NC2A_HUMAN
ID NC2A_HUMAN Reviewed; 205 AA.
AC Q14919; Q13448;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dr1-associated corepressor;
DE AltName: Full=Dr1-associated protein 1;
DE AltName: Full=Negative cofactor 2-alpha;
DE Short=NC2-alpha;
GN Name=DRAP1;
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 [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-31, FUNCTION,
RP PHOSPHORYLATION, INTERACTION WITH DR1, AND TISSUE SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=8670811; DOI=10.1002/j.1460-2075.1996.tb00673.x;
RA Goppelt A.R., Stelzer G., Lottspeich F., Meisterernst M.;
RT "A mechanism for repression of class II gene transcription through specific
RT binding of NC2 to TBP-promoter complexes via heterodimeric histone fold
RT domains.";
RL EMBO J. 15:3105-3116(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 20-26;
RP 30-39 AND 72-91, FUNCTION, INTERACTION WITH DR1, PHOSPHORYLATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=8608938; DOI=10.1101/gad.10.8.1033;
RA Mermelstein F., Yeung K., Cao J., Inostroza J.A., Erdjument-Bromage H.,
RA Eagelson K., Landsman D., Levitt P., Tempst P., Reinberg D.;
RT "Requirement of a corepressor for Dr1-mediated repression of
RT transcription.";
RL Genes Dev. 10:1033-1048(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [4]
RP INTERACTION WITH BTAF1.
RX PubMed=15509807; DOI=10.1128/mcb.24.22.10072-10082.2004;
RA Klejman M.P., Pereira L.A., van Zeeburg H.J.T., Gilfillan S.,
RA Meisterernst M., Timmers H.T.M.;
RT "NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association
RT with TATA-binding protein.";
RL Mol. Cell. Biol. 24:10072-10082(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 1-77 IN COMPLEX WITH DR1; TBP AND
RP DNA.
RX PubMed=11461703; DOI=10.1016/s0092-8674(01)00417-2;
RA Kamada K., Shu F., Chen H., Malik S., Stelzer G., Roeder R.G.,
RA Meisterernst M., Burley S.K.;
RT "Crystal structure of negative cofactor 2 recognizing the TBP-DNA
RT transcription complex.";
RL Cell 106:71-81(2001).
CC -!- FUNCTION: The association of the DR1/DRAP1 heterodimer with TBP results
CC in a functional repression of both activated and basal transcription of
CC class II genes. This interaction precludes the formation of a
CC transcription-competent complex by inhibiting the association of TFIIA
CC and/or TFIIB with TBP. Can bind to DNA on its own.
CC {ECO:0000269|PubMed:8608938, ECO:0000269|PubMed:8670811}.
CC -!- SUBUNIT: Heterodimer with DR1. Binds BTAF1.
CC {ECO:0000269|PubMed:11461703}.
CC -!- INTERACTION:
CC Q14919; Q01658: DR1; NbExp=32; IntAct=EBI-712941, EBI-750300;
CC Q14919; Q14919: DRAP1; NbExp=3; IntAct=EBI-712941, EBI-712941;
CC Q14919; Q00403: GTF2B; NbExp=6; IntAct=EBI-712941, EBI-389564;
CC Q14919; P25791: LMO2; NbExp=3; IntAct=EBI-712941, EBI-739696;
CC Q14919; P25791-3: LMO2; NbExp=3; IntAct=EBI-712941, EBI-11959475;
CC Q14919; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-712941, EBI-739832;
CC Q14919; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-712941, EBI-348259;
CC Q14919; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-712941, EBI-10288852;
CC Q14919; O43639: NCK2; NbExp=3; IntAct=EBI-712941, EBI-713635;
CC Q14919; P25208: NFYB; NbExp=4; IntAct=EBI-712941, EBI-389728;
CC Q14919; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-712941, EBI-79165;
CC Q14919; Q92569: PIK3R3; NbExp=4; IntAct=EBI-712941, EBI-79893;
CC Q14919; Q9NRF9: POLE3; NbExp=7; IntAct=EBI-712941, EBI-744901;
CC Q14919; P32969: RPL9P9; NbExp=3; IntAct=EBI-712941, EBI-358122;
CC Q14919; O00560: SDCBP; NbExp=5; IntAct=EBI-712941, EBI-727004;
CC Q14919; Q16594: TAF9; NbExp=9; IntAct=EBI-712941, EBI-712521;
CC Q14919; Q9HBM6: TAF9B; NbExp=7; IntAct=EBI-712941, EBI-751601;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14919-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14919-2; Sequence=VSP_012215;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in adult testis,
CC heart, skeletal muscle, pancreas and brain, and in fetal brain, liver
CC and kidney. {ECO:0000269|PubMed:8608938, ECO:0000269|PubMed:8670811}.
CC -!- PTM: Phosphorylation reduces DNA binding, but has no effect on
CC heterodimerization and TBP binding. {ECO:0000269|PubMed:8608938,
CC ECO:0000269|PubMed:8670811}.
CC -!- SIMILARITY: Belongs to the NC2 alpha/DRAP1 family. {ECO:0000305}.
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DR EMBL; X96506; CAA65358.1; -; mRNA.
DR EMBL; U41843; AAB02192.1; -; mRNA.
DR EMBL; BC010025; AAH10025.1; -; mRNA.
