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Overview

Uniprot ID	P27694
Protein Name	Replication protein A 70 kDa DNA-binding subunit
Gene Name	RPA1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
157	GMGSTVSKAYGASKT
163	SKAYGASKTFGKAAG
167	GASKTFGKAAGPSLS
267	GTLKIANKQFTAVKN
88	RFIVNTLKDGRRVVI

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:17596542, PubMed:27723717, PubMed:27723720). 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). Also plays 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. Plays a role in telomere maintenance (PubMed:17959650, PubMed:34767620). 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). RPA stimulates 5'-3' helicase activity of the BRIP1/FANCJ (PubMed:17596542)

Protein Sequence

10 MVGQLSEGAI 20 AAIMQKGDTN 30 IKPILQVINI 40 RPITTGNSPP 50 RYRLLMSDGL 60 NTLSSFMLAT 70 QLNPLVEEEQ 80 LSSNCVCQIH 90 RFIVNTLKDG 100 RRVVILMELE 110 VLKSAEAVGV 120 KIGNPVPYNE 130 GLGQPQVAPP 140 APAASPAASS 150 RPQPQNGSSG 160 MGSTVSKAYG 170 ASKTFGKAAG 180 PSLSHTSGGT 190 QSKVVPIASL 200 TPYQSKWTIC 210 ARVTNKSQIR 220 TWSNSRGEGK 230 LFSLELVDES 240 GEIRATAFNE 250 QVDKFFPLIE 260 VNKVYYFSKG 270 TLKIANKQFT 280 AVKNDYEMTF 290 NNETSVMPCE 300 DDHHLPTVQF 310 DFTGIDDLEN 320 KSKDSLVDII 330 GICKSYEDAT 340 KITVRSNNRE 350 VAKRNIYLMD 360 TSGKVVTATL 370 WGEDADKFDG 380 SRQPVLAIKG 390 ARVSDFGGRS 400 LSVLSSSTII 410 ANPDIPEAYK 420 LRGWFDAEGQ 430 ALDGVSISDL 440 KSGGVGGSNT 450 NWKTLYEVKS 460 ENLGQGDKPD 470 YFSSVATVVY 480 LRKENCMYQA 490 CPTQDCNKKV 500 IDQQNGLYRC 510 EKCDTEFPNF 520 KYRMILSVNI 530 ADFQENQWVT 540 CFQESAEAIL 550 GQNAAYLGEL 560 KDKNEQAFEE 570 VFQNANFRSF 580 IFRVRVKVET 590 YNDESRIKAT 600 VMDVKPVDYR 610 EYGRRLVMSI RRSALM

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000781	chromosome, telomeric region
Molecular Function	GO:0003682	chromatin binding
Molecular Function	GO:0140463	chromatin-protein adaptor activity
Molecular Function	GO:0003684	damaged DNA binding
Molecular Function	GO:0098505	G-rich strand telomeric DNA binding
Molecular Function	GO:0003697	single-stranded DNA binding
Molecular Function	GO:0043047	single-stranded telomeric DNA binding
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0006284	base-excision repair
Biological Process	GO:0006974	DNA damage response
Biological Process	GO:0006310	DNA recombination
Biological Process	GO:0006281	DNA repair
Biological Process	GO:0006260	DNA replication
Biological Process	GO:0006261	DNA-templated DNA replication
Biological Process	GO:0000724	double-strand break repair via homologous recombination
Biological Process	GO:0051321	meiotic cell cycle
Biological Process	GO:0006298	mismatch repair
Biological Process	GO:0006289	nucleotide-excision repair
Biological Process	GO:0034502	protein localization to chromosome
Biological Process	GO:1990166	protein localization to site of double-strand break
Biological Process	GO:0000723	telomere maintenance
Biological Process	GO:0007004	telomere maintenance via telomerase
Cellular Component	GO:0005662	DNA replication factor A complex
Cellular Component	GO:0000800	lateral element
Cellular Component	GO:0001673	male germ cell nucleus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0016605	PML body
Cellular Component	GO:0090734	site of DNA damage
Cellular Component	GO:0035861	site of double-strand break

Reference

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[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[5] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[6] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[7] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[8] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[9] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[10] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[11] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[12] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.