Reviewed, UniProtKB/Swiss-Prot P15927 (RFA2_HUMAN)

Names and origin

Protein names

Recommended name:
Replication protein A 32 kDa subunit
Short name=RP-A p32

Alternative name(s):
Replication protein A 34 kDa subunit
Short name=RP-A p34
Replication factor A protein 2
Short name=RF-A protein 2

Gene names

Name:	RPA2
Synonyms:	REPA2, RPA32, RPA34

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	270 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for DNA recombination, repair and replication. The activity of RP-A is mediated by single-stranded DNA binding and protein interactions. Ref.9
Subunit structure	Heterotrimer of 70, 32 and 14 kDa chains. The DNA-binding activity may reside exclusively on the 70 kDa subunit. Binds to SERTAD3/RBT1. Interacts with TIPIN. Ref.7 Ref.10 Ref.11
Subcellular location	Nucleus. Note: Also present in PML nuclear bodies. Redistributes to discrete nuclear foci upon DNA damage. Ref.8
Post-translational modification	Phosphorylated in a cell-cycle-dependent manner (from the S phase until mitosis). Phosphorylated by ATR upon DNA damage, which promotes its translocation to nuclear foci. Can be phosphorylated in vitro by PRKDC/DNA-PK in the presence of Ku and DNA, and by CDC2. Ref.8 Ref.6

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication Ref.1 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.1 Inferred from physical interaction. Source: MGI nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB single-stranded DNA binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREBBP	Q92793	1	EBI-621404,EBI-81215
GAPDH	P04406	1	EBI-621404,EBI-354056

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P15927-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P15927-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MWNS → MGRGDRNKRSIR

Note: No experimental confirmation available.

Isoform 3 (identifier: P15927-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MWNS → MWNSNDGGAG...QALILLFKTG

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 270

270

Replication protein A 32 kDa subunit

PRO_0000097270

Regions

Region

187 – 270

84

Interaction with TIPIN By similarity

Compositional bias

1 – 29

29

Gly/Ser-rich

Compositional bias

37 – 45

9

Arg/Lys-rich (basic)

Compositional bias

95 – 123

29

Asp/Glu-rich (acidic)

Compositional bias

127 – 145

19

Arg/Lys-rich (basic)

Compositional bias

247 – 270

24

Asp/Glu-rich (acidic)

Sites

Site

23

1

Not phosphorylated Probable

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.6 Ref.12

Modified residue

21

1

Phosphothreonine; by PRKDC; in vitro Ref.6

Modified residue

29

1

Phosphoserine; by CDC2; in vitro Ref.6

Modified residue

33

1

Phosphoserine; by PRKDC; in vitro Ref.6

Natural variations

Alternative sequence

1 – 4

4

MWNS → MGRGDRNKRSIR in isoform 2.

VSP_017201

Alternative sequence

1 – 4

4

MWNS → MWNSNDGGAGWRRKRIAGGF SKRASLGSERRVVAGEEGRE RSWGVWGSPAGRRRGRLGRL GQCLKGRSLREPAGFSEAWD VAQALILLFKTG in isoform 3.

VSP_017202

Natural variant

14

1

Y → S: dbSNP rs28988896. Ref.3

VAR_023300

Natural variant

15

1

G → R: dbSNP rs28988897. Ref.3

VAR_023301

Natural variant

203

1

N → S: dbSNP rs28904899. Ref.3

VAR_023302

Experimental info

Mutagenesis

29

1

S → A: Reduces phosphorylation by CDC2. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

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.

.

.

.

.

270

Helix Strand Turn

Details...

