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Calcitonin [Cleaved into: Calcitonin; Katacalcin (Calcitonin carboxyl-terminal peptide) (CCP) (PDN-21)]

 CALC_HUMAN              Reviewed;         141 AA.
P01258; B7ZL39; Q13935; Q13937; Q52LX7;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
08-FEB-2011, sequence version 2.
27-SEP-2017, entry version 174.
RecName: Full=Calcitonin;
Contains:
RecName: Full=Calcitonin;
Contains:
RecName: Full=Katacalcin;
AltName: Full=Calcitonin carboxyl-terminal peptide;
Short=CCP;
AltName: Full=PDN-21;
Flags: Precursor;
Name=CALCA; Synonyms=CALC1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-57.
PubMed=6546550; DOI=10.1016/0014-5793(84)80839-X;
le Moullec J.-M., Jullienne A., Chenais J., Lasmoles F., Guliana J.M.,
Milhaud G., Moukhtar M.S.;
"The complete sequence of human preprocalcitonin.";
FEBS Lett. 167:93-97(1984).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-57.
PubMed=3872459; DOI=10.1073/pnas.82.7.1994;
Jonas V., Lin C.R., Kawashima E., Semon D., Swanson L.W.,
Mermod J.-J., Evans R.M., Rosenfeld M.G.;
"Alternative RNA processing events in human calcitonin/calcitonin
gene-related peptide gene expression.";
Proc. Natl. Acad. Sci. U.S.A. 82:1994-1998(1985).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-57.
PubMed=3034287;
Craig R.K., Riley J.H., Edbrooke M.R., Broad P.M., Foord S.M.,
Al-Kazwini S.J., Holman J.J., Marshall I.;
"Expression and function of the human calcitonin/alpha-CGRP gene in
health and disease.";
Biochem. Soc. Symp. 52:91-105(1986).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-57.
PubMed=3485540; DOI=10.1016/0014-5793(86)81187-5;
Riley J.H., Edbrooke M.R., Craig R.K.;
"Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma
cell line reflects aberrant proteolytic processing.";
FEBS Lett. 198:71-79(1986).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT ASP-57.
TISSUE=Thyroid carcinoma;
PubMed=1761559;
Minvielle S., Giscard-Dartevelle S., Cohen R., Taboulet J., Labye F.,
Jullienne A., Rivaille P., Milhaud G., Moukhtar M.S., Lasmoles F.;
"A novel calcitonin carboxyl-terminal peptide produced in medullary
thyroid carcinoma by alternative RNA processing of the
calcitonin/calcitonin gene-related peptide gene.";
J. Biol. Chem. 266:24627-24631(1991).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-2; ASP-57; LYS-67;
ARG-76; THR-123 AND PRO-138.
NIEHS SNPs program;
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16554811; DOI=10.1038/nature04632;
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
Sakaki Y.;
"Human chromosome 11 DNA sequence and analysis including novel gene
identification.";
Nature 440:497-500(2006).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-57.
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
ASP-57.
TISSUE=Placenta;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[10]
NUCLEOTIDE SEQUENCE [MRNA] OF 48-83 (ISOFORM 1), AND VARIANT ASP-57.
PubMed=6148938; DOI=10.1016/0006-291X(84)90278-X;
Nelkin B.D., Rosenfeld K.I., de Bustros A., Leong S.S., Roos B.A.,
Baylin S.B.;
"Structure and expression of a gene encoding human calcitonin and
calcitonin gene related peptide.";
Biochem. Biophys. Res. Commun. 123:648-655(1984).
[11]
NUCLEOTIDE SEQUENCE [MRNA] OF 50-141 (ISOFORM 1), AND VARIANT ASP-57.
PubMed=2408883;
Edbrooke M.R., Parker D., McVey J.H., Riley J.H., Sorenson G.D.,
Pettengill O.S., Craig R.K.;
"Expression of the human calcitonin/CGRP gene in lung and thyroid
carcinoma.";
EMBO J. 4:715-724(1985).
[12]
PROTEIN SEQUENCE OF 85-116, AND AMIDATION AT PRO-116.
PubMed=5760861; DOI=10.1002/hlca.19680510811;
Neher R., Riniker B., Rittel W., Zuber H.;
"Human calcitonin. Structure of calcitonin M and D.";
Helv. Chim. Acta 51:1900-1905(1968).
[13]
STRUCTURE BY NMR OF CALCITONIN.
PubMed=2001366; DOI=10.1021/bi00223a010;
Motta A., Temussi P.A., Wunsch E., Bovermann G.;
"A 1H NMR study of human calcitonin in solution.";
Biochemistry 30:2364-2371(1991).
[14]
CHARACTERIZATION OF KATACALCIN.
PubMed=6132180; DOI=10.1016/S0140-6736(83)91387-9;
Hillyard C.J., Myers C., Abeyasekera G., Stevvensvenson J.C.,
Craig R.K., MacIntyre I.;
"Katacalcin: a new plasma calcium-lowering hormone.";
Lancet 1:846-848(1983).
