform 1 expression in
CC placenta is predominant in chorion and decidua. Isoform 4 is highly
CC expressed in placental villi. Isoform 2 is expressed in lung, stomach
CC and muscle. Low levels in liver.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- DOMAIN: The extracellular domain is the ligand-binding domain
CC representing the growth hormone-binding protein (GHBP).
CC -!- DOMAIN: The ubiquitination-dependent endocytosis motif (UbE) is
CC required for recruitment of the ubiquitin conjugation system on to the
CC receptor and for its internalization.
CC -!- PTM: The soluble form (GHBP) is produced by phorbol ester-promoted
CC proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE.
CC Shedding is inhibited by growth hormone (GH) binding to the receptor
CC probably due to a conformational change in GHR rendering the receptor
CC inaccessible to ADAM17 (By similarity). {ECO:0000250}.
CC -!- PTM: On GH binding, phosphorylated on tyrosine residues in the
CC cytoplasmic domain by JAK2. {ECO:0000250}.
CC -!- PTM: On ligand binding, ubiquitinated on lysine residues in the
CC cytoplasmic domain. This ubiquitination is not sufficient for GHR
CC internalization (By similarity). {ECO:0000250}.
CC -!- POLYMORPHISM: Genetic variation in GHR may act as phenotype modifier in
CC familial hypercholesterolemia [MIM:143890] patients carrying a mutation
CC in the LDLR gene.
CC -!- DISEASE: Laron syndrome (LARS) [MIM:262500]: A severe form of growth
CC hormone insensitivity characterized by growth impairment, short
CC stature, dysfunctional growth hormone receptor, and failure to generate
CC insulin-like growth factor I in response to growth hormone.
CC {ECO:0000269|PubMed:10870033, ECO:0000269|PubMed:14678285,
CC ECO:0000269|PubMed:2779634, ECO:0000269|PubMed:8137822,
CC ECO:0000269|PubMed:8450064, ECO:0000269|PubMed:8504296,
CC ECO:0000269|PubMed:9024232, ECO:0000269|PubMed:9661642,
CC ECO:0000269|PubMed:9851797}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Growth hormone insensitivity, partial (GHIP) [MIM:604271]: A
CC disease characterized by partial resistance to growth hormone resulting
CC in short stature. Short stature is defined by a standing height more
CC than 2 standard deviations below the mean (or below the 2.5 percentile)
CC for sex and chronological age, compared with a well-nourished, healthy,
CC genetically relevant population. {ECO:0000269|PubMed:7565946}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 4]: Arises by species-specific retrovirus-
CC mediated alternative splice mimicry. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; X06562; CAA29808.1; -; mRNA.
DR EMBL; M28466; AAA52555.1; -; Genomic_DNA.
DR EMBL; M28458; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28459; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28460; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28461; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28462; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28463; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28464; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; M28465; AAA52555.1; JOINED; Genomic_DNA.
DR EMBL; AJ278681; CAC06613.1; -; Genomic_DNA.
DR CCDS; CCDS3940.1; -. [P10912-1]
DR CCDS; CCDS56364.1; -. [P10912-4]
DR PIR; A33991; A33991.
DR RefSeq; NP_000154.1; NM_000163.4. [P10912-1]
DR RefSeq; NP_001229328.1; NM_001242399.2.
DR RefSeq; NP_001229329.1; NM_001242400.2. [P10912-1]
DR RefSeq; NP_001229330.1; NM_001242401.3. [P10912-1]
DR RefSeq; NP_001229331.1; NM_001242402.2. [P10912-1]
DR RefSeq; NP_001229332.1; NM_001242403.2. [P10912-1]
DR RefSeq; NP_001229333.1; NM_001242404.2. [P10912-1]
DR RefSeq; NP_001229334.1; NM_001242405.2. [P10912-1]
DR RefSeq; NP_001229335.1; NM_001242406.2. [P10912-1]
DR RefSeq; NP_001229389.1; NM_001242460.1. [P10912-4]
DR RefSeq; NP_001229391.1; NM_001242462.1.
DR PDB; 1A22; X-ray; 2.60 A; B=19-256.
DR PDB; 1AXI; X-ray; 2.10 A; B=19-254.
