Details for: ABRAXAS1

Gene ID: 84142

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: ABRAXAS1

Ensembl ID: ENSG00000163322

Description: abraxas 1, BRCA1 A complex subunit

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • choroid plexus epithelial cell CL0000706
    CSI 12.87
    rCSI 21.08%
    PRS 80.14
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 5.49
    rCSI 3.24%
    PRS 97.8
  • mature alpha-beta T cell CL0000791
    CSI 4.61
    rCSI 16.69%
    PRS 97.67
  • hematopoietic stem cell CL0000037
    CSI 4.44
    rCSI 2.95%
    PRS 90.07
  • melanocyte CL0000148
    CSI 4.17
    rCSI 3.09%
    PRS 83.67
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.94
    rCSI 2.83%
    PRS 96.71
  • double negative thymocyte CL0002489
    CSI 3.9
    rCSI 2.71%
    PRS 96.13
  • stem cell CL0000034
    CSI 3.46
    rCSI 3.34%
    PRS 83.59
  • pro-B cell CL0000826
    CSI 3.38
    rCSI 2.8%
    PRS 90.11
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.33
    rCSI 2.57%
    PRS 91.3
  • precursor B cell CL0000817
    CSI 3.29
    rCSI 2.89%
    PRS 92.89
  • perivascular cell CL4033054
    CSI 3.13
    rCSI 4.28%
    PRS 91.54
  • early lymphoid progenitor CL0000936
    CSI 2.84
    rCSI 2.49%
    PRS 91.92
  • mesodermal cell CL0000222
    CSI 2.72
    rCSI 3.27%
    PRS 86.96
  • multi-ciliated epithelial cell CL0005012
    CSI 2.68
    rCSI 2.68%
    PRS 82.44
  • keratinocyte CL0000312
    CSI 2.66
    rCSI 2.23%
    PRS 89.26
  • group 3 innate lymphoid cell CL0001071
    CSI 2.55
    rCSI 1.92%
    PRS 91.98
  • interstitial cell of Cajal CL0002088
    CSI 2.55
    rCSI 3.25%
    PRS 92.23
  • hematopoietic precursor cell CL0008001
    CSI 2.5
    rCSI 2.58%
    PRS 94.75
  • neural crest cell CL0011012
    CSI 2.42
    rCSI 1.91%
    PRS 80.06
  • intestinal epithelial cell CL0002563
    CSI 2.39
    rCSI 2.5%
    PRS 85.81
  • ciliated epithelial cell CL0000067
    CSI 2.28
    rCSI 2.01%
    PRS 79.02
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.27
    rCSI 2.31%
    PRS 93.98
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.21
    rCSI 2%
    PRS 87.03
  • enteric smooth muscle cell CL0002504
    CSI 2.12
    rCSI 3.03%
    PRS 88.54
  • stromal cell CL0000499
    CSI 2.1
    rCSI 5.9%
    PRS 83.94
  • mature B cell CL0000785
    CSI 1.96
    rCSI 1.71%
    PRS 94.67
  • vascular associated smooth muscle cell CL0000359
    CSI 1.96
    rCSI 6.35%
    PRS 86.27
  • lung ciliated cell CL1000271
    CSI 1.83
    rCSI 2.12%
    PRS 82.11
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 1.3
    rCSI 3.14%
    PRS 95.9
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.24
    rCSI 2.82%
    PRS 81.21
  • podocyte CL0000653
    CSI 0.93
    rCSI 4.15%
    PRS 88.88
  • mesenchymal cell CL0008019
    CSI 0.83
    rCSI 2.1%
    PRS 82.82
  • stromal cell of ovary CL0002132
    CSI 0.79
    rCSI 2.17%
    PRS 91.86
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.69
    rCSI 1.98%
    PRS 87.37