[15]
SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
Hillman R.T., Green R.E., Brenner S.E.;
"An unappreciated role for RNA surveillance.";
Genome Biol. 5:R8.1-R8.16(2004).
-!- FUNCTION: 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.
-!- FUNCTION: Katacalcin is a potent plasma calcium-lowering peptide.
-!- INTERACTION:
Self; NbExp=3; IntAct=EBI-1018474, EBI-1018474;
Q01814:ATP2B2; NbExp=2; IntAct=EBI-1018474, EBI-1174243;
P23634:ATP2B4; NbExp=2; IntAct=EBI-1018474, EBI-1174388;
-!- SUBCELLULAR LOCATION: Secreted.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=P01258-1; Sequence=Displayed;
Name=2;
IsoId=P01258-2; Sequence=VSP_000709;
Note=May be produced at very low levels due to a premature stop
codon in the mRNA, leading to nonsense-mediated mRNA decay.;
Name=3;
IsoId=P06881-1; Sequence=External;
-!- SIMILARITY: Belongs to the calcitonin family. {ECO:0000305}.
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/calca/";
-!- WEB RESOURCE: Name=Wikipedia; Note=Calcitonin entry;
URL="https://en.wikipedia.org/wiki/Calcitonin";
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EMBL; X00356; CAA25103.1; -; mRNA.
EMBL; M12666; AAA51913.1; -; Genomic_DNA.
EMBL; M12664; AAA51913.1; JOINED; Genomic_DNA.
EMBL; M12665; AAA51913.1; JOINED; Genomic_DNA.
EMBL; M26095; AAA35501.1; -; mRNA.
EMBL; X03662; CAA27299.1; -; mRNA.
EMBL; M64486; AAA58403.1; -; mRNA.
EMBL; DQ080435; AAY68212.1; -; Genomic_DNA.
EMBL; AC090835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471064; EAW68468.1; -; Genomic_DNA.
EMBL; BC069684; AAH69684.1; -; mRNA.
EMBL; BC069704; AAH69704.1; -; mRNA.
EMBL; BC069760; AAH69760.1; -; mRNA.
EMBL; BC069778; AAH69778.1; -; mRNA.
EMBL; BC093753; AAH93753.1; -; mRNA.
EMBL; BC101599; AAI01600.1; -; mRNA.
EMBL; BC143562; AAI43563.1; -; mRNA.
EMBL; K03513; AAA52124.1; -; mRNA.
EMBL; X02330; CAA26189.1; -; mRNA.
CCDS; CCDS7819.1; -. [P01258-1]
PIR; A41716; A41716.
PIR; S07643; TCHU.
RefSeq; NP_001029124.1; NM_001033952.2.
RefSeq; NP_001732.1; NM_001741.2.
RefSeq; XP_016873772.1; XM_017018283.1.
RefSeq; XP_016873773.1; XM_017018284.1.
UniGene; Hs.37058; -.
PDB; 2JXZ; NMR; -; A=85-116.
PDBsum; 2JXZ; -.
ProteinModelPortal; P01258; -.
SMR; P01258; -.
BioGrid; 107247; 11.
IntAct; P01258; 3.
MINT; MINT-2799962; -.
STRING; 9606.ENSP00000331746; -.
iPTMnet; P01258; -.
PhosphoSitePlus; P01258; -.
BioMuta; CYP2R1; -.
DMDM; 322510018; -.
PaxDb; P01258; -.
PeptideAtlas; P01258; -.
PRIDE; P01258; -.
TopDownProteomics; P01258-1; -. [P01258-1]
DNASU; 796; -.
Ensembl; ENST00000331587; ENSP00000331746; ENSG00000110680.
Ensembl; ENST00000396372; ENSP00000379657; ENSG00000110680.
Ensembl; ENST00000469608; ENSP00000420618; ENSG00000110680.
GeneID; 796; -.
KEGG; hsa:796; -.
UCSC; uc001mlv.2; human. [P01258-1]
CTD; 796; -.
DisGeNET; 796; -.
EuPathDB; HostDB:ENSG00000110680.12; -.
GeneCards; CALCA; -.
HGNC; HGNC:1437; CALCA.
MIM; 114130; gene.
neXtProt; NX_P01258; -.
PharmGKB; PA26029; -.
eggNOG; ENOG410IX7S; Eukaryota.
eggNOG; ENOG4111KS6; LUCA.
HOGENOM; HOG000038203; -.
HOVERGEN; HBG031362; -.
InParanoid; P01258; -.
KO; K12332; -.
OrthoDB; EOG091G0RF5; -.
PhylomeDB; P01258; -.
TreeFam; TF333069; -.
Reactome; R-HSA-418555; G alpha (s) signalling events.
Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
Reactome; R-HSA-977225; Amyloid fiber formation.
