CMGA_MOUSE
ID CMGA_MOUSE Reviewed; 463 AA.
AC P26339;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Chromogranin-A;
DE Short=CgA;
DE Contains:
DE RecName: Full=Pancreastatin;
DE Contains:
DE RecName: Full=Beta-granin;
DE Contains:
DE RecName: Full=WE-14;
DE Contains:
DE RecName: Full=Catestatin;
DE Contains:
DE RecName: Full=GE-25;
DE Contains:
DE RecName: Full=Serpinin-RRG;
DE Contains:
DE RecName: Full=Serpinin {ECO:0000303|PubMed:21436258, ECO:0000303|PubMed:21537909};
DE AltName: Full=AL26 {ECO:0000303|PubMed:21436258};
DE Contains:
DE RecName: Full=p-Glu serpinin precursor {ECO:0000303|PubMed:21537909};
DE Flags: Precursor;
GN Name=Chga;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2071596; DOI=10.1016/s0021-9258(18)98814-9;
RA Wu H.J., Rozansky D.J., Parmer R.J., Gill B.M., O'Connor D.T.;
RT "Structure and function of the chromogranin A gene. Clues to evolution and
RT tissue-specific expression.";
RL J. Biol. Chem. 266:13130-13134(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH SCG3, AND SUBCELLULAR LOCATION.
RX PubMed=12388744; DOI=10.1091/mbc.02-03-0040;
RA Hosaka M., Watanabe T., Sakai Y., Uchiyama Y., Takeuchi T.;
RT "Identification of a chromogranin A domain that mediates binding to
RT secretogranin III and targeting to secretory granules in pituitary cells
RT and pancreatic beta-cells.";
RL Mol. Biol. Cell 13:3388-3399(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION (SERPININ), PYROGLUTAMATE FORMATION AT GLN-438, MASS SPECTROMETRY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=21537909; DOI=10.1007/s12031-011-9521-7;
RA Koshimizu H., Cawley N.X., Yergy A.L., Loh Y.P.;
RT "Role of pGlu-serpinin, a novel chromogranin A-derived peptide in
RT inhibition of cell death.";
RL J. Mol. Neurosci. 45:294-303(2011).
RN [6]
RP FUNCTION (SERPININ), MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=21436258; DOI=10.1210/me.2010-0124;
RA Koshimizu H., Cawley N.X., Kim T., Yergey A.L., Loh Y.P.;
RT "Serpinin: a novel chromogranin A-derived, secreted peptide up-regulates
RT protease nexin-1 expression and granule biogenesis in endocrine cells.";
RL Mol. Endocrinol. 25:732-744(2011).
CC -!- FUNCTION: [Pancreastatin]: Strongly inhibits glucose induced insulin
CC release from the pancreas.
CC -!- FUNCTION: [Catestatin]: Inhibits catecholamine release from chromaffin
CC cells and noradrenergic neurons by acting as a non-competitive
CC nicotinic cholinergic antagonist. Can induce mast cell migration,
CC degranulation and production of cytokines and chemokines.
CC {ECO:0000250|UniProtKB:P10645}.
CC -!- FUNCTION: [Serpinin]: Regulates granule biogenesis in endocrine cells
CC by up-regulating the transcription of protease nexin 1 (SERPINE2) via a
CC cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein
CC degradation in the Golgi complex which in turn promotes granule
CC formation (PubMed:21436258). Pyroglutaminated (pGlu)-serpinin exerts an
CC antiapoptotic effect on cells exposed to oxidative stress
CC (PubMed:21537909). {ECO:0000269|PubMed:21436258,
CC ECO:0000269|PubMed:21537909}.
CC -!- SUBUNIT: Interacts with SCG3; this interaction is optimal in conditions
CC mimicking the lumenal milieu of the trans-Golgi network, i.e. pH 5.5
CC and 10 mM Ca(+2). {ECO:0000269|PubMed:12388744}.
