CALCA_HUMAN
ID CALCA_HUMAN Reviewed; 128 AA.
AC P06881; Q93048; Q9UCP0;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Calcitonin gene-related peptide 1;
DE AltName: Full=Alpha-type CGRP;
DE AltName: Full=Calcitonin gene-related peptide I;
DE Short=CGRP-I;
DE Flags: Precursor;
GN Name=CALCA; Synonyms=CALC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3872459; DOI=10.1073/pnas.82.7.1994;
RA Jonas V., Lin C.R., Kawashima E., Semon D., Swanson L.W., Mermod J.-J.,
RA Evans R.M., Rosenfeld M.G.;
RT "Alternative RNA processing events in human calcitonin/calcitonin gene-
RT related peptide gene expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:1994-1998(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2571128; DOI=10.1093/nar/17.17.6999;
RA Broad P.M., Symes A.J., Thakker R.V., Craig R.K.;
RT "Structure and methylation of the human calcitonin/alpha-CGRP gene.";
RL Nucleic Acids Res. 17:6999-7011(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-119.
RX PubMed=6148938; DOI=10.1016/0006-291x(84)90278-x;
RA Nelkin B.D., Rosenfeld K.I., de Bustros A., Leong S.S., Roos B.A.,
RA Baylin S.B.;
RT "Structure and expression of a gene encoding human calcitonin and
RT calcitonin gene related peptide.";
RL Biochem. Biophys. Res. Commun. 123:648-655(1984).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-128.
RX PubMed=2408883; DOI=10.1002/j.1460-2075.1985.tb03688.x;
RA Edbrooke M.R., Parker D., McVey J.H., Riley J.H., Sorenson G.D.,
RA Pettengill O.S., Craig R.K.;
RT "Expression of the human calcitonin/CGRP gene in lung and thyroid
RT carcinoma.";
RL EMBO J. 4:715-724(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-128.
RC TISSUE=Thyroid carcinoma;
RX PubMed=6610687; DOI=10.1210/jcem-59-2-358;
RA Steenbergh P.H., Hoppener J.W., Zandberg J., de Ven W.J., Jansz H.S.,
RA Lips C.J.;
RT "Calcitonin gene related peptide coding sequence is conserved in the human
RT genome and is expressed in medullary thyroid carcinoma.";
RL J. Clin. Endocrinol. Metab. 59:358-360(1984).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 77-128.
RX PubMed=3034287;
RA Craig R.K., Riley J.H., Edbrooke M.R., Broad P.M., Foord S.M.,
RA Al-Kazwini S.J., Holman J.J., Marshall I.;
RT "Expression and function of the human calcitonin/alpha-CGRP gene in health
RT and disease.";
RL Biochem. Soc. Symp. 52:91-105(1986).
RN [8]
RP PROTEIN SEQUENCE OF 83-119, AMIDATION AT PHE-119, AND DISULFIDE BOND.
RX PubMed=6609312; DOI=10.1038/308746a0;
RA Morris H.R., Panico M., Etienne T., Tippins J., Girgis S.I., McIntyre I.;
RT "Isolation and characterization of human calcitonin gene-related peptide.";
RL Nature 308:746-748(1984).
RN [9]
RP PROTEIN SEQUENCE OF 83-117.
RX PubMed=3492492; DOI=10.1016/s0021-9258(19)75816-5;
RA Petermann J.B., Born W., Chang J.Y., Fischer J.A.;
RT "Identification in the human central nervous system, pituitary, and thyroid
RT of a novel calcitonin gene-related peptide, and partial amino acid sequence
RT in the spinal cord.";
RL J. Biol. Chem. 262:542-545(1987).
RN [10]
RP PROTEIN SEQUENCE OF 83-108, AND FUNCTION.
RC TISSUE=Pheochromocytoma;
RX PubMed=1318039; DOI=10.1016/s0006-291x(05)80966-0;
RA Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Matsuo H., Eto T.;
RT "Isolation and characterization of peptides which act on rat platelets,
RT from a pheochromocytoma.";
RL Biochem. Biophys. Res. Commun. 185:134-141(1992).
RN [11]
RP STRUCTURE BY NMR OF CGRP.
RX PubMed=1988044; DOI=10.1021/bi00216a036;
RA Breeze A.L., Harvey T.S., Bazzo R., Campbell I.D.;
RT "Solution structure of human calcitonin gene-related peptide by 1H NMR and
RT distance geometry with restrained molecular dynamics.";
RL Biochemistry 30:575-582(1991).
RN [12]
RP STRUCTURE BY NMR OF CGRP.
RX PubMed=2039456; DOI=10.1042/bj2750785;
RA Hubbard J.A.M., Martin S.R., Chaplin L.C., Bose C., Kelly S.M., Price N.C.;
RT "Solution structures of calcitonin-gene-related-peptide analogues of
RT calcitonin-gene-related peptide and amylin.";
RL Biochem. J. 275:785-788(1991).
CC -!- FUNCTION: CGRP induces vasodilation. It dilates a variety of vessels
CC including the coronary, cerebral and systemic vasculature. Its
CC abundance in the CNS also points toward a neurotransmitter or
CC neuromodulator role. It also elevates platelet cAMP.
CC {ECO:0000269|PubMed:1318039}.
CC -!- INTERACTION:
CC P06881; Q16602: CALCRL; NbExp=5; IntAct=EBI-962928, EBI-962878;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=P06881-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P01258-1; Sequence=External;
CC Name=2;
CC IsoId=P01258-2; Sequence=External;
CC -!- SIMILARITY: Belongs to the calcitonin family. {ECO:0000305}.
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DR EMBL; M12667; AAA51914.1; -; Genomic_DNA.
DR EMBL; M12664; AAA51914.1; JOINED; Genomic_DNA.
