Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcitonin gene-related peptide 1

Gene

CALCA

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

Functioni

CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role. It also elevates platelet cAMP.1 Publication

GO - Molecular functioni

  1. protein complex binding Source: UniProtKB
  2. receptor binding Source: UniProtKB

GO - Biological processi

  1. activation of adenylate cyclase activity Source: UniProtKB
  2. cell-cell signaling Source: ProtInc
  3. cytosolic calcium ion homeostasis Source: UniProtKB
  4. endothelial cell migration Source: UniProtKB
  5. endothelial cell proliferation Source: UniProtKB
  6. G-protein coupled receptor internalization Source: UniProtKB
  7. leukocyte cell-cell adhesion Source: UniProtKB
  8. negative regulation of blood pressure Source: MGI
  9. negative regulation of bone resorption Source: UniProtKB
  10. negative regulation of calcium ion transport into cytosol Source: UniProtKB
  11. negative regulation of osteoclast differentiation Source: UniProtKB
  12. neurological system process involved in regulation of systemic arterial blood pressure Source: MGI
  13. positive regulation of cAMP biosynthetic process Source: UniProtKB
  14. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
  15. positive regulation of interleukin-1 alpha production Source: UniProtKB
  16. positive regulation of interleukin-8 production Source: UniProtKB
  17. positive regulation of macrophage differentiation Source: UniProtKB
  18. positive regulation of vasodilation Source: UniProtKB
  19. protein phosphorylation Source: UniProtKB
  20. receptor internalization Source: UniProtKB
  21. regulation of blood pressure Source: UniProtKB
  22. vasculature development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

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

Protein family/group databases

TCDBi1.C.49.1.2. the cytotoxic amylin (amylin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcitonin gene-related peptide 1
Alternative name(s):
Alpha-type CGRP
Calcitonin gene-related peptide I
Short name:
CGRP-I
Gene namesi
Name:CALCA
Synonyms:CALC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:1437. CALCA.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular region Source: Reactome
  3. extracellular space Source: UniProtKB
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 – 8055PRO_0000004053Add
BLAST
Peptidei83 – 11937Calcitonin gene-related peptide 1PRO_0000004054Add
BLAST
Propeptidei125 – 1284PRO_0000004055

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi84 ↔ 891 Publication
Modified residuei119 – 1191Phenylalanine amide1 Publication

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP06881.
PRIDEiP06881.

Expressioni

Gene expression databases

BgeeiP06881.
CleanExiHS_CALCA.
ExpressionAtlasiP06881. baseline and differential.
GenevestigatoriP06881.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CALCRLQ166022EBI-962928,EBI-962878

Protein-protein interaction databases

BioGridi107247. 4 interactions.
IntActiP06881. 3 interactions.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LS7model-A1-125[»]
ProteinModelPortaliP06881.
SMRiP06881. Positions 83-119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the calcitonin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40787.
HOGENOMiHOG000038203.
HOVERGENiHBG031362.
KOiK12332.
OMAiRAMKEFM.
OrthoDBiEOG7PCJK5.

Family and domain databases

InterProiIPR018360. Calcitonin_CS.
IPR015476. Calcitonin_gene-rel_peptide.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]
PANTHERiPTHR10505. PTHR10505. 1 hit.
PfamiPF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]
PRINTSiPR00817. CALCITONINB.
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 3 (identifier: P06881-1) [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 EREGSRIIAQ KRACDTATCV THRLAGLLSR
110 120
SGGVVKNNFV PTNVGSKAFG RRRRDLQA
Length:128
Mass (Da):13,898
Last modified:October 5, 2010 - v3
Checksum:i2AA1A9AC3060D9B6
GO
Isoform 1 (identifier: P01258-1) [UniParc]FASTAAdd to basket

The sequence of this isoform can be found in the external entry P01258.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:141
Mass (Da):15,466
GO
Isoform 2 (identifier: P01258-2) [UniParc]FASTAAdd to basket

The sequence of this isoform can be found in the external entry P01258.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Length:141
Mass (Da):15,534
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571N → D.3 Publications
Corresponds to variant rs5239 [ dbSNP | Ensembl ].
VAR_048584

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12667, M12664, M12665 Genomic DNA. Translation: AAA51914.1.
X15943 Genomic DNA. Translation: CAA34070.1.
AC090835 Genomic DNA. No translation available.
K03512 mRNA. Translation: AAA52011.1.
X02330 mRNA. Translation: CAA26190.1.
M28637 Genomic DNA. Translation: AAA52012.1.
M26094 Genomic DNA. Translation: AAA51912.1.
CCDSiCCDS31432.1. [P06881-1]
PIRiS07644. TCHUR.
RefSeqiNP_001029125.1. NM_001033953.2.
XP_005253191.2. XM_005253134.2.
UniGeneiHs.37058.

