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P01258

- CALC_HUMAN

UniProt

P01258 - CALC_HUMAN

Protein

Calcitonin

Gene

CALCA

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

    Calcitonin causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.
    Katacalcin is a potent plasma calcium-lowering peptide.

    GO - Molecular functioni

    1. calcitonin receptor binding Source: UniProtKB
    2. identical protein binding Source: IntAct
    3. protein binding Source: IntAct

    GO - Biological processi

    1. activation of protein kinase activity Source: UniProtKB
    2. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Ensembl
    3. aging Source: Ensembl
    4. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
    5. embryo implantation Source: UniProtKB
    6. feeding behavior Source: Ensembl
    7. inflammatory response Source: Ensembl
    8. monocyte chemotaxis Source: BHF-UCL
    9. negative regulation of bone resorption Source: UniProtKB
    10. negative regulation of neurological system process Source: Ensembl
    11. negative regulation of ossification Source: Ensembl
    12. negative regulation of smooth muscle contraction Source: Ensembl
    13. negative regulation of transcription, DNA-templated Source: UniProtKB
    14. neuropeptide signaling pathway Source: Ensembl
    15. positive regulation of adenylate cyclase activity Source: UniProtKB
    16. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
    17. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
    18. positive regulation of ossification Source: Ensembl
    19. regulation of heart rate Source: Ensembl
    20. regulation of inflammatory response Source: Ensembl
    21. response to heat Source: Ensembl
    22. response to pain Source: Ensembl
    23. vasodilation of artery involved in baroreceptor response to increased systemic arterial blood pressure Source: Ensembl

    Keywords - Molecular functioni

    Hormone

    Enzyme and pathway databases

    ReactomeiREACT_18290. Calcitonin-like ligand receptors.
    REACT_19327. G alpha (s) signalling events.
    REACT_75925. Amyloids.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Calcitonin
    Cleaved into the following 2 chains:
    Alternative name(s):
    Calcitonin carboxyl-terminal peptide
    Short name:
    CCP
    PDN-21
    Gene namesi
    Name:CALCA
    Synonyms:CALC1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1437. CALCA.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. extracellular region Source: Reactome
    3. extracellular space Source: UniProtKB
    4. neuronal cell body Source: Ensembl
    5. nucleus Source: Ensembl
    6. terminal bouton Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26029.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Propeptidei26 – 8257PRO_0000004050Add
    BLAST
    Peptidei85 – 11632Calcitonin1 PublicationPRO_0000004051Add
    BLAST
    Peptidei121 – 14121KatacalcinPRO_0000004052Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi85 ↔ 911 Publication
    Modified residuei116 – 1161Proline amide1 Publication

    Keywords - PTMi

    Amidation, Cleavage on pair of basic residues, Disulfide bond

    Proteomic databases

    MaxQBiP01258.
    PRIDEiP01258.

    Expressioni

    Gene expression databases

    ArrayExpressiP01258.
    BgeeiP01258.
    CleanExiHS_CALCA.
    GenevestigatoriP01258.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-1018474,EBI-1018474
    ATP2B2Q018142EBI-1018474,EBI-1174243
    ATP2B4P236342EBI-1018474,EBI-1174388

    Protein-protein interaction databases

    BioGridi107247. 4 interactions.
    IntActiP01258. 3 interactions.
    MINTiMINT-2799962.
    STRINGi9606.ENSP00000331746.

    Structurei

    Secondary structure

    1
    141
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi88 – 10518
    Helixi109 – 1113

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JXZNMR-A85-116[»]
    ProteinModelPortaliP01258.
    SMRiP01258. Positions 85-116.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP01258.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the calcitonin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    HOGENOMiHOG000038203.
    HOVERGENiHBG031362.
    KOiK12332.
    OMAiTENEHEL.
    PhylomeDBiP01258.
    TreeFamiTF333069.

    Family and domain databases

    InterProiIPR021118. Calcitonin.
    IPR018360. Calcitonin_CS.
    IPR001693. Calcitonin_peptide-like.
    IPR021117. Procalcitonin-like.
    IPR021116. Procalcitonin/adrenomedullin.
    [Graphical view]
    PANTHERiPTHR10505. PTHR10505. 1 hit.
    PfamiPF00214. Calc_CGRP_IAPP. 1 hit.
    [Graphical view]
    PRINTSiPR00270. CALCITONINA.
    SMARTiSM00113. CALCITONIN. 1 hit.
    [Graphical view]
    PROSITEiPS00258. CALCITONIN. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P01258-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL    50
    LAALVQNYVQ MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF 100
    NKFHTFPQTA IGVGAPGKKR DMSSDLERDH RPHVSMPQNA N 141
    Length:141
    Mass (Da):15,466
    Last modified:February 8, 2011 - v2
    Checksum:iC3688905D0EB2502
    GO
    Isoform 2 (identifier: P01258-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         134-141: VSMPQNAN → NHCPEESL

