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9.A.14.4.11
Parathyroid hormone/parathyroid hormone-related peptide-1 receptor, PTH1R, of 573 aas and 8 or 9 TMSs in a 1 + 7 or 8 TMS arrangement. PTH1R is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Zhao et al. 2019 reported the cryo-EM structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopted an extended helix with its amino terminus inserted deeply into the receptor TMS, which led to partial unwinding of the carboxyl terminus of TMS6 and induceed a sharp kink at the middle of this helix to allow the receptor to couple with the G protein, while the extracellular domain adopted multiple conformations (Zhao et al. 2019).

Accession Number:Q03431
Protein Name:Parathyroid hormone/parathyroid hormone-related peptide receptor
Length:593
Molecular Weight:66361.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:9
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

Entrez Gene ID: 5745   
Pfam: PF00002    PF02793   
KEGG: hsa:5745   

Gene Ontology

GO:0005737 C:cytoplasm
GO:0005887 C:integral to plasma membrane
GO:0005634 C:nucleus
GO:0004991 F:parathyroid hormone receptor activity
GO:0017046 F:peptide hormone binding
GO:0043621 F:protein self-association

References (20)

[1] “Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor.”  Schipani E.et.al.   8386612
[2] “Cloning and functional expression of a human parathyroid hormone receptor.”  Schneider H.et.al.   8397094
[3] “Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene.”  Schipani E.et.al.   7745008
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a hormone binding domain and reveals a distinct disulfide pattern.”  Grauschopf U.et.al.   10913300
[6] “Binding domain of human parathyroid hormone receptor: from conformation to function.”  Pellegrini M.et.al.   9737850
[7] “Molecular recognition of parathyroid hormone by its G protein-coupled receptor.”  Pioszak A.A.et.al.   18375760
[8] “Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2.”  Johnston C.A.et.al.   18611381
[9] “Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides.”  Pioszak A.A.et.al.   19674967
[10] “Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation.”  Pioszak A.A.et.al.   20172855
[11] “A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia.”  Schipani E.et.al.   7701349
[12] “Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia.”  Schipani E.et.al.   8703170
[13] “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.”  Schipani E.et.al.   9178745
[14] “A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia.”  Zhang P.et.al.   9745456
[15] “A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia.”  Schipani E.et.al.   10487664
[16] “A mutant PTH/PTHrP type I receptor in enchondromatosis.”  Hopyan S.et.al.   11850620
[17] “Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.”  Rozeman L.B.et.al.   15523647
[18] “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.”  Bastepe M.et.al.   15240651
[19] “Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes.”  Duchatelet S.et.al.   15525660
[20] “PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption.”  Decker E.et.al.   19061984
Structure:
1BL1   3C4M   3H3G   3L2J   4Z8J   5EMB   6FJ3   6NBF   6NBH   6NBI   [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGTARIAPGL ALLLCCPVLS SAYALVDADD VMTKEEQIFL LHRAQAQCEK RLKEVLQRPA 
61:	SIMESDKGWT SASTSGKPRK DKASGKLYPE SEEDKEAPTG SRYRGRPCLP EWDHILCWPL 
121:	GAPGEVVAVP CPDYIYDFNH KGHAYRRCDR NGSWELVPGH NRTWANYSEC VKFLTNETRE 
181:	REVFDRLGMI YTVGYSVSLA SLTVAVLILA YFRRLHCTRN YIHMHLFLSF MLRAVSIFVK 
241:	DAVLYSGATL DEAERLTEEE LRAIAQAPPP PATAAAGYAG CRVAVTFFLY FLATNYYWIL 
301:	VEGLYLHSLI FMAFFSEKKY LWGFTVFGWG LPAVFVAVWV SVRATLANTG CWDLSSGNKK 
361:	WIIQVPILAS IVLNFILFIN IVRVLATKLR ETNAGRCDTR QQYRKLLKST LVLMPLFGVH 
421:	YIVFMATPYT EVSGTLWQVQ MHYEMLFNSF QGFFVAIIYC FCNGEVQAEI KKSWSRWTLA 
481:	LDFKRKARSG SSSYSYGPMV SHTSVTNVGP RVGLGLPLSP RLLPTATTNG HPQLPGHAKP 
541:	GTPALETLET TPPAMAAPKD DGFLNGSCSG LDEEASGPER PPALLQEEWE TVM