Details for: ATAD5

Gene ID: 79915

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: ATAD5

Ensembl ID: ENSG00000176208

Description: ATPase family AAA domain containing 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • naive B cell CL0000788
    CSI 6.21
    rCSI 5.33%
    PRS 90.19
  • amacrine cell CL0000561
    CSI 4.54
    rCSI 13.14%
    PRS 75.61
  • pro-B cell CL0000826
    CSI 4.51
    rCSI 3.74%
    PRS 87.45
  • mature T cell CL0002419
    CSI 4.31
    rCSI 3.35%
    PRS 95.29
  • neural crest cell CL0011012
    CSI 3.43
    rCSI 2.71%
    PRS 75.98
  • glioblast CL0000030
    CSI 3.39
    rCSI 5.4%
    PRS 77.14
  • melanocyte CL0000148
    CSI 3.21
    rCSI 2.38%
    PRS 80.05
  • retina horizontal cell CL0000745
    CSI 3.02
    rCSI 4.61%
    PRS 82.36
  • plasmablast CL0000980
    CSI 2.93
    rCSI 2.31%
    PRS 89.04
  • interneuron CL0000099
    CSI 2.71
    rCSI 5.43%
    PRS 77.23
  • retinal cone cell CL0000573
    CSI 2.65
    rCSI 4.27%
    PRS 76.35
  • cerebellar granule cell CL0001031
    CSI 2.65
    rCSI 3.89%
    PRS 78.96
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.56
    rCSI 2.95%
    PRS 77.7
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.38
    rCSI 2.15%
    PRS 83.87
  • common myeloid progenitor CL0000049
    CSI 2.29
    rCSI 1.86%
    PRS 87.29
  • ependymal cell CL0000065
    CSI 2.27
    rCSI 4.61%
    PRS 65.5
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.26
    rCSI 1.95%
    PRS 88.45
  • rod bipolar cell CL0000751
    CSI 2.23
    rCSI 4%
    PRS 79.42
  • retinal bipolar neuron CL0000748
    CSI 2.2
    rCSI 4.13%
    PRS 75.1
  • radial glial cell CL0000681
    CSI 2.15
    rCSI 2.99%
    PRS 83.51
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.11
    rCSI 6.24%
    PRS 85.86
  • erythroblast CL0000765
    CSI 2.11
    rCSI 5.59%
    PRS 88.71
  • neural cell CL0002319
    CSI 2.07
    rCSI 7.8%
    PRS 68.56
  • promyelocyte CL0000836
    CSI 2.06
    rCSI 2.97%
    PRS 89.45
  • intestinal epithelial cell CL0002563
    CSI 2.02
    rCSI 2.11%
    PRS 82.87
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.02
    rCSI 2.41%
    PRS 69.39
  • vascular leptomeningeal cell CL4023051
    CSI 2
    rCSI 3.5%
    PRS 80.25
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.96
    rCSI 2.51%
    PRS 81.52
  • retinal rod cell CL0000604
    CSI 1.92
    rCSI 3.38%
    PRS 80.86
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.78
    rCSI 3.98%
    PRS 70.22
  • extravillous trophoblast CL0008036
    CSI 1.76
    rCSI 2.18%
    PRS 83.59
  • adipocyte CL0000136
    CSI 1.76
    rCSI 2.26%
    PRS 76.05
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.76
    rCSI 2.19%
    PRS 67.2
  • erythrocyte CL0000232
    CSI 1.61
    rCSI 3.65%
    PRS 84.75
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.6
    rCSI 2.83%
    PRS 68.8
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.6
    rCSI 2.06%
    PRS 70.46
  • common dendritic progenitor CL0001029
    CSI 1.58
    rCSI 1.98%
    PRS 91.82
  • promonocyte CL0000559
    CSI 1.54
    rCSI 2.64%
    PRS 89.46
  • Bergmann glial cell CL0000644
    CSI 1.52
    rCSI 2.08%
    PRS 76.93
  • GABAergic neuron CL0000617
    CSI 1.46
    rCSI 4.9%
    PRS 70.07
  • transit amplifying cell of small intestine CL0009012
    CSI 1.42
    rCSI 6.22%
    PRS 90.78
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.4
    rCSI 7.21%
    PRS 95.57
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.38
    rCSI 2.21%
    PRS 70.68
  • retinal ganglion cell CL0000740
    CSI 1.28
    rCSI 2.82%
    PRS 72.52
  • placental villous trophoblast CL2000060
    CSI 1.21
    rCSI 1.87%
    PRS 84
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.21
    rCSI 3.79%
    PRS 72.93
  • large pre-B-II cell CL0000957
    CSI 1.13
    rCSI 3.21%
    PRS 88.17
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.12
    rCSI 1.87%
    PRS 69.24
  • central nervous system neuron CL2000029
    CSI 1.06
    rCSI 7.78%
    PRS 74.29
  • neural progenitor cell CL0011020
    CSI 1.02
    rCSI 4.47%
    PRS 73.97
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.97
    rCSI 2.36%
    PRS 67.1
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 0.97
    rCSI 3.78%
    PRS 96.18
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.89
    rCSI 2.78%
    PRS 70.78
  • erythroid progenitor cell CL0000038
    CSI 0.8
    rCSI 4.56%
    PRS 88.88
  • blood vessel smooth muscle cell CL0019018
    CSI 0.74
    rCSI 5.99%
    PRS 80.66
  • primitive red blood cell CL0002355
    CSI 0.71
    rCSI 3.81%
    PRS 89.14
  • eosinophil CL0000771
    CSI 0.67
    rCSI 4.38%
    PRS 95.75
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.65
    rCSI 2.46%
    PRS 69.64
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.61
    rCSI 2.2%
    PRS 67.26
  • direct pathway medium spiny neuron CL4023026
    CSI 0.38
    rCSI 9.01%
    PRS 67.14
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.35
    rCSI 2.03%
    PRS 69.78
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.32
    rCSI 7.82%
    PRS 67.57
  • pluripotent stem cell CL0002248
    CSI 0.2
    rCSI 6.03%
    PRS 92.33

