P35250 (RFC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Replication factor C subunit 2

Alternative name(s):
Activator 1 40 kDa subunit
Short name=A1 40 kDa subunit
Activator 1 subunit 2
Replication factor C 40 kDa subunit
Short name=RF-C 40 kDa subunit
Short name=RFC40

Gene names

Name:

RFC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit binds ATP By similarity.
Subunit structure	Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA. RFC2 also interacts with PRKAR1A; the complex may be involved in cell survival. Ref.9
Subcellular location	Nucleus Probable.
Involvement in disease	RFC2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
Sequence similarities	Belongs to the activator 1 small subunits family.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Williams-Beuren syndrome
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA strand elongation involved in DNA replication Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement. Source: Reactome nucleotide-excision repair, DNA gap filling Traceable author statement. Source: Reactome telomere maintenance via recombination Traceable author statement. Source: Reactome telomere maintenance via semi-conservative replication Traceable author statement. Source: Reactome transcription-coupled nucleotide-excision repair Traceable author statement. Source: Reactome
Cellular_component	DNA replication factor C complex Inferred from direct assay PubMed 9488738. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Traceable author statement Ref.1. Source: ProtInc DNA binding Inferred from electronic annotation. Source: InterPro nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRKAR1A	P10644	7	EBI-476409,EBI-476431
RFC1	P35251	4	EBI-476409,EBI-476616
RFC4	P35249	8	EBI-476409,EBI-476655

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35250-1)

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: P35250-2)

