DET1

Summary

DET1 (DET1 partner of COP1 E3 ubiquitin ligase, HGNC:25477) is a protein-coding gene on chromosome 15q26.1, encoding DET1 homolog (Q7L5Y6). Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. It is a selective cancer dependency (DepMap: 20.3% of cell lines).

Enables ubiquitin protein ligase binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; and protein-containing complex assembly. Part of Cul4A-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 55070 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 103 total
• Cancer dependency (DepMap): dependent in 20.3% of screened cell lines
• MANE Select transcript: NM_001144074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25477
Approved symbol	DET1
Name	DET1 partner of COP1 E3 ubiquitin ligase
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10103
Ensembl gene	ENSG00000140543
Ensembl biotype	protein_coding
OMIM	608727
Entrez	55070

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000268148, ENST00000444300, ENST00000557837, ENST00000557842, ENST00000558413, ENST00000559656, ENST00000564406, ENST00000606927, ENST00000895600, ENST00000895601, ENST00000895602, ENST00000895603, ENST00000895604, ENST00000917530, ENST00000954629, ENST00000954630, ENST00000954631, ENST00000954632

RefSeq mRNA: 4 — MANE Select: NM_001144074 NM_001144074, NM_001321594, NM_001321596, NM_017996

CCDS: CCDS45343, CCDS45344

Canonical transcript exons

ENST00000268148 — 5 exons

Exon	Start	End
ENSE00001532888	88546540	88546681
ENSE00003506654	88530623	88531715
ENSE00003541674	88527599	88527786
ENSE00003614157	88516782	88516973
ENSE00003902021	88512480	88513140

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 82.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3876 / max 32.9687, expressed in 1529 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151385	3.3876	1529

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	82.06	gold quality
left ovary	UBERON:0002119	81.89	gold quality
right ovary	UBERON:0002118	81.24	gold quality
ventricular zone	UBERON:0003053	80.84	gold quality
muscle of leg	UBERON:0001383	80.55	gold quality
body of uterus	UBERON:0009853	80.21	gold quality
gastrocnemius	UBERON:0001388	80.03	gold quality
embryo	UBERON:0000922	79.82	gold quality
ganglionic eminence	UBERON:0004023	79.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.15	gold quality
adrenal tissue	UBERON:0018303	78.83	gold quality
right adrenal gland	UBERON:0001233	78.54	gold quality
stromal cell of endometrium	CL:0002255	78.13	gold quality
smooth muscle tissue	UBERON:0001135	78.06	gold quality
right adrenal gland cortex	UBERON:0035827	78.04	gold quality
endocervix	UBERON:0000458	77.81	gold quality
skeletal muscle organ	UBERON:0014892	77.80	gold quality
islet of Langerhans	UBERON:0000006	77.67	gold quality
left adrenal gland	UBERON:0001234	77.63	gold quality
left adrenal gland cortex	UBERON:0035825	77.10	gold quality
apex of heart	UBERON:0002098	77.04	gold quality
cortical plate	UBERON:0005343	76.93	gold quality
ovary	UBERON:0000992	76.87	gold quality
right uterine tube	UBERON:0001302	76.73	gold quality
adrenal gland	UBERON:0002369	76.23	gold quality
calcaneal tendon	UBERON:0003701	76.15	gold quality
adrenal cortex	UBERON:0001235	76.01	gold quality
body of pancreas	UBERON:0001150	75.61	gold quality
heart left ventricle	UBERON:0002084	75.56	gold quality
pancreas	UBERON:0001264	75.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.68
E-MTAB-7303	no	760.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting DET1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-556-5P	97.75	66.17	473

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• promotes ubiquitination and degradation of c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1 (PMID:14739464)
• These findings demonstrate that the conserved DET1 complex modulates Cul4A functions by a novel mechanism. (PMID:17452440)
• COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors. (PMID:29360641)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	det1	ENSDARG00000098247
mus_musculus	Det1	ENSMUSG00000030610
rattus_norvegicus	Det1	ENSRNOG00000018515
drosophila_melanogaster	abo	FBGN0000018

Protein

Protein identifiers

DET1 homolog — Q7L5Y6 (reviewed: Q7L5Y6)

Alternative names: De-etiolated-1 homolog

All UniProt accessions (3): Q7L5Y6, H0YK09, H0YN79

UniProt curated annotations — full annotation on UniProt →

Function. Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degradation.

Subunit / interactions. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in the ovary, some lymphoid organs and resting leukocytes.

