DDB2 (damage specific DNA binding protein 2)

Gene

• Entrez ID: 1643
• Gene name: Damage specific DNA binding protein 2
• Gene symbol: DDB2
• Synonyms (NCBI Gene): DDBB, UV-DDB2, XPE
• Chromosome: 11
• Chromosome location: 11p11.2
• Summary: This gene encodes a protein that is necessary for the repair of ultraviolet light-damaged DNA. This protein is the smaller subunit of a heterodimeric protein complex that participates in nucleotide excision repair, and this complex mediates the ubiquityla

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121434639	A>G	Pathogenic	Coding sequence variant, intron variant, missense variant
rs121434640	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs121434641	C>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant, intron variant
rs121434642	G>T	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, missense variant
rs1336484333	AAAG>-	Likely-pathogenic	Stop gained, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020865	hsa-miR-155-5p	Proteomics	18668040
MIRT029978	hsa-miR-26b-5p	Microarray	19088304
MIRT756022	hsa-miR-125a-5p	Luciferase reporter assay, Western blotting, qRT-PCR	36636074
MIRT756025	hsa-miR-125b-5p	Luciferase reporter assay, Western blotting, qRT-PCR	36636074
MIRT928800	hsa-miR-3187-3p	CLIP-seq
MIRT928801	hsa-miR-4264	CLIP-seq
MIRT928802	hsa-miR-4435	CLIP-seq
MIRT928803	hsa-miR-4529-5p	CLIP-seq
MIRT928804	hsa-miR-4701-5p	CLIP-seq
MIRT928805	hsa-miR-4798-5p	CLIP-seq
MIRT928806	hsa-miR-548s	CLIP-seq
MIRT928807	hsa-miR-584	CLIP-seq
MIRT928808	hsa-miR-588	CLIP-seq
MIRT1975060	hsa-miR-3065-3p	CLIP-seq
MIRT1975061	hsa-miR-4726-3p	CLIP-seq
MIRT2514460	hsa-miR-128	CLIP-seq
MIRT2514461	hsa-miR-188-3p	CLIP-seq
MIRT2514462	hsa-miR-198	CLIP-seq
MIRT1975060	hsa-miR-3065-3p	CLIP-seq
MIRT2514463	hsa-miR-3143	CLIP-seq
MIRT2514464	hsa-miR-3150b-3p	CLIP-seq
MIRT2514465	hsa-miR-3184	CLIP-seq
MIRT2514466	hsa-miR-3189-5p	CLIP-seq
MIRT2514467	hsa-miR-326	CLIP-seq
MIRT2514468	hsa-miR-330-5p	CLIP-seq
MIRT2514469	hsa-miR-3609	CLIP-seq
MIRT2514470	hsa-miR-3612	CLIP-seq
MIRT2514471	hsa-miR-3657	CLIP-seq
MIRT2514472	hsa-miR-3663-3p	CLIP-seq
MIRT2514473	hsa-miR-3671	CLIP-seq
MIRT2514474	hsa-miR-371b-3p	CLIP-seq
MIRT2514475	hsa-miR-423-5p	CLIP-seq
MIRT2514476	hsa-miR-4274	CLIP-seq
MIRT2514477	hsa-miR-4443	CLIP-seq
MIRT2514478	hsa-miR-4645-5p	CLIP-seq
MIRT2514479	hsa-miR-4673	CLIP-seq
MIRT2514480	hsa-miR-4719	CLIP-seq
MIRT2514481	hsa-miR-4729	CLIP-seq
MIRT2514482	hsa-miR-4758-3p	CLIP-seq
MIRT2514483	hsa-miR-4784	CLIP-seq
MIRT2514484	hsa-miR-4797-5p	CLIP-seq
MIRT2514485	hsa-miR-4803	CLIP-seq
MIRT2514486	hsa-miR-516b	CLIP-seq
MIRT2514487	hsa-miR-520a-5p	CLIP-seq
MIRT2514488	hsa-miR-525-5p	CLIP-seq
MIRT2514489	hsa-miR-548ah	CLIP-seq
MIRT2514490	hsa-miR-548n	CLIP-seq
MIRT2514491	hsa-miR-548t	CLIP-seq
MIRT2514492	hsa-miR-593	CLIP-seq
MIRT2514493	hsa-miR-650	CLIP-seq
MIRT2514494	hsa-miR-659	CLIP-seq
MIRT2514460	hsa-miR-128	CLIP-seq
MIRT2514461	hsa-miR-188-3p	CLIP-seq
MIRT2514462	hsa-miR-198	CLIP-seq
MIRT2514463	hsa-miR-3143	CLIP-seq
MIRT2514464	hsa-miR-3150b-3p	CLIP-seq
MIRT2514466	hsa-miR-3189-5p	CLIP-seq
MIRT2514467	hsa-miR-326	CLIP-seq
MIRT2514468	hsa-miR-330-5p	CLIP-seq
MIRT2514470	hsa-miR-3612	CLIP-seq
MIRT2514471	hsa-miR-3657	CLIP-seq
MIRT2514474	hsa-miR-371b-3p	CLIP-seq
MIRT2514476	hsa-miR-4274	CLIP-seq
MIRT2514477	hsa-miR-4443	CLIP-seq
MIRT1975061	hsa-miR-4726-3p	CLIP-seq
MIRT2514481	hsa-miR-4729	CLIP-seq
MIRT2514482	hsa-miR-4758-3p	CLIP-seq
MIRT2514483	hsa-miR-4784	CLIP-seq
MIRT2514485	hsa-miR-4803	CLIP-seq
MIRT2514486	hsa-miR-516b	CLIP-seq
MIRT2514487	hsa-miR-520a-5p	CLIP-seq
MIRT2514488	hsa-miR-525-5p	CLIP-seq
MIRT2514490	hsa-miR-548n	CLIP-seq
MIRT2514491	hsa-miR-548t	CLIP-seq
MIRT2514492	hsa-miR-593	CLIP-seq
MIRT2514493	hsa-miR-650	CLIP-seq
MIRT2514494	hsa-miR-659	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
BRCA1	Activation	12170778
NF1	Unknown	12527763
SP1	Unknown	12527763
TP53	Activation	16357511
TP53	Unknown	12771027;12967652;15856024;15927209;22336944
TP63	Unknown	17984111

