DRAP1

Summary

DRAP1 (DR1 associated protein 1, HGNC:3019) is a protein-coding gene on chromosome 11q13.1, encoding Dr1-associated corepressor (Q14919). The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. It is a selective cancer dependency (DepMap: 38.4% of cell lines).

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 and general transcription factors such as TFIIA, TFIIB, and TFIID. DR1 is a repressor that interacts with the TATA-binding protein (TBP) 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 protein encoded by this gene is a corepressor of transcription that interacts with DR1 to enhance DR1-mediated repression. The interaction between this corepressor and DR1 is required for corepressor function and appears to stabilize the TBP-DR1-DNA complex.

Source: NCBI Gene 10589 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 38.4% of screened cell lines
• MANE Select transcript: NM_006442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3019
Approved symbol	DRAP1
Name	DR1 associated protein 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	NC2-alpha
Ensembl gene	ENSG00000175550
Ensembl biotype	protein_coding
OMIM	602289
Entrez	10589

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000312515, ENST00000376991, ENST00000525190, ENST00000525501, ENST00000527119, ENST00000530791, ENST00000531121, ENST00000532933, ENST00000534333

RefSeq mRNA: 1 — MANE Select: NM_006442 NM_006442

CCDS: CCDS8123

Canonical transcript exons

ENST00000312515 — 7 exons

Exon	Start	End
ENSE00001190239	65921330	65921563
ENSE00001190263	65919948	65920041
ENSE00001190268	65919780	65919852
ENSE00001190274	65919426	65919543
ENSE00003458303	65920884	65920972
ENSE00003538359	65920569	65920662
ENSE00003687524	65920343	65920462

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 114.4621 / max 1839.2630, expressed in 1827 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115246	77.7700	1826
115252	7.9342	1502
115249	6.9892	1591
115243	6.7956	1312
115247	6.3111	1628
115245	3.4133	753
115250	1.2865	548
115251	1.0656	497
115253	0.9074	344
115248	0.6092	314

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.13	gold quality
right testis	UBERON:0004534	99.04	gold quality
granulocyte	CL:0000094	98.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.37	gold quality
right frontal lobe	UBERON:0002810	98.31	gold quality
left lobe of thyroid gland	UBERON:0001120	98.30	gold quality
lower esophagus mucosa	UBERON:0035834	98.28	gold quality
right lobe of thyroid gland	UBERON:0001119	98.27	gold quality
cerebellar hemisphere	UBERON:0002245	98.25	gold quality
cerebellar cortex	UBERON:0002129	98.23	gold quality
apex of heart	UBERON:0002098	98.22	gold quality
prefrontal cortex	UBERON:0000451	98.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.03	gold quality
ascending aorta	UBERON:0001496	98.00	gold quality
thoracic aorta	UBERON:0001515	97.98	gold quality
cingulate cortex	UBERON:0003027	97.98	gold quality
anterior cingulate cortex	UBERON:0009835	97.95	gold quality
nucleus accumbens	UBERON:0001882	97.90	gold quality
amygdala	UBERON:0001876	97.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.89	gold quality
left coronary artery	UBERON:0001626	97.85	gold quality
aorta	UBERON:0000947	97.84	gold quality
monocyte	CL:0000576	97.82	gold quality
popliteal artery	UBERON:0002250	97.82	gold quality
tibial artery	UBERON:0007610	97.82	gold quality
right coronary artery	UBERON:0001625	97.81	gold quality
skin of leg	UBERON:0001511	97.80	gold quality
lower esophagus	UBERON:0013473	97.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.77	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	126.47
E-HCAD-4	yes	60.20
E-ANND-3	yes	8.80
E-MTAB-7303	no	456.66
E-CURD-120	no	6.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TBP	Unknown

miRNA regulators (miRDB)

15 targeting DRAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-6813-5P	94.68	64.20	588

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 38.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Hypoxia actively represses transcription by inducing this protein and blocking preinitiation complex assembly. (PMID:12477712)
• physical cooperation between BTAF1 and NC2alpha in TBP regulation (PMID:15509807)
• The global distribution of DRAP1 on promoters was determined. (PMID:17548813)
• provide evidence that negative cofactor-2 (NC2) induces dynamic conformational changes in the TBP-DNA complex that allow it to escape and return to TATA-binding mode (PMID:17994103)
• heterodimerization with NC2alpha masks the nuclear localization signal in NC2beta, which prevents nuclear export of the NC2 complex (PMID:19204005)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	drap1	ENSDARG00000041203
mus_musculus	Drap1	ENSMUSG00000024914
rattus_norvegicus	Drap1	ENSRNOG00000020527
drosophila_melanogaster	NC2alpha	FBGN0034650
caenorhabditis_elegans		WBGENE00009584

Paralogs (2): NFYC (ENSG00000066136), POLE4 (ENSG00000115350)

Protein

Protein identifiers

Dr1-associated corepressor — Q14919 (reviewed: Q14919)

Alternative names: Dr1-associated protein 1, Negative cofactor 2-alpha

All UniProt accessions (5): Q14919, C9JCC6, E9PMW2, E9PNC7, E9PQX9

UniProt curated annotations — full annotation on UniProt →

Function. The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own.

