PTH1R_HUMAN
ID PTH1R_HUMAN Reviewed; 593 AA.
AC Q03431; Q2M1U3;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Parathyroid hormone/parathyroid hormone-related peptide receptor;
DE AltName: Full=PTH/PTHrP type I receptor;
DE Short=PTH/PTHr receptor;
DE AltName: Full=Parathyroid hormone 1 receptor;
DE Short=PTH1 receptor;
DE Flags: Precursor;
GN Name=PTH1R; Synonyms=PTHR, PTHR1;
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].
RC TISSUE=Kidney;
RX PubMed=8386612; DOI=10.1210/endo.132.5.8386612;
RA Schipani E., Karga H., Karaplis A.C., Potts J.T. Jr., Kronenberg H.M.,
RA Abou-Samra A.-B., Segre G.V., Jueppner H.;
RT "Identical complementary deoxyribonucleic acids encode a human renal and
RT bone parathyroid hormone (PTH)/PTH-related peptide receptor.";
RL Endocrinology 132:2157-2165(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PTH, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8397094; DOI=10.1016/0922-4106(93)90092-n;
RA Schneider H., Feyen J.-H., Rao Movva N.;
RT "Cloning and functional expression of a human parathyroid hormone
RT receptor.";
RL Eur. J. Pharmacol. 246:149-155(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7745008; DOI=10.1210/jcem.80.5.7745008;
RA Schipani E., Weinstein L.S., Bergwitz C., Iida-Klein A., Kong X.F.,
RA Stuhrmann M., Kruse K., Whyte M.P., Murray T., Schmidtke J., Dop C.,
RA Brickman A.S., Crawford J.D., Potts J.T. Jr., Kronenberg H.M.,
RA Abou-Samra A.-B., Segre G.V., Jueppner H.;
RT "Pseudohypoparathyroidism type Ib is not caused by mutations in the coding
RT exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor
RT gene.";
RL J. Clin. Endocrinol. Metab. 80:1611-1621(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Levine M.A.;
RT "Characterization of cDNA and genomic DNA encoding the human PTH/PTHrP
RT receptor.";
RL Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "Isolation of cDNA coding for parathyroid hormone receptor 1 (PTHR1).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP DISULFIDE BONDS IN EXTRACELLULAR DOMAIN, AND INTERACTION WITH PTH.
RX PubMed=10913300; DOI=10.1021/bi0001426;
RA Grauschopf U., Lilie H., Honold K., Wozny M., Reusch D., Esswein A.,
RA Schafer W., Rucknagel K.P., Rudolph R.;
RT "The N-terminal fragment of human parathyroid hormone receptor 1
RT constitutes a hormone binding domain and reveals a distinct disulfide
RT pattern.";
RL Biochemistry 39:8878-8887(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-551, 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 [9]
RP STRUCTURE BY NMR OF 168-198.
RX PubMed=9737850; DOI=10.1021/bi981265h;
RA Pellegrini M., Bisello A., Rosenblatt M., Chorev M., Mierke D.F.;
RT "Binding domain of human parathyroid hormone receptor: from conformation to
RT function.";
RL Biochemistry 37:12737-12743(1998).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 29-187 IN COMPLEX WITH PTH, AND
RP DISULFIDE BONDS.
RX PubMed=18375760; DOI=10.1073/pnas.0801027105;
RA Pioszak A.A., Xu H.E.;
RT "Molecular recognition of parathyroid hormone by its G protein-coupled
RT receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5034-5039(2008).
RN [11]
RP RETRACTED PAPER.
RX PubMed=18611381; DOI=10.1016/j.str.2008.04.010;
RA Johnston C.A., Kimple A.J., Giguere P.M., Siderovski D.P.;
RT "Structure of the parathyroid hormone receptor C terminus bound to the G-
RT protein dimer Gbeta1gamma2.";
RL Structure 16:1086-1094(2008).
RN [12]
RP RETRACTION NOTICE OF PUBMED:18611381.
