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 03-AUG-2022, entry version 203.
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. [P01258-1]
DR RefSeq; XP_016873773.1; XM_017018284.1. [P01258-1]
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 SMR; P01258; -.
DR BioGRID; 107247; 18.
DR IntAct; P01258; 4.
DR MINT; P01258; -.
DR STRING; 9606.ENSP00000331746; -.
DR iPTMnet; P01258; -.
DR MetOSite; P01258; -.
DR PhosphoSitePlus; P01258; -.
DR BioMuta; CALCA; -.
DR DMDM; 322510018; -.
DR jPOST; P01258; -.
DR MassIVE; P01258; -.
DR PaxDb; P01258; -.
DR PeptideAtlas; P01258; -.
DR PRIDE; 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; 1836 antibodies from 46 providers.
DR DNASU; 796; -.
DR Ensembl; ENST00000331587.9; ENSP00000331746.4; ENSG00000110680.13. [P01258-1]
DR Ensembl; ENST00000396372.2; ENSP00000379657.2; ENSG00000110680.13. [P01258-1]
DR Ensembl; ENST00000469608.5; ENSP00000420618.1; ENSG00000110680.13. [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 CTD; 796; -.
DR DisGeNET; 796; -.
DR GeneCards; CALCA; -.
DR HGNC; HGNC:1437; CALCA.
DR HPA; ENSG00000110680; Group enriched (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; 1454612at2759; -.
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-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P01258; -.
DR BioGRID-ORCS; 796; 12 hits in 1068 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 123 other tissues.
DR ExpressionAtlas; P01258; baseline and differential.
DR Genevisible; P01258; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; 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:0007190; P:activation of adenylate cyclase activity; IEA:Ensembl.
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:0007568; P:aging; IEA:Ensembl.
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:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
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:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IDA:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl.
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; PTHR10505; 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 88..105
FT /evidence="ECO:0007829|PDB:2JXZ"
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
