NACC1_RAT
ID NACC1_RAT Reviewed; 514 AA.
AC O35260;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Nucleus accumbens-associated protein 1;
DE Short=NAC-1;
DE AltName: Full=BTB/POZ domain-containing protein 14B;
GN Name=Nacc1; Synonyms=Btbd14b, Nac1;
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] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9278521; DOI=10.1523/jneurosci.17-18-06864.1997;
RA Cha X.-Y., Pierce R.C., Kalivas P.W., Mackler S.A.;
RT "NAC-1, a rat brain mRNA, is increased in the nucleus accumbens three weeks
RT after chronic cocaine self-administration.";
RL J. Neurosci. 17:6864-6871(1997).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND ALTERNATIVE
RP SPLICING.
RX PubMed=11906783; DOI=10.1016/s0306-4522(01)00518-8;
RA Korutla L., Wang P.J., Lewis D.M., Neustadter J.H., Stromberg M.F.,
RA Mackler S.A.;
RT "Differences in expression, actions and cocaine regulation of two isoforms
RT for the brain transcriptional regulator NAC1.";
RL Neuroscience 110:421-429(2002).
RN [3]
RP FUNCTION, AND INTERACTION WITH HDAC3 AND HDAC4.
RX PubMed=16033423; DOI=10.1111/j.1471-4159.2005.03206.x;
RA Korutla L., Wang P.J., Mackler S.A.;
RT "The POZ/BTB protein NAC1 interacts with two different histone deacetylases
RT in neuronal-like cultures.";
RL J. Neurochem. 94:786-793(2005).
RN [4]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-245.
RX PubMed=16045493; DOI=10.1111/j.1460-9568.2005.04208.x;
RA Korutla L., Champtiaux N., Shen H.-W., Klugmann M., Kalivas P.W.,
RA Mackler S.A.;
RT "Activity-dependent subcellular localization of NAC1.";
RL Eur. J. Neurosci. 22:397-403(2005).
RN [5]
RP FUNCTION, INTERACTION WITH RCOR1, AND MUTAGENESIS OF GLN-23.
RX PubMed=17254023; DOI=10.1111/j.1471-4159.2006.04387.x;
RA Korutla L., Degnan R., Wang P., Mackler S.A.;
RT "NAC1, a cocaine-regulated POZ/BTB protein interacts with CoREST.";
RL J. Neurochem. 101:611-618(2007).
RN [6]
RP FUNCTION, INTERACTION WITH CUL3 AND PSMD7, AND SUBCELLULAR LOCATION.
RX PubMed=17699672; DOI=10.1523/jneurosci.1571-07.2007;
RA Shen H., Korutla L., Champtiaux N., Toda S., LaLumiere R., Vallone J.,
RA Klugmann M., Blendy J.A., Mackler S.A., Kalivas P.W.;
RT "NAC1 regulates the recruitment of the proteasome complex into dendritic
RT spines.";
RL J. Neurosci. 27:8903-8913(2007).
CC -!- FUNCTION: Functions as a transcriptional repressor. Isoform 1 is a
CC stronger transcriptional repressor than isoform 2. Seems to function as
CC a transcriptional corepressor in neuronal cells through recruitment of
CC HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell
CC proliferation and survival. This may be mediated at least in part
CC through repressing transcriptional activity of GADD45GIP1. Required for
CC recruiting the proteasome from the nucleus to the cytoplasm and
CC dendritic spines. {ECO:0000269|PubMed:11906783,
CC ECO:0000269|PubMed:16033423, ECO:0000269|PubMed:17254023,
CC ECO:0000269|PubMed:17699672}.
CC -!- SUBUNIT: Homooligomer; mediated by the BTB domain (By similarity). Both
CC isoforms interact with HDAC3 and HDAC4. Interacts (via BTB domain) with
CC CUL3, PSMD7 AND RCOR1. {ECO:0000250, ECO:0000269|PubMed:16033423,
CC ECO:0000269|PubMed:17254023, ECO:0000269|PubMed:17699672}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Punctate distribution in
CC nucleus. In differentiated PC12 cells diffusely distributed in the
CC cytoplasm and is dependent on phosphorylation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=lNAC1;
CC IsoId=O35260-1; Sequence=Displayed;
CC Name=2; Synonyms=sNAC1;
CC IsoId=O35260-2; Sequence=VSP_022613;
CC -!- TISSUE SPECIFICITY: Highly expressed in the hippocampus, brain cortex,
CC cerebellum and brainstem. Expressed in the nucleus accumbens, olfactory
CC tubercle, the striatum, frontal and parietal cortex and ventral
CC pallidum. Weakly expressed in the heart, liver, kidney, spleen, testis,
CC and skeletal muscle. Isoform 2 is expressed in the brain and liver,
CC less abundantly expressed in the brain than isoform 1.
