DegronMD - P27694(RPA1)

FUNCTION: As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism (PubMed:27723720, PubMed:27723717). Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:9430682). In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage (PubMed:17765923). Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716). Plays also a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance (PubMed:17959650). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105). {ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:17765923, ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Q181E	TCGA-DM-A1HB	COAD	TCGA	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation rewiring degron network	0.0833
p.A188T	DO228627	GACA	ICGC	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation rewiring degron network	0.2778
p.W197L	DO229041	LICA	ICGC	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation rewiring degron network	0.2778
p.P192L	DO45159	LIRI	ICGC	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation altering degron motif	0.7582
p.T204S	SIDM01007	T-Lymphoblastic Leukemia	GDSC	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation rewiring degron network	0.0833
p.T204S	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	LTPYQS	DEG_SCF_FBW7_1	190:195	Mutation rewiring degron network	0.0833

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

RPA1

UniProt ID: P27694

Entrez ID: 6117

Protein name: Replication protein A 70 kDa DNA-binding subunit (RP-A p70) (Replication factor A protein 1) (RF-A protein 1) (Single-stranded DNA-binding protein) [Cleaved into: Replication protein A 70 kDa DNA-binding subunit, N-terminally processed]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RPA1 in