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Protein

Parathyroid hormone

Gene

PTH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • hormone activity Source: ProtInc
  • parathyroid hormone receptor binding Source: GO_Central
  • peptide hormone receptor binding Source: UniProtKB
  • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
  • bone resorption Source: UniProtKB
  • cAMP metabolic process Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • cellular calcium ion homeostasis Source: Ensembl
  • cellular macromolecule biosynthetic process Source: MGI
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • hormone-mediated apoptotic signaling pathway Source: ProtInc
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of bone mineralization Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: MGI
  • positive regulation of glucose import Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of signal transduction Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of gene expression Source: MGI
  • response to cadmium ion Source: Ensembl
  • response to drug Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to fibroblast growth factor Source: Ensembl
  • response to lead ion Source: Ensembl
  • response to parathyroid hormone Source: Ensembl
  • response to vitamin D Source: Ensembl
  • Rho protein signal transduction Source: Ensembl
  • skeletal system development Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Parathyroid hormone
Short name:
PTH
Alternative name(s):
Parathormone
Parathyrin
Gene namesi
Name:PTH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:9606. PTH.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
  • intracellular Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hypoparathyroidism, familial isolated (FIH)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps.

See also OMIM:146200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181C → 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. 3 Publications
VAR_006047
Natural varianti23 – 231S → P in FIH; recessive, might lead to inefficient processing of the precursor. 1 Publication
VAR_018464

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi16 – 161A → R: Abolishes processing of the precursor; when associated with variant R-18. 1 Publication
Mutagenesisi51 – 511R → A: Reduced affinity for PTH1R. 1 Publication
Mutagenesisi54 – 541W → A: Strongly reduced affinity for PTH1R. 1 Publication
Mutagenesisi55 – 551L → A: Strongly reduced affinity for PTH1R. 1 Publication
Mutagenesisi58 – 581K → A: Reduced affinity for PTH1R. 1 Publication
Mutagenesisi59 – 591L → A: Strongly reduced affinity for PTH1R. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi146200. phenotype.
Orphaneti189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
PharmGKBiPA33951.

Polymorphism and mutation databases

BioMutaiPTH.
DMDMi131547.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 25252 PublicationsAdd
BLAST
Propeptidei26 – 3161 PublicationPRO_0000023249
Chaini32 – 11584Parathyroid hormonePRO_0000023250Add
BLAST

Keywords - PTMi

Cleavage on pair of basic residues

Proteomic databases

PaxDbiP01270.
PeptideAtlasiP01270.
PRIDEiP01270.

PTM databases

PhosphoSiteiP01270.

Miscellaneous databases

PMAP-CutDBP01270.

Expressioni

Gene expression databases

BgeeiP01270.
CleanExiHS_PTH.
GenevisibleiP01270. HS.

Organism-specific databases

HPAiCAB000072.
CAB023409.
CAB026363.

Interactioni

Subunit structurei

Interacts with PTH1R (via N-terminal extracellular domain).1 Publication

Protein-protein interaction databases

BioGridi111713. 6 interactions.
IntActiP01270. 2 interactions.
MINTiMINT-1403915.
STRINGi9606.ENSP00000282091.

Structurei

Secondary structure

1
115
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi34 – 6431Combined sources
Helixi65 – 673Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
DisProtiDP00637.
ProteinModelPortaliP01270.
SMRiP01270. Positions 32-70.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01270.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni51 – 6919Important for receptor bindingAdd
BLAST

Sequence similaritiesi

Belongs to the parathyroid hormone family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG41709.
GeneTreeiENSGT00390000018603.
HOGENOMiHOG000033707.
HOVERGENiHBG008319.
InParanoidiP01270.
KOiK05261.
OMAiEIQFMHN.
OrthoDBiEOG7ZGX5Q.
PhylomeDBiP01270.
TreeFamiTF336197.