RX PubMed=21827955; DOI=10.1016/j.str.2011.07.010;
RA Johnston C.A., Kimple A.J., Giguere P.M., Siderovski D.P.;
RL Structure 19:1200-1200(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 29-187 IN COMPLEX WITH PTHLH,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=19674967; DOI=10.1074/jbc.m109.022905;
RA Pioszak A.A., Parker N.R., Gardella T.J., Xu H.E.;
RT "Structural basis for parathyroid hormone-related protein binding to the
RT parathyroid hormone receptor and design of conformation-selective
RT peptides.";
RL J. Biol. Chem. 284:28382-28391(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.24 ANGSTROMS) OF 29-187, FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-135 AND ASP-137, AND DISULFIDE
RP BONDS.
RX PubMed=20172855; DOI=10.1074/jbc.m109.093138;
RA Pioszak A.A., Harikumar K.G., Parker N.R., Miller L.J., Xu H.E.;
RT "Dimeric arrangement of the parathyroid hormone receptor and a structural
RT mechanism for ligand-induced dissociation.";
RL J. Biol. Chem. 285:12435-12444(2010).
RN [15]
RP VARIANT MCDJ ARG-223.
RX PubMed=7701349; DOI=10.1126/science.7701349;
RA Schipani E., Kruse K., Jueppner H.;
RT "A constitutively active mutant PTH-PTHrP receptor in Jansen-type
RT metaphyseal chondrodysplasia.";
RL Science 268:98-100(1995).
RN [16]
RP VARIANTS MCDJ ARG-223 AND PRO-410.
RX PubMed=8703170; DOI=10.1056/nejm199609053351004;
RA Schipani E., Langman C.B., Parfitt A.M., Jensen G.S., Kikuchi S.,
RA Kooh S.W., Cole W.G., Jueppner H.;
RT "Constitutively activated receptors for parathyroid hormone and parathyroid
RT hormone-related peptide in Jansen's metaphyseal chondrodysplasia.";
RL N. Engl. J. Med. 335:708-714(1996).
RN [17]
RP CHARACTERIZATION OF VARIANTS MCDJ ARG-223 AND PRO-410.
RX PubMed=9178745; DOI=10.1210/mend.11.7.9934;
RA Schipani E., Jensen G.S., Pincus J., Nissenson R.A., Gardella T.J.,
RA Jueppner H.;
RT "Constitutive activation of the cyclic adenosine 3',5'-monophosphate
RT signaling pathway by parathyroid hormone (PTH)/PTH-related peptide
RT receptors mutated at the two loci for Jansen's metaphyseal
RT chondrodysplasia.";
RL Mol. Endocrinol. 11:851-858(1997).
RN [18]
RP VARIANT BOCD LEU-132.
RX PubMed=9745456; DOI=10.1210/jcem.83.9.5243;
RA Zhang P., Jobert A.-S., Couvineau A., Silve C.;
RT "A homozygous inactivating mutation in the parathyroid hormone/parathyroid
RT hormone-related peptide receptor causing Blomstrand chondrodysplasia.";
RL J. Clin. Endocrinol. Metab. 83:3365-3368(1998).
RN [19]
RP VARIANT MCDJ ARG-458.
RX PubMed=10487664; DOI=10.1210/jcem.84.9.6000;
RA Schipani E., Langman C.B., Hunzelman J., Le Merrer M., Loke K.Y.,
RA Dillon M.J., Silve C., Jueppner H.;
RT "A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in
RT Jansen's metaphyseal chondrodysplasia.";
RL J. Clin. Endocrinol. Metab. 84:3052-3057(1999).
RN [20]
RP VARIANT CYS-150.
RX PubMed=11850620; DOI=10.1038/ng844;
RA Hopyan S., Gokgoz N., Poon R., Gensure R.C., Yu C., Cole W.G., Bell R.S.,
RA Jueppner H., Andrulis I.L., Wunder J.S., Alman B.A.;
RT "A mutant PTH/PTHrP type I receptor in enchondromatosis.";
RL Nat. Genet. 30:306-310(2002).
