Human Gene XRCC6 (ENST00000360079.8)
  Description: Homo sapiens X-ray repair cross complementing 6 (XRCC6), transcript variant 1, mRNA. (from RefSeq NM_001469)
RefSeq Summary (NM_001469): 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].
Gencode Transcript: ENST00000360079.8
Gencode Gene: ENSG00000196419.13
Transcript (Including UTRs)
   Position: hg38 chr22:41,621,295-41,664,041 Size: 42,747 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg38 chr22:41,622,005-41,663,815 Size: 41,811 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr22:41,621,295-41,664,041)mRNA (may differ from genome)Protein (609 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: XRCC6_HUMAN
DESCRIPTION: RecName: Full=X-ray repair cross-complementing protein 6; EC=3.6.4.-; EC=4.2.99.-; AltName: Full=5'-deoxyribose-5-phosphate lyase Ku70; Short=5'-dRP lyase Ku70; AltName: Full=70 kDa subunit of Ku antigen; AltName: Full=ATP-dependent DNA helicase 2 subunit 1; AltName: Full=ATP-dependent DNA helicase II 70 kDa subunit; AltName: Full=CTC box-binding factor 75 kDa subunit; Short=CTC75; Short=CTCBF; AltName: Full=DNA repair protein XRCC6; AltName: Full=Lupus Ku autoantigen protein p70; Short=Ku70; AltName: Full=Thyroid-lupus autoantigen; Short=TLAA; AltName: Full=X-ray repair complementing defective repair in Chinese hamster cells 6;
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. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Required for osteocalcin gene expression. 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. 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. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription.
SUBUNIT: Heterodimer of a 70 kDa (XRCC6) and a 80 kDa (XRCC5) subunit. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex. The dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression. In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5. Interacts with ELF3. Interacts with XRCC6BP1. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1. Interacts with CLU (By similarity). Binds to CDK9 isoform 2.
INTERACTION: Q96P48:ARAP1; NbExp=2; IntAct=EBI-353208, EBI-710003; Q07812:BAX; NbExp=2; IntAct=EBI-353208, EBI-516580; P42858:HTT; NbExp=3; IntAct=EBI-353208, EBI-466029; Q92597:NDRG1; NbExp=2; IntAct=EBI-353208, EBI-716486; P78527:PRKDC; NbExp=5; IntAct=EBI-353208, EBI-352053; Q96EB6:SIRT1; NbExp=7; IntAct=EBI-353208, EBI-1802965; Q9NQB0:TCF7L2; NbExp=9; IntAct=EBI-353208, EBI-924724; P04637:TP53; NbExp=2; IntAct=EBI-353208, EBI-366083; Q14191:WRN; NbExp=7; IntAct=EBI-353208, EBI-368417; P13010:XRCC5; NbExp=8; IntAct=EBI-353208, EBI-357997;
SUBCELLULAR LOCATION: Nucleus. Chromosome.
DEVELOPMENTAL STAGE: Expression does not increase during promyelocyte differentiation.
INDUCTION: In osteoblasts, by FGF2.
PTM: Phosphorylation by PRKDC may enhance helicase activity. Phosphorylation of Ser-51 does not affect DNA repair.
MISCELLANEOUS: Individuals with systemic lupus erythematosus (SLE) and related disorders produce extremely large amounts of autoantibodies to XRCC5 and XRCC6. Existence of a major autoantigenic epitope or epitopes on the C-terminal 190 amino acids of XRCC6 containing the leucine repeat. The majority of autoantibodies to XRCC6 in most sera from patients with SLE seem to be reactive with this region.
SIMILARITY: Belongs to the ku70 family.
SIMILARITY: Contains 1 Ku domain.
SIMILARITY: Contains 1 SAP domain.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/g22p1/";

-  MalaCards Disease Associations
  MalaCards Gene Search: XRCC6
Diseases sorted by gene-association score: lupus erythematosus (6), systemic lupus erythematosus (3), lig4 syndrome (1), postencephalitic parkinson disease (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 188.58 RPKM in Testis
Total median expression: 4001.45 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -16.7066-0.253 Picture PostScript Text
3' UTR -63.60226-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006164 - DNA_helicase_ATP-dep_Ku
IPR006165 - DNA_helicase_ATP-dep_Ku70
IPR005160 - Ku_C
IPR005161 - Ku_N
IPR003034 - SAP_DNA-bd
IPR016194 - SPOC-like