Helix

51 – 56

6

Beta strand

58 – 60

3

Beta strand

63 – 66

4

Beta strand

69 – 85

17

Beta strand

87 – 95

9

Beta strand

97 – 100

4

Beta strand

102 – 107

6

Beta strand

125 – 135

11

Beta strand

138 – 148

11

Helix

153 – 172

20

Helix

207 – 218

12

Turn

222 – 224

3

Helix

227 – 233

7

Helix

239 – 251

13

Beta strand

254 – 257

4

Beta strand

263 – 268

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 61A563EA7B34A9B1	FASTA	270	29,247
	10 20 30 40 50 60 MWNSGFESYG SSSYGGAGGY TQSPGGFGSP APSQAEKKSR ARAQHIVPCT ISQLLSATLV 70 80 90 100 110 120 DEVFRIGNVE ISQVTIVGII RHAEKAPTNI VYKIDDMTAA PMDVRQWVDT DDTSSENTVV 130 140 150 160 170 180 PPETYVKVAG HLRSFQNKKS LVAFKIMPLE DMNEFTTHIL EVINAHMVLS KANSQPSAGR 190 200 210 220 230 240 APISNPGMSE AGNFGGNSFM PANGLTVAQN QVLNLIKACP RPEGLNFQDL KNQLKHMSVS 250 260 270 SIKQAVDFLS NEGHIYSTVD DDHFKSTDAE
	Isoform 2. Checksum: 680A88DB44410EBC	FASTA	278	30,156
	10 20 30 40 50 60 MGRGDRNKRS IRGFESYGSS SYGGAGGYTQ SPGGFGSPAP SQAEKKSRAR AQHIVPCTIS 70 80 90 100 110 120 QLLSATLVDE VFRIGNVEIS QVTIVGIIRH AEKAPTNIVY KIDDMTAAPM DVRQWVDTDD 130 140 150 160 170 180 TSSENTVVPP ETYVKVAGHL RSFQNKKSLV AFKIMPLEDM NEFTTHILEV INAHMVLSKA 190 200 210 220 230 240 NSQPSAGRAP ISNPGMSEAG NFGGNSFMPA NGLTVAQNQV LNLIKACPRP EGLNFQDLKN 250 260 270 QLKHMSVSSI KQAVDFLSNE GHIYSTVDDD HFKSTDAE
	Isoform 3. Checksum: B21291661BDEEAFA	FASTA	358	38,810
	10 20 30 40 50 60 MWNSNDGGAG WRRKRIAGGF SKRASLGSER RVVAGEEGRE RSWGVWGSPA GRRRGRLGRL 70 80 90 100 110 120 GQCLKGRSLR EPAGFSEAWD VAQALILLFK TGGFESYGSS SYGGAGGYTQ SPGGFGSPAP 130 140 150 160 170 180 SQAEKKSRAR AQHIVPCTIS QLLSATLVDE VFRIGNVEIS QVTIVGIIRH AEKAPTNIVY 190 200 210 220 230 240 KIDDMTAAPM DVRQWVDTDD TSSENTVVPP ETYVKVAGHL RSFQNKKSLV AFKIMPLEDM 250 260 270 280 290 300 NEFTTHILEV INAHMVLSKA NSQPSAGRAP ISNPGMSEAG NFGGNSFMPA NGLTVAQNQV 310 320 330 340 350 LNLIKACPRP EGLNFQDLKN QLKHMSVSSI KQAVDFLSNE GHIYSTVDDD HFKSTDAE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structure of the 32-kDa subunit of human replication protein A." Erdile L.F., Wold M.S., Kelly T.J. J. Biol. Chem. 265:3177-3182(1990) [PubMed: 2406247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	NIEHS SNPs program Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-14; ARG-15 AND SER-203.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Kidney, Lung and Muscle.
[6]	"Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro." Niu H., Erdjument-Bromage H., Pan Z.-Q., Lee S.-H., Tempst P., Hurwitz J. J. Biol. Chem. 272:12634-12641(1997) [PubMed: 9139719] [Abstract] Cited for: ACETYLATION AT MET-1, PHOSPHORYLATION AT THR-21; SER-29 AND SER-33, MASS SPECTROMETRY, MUTAGENESIS OF SER-29.
[7]	"RBT1, a novel transcriptional co-activator, binds the second subunit of replication protein A." Cho J.M., Song D.J., Bergeron J., Benlimame N., Wold M.S., Alaoui-Jamali M.A. Nucleic Acids Res. 28:3478-3485(2000) [PubMed: 10982866] [Abstract] Cited for: INTERACTION WITH SERTAD3.
[8]	"ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation." Barr S.M., Leung C.G., Chang E.E., Cimprich K.A. Curr. Biol. 13:1047-1051(2003) [PubMed: 12814551] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[9]	"Coordinated regulation of replication protein A activities by its subunits p14 and p32." Weisshart K., Pestryakov P., Smith R.W.P., Hartmann H., Kremmer E., Lavrik O., Nasheuer H.-P. J. Biol. Chem. 279:35368-35376(2004) [PubMed: 15205463] [Abstract] Cited for: FUNCTION.
[10]	"Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors." Gotter A.L., Suppa C., Emanuel B.S. J. Mol. Biol. 366:36-52(2007) [PubMed: 17141802] [Abstract] Cited for: INTERACTION WITH TIPIN.
[11]	"The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement." Uensal-Kacmaz K., Chastain P.D., Qu P.-P., Minoo P., Cordeiro-Stone M., Sancar A., Kaufmann W.K. Mol. Cell. Biol. 27:3131-3142(2007) [PubMed: 17296725] [Abstract] Cited for: INTERACTION WITH TIPIN.
[12]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY.
[13]	"The crystal structure of the complex of replication protein A subunits RPA32 and RPA14 reveals a mechanism for single-stranded DNA binding." Bochkarev A., Bochkareva E., Frappier L., Edwards A.M. EMBO J. 18:4498-4504(1999) [PubMed: 10449415] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 43-171 IN COMPLEX WITH RPA1 AND RPA3.
[14]	"Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA." Mer G., Bochkarev A., Gupta R., Bochkareva E., Frappier L., Ingles C.J., Edwards A.M., Chazin W.J. Cell 103:449-456(2000) [PubMed: 11081631] [Abstract] Cited for: STRUCTURE BY NMR OF 172-270.
[15]	"Structure of the RPA trimerization core and its role in the multistep DNA-binding mechanism of RPA." Bochkareva E., Korolev S., Lees-Miller S.P., Bochkarev A. EMBO J. 21:1855-1863(2002) [PubMed: 11927569] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 44-171.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J05249 mRNA. Translation: AAA36560.1.
CR450348 mRNA. Translation: CAG29344.1.
DQ001128 Genomic DNA. Translation: AAX84514.1.
AL109927 Genomic DNA. Translation: CAI21777.1.
AL109927 Genomic DNA. Translation: CAI21778.1.
AL109927 Genomic DNA. Translation: CAI21775.1.
BC001630 mRNA. Translation: AAH01630.1.
BC012157 mRNA. Translation: AAH12157.1.
BC021257 mRNA. Translation: AAH21257.1.