RN [21]
RP DISCUSSION OF THE ASSOCIATION OF CYS-150 WITH ENCHONDROMATOSIS.
RX PubMed=15523647; DOI=10.1002/humu.20095;
RA Rozeman L.B., Sangiorgi L., Briaire-de Bruijn I.H., Mainil-Varlet P.,
RA Bertoni F., Cleton-Jansen A.-M., Hogendoorn P.C.W., Bovee J.V.M.G.;
RT "Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the
RT PTHR1 mutation p.R150C.";
RL Hum. Mutat. 24:466-473(2004).
RN [22]
RP VARIANT MCDJ ARG-410, AND CHARACTERIZATION OF VARIANT MCDJ ARG-410.
RX PubMed=15240651; DOI=10.1210/jc.2004-0036;
RA Bastepe M., Raas-Rothschild A., Silver J., Weissman I., Wientroub S.,
RA Jueppner H., Gillis D.;
RT "A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and
RT skeletal abnormalities is caused by a novel activating parathyroid hormone
RT (PTH)/PTH-related peptide receptor mutation.";
RL J. Clin. Endocrinol. Metab. 89:3595-3600(2004).
RN [23]
RP INVOLVEMENT IN EKNS.
RX PubMed=15525660; DOI=10.1093/hmg/ddi001;
RA Duchatelet S., Ostergaard E., Cortes D., Lemainque A., Julier C.;
RT "Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in
RT Eiken and Blomstrand syndromes.";
RL Hum. Mol. Genet. 14:1-5(2005).
RN [24]
RP INVOLVEMENT IN PRIMARY FAILURE OF TOOTH ERUPTION.
RX PubMed=19061984; DOI=10.1016/j.ajhg.2008.11.006;
RA Decker E., Stellzig-Eisenhauer A., Fiebig B.S., Rau C., Kress W., Saar K.,
RA Rueschendorf F., Hubner N., Grimm T., Weber B.H.F.;
RT "PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure
RT of tooth eruption.";
RL Am. J. Hum. Genet. 83:781-786(2008).
RN [25]
RP VARIANT MCDJ ARG-223, CHARACTERIZATION OF VARIANT MCDJ ARG-223,
RP GLYCOSYLATION, FUNCTION, AND SUBUNIT.
RX PubMed=27160269; DOI=10.1007/s10266-016-0247-4;
RA Shimomura-Kuroki J., Farooq M., Sekimoto T., Amizuka N., Shimomura Y.;
RT "Characterization of a PTH1R missense mutation responsible for Jansen type
RT metaphyseal chondrodysplasia.";
RL Odontology 105:150-154(2017).
CC -!- FUNCTION: Receptor for parathyroid hormone and for parathyroid hormone-
CC related peptide. The activity of this receptor is mediated by G
CC proteins which activate adenylyl cyclase and also a
CC phosphatidylinositol-calcium second messenger system.
CC {ECO:0000269|PubMed:20172855, ECO:0000269|PubMed:27160269,
CC ECO:0000269|PubMed:8397094}.
CC -!- SUBUNIT: Interacts (via N-terminal extracellular domain) with PTHLH and
CC PTH (PubMed:8397094, PubMed:10913300, PubMed:18375760,
CC PubMed:19674967). Homodimer in the absence of bound ligand. Peptide
CC hormone binding leads to dissociation of the homodimer
CC (PubMed:19674967, PubMed:20172855). {ECO:0000269|PubMed:10913300,
CC ECO:0000269|PubMed:18375760, ECO:0000269|PubMed:19674967,
CC ECO:0000269|PubMed:20172855, ECO:0000269|PubMed:27160269,
CC ECO:0000269|PubMed:8397094}.
