XRCC5 (X-ray repair cross complementing 5)

Gene

• Entrez ID: 7520
• Gene name: X-ray repair cross complementing 5
• Gene symbol: XRCC5
• Synonyms: KARP-1, KARP1, KU80, KUB2, Ku86, NFIV
• Chromosome: 2
• Chromosome location: 2q35
• Summary: The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT042031	hsa-miR-484	CLASH	23622248
MIRT043483	hsa-miR-331-3p	CLASH	23622248
MIRT047762	hsa-miR-7-5p	CLASH	23622248
MIRT048471	hsa-miR-100-5p	CLASH	23622248
MIRT050041	hsa-miR-26b-5p	CLASH	23622248
MIRT119400	hsa-miR-7977	HITS-CLIP	19536157
MIRT651434	hsa-miR-4528	HITS-CLIP	23824327
MIRT651435	hsa-miR-584-5p	HITS-CLIP	23824327
MIRT651436	hsa-miR-758-5p	HITS-CLIP	23824327
MIRT651437	hsa-miR-218-2-3p	HITS-CLIP	23824327
MIRT651438	hsa-miR-29b-1-5p	HITS-CLIP	23824327
MIRT712064	hsa-miR-361-5p	HITS-CLIP	19536157
MIRT712065	hsa-miR-92a-2-5p	HITS-CLIP	19536157
MIRT712066	hsa-miR-3927-5p	HITS-CLIP	19536157
MIRT712067	hsa-miR-4726-3p	HITS-CLIP	19536157
MIRT712068	hsa-miR-6764-5p	HITS-CLIP	19536157
MIRT712069	hsa-miR-1915-3p	HITS-CLIP	19536157
MIRT712070	hsa-miR-6840-3p	HITS-CLIP	19536157
MIRT712071	hsa-miR-1324	HITS-CLIP	19536157
MIRT712072	hsa-miR-2115-3p	HITS-CLIP	19536157
MIRT732442	hsa-miR-31-5p	qRT-PCR, Luciferase reporter assay, Western blot	25082302
MIRT733638	hsa-miR-526b-5p	Luciferase reporter assay, qRT-PCR, Western blot	25596743
MIRT734864	hsa-miR-623	Luciferase reporter assay, Western blot	27685632

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000723	Process	Telomere maintenance	IBA	21873635
GO:0000781	Component	Chromosome, telomeric region	HDA	19135898
GO:0000781	Component	Chromosome, telomeric region	IDA	10535943
GO:0000783	Component	Nuclear telomere cap complex	TAS	15100233
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	18809223
GO:0002218	Process	Activation of innate immune response	IDA	28712728
GO:0003677	Function	DNA binding	NAS	1537839
GO:0003678	Function	DNA helicase activity	IEA
GO:0003684	Function	Damaged DNA binding	IEA
GO:0003690	Function	Double-stranded DNA binding	IBA	21873635
GO:0003691	Function	Double-stranded telomeric DNA binding	IDA	10409678
GO:0003723	Function	RNA binding	HDA	22658674, 22681889
GO:0003723	Function	RNA binding	IDA	14704337
GO:0005515	Function	Protein binding	IPI	8621488, 12145306, 12377759, 14704337, 15075319, 17159921, 17283121, 17308091, 17396150, 19142223, 19303849, 20023628, 20085707, 20098424, 20711232, 21070772, 21679440, 22451927, 22504299, 23178593, 23685356, 24485452, 24610814, 24981860, 25277244, 25574025, 25749521, 25852083, 2603
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IDA	32103174
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA	32103174
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0006302	Process	Double-strand break repair	IMP	19581589
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IBA	21873635
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	26359349
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	20383123
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	TAS	15824061
GO:0006310	Process	DNA recombination	IEA
GO:0006974	Process	Cellular response to DNA damage stimulus	IMP	27248496
GO:0007420	Process	Brain development	IEA
GO:0008022	Function	Protein C-terminus binding	IPI	10783163
GO:0008047	Function	Enzyme activator activity	TAS	19188702
GO:0008094	Function	DNA-dependent ATPase activity	IDA	9368068
GO:0008283	Process	Cell population proliferation	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	22266820
GO:0032040	Component	Small-subunit processome	IDA	32103174
GO:0032204	Process	Regulation of telomere maintenance	TAS	15824061, 18710952, 24095731
GO:0032212	Process	Positive regulation of telomere maintenance via telomerase	IMP	19188702
GO:0032481	Process	Positive regulation of type I interferon production	TAS
GO:0032508	Process	DNA duplex unwinding	IEA
GO:0032991	Component	Protein-containing complex	IDA	22504299
GO:0032993	Component	Protein-DNA complex	IDA	22504299
GO:0034462	Process	Small-subunit processome assembly	IDA	32103174
GO:0034511	Function	U3 snoRNA binding	IDA	32103174
GO:0034774	Component	Secretory granule lumen	TAS
GO:0042162	Function	Telomeric DNA binding	IBA	21873635
GO:0042162	Function	Telomeric DNA binding	IDA	10535943
GO:0042162	Function	Telomeric DNA binding	TAS	12377759
GO:0042493	Process	Response to drug	IEA
GO:0043085	Process	Positive regulation of catalytic activity	TAS	19188702
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043564	Component	Ku70:Ku80 complex	IBA	21873635
GO:0043564	Component	Ku70:Ku80 complex	IDA	20383123, 24095731, 26359349
GO:0043564	Component	Ku70:Ku80 complex	TAS	19188702
GO:0044877	Function	Protein-containing complex binding	IPI	12377759
GO:0045027	Function	DNA end binding	IDA	19549901
GO:0045027	Function	DNA end binding	IDA	9368068
GO:0045087	Process	Innate immune response	IEA
GO:0045860	Process	Positive regulation of protein kinase activity	IDA	22504299
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IMP	8621488
GO:0048660	Process	Regulation of smooth muscle cell proliferation	IMP	25852083
GO:0050769	Process	Positive regulation of neurogenesis	IEA
GO:0051575	Function	5'-deoxyribose-5-phosphate lyase activity	IMP	20383123
GO:0051973	Process	Positive regulation of telomerase activity	TAS	19188702
GO:0060218	Process	Hematopoietic stem cell differentiation	IEA
GO:0070198	Process	Protein localization to chromosome, telomeric region	TAS	19188702
GO:0070419	Component	Nonhomologous end joining complex	IDA	20383123, 25941166
GO:0071398	Process	Cellular response to fatty acid	IEA
GO:0071475	Process	Cellular hyperosmotic salinity response	IEA
GO:0071480	Process	Cellular response to gamma radiation	IBA	21873635
GO:0071480	Process	Cellular response to gamma radiation	IDA	26359349
GO:0071481	Process	Cellular response to X-ray	IBA	21873635
GO:0075713	Process	Establishment of integrated proviral latency	TAS
GO:0090734	Component	Site of DNA damage	IMP	27248496
GO:1904430	Process	Negative regulation of t-circle formation	IMP	19581589
GO:1990830	Process	Cellular response to leukemia inhibitory factor	IEA
GO:1990904	Component	Ribonucleoprotein complex	IDA	14704337

