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Protein

DNA repair protein XRCC4

Gene

XRCC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • identical protein binding Source: IntAct
  • protein C-terminus binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processDNA 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

EuPathDBiHostDB:ENSG00000152422.15
HGNCiHGNC:12831 XRCC4
MIMi194363 gene
neXtProtiNX_Q13426

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 postnatal 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 dbSNP:rs587779351EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs797045017EnsemblClinVar.1

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
Orphaneti99812 LIG4 syndrome
436182 Microcephalic primordial dwarfism-insulin resistance syndrome
PharmGKBiPA37423

Chemistry databases

DrugBankiDB03963 S-(Dimethylarsenic)Cysteine

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
ProteomicsDBi59412
59413 [Q13426-2]
59414 [Q13426-3]

PTM databases

iPTMnetiQ13426
PhosphoSitePlusiQ13426

Miscellaneous databases

PMAP-CutDBiQ13426

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000152422 Expressed in 185 organ(s), highest expression level in myocardium
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 PAXX. Interacts directly with PRKDC but not with the XRCC6/Ku70 and XRCC5/Ku86 dimer. Interacts with APTX and APLF.15 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113352, 48 interactors
CORUMiQ13426
DIPiDIP-37957N
ELMiQ13426
IntActiQ13426, 21 interactors
MINTiQ13426
STRINGi9606.ENSP00000342011

Structurei

Secondary structure

1336
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiNFSKESC
OrthoDBiEOG091G11MG
PhylomeDBiQ13426
TreeFamiTF101204

Family and domain databases

InterProiView protein in InterPro
IPR010585 DNA_repair_prot_XRCC4
IPR009089 XRCC4_N_sf
PfamiView protein in Pfam
PF06632 XRCC4, 1 hit
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 → C1 PublicationCorresponds to variant dbSNP:rs28383138Ensembl.1
Natural variantiVAR_07582243W → R in SSMED; impairs the protein function in DNA double-strand break repair. 3 PublicationsCorresponds to variant dbSNP:rs587779351EnsemblClinVar.1
Natural variantiVAR_02231156A → T1 PublicationCorresponds to variant dbSNP:rs28383151Ensembl.1
Natural variantiVAR_022312134I → T1 PublicationCorresponds to variant dbSNP:rs28360135Ensembl.1
Natural variantiVAR_022313142E → Q1 PublicationCorresponds to variant dbSNP:rs28360136Ensembl.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 PublicationCorresponds to variant dbSNP:rs797045017EnsemblClinVar.1
Natural variantiVAR_017810240Q → P. Corresponds to variant dbSNP:rs2974446Ensembl.1
Natural variantiVAR_017811247A → S1 PublicationCorresponds to variant dbSNP:rs3734091Ensembl.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

Similar proteinsi

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[»]
5WJ7X-ray2.50A/B2-132[»]
5WLZX-ray3.50A/B/C/D2-132[»]
DisProtiDP00152
ProteinModelPortaliQ13426
SMRiQ13426
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113352, 48 interactors
CORUMiQ13426
DIPiDIP-37957N
ELMiQ13426
IntActiQ13426, 21 interactors
MINTiQ13426
STRINGi9606.ENSP00000342011

Chemistry databases

DrugBankiDB03963 S-(Dimethylarsenic)Cysteine

PTM databases

iPTMnetiQ13426
PhosphoSitePlusiQ13426

Polymorphism and mutation databases

BioMutaiXRCC4
DMDMi44888352

Proteomic databases

EPDiQ13426
MaxQBiQ13426
PaxDbiQ13426
PeptideAtlasiQ13426
PRIDEiQ13426
ProteomicsDBi59412
59413 [Q13426-2]
59414 [Q13426-3]

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
EuPathDBiHostDB:ENSG00000152422.15
GeneCardsiXRCC4
HGNCiHGNC:12831 XRCC4
HPAiHPA006801
HPA051538
MalaCardsiXRCC4
MIMi194363 gene
616541 phenotype
neXtProtiNX_Q13426
OpenTargetsiENSG00000152422
Orphaneti99812 LIG4 syndrome
436182 Microcephalic primordial dwarfism-insulin resistance syndrome
PharmGKBiPA37423
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJSN Eukaryota
ENOG410Y7Z3 LUCA
GeneTreeiENSGT00390000017079
HOGENOMiHOG000013067
HOVERGENiHBG059517
InParanoidiQ13426
KOiK10886
OMAiNFSKESC
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-CutDBiQ13426
PROiPR:Q13426
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152422 Expressed in 185 organ(s), highest expression level in myocardium
CleanExiHS_XRCC4
ExpressionAtlasiQ13426 baseline and differential
GenevisibleiQ13426 HS

Family and domain databases

InterProiView protein in InterPro
IPR010585 DNA_repair_prot_XRCC4
IPR009089 XRCC4_N_sf
PfamiView protein in Pfam
PF06632 XRCC4, 1 hit
SUPFAMiSSF50809 SSF50809, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiXRCC4_HUMAN
AccessioniPrimary (citable) accession number: Q13426
Secondary accession number(s): A8K3X4, Q9BS72, Q9UP94
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: November 7, 2018
This is version 176 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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