CC -!- INTERACTION:
CC Q03431; P35222: CTNNB1; NbExp=4; IntAct=EBI-2860297, EBI-491549;
CC Q03431; O95872: GPANK1; NbExp=3; IntAct=EBI-2860297, EBI-751540;
CC Q03431; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-2860297, EBI-11978177;
CC Q03431; P49639: HOXA1; NbExp=3; IntAct=EBI-2860297, EBI-740785;
CC Q03431; Q13064: MKRN3; NbExp=3; IntAct=EBI-2860297, EBI-2340269;
CC Q03431; P01270: PTH; NbExp=6; IntAct=EBI-2860297, EBI-716817;
CC Q03431; P12272: PTHLH; NbExp=4; IntAct=EBI-2860297, EBI-2372758;
CC Q03431; Q92922: SMARCC1; NbExp=3; IntAct=EBI-2860297, EBI-355653;
CC Q03431; O75716: STK16; NbExp=3; IntAct=EBI-2860297, EBI-749295;
CC Q03431; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-2860297, EBI-750487;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20172855,
CC ECO:0000269|PubMed:8397094}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20172855}.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues. Most abundant in kidney,
CC bone and liver. {ECO:0000269|PubMed:8397094}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:27160269}.
CC -!- DISEASE: Metaphyseal chondrodysplasia, Jansen type (MCDJ) [MIM:156400]:
CC A rare autosomal dominant disorder characterized by a short-limbed
CC dwarfism associated with hypercalcemia and normal or low serum
CC concentrations of the two parathyroid hormones.
CC {ECO:0000269|PubMed:10487664, ECO:0000269|PubMed:15240651,
CC ECO:0000269|PubMed:27160269, ECO:0000269|PubMed:7701349,
CC ECO:0000269|PubMed:8703170, ECO:0000269|PubMed:9178745}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Chondrodysplasia Blomstrand type (BOCD) [MIM:215045]: Severe
CC skeletal dysplasia. {ECO:0000269|PubMed:9745456}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Eiken syndrome (EKNS) [MIM:600002]: An autosomal recessive
CC skeletal dysplasia characterized by severely retarded ossification,
CC principally of the epiphyses, pelvis, hands and feet, as well as by
CC abnormal modeling of the bones in hands and feet, abnormal persistence
CC of cartilage in the pelvis and mild growth retardation.
CC {ECO:0000269|PubMed:15525660}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Primary failure of tooth eruption (PFE) [MIM:125350]: Rare
CC condition that has high penetrance and variable expressivity and in
CC which tooth retention occurs without evidence of any obvious mechanical
CC interference. Instead, malfunction of the eruptive mechanism itself
CC appears to cause nonankylosed permanent teeth to fail to erupt,
CC although the eruption pathway has been cleared by bone resorption.
CC {ECO:0000269|PubMed:19061984}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
CC -!- CAUTION: Was shown to interact with G protein subunit GNB1 and GNG2,
CC the interaction was reduced by mutation of Trp-474 and Trp-477. However
CC this paper was retracted due to a lack of clear and continous electron
CC density in the complex structure. {ECO:0000305|PubMed:18611381,
CC ECO:0000305|PubMed:21827955}.
CC -!- CAUTION: PubMed:11850620 suggests PTH1R involvement in multiple
CC enchondromatosis. However, PubMed:15523647 shows evidence that this
CC disease is not caused by PTH1R. {ECO:0000269|PubMed:11850620,
CC ECO:0000269|PubMed:15523647}.
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DR EMBL; L04308; AAA36525.1; -; mRNA.
DR EMBL; X68596; CAA48589.1; -; mRNA.
DR EMBL; U22409; AAB60657.1; -; Genomic_DNA.
DR EMBL; U22401; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22402; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22403; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22404; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22405; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22406; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22407; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U22408; AAB60657.1; JOINED; Genomic_DNA.
DR EMBL; U17418; AAA56774.1; -; mRNA.
DR EMBL; AY449732; AAR18076.1; -; mRNA.
DR EMBL; BC112221; AAI12222.1; -; mRNA.
DR EMBL; BC112247; AAI12248.1; -; mRNA.
DR CCDS; CCDS2747.1; -.
DR PIR; I38139; A49191.