DR PDB; 1HWG; X-ray; 2.50 A; B/C=19-255.
DR PDB; 1HWH; X-ray; 2.90 A; B=19-255.
DR PDB; 1KF9; X-ray; 2.60 A; B/C/E/F=19-256.
DR PDB; 2AEW; X-ray; 2.70 A; A/B=47-251.
DR PDB; 3HHR; X-ray; 2.80 A; B/C=50-254.
DR PDB; 5OEK; NMR; -; A/B=254-294.
DR PDB; 5OHD; NMR; -; A/B=254-294.
DR PDBsum; 1A22; -.
DR PDBsum; 1AXI; -.
DR PDBsum; 1HWG; -.
DR PDBsum; 1HWH; -.
DR PDBsum; 1KF9; -.
DR PDBsum; 2AEW; -.
DR PDBsum; 3HHR; -.
DR PDBsum; 5OEK; -.
DR PDBsum; 5OHD; -.
DR AlphaFoldDB; P10912; -.
DR SMR; P10912; -.
DR BioGRID; 108957; 44.
DR DIP; DIP-630N; -.
DR ELM; P10912; -.
DR IntAct; P10912; 22.
DR STRING; 9606.ENSP00000483403; -.
DR ChEMBL; CHEMBL1976; -.
DR DrugBank; DB16220; Lonapegsomatropin.
DR DrugBank; DB00082; Pegvisomant.
DR DrugBank; DB15093; Somapacitan.
DR DrugBank; DB00052; Somatotropin.
DR DrugBank; DB09098; Somatrem.
DR DrugCentral; P10912; -.
DR GlyGen; P10912; 6 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P10912; -.
DR PhosphoSitePlus; P10912; -.
DR BioMuta; GHR; -.
DR DMDM; 121180; -.
DR EPD; P10912; -.
DR jPOST; P10912; -.
DR MassIVE; P10912; -.
DR PaxDb; P10912; -.
DR PeptideAtlas; P10912; -.
DR PRIDE; P10912; -.
DR ProteomicsDB; 52672; -. [P10912-1]
DR ProteomicsDB; 52673; -. [P10912-2]
DR ProteomicsDB; 52674; -. [P10912-3]
DR ProteomicsDB; 52675; -. [P10912-4]
DR Antibodypedia; 23220; 402 antibodies from 36 providers.
DR DNASU; 2690; -.
DR Ensembl; ENST00000230882.9; ENSP00000230882.4; ENSG00000112964.14. [P10912-1]
DR Ensembl; ENST00000357703.6; ENSP00000350335.3; ENSG00000112964.14. [P10912-4]
DR Ensembl; ENST00000537449.5; ENSP00000442206.2; ENSG00000112964.14. [P10912-1]
DR Ensembl; ENST00000612382.4; ENSP00000478332.1; ENSG00000112964.14. [P10912-1]
DR Ensembl; ENST00000612626.4; ENSP00000479846.1; ENSG00000112964.14. [P10912-1]
DR Ensembl; ENST00000615111.4; ENSP00000478291.1; ENSG00000112964.14. [P10912-1]
DR Ensembl; ENST00000618088.4; ENSP00000482373.1; ENSG00000112964.14. [P10912-1]
DR GeneID; 2690; -.
DR KEGG; hsa:2690; -.
DR MANE-Select; ENST00000230882.9; ENSP00000230882.4; NM_000163.5; NP_000154.1.
DR UCSC; uc003jmt.4; human. [P10912-1]
DR CTD; 2690; -.
DR DisGeNET; 2690; -.
DR GeneCards; GHR; -.
DR HGNC; HGNC:4263; GHR.
DR HPA; ENSG00000112964; Tissue enhanced (adipose tissue, liver).
DR MalaCards; GHR; -.
DR MIM; 143890; phenotype.
DR MIM; 262500; phenotype.
DR MIM; 600946; gene.
DR MIM; 604271; phenotype.
DR neXtProt; NX_P10912; -.
DR OpenTargets; ENSG00000112964; -.
DR Orphanet; 633; Laron syndrome.
DR Orphanet; 314802; Short stature due to partial GHR deficiency.
