Human Gene RPA1 (ENST00000254719.10) from GENCODE V44
Description: Homo sapiens replication protein A1 (RPA1), transcript variant 1, mRNA. (from RefSeq NM_002945) RefSeq Summary (NM_002945): This gene encodes the largest subunit of the heterotrimeric Replication Protein A (RPA) complex, which binds to single-stranded DNA (ssDNA), forming a nucleoprotein complex that plays an important role in DNA metabolism, being involved in DNA replication, repair, recombination, telomere maintenance, and co-ordinating the cellular response to DNA damage through activation of the ataxia telangiectasia and Rad3-related protein (ATR) kinase. The nucleoprotein complex protects the single-stranded DNA from nucleases, prevents formation of secondary structures that would interfere with repair, and co-ordinates the recruitment and departure of different genome maintenance factors. This subunit contains four oligonucleotide/oligosaccharide-binding (OB) domains, though the majority of ssDNA binding occurs in two of these domains. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which ssDNA binding domains are utilized. The different binding modes differ in the length of DNA bound and in the proteins with which it interacts, thereby playing a role in regulating different genomic maintenance pathways. [provided by RefSeq, Sep 2017]. Gencode Transcript: ENST00000254719.10 Gencode Gene: ENSG00000132383.12 Transcript (Including UTRs) Position: hg38 chr17:1,830,005-1,900,082 Size: 70,078 Total Exon Count: 17 Strand: + Coding Region Position: hg38 chr17:1,830,094-1,897,175 Size: 67,082 Coding Exon Count: 17
ID:RFA1_HUMAN DESCRIPTION: RecName: Full=Replication protein A 70 kDa DNA-binding subunit; Short=RP-A p70; AltName: Full=Replication factor A protein 1; Short=RF-A protein 1; AltName: Full=Single-stranded DNA-binding protein; FUNCTION: Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing. FUNCTION: Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S- phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange. SUBUNIT: Heterotrimer composed of RPA1, RPA2 and RPA3 (canonical replication protein A complex). Component of the alternative replication protein A complex (aRPA) composed of RPA1, RPA3 and RPA4. The DNA-binding activity may reside exclusively on the RPA1 subunit. Interacts with RIPK1 and XPA. Interacts with RPA4. Interacts with the polymerase alpha subunit POLA1/p180; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp. Interacts with RAD51 and SENP6 to regulate DNA repair. Interacts with HELB; this interaction promotes HELB recruitment to chromatin following DNA damage. INTERACTION: P54132:BLM; NbExp=3; IntAct=EBI-621389, EBI-621372; P15927:RPA2; NbExp=4; IntAct=EBI-621389, EBI-621404; P35244:RPA3; NbExp=4; IntAct=EBI-621389, EBI-621428; Q14191:WRN; NbExp=8; IntAct=EBI-621389, EBI-368417; SUBCELLULAR LOCATION: Nucleus. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: Sumoylated on lysine residues Lys-449 and Lys-577, with Lys- 449 being the major site. Sumoylation promotes recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Desumoylated by SENP6. SIMILARITY: Belongs to the replication factor A protein 1 family. SEQUENCE CAUTION: Sequence=BAD92969.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rpa1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P27694