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 [ATAD5](/details-gene/79915) (ATPase Family AAA Domain Containing 5) is a protein-coding gene located on chromosome 17q11.2. It encodes a key component of the alternative replication factor C (RFC) complex, known as the Elg1 RFC-like complex. Functionally, [ATAD5](/details-gene/79915) acts as a DNA clamp unloader, playing a critical role in DNA replication, DNA damage response, and the maintenance of genomic stability ([Link](https://doi.org/10.1016/s0960-9822(03)00578-5), [Link](https://doi.org/10.4161/cc.8.19.9752)). Its expression is particularly significant in highly proliferative cell populations, most notably within the adaptive immune system in cell types such as [naive B cell](/details-cell/CL0000788) and [pro-B cell](/details-cell/CL0000826), as well as in various developing or active neural cell types. ## Cellular Roles and Expression Landscape The expression profile of [ATAD5](/details-gene/79915) highlights its essential function in cell proliferation and genome maintenance across diverse lineages. **Overall**, the gene shows its highest significance in the context of lymphocyte development and function. - **Immune System:** [ATAD5](/details-gene/79915) is most prominently expressed in B-lineage cells, with the highest significance observed in [naive B cell](/details-cell/CL0000788) (CSI: 6.21) and [pro-B cell](/details-cell/CL0000826) (CSI: 4.51). Its strong presence in [plasmablast](/details-cell/CL0000980) and [mature T cell](/details-cell/CL0002419) further underscores its importance in the adaptive immune system, likely supporting the rapid proliferation and genetic recombination events characteristic of lymphocyte activation. Its expression in hematopoietic progenitors like [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and [common myeloid progenitor](/details-cell/CL0000049) is consistent with a fundamental role in the maintenance of actively dividing stem and progenitor cell populations. - **Nervous System:** A distinct and significant expression pattern is observed in various neural cell types. This includes high significance in specialized retinal neurons like [amacrine cell](/details-cell/CL0000561) (CSI: 4.54) and [retina horizontal cell](/details-cell/CL0000745), as well as in developing or progenitor-like populations such as [neural crest cell](/details-cell/CL0011012) and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338). Its notable expression in [glioblast](/details-cell/CL0000030) suggests a potential role in the context of brain tumors, which are characterized by uncontrolled proliferation. ## Pathways and Molecular Function The functions of [ATAD5](/details-gene/79915) are tightly linked to the machinery of DNA replication and repair. As a core component of the [Elg1 rfc-like complex](/details-go/GO:0031391), its primary molecular function is [Dna clamp unloader activity](/details-go/GO:0061860). This process is essential for removing the proliferating cell nuclear antigen (PCNA) clamp from DNA after the completion of Okazaki fragment synthesis during [Nuclear dna replication](/details-go/GO:0033260). Consistent with this core function, [ATAD5](/details-gene/79915) is deeply involved in biological processes that ensure genomic integrity. It participates in the [Signal transduction in response to dna damage](/details-go/GO:0042770) and is implicated in the [Intrinsic apoptotic signaling pathway in response to dna damage by p53 class mediator](/details-go/GO:0042771), linking replication stress surveillance directly with apoptosis ([Link](https://doi.org/10.1073/pnas.0504222102)). Furthermore, its functional annotations point to a specific role in immunology, including direct involvement in [Isotype switching](/details-go/GO:0045190) and the [Positive regulation of b cell proliferation](/details-go/GO:0030890), which aligns perfectly with its high expression in B lymphocytes undergoing affinity maturation and class switching. ## Research Directions The dual prominence of [ATAD5](/details-gene/79915) in both the immune and nervous systems, coupled with its central role in DNA replication, opens several avenues for future investigation. **Testable Hypotheses:** 1. Given its high significance in [naive B cell](/details-cell/CL0000788) and its annotated role in [Isotype switching](/details-go/GO:0045190), we hypothesize that [ATAD5](/details-gene/79915) is indispensable for the genomic stability of B cells during the somatic hypermutation and class-switch recombination processes within germinal centers. Its dysregulation may contribute to the genomic instability seen in B-cell lymphomas or result in specific immunodeficiencies. 2. The significant expression of [ATAD5](/details-gene/79915) in diverse, often post-mitotic, neural cells like [amacrine cell](/details-cell/CL0000561) suggests a role beyond canonical DNA replication. We hypothesize that [ATAD5](/details-gene/79915) is involved in DNA repair pathways that are critical for maintaining the long-term genomic integrity of neurons, protecting them from accumulating damage that could lead to neurodegeneration. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [ATAD5](/details-gene/79915) in B cell biology, a B-cell specific conditional knockout mouse model (e.g., Atad5-floxed crossed with a CD19-Cre driver) could be generated. Following immunization with a T-cell dependent antigen (e.g., NP-CGG), key parameters of the immune response should be assessed. This would include quantifying germinal center formation via histology, measuring serum levels of different antibody isotypes (IgM, IgG1, IgA) by ELISA, and performing deep sequencing of immunoglobulin heavy chain variable regions from sorted B cells to analyze the frequency and pattern of somatic hypermutation. A failure to effectively switch isotypes or an altered mutational landscape in knockout mice would confirm the critical role of [ATAD5](/details-gene/79915). **Therapeutic Potential:** As an essential enzyme for DNA replication and repair, [ATAD5](/details-gene/79915) represents a potential therapeutic target in oncology. Its **inhibition** could be a strategy to induce synthetic lethality in cancers with pre-existing defects in other DNA damage response pathways. Given its high expression in [glioblast](/details-cell/CL0000030), developing small molecule inhibitors against the ATPase activity of [ATAD5](/details-gene/79915) could selectively target these and other highly proliferative tumors, potentially enhancing their sensitivity to conventional genotoxic agents like radiation or chemotherapy.

