Full text data of DRAP1
DRAP1
[Confidence: low (only semi-automatic identification from reviews)]
Dr1-associated corepressor (Dr1-associated protein 1; Negative cofactor 2-alpha; NC2-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Dr1-associated corepressor (Dr1-associated protein 1; Negative cofactor 2-alpha; NC2-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14919
ID NC2A_HUMAN Reviewed; 205 AA.
AC Q14919; Q13448;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 113.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-31,
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH DR1, AND TISSUE
RP SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=8670811;
RA Goppelt A.R., Stelzer G., Lottspeich F., Meisterernst M.;
RT "A mechanism for repression of class II gene transcription through
RT specific binding of NC2 to TBP-promoter complexes via heterodimeric
RT histone fold domains.";
RL EMBO J. 15:3105-3116(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF
RP 20-26; 30-39 AND 72-91, FUNCTION, INTERACTION WITH DR1,
RP PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=8608938;
RA Mermelstein F., Yeung K., Cao J., Inostroza J.A.,
RA Erdjument-Bromage H., Eagelson K., Landsman D., Levitt P., Tempst P.,
RA 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
RT project: 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
RT association 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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal 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;
RP TBP AND 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
CC results in a functional repression of both activated and basal
CC transcription of class II genes. This interaction precludes the
CC formation of a transcription-competent complex by inhibiting the
CC association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its
CC own.
CC -!- SUBUNIT: Heterodimer with DR1. Binds BTAF1.
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
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,
CC liver and kidney.
CC -!- PTM: Phosphorylation reduces DNA binding, but has no effect on
CC heterodimerization and TBP binding.
CC -!- SIMILARITY: Belongs to the NC2 alpha/DRAP1 family.
CC -!- SIMILARITY: Contains 1 histone-fold domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X96506; CAA65358.1; -; mRNA.
DR EMBL; U41843; AAB02192.1; -; mRNA.
DR EMBL; BC010025; AAH10025.1; -; mRNA.
DR PIR; S70618; S70618.
DR RefSeq; NP_006433.2; NM_006442.3.
DR UniGene; Hs.356742; -.
DR PDB; 1JFI; X-ray; 2.62 A; A=1-77.
DR PDBsum; 1JFI; -.
DR ProteinModelPortal; Q14919; -.
DR SMR; Q14919; 10-75.
DR IntAct; Q14919; 17.
DR MINT; MINT-1421885; -.
DR STRING; 9606.ENSP00000307850; -.
DR PhosphoSite; Q14919; -.
DR DMDM; 56404465; -.
DR PaxDb; Q14919; -.
DR PRIDE; Q14919; -.
DR DNASU; 10589; -.
DR Ensembl; ENST00000312515; ENSP00000307850; ENSG00000175550.
DR GeneID; 10589; -.
DR KEGG; hsa:10589; -.
DR UCSC; uc001ogj.2; human.
DR CTD; 10589; -.
DR GeneCards; GC11P065686; -.
DR HGNC; HGNC:3019; DRAP1.
DR HPA; HPA006790; -.
DR MIM; 602289; gene.
DR neXtProt; NX_Q14919; -.
DR PharmGKB; PA27476; -.
DR eggNOG; COG5247; -.
DR HOGENOM; HOG000113741; -.
DR HOVERGEN; HBG051403; -.
DR OrthoDB; EOG7FBRJ0; -.
DR PhylomeDB; Q14919; -.
DR ChiTaRS; DRAP1; human.
DR EvolutionaryTrace; Q14919; -.
DR GeneWiki; DRAP1; -.
DR GenomeRNAi; 10589; -.
DR NextBio; 40211; -.
DR PRO; PR:Q14919; -.
DR ArrayExpress; Q14919; -.
DR Bgee; Q14919; -.
DR CleanEx; HS_DRAP1; -.
DR Genevestigator; Q14919; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.20.10; -; 1.
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; Complete proteome;
KW Direct protein sequencing; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 205 Dr1-associated corepressor.
FT /FTId=PRO_0000080001.
FT DOMAIN 14 77 Histone-fold.
FT COMPBIAS 4 7 Poly-Lys.
FT COMPBIAS 158 195 Pro-rich.
FT VAR_SEQ 111 111 G -> WTVPSQR (in isoform 2).
FT /FTId=VSP_012215.
FT CONFLICT 2 15 PSKKKKYNARFPPA -> EF (in Ref. 2; AA
FT sequence).