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:141
    Mass (Da):15,534
    Checksum:i1810E64810E31144
    GO
    Isoform 3 (identifier: P06881-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry P06881.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:128
    Mass (Da):13,898
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti92 – 921M → I in AAA51913. (PubMed:3872459)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21G → R.1 Publication
    Corresponds to variant rs34587547 [ dbSNP | Ensembl ].
    VAR_025271
    Natural varianti57 – 571N → D.10 Publications
    Corresponds to variant rs5239 [ dbSNP | Ensembl ].
    VAR_014592
    Natural varianti67 – 671E → K.1 Publication
    Corresponds to variant rs34164367 [ dbSNP | Ensembl ].
    VAR_025272
    Natural varianti76 – 761S → R.1 Publication
    Corresponds to variant rs5241 [ dbSNP | Ensembl ].
    VAR_014593
    Natural varianti123 – 1231S → T.1 Publication
    Corresponds to variant rs34414857 [ dbSNP | Ensembl ].
    VAR_025273
    Natural varianti138 – 1381Q → P.1 Publication
    Corresponds to variant rs13306224 [ dbSNP | Ensembl ].
    VAR_025274

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei134 – 1418VSMPQNAN → NHCPEESL in isoform 2. 1 PublicationVSP_000709

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X00356 mRNA. Translation: CAA25103.1.
    M12666, M12664, M12665 Genomic DNA. Translation: AAA51913.1.
    M26095 mRNA. Translation: AAA35501.1.
    X03662 mRNA. Translation: CAA27299.1.
    M64486 mRNA. Translation: AAA58403.1.
    DQ080435 Genomic DNA. Translation: AAY68212.1.
    AC090835 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68468.1.
    BC069684 mRNA. Translation: AAH69684.1.
    BC069704 mRNA. Translation: AAH69704.1.
    BC069760 mRNA. Translation: AAH69760.1.
    BC069778 mRNA. Translation: AAH69778.1.
    BC093753 mRNA. Translation: AAH93753.1.
    BC101599 mRNA. Translation: AAI01600.1.
    BC143562 mRNA. Translation: AAI43563.1.
    K03513 mRNA. Translation: AAA52124.1.
    X02330 mRNA. Translation: CAA26189.1.
    CCDSiCCDS7819.1. [P01258-1]
    PIRiA41716.
    S07643. TCHU.
    RefSeqiNP_001029124.1. NM_001033952.2.
    NP_001732.1. NM_001741.2.
    UniGeneiHs.37058.

    Genome annotation databases

    EnsembliENST00000331587; ENSP00000331746; ENSG00000110680. [P01258-1]
    ENST00000396372; ENSP00000379657; ENSG00000110680. [P01258-1]
    ENST00000469608; ENSP00000420618; ENSG00000110680. [P01258-2]
    GeneIDi796.
    KEGGihsa:796.
    UCSCiuc001mlv.1. human. [P01258-1]

    Polymorphism databases

    DMDMi322510018.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Wikipedia

    Calcitonin entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X00356 mRNA. Translation: CAA25103.1 .
    M12666 , M12664 , M12665 Genomic DNA. Translation: AAA51913.1 .
    M26095 mRNA. Translation: AAA35501.1 .
    X03662 mRNA. Translation: CAA27299.1 .
    M64486 mRNA. Translation: AAA58403.1 .
    DQ080435 Genomic DNA. Translation: AAY68212.1 .
    AC090835 Genomic DNA. No translation available.
    CH471064 Genomic DNA. Translation: EAW68468.1 .
    BC069684 mRNA. Translation: AAH69684.1 .
    BC069704 mRNA. Translation: AAH69704.1 .
    BC069760 mRNA. Translation: AAH69760.1 .
    BC069778 mRNA. Translation: AAH69778.1 .
    BC093753 mRNA. Translation: AAH93753.1 .
    BC101599 mRNA. Translation: AAI01600.1 .
    BC143562 mRNA. Translation: AAI43563.1 .
    K03513 mRNA. Translation: AAA52124.1 .
    X02330 mRNA. Translation: CAA26189.1 .
    CCDSi CCDS7819.1. [P01258-1 ]
    PIRi A41716.
    S07643. TCHU.
    RefSeqi NP_001029124.1. NM_001033952.2.
    NP_001732.1. NM_001741.2.
    UniGenei Hs.37058.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2JXZ NMR - A 85-116 [» ]
    ProteinModelPortali P01258.
    SMRi P01258. Positions 85-116.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107247. 4 interactions.
    IntActi P01258. 3 interactions.
    MINTi MINT-2799962.
    STRINGi 9606.ENSP00000331746.

    Polymorphism databases

    DMDMi 322510018.

    Proteomic databases

    MaxQBi P01258.
    PRIDEi P01258.