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 [ABRAXAS1](/details-gene/84142) (Abraxas 1, BRCA1 A complex subunit), also known as CCDC98, is a protein-coding gene located on chromosome 4q21.23. It functions as a critical component of the BRCA1-A complex, a key sensor and effector module in the DNA damage response pathway. Multiple studies have established its role in recruiting BRCA1 to sites of DNA double-strand breaks, thereby facilitating cell cycle checkpoint control and DNA repair ([Link](https://doi.org/10.1126/science.1139476), [Link](https://doi.org/10.1038/nsmb1279)). **Overall**, the expression profile of [ABRAXAS1](/details-gene/84142) shows notable significance in highly proliferative or long-lived cell types, including [choroid plexus epithelial cell](/details-cell/CL0000706), various T-lymphocyte subsets, and hematopoietic progenitors, which is consistent with its fundamental role in maintaining genomic integrity. ## Cellular Roles and Expression Landscape The expression landscape of [ABRAXAS1](/details-gene/84142) highlights its importance in cells requiring robust DNA maintenance and repair mechanisms. **Overall**, the gene shows the highest significance in [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 12.87), suggesting a potentially critical and specialized function in this brain barrier tissue, which is composed of long-lived, mitotically-active secretory cells. Beyond this, [ABRAXAS1](/details-gene/84142) demonstrates a strong signature within the hematopoietic and immune systems. It is highly significant in multiple lymphocyte populations, including [central memory CD4-positive, alpha-beta T cell](/details-cell/CL0000904), [mature alpha-beta T cell](/details-cell/CL0000791), and [CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897). This pattern is consistent with the necessity for stringent DNA repair during V(D)J recombination and the maintenance of genomic stability in long-lived memory lymphocyte pools. Furthermore, its significance in progenitor populations like [hematopoietic stem cell](/details-cell/CL0000037), [pro-B cell](/details-cell/CL0000826), and [early lymphoid progenitor](/details-cell/CL0000936) underscores its foundational role in the development of these lineages. The gene's activity in other cell types such as [melanocyte](/details-cell/CL0000148) and undifferentiated [stem cell](/details-cell/CL0000034) further supports its widespread importance in preserving the genome of diverse cell types. ## Pathways and Molecular Function The functional annotations for [ABRAXAS1](/details-gene/84142) are highly consistent with its role as a core member of the DNA damage response machinery. It is a central component of the [BRCA1-A complex](/details-go/GO:0070531) and localizes to the [nucleus](/details-go/GO:0005634) to execute its functions. Key biological processes associated with [ABRAXAS1](/details-gene/84142) include: * **DNA Repair:** The gene is integral to [double-strand break repair](/details-go/GO:0006302) and the broader [DNA repair](/details-pathway/R-HSA-73894) process. Reactome pathways specify its involvement in both [Homology Directed Repair (HDR)](/details-pathway/R-HSA-5693538) and [Nonhomologous End-Joining (NHEJ)](/details-pathway/R-HSA-5693571), highlighting its versatility in genome maintenance. It plays a role in the [recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks](/details-pathway/R-HSA-5693565). * **Cell Cycle Checkpoint Control:** [ABRAXAS1](/details-gene/84142) is crucial for activating [G2/M checkpoints](/details-pathway/R-HSA-69481) in response to DNA damage, as indicated by its annotation in [mitotic G2 DNA damage checkpoint signaling](/details-go/GO:0007095). This ensures that cells do not enter mitosis with damaged DNA, preventing catastrophic genomic instability. * **Protein Binding and Regulation:** At the molecular level, its function is mediated by [polyubiquitin modification-dependent protein binding](/details-go/GO:0031593), which is essential for localizing the BRCA1 complex to damaged chromatin ([Link](https://doi.org/10.1073/pnas.0710061104)). It is also involved in processes related to [deubiquitination](/details-pathway/R-HSA-5688426), reflecting the complex post-translational regulation of the DNA damage response. ## Research Directions The established role of [ABRAXAS1](/details-gene/84142) in DNA repair provides a clear framework, yet its specific cellular expression patterns suggest several avenues for future research. Based on the available data, several testable hypotheses can be proposed: 1. The exceptionally high significance of [ABRAXAS1](/details-gene/84142) in [choroid plexus epithelial cell](/details-cell/CL0000706) suggests it may have a specialized role in protecting this critical brain barrier from accumulated genotoxic stress, thereby preserving cerebrospinal fluid homeostasis and preventing neurodegeneration. 2. In hematopoietic lineages, [ABRAXAS1](/details-gene/84142) may be indispensable for the long-term maintenance of the [hematopoietic stem cell](/details-cell/CL0000037) pool, and its dysregulation could contribute to hematopoietic stem cell exhaustion or malignant transformation. 3. The gene's prominence in memory T cell subsets indicates that it may be a key factor in ensuring the longevity and functional fitness of the adaptive immune memory, with potential implications for immunosenescence and vaccination efficacy. A key experiment could be designed to test the first hypothesis regarding the choroid plexus. To investigate the specific role of [ABRAXAS1](/details-gene/84142) in choroid plexus function, one could utilize a conditional knockout mouse model (e.g., using Cre-Lox technology with a choroid plexus-specific promoter) to delete *Abraxas1* specifically in these epithelial cells. The resulting phenotype could be assessed for defects in blood-CSF barrier integrity using tracer dyes, changes in cerebrospinal fluid proteome via mass spectrometry, and an increased rate of cellular senescence or apoptosis in response to low-dose irradiation. Therapeutically, [ABRAXAS1](/details-gene/84142) and the BRCA1-A complex it belongs to represent potential targets for cancer treatment. Given its central role in DNA repair, inhibition of [ABRAXAS1](/details-gene/84142) function could serve as a powerful strategy to sensitize cancer cells to DNA-damaging agents like chemotherapy and radiation. This approach, targeting a DNA repair pathway to induce synthetic lethality, could be particularly effective in tumors that have an underlying deficiency in other repair pathways. Therefore, small molecule inhibitors targeting the protein-protein interactions mediated by [ABRAXAS1](/details-gene/84142) would be a promising area for drug development.

