GenomeNet

Database: UniProt
Entry: CALC_HUMAN
LinkDB: CALC_HUMAN
Original site: CALC_HUMAN 
ID   CALC_HUMAN              Reviewed;         141 AA.
AC   P01258; B7ZL39; Q13935; Q13937; Q52LX7;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   12-SEP-2018, sequence version 3.
DT   24-JAN-2024, entry version 211.
DE   RecName: Full=Calcitonin;
DE   Contains:
DE     RecName: Full=Calcitonin;
DE   Contains:
DE     RecName: Full=Katacalcin;
DE     AltName: Full=Calcitonin carboxyl-terminal peptide;
DE              Short=CCP;
DE     AltName: Full=PDN-21;
DE   Flags: Precursor;
GN   Name=CALCA; Synonyms=CALC1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=6546550; DOI=10.1016/0014-5793(84)80839-x;
RA   le Moullec J.-M., Jullienne A., Chenais J., Lasmoles F., Guliana J.M.,
RA   Milhaud G., Moukhtar M.S.;
RT   "The complete sequence of human preprocalcitonin.";
RL   FEBS Lett. 167:93-97(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3872459; DOI=10.1073/pnas.82.7.1994;
RA   Jonas V., Lin C.R., Kawashima E., Semon D., Swanson L.W., Mermod J.-J.,
RA   Evans R.M., Rosenfeld M.G.;
RT   "Alternative RNA processing events in human calcitonin/calcitonin gene-
RT   related peptide gene expression.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:1994-1998(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3034287;
RA   Craig R.K., Riley J.H., Edbrooke M.R., Broad P.M., Foord S.M.,
RA   Al-Kazwini S.J., Holman J.J., Marshall I.;
RT   "Expression and function of the human calcitonin/alpha-CGRP gene in health
RT   and disease.";
RL   Biochem. Soc. Symp. 52:91-105(1986).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3485540; DOI=10.1016/0014-5793(86)81187-5;
RA   Riley J.H., Edbrooke M.R., Craig R.K.;
RT   "Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma cell
RT   line reflects aberrant proteolytic processing.";
RL   FEBS Lett. 198:71-79(1986).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Thyroid carcinoma;
RX   PubMed=1761559; DOI=10.1016/s0021-9258(18)54275-7;
RA   Minvielle S., Giscard-Dartevelle S., Cohen R., Taboulet J., Labye F.,
RA   Jullienne A., Rivaille P., Milhaud G., Moukhtar M.S., Lasmoles F.;
RT   "A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid
RT   carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-
RT   related peptide gene.";
RL   J. Biol. Chem. 266:24627-24631(1991).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-2; LYS-67; ARG-76;
RP   THR-123 AND PRO-138.
RG   NIEHS SNPs program;
RL   Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 48-83 (ISOFORM 1).
RX   PubMed=6148938; DOI=10.1016/0006-291x(84)90278-x;
RA   Nelkin B.D., Rosenfeld K.I., de Bustros A., Leong S.S., Roos B.A.,
RA   Baylin S.B.;
RT   "Structure and expression of a gene encoding human calcitonin and
RT   calcitonin gene related peptide.";
RL   Biochem. Biophys. Res. Commun. 123:648-655(1984).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 50-141 (ISOFORM 1).
RX   PubMed=2408883; DOI=10.1002/j.1460-2075.1985.tb03688.x;
RA   Edbrooke M.R., Parker D., McVey J.H., Riley J.H., Sorenson G.D.,
RA   Pettengill O.S., Craig R.K.;
RT   "Expression of the human calcitonin/CGRP gene in lung and thyroid
RT   carcinoma.";
RL   EMBO J. 4:715-724(1985).
RN   [12]
RP   PROTEIN SEQUENCE OF 85-116, AND AMIDATION AT PRO-116.
RX   PubMed=5760861; DOI=10.1002/hlca.19680510811;
RA   Neher R., Riniker B., Rittel W., Zuber H.;
RT   "Human calcitonin. Structure of calcitonin M and D.";
RL   Helv. Chim. Acta 51:1900-1905(1968).
RN   [13]
RP   STRUCTURE BY NMR OF CALCITONIN.
RX   PubMed=2001366; DOI=10.1021/bi00223a010;
RA   Motta A., Temussi P.A., Wunsch E., Bovermann G.;
RT   "A 1H NMR study of human calcitonin in solution.";
RL   Biochemistry 30:2364-2371(1991).
RN   [14]
RP   CHARACTERIZATION OF KATACALCIN.
RX   PubMed=6132180; DOI=10.1016/s0140-6736(83)91387-9;
RA   Hillyard C.J., Myers C., Abeyasekera G., Stevvensvenson J.C., Craig R.K.,
RA   MacIntyre I.;
RT   "Katacalcin: a new plasma calcium-lowering hormone.";
RL   Lancet 1:846-848(1983).
RN   [15]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
CC   -!- FUNCTION: Calcitonin causes a rapid but short-lived drop in the level
CC       of calcium and phosphate in blood by promoting the incorporation of
CC       those ions in the bones.