DR RefSeq; NP_000307.1; NM_000316.2.
DR RefSeq; NP_001171673.1; NM_001184744.1.
DR RefSeq; XP_016862422.1; XM_017006933.1.
DR PDB; 1BL1; NMR; -; A=168-197.
DR PDB; 3C4M; X-ray; 1.95 A; A/B=29-187.
DR PDB; 3H3G; X-ray; 1.94 A; A=29-187.
DR PDB; 3L2J; X-ray; 3.24 A; A/B=29-187.
DR PDB; 4Z8J; X-ray; 0.95 A; B=586-593.
DR PDB; 5EMB; X-ray; 0.85 A; B=586-593.
DR PDB; 6NBF; EM; 3.00 A; R=27-502.
DR PDB; 6NBH; EM; 3.50 A; R=27-502.
DR PDB; 6NBI; EM; 4.00 A; R=27-502.
DR PDBsum; 1BL1; -.
DR PDBsum; 3C4M; -.
DR PDBsum; 3H3G; -.
DR PDBsum; 3L2J; -.
DR PDBsum; 4Z8J; -.
DR PDBsum; 5EMB; -.
DR PDBsum; 6NBF; -.
DR PDBsum; 6NBH; -.
DR PDBsum; 6NBI; -.
DR AlphaFoldDB; Q03431; -.
DR SMR; Q03431; -.
DR BioGRID; 111717; 106.
DR CORUM; Q03431; -.
DR IntAct; Q03431; 37.
DR MINT; Q03431; -.
DR STRING; 9606.ENSP00000321999; -.
DR BindingDB; Q03431; -.
DR ChEMBL; CHEMBL1793; -.
DR DrugBank; DB05084; Abaloparatide.
DR DrugBank; DB05829; Parathyroid hormone.
DR DrugBank; DB06285; Teriparatide.
DR DrugCentral; Q03431; -.
DR GuidetoPHARMACOLOGY; 331; -.
DR TCDB; 9.A.14.4.11; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; Q03431; 4 sites.
DR iPTMnet; Q03431; -.
DR PhosphoSitePlus; Q03431; -.
DR BioMuta; PTH1R; -.
DR DMDM; 417555; -.
DR REPRODUCTION-2DPAGE; Q03431; -.
DR MassIVE; Q03431; -.
DR PaxDb; Q03431; -.
DR PeptideAtlas; Q03431; -.
DR PRIDE; Q03431; -.
DR TopDownProteomics; Q03431; -.
DR ABCD; Q03431; 23 sequenced antibodies.
DR Antibodypedia; 1960; 424 antibodies from 39 providers.
DR DNASU; 5745; -.
DR Ensembl; ENST00000313049.9; ENSP00000321999.4; ENSG00000160801.14.
DR Ensembl; ENST00000418619.5; ENSP00000411424.1; ENSG00000160801.14.
DR Ensembl; ENST00000430002.6; ENSP00000413774.2; ENSG00000160801.14.
DR Ensembl; ENST00000449590.6; ENSP00000402723.1; ENSG00000160801.14.
DR GeneID; 5745; -.
DR KEGG; hsa:5745; -.
DR MANE-Select; ENST00000449590.6; ENSP00000402723.1; NM_000316.3; NP_000307.1.
DR UCSC; uc003cqm.4; human.
DR CTD; 5745; -.
DR DisGeNET; 5745; -.
DR GeneCards; PTH1R; -.
DR HGNC; HGNC:9608; PTH1R.
DR HPA; ENSG00000160801; Tissue enriched (kidney).
DR MalaCards; PTH1R; -.
DR MIM; 125350; phenotype.
DR MIM; 156400; phenotype.
DR MIM; 168468; gene.
DR MIM; 215045; phenotype.
DR MIM; 600002; phenotype.
DR neXtProt; NX_Q03431; -.
DR OpenTargets; ENSG00000160801; -.
DR Orphanet; 50945; Blomstrand lethal chondrodysplasia.
DR Orphanet; 79106; Eiken syndrome.