EvolutionaryTrace; P01258; -.
GeneWiki; Calcitonin; -.
GenomeRNAi; 796; -.
Proteomes; UP000005640; Chromosome 11.
Bgee; ENSG00000110680; -.
CleanEx; HS_CALCA; -.
ExpressionAtlas; P01258; baseline and differential.
Genevisible; P01258; HS.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IEA:Ensembl.
GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
GO; GO:0031716; F:calcitonin receptor binding; IPI:UniProtKB.
GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0007190; P:activation of adenylate cyclase activity; IEA:Ensembl.
GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IEA:Ensembl.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0001984; P:artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure; IEA:Ensembl.
GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
GO; GO:0007566; P:embryo implantation; IDA:UniProtKB.
GO; GO:0007631; P:feeding behavior; IEA:Ensembl.
GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
GO; GO:0002548; P:monocyte chemotaxis; IDA:BHF-UCL.
GO; GO:0045779; P:negative regulation of bone resorption; IDA:UniProtKB.
GO; GO:0031645; P:negative regulation of neurological system process; IEA:Ensembl.
GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
GO; GO:0045986; P:negative regulation of smooth muscle contraction; IEA:Ensembl.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0007218; P:neuropeptide signaling pathway; IEA:Ensembl.
GO; GO:0045762; P:positive regulation of adenylate cyclase activity; IDA:UniProtKB.
GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway; IDA:UniProtKB.
GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl.
GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl.
GO; GO:0009408; P:response to heat; IEA:Ensembl.
GO; GO:0048265; P:response to pain; IEA:Ensembl.
InterPro; IPR021118; Calcitonin.
InterPro; IPR021117; Calcitonin-like.
InterPro; IPR021116; Calcitonin/adrenomedullin.
InterPro; IPR018360; Calcitonin_CS.
InterPro; IPR001693; Calcitonin_peptide-like.
PANTHER; PTHR10505; PTHR10505; 1.
Pfam; PF00214; Calc_CGRP_IAPP; 1.
PRINTS; PR00270; CALCITONINA.
SMART; SM00113; CALCITONIN; 1.
PROSITE; PS00258; CALCITONIN; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Amidation;
Cleavage on pair of basic residues; Complete proteome;
Direct protein sequencing; Disulfide bond; Hormone; Phosphoprotein;
Polymorphism; Reference proteome; Secreted; Signal.
SIGNAL 1 25 {ECO:0000255}.
PROPEP 26 82
/FTId=PRO_0000004050.
PEPTIDE 85 116 Calcitonin. {ECO:0000269|PubMed:5760861}.
/FTId=PRO_0000004051.
PEPTIDE 121 141 Katacalcin.
/FTId=PRO_0000004052.
MOD_RES 43 43 Phosphoserine.
{ECO:0000250|UniProtKB:P01257}.
MOD_RES 116 116 Proline amide.
{ECO:0000269|PubMed:5760861}.
DISULFID 85 91 {ECO:0000269|PubMed:5760861}.
VAR_SEQ 134 141 VSMPQNAN -> NHCPEESL (in isoform 2).
{ECO:0000303|PubMed:1761559}.
/FTId=VSP_000709.
VARIANT 2 2 G -> R (in dbSNP:rs34587547).
{ECO:0000269|Ref.6}.
/FTId=VAR_025271.
VARIANT 57 57 N -> D (in dbSNP:rs5239).
{ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:1761559,
ECO:0000269|PubMed:2408883,
ECO:0000269|PubMed:3034287,
ECO:0000269|PubMed:3485540,
ECO:0000269|PubMed:3872459,
ECO:0000269|PubMed:6148938,
ECO:0000269|PubMed:6546550,
ECO:0000269|Ref.6, ECO:0000269|Ref.8}.
/FTId=VAR_014592.
VARIANT 67 67 E -> K (in dbSNP:rs34164367).
{ECO:0000269|Ref.6}.
/FTId=VAR_025272.
VARIANT 76 76 S -> R (in dbSNP:rs5241).
{ECO:0000269|Ref.6}.
/FTId=VAR_014593.
VARIANT 123 123 S -> T (in dbSNP:rs34414857).
{ECO:0000269|Ref.6}.
/FTId=VAR_025273.
VARIANT 138 138 Q -> P (in dbSNP:rs13306224).
{ECO:0000269|Ref.6}.
/FTId=VAR_025274.
CONFLICT 92 92 M -> I (in Ref. 2; AAA51913).
{ECO:0000305}.
HELIX 88 105 {ECO:0000244|PDB:2JXZ}.
HELIX 109 111 {ECO:0000244|PDB:2JXZ}.
SEQUENCE 141 AA; 15466 MW; C3688905D0EB2502 CRC64;
MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQNYVQ
MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF NKFHTFPQTA IGVGAPGKKR
DMSSDLERDH RPHVSMPQNA N


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