PTH1R parathyroid hormone 1 receptor [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PTH1Rprovided by HGNC
Official Full Name: parathyroid hormone 1 receptorprovided by HGNC
Primary source: HGNC:9608
See related: Ensembl:ENSG00000160801; HPRD:01347; MIM:168468; Vega:OTTHUMG00000133515
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PFE; PTHR; PTHR1
Summary: The protein encoded by this gene is a member of the G-protein coupled receptor family 2. This protein is a receptor for parathyroid hormone (PTH) and for parathyroid hormone-like hormone (PTHLH). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchodromatosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

Genomic context

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Location :: 3p22-p21.1

Sequence :: Chromosome: 3; NC_000003.11 (46919236..46945289)

See PTH1R in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

beta-catenin binds to the PTHR-1 C-tail and switches the downstream signaling pathway from G(alphas)/cAMP to G(alphaq)/Ca(2+), which is a mechanism by which chondrocyte hypertrophy may be regulated through the PTH/PTHrP signal independent of canonical Wnt pathway
Title: β-catenin regulates parathyroid hormone/parathyroid hormone-related protein receptor signals and chondrocyte hypertrophy through binding to the intracellular C-terminal region of the receptor.
PTHR forms a ternary complex that includes arrestin and Gbetagamma dimer in response to PTH stimulation, which in turn causes an accelerated rate of G(S) activation and increases the steady-state level of activated G(S), leading to prolonged generation of cAMP.
Title: Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gβγ complex.
[review] The PTH1R carboxy-terminal tail directs interactions with a plethora of binding partners, resulting in the activation of many pathways.
Title: The parathyroid hormone receptorsome and the potential for therapeutic intervention.
Elevated levels of PTH1R expression were associated with breast cancer patients with diabetes.
Title: Type 1 receptor parathyroid hormone (PTH1R) influences breast cancer cell proliferation and apoptosis induced by high levels of glucose.
PTH(1-34) promotes coupled PTHR ubiquitination and deubiquitination, whereas PTH(7-34) activates only ubiquitination, thereby leading to PTHR downregulation.
Title: Ubiquitination-deubiquitination balance dictates ligand-stimulated PTHR sorting.
Constitutive expression of PTHrP receptor type 1 in human bone marrow stromal cells declines with age.
Title: Effects of age on parathyroid hormone signaling in human marrow stromal cells.
PTH-receptors regulate norepinephrine release in human heart and kidney
Title: PTH-receptors regulate norepinephrine release in human heart and kidney.
Dynamic Na+-H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains
Title: Dynamic Na+-H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains.
Ezrin promotes PTH1R mediated signaling via phospholipase and PIP2 depletion impedes receptor cell surface expression in HEK293 cells.
Title: Apical membrane segregation of phosphatidylinositol-4,5-bisphosphate influences parathyroid hormone 1 receptor compartmental signaling and localization via direct regulation of ezrin in LLC-PK1 cells.
A novel variant of parathyroid hormone 1 receptor gene (PTH1R), R383Q, was cosegregated in the first primary failure of tooth eruption family.
Title: Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese.

Submit: New GeneRIF Correction See all (79)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q03431	P49407	ARRB1	HPRD	PubMed
Q03431	P62873	GNB1	HPRD	PubMed
Q03431	P01270	PTH	HPRD	PubMed
Q03431	P12272	PTHLH	HPRD	PubMed
Q03431	O14745	SLC9A3R1	HPRD	PubMed
Q03431	Q15599	SLC9A3R2	HPRD	PubMed
Q03431	Q04917	YWHAH	HPRD	PubMed
BioGRID:111717	BioGRID:109032	GNAI1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111717	BioGRID:111713	PTH	BioGRID	PubMed	Reconstituted Complex
BioGRID:111717	BioGRID:111716	PTHLH	BioGRID	PubMed	Reconstituted Complex
BioGRID:111717	BioGRID:114769	SLC9A3R1	BioGRID	PubMed	Affinity Capture-Western; Far Western
BioGRID:111717	BioGRID:114754	SLC9A3R2	BioGRID	PubMed	Affinity Capture-Western; Far Western
BioGRID:111717	BioGRID:113164	UBC	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
Endochondral Ossification, organism-specific biosystem (from WikiPathways)
Endochondral Ossification, organism-specific biosystem
Endochondral Ossification
Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystem (from KEGG)
Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
Endocrine and other factor-regulated calcium reabsorption, conserved biosystem (from KEGG)
Endocrine and other factor-regulated calcium reabsorption, conserved biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class B Secretin-like, organism-specific biosystem (from WikiPathways)
GPCRs, Class B Secretin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Osteoblast Signaling, organism-specific biosystem (from WikiPathways)
Osteoblast Signaling, organism-specific biosystem
Osteoblast Signaling
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

