NEUG_RAT
ID NEUG_RAT Reviewed; 78 AA.
AC Q04940;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Neurogranin;
DE Short=Ng;
DE AltName: Full=Protein kinase C substrate 7.5 kDa protein;
DE AltName: Full=RC3;
DE Contains:
DE RecName: Full=NEUG(55-78);
GN Name=Nrgn;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2231781; DOI=10.1002/jnr.490260402;
RA Watson J.B., Battenberg E.F., Wong K.K., Bloom F.E., Sutcliffe J.G.;
RT "Subtractive cDNA cloning of RC3, a rodent cortex-enriched mRNA encoding a
RT novel 78 residue protein.";
RL J. Neurosci. Res. 26:397-408(1990).
RN [2]
RP PROTEIN SEQUENCE, PHOSPHORYLATION AT SER-36, AND INTERACTION WITH CALM1.
RC TISSUE=Brain;
RX PubMed=8080473; DOI=10.1006/abbi.1993.1463;
RA Huang K.-P., Huang F.L., Chen H.-C.;
RT "Characterization of a 7.5-kDa protein kinase C substrate (RC3 protein,
RT neurogranin) from rat brain.";
RL Arch. Biochem. Biophys. 305:570-580(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=7730337; DOI=10.1074/jbc.270.17.10314;
RA Sato T., Xiao D.M., Li H., Huang F.L., Huang K.P.;
RT "Structure and regulation of the gene encoding the neuron-specific protein
RT kinase C substrate neurogranin (RC3 protein).";
RL J. Biol. Chem. 270:10314-10322(1995).
RN [4]
RP PROTEIN SEQUENCE OF 55-78, AND MASS SPECTROMETRY.
RC STRAIN=Wistar; TISSUE=Corpus striatum;
RX PubMed=19164277; DOI=10.1074/mcp.m800501-mcp200;
RA Bernay B., Gaillard M.-C., Guryca V., Emadali A., Kuhn L., Bertrand A.,
RA Detraz I., Carcenac C., Savasta M., Brouillet E., Garin J., Elalouf J.-M.;
RT "Discovering new bioactive neuropeptides in the striatum secretome using in
RT vivo microdialysis and versatile proteomics.";
RL Mol. Cell. Proteomics 8:946-958(2009).
RN [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=1528865; DOI=10.1073/pnas.89.18.8581;
RA Watson J.B., Sutcliffe J.G., Fisher R.S.;
RT "Localization of the protein kinase C phosphorylation/calmodulin-binding
RT substrate RC3 in dendritic spines of neostriatal neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8581-8585(1992).
RN [6]
RP PHOSPHORYLATION AT SER-36 BY PHK.
RX PubMed=8454596; DOI=10.1016/s0021-9258(18)53240-3;
RA Paudel H.K., Zwiers H., Wang J.H.;
RT "Phosphorylase kinase phosphorylates the calmodulin-binding regulatory
RT regions of neuronal tissue-specific proteins B-50 (GAP-43) and
RT neurogranin.";
RL J. Biol. Chem. 268:6207-6213(1993).
RN [7]
RP DISULFIDE BONDS, INTERACTION WITH CALM1, AND MUTAGENESIS OF CYS-3; CYS-4;
RP CYS-9 AND CYS-51.
RX PubMed=8910523; DOI=10.1074/jbc.271.46.28798;
RA Mahoney C.W., Pak J.H., Huang K.-P.;
RT "Nitric oxide modification of rat brain neurogranin. Identification of the
RT cysteine residues involved in intramolecular disulfide bridge formation
RT using site-directed mutagenesis.";
RL J. Biol. Chem. 271:28798-28804(1996).
RN [8]
RP FUNCTION.
RX PubMed=15262982; DOI=10.1074/jbc.m405352200;
RA Gaertner T.R., Putkey J.A., Waxham M.N.;
RT "RC3/neurogranin and Ca2+/calmodulin-dependent protein kinase II produce
RT opposing effects on the affinity of calmodulin for calcium.";
RL J. Biol. Chem. 279:39374-39382(2004).
CC -!- FUNCTION: Regulates the affinity of calmodulin for calcium. Involved in
CC synaptic plasticity and spatial learning (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:15262982}.
CC -!- SUBUNIT: Interacts with apo-calmodulin; this interaction decreases the
CC affinity of calmodulin for calcium ions. {ECO:0000269|PubMed:8080473,
CC ECO:0000269|PubMed:8910523}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1528865}. Synapse
CC {ECO:0000269|PubMed:1528865}. Cell projection, dendritic spine
CC {ECO:0000269|PubMed:1528865}. Note=Restricted to dendritic spines of a
CC subset of neurons.
CC -!- TISSUE SPECIFICITY: Highly enriched in brain with restricted expression
CC in neuronal subsets primarily in the cortex, striatum, and hippocampus
CC as well as certain nuclei within the thalamus, hypothalamus and
CC olfactory bulb. Accumulates postsynaptically in dendritic spines of
CC neostriatal neurons. {ECO:0000269|PubMed:1528865,
CC ECO:0000269|PubMed:2231781}.
