Reviewed, UniProtKB/Swiss-Prot Q03431 (PTH1R_HUMAN)

Names and origin

Protein names

Recommended name:
    Parathyroid hormone/parathyroid hormone-related peptide receptor
Alternative name(s):
    Parathyroid hormone 1 receptor
      Short name=PTH1 receptor
    PTH/PTHrP type I receptor
      Short name=PTH/PTHr receptor

Gene names

Name:	PTH1R
Synonyms:	PTHR, PTHR1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	593 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

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.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in most tissues. Most abundant in kidney, bone and liver.
Involvement in disease	Defects in PTH1R are the cause of Jansen metaphyseal chondrodysplasia (JMC) [MIM:156400]. JMC is a rare autosomal dominant disorder characterized by a short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two parathyroid hormones. Ref.9 Ref.10 Ref.11 Ref.13 Ref.16 Defects in PTH1R are the cause of chondrodysplasia Blomstrand type (BOCD) [MIM:215045]. BOCD is a severe skeletal dysplasia. Ref.12 Defects in PTH1R may be a cause of enchondromatosis [MIM:166000]. Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to osteosarcoma. Defects in PTH1R are the cause of Eiken syndrome [MIM:600002]; also called Eiken skeletal dysplasia or bone modeling defect of hands and feet. Eiken syndrome is a rare familial autosomal recessive skeletal dysplasia. It is characterized by multiple epiphyseal dysplasia, with extremely retarded ossification, principally of the epiphyses, pelvis, hands and feet, as well as by abnormal modeling of the bones in hands and feet, abnormal persistence of cartilage in the pelvis and mild growth retardation. Ref.17 Defects in PTH1R are a cause of primary failure of tooth eruption (PFE) [MIM:125350]. PFE is a rare condition that has high penetrance and variable expressivity and in which tooth retention occurs without evidence of any obvious mechanical interference. Instead, malfunction of the eruptive mechanism itself appears to cause nonankylosed permanent teeth to fail to erupt, although the eruption pathway has been cleared by bone resorption.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Disease	Disease mutation Dwarfism
Domain	Signal Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Cellular component	cytoplasm Traceable author statement. Source: ProtInc integral to plasma membrane Ref.12 Traceable author statement. Source: ProtInc nucleus Traceable author statement. Source: ProtInc
Molecular function	parathyroid hormone receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Chain

27 – 593

567

Parathyroid hormone/parathyroid hormone-related peptide receptor

PRO_0000012845

Regions

Topological domain

27 – 188

162

Extracellular Potential

Transmembrane

189 – 212

24

1 Potential

Topological domain

213 – 219

7

Cytoplasmic Potential

Transmembrane

220 – 239

20

2 Potential

Topological domain

240 – 282

43

Extracellular Potential

Transmembrane

283 – 306

24

3 Potential

Topological domain

307 – 320

14

Cytoplasmic Potential

Transmembrane

321 – 342

22

4 Potential

Topological domain

343 – 361

19

Extracellular Potential

Transmembrane

362 – 382

21

5 Potential

Topological domain

383 – 409

27

Cytoplasmic Potential

Transmembrane

410 – 428

19

6 Potential

Topological domain

429 – 440

12

Extracellular Potential

Transmembrane

441 – 463

23

7 Potential

Topological domain

464 – 593

130

Cytoplasmic Potential

Amino acid modifications

Glycosylation

151

1

N-linked (GlcNAc...) Potential

Glycosylation

161

1

N-linked (GlcNAc...) Potential

Glycosylation

166

1

N-linked (GlcNAc...) Potential

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Disulfide bond

48 ↔ 117

Ref.7

Disulfide bond

108 ↔ 148

Ref.7

Disulfide bond

131 ↔ 170

Ref.7

Natural variations

Natural variant

132

1

P → L in BOCD. Ref.12

VAR_016062

Natural variant

150

1

R → C in enchondromatosis; Ollier type; may be specific to the Canadian population; unclear pathogenicity. Ref.14

VAR_016063

Natural variant

223

1

H → R in JMC; constitutively activated. Ref.9 Ref.10 Ref.11

VAR_003582

Natural variant

410

1

T → P in JMC; constitutively activated. Ref.10 Ref.11 Ref.16

VAR_003583

Natural variant

410

1

T → R in JMC; leads to agonist-independent cAMP formation which is less pronounced than that observed with the Pro-410 mutant. Ref.10 Ref.11 Ref.16

VAR_038811

Natural variant

458

1

I → R in JMC. Ref.13

VAR_016064

Experimental info

Sequence conflict

471

1

K → N Ref.2

Sequence conflict

473

1

S → C Ref.2

Secondary structure

1

.

.

.

.

.

.

.

593

Helix Strand Turn

Details...