DR CCDS; CCDS8123.1; -. [Q14919-1]
DR PIR; S70618; S70618.
DR RefSeq; NP_006433.2; NM_006442.3. [Q14919-1]
DR PDB; 1JFI; X-ray; 2.62 A; A=1-77.
DR PDBsum; 1JFI; -.
DR AlphaFoldDB; Q14919; -.
DR SMR; Q14919; -.
DR BioGRID; 115838; 49.
DR CORUM; Q14919; -.
DR IntAct; Q14919; 35.
DR MINT; Q14919; -.
DR STRING; 9606.ENSP00000307850; -.
DR iPTMnet; Q14919; -.
DR MetOSite; Q14919; -.
DR PhosphoSitePlus; Q14919; -.
DR SwissPalm; Q14919; -.
DR BioMuta; DRAP1; -.
DR DMDM; 56404465; -.
DR EPD; Q14919; -.
DR jPOST; Q14919; -.
DR MassIVE; Q14919; -.
DR MaxQB; Q14919; -.
DR PaxDb; Q14919; -.
DR PeptideAtlas; Q14919; -.
DR PRIDE; Q14919; -.
DR ProteomicsDB; 60220; -. [Q14919-1]
DR ProteomicsDB; 60221; -. [Q14919-2]
DR Antibodypedia; 1835; 183 antibodies from 22 providers.
DR DNASU; 10589; -.
DR Ensembl; ENST00000312515.7; ENSP00000307850.2; ENSG00000175550.8. [Q14919-1]
DR GeneID; 10589; -.
DR KEGG; hsa:10589; -.
DR MANE-Select; ENST00000312515.7; ENSP00000307850.2; NM_006442.4; NP_006433.2.
DR UCSC; uc001ogj.3; human. [Q14919-1]
DR CTD; 10589; -.
DR DisGeNET; 10589; -.
DR GeneCards; DRAP1; -.
DR HGNC; HGNC:3019; DRAP1.
DR HPA; ENSG00000175550; Low tissue specificity.
DR MIM; 602289; gene.
DR neXtProt; NX_Q14919; -.
DR OpenTargets; ENSG00000175550; -.
DR PharmGKB; PA27476; -.
DR VEuPathDB; HostDB:ENSG00000175550; -.
DR eggNOG; KOG1659; Eukaryota.
DR GeneTree; ENSGT00390000012424; -.
DR HOGENOM; CLU_045277_10_0_1; -.
DR InParanoid; Q14919; -.
DR OMA; QYMHMGN; -.
DR OrthoDB; 1504101at2759; -.
DR PhylomeDB; Q14919; -.
DR TreeFam; TF313964; -.
DR PathwayCommons; Q14919; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1502540; Signaling by Activin.
DR SignaLink; Q14919; -.
DR SIGNOR; Q14919; -.
DR BioGRID-ORCS; 10589; 263 hits in 1082 CRISPR screens.
DR ChiTaRS; DRAP1; human.
DR EvolutionaryTrace; Q14919; -.
DR GeneWiki; DRAP1; -.
DR GenomeRNAi; 10589; -.
DR Pharos; Q14919; Tbio.
DR PRO; PR:Q14919; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q14919; protein.
DR Bgee; ENSG00000175550; Expressed in left testis and 190 other tissues.
DR ExpressionAtlas; Q14919; baseline and differential.
DR Genevisible; Q14919; HS.
DR GO; GO:0017054; C:negative cofactor 2 complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:ARUK-UCL.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0016251; F:RNA polymerase II general transcription initiation factor activity; IDA:ARUK-UCL.
DR GO; GO:0001091; F:RNA polymerase II general transcription initiation factor binding; IDA:ARUK-UCL.
DR GO; GO:0017025; F:TBP-class protein binding; IPI:ARUK-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.20.10; -; 1.
DR IDEAL; IID00385; -.
DR InterPro; IPR003958; CBFA_NFYB_domain.
DR InterPro; IPR009072; Histone-fold.
DR Pfam; PF00808; CBFD_NFYB_HMF; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing; DNA-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8670811"
FT CHAIN 2..205
FT /note="Dr1-associated corepressor"
FT /id="PRO_0000080001"
FT DOMAIN 14..77
FT /note="Histone-fold"
FT REGION 91..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..112
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..138
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..153
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..193
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 111
FT /note="G -> WTVPSQR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8608938"
FT /id="VSP_012215"
FT CONFLICT 2..15
FT /note="PSKKKKYNARFPPA -> EF (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 14..21
FT /evidence="ECO:0007829|PDB:1JFI"
FT HELIX 34..58
FT /evidence="ECO:0007829|PDB:1JFI"
FT HELIX 67..71
FT /evidence="ECO:0007829|PDB:1JFI"
SQ SEQUENCE 205 AA; 22350 MW; 6154C43C6B8DC877 CRC64;
MPSKKKKYNA RFPPARIKKI MQTDEEIGKV AAAVPVIISR ALELFLESLL KKACQVTQSR
NAKTMTTSHL KQCIELEQQF DFLKDLVASV PDMQGDGEDN HMDGDKGARR GRKPGSGGRK
NGGMGTKSKD KKLSGTDSEQ EDESEDTDTD GEEETSQPPP QASHPSAHFQ SPPTPFLPFA
STLPLPPAPP GPSAPDEEDE EDYDS