CC -!- INTERACTION:
CC P26339; P00441: SOD1; Xeno; NbExp=5; IntAct=EBI-990900, EBI-990792;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:12388744}. Cytoplasmic vesicle, secretory vesicle,
CC neuronal dense core vesicle {ECO:0000250|UniProtKB:P10354}. Secreted
CC {ECO:0000269|PubMed:12388744}. Note=Associated with the secretory
CC granule membrane through direct interaction to SCG3 that in turn binds
CC to cholesterol-enriched lipid rafts in intragranular conditions.
CC -!- SUBCELLULAR LOCATION: [Serpinin]: Secreted
CC {ECO:0000269|PubMed:21436258, ECO:0000269|PubMed:21537909}. Cytoplasmic
CC vesicle, secretory vesicle {ECO:0000269|PubMed:21537909}.
CC Note=Pyroglutaminated serpinin localizes to secretory vesicle.
CC {ECO:0000269|PubMed:21537909}.
CC -!- PTM: CgA is O-glycosylated.
CC -!- MASS SPECTROMETRY: [Serpinin]: Mass=2864.4; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21537909};
CC -!- MASS SPECTROMETRY: [Serpinin]: Mass=2864.5; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21436258};
CC -!- MASS SPECTROMETRY: [p-Glu serpinin precursor]: Mass=2532.4;
CC Method=MALDI; Note=With pyrrolidone carboxylic acid at Gln-438.;
CC Evidence={ECO:0000269|PubMed:21537909};
CC -!- MISCELLANEOUS: Binds calcium with a low-affinity.
CC -!- SIMILARITY: Belongs to the chromogranin/secretogranin protein family.
CC {ECO:0000305}.
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DR EMBL; M64278; AAA37457.1; -; mRNA.
DR EMBL; BC026554; AAH26554.1; -; mRNA.
DR CCDS; CCDS26120.1; -.
DR PIR; A39868; A39868.
DR RefSeq; NP_031719.1; NM_007693.2.
DR PDB; 5DMK; X-ray; 2.45 A; B/D/F/H=358-371.
DR PDBsum; 5DMK; -.
DR AlphaFoldDB; P26339; -.
DR SMR; P26339; -.
DR BioGRID; 198696; 3.
DR IntAct; P26339; 3.
DR STRING; 10090.ENSMUSP00000021610; -.
DR iPTMnet; P26339; -.
DR PhosphoSitePlus; P26339; -.
DR CPTAC; non-CPTAC-3903; -.
DR MaxQB; P26339; -.
DR PaxDb; P26339; -.
DR PeptideAtlas; P26339; -.
DR PRIDE; P26339; -.
DR ProteomicsDB; 279118; -.
DR Antibodypedia; 738; 2946 antibodies from 51 providers.
DR DNASU; 12652; -.
DR Ensembl; ENSMUST00000021610; ENSMUSP00000021610; ENSMUSG00000021194.
DR GeneID; 12652; -.
DR KEGG; mmu:12652; -.
DR UCSC; uc007oui.1; mouse.
DR CTD; 1113; -.
DR MGI; MGI:88394; Chga.
DR VEuPathDB; HostDB:ENSMUSG00000021194; -.
DR eggNOG; ENOG502RZBD; Eukaryota.
DR GeneTree; ENSGT00940000154206; -.
DR HOGENOM; CLU_050861_0_0_1; -.
DR InParanoid; P26339; -.
DR OMA; NHIGKNF; -.
DR OrthoDB; 1127088at2759; -.
DR PhylomeDB; P26339; -.
DR TreeFam; TF336596; -.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR BioGRID-ORCS; 12652; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Chga; mouse.
DR PRO; PR:P26339; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P26339; protein.
DR Bgee; ENSMUSG00000021194; Expressed in islet of Langerhans and 150 other tissues.
DR Genevisible; P26339; MM.
