P01270 (PTHY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Parathyroid hormone
Short name=PTH

Alternative name(s):
Parathormone
Parathyrin

Gene names

Name:

PTH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	115 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	PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells. Ref.13
Subunit structure	Interacts with PTH1R (via N-terminal extracellular domain). Ref.19
Subcellular location	Secreted.
Involvement in disease	Familial isolated hypoparathyroidism (FIH) [MIM:146200]: Characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. An autosomal recessive form of FIH also exists. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.21 Ref.22
Sequence similarities	Belongs to the parathyroid hormone family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation
Domain	Signal
Molecular function	Hormone
PTM	Cleavage on pair of basic residues
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement PubMed 7797535. Source: ProtInc Rho protein signal transduction Inferred from electronic annotation. Source: Compara adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara bone resorption Non-traceable author statement PubMed 15080150. Source: UniProtKB cAMP metabolic process Traceable author statement PubMed 9927325. Source: ProtInc cell-cell signaling Traceable author statement PubMed 7721880. Source: ProtInc cellular calcium ion homeostasis Non-traceable author statement. Source: UniProtKB hormone-mediated apoptotic signaling pathway Traceable author statement PubMed 10913913. Source: ProtInc negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17696759. Source: UniProtKB positive regulation of bone mineralization Inferred from direct assay PubMed 17696759. Source: UniProtKB positive regulation of cAMP biosynthetic process Inferred from direct assay PubMed 90087. Source: MGI positive regulation of glucose import Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of glycogen biosynthetic process Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of signal transduction Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19723499. Source: MGI skeletal system development Traceable author statement PubMed 10913913. Source: ProtInc
Cellular_component	extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 17696759. Source: UniProtKB hormone activity Traceable author statement PubMed 10499494. Source: ProtInc peptide hormone receptor binding Inferred from direct assay PubMed 19674967. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.5 Ref.6

Propeptide

26 – 31

6

PRO_0000023249

Chain

32 – 115

84

Parathyroid hormone

PRO_0000023250

Regions

Region

51 – 69

19

Important for receptor binding

Natural variations

Natural variant

18

1

C → R in FIH; dominant; leads to inefficient processing of the precursor; the expressed mutant hormone is trapped intracellularly in the endoplasmic reticulum resulting in apoptosis; mutant protein-expressing cells also show marked up-regulation of the endoplasmic reticulum stress-responsive hormones HSPA5 and EIF2AK3 and the proapoptotic transcription factor DDIT3. Ref.4 Ref.20 Ref.22

VAR_006047

Natural variant

23

1

S → P in FIH; recessive, might lead to inefficient processing of the precursor. Ref.21

VAR_018464

Experimental info

Mutagenesis

16

1

A → R: Abolishes processing of the precursor; when associated with variant R-18. Ref.4

Mutagenesis

51

1

R → A: Reduced affinity for PTH1R. Ref.19

Mutagenesis

54

1

W → A: Strongly reduced affinity for PTH1R. Ref.19

Mutagenesis

55

1

L → A: Strongly reduced affinity for PTH1R. Ref.19

Mutagenesis

58

1

K → A: Reduced affinity for PTH1R. Ref.19

Mutagenesis

59

1

L → A: Strongly reduced affinity for PTH1R. Ref.19

Sequence conflict

107

1

N → D AA sequence Ref.8

Secondary structure

1

.

.

.

.

115

Helix Strand Turn

Details...

