DegronMD - Q13426(XRCC4)

FUNCTION: [DNA repair protein XRCC4]: DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:17124166, PubMed:16412978, PubMed:8548796, PubMed:25742519, PubMed:12517771, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25934149, PubMed:26100018, PubMed:26774286). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:26100018, PubMed:27437582, PubMed:28500754, PubMed:21775435, PubMed:22287571, PubMed:21768349). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:9242410, PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:9242410, PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785). {ECO:0000269|PubMed:10757784, ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:15385968, ECO:0000269|PubMed:16412978, ECO:0000269|PubMed:17124166, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25597996, ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25934149, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:8548796, ECO:0000269|PubMed:9242410}.; FUNCTION: [Protein XRCC4, C-terminus]: Acts as an activator of the phospholipid scramblase activity of XKR4 (PubMed:33725486). This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface (PubMed:33725486). {ECO:0000269|PubMed:33725486}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Q289H	TCGA-05-4424	LUAD	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	TCGA-BR-6852	STAD	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	DO23672	LUAD	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	DO38202	STAD	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	SIDM00333	Endometrial Carcinoma	GDSC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	ACH-000988	Endometrial/Uterine Cancer	CCLE	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.Q289H	MFE-319	endometrium	COSMIC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1667
p.R225Q	TCGA-4Z-AA87	BLCA	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.7329
p.R225Q	DO218990	BLCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.7329
p.T308M	TCGA-A5-A0G2	UCEC	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.0833
p.T308M	TCGA-C5-A901	CESC	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.0833
p.S303Y	TCGA-AA-3510	COAD	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.2222
p.R300M	TCGA-AD-5900	COAD	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.3056
p.E235D	TCGA-BF-A1PU	SKCM	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.2222
p.E235D	DO50278	SKCM	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.2222
p.E220Q	TCGA-BH-A0W7	BRCA	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.1944
p.E220Q	DO1272	BRCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.1944
p.D230N	TCGA-E9-A1NA	BRCA	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.5821
p.D230N	DO1522	BRCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.5821
p.D230N	DO222682	BTCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.5821
p.D230N	SIDM01776	Plasma Cell Myeloma	GDSC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.5821
p.D230N	ACH-001162	Myeloma	CCLE	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.5821
p.R225L	TCGA-EE-A183	SKCM	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.8428
p.R225L	DO37715	SKCM	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.8428
p.P288H	TCGA-EE-A29E	SKCM	TCGA	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1389
p.P288H	DO37831	SKCM	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1389
p.E231K	TCGA-GC-A4ZW	BLCA	TCGA	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.7022
p.E231K	DO219024	BLCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation altering degron motif	0.7022
p.M221I	DO225349	BRCA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.2222
p.T306M	DO49914	CESC	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1389
p.T306M	DO41235	UCEC	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.1389
p.K309R	DO9010	COAD	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.0556
p.S301Y	DO7783	COAD	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.2778
p.K309M	DO228574	LICA	ICGC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation rewiring degron network	0.0556
p.D224Y	DO229024	LICA	ICGC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.3056
p.T215I	SIDM02021	Esophageal Carcinoma	GDSC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.0556
p.S219F	SIDM00923	Cervical Carcinoma	GDSC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.1667
p.S219F	ACH-001336	Cervical Cancer	CCLE	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.1667
p.S219F	Ca-Ski	cervix	COSMIC	RDPVYDE	LIG_APCC_ABBAyCdc20_2	225:231	Mutation rewiring degron network	0.1667
p.S299A	SIDM00193	Colorectal Carcinoma	GDSC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation altering degron motif	0.7588
p.S299A	SNU-81	large intestine	COSMIC	EKENS	DEG_APCC_KENBOX_2	295:299	Mutation altering degron motif	0.7588

Kaplan plot for XRCC4 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

XRCC4

UniProt ID: Q13426

Entrez ID: 7518

Protein name: DNA repair protein XRCC4 (hXRCC4) (X-ray repair cross-complementing protein 4) [Cleaved into: Protein XRCC4, C-terminus (XRCC4/C)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for XRCC4 in