Genular Protein ID: 1996209376

Symbol: ATAD5_HUMAN

Name: Chromosome fragility-associated gene 1 protein

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 11468690

Title: Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions.

PubMed ID: 11468690

DOI: 10.1086/323043

PubMed ID: 15983387

Title: Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis.

PubMed ID: 15983387

DOI: 10.1073/pnas.0504222102

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

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: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 13678589

Title: Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability.

PubMed ID: 13678589

DOI: 10.1016/s0960-9822(03)00578-5

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 18220336

Title: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.

PubMed ID: 18220336

DOI: 10.1021/pr0705441

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19755857

Title: DNA damage responses by human ELG1 in S phase are important to maintain genomic integrity.

PubMed ID: 19755857

DOI: 10.4161/cc.8.19.9752

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: 20147293

Title: Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1.

PubMed ID: 20147293

DOI: 10.1074/jbc.m109.092544

PubMed ID: 20068231

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

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21555454

Title: The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3.

PubMed ID: 21555454

DOI: 10.1128/mcb.01341-10

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: 23937667

Title: Alternative replication factor C protein, Elg1, maintains chromosome stability by regulating PCNA levels on chromatin.

PubMed ID: 23937667

DOI: 10.1111/gtc.12087

PubMed ID: 23277426

Title: ATAD5 regulates the lifespan of DNA replication factories by modulating PCNA level on the chromatin.

PubMed ID: 23277426

DOI: 10.1083/jcb.201206084

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 31844045

Title: ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress.

PubMed ID: 31844045

DOI: 10.1038/s41467-019-13667-4

PubMed ID: 26282398

Title: EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss.

