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Protein

DNA repair protein XRCC4

Gene

XRCC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. Binds to DNA and to DNA ligase IV (LIG4). The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.4 Publications

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

GO - Biological processi

  • cellular response to lithium ion Source: Ensembl
  • DNA ligation involved in DNA repair Source: UniProtKB
  • DNA recombination Source: UniProtKB-KW
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via nonhomologous end joining Source: UniProtKB
  • establishment of integrated proviral latency Source: Reactome
  • positive regulation of ligase activity Source: UniProtKB
  • protein sumoylation Source: Reactome
  • response to X-ray Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA recombination, DNA repair

Enzyme and pathway databases

ReactomeiR-HSA-164843. 2-LTR circle formation.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).

Names & Taxonomyi

Protein namesi
Recommended name:
DNA repair protein XRCC4
Alternative name(s):
X-ray repair cross-complementing protein 4
Gene namesi
Name:XRCC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:12831. XRCC4.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: HPA
  • centrosome Source: HPA
  • cytosol Source: UniProtKB
  • DNA-dependent protein kinase-DNA ligase 4 complex Source: MGI
  • DNA ligase IV complex Source: UniProtKB
  • nonhomologous end joining complex Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Short stature, microcephaly, and endocrine dysfunction (SSMED)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by short stature and microcephaly apparent at birth, progressive post-natal growth failure, and endocrine dysfunction. In affected adults endocrine features include hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus. Variable features observed in some patients are progressive ataxia, and lymphopenia or borderline leukopenia.
See also OMIM:616541
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07582243W → R in SSMED; impairs the protein function in DNA double-strand break repair. 3 PublicationsCorresponds to variant rs587779351dbSNPEnsembl.1
Natural variantiVAR_075823161R → Q in SSMED; no expression of the protein is observed; complete loss of function in DNA double-strand break repair. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140K → R: No change in sumoylation. 1 Publication1
Mutagenesisi210K → R: Abolishes sumoylation. No nuclear location. 5-fold decrease in recombination efficiency. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi7518.
MalaCardsiXRCC4.
MIMi616541. phenotype.
OpenTargetsiENSG00000152422.
PharmGKBiPA37423.

Polymorphism and mutation databases

BioMutaiXRCC4.
DMDMi44888352.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000660471 – 336DNA repair protein XRCC4Add BLAST336

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki210Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei229PhosphotyrosineCombined sources1
Modified residuei233PhosphothreonineCombined sources1
Modified residuei237PhosphoserineCombined sources1
Modified residuei256PhosphoserineCombined sources1
Modified residuei260Phosphoserine; by PRKDCCombined sources1 Publication1
Modified residuei304PhosphoserineCombined sources1
Modified residuei320Phosphoserine; by PRKDCCombined sources1 Publication1
Modified residuei323PhosphothreonineBy similarity1
Modified residuei327PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by PRKDC. The phosphorylation seems not to be necessary for binding to DNA. Phosphorylation by CK2 promotes interaction with APTX.6 Publications
Monoubiquitinated.
Sumoylation at Lys-210 is required for nuclear localization and recombination efficiency. Has no effect on ubiquitination.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13426.
MaxQBiQ13426.
PaxDbiQ13426.
PeptideAtlasiQ13426.
PRIDEiQ13426.

PTM databases

iPTMnetiQ13426.
PhosphoSitePlusiQ13426.

Miscellaneous databases

PMAP-CutDBQ13426.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000152422.
CleanExiHS_XRCC4.
ExpressionAtlasiQ13426. baseline and differential.
GenevisibleiQ13426. HS.

Organism-specific databases

HPAiHPA006801.
HPA051538.

Interactioni

Subunit structurei

Homodimer and homotetramer in solution. The homodimer associates with LIG4. The LIG4-XRCC4 complex associates in a DNA-dependent manner with the DNA-PK complex composed of PRKDC, XRCC6/Ku70 and XRCC5/Ku86 to form the core non-homologous end joining (NHEJ) complex. Additional components of the NHEJ complex include NHEJ1/XLF and C9orf142/PAXX. Interacts directly with PRKDC but not with the XRCC6/Ku70 and XRCC5/Ku86 dimer. Interacts with APTX and APLF.15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-717592,EBI-717592
APLFQ8IW194EBI-717592,EBI-1256044
APTXQ7Z2E33EBI-717592,EBI-847814
ASTE1Q2TB183EBI-717592,EBI-2875586
BIN1O004994EBI-717592,EBI-719094
FAM9BQ8IZU05EBI-717592,EBI-10175124
LIG4P499177EBI-717592,EBI-847896
NHEJ1Q9H9Q48EBI-717592,EBI-847807
PNKPQ96T605EBI-717592,EBI-1045072

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113352. 39 interactors.
DIPiDIP-37957N.
IntActiQ13426. 19 interactors.
MINTiMINT-1205583.
STRINGi9606.ENSP00000342011.

Structurei

Secondary structure

1336
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 10Combined sources9
Beta strandi13 – 26Combined sources14
Helixi28 – 30Combined sources3
Beta strandi31 – 37Combined sources7
Beta strandi42 – 48Combined sources7
Helixi49 – 58Combined sources10
Helixi63 – 74Combined sources12
Beta strandi84 – 88Combined sources5
Turni90 – 92Combined sources3
Beta strandi94 – 100Combined sources7
Beta strandi105 – 112Combined sources8
Helixi119 – 133Combined sources15
Turni173 – 176Combined sources4
Helixi179 – 201Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FU1X-ray2.70A/B1-203[»]
1IK9X-ray2.30A/B1-213[»]
3II6X-ray2.40A/B/C/D1-203[»]
3MUDX-ray2.20A/B2-133[»]
3Q4FX-ray5.50C/D/G/H1-157[»]
3RWRX-ray3.94A/B/F/G/J/K/N/P/R/U/V/Y1-157[»]
3SR2X-ray3.97A/B/E/F1-140[»]
3W03X-ray8.49C/D1-164[»]
4XA4X-ray2.33A/B2-147[»]
5CHXX-ray2.30A/B2-143[»]
5CJ0X-ray2.30A/B2-142[»]
5CJ4X-ray3.10A/B/C/D2-144[»]
5E50X-ray1.38C/D229-236[»]
DisProtiDP00152.
ProteinModelPortaliQ13426.
SMRiQ13426.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13426.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni180 – 213Interaction with LIG4Add BLAST34

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili131 – 165Sequence analysisAdd BLAST35
Coiled coili184 – 212Sequence analysisAdd BLAST29

Sequence similaritiesi

Belongs to the XRCC4 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IJSN. Eukaryota.
ENOG410Y7Z3. LUCA.
GeneTreeiENSGT00390000017079.
HOGENOMiHOG000013067.
HOVERGENiHBG059517.
InParanoidiQ13426.
KOiK10886.
OMAiTDGHSAW.
OrthoDBiEOG091G11MG.
PhylomeDBiQ13426.
TreeFamiTF101204.

Family and domain databases

Gene3Di1.20.5.370. 1 hit.
2.170.210.10. 1 hit.
InterProiIPR010585. DNA_repair_prot_XRCC4.
IPR014751. XRCC4_C.
IPR009089. XRCC4_N.
[Graphical view]
PfamiPF06632. XRCC4. 1 hit.
[Graphical view]
SUPFAMiSSF50809. SSF50809. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13426-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MERKISRIHL VSEPSITHFL QVSWEKTLES GFVITLTDGH SAWTGTVSES
60 70 80 90 100
EISQEADDMA MEKGKYVGEL RKALLSGAGP ADVYTFNFSK ESCYFFFEKN
110 120 130 140 150
LKDVSFRLGS FNLEKVENPA EVIRELICYC LDTIAENQAK NEHLQKENER
160 170 180 190 200
LLRDWNDVQG RFEKCVSAKE ALETDLYKRF ILVLNEKKTK IRSLHNKLLN
210 220 230 240 250
AAQEREKDIK QEGETAICSE MTADRDPVYD ESTDEESENQ TDLSGLASAA
260 270 280 290 300
VSKDDSIISS LDVTDIAPSR KRRQRMQRNL GTEPKMAPQE NQLQEKENSR
310 320 330
PDSSLPETSK KEHISAENMS LETLRNSSPE DLFDEI
Length:336
Mass (Da):38,287
Last modified:March 1, 2004 - v2
Checksum:iBE5FB99153479A4E
GO
Isoform 2 (identifier: Q13426-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     298-300: NSR → K

Show »
Length:334
Mass (Da):38,058
Checksum:iE32CC403854DCE9B
GO
Isoform 3 (identifier: Q13426-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     298-336: NSRPDSSLPETSKKEHISAENMSLETLRNSSPEDLFDEI → KGRKKETSEKEAV

Show »
Length:310
Mass (Da):35,372
Checksum:i30B8DCC13C64A548
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02231012S → C.1 PublicationCorresponds to variant rs28383138dbSNPEnsembl.1
Natural variantiVAR_07582243W → R in SSMED; impairs the protein function in DNA double-strand break repair. 3 PublicationsCorresponds to variant rs587779351dbSNPEnsembl.1
Natural variantiVAR_02231156A → T.1 PublicationCorresponds to variant rs28383151dbSNPEnsembl.1
Natural variantiVAR_022312134I → T.1 PublicationCorresponds to variant rs28360135dbSNPEnsembl.1
Natural variantiVAR_022313142E → Q.1 PublicationCorresponds to variant rs28360136dbSNPEnsembl.1
Natural variantiVAR_075823161R → Q in SSMED; no expression of the protein is observed; complete loss of function in DNA double-strand break repair. 1 Publication1
Natural variantiVAR_017810240Q → P.Corresponds to variant rs2974446dbSNPEnsembl.1
Natural variantiVAR_017811247A → S.1 PublicationCorresponds to variant rs3734091dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009474298 – 336NSRPD…LFDEI → KGRKKETSEKEAV in isoform 3. 2 PublicationsAdd BLAST39
Alternative sequenceiVSP_009473298 – 300NSR → K in isoform 2. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40622 mRNA. Translation: AAC50339.1.
AF055285
, AF055279, AF055280, AF055281, AF055282, AF055283, AF055284 Genomic DNA. Translation: AAD47297.1.
AF055285
, AF055279, AF055280, AF055281, AF055282, AF055283, AF055284 Genomic DNA. Translation: AAD47298.1.
AB017445 mRNA. Translation: BAB20668.1.
BT007216 mRNA. Translation: AAP35880.1.
AK290739 mRNA. Translation: BAF83428.1.
AY940097 Genomic DNA. Translation: AAX14046.1.
CH471084 Genomic DNA. Translation: EAW95898.1.
BC005259 mRNA. Translation: AAH05259.1.
BC016314 mRNA. Translation: AAH16314.1.
CCDSiCCDS4058.1. [Q13426-2]
CCDS4059.1. [Q13426-1]
RefSeqiNP_001304941.1. NM_001318012.1. [Q13426-1]
NP_001304942.1. NM_001318013.1. [Q13426-3]
NP_003392.1. NM_003401.4. [Q13426-2]
NP_071801.1. NM_022406.3. [Q13426-1]
NP_072044.1. NM_022550.3. [Q13426-2]
XP_011541928.1. XM_011543626.1. [Q13426-1]
UniGeneiHs.567359.

