Details for: RAD51AP1

Gene ID: 10635

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: RAD51AP1

Ensembl ID: ENSG00000111247

Description: RAD51 associated protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 5.58
    rCSI 5.04%
    PRS 93.04
  • radial glial cell CL0000681
    CSI 3.84
    rCSI 5.33%
    PRS 92.59
  • large pre-B-II cell CL0000957
    CSI 3.67
    rCSI 10.48%
    PRS 93.2
  • neural crest cell CL0011012
    CSI 3.48
    rCSI 2.75%
    PRS 89.03
  • Hofbauer cell CL3000001
    CSI 3.4
    rCSI 6.43%
    PRS 97.01
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.32
    rCSI 4.26%
    PRS 90.87
  • pro-B cell CL0000826
    CSI 3.02
    rCSI 2.5%
    PRS 94.77
  • erythrocyte CL0000232
    CSI 2.54
    rCSI 5.77%
    PRS 91.92
  • transit amplifying cell of small intestine CL0009012
    CSI 2.52
    rCSI 11.06%
    PRS 95.73
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.48
    rCSI 2.15%
    PRS 95.23
  • mesodermal cell CL0000222
    CSI 2.42
    rCSI 2.91%
    PRS 93.23
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.25
    rCSI 2.17%
    PRS 92.85
  • common myeloid progenitor CL0000049
    CSI 2.23
    rCSI 1.81%
    PRS 94.77
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.19
    rCSI 2.53%
    PRS 87.77
  • enteric smooth muscle cell CL0002504
    CSI 2.03
    rCSI 2.89%
    PRS 93.88
  • fraction A pre-pro B cell CL0002045
    CSI 2.01
    rCSI 2.3%
    PRS 96.13
  • glioblast CL0000030
    CSI 1.96
    rCSI 3.13%
    PRS 87.96
  • promonocyte CL0000559
    CSI 1.79
    rCSI 3.06%
    PRS 95.09
  • placental villous trophoblast CL2000060
    CSI 1.67
    rCSI 2.58%
    PRS 92.39
  • mesenchymal cell CL0008019
    CSI 1.65
    rCSI 4.19%
    PRS 90.38
  • common dendritic progenitor CL0001029
    CSI 1.64
    rCSI 2.06%
    PRS 96.92
  • erythroblast CL0000765
    CSI 1.18
    rCSI 3.12%
    PRS 94
  • forebrain radial glial cell CL0013000
    CSI 0.99
    rCSI 3.19%
    PRS 93.54
  • erythroid progenitor cell CL0000038
    CSI 0.63
    rCSI 3.62%
    PRS 94.87
  • pluripotent stem cell CL0002248
    CSI 0.49
    rCSI 14.71%
    PRS 96.55

