TISIDB

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus Nucleus, nucleolus Chromosome
Domain	PF02735 Ku70/Ku80 beta-barrel domain PF03730 Ku70/Ku80 C-terminal arm PF03731 Ku70/Ku80 N-terminal alpha/beta domain PF08785 Ku C terminal domain like
Function	Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:20383123). The XRCC5/6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.

> Gene Ontology [ TOP ]
Biological Process	GO:0000723 telomere maintenance GO:0000726 non-recombinational repair GO:0001101 response to acid chemical GO:0001819 positive regulation of cytokine production GO:0002244 hematopoietic progenitor cell differentiation GO:0006302 double-strand break repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0006970 response to osmotic stress GO:0006972 hyperosmotic response GO:0009314 response to radiation GO:0009651 response to salt stress GO:0010165 response to X-ray GO:0010212 response to ionizing radiation GO:0010332 response to gamma radiation GO:0010639 negative regulation of organelle organization GO:0010720 positive regulation of cell development GO:0019042 viral latency GO:0019043 establishment of viral latency GO:0032200 telomere organization GO:0032204 regulation of telomere maintenance GO:0032205 negative regulation of telomere maintenance GO:0032392 DNA geometric change GO:0032479 regulation of type I interferon production GO:0032481 positive regulation of type I interferon production GO:0032508 DNA duplex unwinding GO:0032606 type I interferon production GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0033002 muscle cell proliferation GO:0033044 regulation of chromosome organization GO:0042493 response to drug GO:0042538 hyperosmotic salinity response GO:0048659 smooth muscle cell proliferation GO:0048660 regulation of smooth muscle cell proliferation GO:0048863 stem cell differentiation GO:0050769 positive regulation of neurogenesis GO:0051052 regulation of DNA metabolic process GO:0051053 negative regulation of DNA metabolic process GO:0051962 positive regulation of nervous system development GO:0060218 hematopoietic stem cell differentiation GO:0060249 anatomical structure homeostasis GO:0070542 response to fatty acid GO:0071103 DNA conformation change GO:0071214 cellular response to abiotic stimulus GO:0071229 cellular response to acid chemical GO:0071396 cellular response to lipid GO:0071398 cellular response to fatty acid GO:0071470 cellular response to osmotic stress GO:0071472 cellular response to salt stress GO:0071474 cellular hyperosmotic response GO:0071475 cellular hyperosmotic salinity response GO:0071478 cellular response to radiation GO:0071479 cellular response to ionizing radiation GO:0071480 cellular response to gamma radiation GO:0071481 cellular response to X-ray GO:0075713 establishment of integrated proviral latency GO:0090656 t-circle formation GO:1904429 regulation of t-circle formation GO:1904430 negative regulation of t-circle formation GO:2001251 negative regulation of chromosome organization
Molecular Function	GO:0003678 DNA helicase activity GO:0003684 damaged DNA binding GO:0003691 double-stranded telomeric DNA binding GO:0004003 ATP-dependent DNA helicase activity GO:0004386 helicase activity GO:0008022 protein C-terminus binding GO:0008026 ATP-dependent helicase activity GO:0008094 DNA-dependent ATPase activity GO:0016829 lyase activity GO:0016835 carbon-oxygen lyase activity GO:0016887 ATPase activity GO:0031625 ubiquitin protein ligase binding GO:0042162 telomeric DNA binding GO:0042623 ATPase activity, coupled GO:0044389 ubiquitin-like protein ligase binding GO:0051575 5'-deoxyribose-5-phosphate lyase activity GO:0070035 purine NTP-dependent helicase activity
Cellular Component	GO:0000781 chromosome, telomeric region GO:0000782 telomere cap complex GO:0000783 nuclear telomere cap complex GO:0000784 nuclear chromosome, telomeric region GO:0032993 protein-DNA complex GO:0043564 Ku70:Ku80 complex GO:0044454 nuclear chromosome part GO:0070419 nonhomologous end joining complex GO:0098687 chromosomal region GO:1990391 DNA repair complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03450 Non-homologous end-joining
Reactome	R-HSA-164843: 2-LTR circle formation R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-1643685: Disease R-HSA-162594: Early Phase of HIV Life Cycle R-HSA-162906: HIV Infection R-HSA-162587: HIV Life Cycle R-HSA-3270619: IRF3-mediated induction of type I IFN R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-162592: Integration of provirus R-HSA-6798695: Neutrophil degranulation R-HSA-5693571: Nonhomologous End-Joining (NHEJ) R-HSA-1834941: STING mediated induction of host immune responses

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa03450 Non-homologous end-joining

Reactome

R-HSA-164843: 2-LTR circle formation
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-1643685: Disease
R-HSA-162594: Early Phase of HIV Life Cycle
R-HSA-162906: HIV Infection
R-HSA-162587: HIV Life Cycle
R-HSA-3270619: IRF3-mediated induction of type I IFN
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-162592: Integration of provirus
R-HSA-6798695: Neutrophil degranulation
R-HSA-5693571: Nonhomologous End-Joining (NHEJ)
R-HSA-1834941: STING mediated induction of host immune responses

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between XRCC5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of XRCC5 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -2.46; FDR: 0.03680	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of XRCC5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.156	0.356
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.129	0.966
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.178	0.936
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.141	0.695
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.148	0.952
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.508	0.874
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.022	0.966
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.129	0.957
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.187	0.944
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.201	0.919
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.077	0.98
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.086	0.109

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of XRCC5 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of XRCC5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of XRCC5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by XRCC5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of XRCC5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of XRCC5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between XRCC5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	XRCC5
Name	X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)
Aliases	KU80; KARP-1; Ku86; KUB2; Ku autoantigen, 80kDa; X-ray repair complementing defective repair in Chinese hams ......
Chromosomal Location	2q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting XRCC5 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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