Details for: XRCC4

Gene ID: 7518

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: XRCC4

Ensembl ID: ENSG00000152422

Description: X-ray repair cross complementing 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • melanocyte CL0000148
    CSI 11.17
    rCSI 8.27%
    PRS 70.58
  • Kupffer cell CL0000091
    CSI 5.92
    rCSI 13.54%
    PRS 78.3
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 5.58
    rCSI 4.3%
    PRS 80.03
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 5.15
    rCSI 13.42%
    PRS 78.26
  • lung secretory cell CL1000272
    CSI 5.09
    rCSI 12.59%
    PRS 76.83
  • erythroblast CL0000765
    CSI 4.85
    rCSI 12.87%
    PRS 83.8
  • cardiac neuron CL0010022
    CSI 4.85
    rCSI 15.51%
    PRS 74.38
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.95
    rCSI 3.42%
    PRS 81.62
  • amacrine cell CL0000561
    CSI 3.61
    rCSI 10.48%
    PRS 66.59
  • cerebellar granule cell CL0001031
    CSI 3.41
    rCSI 5.02%
    PRS 70.1
  • Hofbauer cell CL3000001
    CSI 3.27
    rCSI 6.17%
    PRS 85.85
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.22
    rCSI 8.16%
    PRS 67.57
  • mononuclear phagocyte CL0000113
    CSI 3.12
    rCSI 6.87%
    PRS 81.26
  • neural crest cell CL0011012
    CSI 3.03
    rCSI 2.39%
    PRS 65.64
  • glioblast CL0000030
    CSI 3
    rCSI 4.79%
    PRS 69.07
  • pro-B cell CL0000826
    CSI 2.94
    rCSI 2.43%
    PRS 79.93
  • retinal bipolar neuron CL0000748
    CSI 2.64
    rCSI 4.95%
    PRS 65.37
  • Mueller cell CL0000636
    CSI 2.63
    rCSI 6%
    PRS 68.72
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.61
    rCSI 1.82%
    PRS 80.67
  • elicited macrophage CL0000861
    CSI 2.57
    rCSI 2.36%
    PRS 85.4
  • radial glial cell CL0000681
    CSI 2.54
    rCSI 3.53%
    PRS 76.09
  • hepatic stellate cell CL0000632
    CSI 2.53
    rCSI 9.48%
    PRS 69.59
  • stem cell CL0000034
    CSI 2.53
    rCSI 2.44%
    PRS 70.29
  • interneuron CL0000099
    CSI 2.51
    rCSI 5.05%
    PRS 67.11
  • intermediate monocyte CL0002393
    CSI 2.51
    rCSI 3.79%
    PRS 82.77
  • cerebral cortex endothelial cell CL1001602
    CSI 2.47
    rCSI 4.27%
    PRS 68.6
  • CD14-positive monocyte CL0001054
    CSI 2.41
    rCSI 3%
    PRS 86.49
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.4
    rCSI 3.4%
    PRS 74.07
  • alveolar macrophage CL0000583
    CSI 2.35
    rCSI 3.87%
    PRS 81.7
  • adipocyte CL0000136
    CSI 2.34
    rCSI 3.01%
    PRS 67.72
  • myeloid dendritic cell CL0000782
    CSI 2.27
    rCSI 3.29%
    PRS 89.88
  • M cell of gut CL0000682
    CSI 2.27
    rCSI 2.41%
    PRS 82.88
  • Bergmann glial cell CL0000644
    CSI 2.16
    rCSI 2.96%
    PRS 69.32
  • blood vessel endothelial cell CL0000071
    CSI 2.13
    rCSI 4.42%
    PRS 74.12
  • rod bipolar cell CL0000751
    CSI 2.13
    rCSI 3.82%
    PRS 70.61
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.12
    rCSI 1.91%
    PRS 75.52
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.11
    rCSI 2.31%
    PRS 79.59
  • suprabasal keratinocyte CL4033013
    CSI 2.07
    rCSI 3.38%
    PRS 44.57
  • tuft cell of colon CL0009041
    CSI 2.07
    rCSI 4.82%
    PRS 84.04
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.06
    rCSI 2.7%
    PRS 88.12
  • direct pathway medium spiny neuron CL4023026
    CSI 2.04
    rCSI 48.89%
    PRS 57.5
  • ependymal cell CL0000065
    CSI 2.02
    rCSI 4.09%
    PRS 55.57
  • BEST4+ enteroycte CL4030026
    CSI 1.95
    rCSI 2.42%
    PRS 78.74
  • blood vessel smooth muscle cell CL0019018
    CSI 1.94
    rCSI 15.81%
    PRS 71.15
  • promyelocyte CL0000836
    CSI 1.9
    rCSI 2.75%
    PRS 83.86
  • endocardial cell CL0002350
    CSI 1.88
    rCSI 8.99%
    PRS 74.13
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.85
    rCSI 2.14%
    PRS 69.64
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.85
    rCSI 2.3%
    PRS 56.97
  • extravillous trophoblast CL0008036
    CSI 1.78
    rCSI 2.2%
    PRS 75.12
  • ciliated epithelial cell CL0000067
    CSI 1.75
