Parathyroid hormone/parathyroid hormone-related peptide receptor

UniProt Q03431 Organism Homo sapiens Gene PTH1R, PTHR, PTHR1

Also known as: PTH1R, PTHR, PTHR1

Function

G protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP). PTH1R is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity. PTHLH dissociates from PTH1R more rapidly than PTH; as consequence, the cAMP response induced by PTHLH decays faster than the response induced by PTH.

Classification

Family (Pfam): PF00002 7tm_2, PF02793 HRM
InterPro: GPCR_2, GPCR_2-like_7TM, GPCR_2_extracell_dom_sf, GPCR_2_extracellular_dom, GPCR_2_parathyroid_rcpt, GPCR_2_secretin-like, GPCR_2_secretin-like_CS
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 40

1BL1 NMR
3C4M X-ray 1.95A
3H3G X-ray 1.94A
3L2J X-ray 3.24A
4Z8J X-ray 0.95A
5EMB X-ray 0.85A
6FJ3 X-ray 2.50A
6NBF EM 3.00A
6NBH EM 3.50A
6NBI EM 4.00A
7UZO X-ray 1.30A
7UZP X-ray 2.29A
… and 28 more

A predicted model is available from AlphaFold.

Gene Ontology · 20

Disease associations

primary failure of tooth eruption MONDO:0007434
metaphyseal chondrodysplasia, Jansen type MONDO:0007982
chondrodysplasia Blomstrand type MONDO:0008970
Eiken syndrome MONDO:0010803

Drugs targeting this protein · 1

TERIPARATIDE agonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Parathyroid hormone-related protein 2 shared papers
Parathyroid hormone 2 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 2 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 2 shared papers

Literature · 25 cited papers

Endogenous ligand recognition and structural transition of a human PTH receptor. Mol. Cell · 2022
Structure and dynamics of the active human parathyroid hormone receptor-1. Science · 2019
Characterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia. Odontology · 2017
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
PMID 21827955 Structure · 2011
Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J. Biol. Chem. · 2010
Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J. Biol. Chem. · 2009
PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am. J. Hum. Genet. · 2008
Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure · 2008
Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. · 2008
Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum. Mol. Genet. · 2005
Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C. Hum. Mutat. · 2004
… and 13 more in the literature graph

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