DR GO; GO:0042583; C:chromaffin granule; ISS:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; ISS:BHF-UCL.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0086030; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in cardiac muscle relaxation; ISS:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0045576; P:mast cell activation; ISS:UniProtKB.
DR GO; GO:0002551; P:mast cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0033604; P:negative regulation of catecholamine secretion; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IBA:GO_Central.
DR GO; GO:1901215; P:negative regulation of neuron death; ISS:BHF-UCL.
DR GO; GO:0006996; P:organelle organization; ISS:BHF-UCL.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; ISS:BHF-UCL.
DR GO; GO:2000707; P:positive regulation of dense core granule biogenesis; IDA:UniProtKB.
DR GO; GO:1900738; P:positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:1901899; P:positive regulation of relaxation of cardiac muscle; ISS:BHF-UCL.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0033366; P:protein localization to secretory granule; IDA:MGI.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:BHF-UCL.
DR InterPro; IPR001819; Chromogranin_AB.
DR InterPro; IPR018054; Chromogranin_CS.
DR InterPro; IPR001990; Granin.
DR PANTHER; PTHR10583; PTHR10583; 1.
DR Pfam; PF01271; Granin; 2.
DR PRINTS; PR00659; CHROMOGRANIN.
DR PROSITE; PS00422; GRANINS_1; 1.
DR PROSITE; PS00423; GRANINS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Oxidation;
KW Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT CHAIN 19..463
FT /note="Chromogranin-A"
FT /id="PRO_0000005422"
FT PEPTIDE 19..151
FT /note="Beta-granin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005423"
FT PEPTIDE 276..329
FT /note="Pancreastatin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005424"
FT PEPTIDE 358..371
FT /note="WE-14"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005425"
FT PEPTIDE 382..402
FT /note="Catestatin"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT /id="PRO_0000432687"
FT PEPTIDE 405..423
FT /note="GE-25"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT /id="PRO_0000432688"
FT PEPTIDE 435..463
FT /note="Serpinin-RRG"
FT /evidence="ECO:0000250|UniProtKB:P10354"
FT /id="PRO_0000432689"
FT PEPTIDE 435..460
FT /note="Serpinin"
FT /evidence="ECO:0000269|PubMed:21436258,
FT ECO:0000269|PubMed:21537909"
FT /id="PRO_0000432690"
FT PEPTIDE 438..460
FT /note="p-Glu serpinin precursor"
FT /evidence="ECO:0000269|PubMed:21537909"
FT /id="PRO_0000432691"
FT REGION 88..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..162
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..440
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 308
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 329
FT /note="Glycine amide"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10354"
FT MOD_RES 384
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10354"
FT MOD_RES 438
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:21537909"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10354"
FT DISULFID 35..56
FT /evidence="ECO:0000250"
SQ SEQUENCE 463 AA; 51789 MW; 1AB3C5FF433C39E4 CRC64;
MRSTAVLALL LCAGQVFALP VNSPMTKGDT KVMKCVLEVI SDSLSKPSPM PVSPECLETL
QGDERILSIL RHQNLLKELQ DLALQGAKER AQQPLKQQQP PKQQQQQQQQ QQQEQQHSSF
EDELSEVFEN QSPDAKHRDA AAEVPSRDTM EKRKDSDKGQ QDGFEATTEG PRPQAFPEPN
QESPMMGDSE SPGEDTATNT QSPTSLPSQE HVDPQATGDS ERGLSAQQQA RKAKQEEKEE
EEEEEAVARE KAGPEEVPTA ASSSHFHAGY KAIQKDDGQS DSQAVDGDGK TEASEALPSE
GKGELEHSQQ EEDGEEAMVG TPQGLFPQGG KGRELEHKQE EEEEEEERLS REWEDKRWSR
MDQLAKELTA EKRLEGEDDP DRSMKLSFRT RAYGFRDPGP QLRRGWRPSS REDSVEARSD
FEEKKEEEGS ANRRAEDQEL ESLSAIEAEL EKVAHQLQAL RRG