Helix

169 – 176

8

Helix

180 – 185

6

Helix

188 – 196

9

Sequences

	Sequence		Length	Mass (Da)
	Q03431-1 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: DA1400640A6C7F2B	FASTA	593	66,361
	10 20 30 40 50 60 MGTARIAPGL ALLLCCPVLS SAYALVDADD VMTKEEQIFL LHRAQAQCEK RLKEVLQRPA 70 80 90 100 110 120 SIMESDKGWT SASTSGKPRK DKASGKLYPE SEEDKEAPTG SRYRGRPCLP EWDHILCWPL 130 140 150 160 170 180 GAPGEVVAVP CPDYIYDFNH KGHAYRRCDR NGSWELVPGH NRTWANYSEC VKFLTNETRE 190 200 210 220 230 240 REVFDRLGMI YTVGYSVSLA SLTVAVLILA YFRRLHCTRN YIHMHLFLSF MLRAVSIFVK 250 260 270 280 290 300 DAVLYSGATL DEAERLTEEE LRAIAQAPPP PATAAAGYAG CRVAVTFFLY FLATNYYWIL 310 320 330 340 350 360 VEGLYLHSLI FMAFFSEKKY LWGFTVFGWG LPAVFVAVWV SVRATLANTG CWDLSSGNKK 370 380 390 400 410 420 WIIQVPILAS IVLNFILFIN IVRVLATKLR ETNAGRCDTR QQYRKLLKST LVLMPLFGVH 430 440 450 460 470 480 YIVFMATPYT EVSGTLWQVQ MHYEMLFNSF QGFFVAIIYC FCNGEVQAEI KKSWSRWTLA 490 500 510 520 530 540 LDFKRKARSG SSSYSYGPMV SHTSVTNVGP RVGLGLPLSP RLLPTATTNG HPQLPGHAKP 550 560 570 580 590 GTPALETLET TPPAMAAPKD DGFLNGSCSG LDEEASGPER PPALLQEEWE TVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor." Schipani E., Karga H., Karaplis A.C., Potts J.T. Jr., Kronenberg H.M., Abou-Samra A.-B., Segre G.V., Jueppner H. Endocrinology 132:2157-2165(1993) [PubMed: 8386612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Cloning and functional expression of a human parathyroid hormone receptor." Schneider H., Feyen J.-H., Rao Movva N. Eur. J. Pharmacol. 246:149-155(1993) [PubMed: 8397094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[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., Weinstein L.S., Bergwitz C., Iida-Klein A., Kong X.F., Stuhrmann M., Kruse K., Whyte M.P., Murray T., Schmidtke J., Dop C., Brickman A.S., Crawford J.D., Potts J.T. Jr., Kronenberg H.M., Abou-Samra A.-B., Segre G.V., Jueppner H. J. Clin. Endocrinol. Metab. 80:1611-1621(1995) [PubMed: 7745008] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of cDNA and genomic DNA encoding the human PTH/PTHrP receptor." Levine M.A. Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[5]	"Isolation of cDNA coding for parathyroid hormone receptor 1 (PTHR1)." King M.M., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[7]	"The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a hormone binding domain and reveals a distinct disulfide pattern." Grauschopf U., Lilie H., Honold K., Wozny M., Reusch D., Esswein A., Schafer W., Rucknagel K.P., Rudolph R. Biochemistry 39:8878-8887(2000) [PubMed: 10913300] [Abstract] Cited for: DISULFIDE BONDS IN EXTRACELLULAR DOMAIN.
[8]	"Binding domain of human parathyroid hormone receptor: from conformation to function." Pellegrini M., Bisello A., Rosenblatt M., Chorev M., Mierke D.F. Biochemistry 37:12737-12743(1998) [PubMed: 9737850] [Abstract] Cited for: STRUCTURE BY NMR OF 168-198.
[9]	"A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia." Schipani E., Kruse K., Jueppner H. Science 268:98-100(1995) [PubMed: 7701349] [Abstract] Cited for: VARIANT JMC ARG-223.
[10]	"Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia." Schipani E., Langman C.B., Parfitt A.M., Jensen G.S., Kikuchi S., Kooh S.W., Cole W.G., Jueppner H. N. Engl. J. Med. 335:708-714(1996) [PubMed: 8703170] [Abstract] Cited for: VARIANTS JMC ARG-223 AND PRO-410.
[11]	"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., Jensen G.S., Pincus J., Nissenson R.A., Gardella T.J., Jueppner H. Mol. Endocrinol. 11:851-858(1997) [PubMed: 9178745] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS JMC ARG-223 AND PRO-410.
[12]	"A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia." Zhang P., Jobert A.-S., Couvineau A., Silve C. J. Clin. Endocrinol. Metab. 83:3365-3368(1998) [PubMed: 9745456] [Abstract] Cited for: VARIANT BOCD LEU-132.
[13]	"A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia." Schipani E., Langman C.B., Hunzelman J., Le Merrer M., Loke K.Y., Dillon M.J., Silve C., Jueppner H. J. Clin. Endocrinol. Metab. 84:3052-3057(1999) [PubMed: 10487664] [Abstract] Cited for: VARIANT JMC ARG-458.
[14]	"A mutant PTH/PTHrP type I receptor in enchondromatosis." Hopyan S., Gokgoz N., Poon R., Gensure R.C., Yu C., Cole W.G., Bell R.S., Jueppner H., Andrulis I.L., Wunder J.S., Alman B.A. Nat. Genet. 30:306-310(2002) [PubMed: 11850620] [Abstract] Cited for: VARIANT ENCHONDROMATOSIS CYS-150.
[15]	"Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C." Rozeman L.B., Sangiorgi L., Briaire-de Bruijn I.H., Mainil-Varlet P., Bertoni F., Cleton-Jansen A.-M., Hogendoorn P.C.W., Bovee J.V.M.G. Hum. Mutat. 24:466-473(2004) [PubMed: 15523647] [Abstract] Cited for: DISCUSSION OF THE ASSOCIATION OF CYS-150 WITH ENCHODROMATOSIS.
[16]	"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., Raas-Rothschild A., Silver J., Weissman I., Wientroub S., Jueppner H., Gillis D. J. Clin. Endocrinol. Metab. 89:3595-3600(2004) [PubMed: 15240651] [Abstract] Cited for: VARIANT JMC ARG-410, CHARACTERIZATION OF VARIANT JMC ARG-410.
[17]	"Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes." Duchatelet S., Ostergaard E., Cortes D., Lemainque A., Julier C. Hum. Mol. Genet. 14:1-5(2005) [PubMed: 15525660] [Abstract] Cited for: INVOLVEMENT IN EIKEN SYNDROME.
[18]	"PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption." Decker E., Stellzig-Eisenhauer A., Fiebig B.S., Rau C., Kress W., Saar K., Rueschendorf F., Hubner N., Grimm T., Weber B.H.F. Am. J. Hum. Genet. 83:781-786(2008) [PubMed: 19061984] [Abstract] Cited for: INVOLVEMENT IN PRIMARY FAILURE OF TOOTH ERUPTION.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