Subunit / interactions. Heterodimer with DR1. Binds BTAF1.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in adult testis, heart, skeletal muscle, pancreas and brain, and in fetal brain, liver and kidney.

Post-translational modifications. Phosphorylation reduces DNA binding, but has no effect on heterodimerization and TBP binding.

Similarity. Belongs to the NC2 alpha/DRAP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14919-1	1	yes
Q14919-2	2

RefSeq proteins (1): NP_006433* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003958	CBFA_NFYB_domain	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR050568	Transcr_DNA_Rep_Reg	Family

Pfam: PF00808

UniProt features (14 total): compositionally biased region 5, helix 3, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1JFI	X-RAY DIFFRACTION	2.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14919-F1	73.87	0.41

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1502540	Signaling by Activin
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 182 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GCM_MSN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, chr11q13, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GALE_APL_WITH_FLT3_MUTATED_DN, GOBP_REGULATION_OF_RNA_POLYMERASE_II_TRANSCRIPTION_PREINITIATION_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), transcription by RNA polymerase II (GO:0006366)

GO Molecular Function (8): core promoter sequence-specific DNA binding (GO:0001046), RNA polymerase II general transcription initiation factor binding (GO:0001091), RNA polymerase II general transcription initiation factor activity (GO:0016251), TBP-class protein binding (GO:0017025), identical protein binding (GO:0042802), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), negative cofactor 2 complex (GO:0017054), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	1
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
general transcription initiation factor binding	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
transcription cis-regulatory region binding	1
RNA polymerase II complex binding	1
general transcription initiation factor activity	1
protein binding	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
RNA polymerase II transcription repressor complex	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DRAP1	DR1	Q01658	990
DRAP1	FOXH1	O75593	925
DRAP1	CFAP20	Q9Y6A4	804
DRAP1	GTF2B	Q00403	785
DRAP1	TBP	P20226	784
DRAP1	BTAF1	O14981	744
DRAP1	H2BC21	Q16778	700
DRAP1	H2AC20	Q16777	626
DRAP1	H2AC19	P20670	625
DRAP1	LEFTY2	O00292	602
DRAP1	SSNA1	O43805	556
DRAP1	NFYB	P25208	555
DRAP1	SAP30L	Q9HAJ7	529
DRAP1	WSB2	Q9NYS7	519
DRAP1	FOXA2	Q9Y261	487

IntAct

151 interactions, top by confidence:

A	B	Type	Score
DR1	DRAP1	psi-mi:“MI:0915”(physical association)	0.950
DR1	DRAP1	psi-mi:“MI:2364”(proximity)	0.950

BioGRID (121): DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), TAF9B (Two-hybrid), POLE3 (Two-hybrid), DRAP1 (Two-hybrid), POLE3 (Two-hybrid), DRAP1 (Two-hybrid), DRAP1 (Two-hybrid), TAF9B (Two-hybrid), DRAP1 (Co-fractionation), DRAP1 (Co-fractionation)

ESM2 similar proteins: A0JPP1, A0JPQ7, A2VDN6, E6ZGB4, O75151, O75376, O88974, P0CH95, P22682, P55265, P55266, Q14919, Q15047, Q15459, Q17R89, Q2YDP3, Q3UIA2, Q3YEC7, Q4KKX4, Q4V7W5, Q5F3B1, Q5R6Y9, Q5SFM8, Q5U3K5, Q60974, Q61909, Q68EM7, Q6P949, Q6ZM86, Q80TJ7, Q86XZ4, Q8CFK2, Q8K1N4, Q8K4S7, Q8K4Z5, Q8N5Y2, Q8R3Y5, Q8VHI6, Q8VI24, Q92625

Diamond homologs: A0JPP1, A6BLW4, A6QQ14, B0XTT5, C6Y4D0, P40096, P70353, Q02516, Q10315, Q13952, Q14919, Q2YDP3, Q4PSE2, Q4X095, Q54DA1, Q58CM8, Q5E9X1, Q5RA23, Q62725, Q655V5, Q6C6M5, Q8L4B2, Q8LCG7, Q9CQ36, Q9D6N5, Q9FGP6, Q9FMV5, Q9NR33, Q9SMP0, Q9XE33, Q9ZVL3, O17072, P79007, Q557I1, Q6BX14, Q6CLM5, Q9FGP7, Q9FGP8, Q9JKP8, Q9NRG0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DRAP1	“form complex”	“NC2 complex”	binding
DRAP1	“up-regulates activity”	BTAF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	6	11.3×	1e-03
Viral Infection Pathways	7	5.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II preinitiation complex assembly	6	34.0×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