    Protocols and materials databases

    DNASUi 796.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000331587 ; ENSP00000331746 ; ENSG00000110680 . [P01258-1 ]
    ENST00000396372 ; ENSP00000379657 ; ENSG00000110680 . [P01258-1 ]
    ENST00000469608 ; ENSP00000420618 ; ENSG00000110680 . [P01258-2 ]
    GeneIDi 796.
    KEGGi hsa:796.
    UCSCi uc001mlv.1. human. [P01258-1 ]

    Organism-specific databases

    CTDi 796.
    GeneCardsi GC11M014945.
    HGNCi HGNC:1437. CALCA.
    MIMi 114130. gene.
    neXtProti NX_P01258.
    PharmGKBi PA26029.
    GenAtlasi Search...

    Phylogenomic databases

    HOGENOMi HOG000038203.
    HOVERGENi HBG031362.
    KOi K12332.
    OMAi TENEHEL.
    PhylomeDBi P01258.
    TreeFami TF333069.

    Enzyme and pathway databases

    Reactomei REACT_18290. Calcitonin-like ligand receptors.
    REACT_19327. G alpha (s) signalling events.
    REACT_75925. Amyloids.

    Miscellaneous databases

    EvolutionaryTracei P01258.
    GeneWikii Calcitonin.
    GenomeRNAii 796.
    NextBioi 3234.
    PROi P01258.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P01258.
    Bgeei P01258.
    CleanExi HS_CALCA.
    Genevestigatori P01258.

    Family and domain databases

    InterProi IPR021118. Calcitonin.
    IPR018360. Calcitonin_CS.
    IPR001693. Calcitonin_peptide-like.
    IPR021117. Procalcitonin-like.
    IPR021116. Procalcitonin/adrenomedullin.
    [Graphical view ]
    PANTHERi PTHR10505. PTHR10505. 1 hit.
    Pfami PF00214. Calc_CGRP_IAPP. 1 hit.
    [Graphical view ]
    PRINTSi PR00270. CALCITONINA.
    SMARTi SM00113. CALCITONIN. 1 hit.
    [Graphical view ]
    PROSITEi PS00258. CALCITONIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-57.
    2. "Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression."
      Jonas V., Lin C.R., Kawashima E., Semon D., Swanson L.W., Mermod J.-J., Evans R.M., Rosenfeld M.G.
      Proc. Natl. Acad. Sci. U.S.A. 82:1994-1998(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-57.
    3. "Expression and function of the human calcitonin/alpha-CGRP gene in health and disease."
      Craig R.K., Riley J.H., Edbrooke M.R., Broad P.M., Foord S.M., Al-Kazwini S.J., Holman J.J., Marshall I.
      Biochem. Soc. Symp. 52:91-105(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-57.
    4. "Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma cell line reflects aberrant proteolytic processing."
      Riley J.H., Edbrooke M.R., Craig R.K.
      FEBS Lett. 198:71-79(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-57.
    5. "A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene."
      Minvielle S., Giscard-Dartevelle S., Cohen R., Taboulet J., Labye F., Jullienne A., Rivaille P., Milhaud G., Moukhtar M.S., Lasmoles F.
      J. Biol. Chem. 266:24627-24631(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ASP-57.
      Tissue: Thyroid carcinoma.
    6. NIEHS SNPs program
      Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-2; ASP-57; LYS-67; ARG-76; THR-123 AND PRO-138.
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASP-57.
    9. "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] (ISOFORM 1), VARIANT ASP-57.
      Tissue: Placenta.
    10. "Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide."
      Nelkin B.D., Rosenfeld K.I., de Bustros A., Leong S.S., Roos B.A., Baylin S.B.
      Biochem. Biophys. Res. Commun. 123:648-655(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 48-83 (ISOFORM 1), VARIANT ASP-57.
    11. "Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma."
      Edbrooke M.R., Parker D., McVey J.H., Riley J.H., Sorenson G.D., Pettengill O.S., Craig R.K.
      EMBO J. 4:715-724(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 50-141 (ISOFORM 1), VARIANT ASP-57.
    12. "Human calcitonin. Structure of calcitonin M and D."
      Neher R., Riniker B., Rittel W., Zuber H.
      Helv. Chim. Acta 51:1900-1905(1968) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 85-116, AMIDATION AT PRO-116.
    13. "A 1H NMR study of human calcitonin in solution."
      Motta A., Temussi P.A., Wunsch E., Bovermann G.
      Biochemistry 30:2364-2371(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF CALCITONIN.
    14. Cited for: CHARACTERIZATION OF KATACALCIN.
    15. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).

    Entry informationi

    Entry nameiCALC_HUMAN
    AccessioniPrimary (citable) accession number: P01258
    Secondary accession number(s): B7ZL39
    , Q13935, Q13937, Q52LX7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: February 8, 2011
    Last modified: October 1, 2014
    This is version 147 of the entry and version 2 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