    rCSI 1.54%
    PRS 66.23
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.75
    rCSI 3.17%
    PRS 68.69
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.74
    rCSI 2.08%
    PRS 59.03
  • renal interstitial pericyte CL1001318
    CSI 1.65
    rCSI 4.54%
    PRS 72.43
  • vascular leptomeningeal cell CL4023051
    CSI 1.62
    rCSI 2.84%
    PRS 70.74
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.62
    rCSI 2.09%
    PRS 60.28
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.56
    rCSI 2.76%
    PRS 58.29
  • placental villous trophoblast CL2000060
    CSI 1.55
    rCSI 2.4%
    PRS 76.41
  • promonocyte CL0000559
    CSI 1.54
    rCSI 2.63%
    PRS 84.04
  • cardiac muscle cell CL0000746
    CSI 1.53
    rCSI 2.2%
    PRS 67.07
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.49
    rCSI 3.34%
    PRS 59.83
  • retinal ganglion cell CL0000740
    CSI 1.49
    rCSI 3.28%
    PRS 62.98
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.45
    rCSI 8.52%
    PRS 59.88
  • renal beta-intercalated cell CL0002201
    CSI 1.44
    rCSI 3.43%
    PRS 77.57
  • multi-ciliated epithelial cell CL0005012
    CSI 1.43
    rCSI 1.43%
    PRS 71.07
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.43
    rCSI 5.41%
    PRS 59.56
  • retinal cone cell CL0000573
    CSI 1.37
    rCSI 2.2%
    PRS 67.19
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.36
    rCSI 3.51%
    PRS 72.65
  • enterocyte CL0000584
    CSI 1.32
    rCSI 2.13%
    PRS 76.97
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.29
    rCSI 31.09%
    PRS 58.03
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.24
    rCSI 2%
    PRS 60.76
  • fibroblast of cardiac tissue CL0002548
    CSI 1.23
    rCSI 5.89%
    PRS 77.24
  • small intestine goblet cell CL1000495
    CSI 1.22
    rCSI 2.68%
    PRS 83.32
  • forebrain radial glial cell CL0013000
    CSI 1.21
    rCSI 3.88%
    PRS 79.79
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.17
    rCSI 2.84%
    PRS 57.13
  • basal cell of epidermis CL0002187
    CSI 1.15
    rCSI 2.04%
    PRS 47.1
  • diffuse bipolar 6 cell CL4033032
    CSI 1.12
    rCSI 5.9%
    PRS 69.95
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.09
    rCSI 1.32%
    PRS 58.89
  • helper T cell CL0000912
    CSI 1.02
    rCSI 1.44%
    PRS 77.42
  • glial cell CL0000125
    CSI 0.99
    rCSI 3.79%
    PRS 68.11
  • enteroglial cell CL4040002
    CSI 0.94
    rCSI 4.96%
    PRS 79.08
  • parietal epithelial cell CL1000452
    CSI 0.93
    rCSI 2.5%
    PRS 68.71
  • regular atrial cardiac myocyte CL0002129
    CSI 0.91
    rCSI 2.94%
    PRS 74.2
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 0.9
    rCSI 1.09%
    PRS 85.23
  • GABAergic neuron CL0000617
    CSI 0.9
    rCSI 3.01%
    PRS 61.3
  • innate lymphoid cell CL0001065
    CSI 0.84
    rCSI 1.73%
    PRS 75.32
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.81
    rCSI 2.54%
    PRS 60.78
  • melanocyte of skin CL1000458
    CSI 0.8
    rCSI 1.08%
    PRS 44.6
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.74
    rCSI 1.25%
    PRS 59.09
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.74
    rCSI 4.63%
    PRS 68.93
  • podocyte CL0000653
    CSI 0.7
    rCSI 3.13%
    PRS 77.79
  • flat midget bipolar cell CL4033033
    CSI 0.7
    rCSI 4.98%
    PRS 68.93
  • diffuse bipolar 3b cell CL4033030
    CSI 0.64
    rCSI 4.24%
    PRS 72.91
  • H2 horizontal cell CL0004218
    CSI 0.58
    rCSI 2.86%
    PRS 72.72
  • diffuse bipolar 3a cell CL4033029
    CSI 0.51
    rCSI 3.48%
    PRS 70.79
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.5
    rCSI 1.79%
    PRS 57.03
  • medium spiny neuron CL1001474
    CSI 0.36
    rCSI 3.07%
    PRS 64.95
  • ON parasol ganglion cell CL4033052
    CSI 0.35
    rCSI 4.91%
    PRS 68.22
  • ON midget ganglion cell CL4033046
    CSI 0.32
    rCSI 6.53%
    PRS 67.17
  • OFF midget ganglion cell CL4033047
    CSI 0.25
    rCSI 5.15%
    PRS 68.51
  • central nervous system neuron CL2000029
    CSI 0.2
    rCSI 1.47%
    PRS 64.39

