Parathyroid hormone/parathyroid hormone-related peptide receptor

Details

Name
Parathyroid hormone/parathyroid hormone-related peptide receptor
Synonyms
  • Parathyroid hormone 1 receptor
  • PTH/PTHr receptor
  • PTH/PTHrP type I receptor
  • PTH1 receptor
  • PTHR
  • PTHR1
Gene Name
PTH1R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0017123|Parathyroid hormone/parathyroid hormone-related peptide receptor
MGTARIAPGLALLLCCPVLSSAYALVDADDVMTKEEQIFLLHRAQAQCEKRLKEVLQRPA
SIMESDKGWTSASTSGKPRKDKASGKLYPESEEDKEAPTGSRYRGRPCLPEWDHILCWPL
GAPGEVVAVPCPDYIYDFNHKGHAYRRCDRNGSWELVPGHNRTWANYSECVKFLTNETRE
REVFDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVK
DAVLYSGATLDEAERLTEEELRAIAQAPPPPATAAAGYAGCRVAVTFFLYFLATNYYWIL
VEGLYLHSLIFMAFFSEKKYLWGFTVFGWGLPAVFVAVWVSVRATLANTGCWDLSSGNKK
WIIQVPILASIVLNFILFINIVRVLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVH
YIVFMATPYTEVSGTLWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSWSRWTLA
LDFKRKARSGSSSYSYGPMVSHTSVTNVGPRVGLGLPLSPRLLPTATTNGHPQLPGHAKP
GTPALETLETTPPAMAAPKDDGFLNGSCSGLDEEASGPERPPALLQEEWETVM
Number of residues
593
Molecular Weight
66359.98
Theoretical pI
8.05
GO Classification
Functions
parathyroid hormone receptor activity / peptide hormone binding / protein self-association
Processes
adenylate cyclase-activating G-protein coupled receptor signaling pathway / adenylate cyclase-modulating G-protein coupled receptor signaling pathway / aging / bone mineralization / bone resorption / cell maturation / cell surface receptor signaling pathway / chondrocyte differentiation / G-protein coupled receptor signaling pathway / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / negative regulation of cell proliferation / osteoblast development / phospholipase C-activating G-protein coupled receptor signaling pathway / positive regulation of cell proliferation / positive regulation of cytosolic calcium ion concentration / positive regulation of inositol phosphate biosynthetic process / skeletal system development
Components
apical plasma membrane / basolateral plasma membrane / brush border membrane / cytoplasm / cytosol / extracellular exosome / integral component of plasma membrane / nucleus / plasma membrane / receptor complex
General Function
Protein self-association
Specific Function
This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.
Pfam Domain Function
Transmembrane Regions
189-212 220-239 283-306 321-342 362-382 410-428 441-463
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0017124|Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)
ATGGGGACCGCCCGGATCGCACCCGGCCTGGCGCTCCTGCTCTGCTGCCCCGTGCTCAGC
TCCGCGTACGCGCTGGTGGATGCAGATGACGTCATGACTAAAGAGGAACAGATCTTCCTG
CTGCACCGTGCTCAGGCCCAGTGCGAAAAACGGCTCAAGGAGGTCCTGCAGAGGCCAGCC
AGCATAATGGAATCAGACAAGGGATGGACATCTGCGTCCACATCAGGGAAGCCCAGGAAA
GATAAGGCATCTGGGAAGCTCTACCCTGAGTCTGAGGAGGACAAGGAGGCACCCACTGGC
AGCAGGTACCGAGGGCGCCCCTGTCTGCCGGAATGGGACCACATCCTGTGCTGGCCGCTG
GGGGCACCAGGTGAGGTGGTGGCTGTGCCCTGTCCGGACTACATTTATGACTTCAATCAC
AAAGGCCATGCCTACCGACGCTGTGACCGCAATGGCAGCTGGGAGCTGGTGCCTGGGCAC
AACAGGACGTGGGCCAACTACAGCGAGTGTGTCAAATTTCTCACCAATGAGACTCGTGAA
CGGGAGGTGTTTGACCGCCTGGGCATGATTTACACCGTGGGCTACTCCGTGTCCCTGGCG
TCCCTCACCGTAGCTGTGCTCATCCTGGCCTACTTTAGGCGGCTGCACTGCACGCGCAAC
TACATCCACATGCACCTGTTCCTGTCCTTCATGCTGCGCGCCGTGAGCATCTTCGTCAAG
GACGCTGTGCTCTACTCTGGCGCCACGCTTGATGAGGCTGAGCGCCTCACCGAGGAGGAG
CTGCGCGCCATCGCCCAGGCGCCCCCGCCGCCTGCCACCGCCGCTGCCGGCTACGCGGGC
TGCAGGGTGGCTGTGACCTTCTTCCTTTACTTCCTGGCCACCAACTACTACTGGATTCTG
GTGGAGGGGCTGTACCTGCACAGCCTCATCTTCATGGCCTTCTTCTCAGAGAAGAAGTAC
CTGTGGGGCTTCACAGTCTTCGGCTGGGGTCTGCCCGCTGTCTTCGTGGCTGTGTGGGTC
AGTGTCAGAGCTACCCTGGCCAACACCGGGTGCTGGGACTTGAGCTCCGGGAACAAAAAG
TGGATCATCCAGGTGCCCATCCTGGCCTCCATTGTGCTCAACTTCATCCTCTTCATCAAT
ATCGTCCGGGTGCTCGCCACCAAGCTGCGGGAGACCAACGCCGGCCGGTGTGACACACGG
CAGCAGTACCGGAAGCTGCTCAAATCCACGCTGGTGCTCATGCCCCTCTTTGGCGTCCAC
TACATTGTCTTCATGGCCACACCATACACCGAGGTCTCAGGGACGCTCTGGCAAGTCCAG
ATGCACTATGAGATGCTCTTCAACTCCTTCCAGGGATTTTTTGTCGCAATCATATACTGT
TTCTGCAATGGCGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTGGACACTGGCA
CTGGACTTCAAGCGAAAGGCACGCAGCGGGAGCAGCAGCTATAGCTACGGCCCCATGGTG
TCCCACACAAGTGTGACCAATGTCGGCCCCCGTGTGGGACTCGGCCTGCCCCTCAGCCCC
CGCCTACTGCCCACTGCCACCACCAACGGCCACCCTCAGCTGCCTGGCCATGCCAAGCCA
GGGACCCCAGCCCTGGAGACCCTCGAGACCACACCACCTGCCATGGCTGCTCCCAAGGAC
GATGGGTTCCTCAACGGCTCCTGCTCAGGCCTGGACGAGGAGGCCTCTGGGCCTGAGCGG
CCACCTGCCCTGCTACAGGAAGAGTGGGAGACAGTCATGTGA
Chromosome Location
3
