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P01270

- PTHY_HUMAN

UniProt

P01270 - PTHY_HUMAN

Protein

Parathyroid hormone

Gene

PTH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    1. hormone activity Source: ProtInc
    2. peptide hormone receptor binding Source: UniProtKB
    3. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
    2. bone resorption Source: UniProtKB
    3. cAMP metabolic process Source: ProtInc
    4. cell-cell signaling Source: ProtInc
    5. cellular calcium ion homeostasis Source: Ensembl
    6. cellular macromolecule biosynthetic process Source: MGI
    7. G-protein coupled receptor signaling pathway Source: ProtInc
    8. hormone-mediated apoptotic signaling pathway Source: ProtInc
    9. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    10. positive regulation of bone mineralization Source: UniProtKB
    11. positive regulation of cAMP biosynthetic process Source: MGI
    12. positive regulation of glucose import Source: UniProtKB
    13. positive regulation of glycogen biosynthetic process Source: UniProtKB
    14. positive regulation of signal transduction Source: Ensembl
    15. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    16. regulation of gene expression Source: MGI
    17. response to cadmium ion Source: Ensembl
    18. response to drug Source: Ensembl
    19. response to ethanol Source: Ensembl
    20. response to fibroblast growth factor Source: Ensembl
    21. response to lead ion Source: Ensembl
    22. response to parathyroid hormone Source: Ensembl
    23. response to vitamin D Source: Ensembl
    24. Rho protein signal transduction Source: Ensembl
    25. skeletal system development Source: ProtInc
    26. transcription from RNA polymerase II promoter Source: GOC

    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: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:9606. PTH.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB
    2. extracellular space Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 2 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.

    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.
    GenevestigatoriP01270.

    Organism-specific databases

    HPAiCAB000072.
    CAB023409.

    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 – 6431
    Helixi65 – 673

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000033707.
    HOVERGENiHBG008319.
    InParanoidiP01270.
    KOiK05261.
    OMAiEIQFMHN.
    OrthoDBiEOG7ZGX5Q.
    PhylomeDBiP01270.
    TreeFamiTF336197.

    Family and domain databases

    InterProiIPR003625. PTH.
    IPR001415. PTH/PTH-rel.
    [Graphical view]
    PANTHERiPTHR10541. PTHR10541. 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

    MIPAKDMAKV MIVMLAICFL TKSDGKSVKK RSVSEIQLMH NLGKHLNSME    50
    RVEWLRKKLQ DVHNFVALGA PLAPRDAGSQ RPRKKEDNVL VESHEKSLGE 100
    ADKADVNVLT KAKSQ 115
    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. 2 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:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi131547.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Parathyroid hormone entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS7812.1.
    PIRi A19339. PTHU.
    RefSeqi NP_000306.1. NM_000315.2.
    UniGenei Hs.37045.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    DisProti DP00637.
    ProteinModelPortali P01270.
    SMRi P01270. Positions 32-70.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111713. 6 interactions.
    IntActi P01270. 2 interactions.
    MINTi MINT-1403915.
    STRINGi 9606.ENSP00000282091.

    PTM databases

    PhosphoSitei P01270.

    Polymorphism databases

    DMDMi 131547.

    Proteomic databases

    PaxDbi P01270.
    PeptideAtlasi P01270.
    PRIDEi P01270.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000282091 ; ENSP00000282091 ; ENSG00000152266 .
    ENST00000529816 ; ENSP00000433208 ; ENSG00000152266 .
    GeneIDi 5741.
    KEGGi hsa:5741.
    UCSCi uc001mlb.3. human.

    Organism-specific databases

    CTDi 5741.
    GeneCardsi GC11M013470.
    HGNCi HGNC:9606. PTH.
    HPAi CAB000072.
    CAB023409.
    MIMi 146200. phenotype.
    168450. gene.
    neXtProti NX_P01270.
    Orphaneti 189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
    PharmGKBi PA33951.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG41709.
    HOGENOMi HOG000033707.
    HOVERGENi HBG008319.
    InParanoidi P01270.
    KOi K05261.
    OMAi EIQFMHN.
    OrthoDBi EOG7ZGX5Q.
    PhylomeDBi P01270.
    TreeFami TF336197.

    Enzyme and pathway databases

    Reactomei REACT_18372. Class B/2 (Secretin family receptors).
    REACT_19327. G alpha (s) signalling events.

    Miscellaneous databases

    EvolutionaryTracei P01270.
    GeneWikii Parathyroid_hormone.
    GenomeRNAii 5741.
    NextBioi 22348.
    PMAP-CutDB P01270.
    PROi P01270.
    SOURCEi Search...

    Gene expression databases

    Bgeei P01270.
    CleanExi HS_PTH.
    Genevestigatori P01270.

    Family and domain databases

    InterProi IPR003625. PTH.
    IPR001415. PTH/PTH-rel.
    [Graphical view ]
    PANTHERi PTHR10541. PTHR10541. 1 hit.
    Pfami PF01279. Parathyroid. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001832. PTH. 1 hit.
    SMARTi SM00087. PTH. 1 hit.
    [Graphical view ]
    PROSITEi PS00335. PARATHYROID. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 152 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