IPI

IPI00013939.
IPI00646500.
IPI00647667.

PIR

A43711.

RefSeq

NP_002937.1.

UniGene

Hs.703070
Hs.79411

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DPU	NMR	-	A	172-270	[»]
1L1O	X-ray	2.80	B/E	44-171	[»]
1QUQ	X-ray	2.50	A/C	43-171	[»]
1Z1D	NMR	-	A	172-270	[»]
2PI2	X-ray	2.00	A/B/C/D	1-270	[»]
2PQA	X-ray	2.50	A/C	42-172	[»]
2Z6K	X-ray	3.00	A/B	1-270	[»]
3KDF	X-ray	1.98	B/D	42-172	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24187N.

IntAct

P15927. 24 interactions.

STRING

P15927.

PTM databases

PhosphoSite

P15927.

Proteomic databases

PRIDE

P15927.

Genome annotation databases

Ensembl

ENST00000373912; ENSP00000363021; ENSG00000117748; Homo sapiens. [Genome view]

GeneID

6118.

KEGG

hsa:6118.

UCSC

uc001bpd.1. human.
uc001bpe.1. human.

Organism-specific databases

CTD

6118.

GeneCards

GC01M028090.

H-InvDB

HIX0000302.

HGNC

HGNC:10290. RPA2.

HPA

CAB016538.

MIM

179836. gene.

PharmGKB

PA34652.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07006.

HOVERGEN

HBG000086.

OMA

THILEVI.

PhylomeDB

P15927.

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

P15927.

Bgee

P15927.

CleanEx

HS_RPA2.

Genevestigator

P15927.

GermOnline

ENSG00000117748. Homo sapiens.

Family and domain databases

InterPro

IPR012340. NA-bd_OB-fold.
IPR016027. NA-bd_OB-fold-like.
IPR004365. NA_bd_OB_tRNA-helicase.
IPR014646. RPA32.
IPR014892. RPA_C.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

Pfam

PF08784. RPA_C. 1 hit.
PF01336. tRNA_anti. 1 hit.
[Graphical view]

PIRSF

PIRSF036949. RPA32. 1 hit.

SUPFAM

SSF50249. Nucleic_acid_OB. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

23759.

SOURCE

Search...

Entry information

Entry name

RFA2_HUMAN

Accession

Primary (citable) accession number: P15927
Secondary accession number(s): Q52II0, Q5TEI9, Q5TEJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	March 2, 2010
This is version 113 of the entry and version 1 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.