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P01270 (PTHY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Parathyroid hormone

Short name=PTH
Alternative name(s):
Parathormone
Parathyrin
Gene names
Name:PTH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length115 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Hypoparathyroidism, familial isolated (FIH) [MIM:146200]: A disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps.
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 componentSecreted
   DiseaseDisease mutation
   DomainSignal
   Molecular functionHormone
   PTMCleavage on pair of basic residues
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement PubMed 7797535. Source: ProtInc

Rho protein signal transduction

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

cellular macromolecule biosynthetic process

Inferred from direct assay PubMed 19723499. Source: MGI

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: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19723499. Source: MGI

regulation of gene expression

Inferred from direct assay PubMed 90087. Source: MGI

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to fibroblast growth factor

Inferred from electronic annotation. Source: Ensembl

response to lead ion

Inferred from electronic annotation. Source: Ensembl

response to parathyroid hormone

Inferred from electronic annotation. Source: Ensembl

response to vitamin D

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Traceable author statement PubMed 10913913. Source: ProtInc

transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17696759. Source: GOC

   Cellular_componentextracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionRNA 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Ref.5 Ref.6
Propeptide26 – 316
PRO_0000023249
Chain32 – 11584Parathyroid hormone
PRO_0000023250

Regions

Region51 – 6919Important for receptor binding

Natural variations

Natural variant181C → 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 variant231S → P in FIH; recessive, might lead to inefficient processing of the precursor. Ref.21
VAR_018464

Experimental info

Mutagenesis161A → R: Abolishes processing of the precursor; when associated with variant R-18. Ref.4
Mutagenesis511R → A: Reduced affinity for PTH1R. Ref.19
Mutagenesis541W → A: Strongly reduced affinity for PTH1R. Ref.19
Mutagenesis551L → A: Strongly reduced affinity for PTH1R. Ref.19
Mutagenesis581K → A: Reduced affinity for PTH1R. Ref.19
Mutagenesis591L → A: Strongly reduced affinity for PTH1R. Ref.19
Sequence conflict1071N → D AA sequence Ref.8

Secondary structure

.... 115
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01270 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: 849015736A6E5597

FASTA11512,861
        10         20         30         40         50         60 
MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME RVEWLRKKLQ 

        70         80         90        100        110 
DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE ADKADVNVLT KAKSQ 

« Hide

References

« Hide '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.
PIRPTHU. A19339.
RefSeqNP_000306.1. NM_000315.2.
UniGeneHs.37045.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BWXNMR-A32-70[»]
1ET1X-ray0.90A/B32-65[»]
1ET2model-A32-65[»]
1FVYNMR-A32-62[»]
1HPHNMR-A32-68[»]
1HPYNMR-A32-65[»]
1HTHNMR-A32-65[»]
1ZWANMR-A32-65[»]
1ZWBNMR-A33-68[»]
1ZWDNMR-A34-68[»]
1ZWENMR-A35-68[»]
1ZWFNMR-A35-68[»]
1ZWGNMR-A35-68[»]
2L1XNMR-A32-65[»]
3C4MX-ray1.95C/D46-65[»]
DisProtDP00637.
ProteinModelPortalP01270.
SMRP01270. Positions 32-70.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111713. 6 interactions.
IntActP01270. 2 interactions.
MINTMINT-1403915.
STRING9606.ENSP00000282091.

PTM databases

PhosphoSiteP01270.

Polymorphism databases

DMDM131547.

Proteomic databases

PaxDbP01270.
PeptideAtlasP01270.
PRIDEP01270.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282091; ENSP00000282091; ENSG00000152266.
ENST00000529816; ENSP00000433208; ENSG00000152266.
GeneID5741.
KEGGhsa:5741.
UCSCuc001mlb.3. human.

Organism-specific databases

CTD5741.
GeneCardsGC11M013470.
HGNCHGNC:9606. PTH.
HPACAB000072.
CAB023409.
MIM146200. phenotype.
168450. gene.
neXtProtNX_P01270.
Orphanet189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
PharmGKBPA33951.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41709.
HOGENOMHOG000033707.
HOVERGENHBG008319.
InParanoidP01270.
KOK05261.
OMAEIQFMHN.
OrthoDBEOG7ZGX5Q.
PhylomeDBP01270.
TreeFamTF336197.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP01270.
CleanExHS_PTH.
GenevestigatorP01270.

Family and domain databases

InterProIPR003625. PTH.
IPR001415. PTH/PTH-rel.
[Graphical view]
PANTHERPTHR10541. PTHR10541. 1 hit.
PfamPF01279. Parathyroid. 1 hit.
[Graphical view]
PIRSFPIRSF001832. PTH. 1 hit.
SMARTSM00087. PTH. 1 hit.
[Graphical view]
PROSITEPS00335. PARATHYROID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01270.
GeneWikiParathyroid_hormone.
GenomeRNAi5741.
NextBio22348.
PMAP-CutDBP01270.
PROP01270.
SOURCESearch...

Entry information

Entry namePTHY_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM