RFC4
Replication factor C subunit 4
Also known as: A1, RFC37, RFC4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P35249
- Gene
- RFC4
- Ensembl
- ENSG00000163918
- Chromosome
- 3
- Canonical length
- 363 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 37 kD subunit. This subunit forms a core complex with the 36 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
363 residues, UniProt reviewed canonical sequence.
>P35249|RFC4
1 MQAFLKGTSI STKPPLTKDR GVAASAGSSG ENKKAKPVPW VEKYRPKCVD EVAFQEEVVA
61 VLKKSLEGAD LPNLLFYGPP GTGKTSTILA AARELFGPEL FRLRVLELNA SDERGIQVVR
121 EKVKNFAQLT VSGSRSDGKP CPPFKIVILD EADSMTSAAQ AALRRTMEKE SKTTRFCLIC
181 NYVSRIIEPL TSRCSKFRFK PLSDKIQQQR LLDIAKKENV KISDEGIAYL VKVSEGDLRK
241 AITFLQSATR LTGGKEITEK VITDIAGVIP AEKIDGVFAA CQSGSFDKLE AVVKDLIDEG
301 HAATQLVNQL HDVVVENNLS DKQKSIITEK LAEVDKCLAD GADEHLQLIS LCATVMQQLS
361 QNCLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RFC4 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)
- 0.33
- Highest tissue expression
- 39 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 39 nTPM
- thymus: 33 nTPM
- tonsil: 32 nTPM
- lymph node: 29 nTPM
- testis: 21 nTPM
- rectum: 19 nTPM
Single-cell type
- early primary spermatocytes: 99 nCPM
- erythrocyte progenitors: 94 nCPM
- extravillous trophoblasts: 65 nCPM
- oocytes: 65 nCPM
- late primary spermatocytes: 62 nCPM
- migrating cytotrophoblasts: 57 nCPM
Immune cell
- T-reg: 22 nTPM
- naive B-cell: 15 nTPM
- non-classical monocyte: 15 nTPM
- memory B-cell: 13 nTPM
- memory CD8 T-cell: 12 nTPM
- gdT-cell: 12 nTPM
Brain region
- cerebellum: 8.3 nTPM
- cerebral cortex: 7.2 nTPM
- white matter: 7.1 nTPM
- thalamus: 6.8 nTPM
- basal ganglia: 5.8 nTPM
- hypothalamus: 5.6 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about RFC4.
Disease | AllUniProt
Conditions RFC4 is implicated in, by any mechanism.
- Morimoto-Ryu-Malicdan neuromuscular syndrome (MRMNS) MIM:621010
Disease | GeneticClinVar
11 pathogenic / likely-pathogenic of 90 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Morimoto-Ryu-Malicdan neuromuscular syndrome
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)
- 0.9
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.29
- DepMap mean gene effect
- -1.2
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 15% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- DNA repair
- DNA strand elongation involved in DNA replication
- DNA-templated DNA replication
- positive regulation of DNA-directed DNA polymerase activity
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- AAA+ ATPase domain
- ATPase, AAA-type, core
- DNA polymerase III, clamp loader complex, gamma/delta/delta subunit, C-terminal
- Replication factor C, C-terminal
- P-loop containing nucleoside triphosphate hydrolase
- Replication factor C, lid domain
- DNA Replication and Repair Clamp Loader Complex
- ATPase family associated with various cellular activities (AAA)
- Replication factor C C-terminal domain
- RCF1/5-like, AAA+ ATPase lid domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RFC4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RFC4 as an antibody target. Whether an autoantibody or antibody against RFC4 could matter depends on whether native RFC4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RFC4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label RFC4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...