Similarity. Belongs to the DET1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L5Y6-1	1	yes
Q7L5Y6-2	2

RefSeq proteins (4): NP_001137546, NP_001308523, NP_001308525, NP_060466 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019138	De-etiolated_protein_1_Det1	Family

Pfam: PF09737

UniProt features (43 total): strand 25, helix 9, turn 7, chain 1, splice variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9LTJ	ELECTRON MICROSCOPY	2.65
9BJZ	ELECTRON MICROSCOPY	2.83
9DHD	ELECTRON MICROSCOPY	2.9
9LTO	ELECTRON MICROSCOPY	2.92
9LTL	ELECTRON MICROSCOPY	2.93
9LTR	ELECTRON MICROSCOPY	3.03
9LTW	ELECTRON MICROSCOPY	3.25
9LTZ	ELECTRON MICROSCOPY	3.26
9LU1	ELECTRON MICROSCOPY	3.62
9W90	ELECTRON MICROSCOPY	3.7
9M0Y	ELECTRON MICROSCOPY	4.25
9LUL	ELECTRON MICROSCOPY	4.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L5Y6-F1	89.29	0.67

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 129 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, SP3_Q3, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SP1_Q2_01, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P

GO Biological Process (3): protein ubiquitination (GO:0016567), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), protein-containing complex assembly (GO:0065003)

GO Molecular Function (4): ubiquitin protein ligase binding (GO:0031625), protein-containing complex binding (GO:0044877), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cullin-RING ubiquitin ligase complex (GO:0031461), Cul4A-RING E3 ubiquitin ligase complex (GO:0031464), Cul4-RING E3 ubiquitin ligase complex (GO:0080008)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
protein modification by small protein conjugation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
cellular component assembly	1
protein-containing complex organization	1
ubiquitin-like protein ligase binding	1
enzyme-substrate adaptor activity	1
intracellular membrane-bounded organelle	1
ubiquitin ligase complex	1
Cul4-RING E3 ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DET1	DDB1	Q16531	999
DET1	CUL4A	Q13619	996
DET1	RBX1	P62877	988
DET1	DDA1	Q9BW61	978
DET1	CUL4B	Q13620	926
DET1	A0A087WZY1	A0A087WZY1	861
DET1	PRH1	P02810	860
DET1	COP1	Q8NHY2	850
DET1	DDB2	Q92466	829
DET1	H2BC1	Q96A08	730
DET1	H2BC17	P23527	729
DET1	H2BK1	A0A2R8Y619	728
DET1	H2BW2	P0C1H6	727
DET1	H2BW1	Q7Z2G1	727
DET1	H2BC13	Q99880	727
DET1	H2BC18	Q5QNW6	727
DET1	H2BC3	P33778	727

IntAct

48 interactions, top by confidence:

A	B	Type	Score
FOS	JUN	psi-mi:“MI:0914”(association)	0.980
FOSL2	JUN	psi-mi:“MI:0914”(association)	0.930
TRIB1	DET1	psi-mi:“MI:0914”(association)	0.640
TRIB2	POTEF	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
TRIB1	UBE2E1	psi-mi:“MI:0914”(association)	0.530
ETV5	DET1	psi-mi:“MI:0914”(association)	0.530
FOS	YEATS4	psi-mi:“MI:0914”(association)	0.530
DET1	UBE2E1	psi-mi:“MI:0914”(association)	0.530
TRIB2	UBE2E1	psi-mi:“MI:0914”(association)	0.530
COP1	ETS2	psi-mi:“MI:0914”(association)	0.460
DET1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
DET1	FKBP5	psi-mi:“MI:0915”(physical association)	0.400
DET1		psi-mi:“MI:0915”(physical association)	0.400
BAG2	DET1	psi-mi:“MI:0915”(physical association)	0.400
DET1	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
STIP1	DET1	psi-mi:“MI:0915”(physical association)	0.400
DET1	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
AARSD1	DET1	psi-mi:“MI:0915”(physical association)	0.400
JUNB	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
DET1	HSPA8	psi-mi:“MI:0914”(association)	0.350
ETV1	DET1	psi-mi:“MI:0914”(association)	0.350

BioGRID (599): DDB1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), CUL4B (Affinity Capture-Western), DET1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), RFWD2 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), RNF14 (Affinity Capture-Western), DET1 (Affinity Capture-MS), DET1 (Affinity Capture-MS), DET1 (Affinity Capture-MS), DET1 (Affinity Capture-MS), DET1 (Affinity Capture-Western), RFWD2 (Affinity Capture-MS), DET1 (Affinity Capture-MS)

ESM2 similar proteins: A2AF47, A2VE39, A7E2V1, D2HRF1, F6Y9J3, O02697, O15327, P48736, Q08D69, Q0E908, Q0VEJ0, Q1LX49, Q28DH9, Q499Q5, Q4R4D7, Q5JSL3, Q5R981, Q5RA60, Q5RCP7, Q5SW45, Q5U2X1, Q5U2Z5, Q5ZL91, Q62717, Q6DDX8, Q6GLR7, Q6P3K3, Q6PGF3, Q7L5Y6, Q7TQK1, Q802U2, Q86UW7, Q8BK06, Q8BYR5, Q8CDG3, Q8CF97, Q8CJF7, Q8N1G2, Q8NFP9, Q8TAP6