CC   -!- FUNCTION: Katacalcin is a potent plasma calcium-lowering peptide.
CC   -!- INTERACTION:
CC       P01258; X5D778: ANKRD11; NbExp=3; IntAct=EBI-1018474, EBI-17183751;
CC       P01258; Q01814: ATP2B2; NbExp=2; IntAct=EBI-1018474, EBI-1174243;
CC       P01258; P23634: ATP2B4; NbExp=2; IntAct=EBI-1018474, EBI-1174388;
CC       P01258; P01258: CALCA; NbExp=3; IntAct=EBI-1018474, EBI-1018474;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P01258-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P01258-2; Sequence=VSP_000709;
CC       Name=3;
CC         IsoId=P06881-1; Sequence=External;
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the calcitonin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/calca/";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Calcitonin entry;
CC       URL="https://en.wikipedia.org/wiki/Calcitonin";
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DR   EMBL; X00356; CAA25103.1; -; mRNA.
DR   EMBL; M12666; AAA51913.1; -; Genomic_DNA.
DR   EMBL; M12664; AAA51913.1; JOINED; Genomic_DNA.
DR   EMBL; M12665; AAA51913.1; JOINED; Genomic_DNA.
DR   EMBL; M26095; AAA35501.1; -; mRNA.
DR   EMBL; X03662; CAA27299.1; -; mRNA.
DR   EMBL; M64486; AAA58403.1; -; mRNA.
DR   EMBL; DQ080435; AAY68212.1; -; Genomic_DNA.
DR   EMBL; AC090835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471064; EAW68468.1; -; Genomic_DNA.
DR   EMBL; BC069684; AAH69684.1; -; mRNA.
DR   EMBL; BC069704; AAH69704.1; -; mRNA.
DR   EMBL; BC069760; AAH69760.1; -; mRNA.
DR   EMBL; BC069778; AAH69778.1; -; mRNA.
DR   EMBL; BC093753; AAH93753.1; -; mRNA.
DR   EMBL; BC101599; AAI01600.1; -; mRNA.
DR   EMBL; BC143562; AAI43563.1; -; mRNA.
DR   EMBL; K03513; AAA52124.1; -; mRNA.
DR   EMBL; X02330; CAA26189.1; -; mRNA.
DR   CCDS; CCDS7819.1; -. [P01258-1]
DR   PIR; A41716; A41716.
DR   PIR; S07643; TCHU.
DR   RefSeq; NP_001029124.1; NM_001033952.2. [P01258-1]
DR   RefSeq; NP_001732.1; NM_001741.2. [P01258-1]
DR   RefSeq; XP_016873772.1; XM_017018283.1.
DR   RefSeq; XP_016873773.1; XM_017018284.1.
DR   PDB; 2JXZ; NMR; -; A=85-116.
DR   PDB; 7TYH; EM; 3.30 A; P=85-116.
DR   PDB; 7TYO; EM; 2.70 A; P=85-116.
DR   PDBsum; 2JXZ; -.
DR   PDBsum; 7TYH; -.
DR   PDBsum; 7TYO; -.
DR   AlphaFoldDB; P01258; -.
DR   BMRB; P01258; -.
DR   EMDB; EMD-26190; -.
DR   SMR; P01258; -.
DR   BioGRID; 107247; 18.
DR   IntAct; P01258; 4.
DR   MINT; P01258; -.
DR   STRING; 9606.ENSP00000331746; -.
DR   GlyGen; P01258; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; P01258; -.
DR   MetOSite; P01258; -.
DR   PhosphoSitePlus; P01258; -.
DR   BioMuta; CALCA; -.
DR   DMDM; 322510018; -.
DR   jPOST; P01258; -.
DR   MassIVE; P01258; -.
DR   PaxDb; 9606-ENSP00000331746; -.
DR   PeptideAtlas; P01258; -.
DR   ProteomicsDB; 51362; -. [P01258-1]
DR   ProteomicsDB; 51363; -. [P01258-2]
DR   TopDownProteomics; P01258-1; -. [P01258-1]
DR   ABCD; P01258; 3 sequenced antibodies.
DR   Antibodypedia; 3493; 1990 antibodies from 46 providers.
DR   DNASU; 796; -.
DR   Ensembl; ENST00000331587.9; ENSP00000331746.4; ENSG00000110680.14. [P01258-1]
DR   Ensembl; ENST00000396372.2; ENSP00000379657.2; ENSG00000110680.14. [P01258-1]
DR   Ensembl; ENST00000469608.5; ENSP00000420618.1; ENSG00000110680.14. [P01258-2]
DR   GeneID; 796; -.
DR   KEGG; hsa:796; -.
DR   MANE-Select; ENST00000331587.9; ENSP00000331746.4; NM_001741.3; NP_001732.1.
DR   UCSC; uc001mlv.2; human. [P01258-1]
DR   AGR; HGNC:1437; -.
DR   CTD; 796; -.
DR   DisGeNET; 796; -.
DR   GeneCards; CALCA; -.
DR   HGNC; HGNC:1437; CALCA.
DR   HPA; ENSG00000110680; Tissue enhanced (parathyroid gland, thyroid gland).