The sequence of this isoform differs from the canonical sequence as follows:
     111-144: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 354	354	Replication factor C subunit 2		PRO_0000121766
Regions
	Nucleotide binding	76 – 83	8	ATP Potential
Amino acid modifications
	Modified residue	163	1	N6-acetyllysine Ref.10
	Modified residue	304	1	N6-acetyllysine Ref.10
Natural variations
	Alternative sequence	111 – 144	34	Missing in isoform 2.		VSP_005660
	Natural variant	232	1	A → V. Ref.4 Corresponds to variant rs3135684 [ dbSNP | Ensembl ].		VAR_023126
Experimental info
	Sequence conflict	244	1	G → L AA sequence Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 3. Checksum: B50AC8EEF89F64A9	FASTA	354	39,157
	10 20 30 40 50 60 MEVEAVCGGA GEVEAQDSDP APAFSKAPGS AGHYELPWVE KYRPVKLNEI VGNEDTVSRL 70 80 90 100 110 120 EVFAREGNVP NIIIAGPPGT GKTTSILCLA RALLGPALKD AMLELNASND RGIDVVRNKI 130 140 150 160 170 180 KMFAQQKVTL PKGRHKIIIL DEADSMTDGA QQALRRTMEI YSKTTRFALA CNASDKIIEP 190 200 210 220 230 240 IQSRCAVLRY TKLTDAQILT RLMNVIEKER VPYTDDGLEA IIFTAQGDMR QALNNLQSTF 250 260 270 280 290 300 SGFGFINSEN VFKVCDEPHP LLVKEMIQHC VNANIDEAYK ILAHLWHLGY SPEDIIGNIF 310 320 330 340 350 RVCKTFQMAE YLKLEFIKEI GYTHMKIAEG VNSLLQMAGL LARLCQKTMA PVAS
	Isoform 2 [UniParc]. Checksum: D6E72DD28EA014E8	FASTA	320	35,244
	10 20 30 40 50 60 MEVEAVCGGA GEVEAQDSDP APAFSKAPGS AGHYELPWVE KYRPVKLNEI VGNEDTVSRL 70 80 90 100 110 120 EVFAREGNVP NIIIAGPPGT GKTTSILCLA RALLGPALKD AMLELNASND SMTDGAQQAL 130 140 150 160 170 180 RRTMEIYSKT TRFALACNAS DKIIEPIQSR CAVLRYTKLT DAQILTRLMN VIEKERVPYT 190 200 210 220 230 240 DDGLEAIIFT AQGDMRQALN NLQSTFSGFG FINSENVFKV CDEPHPLLVK EMIQHCVNAN 250 260 270 280 290 300 IDEAYKILAH LWHLGYSPED IIGNIFRVCK TFQMAEYLKL EFIKEIGYTH MKIAEGVNSL 310 320 LQMAGLLARL CQKTMAPVAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and expression in Escherichia coli of the 40-kDa subunit of activator 1 (replication factor C) of HeLa cells." Chen M., Pan Z.-Q., Hurwitz J. Proc. Natl. Acad. Sci. U.S.A. 89:2516-2520(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 232-249.
[2]	Hurwitz J. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23." Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V., Koop B.F. Mamm. Genome 11:890-898(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[4]	NIEHS SNPs program Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-232.
[5]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
[7]	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].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[9]	"The second subunit of the replication factor C complex (RFC40) and the regulatory subunit (RIalpha) of protein kinase A form a protein complex promoting cell survival." Gupte R.S., Weng Y., Liu L., Lee M.Y. Cell Cycle 4:323-329(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKAR1A.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-163 AND LYS-304, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	M87338 mRNA. Translation: AAB09786.1. AF045555 Genomic DNA. Translation: AAC04860.1. AF483622 Genomic DNA. Translation: AAL82503.1. AC005081 Genomic DNA. Translation: AAP22334.1. AB451243 mRNA. Translation: BAG70057.1. CH471200 Genomic DNA. Translation: EAW69607.1. CH471200 Genomic DNA. Translation: EAW69608.1. BC002813 mRNA. Translation: AAH02813.1.
IPI	IPI00017412. IPI00218280.
PIR	A42700.
RefSeq	NP_002905.2. NM_002914.3. NP_852136.1. NM_181471.1.
UniGene	Hs.647062.
3D structure databases
ProteinModelPortal	P35250.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-34367N.
IntAct	P35250. 10 interactions.
MINT	MINT-3013724.
STRING	9606.ENSP00000055077.
PTM databases
PhosphoSite	P35250.
Polymorphism databases
DMDM	2507300.
Proteomic databases
PaxDb	P35250.
PeptideAtlas	P35250.
PRIDE	P35250.
Protocols and materials databases
DNASU	5982.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000055077; ENSP00000055077; ENSG00000049541. ENST00000352131; ENSP00000275627; ENSG00000049541. ENST00000573234; ENSP00000460590; ENSG00000261911. ENST00000576908; ENSP00000458995; ENSG00000261911.
GeneID	5982.
KEGG	hsa:5982.
UCSC	uc003uaj.3. human.
Organism-specific databases
CTD	5982.
GeneCards	GC07M073645.
HGNC	HGNC:9970. RFC2.
HPA	HPA029493.
MIM	194050. phenotype. 600404. gene.
neXtProt	NX_P35250.
Orphanet	904. Williams syndrome.
PharmGKB	PA34339.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0470.
HOGENOM	HOG000224155.
HOVERGEN	HBG002053.
InParanoid	P35250.
KO	K10755.
OMA	IQCLARI.
PhylomeDB	P35250.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_216. DNA Repair. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	P35250.
Bgee	P35250.
CleanEx	HS_RFC2.
Genevestigator	P35250.
GermOnline	ENSG00000049541. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR003959. ATPase_AAA_core. IPR008921. DNA_pol3_clamp-load_cplx_C. IPR027417. P-loop_NTPase. IPR013748. Rep_factorC_C_dom. [Graphical view]
Pfam	PF00004. AAA. 1 hit. PF08542. Rep_fac_C. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. [Graphical view]
SUPFAM	SSF48019. Pol_clamp_load_C. 1 hit. SSF52540. SSF52540. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	RFC2. human.
GenomeRNAi	5982.
NextBio	23285.
SOURCE	Search...

Entry information

Entry name

RFC2_HUMAN

Accession

Primary (citable) accession number: P35250
Secondary accession number(s): B5BU07 , D3DXG3, P32846, Q9BU93

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	November 1, 1997
Last modified:	May 29, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.