FT HELIX 14 21
FT HELIX 34 58
FT HELIX 67 71
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
//
ID NC2A_HUMAN Reviewed; 205 AA.
AC Q14919; Q13448;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 113.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-31,
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH DR1, AND TISSUE
RP SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=8670811;
RA Goppelt A.R., Stelzer G., Lottspeich F., Meisterernst M.;
RT "A mechanism for repression of class II gene transcription through
RT specific binding of NC2 to TBP-promoter complexes via heterodimeric
RT histone fold domains.";
RL EMBO J. 15:3105-3116(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF
RP 20-26; 30-39 AND 72-91, FUNCTION, INTERACTION WITH DR1,
RP PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=8608938;
RA Mermelstein F., Yeung K., Cao J., Inostroza J.A.,
RA Erdjument-Bromage H., Eagelson K., Landsman D., Levitt P., Tempst P.,
RA 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
RT project: 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
RT association 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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal 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;
RP TBP AND 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
CC results in a functional repression of both activated and basal
CC transcription of class II genes. This interaction precludes the
CC formation of a transcription-competent complex by inhibiting the
CC association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its
CC own.
CC -!- SUBUNIT: Heterodimer with DR1. Binds BTAF1.
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
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,
CC liver and kidney.
CC -!- PTM: Phosphorylation reduces DNA binding, but has no effect on
CC heterodimerization and TBP binding.
CC -!- SIMILARITY: Belongs to the NC2 alpha/DRAP1 family.
CC -!- SIMILARITY: Contains 1 histone-fold domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X96506; CAA65358.1; -; mRNA.
DR EMBL; U41843; AAB02192.1; -; mRNA.
DR EMBL; BC010025; AAH10025.1; -; mRNA.
DR PIR; S70618; S70618.
DR RefSeq; NP_006433.2; NM_006442.3.
DR UniGene; Hs.356742; -.
DR PDB; 1JFI; X-ray; 2.62 A; A=1-77.
DR PDBsum; 1JFI; -.
DR ProteinModelPortal; Q14919; -.
DR SMR; Q14919; 10-75.
DR IntAct; Q14919; 17.
DR MINT; MINT-1421885; -.
DR STRING; 9606.ENSP00000307850; -.
DR PhosphoSite; Q14919; -.
DR DMDM; 56404465; -.
DR PaxDb; Q14919; -.
DR PRIDE; Q14919; -.
DR DNASU; 10589; -.
DR Ensembl; ENST00000312515; ENSP00000307850; ENSG00000175550.
DR GeneID; 10589; -.
DR KEGG; hsa:10589; -.
DR UCSC; uc001ogj.2; human.
DR CTD; 10589; -.
DR GeneCards; GC11P065686; -.
DR HGNC; HGNC:3019; DRAP1.
DR HPA; HPA006790; -.
DR MIM; 602289; gene.
DR neXtProt; NX_Q14919; -.
DR PharmGKB; PA27476; -.
DR eggNOG; COG5247; -.
DR HOGENOM; HOG000113741; -.
DR HOVERGEN; HBG051403; -.
DR OrthoDB; EOG7FBRJ0; -.
DR PhylomeDB; Q14919; -.
DR ChiTaRS; DRAP1; human.
DR EvolutionaryTrace; Q14919; -.
DR GeneWiki; DRAP1; -.
DR GenomeRNAi; 10589; -.
DR NextBio; 40211; -.
DR PRO; PR:Q14919; -.
DR ArrayExpress; Q14919; -.
DR Bgee; Q14919; -.
DR CleanEx; HS_DRAP1; -.
DR Genevestigator; Q14919; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.20.10; -; 1.
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; Complete proteome;
KW Direct protein sequencing; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 205 Dr1-associated corepressor.
FT /FTId=PRO_0000080001.
FT DOMAIN 14 77 Histone-fold.
FT COMPBIAS 4 7 Poly-Lys.
FT COMPBIAS 158 195 Pro-rich.
FT VAR_SEQ 111 111 G -> WTVPSQR (in isoform 2).
FT /FTId=VSP_012215.
FT CONFLICT 2 15 PSKKKKYNARFPPA -> EF (in Ref. 2; AA
FT sequence).
FT HELIX 14 21
FT HELIX 34 58
FT HELIX 67 71
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
//
MIM
602289
*RECORD*
*FIELD* NO
602289
*FIELD* TI
*602289 DR1-ASSOCIATED PROTEIN 1; DRAP1
;;NEGATIVE COFACTOR 2-ALPHA;;
NC2-ALPHA
*FIELD* TX
read more
DESCRIPTION
Transcriptional repression is a general mechanism for regulating
transcriptional initiation in organisms ranging from yeast to humans.