DR   MIM; 114130; gene.
DR   neXtProt; NX_P01258; -.
DR   OpenTargets; ENSG00000110680; -.
DR   PharmGKB; PA26029; -.
DR   VEuPathDB; HostDB:ENSG00000110680; -.
DR   eggNOG; ENOG502RZI5; Eukaryota.
DR   GeneTree; ENSGT00940000162876; -.
DR   HOGENOM; CLU_122444_0_0_1; -.
DR   InParanoid; P01258; -.
DR   OrthoDB; 4002581at2759; -.
DR   PhylomeDB; P01258; -.
DR   TreeFam; TF333069; -.
DR   PathwayCommons; P01258; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR   Reactome; R-HSA-977225; Amyloid fiber formation.
DR   SignaLink; P01258; -.
DR   BioGRID-ORCS; 796; 15 hits in 1146 CRISPR screens.
DR   ChiTaRS; CALCA; human.
DR   EvolutionaryTrace; P01258; -.
DR   GeneWiki; Calcitonin; -.
DR   GenomeRNAi; 796; -.
DR   Pharos; P01258; Tbio.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P01258; Protein.
DR   Bgee; ENSG00000110680; Expressed in dorsal root ganglion and 124 other cell types or tissues.
DR   ExpressionAtlas; P01258; baseline and differential.
DR   Genevisible; P01258; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl.
DR   GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR   GO; GO:0031716; F:calcitonin receptor binding; IPI:UniProtKB.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0001984; P:artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure; IEA:Ensembl.
DR   GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR   GO; GO:0007566; P:embryo implantation; IDA:UniProtKB.
DR   GO; GO:0007631; P:feeding behavior; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR   GO; GO:0002548; P:monocyte chemotaxis; IDA:BHF-UCL.
DR   GO; GO:0045779; P:negative regulation of bone resorption; IDA:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR   GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:Ensembl.
DR   GO; GO:0001503; P:ossification; IEA:Ensembl.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR   GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR   GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR   GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR   GO; GO:0006939; P:smooth muscle contraction; IEA:Ensembl.
DR   InterPro; IPR021118; Calcitonin.
DR   InterPro; IPR021117; Calcitonin-like.
DR   InterPro; IPR021116; Calcitonin/adrenomedullin.
DR   InterPro; IPR018360; Calcitonin_CS.
DR   InterPro; IPR001693; Calcitonin_peptide-like.
DR   PANTHER; PTHR10505:SF16; CALCITONIN; 1.
DR   PANTHER; PTHR10505; CALCITONIN-RELATED; 1.
DR   Pfam; PF00214; Calc_CGRP_IAPP; 1.
DR   PRINTS; PR00270; CALCITONINA.
DR   SMART; SM00113; CALCITONIN; 1.
DR   PROSITE; PS00258; CALCITONIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disulfide bond; Hormone; Phosphoprotein; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..82
FT                   /id="PRO_0000004050"
FT   PEPTIDE         85..116
FT                   /note="Calcitonin"
FT                   /evidence="ECO:0000269|PubMed:5760861"
FT                   /id="PRO_0000004051"
FT   PEPTIDE         121..141
FT                   /note="Katacalcin"
FT                   /id="PRO_0000004052"
FT   REGION          64..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          111..141
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        64..79
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        120..134
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         43
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P01257"
FT   MOD_RES         116
FT                   /note="Proline amide"
FT                   /evidence="ECO:0000269|PubMed:5760861"
FT   DISULFID        85..91
FT                   /evidence="ECO:0000269|PubMed:5760861"
FT   VAR_SEQ         134..141
FT                   /note="VSMPQNAN -> NHCPEESL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:1761559"
FT                   /id="VSP_000709"
FT   VARIANT         2
FT                   /note="G -> R (in dbSNP:rs34587547)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_025271"
FT   VARIANT         57
FT                   /note="D -> N (in dbSNP:rs5239)"
FT                   /id="VAR_014592"
FT   VARIANT         67
FT                   /note="E -> K (in dbSNP:rs34164367)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_025272"
FT   VARIANT         76
FT                   /note="S -> R (in dbSNP:rs5241)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_014593"
FT   VARIANT         123
FT                   /note="S -> T (in dbSNP:rs34414857)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_025273"
FT   VARIANT         138
FT                   /note="Q -> P (in dbSNP:rs13306224)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_025274"
FT   CONFLICT        92
FT                   /note="M -> I (in Ref. 2; AAA51913)"
FT                   /evidence="ECO:0000305"
FT   HELIX           92..101
FT                   /evidence="ECO:0007829|PDB:7TYO"
FT   TURN            102..104
FT                   /evidence="ECO:0007829|PDB:7TYO"
FT   HELIX           109..111
FT                   /evidence="ECO:0007829|PDB:2JXZ"
SQ   SEQUENCE   141 AA;  15467 MW;  99622305DD8B286F CRC64;
     MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQDYVQ
     MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF NKFHTFPQTA IGVGAPGKKR
     DMSSDLERDH RPHVSMPQNA N
//
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