DegronMD - O75417(POLQ)

FUNCTION: DNA polymerase that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery triggered in response to double-strand breaks in DNA (PubMed:25642963, PubMed:25643323). MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25642963, PubMed:25643323). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). POLQ-mediated MMEJ may be required to promote the survival of cells with a compromised HR repair pathway, thereby preventing genomic havoc by resolving unrepaired lesions (By similarity). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (PubMed:25643323). The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). Also exhibits low-fidelity DNA synthesis, translesion synthesis and lyase activity, and it is implicated in interstrand-cross-link repair, base excision repair and DNA end-joining (PubMed:14576298, PubMed:18503084, PubMed:19188258, PubMed:24648516). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (By similarity). {ECO:0000250|UniProtKB:Q8CGS6, ECO:0000269|PubMed:14576298, ECO:0000269|PubMed:18503084, ECO:0000269|PubMed:19188258, ECO:0000269|PubMed:21050863, ECO:0000269|PubMed:22135286, ECO:0000269|PubMed:24648516, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:25643323}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R2460L	TCGA-68-8251	LUSC	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.R2460L	DO26858	LUSC	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.G2452E	TCGA-AA-3510	COAD	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.6087
p.G2452E	DO7783	COAD	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.6087
p.G1733D	TCGA-B5-A3FA	UCEC	TCGA	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.2778
p.G1733D	DO52402	UCEC	ICGC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.2778
p.G2445V	TCGA-B6-A0RU	BRCA	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.3056
p.G2445V	DO1954	BRCA	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.3056
p.P2451S	TCGA-CG-5723	STAD	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.5641
p.P2451S	DO38376	STAD	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.5641
p.Q2441E	TCGA-CV-7099	HNSC	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1944
p.Q2441E	DO15294	HNSC	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1944
p.H2539Y	TCGA-D6-6516	HNSC	TCGA	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation altering degron motif	0.6118
p.H2539Y	DO15623	HNSC	ICGC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation altering degron motif	0.6118
p.F2533V	TCGA-DK-AA71	BLCA	TCGA	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.25
p.F2533V	DO219010	BLCA	ICGC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.25
p.R2436I	TCGA-EM-A2CN	THCA	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.0556
p.R2436I	DO39886	THCA	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.0556
p.R2447H	TCGA-HT-8013	LGG	TCGA	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.R2447H	DO50412	ESAD	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.R2447H	DO22181	LGG	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.R2447H	SIDM00777	Colorectal Carcinoma	GDSC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.R2447H	ACH-000360	Colon/Colorectal Cancer	CCLE	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.R2447H	NCI-H508	large intestine	COSMIC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.8244
p.L1808S	TCGA-KK-A6E3	PRAD	TCGA	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.1944
p.L1808S	DO51357	PRAD	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.1944
p.E2548D	TCGA-MP-A4SV	LUAD	TCGA	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.1389
p.E2548D	DO45339	LUAD	ICGC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.1389
p.V1830L	TCGA-NC-A5HI	LUSC	TCGA	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.0556
p.V1830L	DO45461	LUSC	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.0556
p.S1805L	TCGA-TN-A7HL	HNSC	TCGA	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.1111
p.S1805L	DO219080	HNSC	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.1111
p.P2451Q	DO52603	BOCA	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.5924
p.L1813S	DO225346	BRCA	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7667
p.I2453M	DO1073	BRCA	ICGC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.6507
p.A2547T	DO233855	GACA	ICGC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.1667
p.A2547V	DO229505	LAML	ICGC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.1667
p.P1741Q	DO229015	LICA	ICGC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation altering degron motif	0.5924
p.T1738K	DO229022	LICA	ICGC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation altering degron motif	0.7306
p.A1818D	DO229041	LICA	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.6682
p.S1824N	DO23524	LIRI	ICGC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.2222
p.G1751W	SIDM00773	Non-Cancerous	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.0833
p.G1751W	SIDM00849	Kidney Carcinoma	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.0833
p.G1751W	SIDM00774	Breast Carcinoma	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.0833
p.G1751W	SIDM01409	Bladder Carcinoma	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.0833
p.H2463R	SIDM00122	Breast Carcinoma	GDSC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.0833
p.H2463R	BT-549	breast	COSMIC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.0833
p.P1817A	SIDM00841	Colorectal Carcinoma	GDSC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.P1817A	SIDM00956	Esophageal Squamous Cell Carcinoma	GDSC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.P1817A	ACH-000651	Colon/Colorectal Cancer	CCLE	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.P1817A	ACH-000717	Esophageal Cancer	CCLE	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.P1817A	COLO-680N	oesophagus	COSMIC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.P1817A	SW620	large intestine	COSMIC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation altering degron motif	0.7503
p.T1748S	SIDM01124	Non-Small Cell Lung Carcinoma	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1667
p.T1748S	ACH-000945	Lung Cancer	CCLE	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1667
p.T1748S	NCI-H650	lung	COSMIC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1667
p.V2551D	SIDM00003	Melanoma	GDSC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.0556
p.V2551D	ACH-000884	Skin Cancer	CCLE	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.0556
p.V2551D	ACH-002159	Skin Cancer	CCLE	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.0556
p.V2551D	M14	skin	COSMIC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.0556
p.D1730N	SIDM00988	Kidney Carcinoma	GDSC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1944
p.D1730N	ACH-000792	Kidney Cancer	CCLE	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1944
p.D1730N	BFTC-909	kidney	COSMIC	IPPTPIPT	DEG_SCF_FBW7_1	1735:1742	Mutation rewiring degron network	0.1944
p.R2460H	SIDM00451	T-Lymphoblastic Leukemia	GDSC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.R2460H	ACH-000937	Leukemia	CCLE	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.R2460H	PF-382	haematopoietic and lymphoid tissue	COSMIC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.V2440I	SIDM01570	Ovarian Carcinoma	GDSC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1667
p.G2438R	ACH-001164	Sarcoma	CCLE	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation rewiring degron network	0.1111
p.F2453S	LS-180	large intestine	COSMIC	RRRYLPGIK	DEG_APCC_DBOX_1	2446:2454	Mutation altering degron motif	0.7982
p.G2527E	HCT-15	large intestine	COSMIC	LQLHDE	LIG_APCC_ABBA_1	2536:2541	Mutation rewiring degron network	0.0833
p.R1805I	SNU-81	large intestine	COSMIC	LQLTPASS	DEG_SCF_FBW7_1	1813:1820	Mutation rewiring degron network	0.1111

Kaplan plot for POLQ in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

POLQ

UniProt ID: O75417

Entrez ID: 10721

Protein name: DNA polymerase theta (EC 2.7.7.7) (DNA polymerase eta)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for POLQ in