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 **RAD51 associated protein 1** ([RAD51AP1](/details-gene/10635)) is a protein critically involved in the maintenance of genomic integrity. Its primary function is to act as an accessory factor in the DNA damage response, specifically by promoting the repair of double-strand breaks through the homologous recombination (HR) pathway ([Link](https://doi.org/10.1016/j.molcel.2007.08.027)). By interacting with and enhancing the activity of the RAD51 recombinase, [RAD51AP1](/details-gene/10635) facilitates key steps in DNA strand exchange, a process essential for error-free repair ([Link](https://doi.org/10.1016/j.molcel.2007.08.025)). **Overall**, expression data reveals that [RAD51AP1](/details-gene/10635) shows the highest significance in highly proliferative cell populations, including hematopoietic progenitors such as the [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), developing neural cells like the [radial glial cell](/details-cell/CL0000681), and various B-cell precursors. This expression pattern underscores its fundamental role in safeguarding the genome during rapid cell division and differentiation. ## Cellular Roles and Expression Landscape The expression profile of [RAD51AP1](/details-gene/10635) strongly suggests a specialized role in contexts requiring high-fidelity DNA replication and repair. Its significance is most pronounced in progenitor and transit-amplifying cells across multiple lineages, highlighting a common requirement for robust genome maintenance during development and tissue renewal. Functionally, the top cell types can be grouped into several key categories: * **Hematopoietic Progenitors:** [RAD51AP1](/details-gene/10635) is a highly significant gene in several hematopoietic precursors, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 5.58), [large pre-B-II cell](/details-cell/CL0000957) (CSI: 3.67), [pro-B cell](/details-cell/CL0000826) (CSI: 3.02), [granulocyte monocyte progenitor cell](/details-cell/CL0000557) (CSI: 2.48), and the [common myeloid progenitor](/details-cell/CL0000049) (CSI: 2.23). This indicates a crucial function in maintaining genomic stability throughout the complex and rapid cell divisions that characterize hematopoiesis. * **Neural Development:** The gene also shows high significance in developing cells of the nervous system, such as the [radial glial cell](/details-cell/CL0000681) (CSI: 3.84), [neural crest cell](/details-cell/CL0011012) (CSI: 3.48), and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 3.32). This is consistent with the need for stringent DNA repair mechanisms to ensure proper neurogenesis and prevent developmental abnormalities. * **Highly Proliferative Tissues:** Elevated significance in cells like the [transit amplifying cell of small intestine](/details-cell/CL0009012) (CSI: 2.52) and [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 2.25) further supports its role in tissues characterized by high rates of cell turnover. **Overall**, the cellular landscape of [RAD51AP1](/details-gene/10635) expression is tightly linked to proliferation. Its activity appears essential for progenitor cells to accurately replicate their DNA and prevent the accumulation of mutations that could lead to cell death, developmental failure, or malignant transformation. ## Pathways and Molecular Function The functional annotations for [RAD51AP1](/details-gene/10635) confirm its central role as a facilitator of homologous recombination. **Molecularly**, [RAD51AP1](/details-gene/10635) is a structure-specific DNA binding protein ([Link](https://doi.org/10.1016/j.molcel.2007.08.025)). Its functions include [Dna binding](/details-ontology/GO:0003677), with a preference for intermediates in the recombination process such as [single-stranded dna binding](/details-ontology/GO:0003697) and [D-loop dna binding](/details-ontology/GO:0062037). Through its [Protein binding](/details-ontology/GO:0005515) capacity, it interacts directly with the RAD51 recombinase, the core enzyme of homologous recombination. **Biologically**, these molecular activities translate into a key role in the [Dna damage response](/details-ontology/GO:0006974), particularly in response to severe lesions like double-strand breaks and interstrand cross-links. It is a known component of the [Double-strand break repair via homologous recombination](/details-ontology/GO:0000724) pathway, where it functions as a [Positive regulation of double-strand break repair via homologous recombination](/details-ontology/GO:1905168). This enhancing role is critical for efficient joint molecule formation and resolution of recombination intermediates ([Link](https://doi.org/10.1016/j.molcel.2007.08.027), [Link](https://doi.org/10.1074/jbc.c112.352161)). Its involvement also extends to the specialized recombination events of the [Meiotic cell cycle](/details-ontology/GO:0051321), where it interacts with the meiotic-specific recombinase DMC1 ([Link](https://doi.org/10.1074/jbc.m111.290015)). Reactome pathway analysis places [RAD51AP1](/details-gene/10635) squarely within the [Hdr through homologous recombination (hrr)](https://reactome.org/content/detail/R-HSA-5685942) and [Homologous dna pairing and strand exchange](https://reactome.org/content/detail/R-HSA-5693579) pathways. Notably, it is also implicated in pathways describing [Diseases of dna double-strand break repair](https://reactome.org/content/detail/R-HSA-9675136), including scenarios where HR is defective due to mutations in key tumor suppressors like BRCA1, BRCA2, and PALB2. This highlights its clinical relevance in the context of cancers arising from genomic instability. ## Research Directions The established role of [RAD51AP1](/details-gene/10635) in promoting DNA repair, combined with its expression pattern in highly proliferative cells, positions it as a significant factor in both normal development and cancer biology. **Testable Hypotheses:** 1. *Overexpression of [RAD51AP1](/details-gene/10635) in cancers with high proliferative rates, such as acute myeloid leukemia or glioblastoma, may confer resistance to DNA-damaging therapies (e.g., platinum agents, ionizing radiation) and PARP inhibitors by hyper-activating the homologous recombination repair pathway.* 2. *Loss-of-function mutations or haploinsufficiency of [RAD51AP1](/details-gene/10635) could predispose individuals to developmental disorders characterized by progenitor cell depletion, such as bone marrow failure or microcephaly, due to an inability to cope with endogenous DNA damage during rapid developmental expansion.* **Proposed Experiment:** To test the first hypothesis regarding chemoresistance, a definitive experiment would involve modulating [RAD51AP1](/details-gene/10635) levels in a relevant cancer model. One could use CRISPR-Cas9 to knock out [RAD51AP1](/details-gene/10635) in a leukemia cell line (e.g., MOLM-13) that shows high baseline expression. These knockout cells, along with isogenic wild-type controls, would then be treated with a PARP inhibitor (e.g., olaparib) or a DNA crosslinking agent (e.g., cisplatin) across a range of concentrations. Cell viability would be measured via MTS or flow cytometry-based apoptosis assays. A significant increase in sensitivity to these agents in the knockout cells compared to controls would provide strong evidence that [RAD51AP1](/details-gene/10635) is a mediator of therapeutic resistance. **Therapeutic Potential:** Given its function as a positive regulator of DNA repair, [RAD51AP1](/details-gene/10635) is a compelling target for therapeutic **inhibition**. Developing small molecule inhibitors that disrupt its interaction with RAD51 could effectively cripple the homologous recombination pathway. Such an agent could have two primary applications: first, as a sensitizer to radio- or chemotherapy, preventing cancer cells from repairing the damage induced by these treatments; and second, as a monotherapy in tumors that harbor defects in other DNA repair pathways (e.g., BRCA1/2 mutations), creating a synthetic lethal vulnerability analogous to the mechanism of PARP inhibitors. Its specificity for proliferative cells might offer a therapeutic window, potentially reducing toxicity to quiescent, healthy tissues.

