GENERAL INFORMATIONi
Gene namei XRCC6
Synonyms D22S671, D22S731, G22P1, KU70, ML8
Gene descriptioni X-ray repair cross complementing 6
Protein classi Cancer-related genes
Plasma proteins
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 22
Cytoband q13.2
Chromosome location (bp) 41621163 - 41664048
Number of transcriptsi 6
Ensembl ENSG00000196419 (version 109)
Entrez gene 2547
HGNC HGNC:4055
UniProt P12956 (UniProt - Evidence at protein level)
neXtProt NX_P12956
GeneCards XRCC6
Antibodypedia XRCC6 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA 1, 2, 3, 4, 5, 6, 7. Required for double-strand break repair and V(D)J recombination 8, 9, 10, 11, 12, 13, 14. Also has a role in chromosome translocation 15, 16, 17, 18, 19, 20, 21. Has a role in chromosome translocation 22, 23, 24, 25, 26, 27, 28. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner 29, 30, 31, 32, 33, 34, 35. It works in the 3'-5' direction 36, 37, 38, 39, 40, 41, 42. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection 43, 44, 45, 46, 47, 48, 49. Binding to DNA may be mediated by XRCC6 50, 51, 52, 53, 54, 55, 56. The XRCC5-XRRC6 dimer acts as a 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 57, 58, 59, 60, 61, 62, 63. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together 64, 65, 66, 67, 68, 69, 70. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step 71, 72, 73, 74, 75, 76, 77. 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 78. 5'-dRP lyase activity 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 79. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription 80. In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression 81. 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 82. show less
Molecular function (UniProt)i Activator, DNA-binding, Helicase, Hydrolase, Lyase, Multifunctional enzyme
Biological process (UniProt)i DNA damage, DNA recombination, DNA repair, Host-virus interaction, Immunity, Innate immunity, Transcription, Transcription regulation
Ligand (UniProt)i ATP-binding, Nucleotide-binding
Gene summary (Entrez)i The p70/p80 autoantigen is a nuclear complex consisting of two subunits with molecular masses of approximately 70 and 80 kDa. The complex functions as a single-stranded DNA-dependent ATP-dependent helicase. The complex may be involved in the repair of nonhomologous DNA ends such as that required for double-strand break repair, transposition, and V(D)J recombination. High levels of autoantibodies to p70 and p80 have been found in some patients with systemic lupus erythematosus. [provided by RefSeq, Jul 2008] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
XRCC6-201
ENSP00000352257
ENST00000359308
P12956
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
A0A024R1N4
[Target identity:100%; Query identity:100%] X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Plasma proteins
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0000725 [recombinational repair]
GO:0000781 [chromosome, telomeric region]
GO:0000783 [nuclear telomere cap complex]
GO:0000976 [transcription cis-regulatory region binding]
GO:0002218 [activation of innate immune response]
GO:0002376 [immune system process]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0003690 [double-stranded DNA binding]
GO:0003691 [double-stranded telomeric DNA binding]
GO:0003723 [RNA binding]
GO:0003824 [catalytic activity]
GO:0004386 [helicase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005667 [transcription regulator complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0006266 [DNA ligation]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0008022 [protein C-terminus binding]
GO:0008094 [ATP-dependent activity, acting on DNA]
GO:0008152 [metabolic process]
GO:0016020 [membrane]
GO:0016787 [hydrolase activity]
GO:0016829 [lyase activity]
GO:0016887 [ATP hydrolysis activity]
GO:0030332 [cyclin binding]
GO:0032508 [DNA duplex unwinding]
GO:0032991 [protein-containing complex]
GO:0032993 [protein-DNA complex]
GO:0034774 [secretory granule lumen]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
GO:0044877 [protein-containing complex binding]
GO:0045027 [DNA end binding]
GO:0045087 [innate immune response]
GO:0045621 [positive regulation of lymphocyte differentiation]
