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P06881 (CALCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcitonin gene-related peptide 1
Alternative name(s):
Alpha-type CGRP
Calcitonin gene-related peptide I
Short name=CGRP-I
Gene names
Name:CALCA
Synonyms:CALC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length128 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10

Subcellular location

Secreted.

Sequence similarities

Belongs to the calcitonin family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
Disulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor internalization

Inferred from direct assay PubMed 10882736. Source: UniProtKB

activation of adenylate cyclase activity

Inferred from direct assay PubMed 10822112PubMed 16014619. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.5. Source: ProtInc

cytosolic calcium ion homeostasis

Inferred from direct assay PubMed 9685362. Source: UniProtKB

endothelial cell migration

Inferred from direct assay PubMed 17267696. Source: UniProtKB

endothelial cell proliferation

Inferred from direct assay PubMed 17267696. Source: UniProtKB

leukocyte cell-cell adhesion

Inferred from direct assay PubMed 1326102. Source: UniProtKB

negative regulation of blood pressure

Inferred from direct assay PubMed 10642343. Source: MGI

negative regulation of bone resorption

Inferred from direct assay PubMed 10822112. Source: UniProtKB

negative regulation of calcium ion transport into cytosol

Inferred from direct assay PubMed 16014619. Source: UniProtKB

negative regulation of osteoclast differentiation

Inferred from direct assay PubMed 10822112. Source: UniProtKB

neurological system process involved in regulation of systemic arterial blood pressure

Inferred from direct assay PubMed 10642343. Source: MGI

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 10882736PubMed 14722252. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway

Inferred from direct assay PubMed 9685362. Source: UniProtKB

positive regulation of interleukin-1 alpha production

Inferred from direct assay PubMed 16904178. Source: UniProtKB

positive regulation of interleukin-8 production

Inferred from direct assay PubMed 16904178. Source: UniProtKB

positive regulation of macrophage differentiation

Inferred from direct assay PubMed 10822112. Source: UniProtKB

positive regulation of vasodilation

Inferred from direct assay PubMed 3266556. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 20596610. Source: UniProtKB

receptor internalization

Inferred from direct assay PubMed 10882736. Source: UniProtKB

regulation of blood pressure

Non-traceable author statement Ref.10. Source: UniProtKB

vasculature development

Inferred from direct assay PubMed 17267696. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17267696. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionprotein complex binding

Inferred from direct assay PubMed 14722252. Source: UniProtKB

receptor binding

Inferred from direct assay PubMed 16014619. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CALCRLQ166022EBI-962928,EBI-962878

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 3 (identifier: P06881-1)

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 1 (identifier: P01258-1)

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.
Isoform 2 (identifier: P01258-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 8055
PRO_0000004053
Peptide83 – 11937Calcitonin gene-related peptide 1 Ref.8
PRO_0000004054
Propeptide125 – 1284
PRO_0000004055

Amino acid modifications

Modified residue1191Phenylalanine amide
Disulfide bond84 ↔ 89

Natural variations

Natural variant571N → D. Ref.1 Ref.2 Ref.4
Corresponds to variant rs5239 [ dbSNP | Ensembl ].
VAR_048584

Secondary structure

................... 128
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 3 [UniParc].

Last modified October 5, 2010. Version 3.
Checksum: 2AA1A9AC3060D9B6

FASTA12813,898
        10         20         30         40         50         60 
MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQNYVQ 

        70         80         90        100        110        120 
MKASELEQEQ EREGSRIIAQ KRACDTATCV THRLAGLLSR SGGVVKNNFV PTNVGSKAFG 


RRRRDLQA 

« Hide

Isoform 1 [UniParc].

See P01258.

Isoform 2 [UniParc].

See P01258.

References

« Hide 'large scale' references
[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]"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. expand/collapse author list , 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].
[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.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRTCHUR. S07644.
RefSeqNP_001029125.1. NM_001033953.2.
XP_005253191.2. XM_005253134.2.
UniGeneHs.37058.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LS7model-A1-125[»]
ProteinModelPortalP06881.
SMRP06881. Positions 83-119.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107247. 4 interactions.
IntActP06881. 3 interactions.

Chemistry

BindingDBP06881.
ChEMBLCHEMBL5293.
DrugBankDB00692. Phentolamine.

Protein family/group databases

TCDB1.C.49.1.2. the cytotoxic amylin (amylin) family.

Polymorphism databases

DMDM308153625.

Proteomic databases

PaxDbP06881.
PRIDEP06881.

Protocols and materials databases

DNASU796.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361010; ENSP00000354286; ENSG00000110680. [P06881-1]
ENST00000486207; ENSP00000417833; ENSG00000110680. [P06881-1]
ENST00000570728; ENSP00000461551; ENSG00000262933.
GeneID796.
KEGGhsa:796.
UCSCuc001mlt.2. human. [P06881-1]

Organism-specific databases

CTD796.
GeneCardsGC11M014945.
HGNCHGNC:1437. CALCA.
HPACAB000005.
MIM114130. gene.
neXtProtNX_P06881.
PharmGKBPA26029.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40787.
HOGENOMHOG000038203.
HOVERGENHBG031362.
KOK12332.
OMALERDHCP.
OrthoDBEOG7PCJK5.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP06881.
BgeeP06881.
CleanExHS_CALCA.
GenevestigatorP06881.

Family and domain databases

InterProIPR018360. Calcitonin_CS.
IPR015476. Calcitonin_gene-rel_peptide.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]
PANTHERPTHR10505. PTHR10505. 1 hit.
PTHR10505:SF2. PTHR10505:SF2. 1 hit.
PfamPF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]
PRINTSPR00817. CALCITONINB.
SMARTSM00113. CALCITONIN. 1 hit.
[Graphical view]
PROSITEPS00258. CALCITONIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi796.
NextBio3234.
PROP06881.
SOURCESearch...

Entry information

Entry nameCALCA_HUMAN
AccessionPrimary (citable) accession number: P06881
Secondary accession number(s): Q93048, Q9UCP0
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM