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RFC4 replication factor C subunit 4 [ Homo sapiens (human) ]

Gene ID: 5984, updated on 3-Nov-2024

Summary

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Official Symbol
RFC4provided by HGNC
Official Full Name
replication factor C subunit 4provided by HGNC
Primary source
HGNC:HGNC:9972
See related
Ensembl:ENSG00000163918 MIM:102577; AllianceGenome:HGNC:9972
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A1; RFC37
Summary
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]
Expression
Ubiquitous expression in adrenal (RPKM 108.6), ovary (RPKM 88.0) and 25 other tissues See more
Orthologs
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Genomic context

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See RFC4 in Genome Data Viewer
Location:
3q27.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (186789900..186806482, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (189611930..189628517, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (186507689..186524271, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene eukaryotic translation initiation factor 4A2 Neighboring gene small nucleolar RNA, H/ACA box 63 Neighboring gene small nucleolar RNA, H/ACA box 4 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:186523827-186524438 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:186524439-186525050 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:186529516-186529618 Neighboring gene long intergenic non-protein coding RNA 2043 Neighboring gene MCF2L2 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Studies of the cloned 37-kDa subunit of activator 1 (replication factor C) of HeLa cells. Chen M, et al. Proc Natl Acad Sci U S A, 1992 Jun 15. PMID 1351677, Free PMC Article
  2. Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker. Zhang J, et al. BMC Med, 2022 Nov 9. PMID 36352434, Free PMC Article
  3. Characterization of telomere-binding activity of replication factor C large subunit p140. Uchiumi F, et al. Biochem Biophys Res Commun, 1999 May 10. PMID 10329413
  4. Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer. Xiang J, et al. J Transl Med, 2014 Nov 19. PMID 25407051, Free PMC Article
  5. RFC4 promotes the progression and growth of Oral Tongue squamous cell carcinoma in vivo and vitro. Zhang J, et al. J Clin Lab Anal, 2021 May. PMID 33783864, Free PMC Article

See all (204) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo.
    Title: Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo.
  2. Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker.
    Title: Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker.
  3. The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis.
    Title: The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis.
  4. RFC4 promotes the progression and growth of Oral Tongue squamous cell carcinoma in vivo and vitro.
    Title: RFC4 promotes the progression and growth of Oral Tongue squamous cell carcinoma in vivo and vitro.
  5. An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.
    Title: An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.
  6. High RFC4 levels are associated with radioresistance.
    Title: Genome-wide RNAi Screening Identifies RFC4 as a Factor That Mediates Radioresistance in Colorectal Cancer by Facilitating Nonhomologous End Joining Repair.
  7. Expression level of RFC4 was up regulated in cervical squamous cell carcinoma.
    Title: Systematic identification of key genes and pathways in the development of invasive cervical cancer.
  8. RFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4
    Title: Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Polymorphisms in the base excision repair pathway and graft-versus-host disease.
  10. Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator)
    Title: Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Expression of HIV-1 Tat downregulates the abundance of replication factor C, subunit 4 (RFC4, 37kDa) in the nucleoli of Jurkat T-cells PubMed
tat HIV-1 Tat interacts with the RNA polymerase II holoenzyme, which includes RFC, during Tat-mediated transactivation of the HIV-1 LTR PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC27291

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
contributes_to DNA clamp loader activity IBA
Inferred from Biological aspect of Ancestor
more info
  
contributes_to DNA clamp loader activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to single-stranded DNA helicase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA duplex unwinding IEA
Inferred from Electronic Annotation
more info
  
involved_in DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in DNA strand elongation involved in DNA replication TAS
Traceable Author Statement
more info
 PubMed 
involved_in DNA-templated DNA replication IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in DNA-templated DNA replication IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA-directed DNA polymerase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of Ctf18 RFC-like complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of DNA replication factor C complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of DNA replication factor C complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of DNA replication factor C complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of Elg1 RFC-like complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
replication factor C subunit 4
Names
A1 37 kDa subunit
RF-C 37 kDa subunit
RFC 37 kDa subunit
activator 1 37 kDa subunit
activator 1 subunit 4
replication factor C (activator 1) 4, 37kDa
replication factor C 37 kDa subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_002916.5 → NP_002907.1  replication factor C subunit 4

    See identical proteins and their annotated locations for NP_002907.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 encode the same isoform.
    Source sequence(s)
    AA521171, AC112907, BC017452, DA359927
    Consensus CDS
    CCDS3283.1
    UniProtKB/Swiss-Prot
    B4DM41, D3DNV2, P35249, Q6FHX7
    UniProtKB/TrEMBL
    C9JZI1
    Related
    ENSP00000296273.2, ENST00000296273.7
    Conserved Domains (1) summary
    cl25702
    Location:39 → 353
    Rad17; Rad17 cell cycle checkpoint protein

  2. NM_181573.3 → NP_853551.1  replication factor C subunit 4

    See identical proteins and their annotated locations for NP_853551.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform.
    Source sequence(s)
    AA521171, AC112907, CX788139
    Consensus CDS
    CCDS3283.1
    UniProtKB/Swiss-Prot
    B4DM41, D3DNV2, P35249, Q6FHX7
    UniProtKB/TrEMBL
    C9JZI1
    Related
    ENSP00000376272.2, ENST00000392481.6
    Conserved Domains (1) summary
    cl25702
    Location:39 → 353
    Rad17; Rad17 cell cycle checkpoint protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    186789900..186806482 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    189611930..189628517 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P35249.2 GenPept UniProtKB/Swiss-Prot:P35249

Gene LinkOut

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