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P06881

- CALCA_HUMAN

UniProt

P06881 - CALCA_HUMAN

Protein

Calcitonin gene-related peptide 1

Gene

CALCA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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

    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

    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.
    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. 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]
    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 ]
    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

    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: October 1, 2014
    This is version 150 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