Details for: RAD54L

Gene ID: 8438

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RAD54L

Ensembl ID: ENSG00000085999

Description: RAD54 like

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • large pre-B-II cell CL0000957
    CSI 1.57
    rCSI 4.49%
    PRS 99.08

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RAD54L](/details-gene/8438) is a protein-coding gene located on chromosome 1p34.1 that functions as a core component of the homologous recombination (HR) pathway for DNA repair. As a member of the SWI/SNF family of DNA-dependent ATPases, it possesses DNA helicase and translocase activity, playing a critical role in repairing DNA double-strand breaks, maintaining genomic stability, and participating in meiotic recombination [Link](https://doi.org/10.1074/jbc.273.43.28292). Its function is highly conserved across species [Link](https://doi.org/10.1016/s0960-9822(02)00606-1). **Overall**, expression data indicates that [RAD54L](/details-gene/8438) is a significant gene in the [large pre-B-II cell](/details-cell/CL0000957), suggesting a vital role in the development and genomic maintenance of these rapidly proliferating lymphocytes. ## Cellular Roles and Expression Landscape The expression profile of [RAD54L](/details-gene/8438) points towards a specialized function within the hematopoietic system, particularly during lymphocyte development. * **Overall Context:** The gene shows its highest significance in the [large pre-B-II cell](/details-cell/CL0000957) (CSI: 1.57). This specific cell type is characterized by active proliferation and the initiation of immunoglobulin light chain gene rearrangement, a process that involves the deliberate creation and precise repair of DNA double-strand breaks through V(D)J recombination. The high significance of [RAD54L](/details-gene/8438) in this context is consistent with its fundamental role in homologous recombination, which is essential for ensuring the fidelity of this process and preventing chromosomal translocations that can lead to B-cell malignancies. The localization of [RAD54L](/details-gene/8438) to a region on chromosome 1p frequently exhibiting loss of heterozygosity in breast and other cancers suggests it may function as a tumor suppressor [Link](https://pubmed.ncbi.nlm.nih.gov/9192813). ## Pathways and Molecular Function [RAD54L](/details-gene/8438) is a multifunctional enzyme primarily located in the [nucleus](/details-go/GO:0005634) and [nucleoplasm](/details-go/GO:0005654), where it acts within larger [protein-containing complexes](/details-go/GO:0032991) to maintain genome integrity. * **Molecular Activity:** Its core molecular functions are centered on DNA manipulation, driven by its [ATP binding](/details-go/GO:0005524) and [ATP hydrolysis activity](/details-go/GO:0016887). This energy is used to power its [helicase activity](/details-go/GO:0004386) and [DNA translocase activity](/details-go/GO:0015616), allowing it to move along DNA and remodel chromatin [Link](https://doi.org/10.1073/pnas.151056798). It also exhibits [ATP-dependent DNA/DNA annealing activity](/details-go/GO:0036310) and is involved in [ATP-dependent chromatin remodeler activity](/details-go/GO:0140658). * **Biological Processes:** These molecular activities enable [RAD54L](/details-gene/8438) to participate in crucial biological processes, most notably [DNA repair](/details-go/GO:0006281) and [DNA recombination](/details-go/GO:0006310). It is a key player in the repair of DNA double-strand breaks, specifically through [synthesis-dependent strand annealing](/details-go/GO:0045003), and is essential for cellular [response to ionizing radiation](/details-go/GO:0010212). [RAD54L](/details-gene/8438) works in concert with RAD51 to facilitate homologous DNA pairing [Link](https://doi.org/10.1074/jbc.m208004200). Its functions extend to broader processes such as [chromosome organization](/details-go/GO:0051276), the [meiotic cell cycle](/details-go/GO:0051321), and has been implicated in the [determination of adult lifespan](/details-go/GO:0008340). ## Research Directions The established role of [RAD54L](/details-gene/8438) in DNA repair and its specific expression context provide a foundation for several research avenues, particularly concerning its role in cancer biology and as a potential therapeutic target. **Proposed Hypotheses:** 1. Given its high significance in [large pre-B-II cells](/details-cell/CL0000957) and its role in HR, [RAD54L](/details-gene/8438) haploinsufficiency or mutation may be a critical event in the etiology of B-cell acute lymphoblastic leukemia (B-ALL) by impairing the fidelity of V(D)J recombination, leading to oncogenic chromosomal translocations. 2. The regulatory network controlling [RAD54L](/details-gene/8438) activity, which involves proteins like NEK1 [Link](https://doi.org/10.1016/j.molcel.2016.04.032) and BRD9 [Link](https://doi.org/10.1038/s41467-020-16443-x), is likely dysregulated in certain cancers, leading to a state of "recombination addiction" where tumor cells become uniquely dependent on [RAD54L](/details-gene/8438) for survival amidst high levels of replication stress. **Key Experimental Approach:** * To test the first hypothesis, a robust experimental plan would involve generating a conditional knockout of [RAD54L](/details-gene/8438) in a mouse model of B-cell development (e.g., using a CD19-Cre driver). Pro-B/pre-B cells from these mice could be isolated and analyzed for defects in V(D)J recombination using specialized sequencing assays. Furthermore, these mice could be monitored for an increased incidence of spontaneous B-cell lymphomas, and the resulting tumors could be sequenced to identify characteristic genomic alterations. **Therapeutic Potential:** * [RAD54L](/details-gene/8438) represents a promising therapeutic target, primarily for **inhibition**. Its ATPase and helicase activities are druggable domains. Inhibitors of [RAD54L](/details-gene/8438) could be particularly effective in tumors that have deficiencies in other DNA repair pathways (e.g., those with BRCA1/2 mutations) through a synthetic lethality mechanism. Such a strategy could sensitize cancer cells to DNA-damaging agents like PARP inhibitors or chemotherapy, offering a targeted approach to exploit the genomic instability inherent in many tumors.

