Reviewed, UniProtKB/Swiss-Prot P27694 (RFA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Replication protein A 70 kDa DNA-binding subunit
      Short name=RP-A p70
Alternative name(s):
    Replication factor A protein 1
      Short name=RF-A protein 1
    Single-stranded DNA-binding protein

Gene names

Name:	RPA1
Synonyms:	REPA1, RPA70

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	616 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

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.
Subunit structure	Heterotrimer composed of RPA1, RPA2 and RPA3. The DNA-binding activity may reside exclusively on the RPA1 subunit. Interacts with RIP 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.14 Ref.15 Ref.17
Sequence similarities	Belongs to the replication factor A protein 1 family.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication Traceable author statement. Source: ProtInc nucleotide-excision repair, DNA damage removal Inferred from Experiment. Source: Reactome nucleotide-excision repair, DNA gap filling Inferred from Experiment. Source: Reactome
Cellular component	DNA replication factor A complex Ref.13 Inferred from physical interaction. Source: MGI PML body Ref.13 Inferred from direct assay. Source: MGI cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB single-stranded DNA binding Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BLM	P54132	1	EBI-621389,EBI-621372
TP53	P04637	1	EBI-621389,EBI-366083
WRN	Q14191	4	EBI-621389,EBI-368417

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 616

615

Replication protein A 70 kDa DNA-binding subunit

PRO_0000097260

Regions

Zinc finger

481 – 503

23

C4-type Potential

Amino acid modifications

Modified residue

163

1

N6-acetyllysine Ref.18

Modified residue

167

1

N6-acetyllysine Ref.18

Modified residue

180

1

Phosphothreonine Ref.14

Modified residue

191

1

Phosphothreonine Ref.17

Modified residue

259

1

N6-acetyllysine Ref.18

Modified residue

384

1

Phosphoserine Ref.15

Natural variations

Natural variant

351

1

T → A: dbSNP rs5030755. Ref.4 Ref.5

VAR_019236

Secondary structure

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616

Helix Strand Turn

Details...