DR PharmGKB; PA28674; -.
DR VEuPathDB; HostDB:ENSG00000112964; -.
DR eggNOG; KOG3555; Eukaryota.
DR GeneTree; ENSGT00940000159987; -.
DR HOGENOM; CLU_022322_0_0_1; -.
DR InParanoid; P10912; -.
DR OMA; YCIKLTN; -.
DR OrthoDB; 346239at2759; -.
DR PhylomeDB; P10912; -.
DR TreeFam; TF330851; -.
DR PathwayCommons; P10912; -.
DR Reactome; R-HSA-1170546; Prolactin receptor signaling.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SignaLink; P10912; -.
DR SIGNOR; P10912; -.
DR BioGRID-ORCS; 2690; 10 hits in 1075 CRISPR screens.
DR ChiTaRS; GHR; human.
DR EvolutionaryTrace; P10912; -.
DR GeneWiki; Growth_hormone_receptor; -.
DR GenomeRNAi; 2690; -.
DR Pharos; P10912; Tclin.
DR PRO; PR:P10912; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P10912; protein.
DR Bgee; ENSG00000112964; Expressed in skeletal muscle tissue of rectus abdominis and 165 other tissues.
DR ExpressionAtlas; P10912; baseline and differential.
DR Genevisible; P10912; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0070195; C:growth hormone receptor complex; IDA:CAFA.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0019838; F:growth factor binding; IPI:BHF-UCL.
DR GO; GO:0004903; F:growth hormone receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0017046; F:peptide hormone binding; IPI:BHF-UCL.
DR GO; GO:0070064; F:proline-rich region binding; ISS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; ISS:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR GO; GO:0042976; P:activation of Janus kinase activity; IEA:Ensembl.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IMP:BHF-UCL.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0042445; P:hormone metabolic process; IMP:BHF-UCL.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:BHF-UCL.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:BHF-UCL.
DR GO; GO:0031623; P:receptor internalization; IDA:BHF-UCL.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISS:BHF-UCL.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:BHF-UCL.
DR GO; GO:0046898; P:response to cycloheximide; IDA:BHF-UCL.
DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009629; P:response to gravity; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR GO; GO:0019530; P:taurine metabolic process; ISS:BHF-UCL.
DR CDD; cd00063; FN3; 1.
DR DisProt; DP00033; -.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR025871; GHBP.
DR InterPro; IPR015152; Growth/epo_recpt_lig-bind.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003528; Long_hematopoietin_rcpt_CS.
DR Pfam; PF09067; EpoR_lig-bind; 1.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF12772; GHBP; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism;
KW Endocytosis; Glycoprotein; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..638
FT /note="Growth hormone receptor"
FT /id="PRO_0000010957"
FT CHAIN 19..256
FT /note="Growth hormone-binding protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000010958"
FT TOPO_DOM 19..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..638
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 151..254
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 260..262
FT /note="Required for ADAM17-mediated proteolysis"
FT /evidence="ECO:0000250"
FT REGION 353..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 240..244
FT /note="WSXWS motif"
FT MOTIF 297..305
FT /note="Box 1 motif"
FT MOTIF 340..349
FT /note="UbE motif"
FT COMPBIAS 359..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 345
FT /note="Required for endocytosis and down-regulation"