Genular Protein ID: 2134074733

Symbol: R51A1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96B01 A8K7D3 O43403 Q7Z779

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 21 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 8 RefSeq 2 SIGNOR 1 STRING 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9396801

Title: A novel nucleic acid-binding protein that interacts with human rad51 recombinase.

PubMed ID: 9396801

DOI: 10.1093/nar/25.24.4946

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 16990250

Title: RAD51AP2, a novel vertebrate- and meiotic-specific protein, shares a conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51.

PubMed ID: 16990250

DOI: 10.1093/nar/gkl665

PubMed ID: 17996710

Title: RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination.

PubMed ID: 17996710

DOI: 10.1016/j.molcel.2007.08.025

PubMed ID: 17996711

Title: Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement.

PubMed ID: 17996711

DOI: 10.1016/j.molcel.2007.08.027

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 20871616

Title: Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.

PubMed ID: 20871616

DOI: 10.1038/nsmb.1916

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21903585

Title: RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic recombinase DMC1 through a conserved motif.

PubMed ID: 21903585

DOI: 10.1074/jbc.m111.290015

PubMed ID: 21307306

Title: Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 associated protein 1 (RAD51AP1).

PubMed ID: 21307306

DOI: 10.1073/pnas.1016454108

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 22375013

Title: Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in homologous DNA repair.

PubMed ID: 22375013

DOI: 10.1074/jbc.c112.352161

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23754376

Title: FIGNL1-containing protein complex is required for efficient homologous recombination repair.

PubMed ID: 23754376

DOI: 10.1073/pnas.1220662110

PubMed ID: 25288561

Title: RAD51AP1-deficiency in vertebrate cells impairs DNA replication.

PubMed ID: 25288561

DOI: 10.1016/j.dnarep.2014.09.007

PubMed ID: 26323318

Title: NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability.

PubMed ID: 26323318

DOI: 10.1093/nar/gkv859

PubMed ID: 27463890

Title: The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

PubMed ID: 27463890

DOI: 10.1080/15384101.2016.1209613

PubMed ID: 27239033

Title: Promotion of RAD51-mediated homologous DNA pairing by the RAD51AP1-UAF1 complex.

PubMed ID: 27239033

DOI: 10.1016/j.celrep.2016.05.007

PubMed ID: 31253762

Title: DNA requirement in FANCD2 deubiquitination by USP1-UAF1-RAD51AP1 in the Fanconi anemia DNA damage response.

PubMed ID: 31253762

DOI: 10.1038/s41467-019-10408-5

PubMed ID: 31400850

Title: RAD51AP1 is an essential mediator of alternative lengthening of telomeres.

PubMed ID: 31400850

DOI: 10.1016/j.molcel.2019.06.043

PubMed ID: 31585101

Title: RAD51AP1 is an essential mediator of alternative lengthening of telomeres.

PubMed ID: 31585101

DOI: 10.1016/j.molcel.2019.08.009

PubMed ID: 32350107

Title: The DNA-binding activity of USP1-associated factor 1 is required for efficient RAD51-mediated homologous DNA pairing and homology-directed DNA repair.

PubMed ID: 32350107

DOI: 10.1074/jbc.ra120.013714

Sequence Information:

  • Length: 352
  • Mass: 38457
  • Checksum: E582EE4BC459DD92
  • Sequence:
    • MVRPVRHKKP VNYSQFDHSD SDDDFVSATV PLNKKSRTAP KELKQDKPKP NLNNLRKEEI 
PVQEKTPKKR LPEGTFSIPA SAVPCTKMAL DDKLYQRDLE VALALSVKEL PTVTTNVQNS 
QDKSIEKHGS SKIETMNKSP HISNCSVASD YLDLDKITVE DDVGGVQGKR KAASKAAAQQ 
RKILLEGSDG DSANDTEPDF APGEDSEDDS DFCESEDNDE DFSMRKSKVK EIKKKEVKVK 
SPVEKKEKKS KSKCNALVTS VDSAPAAVKS ESQSLPKKVS LSSDTTRKPL EIRSPSAESK 
KPKWVPPAAS GGSRSSSSPL VVVSVKSPNQ SLRLGLSRLA RVKPLHPNAT ST