GO:0045860 [positive regulation of protein kinase activity]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045893 [positive regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0048660 [regulation of smooth muscle cell proliferation]
GO:0051575 [5'-deoxyribose-5-phosphate lyase activity]
GO:0070418 [DNA-dependent protein kinase complex]
GO:0070419 [nonhomologous end joining complex]
GO:0071480 [cellular response to gamma radiation]
GO:0071481 [cellular response to X-ray]
GO:0097110 [scaffold protein binding]
GO:0097680 [double-strand break repair via classical nonhomologous end joining]
GO:1904813 [ficolin-1-rich granule lumen]
Show all
 609 aa
69.8 kDa 		No 0
XRCC6-202
ENSP00000353192
ENST00000360079
P12956
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
A0A024R1N4
[Target identity:100%; Query identity:100%] X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Plasma proteins
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0000725 [recombinational repair]
GO:0000781 [chromosome, telomeric region]
GO:0000783 [nuclear telomere cap complex]
GO:0000976 [transcription cis-regulatory region binding]
GO:0002218 [activation of innate immune response]
GO:0002376 [immune system process]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0003690 [double-stranded DNA binding]
GO:0003691 [double-stranded telomeric DNA binding]
GO:0003723 [RNA binding]
GO:0003824 [catalytic activity]
GO:0004386 [helicase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005667 [transcription regulator complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0006266 [DNA ligation]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0008022 [protein C-terminus binding]
GO:0008094 [ATP-dependent activity, acting on DNA]
GO:0008152 [metabolic process]
GO:0016020 [membrane]
GO:0016787 [hydrolase activity]
GO:0016829 [lyase activity]
GO:0016887 [ATP hydrolysis activity]
GO:0030332 [cyclin binding]
GO:0032508 [DNA duplex unwinding]
GO:0032991 [protein-containing complex]
GO:0032993 [protein-DNA complex]
GO:0034774 [secretory granule lumen]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
GO:0044877 [protein-containing complex binding]
GO:0045027 [DNA end binding]
GO:0045087 [innate immune response]
GO:0045621 [positive regulation of lymphocyte differentiation]
GO:0045860 [positive regulation of protein kinase activity]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045893 [positive regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0048660 [regulation of smooth muscle cell proliferation]
GO:0051575 [5'-deoxyribose-5-phosphate lyase activity]
GO:0070418 [DNA-dependent protein kinase complex]
GO:0070419 [nonhomologous end joining complex]
GO:0071480 [cellular response to gamma radiation]
GO:0071481 [cellular response to X-ray]
GO:0097110 [scaffold protein binding]
GO:0097680 [double-strand break repair via classical nonhomologous end joining]
GO:1904813 [ficolin-1-rich granule lumen]
Show all
 609 aa
69.8 kDa 		No 0
XRCC6-203
ENSP00000384941
ENST00000402580
P12956
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Plasma proteins
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0000725 [recombinational repair]
GO:0000781 [chromosome, telomeric region]
GO:0000783 [nuclear telomere cap complex]
GO:0000976 [transcription cis-regulatory region binding]
GO:0002218 [activation of innate immune response]
GO:0002376 [immune system process]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0003690 [double-stranded DNA binding]
GO:0003691 [double-stranded telomeric DNA binding]
GO:0003723 [RNA binding]
GO:0003824 [catalytic activity]
GO:0004386 [helicase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005667 [transcription regulator complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0006266 [DNA ligation]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0008022 [protein C-terminus binding]
GO:0008094 [ATP-dependent activity, acting on DNA]
GO:0008152 [metabolic process]
GO:0016020 [membrane]
GO:0016787 [hydrolase activity]
GO:0016829 [lyase activity]
GO:0016887 [ATP hydrolysis activity]
GO:0030332 [cyclin binding]
GO:0032508 [DNA duplex unwinding]
GO:0032991 [protein-containing complex]
GO:0032993 [protein-DNA complex]
GO:0034774 [secretory granule lumen]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
GO:0044877 [protein-containing complex binding]
GO:0045027 [DNA end binding]