Helix

34 – 64

31

Helix

65 – 67

3

Sequences

	Sequence		Length	Mass (Da)
	P01270 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 849015736A6E5597	FASTA	115	12,861
	10 20 30 40 50 60 MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME RVEWLRKKLQ 70 80 90 100 110 DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE ADKADVNVLT KAKSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone." Hendy G.N., Kronenberg H.M., Potts J.T. Jr., Rich A. Proc. Natl. Acad. Sci. U.S.A. 78:7365-7369(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence of the human parathyroid hormone gene." Vasicek T.J., McCevitt B.E., Freeman M.W., Fennick B.J., Hendy G.N., Potts J.T. Jr., Rich A., Kronenberg H.M. Proc. Natl. Acad. Sci. U.S.A. 80:2127-2131(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Inefficient membrane targeting, translocation, and proteolytic processing by signal peptidase of a mutant preproparathyroid hormone protein." Karaplis A.C., Lim S.-K., Baba H., Arnold A., Kronenberg H.M. J. Biol. Chem. 270:1629-1635(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-31, MUTAGENESIS OF ALA-16, VARIANT ARG-18.
[5]	"Structural analysis of human proparathyroid hormone by a new microsequencing approach." Jacobs J.W., Kemper B., Niall H.D., Habener J.F., Potts J.T. Jr. Nature 249:155-157(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-37.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40.
[7]	"The amino-acid sequence of the amino-terminal 37 residues of human parathyroid hormone." Niall H.D., Sauer R.T., Jacobs J.W., Keutmann H.T., Segre G.V., O'Riordan J.L.H., Aurbach G.D., Potts J.T. Jr. Proc. Natl. Acad. Sci. U.S.A. 71:384-388(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-68.
[8]	"Complete amino acid sequence of human parathyroid hormone." Keutmann H.T., Sauer M.M., Hendy G.N., O'Riordan J.L.H., Potts J.T. Jr. Biochemistry 17:5723-5729(1978) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 61-83 AND 84-115.
[9]	Keutmann H.T., Niall H.D., Jacobs J.W., Barling P.M., Hendy G.N., O'Riordan J.L.H., Potts J.T. Jr. (In) Talmadge R.V., Owen M., Parsons J.A. (eds.); Calcium-regulating hormones, pp.9-14, Excerpta Medica Foundation, Amsterdam (1975) Cited for: PROTEIN SEQUENCE OF 75-100.
[10]	"A reinvestigation of the amino-terminal sequence of human parathyroid hormone." Keutmann H.T., Niall H.D., O'Riordan J.L.H., Potts J.T. Jr. Biochemistry 14:1842-1847(1975) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[11]	"Solid-phase synthesis of the biologically active N-terminal 1-34 peptide of human parathyroid hormone." Tregear G.W., van Rietschoten J., Green E., Niall H.D., Keutmann H.T., Parsons J.A., O'Riordan J.L.H., Potts J.T. Jr. Hoppe-Seyler's Z. Physiol. Chem. 355:415-421(1974) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 32-65.
[12]	"Synthesis of sequence 1-34 of human parathyroid hormone." Andreatta R.H., Hartmann A., Joehl A., Kamber B., Maier R., Riniker B., Rittel W., Sieber P. Helv. Chim. Acta 56:470-473(1973) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 32-65.
[13]	"Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I." Zoidis E., Ghirlanda-Keller C., Schmid C. Mol. Cell. Biochem. 348:33-42(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Investigation of the solution structure of the human parathyroid hormone fragment (1-34) by 1H NMR spectroscopy, distance geometry, and molecular dynamics calculations." Klaus W., Dieckmann T., Wray V., Schomburg D., Wingender E., Mayer H. Biochemistry 30:6936-6942(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 32-65.
[15]	"Stabilized NMR structure of human parathyroid hormone(1-34)." Barden J.A., Cuthbertson R.M. Eur. J. Biochem. 215:315-321(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 32-65.
[16]	"Structure of human parathyroid hormone 1-37 in solution." Marx U.C., Austermann S., Bayer P., Adermann K., Ejchart A., Sticht H., Walter S., Schmid F.-X., Jaenicke R., Forssmann W.-G., Roesch P. J. Biol. Chem. 270:15194-15202(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 32-68.
[17]	"Solution structures of human parathyroid hormone fragments hPTH(1-34) and hPTH(1-39) and bovine parathyroid hormone fragment bPTH(1-37)." Marx U.C., Adermann K., Bayer P., Forssmann W.-G., Rosch P. Biochem. Biophys. Res. Commun. 267:213-220(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 32-70.
[18]	"Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution." Jin L., Briggs S.L., Chandrasekhar S., Chirgadze N.Y., Clawson D.K., Schevitz R.W., Smiley D.L., Tashjian A.H., Zhang F. J. Biol. Chem. 275:27238-27244(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (0.9 ANGSTROMS) OF 32-65.
[19]	"Molecular recognition of parathyroid hormone by its G protein-coupled receptor." Pioszak A.A., Xu H.E. Proc. Natl. Acad. Sci. U.S.A. 105:5034-5039(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 46-65 IN COMPLEX WITH PTH1R, INTERACTION WITH PTH1R, MUTAGENESIS OF ARG-51; TRP-54; LEU-55; LYS-58 AND LEU-59.
[20]	"Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism." Arnold A., Horst S.A., Gardella T.J., Baba H., Levine M.A., Kronenberg H.M. J. Clin. Invest. 86:1084-1087(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FIH ARG-18.
[21]	"A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism." Sunthornthepvarakul T., Churesigaew S., Ngowngarmratana S. J. Clin. Endocrinol. Metab. 84:3792-3796(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FIH PRO-23.
[22]	"Signal sequence mutation in autosomal dominant form of hypoparathyroidism induces apoptosis that is corrected by a chemical chaperone." Datta R., Waheed A., Shah G.N., Sly W.S. Proc. Natl. Acad. Sci. U.S.A. 104:19989-19994(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT FIH ARG-18.
+	Additional computationally mapped references.