Pfam Domains:
PF02735 - Ku70/Ku80 beta-barrel domain
PF03730 - Ku70/Ku80 C-terminal arm
PF03731 - Ku70/Ku80 N-terminal alpha/beta domain
PF02037 - SAP domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1JEQ
- X-ray MuPIT

1JEY
- X-ray MuPIT

1JJR
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3RZX - X-ray


ModBase Predicted Comparative 3D Structure on P12956
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003677 DNA binding
GO:0003684 damaged DNA binding
GO:0003690 double-stranded DNA binding
GO:0003723 RNA binding
GO:0003824 catalytic activity
GO:0004003 ATP-dependent DNA helicase activity
GO:0004386 helicase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008022 protein C-terminus binding
GO:0016787 hydrolase activity
GO:0016829 lyase activity
GO:0030332 cyclin binding
GO:0042162 telomeric DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0044877 macromolecular complex binding
GO:0051575 5'-deoxyribose-5-phosphate lyase activity
GO:0003691 double-stranded telomeric DNA binding

Biological Process:
GO:0000723 telomere maintenance
GO:0002218 activation of innate immune response
GO:0002376 immune system process
GO:0006266 DNA ligation
GO:0006281 DNA repair
GO:0006303 double-strand break repair via nonhomologous end joining
GO:0006310 DNA recombination
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006974 cellular response to DNA damage stimulus
GO:0007420 brain development
GO:0008152 metabolic process
GO:0032481 positive regulation of type I interferon production
GO:0032508 DNA duplex unwinding
GO:0043312 neutrophil degranulation
GO:0045087 innate immune response
GO:0045860 positive regulation of protein kinase activity
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048660 regulation of smooth muscle cell proliferation
GO:0051290 protein heterotetramerization
GO:0071475 cellular hyperosmotic salinity response
GO:0071480 cellular response to gamma radiation
GO:0071481 cellular response to X-ray
GO:0075713 establishment of integrated proviral latency
GO:0097680 double-strand break repair via classical nonhomologous end joining

Cellular Component:
GO:0000783 nuclear telomere cap complex
GO:0000784 nuclear chromosome, telomeric region
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005694 chromosome
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0032991 macromolecular complex
GO:0032993 protein-DNA complex
GO:0034774 secretory granule lumen
GO:0043564 Ku70:Ku80 complex
GO:0070419 nonhomologous end joining complex
GO:1904813 ficolin-1-rich granule lumen