FT /evidence="ECO:0000250"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 56..66
FT /evidence="ECO:0000269|PubMed:2406245"
FT DISULFID 101..112
FT /evidence="ECO:0000269|PubMed:2406245"
FT DISULFID 126..140
FT /evidence="ECO:0000269|PubMed:2406245"
FT VAR_SEQ 24
FT /note="A -> D (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:1569971"
FT /id="VSP_010225"
FT VAR_SEQ 25..46
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:1569971"
FT /id="VSP_010226"
FT VAR_SEQ 292..297
FT /note="RIKMLI -> SSSSKD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8855247,
FT ECO:0000303|PubMed:9058373, ECO:0000303|PubMed:9360546"
FT /id="VSP_010227"
FT VAR_SEQ 292..294
FT /note="RIK -> KEN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9058373"
FT /id="VSP_010229"
FT VAR_SEQ 295..638
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9058373"
FT /id="VSP_010230"
FT VAR_SEQ 298..638
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8855247,
FT ECO:0000303|PubMed:9058373, ECO:0000303|PubMed:9360546"
FT /id="VSP_010228"
FT VARIANT 56
FT /note="C -> S (in LARS)"
FT /evidence="ECO:0000269|PubMed:9024232"
FT /id="VAR_018426"
FT VARIANT 58
FT /note="S -> L (in LARS)"
FT /evidence="ECO:0000269|PubMed:9024232"
FT /id="VAR_018427"
FT VARIANT 62
FT /note="E -> K (in GHIP; dbSNP:rs121909361)"
FT /evidence="ECO:0000269|PubMed:7565946"
FT /id="VAR_002708"
FT VARIANT 68
FT /note="W -> R (in LARS)"
FT /evidence="ECO:0000269|PubMed:9024232"
FT /id="VAR_018428"
FT VARIANT 89
FT /note="R -> K (in LARS)"
FT /evidence="ECO:0000269|PubMed:8504296"
FT /id="VAR_002709"
FT VARIANT 114
FT /note="F -> S (in LARS; loss of ability to bind ligand;
FT dbSNP:rs121909357)"
FT /evidence="ECO:0000269|PubMed:2779634,
FT ECO:0000269|PubMed:8450064"
FT /id="VAR_002710"
FT VARIANT 143
FT /note="V -> A (in LARS)"
FT /id="VAR_002711"
FT VARIANT 149
FT /note="P -> Q (in LARS; disrupts GH binding;
FT dbSNP:rs121909365)"
FT /evidence="ECO:0000269|PubMed:8504296,
FT ECO:0000269|PubMed:9661642"
FT /id="VAR_018429"
FT VARIANT 162
FT /note="V -> D (in LARS)"
FT /evidence="ECO:0000269|PubMed:8504296"
FT /id="VAR_002712"
FT VARIANT 162
FT /note="V -> F (in dbSNP:rs6413484)"
FT /id="VAR_020002"
FT VARIANT 162
FT /note="V -> I (found in a patient with idiopathic short
FT stature; unknown pathological significance;
FT dbSNP:rs6413484)"
FT /evidence="ECO:0000269|PubMed:9814495"
FT /id="VAR_018430"
FT VARIANT 170
FT /note="D -> H (in LARS; abolishes receptor
FT homodimerization; dbSNP:rs121909366)"
FT /evidence="ECO:0000269|PubMed:8137822,
FT ECO:0000269|PubMed:9851797"
FT /id="VAR_002713"
FT VARIANT 171
FT /note="I -> T (in LARS; almost completely abolishes GH-
FT binding at cell surface: 53% binding to membrane fractions;
FT dbSNP:rs121909367)"
FT /evidence="ECO:0000269|PubMed:9851797"
FT /id="VAR_018431"
FT VARIANT 172
FT /note="Q -> P (in LARS; almost completely abolishes GH-
FT binding at cell surface and in membrane fractions;
FT dbSNP:rs121909368)"
FT /evidence="ECO:0000269|PubMed:9851797"
FT /id="VAR_018432"
FT VARIANT 173
FT /note="V -> G (in LARS; almost completely abolishes GH-
FT binding at cell surface: 26% binding to membrane fractions;
FT dbSNP:rs121909369)"
FT /evidence="ECO:0000269|PubMed:9851797"
FT /id="VAR_018433"
FT VARIANT 179
FT /note="R -> C (in LARS and GHIP; dbSNP:rs121909362)"
FT /evidence="ECO:0000269|PubMed:7565946,
FT ECO:0000269|PubMed:8504296"
FT /id="VAR_002714"
FT VARIANT 179
FT /note="R -> H (in dbSNP:rs6181)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_013937"
FT VARIANT 226
FT /note="Y -> C (in LARS)"
FT /evidence="ECO:0000269|PubMed:10870033"
FT /id="VAR_018434"
