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 27-MAR-2024, entry version 228. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7UZO; X-ray; 1.30 A; A=30-174. DR PDB; 7UZP; X-ray; 2.29 A; A/C/E=29-174. DR PDB; 7VVJ; EM; 3.20 A; R=27-501. DR PDB; 7VVK; EM; 3.30 A; R=27-491. DR PDB; 7VVL; EM; 2.80 A; R=27-491. DR PDB; 7VVM; EM; 3.20 A; R=27-491. DR PDB; 7VVN; EM; 3.80 A; R=27-491. DR PDB; 7VVO; EM; 4.10 A; R=27-491. DR PDB; 7Y35; EM; 2.90 A; R=27-593. DR PDB; 7Y36; EM; 2.80 A; R=27-593. DR PDB; 8BIA; X-ray; 2.40 A; C=586-593. DR PDB; 8BJ0; X-ray; 2.60 A; B=586-593. DR PDB; 8D51; X-ray; 2.00 A; A=29-174. DR PDB; 8D52; X-ray; 2.02 A; A=29-174. DR PDB; 8FLQ; EM; 2.55 A; R=28-593. DR PDB; 8FLR; EM; 2.94 A; R=28-593. DR PDB; 8FLS; EM; 3.09 A; R=28-593. DR PDB; 8FLT; EM; 3.03 A; R=28-593. DR PDB; 8FLU; EM; 2.76 A; R=28-593. DR PDB; 8GW8; EM; 2.90 A; R=27-491. DR PDB; 8HA0; EM; 2.62 A; R=27-502. DR PDB; 8HAF; EM; 3.25 A; R=27-502. DR PDB; 8HAO; EM; 3.76 A; I/R=27-502. DR PDB; 8JR9; EM; 2.57 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 PDBsum; 7UZO; -. DR PDBsum; 7UZP; -. DR PDBsum; 7VVJ; -. DR PDBsum; 7VVK; -. DR PDBsum; 7VVL; -. DR PDBsum; 7VVM; -. DR PDBsum; 7VVN; -. DR PDBsum; 7VVO; -. DR PDBsum; 7Y35; -. DR PDBsum; 7Y36; -. DR PDBsum; 8BIA; -. DR PDBsum; 8BJ0; -. DR PDBsum; 8D51; -. DR PDBsum; 8D52; -. DR PDBsum; 8FLQ; -. DR PDBsum; 8FLR; -. DR PDBsum; 8FLS; -. DR PDBsum; 8FLT; -. DR PDBsum; 8FLU; -. DR PDBsum; 8GW8; -. DR PDBsum; 8HA0; -. DR PDBsum; 8HAF; -. DR PDBsum; 8HAO; -. DR PDBsum; 8JR9; -. DR AlphaFoldDB; Q03431; -. DR EMDB; EMD-0410; -. DR EMDB; EMD-0411; -. DR EMDB; EMD-0412; -. DR EMDB; EMD-27872; -. DR EMDB; EMD-32141; -. DR EMDB; EMD-32142; -. DR EMDB; EMD-32143; -. DR EMDB; EMD-32144; -. DR EMDB; EMD-32145; -. DR EMDB; EMD-32146; -. DR EMDB; EMD-34305; -. DR EMDB; EMD-34585; -. DR EMDB; EMD-34587; -. DR EMDB; EMD-34598; -. DR EMDB; EMD-36593; -. DR SMR; Q03431; -. DR BioGRID; 111717; 107. DR CORUM; Q03431; -. DR IntAct; Q03431; 37. DR MINT; Q03431; -. DR STRING; 9606.ENSP00000402723; -. 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 GlyCosmos; Q03431; 4 sites, No reported glycans. 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; 9606-ENSP00000321999; -. DR PeptideAtlas; Q03431; -. DR TopDownProteomics; Q03431; -. DR ABCD; Q03431; 23 sequenced antibodies. DR Antibodypedia; 1960; 456 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 AGR; HGNC:9608; -. 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; CDARQQY; -. DR OrthoDB; 5397182at2759; -. 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 SignaLink; Q03431; -. DR SIGNOR; Q03431; -. DR BioGRID-ORCS; 5745; 20 hits in 1155 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 148 other cell types or tissues. DR ExpressionAtlas; Q03431; baseline and differential. 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:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. 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: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:0006874; P:intracellular calcium ion homeostasis; IBA:GO_Central. 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; GPCR, family 2, extracellular hormone receptor domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR017981; GPCR_2-like_7TM. 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; PARATHYROID HORMONE_PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR; 1. DR PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 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; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF111418; Hormone receptor domain; 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. DR Genevisible; Q03431; HS. 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 FT G-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:7UZO" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:8HAF" FT STRAND 126..130 FT /evidence="ECO:0007829|PDB:7UZO" FT STRAND 136..138 FT /evidence="ECO:0007829|PDB:8FLQ" FT STRAND 143..148 FT /evidence="ECO:0007829|PDB:7UZO" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:3C4M" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:7UZO" FT HELIX 168..171 FT /evidence="ECO:0007829|PDB:7UZO" FT HELIX 178..211 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:8JR9" FT HELIX 218..245 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 274..277 FT /evidence="ECO:0007829|PDB:6NBH" FT HELIX 279..311 FT /evidence="ECO:0007829|PDB:8FLQ" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 317..346 FT /evidence="ECO:0007829|PDB:8FLQ" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:8FLS" FT HELIX 357..360 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 361..391 FT /evidence="ECO:0007829|PDB:8FLQ" FT TURN 393..396 FT /evidence="ECO:0007829|PDB:7VVJ" FT HELIX 400..417 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 419..422 FT /evidence="ECO:0007829|PDB:8FLQ" FT TURN 423..426 FT /evidence="ECO:0007829|PDB:8FLQ" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:8FLQ" FT HELIX 435..459 FT /evidence="ECO:0007829|PDB:8FLQ" FT TURN 460..462 FT /evidence="ECO:0007829|PDB:8JR9" FT HELIX 464..478 FT /evidence="ECO:0007829|PDB:8FLQ" 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 //