Genular Protein ID: 2929860302

Symbol: RAD54_HUMAN

Name: DNA repair and recombination protein RAD54-like

UniProtKB Accession Codes:

Q92698 Q5TE31 Q6IUY3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 6 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 ELM 1 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 19 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 2 Rhea 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8805304

Title: Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: evidence for functional conservation.

PubMed ID: 8805304

DOI: 10.1016/s0960-9822(02)00606-1

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9192813

Title: Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors.

PubMed ID: 9192813

PubMed ID: 9321665

Title: Interaction of human recombination proteins Rad51 and Rad54.

PubMed ID: 9321665

DOI: 10.1093/nar/25.20.4106

PubMed ID: 9774452

Title: The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase.

PubMed ID: 9774452

DOI: 10.1074/jbc.273.43.28292

PubMed ID: 10449612

Title: Analysis of the RAD54 gene on chromosome 1p as a potential tumor-suppressor gene in parathyroid adenomas.

PubMed ID: 10449612

DOI: 10.1002/(sici)1097-0215(19990924)83:1<80::aid-ijc15>3.0.co;2-e

PubMed ID: 11459989

Title: The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA.

PubMed ID: 11459989

DOI: 10.1073/pnas.151056798

PubMed ID: 12205100

Title: Homologous DNA pairing by human recombination factors Rad51 and Rad54.

PubMed ID: 12205100

DOI: 10.1074/jbc.m208004200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24798879

Title: Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1.

PubMed ID: 24798879

DOI: 10.1038/srep04863

PubMed ID: 27264870

Title: Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.

PubMed ID: 27264870

DOI: 10.1016/j.molcel.2016.04.032

PubMed ID: 32457312

Title: The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair.

PubMed ID: 32457312

DOI: 10.1038/s41467-020-16443-x

PubMed ID: 10362365

Title: Mutations in the RAD54 recombination gene in primary cancers.