Accurate initiation of transcription from eukaryotic protein-encoding
genes requires the assembly of a large multiprotein complex consisting
of RNA polymerase II (see 180660) and general transcription factors such
as TFIIA (see 600519, 600520), TFIIB (see 189963), and TFIID (see
313650). DR1 (601482) is a repressor that interacts with the
TATA-binding protein (TBP; 600075) of TFIID and prevents the formation
of an active transcription complex by precluding the entry of TFIIA
and/or TFIIB into the preinitiation complex. The DR1-associated protein
DRAP1 is a corepressor of transcription that interacts with DR1 to
enhance DR1-mediated repression (Mermelstein et al., 1996). The
interaction between DRAP1 and DR1 is required for corepressor function
and appears to stabilize the TBP-DR1-DNA complex.
CLONING
Mermelstein et al. (1996) cloned a cDNA corresponding to DRAP1 by
screening HeLa cell and human liver cDNA libraries with a degenerative
oligonucleotide based on the amino acid sequence of DRAP1. Two types of
cDNA clones were isolated by them: a shorter cDNA, derived from the HeLa
cell library, that encodes a 193-amino acid protein, and a longer cDNA,
derived from the liver library, that contains a 7-amino acid insertion
at residue 98. Mermelstein et al. (1996) determined that the 2 cDNA
forms result from alternative splicing of the DRAP1 gene. Goppelt et al.
(1996) independently cloned the DRAP1 cDNA from a human B-cell cDNA
library and found that the cDNA encodes a 205-amino acid protein. The
DRAP1 protein contains a histone fold motif at the N terminus and a
proline-rich region at the C terminus. The binding of DRAP1 to DR1 is
dependent on the histone fold motif present in each protein.
GENE FUNCTION
Mermelstein et al. (1996) showed by Northern blot analysis that DRAP1
was expressed as a 1.1-kb transcript in every tissue examined, but at
higher levels in tissues containing a lower percentage of actively
dividing cells. Immunohistochemical analysis of the developing rat brain
demonstrated high levels of DRAP1 protein in highly differentiated,
nondividing cells, but undetectable levels in actively dividing cells.
Mermelstein et al. (1996) proposed that DRAP1 expression facilitates the
maintenance of a differentiated state by silencing specific genes.
Willy et al. (2000) identified an activity that was required for
transcription of downstream promoter element (DPE)-containing core
promoters in vitro. The purified factor was found to be the Drosophila
homolog of the NC2 transcriptional repressor, also known as DR1-DRAP1.
Drosophila Nc2 is composed of a 43-kD subunit homologous to DRAP1
(NC2-alpha) and a 22-kD subunit homologous to DR1 (NC2-beta). Purified
recombinant Drosophila Nc2 activated DPE-driven promoters and repressed
TATA-driven promoters. A mutant version of Drosophila Nc2 could activate
DPE promoters but was unable to repress TATA promoters. Thus, the
activation and repression functions are distinct. Willy et al. (2000)
concluded that NC2 is a bifunctional basal transcription factor that
differentially regulates gene transcription through DPE or TATA box
motifs.
Iratni et al. (2002) demonstrated that the transcriptional corepressor
DRAP1 has a very specific role in regulation of Nodal activity during
mouse embryogenesis. Iratni et al. (2002) found that loss of DRAP1 leads
to severe gastrulation defects that are consistent with increased
expression of Nodal and can be partially suppressed by Nodal
heterozygosity. Biochemical studies indicated that DRAP1 interacts with
and inhibits DNA binding by the winged-helix transcription factor FOXH1
(FAST1; 603621), a critical component of a positive feedback loop for
Nodal activity. Iratni et al. (2002) proposed that DRAP1 limits the
spread of a morphogenetic signal by downmodulating the response to the
Nodal autoregulatory loop.
BIOCHEMICAL FEATURES
- Crystal Structure
Kamada et al. (2001) determined the x-ray structure of a ternary complex
of NC2, TBP, and DNA at 2.6-angstrom resolution. The N termini of
NC2-alpha and -beta resemble histones H2A (see 613499) and H2B (see
609904), respectively, and form a heterodimer that binds to the bent DNA
double helix on the underside of the preformed TBP-DNA complex via
electrostatic interactions. NC2-beta contributes to inhibition of
TATA-dependent transcription through interactions of its C-terminal
alpha helix with a conserved hydrophobic feature on the upper surface of
TBP, which in turn positions the penultimate alpha helix of NC2-beta to
block recognition of the TBP-DNA complex by TFIIB.
