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Protein

Calcitonin

Gene

CALCA

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

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

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

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 Componenti: 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
Complete GO annotation...

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

PRIDEiP01258.

Expressioni

Gene expression databases

BgeeiP01258.
CleanExiHS_CALCA.
ExpressionAtlasiP01258. baseline and differential.
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 – 10518Combined sources
Helixi109 – 1113Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
InParanoidiP01258.
KOiK12332.
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. AlignAdd to basket

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

        10         20         30         40         50
MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL
60 70 80 90 100
LAALVQNYVQ MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF
110 120 130 140
NKFHTFPQTA IGVGAPGKKR DMSSDLERDH RPHVSMPQNA N
Length:141
Mass (Da):15,466
Last modified:February 7, 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:
EMBLi
GenBanki
DDBJi
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.
ENST00000396372; ENSP00000379657; ENSG00000110680.
ENST00000469608; ENSP00000420618; ENSG00000110680.
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

Polymorphism databases

DMDMi322510018.

Proteomic databases

PRIDEiP01258.

Protocols and materials databases

DNASUi796.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi796.
GeneCardsiGC11M014945.
HGNCiHGNC:1437. CALCA.
MIMi114130. gene.
neXtProtiNX_P01258.
PharmGKBiPA26029.
GenAtlasiSearch...

Phylogenomic databases

HOGENOMiHOG000038203.
HOVERGENiHBG031362.
InParanoidiP01258.
KOiK12332.
PhylomeDBiP01258.
TreeFamiTF333069.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP01258.
GeneWikiiCalcitonin.
GenomeRNAii796.
NextBioi3234.
PROiP01258.
SOURCEiSearch...

Gene expression databases

BgeeiP01258.
CleanExiHS_CALCA.
ExpressionAtlasiP01258. baseline and differential.
GenevestigatoriP01258.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1984) [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(1985) [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(1985) [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(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ASP-57.
    Tissue: Thyroid carcinoma.
  6. NIEHS SNPs program
    Submitted (APR-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(2003) [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(1983) [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(1984) [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(1967) [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(1990) [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 20, 1986
Last sequence update: February 7, 2011
Last modified: March 3, 2015
This is version 152 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.