CC {ECO:0000269|PubMed:9278521}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain at E16, E18, P2, P8 and
CC P90. {ECO:0000269|PubMed:11906783, ECO:0000269|PubMed:9278521}.
CC -!- INDUCTION: Expression is increased by cocaine, selectively in the
CC nucleus accumbens. mRNA is present at increased levels in the nucleus
CC accumbens 3 weeks after withdrawal from cocaine self-administration.
CC {ECO:0000269|PubMed:9278521}.
CC -!- PTM: Phosphorylated by protein kinase C (PKC).
CC {ECO:0000269|PubMed:16045493}.
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DR EMBL; AF015911; AAB69864.1; -; mRNA.
DR RefSeq; NP_599240.1; NM_134413.2. [O35260-1]
DR RefSeq; XP_008770568.1; XM_008772346.2. [O35260-1]
DR AlphaFoldDB; O35260; -.
DR SMR; O35260; -.
DR BioGRID; 251261; 1.
DR STRING; 10116.ENSRNOP00000003884; -.
DR iPTMnet; O35260; -.
DR PhosphoSitePlus; O35260; -.
DR jPOST; O35260; -.
DR PaxDb; O35260; -.
DR PRIDE; O35260; -.
DR Ensembl; ENSRNOT00000091670; ENSRNOP00000071927; ENSRNOG00000002864. [O35260-2]
DR GeneID; 171454; -.
DR KEGG; rno:171454; -.
DR CTD; 112939; -.
DR RGD; 621003; Nacc1.
DR VEuPathDB; HostDB:ENSRNOG00000002864; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159327; -.
DR InParanoid; O35260; -.
DR OMA; GKMEPDM; -.
DR OrthoDB; 567120at2759; -.
DR PhylomeDB; O35260; -.
DR PRO; PR:O35260; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000002864; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; O35260; RN.
DR GO; GO:0030054; C:cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR018379; BEN_domain.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR Pfam; PF10523; BEN; 1.
DR Pfam; PF00651; BTB; 1.
DR SMART; SM01025; BEN; 1.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS51457; BEN; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..514
FT /note="Nucleus accumbens-associated protein 1"
FT /id="PRO_0000274043"
FT DOMAIN 30..94
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 360..457
FT /note="BEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00784"
FT REGION 183..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT MOD_RES 245
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:16045493"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSZ8"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSZ8"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 182
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 304
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 466
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT CROSSLNK 485
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96RE7"
FT VAR_SEQ 275..301
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_022613"
FT MUTAGEN 23
FT /note="Q->L: Abrogates transcriptional repression."
FT /evidence="ECO:0000269|PubMed:17254023"
SQ SEQUENCE 514 AA; 56450 MW; 5980514174B4BFF5 CRC64;
MAQTLQMEIP NFGNSILECL NEQRLQGLYC DVSVVVKGHA FKAHRAVLAA SSSYFRDLFN
SSRSAVVELP AAVQPQSFQQ ILTFCYTGRL SMNMGDQFLL IYTAGFLQIQ EIMEKGTEFF
LKVSSPSCDS QGLHPEEAPS SEPQSPVAQI LGWPACSTPL PLVSRVKTEQ ELDSVQCTPM
AKRLWDSSQK EAGGSGGNNG SRKMAKFSTP DLAPNRMPQP VSVATATAAV AVVAVGGCVS
GPSMSERTSP GTSSAYTSDS PSSYHNEEDE EEDAGEEGTD EQYRQICNMY TMYSMLNVGQ
TVEKVEALPE QVVLESHSRI RVRQDLASLP AELINQIGNR CHPKLYDEGD PSEKLELVTG
TNVYITRAQL MNCHVSAGTR HKVLLRRLLA SFFDRNTLAN SCGTGIRSST NDPRRKPLDS
RVLHAVKYYC QNFAPNFKES EMNAIAADMC TNARRVVRKS WLPKTKPLHL VEGDNYSSFI
SDTGKIEPDM MSMEHSFETA SHDGEAGPSA EVLQ