PubMed ID: 10362365

DOI: 10.1038/sj.onc.1202692

Sequence Information:

  • Length: 747
  • Mass: 84352
  • Checksum: 718100974CA6687B
  • Sequence:
    • MRRSLAPSQL AKRKPEGRSC DDEDWQPGLV TPRKRKSSSE TQIQECFLSP FRKPLSQLTN 
QPPCLDSSQH EAFIRSILSK PFKVPIPNYQ GPLGSRALGL KRAGVRRALH DPLEKDALVL 
YEPPPLSAHD QLKLDKEKLP VHVVVDPILS KVLRPHQREG VKFLWECVTS RRIPGSHGCI 
MADEMGLGKT LQCITLMWTL LRQSPECKPE IDKAVVVSPS SLVKNWYNEV GKWLGGRIQP 
LAIDGGSKDE IDQKLEGFMN QRGARVSSPI LIISYETFRL HVGVLQKGSV GLVICDEGHR 
LKNSENQTYQ ALDSLNTSRR VLISGTPIQN DLLEYFSLVH FVNSGILGTA HEFKKHFELP 
ILKGRDAAAS EADRQLGEER LRELTSIVNR CLIRRTSDIL SKYLPVKIEQ VVCCRLTPLQ 
TELYKRFLRQ AKPAEELLEG KMSVSSLSSI TSLKKLCNHP ALIYDKCVEE EDGFVGALDL 
FPPGYSSKAL EPQLSGKMLV LDYILAVTRS RSSDKVVLVS NYTQTLDLFE KLCRARRYLY 
VRLDGTMSIK KRAKVVERFN SPSSPDFVFM LSSKAGGCGL NLIGANRLVM FDPDWNPAND 
EQAMARVWRD GQKKTCYIYR LLSAGTIEEK IFQRQSHKKA LSSCVVDEEQ DVERHFSLGE 
LKELFILDEA SLSDTHDRLH CRRCVNSRQI RPPPDGSDCT SDLAGWNHCT DKWGLRDEVL 
QAAWDAASTA ITFVFHQRSH EEQRGLR

Genular Protein ID: 2443390112

Symbol: A8K996_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K996

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 8 Gene3D 3 InterPro 7 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 1 SMART 2 SUPFAM 1

Sequence Information:

  • Length: 747
  • Mass: 84318
  • Checksum: 2B810DF741CB0876
  • Sequence:
    • MRRSLAPSQL AKRKPEGRSC DDEDWQPGLV TPRKRKSSSE TQIQECFLSP FRKPLSQLTN 
QPPCLDSSQH EAFIRSILSK PFKVPIPNYQ GPLGSRALGL KRAGVRRALH DPLEKDALVL 
YEPPPLSAHD QLKLDKEKLP VHVVVDPILS KVLRPHQREG VKFLWECVTS RRIPGSHGCI 
MADEMGLGKT LQCITLMWTL LRQSPECKPE IDKAVVVSPS SLVKNWYNEV GKWLGGRIQP 
LAIDGGSKDE IDQKLEGFMN QRGARVSSPI LIISYETFRL HVGVLQKGSV GLVICDEGHR 
LKNSENQTYQ ALDSLNTSRR VLISGTPIQN DLLEYFSLVH FVNSGILGTA HEFKKHFELP 
ILKGRDAAAS EADRQLGEER LRELTSIVNR CLIRRTSDIL SKYLPVKIEQ VVCCRLTPLQ 
TELYKRFLRQ AKPAEELLEG KMSVSSLSSI TSLKKLCNHP ALIYDKCVEE EDGFVGALDL 
FPPGYSSKAL EPQLSGKMLV LDYILAVTRS RSSDKVVLVS NYTQTLDLFE KLCRARRYLY 
VRLDGTMSIK KRAKVVERFN SPSSPDFVFM LSSKAGGCGL NLIGANRLVM FDPDWNPAND 
EQAMARVWRD GQKKTCYIYR LLSAGTIEEK IFQRQSHKKA LSSCVVDEEQ DVERHFSLGE 
LKELLILDEA SLSDTHDRLH CRRCVNSRQI RPPPDGSDCT SDLAGWNHCT DKWGLRDEVL 
QAAWDAASTA ITFVFHQRSH EEQRGLR