Genular Protein ID: 2930595778

Symbol: ABRX1_HUMAN

Name: Coiled-coil domain-containing protein 98

UniProtKB Accession Codes:

Q6UWZ7 A5JJ07 Q9H8I1 Q9H9N4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 ELM 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 16 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 5 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 17525340

Title: Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response.

PubMed ID: 17525340

DOI: 10.1126/science.1139476

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17643121

Title: CCDC98 targets BRCA1 to DNA damage sites.

PubMed ID: 17643121

DOI: 10.1038/nsmb1279

PubMed ID: 17643122

Title: CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response.

PubMed ID: 17643122

DOI: 10.1038/nsmb1277

PubMed ID: 18077395

Title: Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.

PubMed ID: 18077395

DOI: 10.1073/pnas.0710061104

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: 19261746

Title: MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.

PubMed ID: 19261746

DOI: 10.1101/gad.1739609

PubMed ID: 19261749

Title: NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.

PubMed ID: 19261749

DOI: 10.1101/gad.1770309

PubMed ID: 19261748

Title: MERIT40 facilitates BRCA1 localization and DNA damage repair.

PubMed ID: 19261748

DOI: 10.1101/gad.1770609

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

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

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

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: 24075985

Title: A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses.

PubMed ID: 24075985

DOI: 10.1016/j.celrep.2013.08.025

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24316840

Title: Preliminary crystallographic studies of BRCA1 BRCT-ABRAXAS complex.

PubMed ID: 24316840

DOI: 10.1107/s1744309113030649

PubMed ID: 26778126

Title: Structure of BRCA1-BRCT/Abraxas complex reveals phosphorylation-dependent BRCT dimerization at DNA damage sites.

PubMed ID: 26778126

DOI: 10.1016/j.molcel.2015.12.017

PubMed ID: 18695986

Title: Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases.

PubMed ID: 18695986

DOI: 10.1007/s10549-008-0134-y

PubMed ID: 22357538

Title: Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions.

PubMed ID: 22357538

DOI: 10.1126/scitranslmed.3003223

PubMed ID: 25105795

Title: Mislocalization of BRCA1-complex due to ABRAXAS Arg361Gln mutation.

PubMed ID: 25105795

DOI: 10.1080/07391102.2014.945484

Sequence Information:

  • Length: 409
  • Mass: 46663
  • Checksum: A1ACA4F759BD1AEE
  • Sequence:
    • MEGESTSAVL SGFVLGALAF QHLNTDSDTE GFLLGEVKGE AKNSITDSQM DDVEVVYTID 
IQKYIPCYQL FSFYNSSGEV NEQALKKILS NVKKNVVGWY KFRRHSDQIM TFRERLLHKN 
LQEHFSNQDL VFLLLTPSII TESCSTHRLE HSLYKPQKGL FHRVPLVVAN LGMSEQLGYK 
TVSGSCMSTG FSRAVQTHSS KFFEEDGSLK EVHKINEMYA SLQEELKSIC KKVEDSEQAV 
DKLVKDVNRL KREIEKRRGA QIQAAREKNI QKDPQENIFL CQALRTFFPN SEFLHSCVMS 
LKNRHVSKSS CNYNHHLDVV DNLTLMVEHT DIPEASPAST PQIIKHKALD LDDRWQFKRS 
RLLDTQDKRS KADTGSSNQD KASKMSSPET DEEIEKMKGF GEYSRSPTF