RFC1

Protein identityUniProt · HPA

UniProt accession

P35251

Gene

RFC1

Ensembl

ENSG00000035928

Chromosome

4

Canonical length

1148 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

Canonical amino-acid sequenceUniProt

1148 residues, UniProt reviewed canonical sequence.

>P35251|RFC1
     1  MDIRKFFGVI PSGKKLVSET VKKNEKTKSD EETLKAKKGI KEIKVNSSRK EDDFKQKQPS
    61  KKKRIIYDSD SESEETLQVK NAKKPPEKLP VSSKPGKISR QDPVTYISET DEEDDFMCKK
   121  AASKSKENGR STNSHLGTSN MKKNEENTKT KNKPLSPIKL TPTSVLDYFG TGSVQRSNKK
   181  MVASKRKELS QNTDESGLND EAIAKQLQLD EDAELERQLH EDEEFARTLA MLDEEPKTKK
   241  ARKDTEAGET FSSVQANLSK AEKHKYPHKV KTAQVSDERK SYSPRKQSKY ESSKESQQHS
   301  KSSADKIGEV SSPKASSKLA IMKRKEESSY KEIEPVASKR KENAIKLKGE TKTPKKTKSS
   361  PAKKESVSPE DSEKKRTNYQ AYRSYLNREG PKALGSKEIP KGAENCLEGL IFVITGVLES
   421  IERDEAKSLI ERYGGKVTGN VSKKTNYLVM GRDSGQSKSD KAAALGTKII DEDGLLNLIR
   481  TMPGKKSKYE IAVETEMKKE SKLERTPQKN VQGKRKISPS KKESESKKSR PTSKRDSLAK
   541  TIKKETDVFW KSLDFKEQVA EETSGDSKAR NLADDSSENK VENLLWVDKY KPTSLKTIIG
   601  QQGDQSCANK LLRWLRNWQK SSSEDKKHAA KFGKFSGKDD GSSFKAALLS GPPGVGKTTT
   661  ASLVCQELGY SYVELNASDT RSKSSLKAIV AESLNNTSIK GFYSNGAASS VSTKHALIMD
   721  EVDGMAGNED RGGIQELIGL IKHTKIPIIC MCNDRNHPKI RSLVHYCFDL RFQRPRVEQI
   781  KGAMMSIAFK EGLKIPPPAM NEIILGANQD IRQVLHNLSM WCARSKALTY DQAKADSHRA
   841  KKDIKMGPFD VARKVFAAGE ETAHMSLVDK SDLFFHDYSI APLFVQENYI HVKPVAAGGD
   901  MKKHLMLLSR AADSICDGDL VDSQIRSKQN WSLLPAQAIY ASVLPGELMR GYMTQFPTFP
   961  SWLGKHSSTG KHDRIVQDLA LHMSLRTYSS KRTVNMDYLS LLRDALVQPL TSQGVDGVQD
  1021  VVALMDTYYL MKEDFENIME ISSWGGKPSP FSKLDPKVKA AFTRAYNKEA HLTPYSLQAI
  1081  KASRHSTSPS LDSEYNEELN EDDSQSDEKD QDAIETDAMI KKKTKSSKPS KPEKDKEPRK
  1141  GKGKSSKK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RFC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.49

Highest tissue expression

31 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RFC1.

Disease | AllUniProt

Conditions RFC1 is implicated in, by any mechanism.

• Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) MIM:614575

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 216 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome
• Parkinson disease, late-onset

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.31

gnomAD pLI

0.97

gnomAD missense Z

1.38

DepMap mean gene effect

-0.53

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA repair
• DNA-templated DNA replication
• negative regulation of transcription by RNA polymerase II
• positive regulation of DNA-templated transcription
• telomere maintenance via telomerase

Molecular functions

• ATP binding
• ATP hydrolysis activity
• DNA binding
• DNA clamp loader activity
• DNA clamp unloader activity
• DNA-binding transcription factor binding
• double-stranded DNA binding
• enzyme activator activity
• protein domain specific binding
• sequence-specific DNA binding

Cellular components

• DNA replication factor C complex
• Elg1 RFC-like complex
• extracellular exosome
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• BRCT domain
• AAA+ ATPase domain
• ATPase, AAA-type, core
• DNA polymerase III, clamp loader complex, gamma/delta/delta subunit, C-terminal
• P-loop containing nucleoside triphosphate hydrolase
• BRCT domain superfamily
• Replication factor C, lid domain
• ATPase family associated with various cellular activities (AAA)
• BRCA1 C Terminus (BRCT) domain
• Replication factor C subunit 1
• DNA replication factor RFC1, C-terminal
• Replication factor RFC1 C terminal domain
• RFC1-like, AAA+ ATPase lid domain

KeywordsUniProt

• Activator
• ATP-binding
• DNA replication
• DNA-binding
• Isopeptide bond
• Neuropathy
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of RFC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PCNA
• POLD1
• RFC2
• RFC3
• RFC4
• RFC5