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [XRCC4](/details-gene/7518) (X-ray repair cross complementing 4) is a protein-coding gene located on chromosome 5q14.2, critically involved in the repair of DNA double-strand breaks (DSBs). It functions as a core component of the non-homologous end-joining (NHEJ) pathway, the primary mechanism for repairing DSBs in mammalian cells. [XRCC4](/details-gene/7518) forms a stable complex with DNA Ligase IV, which it stimulates and stabilizes to perform the final ligation step of DNA repair [Link](https://doi.org/10.1038/41358). This interaction is essential for maintaining genomic integrity, particularly during processes like V(D)J recombination in developing lymphocytes [Link](https://doi.org/10.1016/0092-8674(95)90135-3). Expression data indicates that while its function is fundamental, its significance is particularly high in a diverse range of cell types, including [melanocyte](/details-cell/CL0000148)s, various mononuclear phagocytes like [Kupffer cell](/details-cell/CL0000091)s, and hematopoietic progenitors, suggesting a key role in contexts with high potential for DNA damage or genomic rearrangement. Clinical associations with OMIM entry [194363](https://omim.org/entry/194363) underscore its importance in human health. ## Cellular Roles and Expression Landscape The expression profile of [XRCC4](/details-gene/7518) highlights its role as a fundamental but differentially regulated component of the cellular DNA repair machinery. **Overall**, its significance is highest in a functionally diverse set of cells, suggesting its activity is tailored to specific cellular stresses and developmental programs. The gene shows the highest cell significance index in [melanocyte](/details-cell/CL0000148)s (CSI: 11.17), cells chronically exposed to mutagenic UV radiation, implying a crucial role in preventing UV-induced DNA damage. High significance is also observed across the mononuclear phagocyte system, including in [Kupffer cell](/details-cell/CL0000091)s (CSI: 5.92), [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s (CSI: 5.58), and [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695)s (CSI: 5.15). This pattern may reflect a need to repair DNA damage generated by reactive oxygen species during phagocytosis and inflammatory responses. Furthermore, [XRCC4](/details-gene/7518) is significant in progenitor and developing cells, such as [erythroblast](/details-cell/CL0000765)s (CSI: 4.85) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557)s (CSI: 3.95), where maintaining genomic stability during rapid proliferation and differentiation is paramount. Its notable significance in various neuronal cell types, including [cardiac neuron](/details-cell/CL0010022)s (CSI: 4.85) and [cerebellar granule cell](/details-cell/CL0001031)s (CSI: 3.41), points to a vital housekeeping function in protecting the integrity of the genome in these long-lived, post-mitotic cells. The broad but distinct cellular landscape of [XRCC4](/details-gene/7518) expression underscores its universal importance in DNA repair, with heightened relevance in cells facing specific genotoxic stresses. ## Pathways and Molecular Function The functional annotations for [XRCC4](/details-gene/7518) confirm its central role in DNA metabolism, specifically in the maintenance of genomic integrity. Its primary function is within the [Nonhomologous end-joining (nhej)](https://reactome.org/content/detail/R-HSA-5693571) pathway, a major process for [Dna double-strand break repair](https://reactome.org/content/detail/R-HSA-5693532). Gene Ontology terms describe its involvement in [Double-strand break repair](/details-go/GO:0006302) and, more specifically, [Double-strand break repair via nonhomologous end joining](/details-go/GO:0006303). At the molecular level, [XRCC4](/details-gene/7518) functions by forming a critical complex with DNA Ligase IV. It engages in [Identical protein binding](/details-go/GO:0042802) to form a homodimer, which then recruits and stabilizes the ligase at the site of a DNA break [Link](https://doi.org/10.1016/s0960-9822(06)00258-2). This is reflected in its annotation as part of the [Dna ligase iv complex](/details-go/GO:0032807) and the broader [Nonhomologous end joining complex](/details-go/GO:0070419). The recruitment of this complex to DNA breaks is facilitated by interactions with the