NACC2_HUMAN
ID NACC2_HUMAN Reviewed; 587 AA.
AC Q96BF6;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Nucleus accumbens-associated protein 2;
DE Short=NAC-2;
DE AltName: Full=BTB/POZ domain-containing protein 14A;
DE AltName: Full=Repressor with BTB domain and BEN domain;
GN Name=NACC2; Synonyms=BTBD14A, NAC2, RBB;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 SUBCELLULAR LOCATION, SUBUNIT, FUNCTION, INTERACTION WITH MTA1; MTA2; MTA3
RP AND HDAC2, AND ASSOCIATION WITH THE NURD RP COMPLEX.
RX PubMed=22926524; DOI=10.1038/onc.2012.386;
RA Xuan C., Wang Q., Han X., Duan Y., Li L., Shi L., Wang Y., Shan L., Yao Z.,
RA Shang Y.;
RT "RBB, a novel transcription repressor, represses the transcription of HDM2
RT oncogene.";
RL Oncogene 32:3711-3721(2013).
RN [4]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-299, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [5]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-174; LYS-217; LYS-299; LYS-429
RP AND LYS-456, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Functions as a transcriptional repressor through its
CC association with the NuRD complex. Recruits the NuRD complex to the
CC promoter of MDM2, leading to the repression of MDM2 transcription and
CC subsequent stability of p53/TP53. {ECO:0000269|PubMed:22926524}.
CC -!- SUBUNIT: Homooligomer; mediated by the BTB domain. Interacts with the
CC NuRD complex. Interacts (via C-terminal part) with HDAC2. Interacts
CC (via BTB domain) with MTA1, MTA2 and MTA3.
CC {ECO:0000269|PubMed:22926524}.
CC -!- INTERACTION:
CC Q96BF6; P40337-2: VHL; NbExp=3; IntAct=EBI-3942475, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22926524}.
CC Note=Predominantly associated with chromatin.
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DR EMBL; AL591038; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355574; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015649; AAH15649.1; -; mRNA.
DR CCDS; CCDS6993.1; -.
DR RefSeq; NP_653254.1; NM_144653.4.
DR RefSeq; XP_011516523.1; XM_011518221.2.
DR AlphaFoldDB; Q96BF6; -.
DR SMR; Q96BF6; -.
DR BioGRID; 126501; 59.
DR IntAct; Q96BF6; 3.
DR MINT; Q96BF6; -.
DR STRING; 9606.ENSP00000277554; -.
DR iPTMnet; Q96BF6; -.
DR PhosphoSitePlus; Q96BF6; -.
DR BioMuta; NACC2; -.
DR DMDM; 74751767; -.
DR EPD; Q96BF6; -.
DR jPOST; Q96BF6; -.
DR MassIVE; Q96BF6; -.
DR MaxQB; Q96BF6; -.
DR PaxDb; Q96BF6; -.
DR PeptideAtlas; Q96BF6; -.
DR PRIDE; Q96BF6; -.
DR ProteomicsDB; 76074; -.
DR Antibodypedia; 18675; 119 antibodies from 21 providers.
DR DNASU; 138151; -.
DR Ensembl; ENST00000277554.4; ENSP00000277554.2; ENSG00000148411.8.
DR Ensembl; ENST00000371753.5; ENSP00000360818.1; ENSG00000148411.8.
DR GeneID; 138151; -.
DR KEGG; hsa:138151; -.
DR MANE-Select; ENST00000277554.4; ENSP00000277554.2; NM_144653.5; NP_653254.1.
DR UCSC; uc004cgv.4; human.
DR CTD; 138151; -.
DR DisGeNET; 138151; -.
DR GeneCards; NACC2; -.
DR HGNC; HGNC:23846; NACC2.
DR HPA; ENSG00000148411; Tissue enriched (brain).
DR MIM; 615786; gene.
DR neXtProt; NX_Q96BF6; -.
DR OpenTargets; ENSG00000148411; -.
DR PharmGKB; PA164723421; -.
DR VEuPathDB; HostDB:ENSG00000148411; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159244; -.
DR HOGENOM; CLU_029038_1_0_1; -.
DR InParanoid; Q96BF6; -.
DR OMA; RVSYYGM; -.
DR OrthoDB; 567120at2759; -.
DR PhylomeDB; Q96BF6; -.
DR TreeFam; TF331184; -.
DR PathwayCommons; Q96BF6; -.
DR SignaLink; Q96BF6; -.
DR BioGRID-ORCS; 138151; 11 hits in 1119 CRISPR screens.
DR ChiTaRS; NACC2; human.
DR GenomeRNAi; 138151; -.
DR Pharos; Q96BF6; Tbio.
DR PRO; PR:Q96BF6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96BF6; protein.
DR Bgee; ENSG00000148411; Expressed in dorsal motor nucleus of vagus nerve and 195 other tissues.
DR ExpressionAtlas; Q96BF6; baseline and differential.
DR Genevisible; Q96BF6; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1900477; P:negative regulation of G1/S transition of mitotic cell cycle by negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IDA:BHF-UCL.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0031503; P:protein-containing complex localization; IDA:BHF-UCL.
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 Isopeptide bond; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..587
FT /note="Nucleus accumbens-associated protein 2"
FT /id="PRO_0000263668"
FT DOMAIN 30..94
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 351..448
FT /note="BEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00784"
FT REGION 240..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 217
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 429
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 456
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 587 AA; 62837 MW; BE1EF06B210EEDBA CRC64;
MSQMLHIEIP NFGNTVLGCL NEQRLLGLYC DVSIVVKGQA FKAHRAVLAA SSLYFRDLFS
GNSKSAFELP GSVPPACFQQ ILSFCYTGRL TMTASEQLVV MYTAGFLQIQ HIVERGTDLM
FKVSSPHCDS QTAVIEDAGS EPQSPCNQLQ PAAAAAAPYV VSPSVPIPLL TRVKHEAMEL
PPAGPGLAPK RPLETGPRDG VAVAAGAAVA AGTAPLKLPR VSYYGVPSLA TLIPGIQQMP
YPQGERTSPG ASSLPTTDSP TSYHNEEDEE DDEAYDTMVE EQYGQMYIKA SGSYAVQEKP
EPVPLESRSC VLIRRDLVAL PASLISQIGY RCHPKLYSEG DPGEKLELVA GSGVYITRGQ
LMNCHLCAGV KHKVLLRRLL ATFFDRNTLA NSCGTGIRSS TSDPSRKPLD SRVLNAVKLY
CQNFAPSFKE SEMNVIAADM CTNARRVRKR WLPKIKSMLP EGVEMYRTVM GSAAASVPLD
PEFPPAAAQV FEQRIYAERR GDAATIVALR TDAVNVDLSA AANPAFDAGE EVDGAGSVIQ
EVAAPEPLPA DGQSPPQPFE QGGGGPSRPQ TPAAAARRPE GTYAGTL