Family and domain databases

InterProiIPR003625. PTH.
IPR001415. PTH/PTH-rel.
[Graphical view]
PANTHERiPTHR10541:SF2. PTHR10541:SF2. 1 hit.
PfamiPF01279. Parathyroid. 1 hit.
[Graphical view]
PIRSFiPIRSF001832. PTH. 1 hit.
SMARTiSM00087. PTH. 1 hit.
[Graphical view]
PROSITEiPS00335. PARATHYROID. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01270-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME
60 70 80 90 100
RVEWLRKKLQ DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE
110
ADKADVNVLT KAKSQ
Length:115
Mass (Da):12,861
Last modified:August 13, 1987 - v1
Checksum:i849015736A6E5597
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti107 – 1071N → D AA sequence (PubMed:728431).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181C → 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. 3 Publications
VAR_006047
Natural varianti23 – 231S → P in FIH; recessive, might lead to inefficient processing of the precursor. 1 Publication
VAR_018464

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7812.1.
PIRiA19339. PTHU.
RefSeqiNP_000306.1. NM_000315.2.
UniGeneiHs.37045.

Genome annotation databases

EnsembliENST00000282091; ENSP00000282091; ENSG00000152266.
ENST00000529816; ENSP00000433208; ENSG00000152266.
GeneIDi5741.
KEGGihsa:5741.
UCSCiuc001mlb.3. human.

Cross-referencesi

Web resourcesi

Wikipedia

Parathyroid hormone entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7812.1.
PIRiA19339. PTHU.
RefSeqiNP_000306.1. NM_000315.2.
UniGeneiHs.37045.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
DisProtiDP00637.
ProteinModelPortaliP01270.
SMRiP01270. Positions 32-70.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111713. 6 interactions.
IntActiP01270. 2 interactions.
MINTiMINT-1403915.
STRINGi9606.ENSP00000282091.

PTM databases

PhosphoSiteiP01270.

Polymorphism and mutation databases

BioMutaiPTH.
DMDMi131547.

Proteomic databases

PaxDbiP01270.
PeptideAtlasiP01270.
PRIDEiP01270.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282091; ENSP00000282091; ENSG00000152266.
ENST00000529816; ENSP00000433208; ENSG00000152266.
GeneIDi5741.
KEGGihsa:5741.
UCSCiuc001mlb.3. human.

Organism-specific databases

CTDi5741.
GeneCardsiGC11M013470.
HGNCiHGNC:9606. PTH.
HPAiCAB000072.
CAB023409.
CAB026363.
MIMi146200. phenotype.
168450. gene.
neXtProtiNX_P01270.
Orphaneti189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
PharmGKBiPA33951.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG41709.
GeneTreeiENSGT00390000018603.
HOGENOMiHOG000033707.
HOVERGENiHBG008319.
InParanoidiP01270.
KOiK05261.
OMAiEIQFMHN.
OrthoDBiEOG7ZGX5Q.
PhylomeDBiP01270.
TreeFamiTF336197.

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTraceiP01270.
GeneWikiiParathyroid_hormone.
GenomeRNAii5741.
NextBioi22348.
PMAP-CutDBP01270.
PROiP01270.
SOURCEiSearch...

Gene expression databases

BgeeiP01270.
CleanExiHS_PTH.
GenevisibleiP01270. HS.

Family and domain databases

InterProiIPR003625. PTH.
IPR001415. PTH/PTH-rel.
[Graphical view]
PANTHERiPTHR10541:SF2. PTHR10541:SF2. 1 hit.
PfamiPF01279. Parathyroid. 1 hit.
[Graphical view]
PIRSFiPIRSF001832. PTH. 1 hit.
SMARTiSM00087. PTH. 1 hit.
[Graphical view]
PROSITEiPS00335. PARATHYROID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. 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. 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. 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.

Entry informationi

Entry nameiPTHY_HUMAN
AccessioniPrimary (citable) accession number: P01270
Secondary accession number(s): Q4VB48, Q9UD38
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: July 22, 2015
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.