DNA-dependent protein kinase (DNA-PK) complex [Link](https://doi.org/10.1128/mcb.20.9.2996-3003.2000), highlighting a coordinated cellular response. Beyond general DNA repair, [XRCC4](/details-gene/7518) is indispensable for programmed genomic rearrangements, such as [Immunoglobulin v(d)j recombination](/details-go/GO:0033152), a process essential for generating antibody diversity in the adaptive immune system. The Reactome database also implicates the NHEJ machinery, and thus [XRCC4](/details-gene/7518), in viral life cycles, such as the [Early phase of hiv life cycle](https://reactome.org/content/detail/R-HSA-162594), where cellular repair factors can be co-opted by retroviruses during integration into the host genome. ## Research Directions The expression data and known functions of [XRCC4](/details-gene/7518) suggest several avenues for future research into its specific roles in tissue homeostasis and pathology. ### Testable Hypotheses 1. **Role in Melanocyte UV Resistance:** The exceptionally high significance of [XRCC4](/details-gene/7518) in [melanocyte](/details-cell/CL0000148)s suggests it is a primary defense mechanism against UV-induced DNA double-strand breaks. We hypothesize that reduced [XRCC4](/details-gene/7518) function in melanocytes leads to increased genomic instability upon UV exposure, accelerating the process of melanomagenesis. 2. **Function in Phagocyte-Induced DNA Damage:** The high expression in multiple phagocytic cell types ([Kupffer cell](/details-cell/CL0000091), [macrophage](/details-cell/CL1000695)) may be necessary to counteract DNA damage from reactive oxygen species (ROS) produced during inflammatory responses. We hypothesize that [XRCC4](/details-gene/7518) is critical for maintaining the viability and function of macrophages in chronically inflamed tissues by repairing ROS-induced DNA lesions. 3. **Genomic Integrity in Neurogenesis:** The significant expression in neuronal populations like [cerebellar granule cell](/details-cell/CL0001031)s suggests a key role in protecting the genome of these long-lived cells. We hypothesize that defects in [XRCC4](/details-gene/7518)-mediated repair contribute to the accumulation of DNA damage and subsequent neuronal loss observed in certain neurodegenerative disorders. ### Proposed Key Experiment To test the hypothesis regarding the role of [XRCC4](/details-gene/7518) in melanocyte UV resistance (Hypothesis 1), a targeted experimental approach could be employed. Primary human melanocytes would be cultured and transduced with lentiviral vectors expressing either a CRISPR-Cas9 system targeting [XRCC4](/details-gene/7518) for knockout or a non-targeting control. Following selection, the knockout and control cell lines would be exposed to physiologically relevant doses of UV-B radiation. The cellular response would be assessed by quantifying the formation and resolution of γH2AX foci, a marker for DNA double-strand breaks, via immunofluorescence microscopy at multiple time points post-exposure. Furthermore, long-term consequences could be evaluated by measuring cell viability, apoptosis rates (e.g., via Annexin V/PI staining), and the accumulation of chromosomal aberrations using metaphase spread analysis. This experiment would directly determine if [XRCC4](/details-gene/7518) is essential for repairing UV-induced DSBs and preventing genomic instability in melanocytes. ### Therapeutic Potential Given its central function in the NHEJ pathway, [XRCC4](/details-gene/7518) presents a compelling therapeutic target, primarily for **inhibition**, in the context of oncology. Many cancer therapies, including radiation and certain chemotherapies, function by inducing extensive DNA damage. Cancer cells often upregulate DNA repair pathways to survive this damage. Inhibiting [XRCC4](/details-gene/7518) or its interaction with DNA Ligase IV could act as a potent sensitizer, increasing the efficacy of these standard treatments. Such a strategy would be particularly promising in tumors that have defects in alternative repair pathways like homologous recombination (e.g., those with BRCA1/2 mutations), creating a synthetic lethal vulnerability where the cancer cell cannot repair DSBs and is driven into apoptosis. The development of small molecule inhibitors that disrupt the XRCC4-Ligase IV interface could therefore be a valuable addition to cancer therapy regimens.