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000209	Process	Protein polyubiquitination	IDA	12732143
GO:0000785	Component	Chromatin	ISS	33937266
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	8798680
GO:0003684	Function	Damaged DNA binding	IBA
GO:0003684	Function	Damaged DNA binding	IDA	22334663
GO:0003684	Function	Damaged DNA binding	IEA
GO:0003684	Function	Damaged DNA binding	ISS	33937266
GO:0003684	Function	Damaged DNA binding	TAS	8407967
GO:0004842	Function	Ubiquitin-protein transferase activity	IDA	12732143
GO:0005515	Function	Protein binding	IPI	9418871, 12732143, 16473935, 16949367, 17041588, 17360488, 19109893, 19966799, 21145461, 22039351, 22822215, 26496610, 28514442, 30945288, 32814053, 33961781, 35271311
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	14751237
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	NAS	22118460
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0006281	Process	DNA repair	IBA
GO:0006281	Process	DNA repair	IEA
GO:0006281	Process	DNA repair	TAS	8798680
GO:0006289	Process	Nucleotide-excision repair	IDA	19109893
GO:0006289	Process	Nucleotide-excision repair	ISS	33937266
GO:0006289	Process	Nucleotide-excision repair	ISS	33937266
GO:0006289	Process	Nucleotide-excision repair	TAS	8407967
GO:0006290	Process	Pyrimidine dimer repair	IEA
GO:0006974	Process	DNA damage response	EXP	22118460
GO:0006974	Process	DNA damage response	IEA
GO:0006974	Process	DNA damage response	ISS
GO:0009411	Process	Response to UV	IBA
GO:0009411	Process	Response to UV	IDA	12732143
GO:0016567	Process	Protein ubiquitination	IEA
GO:0030054	Component	Cell junction	IDA
GO:0031464	Component	Cul4A-RING E3 ubiquitin ligase complex	EXP	22118460
GO:0031464	Component	Cul4A-RING E3 ubiquitin ligase complex	IEA
GO:0031465	Component	Cul4B-RING E3 ubiquitin ligase complex	IDA	22334663
GO:0032991	Component	Protein-containing complex	IDA	12732143
GO:0034644	Process	Cellular response to UV	EXP	22118460
GO:0034644	Process	Cellular response to UV	IEA
GO:0034644	Process	Cellular response to UV	ISS
GO:0044877	Function	Protein-containing complex binding	IPI	11564863
GO:0051865	Process	Protein autoubiquitination	IDA	12732143
GO:0070914	Process	UV-damage excision repair	IDA	14751237, 22334663
GO:0080008	Component	Cul4-RING E3 ubiquitin ligase complex	IEA
GO:0080008	Component	Cul4-RING E3 ubiquitin ligase complex	IMP	16949367
GO:0090734	Component	Site of DNA damage	IDA	19109893

