CMGA_RAT
ID CMGA_RAT Reviewed; 466 AA.
AC P10354;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 136.
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 {ECO:0000303|PubMed:22459152};
DE Contains:
DE RecName: Full=Serpinin {ECO:0000303|PubMed:22459152};
DE Contains:
DE RecName: Full=p-Glu serpinin precursor;
DE Flags: Precursor;
GN Name=Chga;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2828116; DOI=10.1016/0014-5793(88)80880-9;
RA Iacangelo A., Okayama H., Eiden L.E.;
RT "Primary structure of rat chromogranin A and distribution of its mRNA.";
RL FEBS Lett. 227:115-121(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-466.
RC TISSUE=Pancreas;
RX PubMed=3044825; DOI=10.1016/0014-5793(88)80036-x;
RA Hutton J.C., Nielsen E., Kastern W.;
RT "The molecular cloning of the chromogranin A-like precursor of beta-granin
RT and pancreastatin from the endocrine pancreas.";
RL FEBS Lett. 236:269-274(1988).
RN [3]
RP PROTEIN SEQUENCE OF 19-32.
RX PubMed=3896848; DOI=10.1016/0014-5793(85)80398-7;
RA Hutton J.C., Hansen F., Peshavaria M.;
RT "Beta-granins: 21 kDa co-secreted peptides of the insulin granule closely
RT related to adrenal medullary chromogranin A.";
RL FEBS Lett. 188:336-340(1985).
RN [4]
RP INTERACTION WITH SCG3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [5]
RP SUBCELLULAR LOCATION.
RX PubMed=14597614; DOI=10.1074/jbc.m310104200;
RA Hosaka M., Suda M., Sakai Y., Izumi T., Watanabe T., Takeuchi T.;
RT "Secretogranin III binds to cholesterol in the secretory granule membrane
RT as an adapter for chromogranin A.";
RL J. Biol. Chem. 279:3627-3634(2004).
RN [6]
RP IDENTIFICATION OF SERPININ PEPTIDE; SERPININ-RRG PEPTIDE AND
RP PYROGLUTAMINATED SERPININ, FUNCTION (SERPININ), AND PYROGLUTAMATE FORMATION
RP AT GLN-441.
RX PubMed=22459152; DOI=10.1096/fj.11-201111;
RA Tota B., Gentile S., Pasqua T., Bassino E., Koshimizu H., Cawley N.X.,
RA Cerra M.C., Loh Y.P., Angelone T.;
RT "The novel chromogranin A-derived serpinin and pyroglutaminated serpinin
RT peptides are positive cardiac beta-adrenergic-like inotropes.";
RL FASEB J. 26:2888-2898(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312; SER-353; SER-386;
RP SER-417; SER-433 AND SER-447, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=29166604; DOI=10.1016/j.celrep.2017.10.084;
RA Bharat V., Siebrecht M., Burk K., Ahmed S., Reissner C.,
RA Kohansal-Nodehi M., Steubler V., Zweckstetter M., Ting J.T., Dean C.;
RT "Capture of Dense Core Vesicles at Synapses by JNK-Dependent
RT Phosphorylation of Synaptotagmin-4.";
RL Cell Rep. 21:2118-2133(2017).
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 by
CC 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 (By similarity). Serpinin and pGlu-serpinin can enhance both
CC myocardial contractility (inotropy) and relaxation (lusitropy) and this
CC cardio-stimulation requires a beta 1-adrenergic receptor/adenylate
CC cyclase/cAMP/PKA pathway (PubMed:22459152).
CC {ECO:0000250|UniProtKB:P26339, ECO:0000269|PubMed:22459152}.
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 -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:12388744, ECO:0000269|PubMed:3896848}. Cytoplasmic
CC vesicle, secretory vesicle, neuronal dense core vesicle
CC {ECO:0000269|PubMed:29166604}. Secreted. Note=Associated with the
CC secretory granule membrane through direct interaction to SCG3 that in
CC turn binds to cholesterol-enriched lipid rafts in intragranular
CC conditions. In pituitary gonadotropes, located in large secretory
CC granules.