Genome annotation databases

EnsembliENST00000361010; ENSP00000354286; ENSG00000110680.
ENST00000486207; ENSP00000417833; ENSG00000110680.
GeneIDi796.
KEGGihsa:796.
UCSCiuc001mlt.2. human. [P06881-1]

Polymorphism databases

DMDMi308153625.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12667, M12664, M12665 Genomic DNA. Translation: AAA51914.1.
X15943 Genomic DNA. Translation: CAA34070.1.
AC090835 Genomic DNA. No translation available.
K03512 mRNA. Translation: AAA52011.1.
X02330 mRNA. Translation: CAA26190.1.
M28637 Genomic DNA. Translation: AAA52012.1.
M26094 Genomic DNA. Translation: AAA51912.1.
CCDSiCCDS31432.1. [P06881-1]
PIRiS07644. TCHUR.
RefSeqiNP_001029125.1. NM_001033953.2.
XP_005253191.2. XM_005253134.2.
UniGeneiHs.37058.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LS7model-A1-125[»]
ProteinModelPortaliP06881.
SMRiP06881. Positions 83-119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107247. 4 interactions.
IntActiP06881. 3 interactions.

Chemistry

BindingDBiP06881.
ChEMBLiCHEMBL5293.

Protein family/group databases

TCDBi1.C.49.1.2. the cytotoxic amylin (amylin) family.

Polymorphism databases

DMDMi308153625.

Proteomic databases

PaxDbiP06881.
PRIDEiP06881.

Protocols and materials databases

DNASUi796.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361010; ENSP00000354286; ENSG00000110680.
ENST00000486207; ENSP00000417833; ENSG00000110680.
GeneIDi796.
KEGGihsa:796.
UCSCiuc001mlt.2. human. [P06881-1]

Organism-specific databases

CTDi796.
GeneCardsiGC11M014945.
HGNCiHGNC:1437. CALCA.
MIMi114130. gene.
neXtProtiNX_P06881.
PharmGKBiPA26029.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40787.
HOGENOMiHOG000038203.
HOVERGENiHBG031362.
KOiK12332.
OMAiRAMKEFM.
OrthoDBiEOG7PCJK5.

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii796.
NextBioi3234.
PROiP06881.
SOURCEiSearch...

Gene expression databases

BgeeiP06881.
CleanExiHS_CALCA.
ExpressionAtlasiP06881. baseline and differential.
GenevestigatoriP06881.

Family and domain databases

InterProiIPR018360. Calcitonin_CS.
IPR015476. Calcitonin_gene-rel_peptide.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]
PANTHERiPTHR10505. PTHR10505. 1 hit.
PfamiPF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]
PRINTSiPR00817. CALCITONINB.
SMARTiSM00113. CALCITONIN. 1 hit.
[Graphical view]
PROSITEiPS00258. CALCITONIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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.
  2. "Structure and methylation of the human calcitonin/alpha-CGRP gene."
    Broad P.M., Symes A.J., Thakker R.V., Craig R.K.
    Nucleic Acids Res. 17:6999-7011(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-57.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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 48-119, VARIANT ASP-57.
  5. "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 76-128.
  6. "Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma."
    Steenbergh P.H., Hoppener J.W., Zandberg J., de Ven W.J., Jansz H.S., Lips C.J.
    J. Clin. Endocrinol. Metab. 59:358-360(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-128.
    Tissue: Thyroid carcinoma.
  7. "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 [GENOMIC DNA] OF 77-128.
  8. "Isolation and characterization of human calcitonin gene-related peptide."
    Morris H.R., Panico M., Etienne T., Tippins J., Girgis S.I., McIntyre I.
    Nature 308:746-748(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 83-119, AMIDATION AT PHE-119, DISULFIDE BOND.
  9. "Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord."
    Petermann J.B., Born W., Chang J.Y., Fischer J.A.
    J. Biol. Chem. 262:542-545(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 83-117.
  10. "Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma."
    Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Matsuo H., Eto T.
    Biochem. Biophys. Res. Commun. 185:134-141(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 83-108, FUNCTION.
    Tissue: Pheochromocytoma.
  11. "Solution structure of human calcitonin gene-related peptide by 1H NMR and distance geometry with restrained molecular dynamics."
    Breeze A.L., Harvey T.S., Bazzo R., Campbell I.D.
    Biochemistry 30:575-582(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF CGRP.
  12. "Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin."
    Hubbard J.A.M., Martin S.R., Chaplin L.C., Bose C., Kelly S.M., Price N.C.
    Biochem. J. 275:785-788(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF CGRP.

Entry informationi

Entry nameiCALCA_HUMAN
AccessioniPrimary (citable) accession number: P06881
Secondary accession number(s): Q93048, Q9UCP0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 5, 2010
Last modified: March 4, 2015
This is version 154 of the entry and version 3 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.