Genular Protein ID: 868935120

Symbol: XRCC4_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q13426 A8K3X4 Q9BS72 Q9UP94

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 DrugBank 1 ELM 1 EMBL 22 EMDB 14 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 17 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 27 PDBsum 27 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 3 RefSeq 6 SASBDB 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8548796

Title: The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination.

PubMed ID: 8548796

DOI: 10.1016/0092-8674(95)90135-3

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9259561

Title: Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV.

PubMed ID: 9259561

DOI: 10.1016/s0960-9822(06)00258-2

PubMed ID: 9430729

Title: The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.

PubMed ID: 9430729

DOI: 10.1074/jbc.273.3.1794

PubMed ID: 15177042

Title: Identification of DNA-PKcs phosphorylation sites in XRCC4 and effects of mutations at these sites on DNA end joining in a cell-free system.

PubMed ID: 15177042

DOI: 10.1016/j.dnarep.2003.11.005

PubMed ID: 9242410

Title: Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells.

PubMed ID: 9242410

DOI: 10.1038/41358

PubMed ID: 10922471

Title: Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.

PubMed ID: 10922471

DOI: 10.1016/s0014-5793(00)01800-7

PubMed ID: 10854421

Title: Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase.

PubMed ID: 10854421

DOI: 10.1074/jbc.m000491200

PubMed ID: 10757784

Title: Ku recruits the XRCC4-ligase IV complex to DNA ends.

PubMed ID: 10757784

DOI: 10.1128/mcb.20.9.2996-3003.2000

PubMed ID: 12509254

Title: Defining interactions between DNA-PK and ligase IV/XRCC4.

PubMed ID: 12509254

DOI: 10.1016/s1568-7864(01)00018-0

PubMed ID: 12517771

Title: Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for nonhomologous DNA end joining in vitro.

PubMed ID: 12517771

PubMed ID: 14599745

Title: DNA-PK phosphorylation sites in XRCC4 are not required for survival after radiation or for V(D)J recombination.

PubMed ID: 14599745

DOI: 10.1016/s1568-7864(03)00143-5

PubMed ID: 12547193

Title: Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.

PubMed ID: 12547193

DOI: 10.1016/s0022-2836(02)01328-1

PubMed ID: 15380105

Title: The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.

PubMed ID: 15380105

DOI: 10.1016/j.dnarep.2004.06.017

PubMed ID: 15385968

Title: Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV.

PubMed ID: 15385968

DOI: 10.1038/sj.emboj.7600375

PubMed ID: 16412978

Title: Monoubiquitination of the nonhomologous end joining protein XRCC4.

PubMed ID: 16412978

DOI: 10.1016/j.bbrc.2005.12.166

PubMed ID: 16439205

Title: XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining.

PubMed ID: 16439205

DOI: 10.1016/j.cell.2005.12.031

PubMed ID: 17124166

Title: Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4.

PubMed ID: 17124166

DOI: 10.1073/pnas.0609061103

PubMed ID: 16478998

Title: SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair.

PubMed ID: 16478998

DOI: 10.1128/mcb.26.5.1786-1794.2006

PubMed ID: 17290226

Title: XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps.

PubMed ID: 17290226

DOI: 10.1038/sj.emboj.7601559

PubMed ID: 18158905

Title: Crystal structure of human XLF: a twist in nonhomologous DNA end-joining.

PubMed ID: 18158905

DOI: 10.1016/j.molcel.2007.10.024

PubMed ID: 17396150

Title: A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses.

