DegronMD - Q15054(POLD3)

FUNCTION: Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:22801543, PubMed:17317665, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:25628356, ECO:0000269|PubMed:27185888}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A140S	TCGA-60-2704	LUSC	TCGA	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1667
p.S152F	TCGA-D9-A1JW	SKCM	TCGA	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.2778
p.L160I	TCGA-DU-6392	LGG	TCGA	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.0556
p.S148F	TCGA-EE-A3JD	SKCM	TCGA	AESSS	DEG_SPOP_SBC_1	146:150	Mutation altering degron motif	0.7982
p.S158P	TCGA-EK-A2RK	CESC	TCGA	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1111
p.G137D	DO14214	HNSC	ICGC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.0833
p.G137C	DO229028	LICA	ICGC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.0833
p.E156K	SIDM00454	Rhabdomyosarcoma	GDSC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1667
p.E156K	RH-18	soft tissue	COSMIC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1667
p.S150L	SIDM00656	Burkitt's Lymphoma	GDSC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation altering degron motif	0.7667
p.S150L	SIDM00844	Burkitt's Lymphoma	GDSC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation altering degron motif	0.7667
p.S150L	SIDM00907	Burkitt's Lymphoma	GDSC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation altering degron motif	0.7667
p.S150L	SIDM00641	Burkitt's Lymphoma	GDSC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation altering degron motif	0.7667
p.V141I	ACH-001061	Colon/Colorectal Cancer	CCLE	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1944
p.K160R	RF-48	stomach	COSMIC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.0556
p.Q159R	AN3-CA	endometrium	COSMIC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.0833
p.A158T	KNS-81-FD	central nervous system	COSMIC	AESSS	DEG_SPOP_SBC_1	146:150	Mutation rewiring degron network	0.1111

Kaplan plot for POLD3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

POLD3

UniProt ID: Q15054

Entrez ID: 10714

Protein name: DNA polymerase delta subunit 3 (DNA polymerase delta subunit C) (DNA polymerase delta subunit p66) (DNA polymerase delta subunit p68)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for POLD3 in