General gene information

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Markers

RH80066 (e-PCR)
- UniSTS:87823

STS-L04308 (e-PCR)
- UniSTS:43036

PMC152287P1 (e-PCR)
- UniSTS:271213

Genotypes

See PTH1R SNP Geneview Report
See PTH1R SNP Genotype Report
See PTH1R SNP Variation Viewer Report

Homology

Homologs of the PTH1R gene: The PTH1R gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
parathyroid hormone receptor activity	IDA Inferred from Direct Assay more info	PubMed
peptide hormone binding	IDA Inferred from Direct Assay more info	PubMed
protein self-association	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
G-protein coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS Traceable Author Statement more info	PubMed
adenylate cyclase-activating G-protein coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
adenylate cyclase-modulating G-protein coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
aging	IEA Inferred from Electronic Annotation more info
bone mineralization	IEA Inferred from Electronic Annotation more info
bone resorption	IEA Inferred from Electronic Annotation more info
cell maturation	IEA Inferred from Electronic Annotation more info
chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
elevation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
osteoblast development	IEA Inferred from Electronic Annotation more info
phospholipase C-activating G-protein coupled receptor signaling pathway	IC Inferred by Curator more info	PubMed
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of inositol phosphate biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
skeletal system development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
brush border membrane	IEA Inferred from Electronic Annotation more info
cytoplasm	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
receptor complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: parathyroid hormone/parathyroid hormone-related peptide receptor

Names: parathyroid hormone/parathyroid hormone-related peptide receptor; PTH1 receptor; PTH/PTHr receptor; PTH/PTHrP type I receptor; parathyroid hormone receptor 1; seven transmembrane helix receptor; parathyroid hormone/parathyroid hormone-related protein receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008864.1 RefSeqGene

Range

5001..31054

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000316.2 → NP_000307.1 parathyroid hormone/parathyroid hormone-related peptide receptor precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 both encode the same protein.

Source sequence(s)

CA412652, U17418

Consensus CDS

CCDS2747.1

UniProtKB/Swiss-Prot

Q03431

Related

ENSP00000402723, OTTHUMP00000209970, ENST00000449590, OTTHUMT00000344355

Conserved Domains (2) summary

pfam00002
Location:184 – 455
Blast Score: 828

7tm_2; 7 transmembrane receptor (Secretin family)

pfam02793
Location:105 – 173
Blast Score: 229

HRM; Hormone receptor domain
NM_001184744.1 → NP_001171673.1 parathyroid hormone/parathyroid hormone-related peptide receptor precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein.

Source sequence(s)

BC110388, BQ574694, L04308

Consensus CDS

CCDS2747.1

UniProtKB/Swiss-Prot

Q03431

UniProtKB/TrEMBL

Q0VGD7

Related

ENSP00000413774, ENST00000430002

Conserved Domains (2) summary

pfam00002
Location:184 – 455
Blast Score: 828

7tm_2; 7 transmembrane receptor (Secretin family)

pfam02793
Location:105 – 173
Blast Score: 229

HRM; Hormone receptor domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p10 Primary Assembly

Range

46919236..46945289

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

46962340..46988376

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018914.1 Alternate CHM1_1.0

Range

46850011..46876065

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB065462.1	BAC05721.1
genomic	ABBA01024711.1 (2930..27755)	None
genomic	ABBA01024712.1	None
genomic	AC109583.2 (123997..150050)	None
genomic	AF077526.1	AAC27643.1
genomic	AMYH01013135.1 (90319..94803)	None
genomic	AMYH01013136.1	None
genomic	AMYH01013137.1	None
genomic	CH471055.1	EAW64793.1
		EAW64794.1
genomic	U22409.1	AAB60657.1
mRNA	AY449732.1	AAR18076.1
mRNA	BC031578.1	None
mRNA	BC110388.1	AAI10389.1
mRNA	BC112221.1	AAI12222.1
mRNA	BC112247.1	AAI12248.1
mRNA	BQ574694.1	None
mRNA	CA412652.1	None
mRNA	L04308.1	AAA36525.1
mRNA	U17418.1	AAA56774.1
mRNA	X68596.1	CAA48589.1
other-genetic	HQ258471.1	ADR83225.1