CC -!- SUBCELLULAR LOCATION: [Serpinin]: Secreted
CC {ECO:0000250|UniProtKB:P26339}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:P26339}. Note=Pyroglutaminated serpinin
CC localizes to secretory vesicle. {ECO:0000250|UniProtKB:P26339}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain and adrenal and pituitary
CC glands. {ECO:0000269|PubMed:12388744}.
CC -!- PTM: CgA is O-glycosylated.
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; X06832; CAA29988.1; -; mRNA.
DR PIR; A23996; A23996.
DR AlphaFoldDB; P10354; -.
DR SMR; P10354; -.
DR iPTMnet; P10354; -.
DR PhosphoSitePlus; P10354; -.
DR jPOST; P10354; -.
DR PRIDE; P10354; -.
DR RGD; 2338; Chga.
DR InParanoid; P10354; -.
DR PhylomeDB; P10354; -.
DR Reactome; R-RNO-6803157; Antimicrobial peptides.
DR PRO; PR:P10354; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0042583; C:chromaffin granule; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0098992; C:neuronal dense core vesicle; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
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; IDA:UniProtKB.
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; IDA:RGD.
DR GO; GO:0006996; P:organelle organization; IMP:RGD.
DR GO; GO:0042698; P:ovulation cycle; IEP:RGD.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:RGD.
DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IDA:UniProtKB.
DR GO; GO:2000707; P:positive regulation of dense core granule biogenesis; ISS:UniProtKB.
DR GO; GO:1900738; P:positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:1901899; P:positive regulation of relaxation of cardiac muscle; IDA:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IDA:RGD.
DR GO; GO:0033366; P:protein localization to secretory granule; ISO:RGD.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IDA:RGD.
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 Amidation; Calcium; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Oxidation; Phosphoprotein; Pyrrolidone carboxylic acid;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:3896848"
FT CHAIN 19..466
FT /note="Chromogranin-A"
FT /id="PRO_0000005430"
FT PEPTIDE 19..146
FT /note="Beta-granin"
FT /id="PRO_0000005431"
FT PEPTIDE 281..332
FT /note="Pancreastatin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000005432"
FT PEPTIDE 361..374
FT /note="WE-14"
FT /id="PRO_0000005433"
FT PEPTIDE 385..405
FT /note="Catestatin"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT /id="PRO_0000432697"
FT PEPTIDE 408..426
FT /note="GE-25"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT /id="PRO_0000432698"
FT PEPTIDE 438..466
FT /note="Serpinin-RRG"
FT /evidence="ECO:0000269|PubMed:22459152"
FT /id="PRO_0000432699"
FT PEPTIDE 438..463
FT /note="Serpinin"
FT /evidence="ECO:0000269|PubMed:22459152"
FT /id="PRO_0000432700"
FT PEPTIDE 441..463
FT /note="p-Glu serpinin precursor"
FT /evidence="ECO:0000250|UniProtKB:P26339"
FT /id="PRO_0000432701"
FT REGION 91..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..116
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..318
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..389
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26339"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 332
FT /note="Glycine amide"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 387
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P10645"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05059"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 441
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P26339,
FT ECO:0000303|PubMed:22459152"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT DISULFID 35..56
FT /evidence="ECO:0000250"
SQ SEQUENCE 466 AA; 52024 MW; 05D135FFA657C48C CRC64;
MRSSAALALL LCAGQVFALP VNSPMTKGDT KVMKCVLEVI SDSLSKPSPM PVSPECLETL
QGDERVLSIL RHQNLLKELQ DLALQGAKER AQQQQQQQQQ QQQQQQQQQQ QHSSFEDELS
EVFENQSPAA KHGDAASEAP SKDTVEKRED SDKGQQDAFE GTTEGPRPQA FPEPKQESSM
MGNSQSPGED TANNTQSPTS LPSQEHGIPQ TTEGSERGPS AQQQARKAKQ EEKEEEEEEK
EEEEEEKEEK AIAREKAGPK EVPTAASSSH FYSGYKKIQK DDDGQSESQA VNGKTGASEA
VPSEGKGELE HSQQEEDGEE AMAGPPQGLF PGGKGQELER KQQEEEEEEE RLSREWEDKR
WSRMDQLAKE LTAEKRLEGE DDPDRSMKLS FRARAYGFRD PGPQLRRGWR PSSREDSVEA
RGDFEEKKEE EGSANRRAED QELESLSAIE AELEKVAHQL QALRRG