PubMed ID: 17396150

DOI: 10.1038/sj.emboj.7601663

PubMed ID: 17353262

Title: APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks.

PubMed ID: 17353262

DOI: 10.1128/mcb.02269-06

PubMed ID: 18077224

Title: APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation.

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DOI: 10.1016/j.dnarep.2007.10.008

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

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Title: Electron microscopy of Xrcc4 and the DNA ligase IV-Xrcc4 DNA repair complex.

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PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

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PubMed ID: 20558749

Title: Delineation of the Xrcc4-interacting region in the globular head domain of cernunnos/XLF.

PubMed ID: 20558749

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PubMed ID: 20852255

Title: Dual modes of interaction between XRCC4 and polynucleotide kinase/phosphatase: implications for nonhomologous end joining.

PubMed ID: 20852255

DOI: 10.1074/jbc.m109.058719

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 22102241

Title: Crystallization and preliminary X-ray diffraction analysis of the human XRCC4-XLF complex.

PubMed ID: 22102241

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PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21982441

Title: XRCC4 controls nuclear import and distribution of Ligase IV and exchanges faster at damaged DNA in complex with Ligase IV.

PubMed ID: 21982441

DOI: 10.1016/j.dnarep.2011.09.012

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 22228831

Title: XRCC4's interaction with XLF is required for coding (but not signal) end joining.

PubMed ID: 22228831

DOI: 10.1093/nar/gkr1315

PubMed ID: 22658747

Title: Structural insights into the role of domain flexibility in human DNA ligase IV.

PubMed ID: 22658747

DOI: 10.1016/j.str.2012.04.012

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24984242

Title: DNA Ligase IV regulates XRCC4 nuclear localization.

PubMed ID: 24984242

DOI: 10.1016/j.dnarep.2014.05.010

PubMed ID: 24389050

Title: Genomic analysis of primordial dwarfism reveals novel disease genes.

PubMed ID: 24389050

DOI: 10.1101/gr.160572.113

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25597996

Title: Asparagine 326 in the extremely C-terminal region of XRCC4 is essential for the cell survival after irradiation.

PubMed ID: 25597996

DOI: 10.1016/j.bbrc.2015.01.015

PubMed ID: 25934149

Title: Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear localization of XRCC4 and DNA ligase IV.

PubMed ID: 25934149

DOI: 10.1016/j.bbrc.2015.04.093

PubMed ID: 25941166

Title: XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.

PubMed ID: 25941166

DOI: 10.1038/cdd.2015.22

PubMed ID: 26100018

Title: XRCC4/XLF interaction is variably required for DNA repair and is not required for ligase IV stimulation.

PubMed ID: 26100018

DOI: 10.1128/mcb.01503-14

PubMed ID: 25670504

Title: Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway.

PubMed ID: 25670504

DOI: 10.1038/ncomms7233

PubMed ID: 25574025

Title: DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.

PubMed ID: 25574025

DOI: 10.1126/science.1261971

PubMed ID: 26666690

Title: In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage.

PubMed ID: 26666690

DOI: 10.1093/jrr/rrv086

PubMed ID: 26774286

Title: FBXW7 facilitates nonhomologous end-joining via K63-linked polyubiquitylation of XRCC4.

PubMed ID: 26774286

DOI: 10.1016/j.molcel.2015.12.010

PubMed ID: 27437582

Title: Sliding sleeves of XRCC4-XLF bridge DNA and connect fragments of broken DNA.

PubMed ID: 27437582

DOI: 10.1038/nature18643

PubMed ID: 28500754

Title: Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF C-terminal tails in modulating DNA bridging during classical non-homologous end joining.

PubMed ID: 28500754

DOI: 10.7554/elife.22900

PubMed ID: 28453785

Title: Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.

PubMed ID: 28453785

DOI: 10.1093/nar/gkx275

PubMed ID: 30247612

Title: In cellulo phosphorylation of DNA double-strand break repair protein XRCC4 on Ser260 by DNA-PK.

PubMed ID: 30247612

DOI: 10.1093/jrr/rry072

PubMed ID: 30250067

Title: PAXX and its paralogs synergistically direct DNA polymerase lambda activity in DNA repair.

PubMed ID: 30250067

DOI: 10.1038/s41467-018-06127-y

PubMed ID: 33725486

Title: Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane.