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ03431
UniProtKB Entry NamePTH1R_HUMAN
GenBank Gene IDBC112247
GenAtlas IDPTHR1
HGNC IDHGNC:9608
General References
  1. Schipani E, Karga H, Karaplis AC, Potts JT Jr, Kronenberg HM, Segre GV, Abou-Samra AB, Juppner H: Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor. Endocrinology. 1993 May;132(5):2157-65. [Article]
  2. Schneider H, Feyen JH, Seuwen K, Movva NR: Cloning and functional expression of a human parathyroid hormone receptor. Eur J Pharmacol. 1993 Jul 15;246(2):149-55. [Article]
  3. Schipani E, Weinstein LS, Bergwitz C, Iida-Klein A, Kong XF, Stuhrmann M, Kruse K, Whyte MP, Murray T, Schmidtke J, et al.: Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene. J Clin Endocrinol Metab. 1995 May;80(5):1611-21. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Grauschopf U, Lilie H, Honold K, Wozny M, Reusch D, Esswein A, Schafer W, Rucknagel KP, Rudolph R: The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a hormone binding domain and reveals a distinct disulfide pattern. Biochemistry. 2000 Aug 1;39(30):8878-87. [Article]
  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  7. Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF: Binding domain of human parathyroid hormone receptor: from conformation to function. Biochemistry. 1998 Sep 15;37(37):12737-43. [Article]
  8. Pioszak AA, Xu HE: Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5034-9. doi: 10.1073/pnas.0801027105. Epub 2008 Mar 28. [Article]
  9. Johnston CA, Kimple AJ, Giguere PM, Siderovski DP: Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. doi: 10.1016/j.str.2008.04.010. [Article]
  10. Pioszak AA, Parker NR, Gardella TJ, Xu HE: Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009 Oct 9;284(41):28382-91. doi: 10.1074/jbc.M109.022905. Epub 2009 Aug 12. [Article]
  11. Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE: Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J Biol Chem. 2010 Apr 16;285(16):12435-44. doi: 10.1074/jbc.M109.093138. Epub 2010 Feb 19. [Article]
  12. Schipani E, Kruse K, Juppner H: A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science. 1995 Apr 7;268(5207):98-100. [Article]
  13. Schipani E, Langman CB, Parfitt AM, Jensen GS, Kikuchi S, Kooh SW, Cole WG, Juppner H: Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia. N Engl J Med. 1996 Sep 5;335(10):708-14. [Article]
  14. Schipani E, Jensen GS, Pincus J, Nissenson RA, Gardella TJ, Juppner H: Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia. Mol Endocrinol. 1997 Jun;11(7):851-8. [Article]
  15. Zhang P, Jobert AS, Couvineau A, Silve C: A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. J Clin Endocrinol Metab. 1998 Sep;83(9):3365-8. [Article]
  16. Schipani E, Langman C, Hunzelman J, Le Merrer M, Loke KY, Dillon MJ, Silve C, Juppner H: A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia. J Clin Endocrinol Metab. 1999 Sep;84(9):3052-7. [Article]
  17. Hopyan S, Gokgoz N, Poon R, Gensure RC, Yu C, Cole WG, Bell RS, Juppner H, Andrulis IL, Wunder JS, Alman BA: A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Genet. 2002 Mar;30(3):306-10. Epub 2002 Feb 19. [Article]
  18. Rozeman LB, Sangiorgi L, Briaire-de Bruijn IH, Mainil-Varlet P, Bertoni F, Cleton-Jansen AM, Hogendoorn PC, Bovee JV: Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C. Hum Mutat. 2004 Dec;24(6):466-73. [Article]
  19. Bastepe M, Raas-Rothschild A, Silver J, Weissman I, Wientroub S, Juppner H, Gillis D: A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and skeletal abnormalities is caused by a novel activating parathyroid hormone (PTH)/PTH-related peptide receptor mutation. J Clin Endocrinol Metab. 2004 Jul;89(7):3595-600. [Article]
  20. Duchatelet S, Ostergaard E, Cortes D, Lemainque A, Julier C: Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum Mol Genet. 2005 Jan 1;14(1):1-5. Epub 2004 Nov 3. [Article]
  21. Decker E, Stellzig-Eisenhauer A, Fiebig BS, Rau C, Kress W, Saar K, Ruschendorf F, Hubner N, Grimm T, Weber BH: PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet. 2008 Dec;83(6):781-6. doi: 10.1016/j.ajhg.2008.11.006. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06285Teriparatideapproved, investigationalunknownbinderDetails
DB05829Parathyroid hormoneapproved, investigationalunknownactivatorDetails
DB05084Abaloparatideapproved, investigationalyesligandDetails