Diamond homologs: P48732, Q7L5Y6, Q9D0A0, Q9ZNU6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DET1	“form complex”	“DCX DET1-COP1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	16.8×	2e-04
regulation of cell cycle	5	10.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1291 predictions. Top by Δscore:

Variant	Effect	Δscore
15:88527593:GCTTA:G	donor_loss	1.0000
15:88527594:CTTAC:C	donor_loss	1.0000
15:88527595:TTACC:T	donor_loss	1.0000
15:88527596:T:TG	donor_loss	1.0000
15:88527597:A:AG	donor_loss	1.0000
15:88527598:C:G	donor_loss	1.0000
15:88527598:CCGG:C	donor_gain	1.0000
15:88527782:GATGC:G	acceptor_gain	1.0000
15:88527783:ATGC:A	acceptor_gain	1.0000
15:88527784:TGC:T	acceptor_gain	1.0000
15:88527784:TGCC:T	acceptor_loss	1.0000
15:88527785:GC:G	acceptor_gain	1.0000
15:88527785:GCCT:G	acceptor_loss	1.0000
15:88527786:CC:C	acceptor_gain	1.0000
15:88527786:CCTG:C	acceptor_loss	1.0000
15:88527787:C:CA	acceptor_loss	1.0000
15:88527787:C:CC	acceptor_gain	1.0000
15:88527788:T:C	acceptor_loss	1.0000
15:88531711:CATCT:C	acceptor_gain	1.0000
15:88531716:C:CC	acceptor_gain	1.0000
15:88527592:AGCTT:A	donor_loss	0.9900
15:88527597:A:AC	donor_gain	0.9900
15:88527598:C:CC	donor_gain	0.9900
15:88527656:T:TA	donor_gain	0.9900
15:88527656:TC:T	donor_gain	0.9900
15:88527790:C:CT	acceptor_gain	0.9900
15:88527791:A:T	acceptor_gain	0.9900
15:88529668:A:C	donor_gain	0.9900
15:88530617:TCATA:T	donor_loss	0.9900
15:88530618:CATAC:C	donor_loss	0.9900

AlphaMissense

3627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:88512976:A:G	F543S	1.000
15:88512989:A:G	Y539H	1.000
15:88513002:C:A	R534S	1.000
15:88513002:C:G	R534S	1.000
15:88513012:G:A	S531F	1.000
15:88513013:A:G	S531P	1.000
15:88513015:A:T	I530N	1.000
15:88513018:G:T	A529D	1.000
15:88513048:G:T	A519D	1.000
15:88513107:A:C	F499L	1.000
15:88513107:A:T	F499L	1.000
15:88513109:A:G	F499L	1.000
15:88513137:G:C	F489L	1.000
15:88513137:G:T	F489L	1.000
15:88513138:A:G	F489S	1.000
15:88513139:A:G	F489L	1.000
15:88516785:A:T	I487N	1.000
15:88516847:G:C	F466L	1.000
15:88516847:G:T	F466L	1.000
15:88516849:A:G	F466L	1.000
15:88516871:G:C	S458R	1.000
15:88516871:G:T	S458R	1.000
15:88516873:T:G	S458R	1.000
15:88516899:G:T	P449H	1.000
15:88527768:A:C	Y368D	1.000
15:88530681:A:G	L342P	1.000
15:88530937:C:G	G257R	1.000
15:88531008:G:A	S233F	1.000
15:88531020:A:G	L229P	1.000
15:88531045:C:G	G221R	1.000

dbSNP variants (sampled 300 via entrez): RS1000015123 (15:88539144 C>A,G,T), RS1000081009 (15:88503800 C>T), RS1000102029 (15:88522390 A>T), RS1000114309 (15:88512338 T>C,G), RS1000154076 (15:88538984 G>C), RS1000186343 (15:88523898 C>T), RS1000277390 (15:88515878 T>A), RS1000334004 (15:88509660 A>C), RS1000364951 (15:88509981 A>G), RS1000366907 (15:88508946 G>T), RS1000375194 (15:88546891 A>C), RS1000430099 (15:88534482 GC>G), RS1000441090 (15:88546646 G>A,C), RS1000486673 (15:88514863 A>G), RS1000587 (15:88507397 G>A,C)

Disease associations

OMIM: gene MIM:608727 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002541_104	Menarche (age at onset)	3.000000e-12
GCST010653_87	Thyroid stimulating hormone levels	1.000000e-31

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Air Pollutants	decreases expression, affects cotreatment, increases abundance	3
bisphenol A	decreases expression, increases expression	2
Cyclosporine	increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Fulvestrant	increases methylation	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cisplatin	affects expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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