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P06881

- CALCA_HUMAN

UniProt

P06881 - CALCA_HUMAN

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Protein

Calcitonin gene-related peptide 1

Gene
CALCA, CALC1
Organism
Homo sapiens (Human)
Status
Reviewed - 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 binding Source: UniProtKB
  2. protein complex binding Source: UniProtKB
  3. 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 – 2525 Reviewed predictionAdd
BLAST
Propeptidei26 – 8055PRO_0000004053Add
BLAST
Peptidei83 – 11937Calcitonin gene-related peptide 11 PublicationPRO_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

ArrayExpressiP06881.
BgeeiP06881.
CleanExiHS_CALCA.
GenevestigatoriP06881.

Organism-specific databases

HPAiCAB000005.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi107247. 4 interactions.
IntActiP06881. 3 interactions.

Structurei

Secondary structure

1
128
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 1917
Helixi22 – 3211
Helixi41 – 5414
Helixi61 – 7212
Helixi75 – 817
Turni82 – 854
Helixi94 – 996
Helixi101 – 1055
Beta strandi113 – 1153
Helixi116 – 1205

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LS7model-A1-125[»]
ProteinModelPortaliP06881.
SMRiP06881. Positions 83-119.

Family & Domainsi

Sequence similaritiesi

Belongs to the calcitonin family.

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. Align

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

MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL    50
LAALVQNYVQ MKASELEQEQ EREGSRIIAQ KRACDTATCV THRLAGLLSR 100
SGGVVKNNFV PTNVGSKAFG RRRRDLQA 128
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:
EMBL
GenBank
DDBJ
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. [P06881-1]
ENST00000486207; ENSP00000417833; ENSG00000110680. [P06881-1]
ENST00000570728; ENSP00000461551; ENSG00000262933.
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS31432.1. [P06881-1 ]
PIRi S07644. TCHUR.
RefSeqi NP_001029125.1. NM_001033953.2.
XP_005253191.2. XM_005253134.2.
UniGenei Hs.37058.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LS7 model - A 1-125 [» ]
ProteinModelPortali P06881.
SMRi P06881. Positions 83-119.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107247. 4 interactions.
IntActi P06881. 3 interactions.

Chemistry

BindingDBi P06881.
ChEMBLi CHEMBL5293.
DrugBanki DB00692. Phentolamine.

Protein family/group databases

TCDBi 1.C.49.1.2. the cytotoxic amylin (amylin) family.

Polymorphism databases

DMDMi 308153625.

Proteomic databases

PaxDbi P06881.
PRIDEi P06881.

Protocols and materials databases

DNASUi 796.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000361010 ; ENSP00000354286 ; ENSG00000110680 . [P06881-1 ]
ENST00000486207 ; ENSP00000417833 ; ENSG00000110680 . [P06881-1 ]
ENST00000570728 ; ENSP00000461551 ; ENSG00000262933 .
GeneIDi 796.
KEGGi hsa:796.
UCSCi uc001mlt.2. human. [P06881-1 ]

Organism-specific databases

CTDi 796.
GeneCardsi GC11M014945.
HGNCi HGNC:1437. CALCA.
HPAi CAB000005.
MIMi 114130. gene.
neXtProti NX_P06881.
PharmGKBi PA26029.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40787.
HOGENOMi HOG000038203.
HOVERGENi HBG031362.
KOi K12332.
OMAi RAMKEFM.
OrthoDBi EOG7PCJK5.

Enzyme and pathway databases

Reactomei REACT_18290. Calcitonin-like ligand receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GenomeRNAii 796.
NextBioi 3234.
PROi P06881.
SOURCEi Search...

Gene expression databases

ArrayExpressi P06881.
Bgeei P06881.
CleanExi HS_CALCA.
Genevestigatori P06881.

Family and domain databases

InterProi IPR018360. Calcitonin_CS.
IPR015476. Calcitonin_gene-rel_peptide.
IPR001693. Calcitonin_peptide-like.
IPR021117. Procalcitonin-like.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view ]
PANTHERi PTHR10505. PTHR10505. 1 hit.
Pfami PF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view ]
PRINTSi PR00817. CALCITONINB.
SMARTi SM00113. CALCITONIN. 1 hit.
[Graphical view ]
PROSITEi PS00258. CALCITONIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 149 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

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