DR EMBL; M12665; AAA51914.1; JOINED; Genomic_DNA.
DR EMBL; X15943; CAA34070.1; -; Genomic_DNA.
DR EMBL; AC090835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; K03512; AAA52011.1; -; mRNA.
DR EMBL; X02330; CAA26190.1; -; mRNA.
DR EMBL; M28637; AAA52012.1; -; Genomic_DNA.
DR EMBL; M26094; AAA51912.1; -; Genomic_DNA.
DR CCDS; CCDS31432.1; -. [P06881-1]
DR PIR; S07644; TCHUR.
DR RefSeq; NP_001029125.1; NM_001033953.2. [P06881-1]
DR PDB; 6E3Y; EM; 3.30 A; P=83-119.
DR PDB; 7KNU; EM; 3.49 A; P=83-119.
DR PDBsum; 6E3Y; -.
DR PDBsum; 7KNU; -.
DR AlphaFoldDB; P06881; -.
DR BMRB; P06881; -.
DR SMR; P06881; -.
DR BioGRID; 107247; 18.
DR IntAct; P06881; 7.
DR BindingDB; P06881; -.
DR ChEMBL; CHEMBL5293; -.
DR DrugBank; DB14040; Eptinezumab.
DR DrugBank; DB14041; Fremanezumab.
DR DrugBank; DB14042; Galcanezumab.
DR DrugBank; DB04869; Olcegepant.
DR DrugBank; DB12228; Telcagepant.
DR DrugCentral; P06881; -.
DR TCDB; 1.C.49.1.2; the cytotoxic amylin (amylin) family.
DR iPTMnet; P06881; -.
DR BioMuta; CALCA; -.
DR DMDM; 308153625; -.
DR jPOST; P06881; -.
DR MassIVE; P06881; -.
DR PeptideAtlas; P06881; -.
DR PRIDE; P06881; -.
DR ProteomicsDB; 51940; -. [P06881-1]
DR ABCD; P06881; 3 sequenced antibodies.
DR Antibodypedia; 3493; 1836 antibodies from 46 providers.
DR DNASU; 796; -.
DR Ensembl; ENST00000361010.7; ENSP00000354286.3; ENSG00000110680.13. [P06881-1]
DR Ensembl; ENST00000486207.5; ENSP00000417833.1; ENSG00000110680.13. [P06881-1]
DR GeneID; 796; -.
DR UCSC; uc001mlt.2; human. [P06881-1]
DR CTD; 796; -.
DR DisGeNET; 796; -.
DR GeneCards; CALCA; -.
DR HGNC; HGNC:1437; CALCA.
DR HPA; ENSG00000110680; Group enriched (parathyroid gland, thyroid gland).
DR MIM; 114130; gene.
DR neXtProt; NX_P06881; -.
DR OpenTargets; ENSG00000110680; -.
DR PharmGKB; PA26029; -.
DR VEuPathDB; HostDB:ENSG00000110680; -.
DR GeneTree; ENSGT00940000162876; -.
DR HOGENOM; CLU_122444_1_0_1; -.
DR OMA; QMKASAG; -.
DR PathwayCommons; P06881; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P06881; -.
DR BioGRID-ORCS; 796; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; CALCA; human.
DR GenomeRNAi; 796; -.
DR Pharos; P06881; Tclin.
DR Proteomes; UP000005640; Chromosome 11.
DR Bgee; ENSG00000110680; Expressed in dorsal root ganglion and 123 other tissues.
DR ExpressionAtlas; P06881; baseline and differential.
DR Genevisible; P06881; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0097647; P:amylin receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:1990408; P:calcitonin gene-related peptide receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; IDA:MGI.
DR GO; GO:0045779; P:negative regulation of bone resorption; IDA:UniProtKB.
DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IDA:UniProtKB.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB.
DR GO; GO:0001976; P:nervous system process involved in regulation of systemic arterial blood pressure; IDA:MGI.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IDA:UniProtKB.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:0001878; P:response to yeast; IDA:UniProtKB.
DR GO; GO:0001944; P:vasculature development; IDA:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IDA:UniProtKB.
DR InterPro; IPR021117; Calcitonin-like.
DR InterPro; IPR021116; Calcitonin/adrenomedullin.
DR InterPro; IPR018360; Calcitonin_CS.
DR InterPro; IPR015476; Calcitonin_gene-rel_peptide.
DR InterPro; IPR001693; Calcitonin_peptide-like.
DR PANTHER; PTHR10505; PTHR10505; 1.
DR Pfam; PF00214; Calc_CGRP_IAPP; 1.
DR PRINTS; PR00817; CALCITONINB.
DR SMART; SM00113; CALCITONIN; 1.
DR PROSITE; PS00258; CALCITONIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amidation;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..80
FT /id="PRO_0000004053"
FT PEPTIDE 83..119
FT /note="Calcitonin gene-related peptide 1"
FT /id="PRO_0000004054"
FT PROPEP 125..128
FT /id="PRO_0000004055"
FT MOD_RES 119
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:6609312"
FT DISULFID 84..89
FT /evidence="ECO:0000269|PubMed:6609312"
FT VARIANT 57
FT /note="D -> N (in dbSNP:rs5239)"
FT /id="VAR_048584"
FT HELIX 90..101
FT /evidence="ECO:0007829|PDB:6E3Y"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:6E3Y"
SQ SEQUENCE 128 AA; 13899 MW; A003A1069260D9B8 CRC64;
MGFQKFSPFL ALSILVLLQA GSLHAAPFRS ALESSPADPA TLSEDEARLL LAALVQDYVQ
MKASELEQEQ EREGSRIIAQ KRACDTATCV THRLAGLLSR SGGVVKNNFV PTNVGSKAFG
RRRRDLQA