Other IDs

• MIM: 600811
• HGNC: 2718
• e!Ensembl: ENSG00000134574

Protein

• UniProt ID: Q92466
• Protein name: DNA damage-binding protein 2 (DDB p48 subunit) (DDBb) (Damage-specific DNA-binding protein 2) (UV-damaged DNA-binding protein 2) (UV-DDB 2)
• Protein function: Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:10882109, PubMed:11278856, PubMed:11705987, PubMed:12732143, PubMed:15882621, PubMe
• PDB: 3EI4, 3I7L, 4E54, 4E5Z, 6R8Y, 6R8Z, 6R90, 6R91, 6R92
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00400	WD40	232 → 271	WD domain, G-beta repeat	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed; with highest levels in corneal endothelium and lowest levels in brain. Isoform D1 is highly expressed in brain and heart. Isoform D2, isoform D3 and isoform D4 are weakly expressed. {ECO:0000269|PubMed:14751237}
• Sequence:

  MAPKKRPETQKTSEIVLRPRNKRSRSPLELEPEAKKLCAKGSGPSRRCDSDCLWVGLAGP
  QILPPCRSIVRTLHQHKLGRASWPSVQQGLQQSFLHTLDSYRILQKAAPFDRRATSLAWH
  PTHPSTVAVGSKGGDIMLWNFGIKDKPTFIKGIGAGGSITGLKFNPLNTNQFYASSMEGT
  TRLQDFKGNILRVFASSDTINIWFCSLDVSASSRMVVTGDNVGNVILLNMDGKELWNLRM
  HKKKVTHVALNPCCDWFLATASVDQTVKIWDLRQVRGKASFLYSLPHRHPVNAACFSPDG
  ARLLTTDQKSEIRVYSASQWDCPLGLIPHPHRHFQHLTPIKAAWHPRYNLIVVGRYPDPN
  FKSCTPYELRTIDVFDGNSGKMMCQLYDPESSGISSLNEFNPMGDTLASAMGYHILIWSQ
  EEARTRK

• Sequence length: 427

Pathways

KEGG:

Nucleotide excision repair
p53 signaling pathway
Ubiquitin mediated proteolysis
Hepatitis B
Epstein-Barr virus infection
Pathways in cancer
Transcriptional misregulation in cancer
Colorectal cancer
Pancreatic cancer
Endometrial cancer
Glioma
Thyroid cancer
Basal cell carcinoma
Melanoma
Chronic myeloid leukemia
Small cell lung cancer
Non-small cell lung cancer
Breast cancer
Hepatocellular carcinoma
Gastric cancer

Reactome:

Ub-specific processing proteases
DNA Damage Recognition in GG-NER
Formation of Incision Complex in GG-NER
Dual Incision in GG-NER
TP53 Regulates Transcription of DNA Repair Genes
Neddylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Xeroderma pigmentosum, group E	Pathogenic; Likely pathogenic	rs781655324, rs121434639, rs121434640, rs121434641, rs121434642, rs2540389596, rs1336484333	RCV001808076 RCV000009332 RCV000009333 RCV000009334 RCV000009335 RCV003225889 RCV002249484