Other IDs

• MIM: 194364
• HGNC: 12833
• e!Ensembl: ENSG00000079246

Protein

• UniProt ID: P13010
• Protein name: X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining))
• Protein 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). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). 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.
• PDB: 1JEQ, 1JEY, 1Q2Z, 1RW2, 3RZ9, 5Y3R, 6ERF, 6ERG, 6ERH, 6ZH6, 6ZHA, 6ZHE, 7AXZ, 7K0Y, 7K17, 7K1J, 7K1K, 7K1N
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03731	Ku_N	9 → 244	Ku70/Ku80 N-terminal alpha/beta domain	Domain
  PF02735	Ku	253 → 453	Ku70/Ku80 beta-barrel domain	Domain
  PF03730	Ku_C	476 → 569	Ku70/Ku80 C-terminal arm	Family
  PF08785	Ku_PK_bind	593 → 706	Ku C terminal domain like	Domain

• Sequence:

  MVRSGNKAAVVLCMDVGFTMSNSIPGIESPFEQAKKVITMFVQRQVFAENKDEIALVLFG
  TDGTDNPLSGGDQYQNITVHRHLMLPDFDLLEDIESKIQPGSQQADFLDALIVSMDVIQH
  ETIGKKFEKRHIEIFTDLSSRFSKSQLDIIIHSLKKCDISLQFFLPFSLGKEDGSGDRGD
  GPFRLGGHGPSFPLKGITEQQKEGLEIVKMVMISLEGEDGLDEIYSFSESLRKLCVFKKI
  ERHSIHWPCRLTIGSNLSIRIAAYKSILQERVKKTWTVVDAKTLKKEDIQKETVYCLNDD
  DETEVLKEDIIQGFRYGSDIVPFSKVDEEQMKYKSEGKCFSVLGFCKSSQVQRRFFMGNQ
  VLKVFAARDDEAAAVALSSLIHALDDLDMVAIVRYAYDKRANPQVGVAFPHIKHNYECLV
  YVQLPFMEDLRQYMFSSLKNSKKYAPTEAQLNAVDALIDSMSLAKKDEKTDTLEDLFPTT
  KIPNPRFQRLFQCLLHRALHPREPLPPIQQHIWNMLNPPAEVTTKSQIPLSKIKTLFPLI
  EAKKKDQVTAQEIFQDNHEDGPTAKKLKTEQGGAHFSVSSLAEGSVTSVGSVNPAENFRV
  LVKQKKASFEEASNQLINHIEQFLDTNETPYFMKSIDCIRAFREEAIKFSEEQRFNNFLK
  ALQEKVEIKQLNHFWEIVVQDGITLITKEEASGSSVTAEEAKKFLAPKDKPSGDTAAVFE
  EGGDVDDLLDMI

• Sequence length: 732