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK289704 - Homo sapiens cDNA FLJ75577 complete cds, highly similar to Homo sapiens replication protein A1, 70kDa (RPA1), mRNA. M63488 - Human replication protein A 70kDa subunit mRNA complete cds. AB209732 - Homo sapiens mRNA for replication protein A1, 70kDa variant protein. BC018126 - Homo sapiens replication protein A1, 70kDa, mRNA (cDNA clone MGC:9195 IMAGE:3912837), complete cds. AB385027 - Synthetic construct DNA, clone: pF1KB5072, Homo sapiens RPA1 gene for replication protein A 70 kDa DNA-binding subunit, complete cds, without stop codon, in Flexi system. HQ258560 - Synthetic construct Homo sapiens clone IMAGE:100073067 replication protein A1, 70kDa (RPA1) gene, encodes complete protein. KJ901049 - Synthetic construct Homo sapiens clone ccsbBroadEn_10443 RPA1 gene, encodes complete protein. JD538258 - Sequence 519282 from Patent EP1572962. HV214678 - JP 2003503008-A/5: METHODS FOR TARGETING RNA MOLECULES. HV214677 - JP 2003503008-A/4: METHODS FOR TARGETING RNA MOLECULES. JD539483 - Sequence 520507 from Patent EP1572962. JD196912 - Sequence 177936 from Patent EP1572962. JD302637 - Sequence 283661 from Patent EP1572962. JD374302 - Sequence 355326 from Patent EP1572962. JD279731 - Sequence 260755 from Patent EP1572962. JD232384 - Sequence 213408 from Patent EP1572962. JD096055 - Sequence 77079 from Patent EP1572962. JD329269 - Sequence 310293 from Patent EP1572962. JD366894 - Sequence 347918 from Patent EP1572962. JD419527 - Sequence 400551 from Patent EP1572962. JD346285 - Sequence 327309 from Patent EP1572962. JD323138 - Sequence 304162 from Patent EP1572962. JD262778 - Sequence 243802 from Patent EP1572962. JD313624 - Sequence 294648 from Patent EP1572962. JD240191 - Sequence 221215 from Patent EP1572962. JD312977 - Sequence 294001 from Patent EP1572962. AF167994 - Homo sapiens MSTP075 (MST075) mRNA, complete cds.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03030 - DNA replication hsa03420 - Nucleotide excision repair hsa03430 - Mismatch repair hsa03440 - Homologous recombination
BioCarta from NCI Cancer Genome Anatomy Project h_p53hypoxiaPathway - Hypoxia and p53 in the Cardiovascular system
Reactome (by CSHL, EBI, and GO)
Protein P27694 (Reactome details) participates in the following event(s):
R-HSA-4551616 SUMOylation of RPA1 (RPA70) with SUMO2,3 R-HSA-69140 RPA binds to the Flap R-HSA-174445 RPA binds to the Flap on the C-strand R-HSA-176175 Stalling of DNA replication fork and RPA binding R-HSA-5333051 RPA1 binds HSF1 R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-6788385 The complex of ATR and ATRIP is recruited to ICL-DNA R-HSA-69144 Removal of RNA primer and dissociation of RPA and Dna2 R-HSA-174441 Removal of RNA primer and dissociation of RPA and Dna2 from the C-strand R-HSA-5358579 DNA polymerase delta polymerizes DNA across single stranded gap R-HSA-5687758 PPP4C:PPP4R2 dephosphorylates RPA2 R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-6788392 ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA R-HSA-69142 Recruitment of Dna2 endonuclease R-HSA-174451 Recruitment of Dna2 endonuclease to the C strand R-HSA-176101 Recruitment of Rad17-RFC complex to DNA R-HSA-176250 Binding of ATR-ATRIP to the RPA-ssDNA complex R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1 R-HSA-5651992 PCNA-containing replication complex binds damaged dsDNA R-HSA-5651809 LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA R-HSA-5653840 POLD,POLE complete replication of damaged DNA after TLS R-HSA-5653766 USP10 binds monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-5653754 UBE2L6:TRIM25 ISGylates monoUb:K164-PCNA R-HSA-5653780 USP43 binds ISG:K164,ISG:K168-PCNA R-HSA-5653770 USP10 deubiquitinates monoUb:K164,ISG:K164,ISG:K168-PCNA R-HSA-5653838 POLD,POLE binds deISGylated PCNA after TLS R-HSA-5653786 USP43 deISGylates ISG:K164,ISG:K168-PCNA R-HSA-5655466 USP1:WDR48 deubiquitinates monoUb:K164-PCNA R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-5690997 Ligation of newly synthesized repair patch to incised DNA in GG-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-176264 Recruitment of the Rad9-Hus1-Rad1 complex to DNA R-HSA-110368 POLD,POLE-mediated DNA strand displacement synthesis R-HSA-110371 LIG1 binds APEX1 and PCNA at SSB R-HSA-110363 FEN1 