767 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65919540:GCCG:G	donor_gain	1.0000
11:65919544:G:GG	donor_gain	1.0000
11:65919777:CAGGC:C	acceptor_loss	1.0000
11:65919778:A:AG	acceptor_gain	1.0000
11:65919778:A:G	acceptor_loss	1.0000
11:65919778:AG:A	acceptor_gain	1.0000
11:65919779:G:GT	acceptor_gain	1.0000
11:65919779:GG:G	acceptor_gain	1.0000
11:65919779:GGC:G	acceptor_gain	1.0000
11:65919779:GGCGC:G	acceptor_gain	1.0000
11:65919821:G:GT	donor_gain	1.0000
11:65919853:G:GG	donor_gain	1.0000
11:65920042:G:GG	donor_gain	1.0000
11:65920425:G:GT	donor_gain	1.0000
11:65920425:G:T	donor_gain	1.0000
11:65920452:G:GT	donor_gain	1.0000
11:65920659:GGAG:G	donor_gain	1.0000
11:65920660:GAGG:G	donor_gain	1.0000
11:65920661:AGG:A	donor_loss	1.0000
11:65920854:T:A	acceptor_gain	1.0000
11:65920858:A:AG	acceptor_gain	1.0000
11:65920859:A:AG	acceptor_gain	1.0000
11:65920859:ACTCT:A	acceptor_gain	1.0000
11:65920863:T:TA	acceptor_gain	1.0000
11:65920872:C:CA	acceptor_gain	1.0000
11:65920873:G:A	acceptor_gain	1.0000
11:65920882:A:AG	acceptor_gain	1.0000
11:65920883:G:GA	acceptor_loss	1.0000
11:65920883:G:GG	acceptor_gain	1.0000
11:65920883:GGAT:G	acceptor_gain	1.0000

AlphaMissense

1350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65919535:T:C	F12L	1.000
11:65919535:T:G	F12V	1.000
11:65919536:T:C	F12S	1.000
11:65919536:T:G	F12C	1.000
11:65919537:C:A	F12L	1.000
11:65919537:C:G	F12L	1.000
11:65919787:T:A	I17N	1.000
11:65919787:T:C	I17T	1.000
11:65919787:T:G	I17S	1.000
11:65919789:A:G	K18E	1.000
11:65919790:A:T	K18M	1.000
11:65919791:G:C	K18N	1.000
11:65919791:G:T	K18N	1.000
11:65919792:A:G	K19E	1.000
11:65919794:G:C	K19N	1.000
11:65919794:G:T	K19N	1.000
11:65919796:T:A	I20N	1.000
11:65919796:T:C	I20T	1.000
11:65919796:T:G	I20S	1.000
11:65919799:T:A	M21K	1.000
11:65919799:T:C	M21T	1.000
11:65919799:T:G	M21R	1.000
11:65919802:A:C	Q22P	1.000
11:65919803:G:C	Q22H	1.000
11:65919803:G:T	Q22H	1.000
11:65919807:G:C	D24H	1.000
11:65919807:G:T	D24Y	1.000
11:65919808:A:C	D24A	1.000
11:65919808:A:G	D24G	1.000
11:65919808:A:T	D24V	1.000

dbSNP variants (sampled 300 via entrez): RS1000508303 (11:65921606 C>G,T), RS1001663632 (11:65917485 G>A,C), RS1002002692 (11:65919076 G>A), RS1002118650 (11:65919003 G>A,T), RS1002352172 (11:65921785 G>A), RS1002514295 (11:65919291 C>A,G,T), RS1002790477 (11:65922014 C>A,G), RS1003675475 (11:65919951 G>A,C), RS1004339217 (11:65919099 TCAGCGGCCG>T,TCAGCGGCCGCAGCGGCCG), RS1004490173 (11:65922044 G>A), RS1004558761 (11:65920232 C>T), RS1004643144 (11:65921327 C>T), RS1005076716 (11:65920047 C>G,T), RS1005230510 (11:65921114 C>T), RS1006663431 (11:65918717 G>A)

Disease associations

OMIM: gene MIM:602289 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST003123_24	Severe influenza A (H1N1) infection	3.000000e-17
GCST004617_136	Eosinophil percentage of granulocytes	7.000000e-16
GCST004623_51	Neutrophil percentage of granulocytes	5.000000e-14
GCST009597_43	Multiple sclerosis	1.000000e-09
GCST009798_25	Asthma	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric chloride	increases expression	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cisplatin	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Indomethacin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.