GO:0045087 [innate immune response]
GO:0045621 [positive regulation of lymphocyte differentiation]
GO:0045860 [positive regulation of protein kinase activity]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045893 [positive regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0048660 [regulation of smooth muscle cell proliferation]
GO:0051575 [5'-deoxyribose-5-phosphate lyase activity]
GO:0070418 [DNA-dependent protein kinase complex]
GO:0070419 [nonhomologous end joining complex]
GO:0071480 [cellular response to gamma radiation]
GO:0071481 [cellular response to X-ray]
GO:0097110 [scaffold protein binding]
GO:0097680 [double-strand break repair via classical nonhomologous end joining]
GO:1904813 [ficolin-1-rich granule lumen]
Show all
 568 aa
65.1 kDa 		No 0
XRCC6-204
ENSP00000384082
ENST00000405506
B1AHC9
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0004386 [helicase activity]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0016787 [hydrolase activity]
GO:0032508 [DNA duplex unwinding]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
Show all
 559 aa
64.3 kDa 		No 0
XRCC6-205
ENSP00000384257
ENST00000405878
P12956
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
A0A024R1N4
[Target identity:100%; Query identity:100%] X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa), isoform CRA_a
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Plasma proteins
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0000725 [recombinational repair]
GO:0000781 [chromosome, telomeric region]
GO:0000783 [nuclear telomere cap complex]
GO:0000976 [transcription cis-regulatory region binding]
GO:0002218 [activation of innate immune response]
GO:0002376 [immune system process]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0003690 [double-stranded DNA binding]
GO:0003691 [double-stranded telomeric DNA binding]
GO:0003723 [RNA binding]
GO:0003824 [catalytic activity]
GO:0004386 [helicase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005667 [transcription regulator complex]
GO:0005694 [chromosome]
GO:0005730 [nucleolus]
GO:0005829 [cytosol]
GO:0006266 [DNA ligation]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0008022 [protein C-terminus binding]
GO:0008094 [ATP-dependent activity, acting on DNA]
GO:0008152 [metabolic process]
GO:0016020 [membrane]
GO:0016787 [hydrolase activity]
GO:0016829 [lyase activity]
GO:0016887 [ATP hydrolysis activity]
GO:0030332 [cyclin binding]
GO:0032508 [DNA duplex unwinding]
GO:0032991 [protein-containing complex]
GO:0032993 [protein-DNA complex]
GO:0034774 [secretory granule lumen]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
GO:0044877 [protein-containing complex binding]
GO:0045027 [DNA end binding]
GO:0045087 [innate immune response]
GO:0045621 [positive regulation of lymphocyte differentiation]
GO:0045860 [positive regulation of protein kinase activity]
GO:0045892 [negative regulation of DNA-templated transcription]
GO:0045893 [positive regulation of DNA-templated transcription]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0048660 [regulation of smooth muscle cell proliferation]
GO:0051575 [5'-deoxyribose-5-phosphate lyase activity]
GO:0070418 [DNA-dependent protein kinase complex]
GO:0070419 [nonhomologous end joining complex]
GO:0071480 [cellular response to gamma radiation]
GO:0071481 [cellular response to X-ray]
GO:0097110 [scaffold protein binding]
GO:0097680 [double-strand break repair via classical nonhomologous end joining]
GO:1904813 [ficolin-1-rich granule lumen]
Show all
 609 aa
69.8 kDa 		No 0
XRCC6-206
ENSP00000403679
ENST00000428575
B1AHC9
[Direct mapping] X-ray repair cross-complementing protein 6
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0000723 [telomere maintenance]
GO:0003677 [DNA binding]
GO:0003678 [DNA helicase activity]
GO:0003684 [damaged DNA binding]
GO:0004386 [helicase activity]
GO:0005524 [ATP binding]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0006281 [DNA repair]
GO:0006303 [double-strand break repair via nonhomologous end joining]
GO:0006310 [DNA recombination]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0016787 [hydrolase activity]
GO:0032508 [DNA duplex unwinding]
GO:0042162 [telomeric DNA binding]
GO:0043564 [Ku70:Ku80 complex]
Show all
 559 aa
64.3 kDa 		No 0

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