-  Descriptions from all associated GenBank mRNAs
  AK315618 - Homo sapiens cDNA, FLJ96699, highly similar to Homo sapiens thyroid autoantigen 70kDa (Ku antigen) (G22P1), mRNA.
AK055786 - Homo sapiens cDNA FLJ31224 fis, clone KIDNE2004305, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC 3.6.1.-).
AK304580 - Homo sapiens cDNA FLJ54993 complete cds, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC 3.6.1.-).
AK293439 - Homo sapiens cDNA FLJ53970 complete cds, highly similar to ATP-dependent DNA helicase 2 subunit 1 (EC3.6.1.-).
BC010034 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:19717 IMAGE:3536083), complete cds.
BC018259 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:17453 IMAGE:3448510), complete cds.
J04611 - Human lupus p70 (Ku) autoantigen protein mRNA, complete cds.
BC008343 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:15860 IMAGE:3509801), complete cds.
CR456492 - Homo sapiens G22P1 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.G22P1.V2).
BC072449 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:87834 IMAGE:6167735), complete cds.
BC012154 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone MGC:20380 IMAGE:4561541), complete cds.
M32865 - Human Ku protein subunit mRNA, complete cds.
S38729 - Ku autoantigen p70 subunit [human, mRNA, 2123 nt].
J04607 - Human thyroid autoantigen mRNA, complete cds.
EU446892 - Synthetic construct Homo sapiens clone IMAGE:100070056; IMAGE:100012101; FLH257162.01L X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) (XRCC6) gene, encodes complete protein.
EU831572 - Synthetic construct Homo sapiens clone HAIB:100066601; DKFZo004H0318 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) protein (XRCC6) gene, encodes complete protein.
EU831485 - Synthetic construct Homo sapiens clone HAIB:100066514; DKFZo008H0317 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa) protein (XRCC6) gene, encodes complete protein.
JD052967 - Sequence 33991 from Patent EP1572962.
CU676222 - Synthetic construct Homo sapiens gateway clone IMAGE:100019936 5' read XRCC6 mRNA.
CU680242 - Synthetic construct Homo sapiens gateway clone IMAGE:100017426 5' read XRCC6 mRNA.
AB385096 - Synthetic construct DNA, clone: pF1KB5432, Homo sapiens XRCC6 gene for ATP-dependent DNA helicase 2 subunit 1, complete cds, without stop codon, in Flexi system.
CU013377 - Homo sapiens XRCC6, mRNA (cDNA clone IMAGE:100000252), complete cds, without stop codon, in Gateway system.
CU013089 - Homo sapiens XRCC6, mRNA (cDNA clone IMAGE:100000348), complete cds, with stop codon, in Gateway system.
KJ891210 - Synthetic construct Homo sapiens clone ccsbBroadEn_00604 XRCC6 gene, encodes complete protein.
KJ896842 - Synthetic construct Homo sapiens clone ccsbBroadEn_06236 XRCC6 gene, encodes complete protein.
CR542219 - Homo sapiens full open reading frame cDNA clone RZPDo834D0725D for gene G22P1, thyroid autoantigen 70kDa (Ku antigen); complete cds, incl. stopcodon.
BC001583 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 6, mRNA (cDNA clone IMAGE:3460998).
DQ570184 - Homo sapiens piRNA piR-30296, complete sequence.
AF052148 - Homo sapiens clone 24507 mRNA sequence.
DQ588804 - Homo sapiens piRNA piR-55916, complete sequence.
JD023268 - Sequence 4292 from Patent EP1572962.
JD035977 - Sequence 17001 from Patent EP1572962.
JD555240 - Sequence 536264 from Patent EP1572962.
JD455474 - Sequence 436498 from Patent EP1572962.
JD428234 - Sequence 409258 from Patent EP1572962.
JD293044 - Sequence 274068 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03450 - Non-homologous end-joining

BioCarta from NCI Cancer Genome Anatomy Project
h_telPathway - Telomeres, Telomerase, Cellular Aging, and Immortality

Reactome (by CSHL, EBI, and GO)

Protein P12956 (Reactome details) participates in the following event(s):

R-HSA-175174 Association of Ku heterodimer with viral DNA ends
R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break
R-HSA-175258 2-LTR formation due to circularization of viral DNA
R-HSA-5693604 XRCC4:LIG4 ligates DNA DSB ends during NHEJ
R-HSA-3134821 DNA-PK binds microbial dsDNA
R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-6798748 Exocytosis of secretory granule lumen proteins
R-HSA-5693615 Association of DNA-PKcs with Ku-bound ends of DNA double-strand breaks - synapsis
R-HSA-175177 Association of XRCC4:DNA ligase IV complex with viral DNA ends
R-HSA-5693575 DNA-PKcs autophosphorylates
R-HSA-5686924 DCLRE1C binds PRKDC:XRCC5:XRCC6 at DNA DSBs
R-HSA-5693574 XRCC4:LIG4, NHEJ1 and POLL or POLM bind DNA DSBs in NHEJ
R-HSA-5693578 TDP1 and TDP2 process unligatable DSB ends
R-HSA-5687360 POLL or POLM extends aligned DNA DSB ends to fill gaps
R-HSA-5693533 DCLRE1C (ARTEMIS) processes DNA DSB ends
R-HSA-5687183 PRKDC phosphorylates DCLRE1C at DNA DSBs
R-HSA-164843 2-LTR circle formation
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-6798695 Neutrophil degranulation
R-HSA-162592 Integration of provirus
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-168249 Innate Immune System
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-73894 DNA Repair
R-HSA-168256 Immune System
R-HSA-162587 HIV Life Cycle
R-HSA-162906 HIV Infection
R-HSA-5663205 Infectious disease
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000360079.1, ENST00000360079.2, ENST00000360079.3, ENST00000360079.4, ENST00000360079.5, ENST00000360079.6, ENST00000360079.7, G22P1, NM_001469, P12956, Q6FG89, Q9UCQ2, Q9UCQ3, uc003bao.1, uc003bao.2, uc003bao.3, uc003bao.4, XRCC6_HUMAN
UCSC ID: ENST00000360079.8
RefSeq Accession: NM_001469
Protein: P12956 (aka XRCC6_HUMAN)
CCDS: CCDS14021.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.