Genome annotation databases

EnsembliENST00000282268; ENSP00000282268; ENSG00000152422. [Q13426-2]
ENST00000338635; ENSP00000342011; ENSG00000152422. [Q13426-1]
ENST00000396027; ENSP00000379344; ENSG00000152422. [Q13426-2]
ENST00000511817; ENSP00000421491; ENSG00000152422. [Q13426-1]
GeneIDi7518.
KEGGihsa:7518.
UCSCiuc003kib.4. human. [Q13426-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40622 mRNA. Translation: AAC50339.1.
AF055285
, AF055279, AF055280, AF055281, AF055282, AF055283, AF055284 Genomic DNA. Translation: AAD47297.1.
AF055285
, AF055279, AF055280, AF055281, AF055282, AF055283, AF055284 Genomic DNA. Translation: AAD47298.1.
AB017445 mRNA. Translation: BAB20668.1.
BT007216 mRNA. Translation: AAP35880.1.
AK290739 mRNA. Translation: BAF83428.1.
AY940097 Genomic DNA. Translation: AAX14046.1.
CH471084 Genomic DNA. Translation: EAW95898.1.
BC005259 mRNA. Translation: AAH05259.1.
BC016314 mRNA. Translation: AAH16314.1.
CCDSiCCDS4058.1. [Q13426-2]
CCDS4059.1. [Q13426-1]
RefSeqiNP_001304941.1. NM_001318012.1. [Q13426-1]
NP_001304942.1. NM_001318013.1. [Q13426-3]
NP_003392.1. NM_003401.4. [Q13426-2]
NP_071801.1. NM_022406.3. [Q13426-1]
NP_072044.1. NM_022550.3. [Q13426-2]
XP_011541928.1. XM_011543626.1. [Q13426-1]
UniGeneiHs.567359.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FU1X-ray2.70A/B1-203[»]
1IK9X-ray2.30A/B1-213[»]
3II6X-ray2.40A/B/C/D1-203[»]
3MUDX-ray2.20A/B2-133[»]
3Q4FX-ray5.50C/D/G/H1-157[»]
3RWRX-ray3.94A/B/F/G/J/K/N/P/R/U/V/Y1-157[»]
3SR2X-ray3.97A/B/E/F1-140[»]
3W03X-ray8.49C/D1-164[»]
4XA4X-ray2.33A/B2-147[»]
5CHXX-ray2.30A/B2-143[»]
5CJ0X-ray2.30A/B2-142[»]
5CJ4X-ray3.10A/B/C/D2-144[»]
5E50X-ray1.38C/D229-236[»]
DisProtiDP00152.
ProteinModelPortaliQ13426.
SMRiQ13426.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113352. 39 interactors.
DIPiDIP-37957N.
IntActiQ13426. 19 interactors.
MINTiMINT-1205583.
STRINGi9606.ENSP00000342011.

PTM databases

iPTMnetiQ13426.
PhosphoSitePlusiQ13426.

Polymorphism and mutation databases

BioMutaiXRCC4.
DMDMi44888352.

Proteomic databases

EPDiQ13426.
MaxQBiQ13426.
PaxDbiQ13426.
PeptideAtlasiQ13426.
PRIDEiQ13426.

Protocols and materials databases

DNASUi7518.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282268; ENSP00000282268; ENSG00000152422. [Q13426-2]
ENST00000338635; ENSP00000342011; ENSG00000152422. [Q13426-1]
ENST00000396027; ENSP00000379344; ENSG00000152422. [Q13426-2]
ENST00000511817; ENSP00000421491; ENSG00000152422. [Q13426-1]
GeneIDi7518.
KEGGihsa:7518.
UCSCiuc003kib.4. human. [Q13426-1]

Organism-specific databases

CTDi7518.
DisGeNETi7518.
GeneCardsiXRCC4.
HGNCiHGNC:12831. XRCC4.
HPAiHPA006801.
HPA051538.
MalaCardsiXRCC4.
MIMi194363. gene.
616541. phenotype.
neXtProtiNX_Q13426.
OpenTargetsiENSG00000152422.
PharmGKBiPA37423.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJSN. Eukaryota.
ENOG410Y7Z3. LUCA.
GeneTreeiENSGT00390000017079.
HOGENOMiHOG000013067.
HOVERGENiHBG059517.
InParanoidiQ13426.
KOiK10886.
OMAiTDGHSAW.
OrthoDBiEOG091G11MG.
PhylomeDBiQ13426.
TreeFamiTF101204.

Enzyme and pathway databases

ReactomeiR-HSA-164843. 2-LTR circle formation.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).

Miscellaneous databases

ChiTaRSiXRCC4. human.
EvolutionaryTraceiQ13426.
GeneWikiiXRCC4.
GenomeRNAii7518.
PMAP-CutDBQ13426.
PROiQ13426.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152422.
CleanExiHS_XRCC4.
ExpressionAtlasiQ13426. baseline and differential.
GenevisibleiQ13426. HS.

Family and domain databases

Gene3Di1.20.5.370. 1 hit.
2.170.210.10. 1 hit.
InterProiIPR010585. DNA_repair_prot_XRCC4.
IPR014751. XRCC4_C.
IPR009089. XRCC4_N.
[Graphical view]
PfamiPF06632. XRCC4. 1 hit.
[Graphical view]
SUPFAMiSSF50809. SSF50809. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiXRCC4_HUMAN
AccessioniPrimary (citable) accession number: Q13426
Secondary accession number(s): A8K3X4, Q9BS72, Q9UP94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: November 30, 2016
This is version 160 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.