DR Orphanet; 33067; Metaphyseal chondrodysplasia, Jansen type.
DR Orphanet; 296; Ollier disease.
DR Orphanet; 412206; Primary failure of tooth eruption.
DR PharmGKB; PA33953; -.
DR VEuPathDB; HostDB:ENSG00000160801; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000158574; -.
DR InParanoid; Q03431; -.
DR OMA; ESDKGWM; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; Q03431; -.
DR TreeFam; TF315710; -.
DR PathwayCommons; Q03431; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q03431; -.
DR SIGNOR; Q03431; -.
DR BioGRID-ORCS; 5745; 20 hits in 1083 CRISPR screens.
DR ChiTaRS; PTH1R; human.
DR EvolutionaryTrace; Q03431; -.
DR GeneWiki; Parathyroid_hormone_1_receptor; -.
DR GenomeRNAi; 5745; -.
DR Pharos; Q03431; Tclin.
DR PRO; PR:Q03431; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q03431; protein.
DR Bgee; ENSG00000160801; Expressed in adult mammalian kidney and 146 other tissues.
DR ExpressionAtlas; Q03431; baseline and differential.
DR Genevisible; Q03431; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISS:BHF-UCL.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004991; F:parathyroid hormone receptor activity; IDA:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IC:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR InterPro; IPR001879; GPCR_2_extracellular_dom.
DR InterPro; IPR002170; GPCR_2_parathyroid_rcpt.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR PANTHER; PTHR45620:SF27; PTHR45620:SF27; 1.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF02793; HRM; 1.
DR PRINTS; PR00249; GPCRSECRETIN.
DR PRINTS; PR00393; PTRHORMONER.
DR SMART; SM00008; HormR; 1.
DR SUPFAM; SSF111418; SSF111418; 1.
DR PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1.
DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disease variant; Disulfide bond; Dwarfism;
KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..593
FT /note="Parathyroid hormone/parathyroid hormone-related
FT peptide receptor"
FT /id="PRO_0000012845"
FT TOPO_DOM 27..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..212
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..239
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..282
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..306
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..342
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 343..361
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..409
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..428
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 429..440
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..463
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..593
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 66..102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 474..477
FT /note="Important for interaction with G proteins"
FT COMPBIAS 79..101
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 551
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 151
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 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 48..117
FT /evidence="ECO:0000269|PubMed:10913300,
FT ECO:0000269|PubMed:18375760, ECO:0000269|PubMed:19674967,
FT ECO:0007744|PDB:3C4M, ECO:0007744|PDB:3H3G,
FT ECO:0007744|PDB:3L2J"
FT DISULFID 108..148
FT /evidence="ECO:0000269|PubMed:10913300,
FT ECO:0000269|PubMed:18375760, ECO:0000269|PubMed:19674967,
FT ECO:0007744|PDB:3C4M, ECO:0007744|PDB:3H3G,
FT ECO:0007744|PDB:3L2J"
FT DISULFID 131..170
FT /evidence="ECO:0000269|PubMed:10913300,
FT ECO:0000269|PubMed:18375760, ECO:0000269|PubMed:19674967,
FT ECO:0007744|PDB:3C4M, ECO:0007744|PDB:3H3G,
FT ECO:0007744|PDB:3L2J"
FT VARIANT 132
FT /note="P -> L (in BOCD; dbSNP:rs121434599)"
FT /evidence="ECO:0000269|PubMed:9745456"
FT /id="VAR_016062"
FT VARIANT 150
FT /note="R -> C (in dbSNP:rs121434601)"
FT /evidence="ECO:0000269|PubMed:11850620"
FT /id="VAR_016063"
FT VARIANT 223
FT /note="H -> R (in MCDJ; constitutively activated;
FT constitutively increases adenylate cyclase-activating G-
FT protein coupled receptor signaling pathway; decreases the
FT degree of N-glycosylation; does not affect
FT homodimerization; dbSNP:rs121434597)"
FT /evidence="ECO:0000269|PubMed:27160269,
FT ECO:0000269|PubMed:7701349, ECO:0000269|PubMed:8703170,
FT ECO:0000269|PubMed:9178745"
FT /id="VAR_003582"
FT VARIANT 410
FT /note="T -> P (in MCDJ; constitutively activated;
FT dbSNP:rs121434598)"
FT /evidence="ECO:0000269|PubMed:8703170,
FT ECO:0000269|PubMed:9178745"
FT /id="VAR_003583"
FT VARIANT 410
FT /note="T -> R (in MCDJ; leads to agonist-independent cAMP
FT formation which is less pronounced than that observed with
FT the Pro-410 mutant; dbSNP:rs121434602)"
FT /evidence="ECO:0000269|PubMed:15240651"
FT /id="VAR_038811"
FT VARIANT 458
FT /note="I -> R (in MCDJ; dbSNP:rs121434600)"
FT /evidence="ECO:0000269|PubMed:10487664"
FT /id="VAR_016064"
FT MUTAGEN 135
FT /note="I->K: Abolishes hormone binding and
FT homodimerization."