FT VARIANT 229
FT /note="R -> G (in LARS)"
FT /evidence="ECO:0000269|PubMed:8504296"
FT /id="VAR_002715"
FT VARIANT 229
FT /note="R -> H (found in a patient with idiopathic short
FT stature; unknown pathological significance; dbSNP:rs6177)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:7565946"
FT /id="VAR_013938"
FT VARIANT 242
FT /note="E -> D (found in a patient with idiopathic short
FT stature; unknown pathological significance;
FT dbSNP:rs45588036)"
FT /evidence="ECO:0000269|PubMed:7565946"
FT /id="VAR_002716"
FT VARIANT 244
FT /note="S -> I (in LARS; dbSNP:rs1164396446)"
FT /evidence="ECO:0000269|PubMed:14678285"
FT /id="VAR_018435"
FT VARIANT 262
FT /note="D -> N (in LARS)"
FT /evidence="ECO:0000269|PubMed:10870033"
FT /id="VAR_018436"
FT VARIANT 440
FT /note="C -> F (in dbSNP:rs6182)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:8421103"
FT /id="VAR_013939"
FT VARIANT 465
FT /note="E -> K (in dbSNP:rs34283856)"
FT /id="VAR_032704"
FT VARIANT 495
FT /note="P -> T (in dbSNP:rs6183)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_013940"
FT VARIANT 544
FT /note="I -> L (benign variant; associated with lower plasma
FT HDL cholesterol levels in hypercholesterolemia patients
FT that carry a pathogenic variant in LDLR; dbSNP:rs6180)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12910492, ECO:0000269|PubMed:2813379"
FT /id="VAR_013941"
FT VARIANT 579
FT /note="P -> T (in dbSNP:rs6184)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_013942"
FT MUTAGEN 260
FT /note="E->A: No change in shedding activity: No change in
FT hormone binding."
FT /evidence="ECO:0000269|PubMed:11785980"
FT MUTAGEN 261
FT /note="E->A: No change in shedding activity: No change in
FT hormone binding."
FT /evidence="ECO:0000269|PubMed:11785980"
FT MUTAGEN 262
FT /note="D->A: No change in shedding activity: No change in
FT hormone binding."
FT /evidence="ECO:0000269|PubMed:11785980"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:1AXI"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:1HWG"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:3HHR"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1AXI"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 121..131
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 134..142
FT /evidence="ECO:0007829|PDB:1AXI"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 167..176
FT /evidence="ECO:0007829|PDB:1AXI"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 190..198
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 210..221
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:1AXI"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:2AEW"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:1AXI"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:5OHD"
FT HELIX 266..292
FT /evidence="ECO:0007829|PDB:5OEK"
SQ SEQUENCE 638 AA; 71500 MW; EAF77EADE4787822 CRC64;
MDLWQLLLTL ALAGSSDAFS GSEATAAILS RAPWSLQSVN PGLKTNSSKE PKFTKCRSPE
RETFSCHWTD EVHHGTKNLG PIQLFYTRRN TQEWTQEWKE CPDYVSAGEN SCYFNSSFTS
IWIPYCIKLT SNGGTVDEKC FSVDEIVQPD PPIALNWTLL NVSLTGIHAD IQVRWEAPRN
ADIQKGWMVL EYELQYKEVN ETKWKMMDPI LTTSVPVYSL KVDKEYEVRV RSKQRNSGNY
GEFSEVLYVT LPQMSQFTCE EDFYFPWLLI IIFGIFGLTV MLFVFLFSKQ QRIKMLILPP
VPVPKIKGID PDLLKEGKLE EVNTILAIHD SYKPEFHSDD SWVEFIELDI DEPDEKTEES
DTDRLLSSDH EKSHSNLGVK DGDSGRTSCC EPDILETDFN ANDIHEGTSE VAQPQRLKGE
ADLLCLDQKN QNNSPYHDAC PATQQPSVIQ AEKNKPQPLP TEGAESTHQA AHIQLSNPSS
LSNIDFYAQV SDITPAGSVV LSPGQKNKAG MSQCDMHPEM VSLCQENFLM DNAYFCEADA
KKCIPVAPHI KVESHIQPSL NQEDIYITTE SLTTAAGRPG TGEHVPGSEM PVPDYTSIHI
VQSPQGLILN ATALPLPDKE FLSSCGYVST DQLNKIMP