*FIELD* RF
1. Goppelt, A.; Stelzer, G.; Lottspeich, F.; Meisterernst, M.: A
mechanism for repression of class II gene transcription through specific
binding of NC2 to TBP-promoter complexes via heterodimeric histone
fold domains. EMBO J. 15: 3105-3116, 1996.
2. Iratni, R.; Yan, Y.-T.; Chen, C.; Ding, J.; Zhang, Y.; Price, S.
M.; Reinberg, D.; Shen, M. M.: Inhibition of excess Nodal signaling
during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298:
1996-1999, 2002.
3. Kamada, K.; Shu, F.; Chen, H.; Malik, S.; Stelzer, G.; Roeder,
R. G.; Meisterernst, M.; Burley, S. K.: Crystal structure of negative
cofactor 2 recognizing the TBP-DNA transcription complex. Cell 106:
71-81, 2001.
4. Mermelstein, F.; Yeung, K.; Cao, J.; Inostroza, J. A.; Erdjument-Bromage,
H.; Eagelson, K.; Landsman, D.; Levitt, P.; Tempst, P.; Reinberg,
D.: Requirement of a corepressor for Dr1-mediated repression of transcription. Genes
Dev. 10: 1033-1048, 1996.
5. Willy, P. J.; Kobayashi, R.; Kadonaga, J. T.: A basal transcription
factor that activates or represses transcription. Science 290: 982-984,
2000.
*FIELD* CN
Ada Hamosh - updated: 2/5/2003
Stylianos E. Antonarakis - updated: 8/2/2001
Ada Hamosh - updated: 11/16/2000
*FIELD* CD
Patti M. Sherman: 1/28/1998
*FIELD* ED
mgross: 01/29/2013
mgross: 1/11/2013
alopez: 2/10/2003
terry: 2/5/2003
mgross: 8/2/2001
mgross: 11/16/2000
psherman: 9/18/1998
dholmes: 1/28/1998
*RECORD*
*FIELD* NO
602289
*FIELD* TI
*602289 DR1-ASSOCIATED PROTEIN 1; DRAP1
;;NEGATIVE COFACTOR 2-ALPHA;;
NC2-ALPHA
*FIELD* TX
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DESCRIPTION
Transcriptional repression is a general mechanism for regulating
transcriptional initiation in organisms ranging from yeast to humans.
Accurate initiation of transcription from eukaryotic protein-encoding
genes requires the assembly of a large multiprotein complex consisting
of RNA polymerase II (see 180660) and general transcription factors such
as TFIIA (see 600519, 600520), TFIIB (see 189963), and TFIID (see
313650). DR1 (601482) is a repressor that interacts with the
TATA-binding protein (TBP; 600075) of TFIID and prevents the formation
of an active transcription complex by precluding the entry of TFIIA
and/or TFIIB into the preinitiation complex. The DR1-associated protein
DRAP1 is a corepressor of transcription that interacts with DR1 to
enhance DR1-mediated repression (Mermelstein et al., 1996). The
interaction between DRAP1 and DR1 is required for corepressor function
and appears to stabilize the TBP-DR1-DNA complex.
CLONING
Mermelstein et al. (1996) cloned a cDNA corresponding to DRAP1 by
screening HeLa cell and human liver cDNA libraries with a degenerative
oligonucleotide based on the amino acid sequence of DRAP1. Two types of
cDNA clones were isolated by them: a shorter cDNA, derived from the HeLa
cell library, that encodes a 193-amino acid protein, and a longer cDNA,
derived from the liver library, that contains a 7-amino acid insertion
at residue 98. Mermelstein et al. (1996) determined that the 2 cDNA
forms result from alternative splicing of the DRAP1 gene. Goppelt et al.
(1996) independently cloned the DRAP1 cDNA from a human B-cell cDNA
library and found that the cDNA encodes a 205-amino acid protein. The
DRAP1 protein contains a histone fold motif at the N terminus and a
proline-rich region at the C terminus. The binding of DRAP1 to DR1 is
dependent on the histone fold motif present in each protein.
GENE FUNCTION
Mermelstein et al. (1996) showed by Northern blot analysis that DRAP1
was expressed as a 1.1-kb transcript in every tissue examined, but at
higher levels in tissues containing a lower percentage of actively
dividing cells. Immunohistochemical analysis of the developing rat brain
demonstrated high levels of DRAP1 protein in highly differentiated,
nondividing cells, but undetectable levels in actively dividing cells.