FT /evidence="ECO:0000269|PubMed:20172855"
FT MUTAGEN 137
FT /note="D->A: Abolishes hormone binding. No effect on
FT homodimerization."
FT /evidence="ECO:0000269|PubMed:20172855"
FT CONFLICT 471
FT /note="K -> N (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="S -> C (in Ref. 2)"
FT /evidence="ECO:0000305"
FT HELIX 34..55
FT /evidence="ECO:0007829|PDB:3H3G"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:3H3G"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:3H3G"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:3C4M"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:3H3G"
FT TURN 168..173
FT /evidence="ECO:0007829|PDB:3H3G"
FT HELIX 181..200
FT /evidence="ECO:0007829|PDB:6NBF"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 219..245
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:6NBH"
FT HELIX 279..311
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 317..345
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 361..368
FT /evidence="ECO:0007829|PDB:6NBF"
FT TURN 369..371
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 372..390
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 400..411
FT /evidence="ECO:0007829|PDB:6NBF"
FT TURN 412..418
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 420..423
FT /evidence="ECO:0007829|PDB:6NBF"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:6NBF"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 435..459
FT /evidence="ECO:0007829|PDB:6NBF"
FT HELIX 464..480
FT /evidence="ECO:0007829|PDB:6NBF"
FT STRAND 588..592
FT /evidence="ECO:0007829|PDB:5EMB"
SQ SEQUENCE 593 AA; 66361 MW; DA1400640A6C7F2B CRC64;
MGTARIAPGL ALLLCCPVLS SAYALVDADD VMTKEEQIFL LHRAQAQCEK RLKEVLQRPA
SIMESDKGWT SASTSGKPRK DKASGKLYPE SEEDKEAPTG SRYRGRPCLP EWDHILCWPL
GAPGEVVAVP CPDYIYDFNH KGHAYRRCDR NGSWELVPGH NRTWANYSEC VKFLTNETRE
REVFDRLGMI YTVGYSVSLA SLTVAVLILA YFRRLHCTRN YIHMHLFLSF MLRAVSIFVK
DAVLYSGATL DEAERLTEEE LRAIAQAPPP PATAAAGYAG CRVAVTFFLY FLATNYYWIL
VEGLYLHSLI FMAFFSEKKY LWGFTVFGWG LPAVFVAVWV SVRATLANTG CWDLSSGNKK
WIIQVPILAS IVLNFILFIN IVRVLATKLR ETNAGRCDTR QQYRKLLKST LVLMPLFGVH
YIVFMATPYT EVSGTLWQVQ MHYEMLFNSF QGFFVAIIYC FCNGEVQAEI KKSWSRWTLA
LDFKRKARSG SSSYSYGPMV SHTSVTNVGP RVGLGLPLSP RLLPTATTNG HPQLPGHAKP
GTPALETLET TPPAMAAPKD DGFLNGSCSG LDEEASGPER PPALLQEEWE TVM