Helix

9 – 16

8

Beta strand

24 – 33

10

Beta strand

41 – 47

7

Beta strand

49 – 58

10

Helix

60 – 62

3

Helix

63 – 67

5

Beta strand

76 – 86

11

Beta strand

88 – 90

3

Beta strand

92 – 103

12

Helix

445 – 451

7

Turn

452 – 454

3

Beta strand

455 – 458

4

Beta strand

460 – 471

12

Beta strand

477 – 480

4

Beta strand

491 – 493

3

Turn

494 – 496

3

Beta strand

497 – 500

4

Turn

501 – 504

4

Beta strand

505 – 509

5

Beta strand

512 – 521

10

Beta strand

526 – 532

7

Helix

533 – 540

8

Helix

544 – 550

7

Helix

555 – 564

10

Turn

565 – 567

3

Beta strand

569 – 577

9

Beta strand

588 – 596

9

Helix

599 – 615

17

Sequences

	Sequence		Length	Mass (Da)
	P27694-1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: FE038F40F5886CD1	FASTA	616	68,138
	10 20 30 40 50 60 MVGQLSEGAI AAIMQKGDTN IKPILQVINI RPITTGNSPP RYRLLMSDGL NTLSSFMLAT 70 80 90 100 110 120 QLNPLVEEEQ LSSNCVCQIH RFIVNTLKDG RRVVILMELE VLKSAEAVGV KIGNPVPYNE 130 140 150 160 170 180 GLGQPQVAPP APAASPAASS RPQPQNGSSG MGSTVSKAYG ASKTFGKAAG PSLSHTSGGT 190 200 210 220 230 240 QSKVVPIASL TPYQSKWTIC ARVTNKSQIR TWSNSRGEGK LFSLELVDES GEIRATAFNE 250 260 270 280 290 300 QVDKFFPLIE VNKVYYFSKG TLKIANKQFT AVKNDYEMTF NNETSVMPCE DDHHLPTVQF 310 320 330 340 350 360 DFTGIDDLEN KSKDSLVDII GICKSYEDAT KITVRSNNRE VAKRNIYLMD TSGKVVTATL 370 380 390 400 410 420 WGEDADKFDG SRQPVLAIKG ARVSDFGGRS LSVLSSSTII ANPDIPEAYK LRGWFDAEGQ 430 440 450 460 470 480 ALDGVSISDL KSGGVGGSNT NWKTLYEVKS ENLGQGDKPD YFSSVATVVY LRKENCMYQA 490 500 510 520 530 540 CPTQDCNKKV IDQQNGLYRC EKCDTEFPNF KYRMILSVNI ADFQENQWVT CFQESAEAIL 550 560 570 580 590 600 GQNAAYLGEL KDKNEQAFEE VFQNANFRSF IFRVRVKVET YNDESRIKAT VMDVKPVDYR 610 EYGRRLVMSI RRSALM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a cDNA encoding the 70-kDa single-stranded DNA-binding subunit of human replication protein A and the role of the protein in DNA replication." Erdile L.F., Heyer W.-D., Kolodner R., Kelly T.J. J. Biol. Chem. 266:12090-12098(1991) [PubMed: 2050703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing." Erdile L.F., Heyer W.-D., Kolodner R., Kelly T.J. J. Biol. Chem. 268:2268-2268(1993) [PubMed: 8420996] [Abstract] Cited for: SEQUENCE REVISION TO 217.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-351. Tissue: Aortic endothelium.
[5]	NIEHS SNPs program Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-351.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[8]	Bienvenut W.V., Vousden K.H., Lukashchuk N. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-41; 82-88; 93-103; 168-196; 221-259; 314-324; 345-379; 390-410; 413-472; 490-499; 503-511; 552-568; 576-586 AND 589-600, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[9]	"Rpa4, a homolog of the 34-kilodalton subunit of the replication protein A complex." Keshav K.F., Chen C., Dutta A. Mol. Cell. Biol. 15:3119-3128(1995) [PubMed: 7760808] [Abstract] Cited for: INTERACTION WITH RPA4.
[10]	"Role of protein-protein interactions in the function of replication protein A (RPA): RPA modulates the activity of DNA polymerase alpha by multiple mechanisms." Braun K.A., Lao Y., He Z., Ingles C.J., Wold M.S. Biochemistry 36:8443-8454(1997) [PubMed: 9214288] [Abstract] Cited for: INTERACTION WITH POLA1.
[11]	"Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA." Ikegami T., Kuraoka I., Saijo M., Kodo N., Kyogoku Y., Morikawa K., Tanaka K., Shirakawa M. Nat. Struct. Biol. 5:701-706(1998) [PubMed: 9699634] [Abstract] Cited for: INTERACTION WITH XPA.
[12]	"Interactions of human nucleotide excision repair protein XPA with DNA and RPA70 Delta C327: chemical shift mapping and 15N NMR relaxation studies." Buchko G.W., Daughdrill G.W., de Lorimier R., Sudha Rao B.K., Isern N.G., Lingbeck J.M., Taylor J.-S., Wold M.S., Gochin M., Spicer L.D., Lowry D.F., Kennedy M.A. Biochemistry 38:15116-15128(1999) [PubMed: 10563794] [Abstract] Cited for: INTERACTION WITH XPA.
[13]	"Sumoylation of the novel protein hRIPbeta is involved in replication protein A deposition in PML nuclear bodies." Park J., Seo T., Kim H., Choe J. Mol. Cell. Biol. 25:8202-8214(2005) [PubMed: 16135809] [Abstract] Cited for: INTERACTION WITH RIP.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180, MASS SPECTROMETRY.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-384, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-191, MASS SPECTROMETRY.
[18]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-163; LYS-167 AND LYS-259, MASS SPECTROMETRY.
[19]	"Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA." Bochkarev A., Pfuetzner R.A., Edwards A.M., Frappier L. Nature 385:176-181(1997) [PubMed: 8990123] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 183-420.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63488 mRNA. Translation: AAA36584.1.
AK289704 mRNA. Translation: BAF82393.1.
AB209732 mRNA. Translation: BAD92969.1. Different initiation.
AY599563 Genomic DNA. Translation: AAS94324.1.
CH471108 Genomic DNA. Translation: EAW90574.1.
BC018126 mRNA. Translation: AAH18126.1.

IPI

IPI00020127.

PIR

A40457.

RefSeq

NP_002936.1.

UniGene

Hs.461925
Hs.595562

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EWI	NMR	-	A	1-114	[»]
1FGU	X-ray	2.50	A/B	182-432	[»]
1JMC	X-ray	2.40	A	181-422	[»]
1L1O	X-ray	2.80	C/F	436-616	[»]
2B29	X-ray	1.60	A	1-120	[»]
2B3G	X-ray	1.60	A	1-120	[»]

DisProt

DP00061.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24189N.

IntAct

P27694. 17 interactions.

STRING

P27694.

PTM databases

PhosphoSite

P27694.

Proteomic databases

PeptideAtlas

P27694.

PRIDE

P27694.

Genome annotation databases

Ensembl

ENST00000254719; ENSP00000254719; ENSG00000132383; Homo sapiens. [Genome view]

GeneID

6117.

KEGG

hsa:6117.

UCSC

uc002fto.2. human.

Organism-specific databases

CTD

6117.

GeneCards

GC17P001680.

H-InvDB

HIX0017624.

HGNC

HGNC:10289. RPA1.

HPA

CAB004563.
HPA006914.

MIM

179835. gene.

PharmGKB

PA29353.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17565.

HOGENOM

HBG618684.

HOVERGEN

P27694.

InParanoid

P27694.

OMA

RNIYLMD.

OrthoDB

EOG979HST.

PhylomeDB

P27694.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_216. DNA Repair.
REACT_383. DNA Replication.
REACT_7970. Telomere Maintenance.

Gene expression databases

ArrayExpress

P27694.

Bgee

P27694.

CleanEx

HS_RPA1.

Genevestigator

P27694.

GermOnline

ENSG00000132383. Homo sapiens.

Family and domain databases

InterPro

IPR012340. NA-bd_OB-fold.
IPR016027. NA-bd_OB-fold-like.
IPR004365. NA_bd_OB_tRNA-helicase.
IPR007199. Rep-A_N.
IPR004591. Rpa1.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 4 hits.

Pfam

PF04057. Rep-A_N. 1 hit.
PF01336. tRNA_anti. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00617. rpa1. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

23755.

SOURCE

Search...

Entry information

Entry name

RFA1_HUMAN

Accession

Primary (citable) accession number: P27694
Secondary accession number(s): A8K0Y9, Q59ES9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	February 1, 1996
Last modified:	February 9, 2010
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.