PubMed ID: 26282398

DOI: 10.1186/s13023-015-0316-8

Sequence Information:

  • Length: 1844
  • Mass: 207570
  • Checksum: A09A3C76CFC77BD1
  • Sequence:
  • MVGVLAMAAA AAPPPVKDCE IEPCKKRKKD DDTSTCKTIT KYLSPLGKTR DRVFAPPKPS 
    NILDYFRKTS PTNEKTQLGK ECKIKSPESV PVDSNKDCTT PLEMFSNVEF KKKRKRVNLS 
    HQLNNIKTEN EAPIEISSDD SKEDYSLNND FVESSTSVLR YKKQVEVLAE NIQDTKSQPN 
    TMTSLQNSKK VNPKQGTTKN DFKKLRKRKC RDVVDLSESL PLAEELNLLK KDGKDTKQME 
    NTTSHANSRD NVTEAAQLND SIITVSYEEF LKSHKENKVE EIPDSTMSIC VPSETVDEIV 
    KSGYISESEN SEISQQVRFK TVTVLAQVHP IPPKKTGKIP RIFLKQKQFE MENSLSDPEN 
    EQTVQKRKSN VVIQEEELEL AVLEAGSSEA VKPKCTLEER QQFMKAFRQP ASDALKNGVK 
    KSSDKQKDLN EKCLYEVGRD DNSKKIMENS GIQMVSKNGN LQLHTDKGSF LKEKNKKLKK 
    KNKKTLDTGA IPGKNREGNT QKKETTFFLK EKQYQNRMSL RQRKTEFFKS STLFNNESLV 
    YEDIANDDLL KVSSLCNNNK LSRKTSIPVK DIKLTQSKAE SEASLLNVST PKSTRRSGRI 
    SSTPTTETIR GIDSDDVQDN SQLKASTQKA ANLSEKHSLY TAELITVPFD SESPIRMKFT 
    RISTPKKSKK KSNKRSEKSE ATDGGFTSQI RKASNTSKNI SKAKQLIEKA KALHISRSKV 
    TEEIAIPLRR SSRHQTLPER KKLSETEDSV IIIDSSPTAL KHPEKNQKKL QCLNDVLGKK 
    LNTSTKNVPG KMKVAPLFLV RKAQKAADPV PSFDESSQDT SEKSQDCDVQ CKAKRDFLMS 
    GLPDLLKRQI AKKAAALDVY NAVSTSFQRV VHVQQKDDGC CLWHLKPPSC PLLTKFKELN 
    TKVIDLSKCG IALGEFSTLN SKLKSGNSAA VFMRTRKEFT EEVRNLLLEE IRWSNPEFSL 
    KKYFPLLLKK QIEHQVLSSE CHSKQELEAD VSHKETKRKL VEAENSKSKR KKPNEYSKNL 
    EKTNRKSEEL SKRNNSSGIK LDSSKDSGTE DMLWTEKYQP QTASELIGNE LAIKKLHSWL 
    KDWKRRAELE ERQNLKGKRD EKHEDFSGGI DFKGSSDDEE ESRLCNTVLI TGPTGVGKTA 
    AVYACAQELG FKIFEVNASS QRSGRQILSQ LKEATQSHQV DKQGVNSQKP CFFNSYYIGK 
    SPKKISSPKK VVTSPRKVPP PSPKSSGPKR ALPPKTLANY FKVSPKPKNN EEIGMLLENN 
    KGIKNSFEQK QITQTKSTNA TNSNVKDVGA EEPSRKNATS LILFEEVDVI FDEDAGFLNA 
    IKTFMATTKR PVILTTSDPT FSLMFDGCFE EIKFSTPSLL NVASYLQMIC LTENFRTDVK 
    DFVTLLTANT CDIRKSILYL QFWIRSGGGV LEERPLTLYR GNSRNVQLVC SEHGLDNKIY 
    PKNTKKKRVD LPKCDSGCAE TLFGLKNIFS PSEDLFSFLK HKITMKEEWH KFIQLLTEFQ 
    MRNVDFLYSN LEFILPLPVD TIPETKNFCG PSVTVDASAA TKSMNCLARK HSEREQPLKK 
    SQKKKQKKTL VILDDSDLFD TDLDFPDQSI SLSSVSSSSN AEESKTGDEE SKARDKGNNP 
    ETKKSIPCPP KTTAGKKCSA LVSHCLNSLS EFMDNMSFLD ALLTDVREQN KYGRNDFSWT 
    NGKVTSGLCD EFSLESNDGW TSQSSGELKA AAEALSFTKC SSAISKALET LNSCKKLGRD 
    PTNDLTFYVS QKRNNVYFSQ SAANLDNAWK RISVIKSVFS SRSLLYVGNR QASIIEYLPT 
    LRNICKTEKL KEQGKSKRRF LHYFEGIHLD IPKETVNTLA ADFP