Web resources

Wikipedia

Parathyroid hormone entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V00597 mRNA. Translation: CAA23843.1.
J00301 Genomic DNA. Translation: AAA60215.1.
BC096142 mRNA. Translation: AAH96142.1.
BC096143 mRNA. Translation: AAH96143.1.
BC096144 mRNA. Translation: AAH96144.1.
BC096145 mRNA. Translation: AAH96145.1.

IPI

IPI00000940.

PIR

PTHU. A19339.

RefSeq

NP_000306.1. NM_000315.2.

UniGene

Hs.37045.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BWX	NMR	-	A	32-70	[»]
1ET1	X-ray	0.90	A/B	32-65	[»]
1ET2	model	-	A	32-65	[»]
1FVY	NMR	-	A	32-62	[»]
1HPH	NMR	-	A	32-68	[»]
1HPY	NMR	-	A	32-65	[»]
1HTH	NMR	-	A	32-65	[»]
1ZWA	NMR	-	A	32-65	[»]
1ZWB	NMR	-	A	33-68	[»]
1ZWD	NMR	-	A	34-68	[»]
1ZWE	NMR	-	A	35-68	[»]
1ZWF	NMR	-	A	35-68	[»]
1ZWG	NMR	-	A	35-68	[»]
2L1X	NMR	-	A	32-65	[»]
3C4M	X-ray	1.95	C/D	46-65	[»]

ProteinModelPortal

P01270.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01270. 2 interactions.

MINT

MINT-1403915.

STRING

9606.ENSP00000282091.

PTM databases

PhosphoSite

P01270.

Polymorphism databases

DMDM

131547.

Proteomic databases

PaxDb

P01270.

PeptideAtlas

P01270.

PRIDE

P01270.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282091; ENSP00000282091; ENSG00000152266.
ENST00000529816; ENSP00000433208; ENSG00000152266.

GeneID

5741.

KEGG

hsa:5741.

UCSC

uc001mlb.3. human.

Organism-specific databases

CTD

5741.

GeneCards

GC11M013470.

HGNC

HGNC:9606. PTH.

HPA

CAB000072.
CAB023409.

MIM

146200. phenotype.
168450. gene.

neXtProt

NX_P01270.

Orphanet

189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.

PharmGKB

PA33951.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41709.

HOGENOM

HOG000033707.

HOVERGEN

HBG008319.

InParanoid

P01270.

KO

K05261.

OMA

EIQFMHN.

OrthoDB

EOG4GHZQM.

PhylomeDB

P01270.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

P01270.

CleanEx

HS_PTH.

Genevestigator

P01270.

GermOnline

ENSG00000152266. Homo sapiens.

Family and domain databases

InterPro

IPR003625. PTH.
IPR001415. PTH/PTH-rel.
[Graphical view]

PANTHER

PTHR10541. PTHR10541. 1 hit.

Pfam

PF01279. Parathyroid. 1 hit.
[Graphical view]

PIRSF

PIRSF001832. PTH. 1 hit.

SMART

SM00087. PTH. 1 hit.
[Graphical view]

PROSITE

PS00335. PARATHYROID. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01270.

GenomeRNAi

5741.

NextBio

22348.

PMAP-CutDB

P01270.

SOURCE

Search...

Entry information

Entry name

PTHY_HUMAN

Accession

Primary (citable) accession number: P01270
Secondary accession number(s): Q4VB48, Q9UD38

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	May 1, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.