L04308 mRNA. Translation: AAA36525.1.
X68596 mRNA. Translation: CAA48589.1.
U22409 , U22401, U22402, U22403, U22404, U22405, U22406, U22407, U22408 Genomic DNA. Translation: AAB60657.1.
U17418 mRNA. Translation: AAA56774.1.
AY449732 mRNA. Translation: AAR18076.1.
BC112221 mRNA. Translation: AAI12222.1.
BC112247 mRNA. Translation: AAI12248.1.

IPI

IPI00010732.

PIR

A49191. I38139.

RefSeq

NP_000307.1.

UniGene

Hs.1019

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BL1	NMR	-	A	168-197	[»]
1ET2	model	-	S	168-469	[»]
1ET3	model	-	S	168-469	[»]
3C4M	X-ray	1.95	A/B	29-187	[»]

ModBase

Search...

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q03431.

2-D gel databases

REPRODUCTION-2DPAGE

Q03431.

Proteomic databases

PRIDE

Q03431.

Genome annotation databases

Ensembl

ENSG00000160801. Homo sapiens. [Contig view]

GeneID

5745.

KEGG

hsa:5745.

UCSC

uc003cqm.1. human.

Organism-specific databases

GeneCards

GC03P046895.

H-InvDB

HIX0003255.

HGNC

HGNC:9608. PTH1R.

HPA

CAB016053.
HPA007978.

MIM

125350. phenotype.
156400. phenotype.
166000. phenotype.
168468. gene.
215045. phenotype.
600002. phenotype.

Orphanet

1077. Ankylosis of teeth.
50945. Chondrodysplasia, Blomstrand type.
79106. Eiken syndrome.
296. Enchondromatosis.
33067. Metaphyseal chondrodysplasia, Jansen type.

PharmGKB

PA33953.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q03431.

OMA

Q03431. TRQQYRK.

Gene expression databases

ArrayExpress

Q03431.

Bgee

Q03431.

CleanEx

HS_PTH1R.

GermOnline

ENSG00000160801. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular.
IPR002170. GPCR_2_parathyroid_rcpt.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

PANTHER

PTHR12011:SF24. Parath_hrmn_rcpt. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR00249. GPCRSECRETIN.
PR00393. PTRHORMONER.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

22372.

PMAP-CutDB

Q03431.

SOURCE

Search...

Entry information

Entry name

PTH1R_HUMAN

Accession

Primary (citable) accession number: Q03431
Secondary accession number(s): Q2M1U3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	July 7, 2009
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)