CC -!- DOMAIN: Neurogranin is intrinsically unstructured; however, upon
CC binding with CaM, The IQ domain adopts a helical conformation.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-36 by PHK and PKC. Phosphorylation prevents
CC interaction with Calmodulin and interrupts several learning- and
CC memory-associated functions (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation is activated by calcium, phospholipids, and
CC diacylglycerol. Phosphorylation inhibits binding to calmodulin both in
CC the presence and absence of calcium. {ECO:0000269|PubMed:8080473,
CC ECO:0000269|PubMed:8454596}.
CC -!- PTM: Disulfide bond formation is redox-sensitive. The cysteine residues
CC are readily oxidized by several nitric acid (NO) donors and other
CC oxidants to form intramolecular disulfide. Cys-51 can form a disulfide
CC with any other of the cysteine residues with an order of reactivity
CC Cys-9 > Cys-4 > Cys-3.
CC -!- MASS SPECTROMETRY: [NEUG(55-78)]: Mass=1775.78; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19164277};
CC -!- SIMILARITY: Belongs to the neurogranin family. {ECO:0000305}.
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DR EMBL; L09119; AAA42023.1; -; mRNA.
DR EMBL; U22062; AAA80223.1; -; Genomic_RNA.
DR PIR; A57288; A57288.
DR RefSeq; NP_077054.1; NM_024140.2.
DR AlphaFoldDB; Q04940; -.
DR BMRB; Q04940; -.
DR SMR; Q04940; -.
DR BioGRID; 249041; 3.
DR STRING; 10116.ENSRNOP00000014404; -.
DR iPTMnet; Q04940; -.
DR PhosphoSitePlus; Q04940; -.
DR PaxDb; Q04940; -.
DR GeneID; 64356; -.
DR KEGG; rno:64356; -.
DR UCSC; RGD:61833; rat.
DR CTD; 4900; -.
DR RGD; 61833; Nrgn.
DR VEuPathDB; HostDB:ENSRNOG00000010688; -.
DR eggNOG; ENOG502S6YP; Eukaryota.
DR HOGENOM; CLU_129609_1_0_1; -.
DR InParanoid; Q04940; -.
DR OMA; KSKDPEC; -.
DR PhylomeDB; Q04940; -.
DR TreeFam; TF342962; -.
DR PRO; PR:Q04940; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000010688; Expressed in frontal cortex and 20 other tissues.
DR Genevisible; Q04940; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0044327; C:dendritic spine head; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0012510; C:trans-Golgi network transport vesicle membrane; IDA:RGD.
DR GO; GO:0005516; F:calmodulin binding; IDA:RGD.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:RGD.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:RGD.
DR GO; GO:0008306; P:associative learning; IEP:RGD.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IMP:RGD.
DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR GO; GO:0021537; P:telencephalon development; IEP:RGD.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR Pfam; PF00612; IQ; 1.
DR SMART; SM00015; IQ; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW Acetylation; Calmodulin-binding; Cell projection; Citrullination;
KW Cytoplasm; Direct protein sequencing; Disulfide bond; Methylation;
KW Phosphoprotein; Reference proteome; Synapse.
FT CHAIN 1..78
FT /note="Neurogranin"
FT /id="PRO_0000159593"
FT PEPTIDE 55..78
FT /note="NEUG(55-78)"
FT /id="PRO_0000375992"
FT DOMAIN 26..47
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 48..78
FT /note="Collagen-like"
FT REGION 39..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 38
FT /note="Crucial for interaction with calmodulin"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P35722, ECO:0000305"
FT MOD_RES 36
FT /note="Phosphoserine; by PHK and PKC"
FT /evidence="ECO:0000269|PubMed:8080473,
FT ECO:0000269|PubMed:8454596"
FT MOD_RES 68
FT /note="Citrulline; partial"
FT /evidence="ECO:0000250"
FT MOD_RES 68
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q92686"
FT DISULFID 3..51
FT /note="Or C-51 with C-4 or C-9"
FT /evidence="ECO:0000269|PubMed:8910523"
FT MUTAGEN 3
FT /note="C->S: No effect on oxidant-mediated disulfide bond
FT formation nor on in vitro PKC-mediated phosphorylation. No
FT effect on oxidant-mediated disulfide bond formation; when
FT associated with G-4 or S-9."
FT /evidence="ECO:0000269|PubMed:8910523"
FT MUTAGEN 4
FT /note="C->G: No effect on oxidant-mediated disulfide bond
FT formation nor on in vitro PKC-mediated phosphorylation. No
FT effect on oxidant-mediated disulfide bond formation; when
FT associated with S-3 or S-9."
FT /evidence="ECO:0000269|PubMed:8910523"
FT MUTAGEN 9
FT /note="C->S: No effect on oxidant-mediated disulfide bond
FT formation nor on in vitro PKC-mediated phosphorylation. No
FT effect on oxidant-mediated disulfide bond formation; when
FT associated with S-3 or G-4."
FT /evidence="ECO:0000269|PubMed:8910523"
FT MUTAGEN 51
FT /note="C->G: No oxidant-mediated disulfide bond formation.
FT No effect on in vitro PKC-mediated phosphorylation. No
FT oxidant-mediated disulfide bond formation; when associated
FT with S-3; G-4 and S-9."
FT /evidence="ECO:0000269|PubMed:8910523"
SQ SEQUENCE 78 AA; 7496 MW; 8E47CDB38E095794 CRC64;
MDCCTESACS KPDDDILDIP LDDPGANAAA AKIQASFRGH MARKKIKSGE CGRKGPGPGG
PGGAGGARGG AGGGPSGD