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
DDB2-related disorder	Conflicting classifications of pathogenicity; Benign	rs143049891, rs549726695	RCV003935146 RCV003958406
Melanoma	-	rs2135519486	RCV005922550
Ovarian cancer	Conflicting classifications of pathogenicity	rs1953383789	RCV003154649
Xeroderma pigmentosum	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	rs143049891, rs148299549, rs375649516, rs1275847261, rs1440844986, rs2135511675, rs753070223, rs202083037, rs764606058, rs2135512289, rs376783024, rs758199547, rs375840702, rs756484790, rs374094218, rs549041558, rs4647761, rs199965459, rs61741581, rs4647750, rs373622283	RCV002257417 RCV002255846 RCV002259193 RCV002257069 RCV002257070 RCV002259194 RCV002258481 RCV002257072 RCV002257073 RCV002259195 RCV002257074 RCV002259196 RCV000354019 RCV000351378 RCV002257631 RCV002257632 RCV000393321 RCV002257998 RCV002256631 RCV002259044 RCV002258135

Associations from Text Mining
Disease Name	Relationship Type	References
Acne Vulgaris	Associate	24399259
Acute Radiation Syndrome	Associate	33476246, 35680903, 37676284, 38499035
Adenomatous Polyposis Coli	Associate	24259968
Alzheimer Disease	Associate	26263968
Anti N Methyl D Aspartate Receptor Encephalitis	Associate	34584012
Breast Neoplasms	Associate	18431487, 19339246, 26650177, 33017027
Carcinogenesis	Associate	10469312
Carcinoma Hepatocellular	Associate	32090112
Carcinoma Non Small Cell Lung	Associate	27553023
Carcinoma Renal Cell	Associate	36385010
Carcinoma Squamous Cell	Associate	25491297, 32508265
Cell Transformation Neoplastic	Associate	31664956
Chromosome Aberrations	Associate	24770583
Colorectal Neoplasms	Associate	24259968, 35817785
Colorectal Neoplasms	Stimulate	29568775
COVID 19	Associate	37573316
Death	Stimulate	23407396
Drug Hypersensitivity	Associate	24753253
Drug Related Side Effects and Adverse Reactions	Associate	20013802
Endometrial Neoplasms	Associate	37142958
Facial Neoplasms	Associate	17660462
Gastritis Atrophic	Associate	26760766
Genetic Diseases Inborn	Associate	24753253
Genomic Instability	Associate	35817785
Glioma	Associate	16247447
Hematologic Diseases	Associate	37676284
Hereditary Breast and Ovarian Cancer Syndrome	Associate	16357511, 18431487
Hypoxia	Stimulate	31740787
Hypoxia	Associate	35813480
Infections	Associate	24335308
Inflammation	Associate	24399259
Leukemia Lymphocytic Chronic B Cell	Associate	18945750
Lysosomal Storage Diseases	Associate	17357082
Melanoma	Inhibit	16888633
Melanoma	Associate	17597816, 23407396, 27487145, 37573316
Mesothelioma Malignant	Associate	30700254
Neoplasms	Associate	12170778, 17660462, 18431487, 24770583, 25491297, 26130719
Neoplasms	Inhibit	31740787
Obesity	Associate	29459183
Osteosarcoma	Associate	31337976
Ovarian Diseases	Inhibit	29752431
Ovarian Neoplasms	Associate	20013802, 24249678, 26130719
Ovarian Neoplasms	Inhibit	29752431
Prostatic Neoplasms	Associate	28212551
Skin Neoplasms	Associate	21388382, 24753253, 37573316
Small Cell Lung Carcinoma	Associate	32457468
Smoke Inhalation Injury	Associate	23720401, 26760766
Spinocerebellar Ataxia Autosomal Recessive 2	Associate	17984111
Squamous Cell Carcinoma of Head and Neck	Associate	31740787
Stomach Neoplasms	Inhibit	26760766
Stomach Neoplasms	Associate	26760766, 27340861, 36672781
Supranuclear Palsy Progressive	Associate	17357082
Triple Negative Breast Neoplasms	Associate	31541611
UV Sensitive Syndrome	Associate	32457468
Xeroderma Pigmentosum	Associate	10469312, 10771487, 12732143, 14560002, 21388382, 24335308, 24753253, 24770583, 25491297, 28719581, 30251654
Xeroderma Pigmentosum	Inhibit	16473935
Xeroderma Pigmentosum Complementation Group E	Associate	12170778, 12181326, 12527763, 16527807, 20368362, 22334663, 24760829, 37573316
Xeroderma Pigmentosum Complementation Group E	Inhibit	16473935