P01258 (CALC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcitonin

Cleaved into the following 2 chains:

1. Calcitonin
2. Katacalcin
   Alternative name(s):
   Calcitonin carboxyl-terminal peptide
   Short name=CCP
   PDN-21

Gene names

Name:	CALCA
Synonyms:	CALC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	141 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Katacalcin is a potent plasma calcium-lowering peptide.
Subcellular location	Secreted.
Sequence similarities	Belongs to the calcitonin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of protein kinase activity Inferred from direct assay PubMed 17983652. Source: UniProtKB adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara detection of temperature stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from direct assay PubMed 8078488. Source: UniProtKB embryo implantation Inferred from direct assay PubMed 17983652. Source: UniProtKB feeding behavior Inferred from electronic annotation. Source: Compara inflammatory response Inferred from electronic annotation. Source: Compara monocyte chemotaxis Inferred from direct assay PubMed 15248232. Source: BHF-UCL negative regulation of bone resorption Inferred from direct assay PubMed 17241109. Source: UniProtKB negative regulation of neurological system process Inferred from electronic annotation. Source: Compara negative regulation of ossification Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle contraction Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 11014233. Source: UniProtKB neuropeptide signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of adenylate cyclase activity Inferred from direct assay PubMed 11014233PubMed 8078488. Source: UniProtKB positive regulation of ossification Inferred from electronic annotation. Source: Compara regulation of heart rate Inferred from electronic annotation. Source: Compara regulation of inflammatory response Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to pain Inferred from electronic annotation. Source: Compara vasodilation of artery involved in baroreceptor response to increased systemic arterial blood pressure Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 18057382. Source: UniProtKB neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara terminal bouton Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALCR	P79222-1	1	EBI-1018474,EBI-1188415	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P01258-1)

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.

Isoform 2 (identifier: P01258-2)

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.

Isoform 3 (identifier: P06881-1)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Propeptide

26 – 82

57

PRO_0000004050

Peptide

85 – 116

32

Calcitonin Ref.12

PRO_0000004051

Peptide

121 – 141

21

Katacalcin

PRO_0000004052

Amino acid modifications

Modified residue

116

1

Proline amide Ref.12

Disulfide bond

85 ↔ 91

Ref.12

Natural variations

Alternative sequence

134 – 141

8

VSMPQNAN → NHCPEESL in isoform 2.

VSP_000709

Natural variant

2

1

G → R. Ref.6
Corresponds to variant rs34587547 [ dbSNP | Ensembl ].

VAR_025271

Natural variant

57

1

N → D. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11
Corresponds to variant rs5239 [ dbSNP | Ensembl ].

VAR_014592

Natural variant

67

1

E → K. Ref.6
Corresponds to variant rs34164367 [ dbSNP | Ensembl ].

VAR_025272

Natural variant

76

1

S → R. Ref.6
Corresponds to variant rs5241 [ dbSNP | Ensembl ].

VAR_014593

Natural variant

123

1

S → T. Ref.6
Corresponds to variant rs34414857 [ dbSNP | Ensembl ].

VAR_025273

Natural variant

138

1

Q → P. Ref.6
Corresponds to variant rs13306224 [ dbSNP | Ensembl ].

VAR_025274

Experimental info

Sequence conflict

92

1

M → I in AAA51913. Ref.2

Secondary structure

1

.

.

.

.

.

141

Helix Strand Turn

Details...

Helix

88 – 105

18

Helix

109 – 111

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: C3688905D0EB2502	FASTA	141	15,466
	10 20 30 40 50 60 MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQNYVQ 70 80 90 100 110 120 MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF NKFHTFPQTA IGVGAPGKKR 130 140 DMSSDLERDH RPHVSMPQNA N
	Isoform 2 [UniParc]. Checksum: 1810E64810E31144	FASTA	141	15,534
	10 20 30 40 50 60 MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQNYVQ 70 80 90 100 110 120 MKASELEQEQ EREGSSLDSP RSKRCGNLST CMLGTYTQDF NKFHTFPQTA IGVGAPGKKR 130 140 DMSSDLERDH RPHNHCPEES L
	Isoform 3 [UniParc]. See P06881.		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete sequence of human preprocalcitonin." le Moullec J.-M., Jullienne A., Chenais J., Lasmoles F., Guliana J.M., Milhaud G., Moukhtar M.S. FEBS Lett. 167:93-97(1984) [PubMed] [Europe PMC] [Abstract] 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]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." 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. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 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]	"Katacalcin: a new plasma calcium-lowering hormone." Hillyard C.J., Myers C., Abeyasekera G., Stevvensvenson J.C., Craig R.K., MacIntyre I. Lancet 1:846-848(1983) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF KATACALCIN.
[15]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Calcitonin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00000914.
IPI00215863.

PIR

A41716.
TCHU. S07643.

RefSeq

NP_001029124.1. NM_001033952.2.
NP_001732.1. NM_001741.2.

UniGene

Hs.37058.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JXZ	NMR	-	A	85-114	[»]

ProteinModelPortal

P01258.

SMR

P01258. Positions 85-116.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01258. 1 interaction.

MINT

MINT-2799962.

STRING

9606.ENSP00000331746.

Polymorphism databases

DMDM

115478.

Proteomic databases

PRIDE

P01258.

Protocols and materials databases

DNASU

796.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331587; ENSP00000331746; ENSG00000110680.
ENST00000359642; ENSP00000352663; ENSG00000110680.
ENST00000396372; ENSP00000379657; ENSG00000110680.
ENST00000469608; ENSP00000420618; ENSG00000110680.
ENST00000570903; ENSP00000460716; ENSG00000262933.
ENST00000571711; ENSP00000459971; ENSG00000262933.
ENST00000574146; ENSP00000459562; ENSG00000262933.

GeneID

796.

KEGG

hsa:796.

UCSC

uc001mlv.1. human.

Organism-specific databases

CTD

796.

GeneCards

GC11M014945.

HGNC

HGNC:1437. CALCA.

HPA

CAB000005.

MIM

114130. gene.

neXtProt

NX_P01258.

PharmGKB

PA26029.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000038203.

HOVERGEN

HBG031362.

KO

K12332.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpress

P01258.

Bgee

P01258.

CleanEx

HS_CALCA.

Genevestigator

P01258.

GermOnline

ENSG00000110680. Homo sapiens.

Family and domain databases

InterPro

IPR018360. Calcitonin_CS.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
IPR021118. Procalcitonin_A-typ.
[Graphical view]

PANTHER

PTHR10505. PTHR10505. 1 hit.
PTHR10505:SF3. PTHR10505:SF3. 1 hit.

Pfam

PF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]

PRINTS

PR00270. CALCITONINA.

SMART

SM00113. CALCITONIN. 1 hit.
[Graphical view]

PROSITE

PS00258. CALCITONIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01258.

GenomeRNAi

796.

NextBio

3234.

SOURCE

Search...

Entry information

Entry name

CALC_HUMAN

Accession

Primary (citable) accession number: P01258
Secondary accession number(s): B7ZL39 , Q13935, Q13937, Q52LX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 8, 2011
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.