bound to PCNA and APEX1 cleaves flap ssDNA R-HSA-5651805 LIG1 bound to APEX1 and PCNA ligates SSB R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5655481 USP1:WDR48 binds monoUb:K164-PCNA R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-110307 REV1 binds AP-dsDNA R-HSA-110311 POLZ extends translesion synthesis R-HSA-5653756 TRIM25 binds monoUb:164-PCNA R-HSA-110316 POLH binds monoUb:K164-PCNA at damaged TT-CPD-DNA template R-HSA-5654986 SPRTN binds monoUb:K164-PCNA associated with POLH R-HSA-110319 Elongation by POLH R-HSA-5654989 SPRTN:VCP-mediated release of POLH from monoUb:K164-PCNA R-HSA-5655835 POLK forms a quaternary complex with REV1 and POLZ on damaged DNA template R-HSA-5656105 POLI simultaneously binds REV1 and monoUb:K164-PCNA at damaged DNA R-HSA-110317 Insertion of correct bases opposite the lesion by POLH R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-5691001 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in GG-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5652151 REV1 recruits POLZ to (AP:Cyt)-DNA Template R-HSA-110308 REV1 inserts dCMP opposite to AP sites in DNA R-HSA-5654985 SPRTN recruits VCP to monoUb:K164-PCNA associated with POLH R-HSA-5655892 POLK incorporates dNMP opposite to damaged DNA base R-HSA-5655965 POLK and POLZ cooperate in elongation of mispaired primer termini R-HSA-5656148 POLI incorporates dNMP opposite to damaged DNA base R-HSA-5656158 POLZ elongates POLI-incorporated dNMP R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-3108214 SUMOylation of DNA damage response and repair proteins R-HSA-69166 Removal of the Flap Intermediate R-HSA-174437 Removal of the Flap Intermediate from the C-strand R-HSA-176187 Activation of ATR in response to replication stress R-HSA-912446 Meiotic recombination R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-6782135 Dual incision in TC-NER R-HSA-6783310 Fanconi Anemia Pathway R-HSA-68962 Activation of the pre-replicative complex R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-5696400 Dual Incision in GG-NER R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-69183 Processive synthesis on the lagging strand R-HSA-174414 Processive synthesis on the C-strand of the telomere R-HSA-69481 G2/M Checkpoints R-HSA-1500620 Meiosis R-HSA-3371556 Cellular response to heat stress R-HSA-5358508 Mismatch Repair R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-73894 DNA Repair R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-2990846 SUMOylation R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-73893 DNA Damage Bypass R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-110312 Translesion synthesis by REV1 R-HSA-110320 Translesion Synthesis by POLH R-HSA-5655862 Translesion synthesis by POLK R-HSA-5656121 Translesion synthesis by POLI R-HSA-69186 Lagging Strand Synthesis R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis R-HSA-69620 Cell Cycle Checkpoints R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-2262752 Cellular responses to stress R-HSA-5696398 Nucleotide Excision Repair R-HSA-5693538 Homology Directed Repair R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-597592 Post-translational protein modification R-HSA-73933 Resolution of Abasic Sites (AP sites) R-HSA-69190 DNA strand elongation R-HSA-180786 Extension of Telomeres R-HSA-8953897 Cellular responses to external stimuli R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-69278 Cell Cycle (Mitotic) R-HSA-69306 DNA Replication R-HSA-392499 Metabolism of proteins R-HSA-73884 Base Excision Repair R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69239 Synthesis of DNA R-HSA-157579 Telomere Maintenance R-HSA-5633007 Regulation of TP53 Activity R-HSA-69242 S Phase R-HSA-73886 Chromosome Maintenance R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