Mermelstein et al. (1996) proposed that DRAP1 expression facilitates the
maintenance of a differentiated state by silencing specific genes.
Willy et al. (2000) identified an activity that was required for
transcription of downstream promoter element (DPE)-containing core
promoters in vitro. The purified factor was found to be the Drosophila
homolog of the NC2 transcriptional repressor, also known as DR1-DRAP1.
Drosophila Nc2 is composed of a 43-kD subunit homologous to DRAP1
(NC2-alpha) and a 22-kD subunit homologous to DR1 (NC2-beta). Purified
recombinant Drosophila Nc2 activated DPE-driven promoters and repressed
TATA-driven promoters. A mutant version of Drosophila Nc2 could activate
DPE promoters but was unable to repress TATA promoters. Thus, the
activation and repression functions are distinct. Willy et al. (2000)
concluded that NC2 is a bifunctional basal transcription factor that
differentially regulates gene transcription through DPE or TATA box
motifs.
Iratni et al. (2002) demonstrated that the transcriptional corepressor
DRAP1 has a very specific role in regulation of Nodal activity during
mouse embryogenesis. Iratni et al. (2002) found that loss of DRAP1 leads
to severe gastrulation defects that are consistent with increased
expression of Nodal and can be partially suppressed by Nodal
heterozygosity. Biochemical studies indicated that DRAP1 interacts with
and inhibits DNA binding by the winged-helix transcription factor FOXH1
(FAST1; 603621), a critical component of a positive feedback loop for
Nodal activity. Iratni et al. (2002) proposed that DRAP1 limits the
spread of a morphogenetic signal by downmodulating the response to the
Nodal autoregulatory loop.
BIOCHEMICAL FEATURES
- Crystal Structure
Kamada et al. (2001) determined the x-ray structure of a ternary complex
of NC2, TBP, and DNA at 2.6-angstrom resolution. The N termini of
NC2-alpha and -beta resemble histones H2A (see 613499) and H2B (see
609904), respectively, and form a heterodimer that binds to the bent DNA
double helix on the underside of the preformed TBP-DNA complex via
electrostatic interactions. NC2-beta contributes to inhibition of
TATA-dependent transcription through interactions of its C-terminal
alpha helix with a conserved hydrophobic feature on the upper surface of
TBP, which in turn positions the penultimate alpha helix of NC2-beta to
block recognition of the TBP-DNA complex by TFIIB.
*FIELD* RF
1. Goppelt, A.; Stelzer, G.; Lottspeich, F.; Meisterernst, M.: A
mechanism for repression of class II gene transcription through specific
binding of NC2 to TBP-promoter complexes via heterodimeric histone
fold domains. EMBO J. 15: 3105-3116, 1996.
2. Iratni, R.; Yan, Y.-T.; Chen, C.; Ding, J.; Zhang, Y.; Price, S.
M.; Reinberg, D.; Shen, M. M.: Inhibition of excess Nodal signaling
during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298:
1996-1999, 2002.
3. Kamada, K.; Shu, F.; Chen, H.; Malik, S.; Stelzer, G.; Roeder,
R. G.; Meisterernst, M.; Burley, S. K.: Crystal structure of negative
cofactor 2 recognizing the TBP-DNA transcription complex. Cell 106:
71-81, 2001.
4. Mermelstein, F.; Yeung, K.; Cao, J.; Inostroza, J. A.; Erdjument-Bromage,
H.; Eagelson, K.; Landsman, D.; Levitt, P.; Tempst, P.; Reinberg,
D.: Requirement of a corepressor for Dr1-mediated repression of transcription. Genes
Dev. 10: 1033-1048, 1996.
5. Willy, P. J.; Kobayashi, R.; Kadonaga, J. T.: A basal transcription
factor that activates or represses transcription. Science 290: 982-984,
2000.
*FIELD* CN
Ada Hamosh - updated: 2/5/2003
Stylianos E. Antonarakis - updated: 8/2/2001
Ada Hamosh - updated: 11/16/2000
*FIELD* CD
Patti M. Sherman: 1/28/1998
*FIELD* ED
mgross: 01/29/2013
mgross: 1/11/2013
alopez: 2/10/2003
terry: 2/5/2003
mgross: 8/2/2001
mgross: 11/16/2000
psherman: 9/18/1998
dholmes: 1/28/1998