PubMed ID: 33725486

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PubMed ID: 11080143

Title: Crystal structure of the Xrcc4 DNA repair protein and implications for end joining.

PubMed ID: 11080143

DOI: 10.1093/emboj/19.22.5962

PubMed ID: 11702069

Title: Crystal structure of an Xrcc4-DNA ligase IV complex.

PubMed ID: 11702069

DOI: 10.1038/nsb725

PubMed ID: 14607114

Title: Tetramerization and DNA ligase IV interaction of the DNA double-strand break repair protein XRCC4 are mutually exclusive.

PubMed ID: 14607114

DOI: 10.1016/j.jmb.2003.09.031

PubMed ID: 19332554

Title: Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4.

PubMed ID: 19332554

DOI: 10.1128/mcb.01895-08

PubMed ID: 21936820

Title: Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions.

PubMed ID: 21936820

DOI: 10.1042/bst0391387

PubMed ID: 21775435

Title: XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair.

PubMed ID: 21775435

DOI: 10.1074/jbc.m111.272641

PubMed ID: 22287571

Title: A human XRCC4-XLF complex bridges DNA.

PubMed ID: 22287571

DOI: 10.1093/nar/gks022

PubMed ID: 21768349

Title: Structural characterization of filaments formed by human Xrcc4-Cernunnos/XLF complex involved in nonhomologous DNA end-joining.

PubMed ID: 21768349

DOI: 10.1073/pnas.1100758108

PubMed ID: 31548606

Title: The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis.

PubMed ID: 31548606

DOI: 10.1038/s41556-019-0388-0

PubMed ID: 34352203

Title: Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.

PubMed ID: 34352203

DOI: 10.1016/j.molcel.2021.07.005

PubMed ID: 33854234

Title: Structural basis of long-range to short-range synaptic transition in NHEJ.

PubMed ID: 33854234

DOI: 10.1038/s41586-021-03458-7

PubMed ID: 25728776

Title: Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

PubMed ID: 25728776

DOI: 10.1016/j.ajhg.2015.01.013

PubMed ID: 25872942

Title: A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy.

PubMed ID: 25872942

DOI: 10.15252/emmm.201404803

PubMed ID: 25839420

Title: Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability.

PubMed ID: 25839420

DOI: 10.1093/hmg/ddv115

PubMed ID: 26255102

Title: XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency.

PubMed ID: 26255102

DOI: 10.1016/j.jaci.2015.06.007

PubMed ID: 25742519

Title: An XRCC4 splice mutation associated with severe short stature, gonadal failure, and early-onset metabolic syndrome.

PubMed ID: 25742519

DOI: 10.1210/jc.2015-1098

PubMed ID: 32524007

Title: Novel XRCC4 mutations in an infant with microcephalic primordial dwarfism, dilated cardiomyopathy, subclinical hypothyroidism, and early death: expanding the phenotype of XRCC4 mutations.

PubMed ID: 32524007

DOI: 10.4158/accr-2019-0283

Sequence Information:

  • Length: 336
  • Mass: 38287
  • Checksum: BE5FB99153479A4E
  • Sequence:
    • MERKISRIHL VSEPSITHFL QVSWEKTLES GFVITLTDGH SAWTGTVSES EISQEADDMA 
MEKGKYVGEL RKALLSGAGP ADVYTFNFSK ESCYFFFEKN LKDVSFRLGS FNLEKVENPA 
EVIRELICYC LDTIAENQAK NEHLQKENER LLRDWNDVQG RFEKCVSAKE ALETDLYKRF 
ILVLNEKKTK IRSLHNKLLN AAQEREKDIK QEGETAICSE MTADRDPVYD ESTDEESENQ 
TDLSGLASAA VSKDDSIISS LDVTDIAPSR KRRQRMQRNL GTEPKMAPQE NQLQEKENSR 
PDSSLPETSK KEHISAENMS LETLRNSSPE DLFDEI

Genular Protein ID: 174272937

Symbol: Q7Z763_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7Z763

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 4 SAM 1

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 61
  • Mass: 6935
  • Checksum: A9B9CA60D5C99F98
  • Sequence:
    • MQRNLGTEPK MAPQENQLQE KENSRPDSSL PETSKKEHIS AENMSLETLR NSSPEETFCS 
I