Ask about this productRelated genes to: KIAA0692 antibody
- Gene:
- ANKLE2 NIH gene
- Name:
- ankyrin repeat and LEM domain containing 2
- Previous symbol:
- KIAA0692
- Synonyms:
- LEMD7, Lem4
- Chromosome:
- 12q24.33
- Locus Type:
- gene with protein product
- Date approved:
- 2006-01-17
- Date modifiied:
- 2014-11-19
Related products to: KIAA0692 antibody
Related articles to: KIAA0692 antibody
- ANKLE2 is an enigmatic protein with emerging roles in cell division, development, and virus replication. While ANKLE2 orthologs are present in all animals, its domain composition has evolved over time. ANKLE2's two namesake domains, the ankyrin repeat and LEM domains (named for LAP2, Emerin, and MAN1), have clear and defined roles; however nearly all ANKLE2 orthologs have at least three other structured domains with poorly understood purposes. In this study, we performed sequence and structural alignments of ANKLE2 orthologs to improve our understanding of the protein's evolution and function. We identified that ANKLE2's transmembrane domain likely evolved more recently and coincided with loss of VAPA interaction as a membrane anchoring mechanism. We show that despite stark differences in amino acid sequence, the structure of the LEM and ankyrin repeat domains are highly conserved across ANKLE2 orthologs. To investigate ANKLE2's uncharacterized domains, we performed structural alignments to identify similar proteins. This revealed surprising similarities between portions of ANKLE2 and nuclease or nucleic acid-binding proteins. However, ANKLE2 lacks key motifs imparting function in these domains, which was confirmed by experimental interrogation. We further identified that loss of ANKLE2 is correlated with changes in DNA damage response and micronuclei formation. We believe this methodology demonstrates the power of combining structural predictions with classical molecular techniques in exploring poorly understood proteins. - Source: PubMed
Fishburn Adam TFlorio Cole JSkawinski Chase L SBecker Sydney SHolleman EthanRobertson Avery ESitchon ReesChédin FrédéricShah Priya S - Nuclear envelope dysfunction is increasingly recognized as a driver of cancer-associated alterations in chromatin organization, genome stability, and mechanotransduction. Among inner nuclear membrane components are the LEM-domain (LEM-D) proteins LAP2/TMPO, emerin (EMD), LEMD1, LEMD2, MAN1/LEMD3, ANKLE1, and ANKLE2. Accumulating evidence links dysregulation of these proteins to hallmark cancer processes, including cell-cycle control, epithelial-mesenchymal transition, genome instability, and therapeutic resistance. This review synthesizes recent mechanistic and translational findings on LEM-D proteins in cancer, highlighting isoform-specific functions, context-dependent oncogenic versus tumor-suppressive roles, and convergence on key pathways such as Wnt/β-catenin, PI3K/AKT, MAPK, and TGF-β signaling. Concrete evidence for prognostic value varies across the LEM-D proteins. While much of the current evidence derives from transcript-level and preclinical studies, emerging data suggest that LEM-D proteins contribute to nuclear stress adaptation and may represent context-dependent therapeutic vulnerabilities. We discuss their prognostic and predictive potential, critically evaluate limitations in current datasets, and present a unifying framework linking LEM-D dysfunction to genome instability, altered signalling, and therapy resistance. Thus, despite growing evidence of therapeutic potential, these proteins are better positioned as biomarkers to guide current therapies. - Source: PubMed
Publication date: 2026/04/22
Jobe AmieMirza SameerVijayan Ranjit - ANKLE2 (Ankyrin repeat and LEM domain-containing protein 2) is an emerging host factor with previously undefined roles in antiviral defense. Here, we show that ANKLE2 can exert robust antiviral activity against vaccinia virus by regulating the phosphorylation status of barrier-to-autointegration factor (BAF), a ubiquitous DNA-binding protein that compacts DNA and restricts viral replication. We first demonstrate that depletion of endogenous ANKLE2 increased BAF phosphorylation and rescued replication of B1-knockout vaccinia virus, whereas reconstitution restored restriction. We then perform domain-mapping experiments of ANKLE2, revealing that its LEM domain and Caulimovirus domain (CD domain) are essential for BAF dephosphorylation, ANKLE2-BAF association, and/or antipoxviral activity, whereas the transmembrane (TM) domain restricts cytoplasmic redistribution and functions as a negative regulator. Together, these findings uncover a previously unrecognized host defense pathway against poxviruses, provide new insight into how host ANKLE2 proteins coordinate antiviral responses, and reveal a novel antiviral role for ANKLE2 in limiting vaccinia virus DNA replication and progeny release through regulation of BAF phosphorylation.IMPORTANCEVaccinia virus relies on disabling host defenses to replicate efficiently, with the host DNA-binding protein BAF representing a key target for viral kinases. Here, we uncover ANKLE2 as a critical host factor that counteracts vaccinia virus by sustaining the antiviral activity of BAF. ANKLE2 promotes BAF dephosphorylation, thereby preventing viral escape from BAF-mediated restriction. Our results reveal that distinct domains of ANKLE2 differentially regulate its antiviral activity, with the LEM and CD domains promoting BAF dephosphorylation and antiviral activity, and the transmembrane domain acting as a negative regulator by limiting cytoplasmic redistribution. These findings highlight ANKLE2 as a domain-dependent regulator of host defense and expand our understanding of the molecular circuitry that controls poxvirus replication. - Source: PubMed
Publication date: 2025/11/18
Saeng-Chuto KepaleeWang ZhigangKrueger Alexandria CBargeron KayleeWiebe Matthew S - Three decades of research aimed at understanding the basis for autosomal recessive primary microcephaly (MCPH), a human clinical disorder defined by a significant reduction in head and brain size, has uncovered a suite of ~30 genes that participate in this process. Work in both vertebrate and invertebrate model systems have been instrumental in attempting to link MCPH gene function to the brain growth phenotype. However, we still lack definitive evidence as to what these functions are for many of these genes. In this review, we summarize recent work in aimed at overcoming these limitations in our knowledge of MCPH gene function that may be applicable to humans. We discuss the clinical features of MCPH, parallels between human and neurogenesis modes with a particular focus on the fly optic lobe, and highlight four of the most well-studied MCPH orthologs: , and /. We focus on the multifunctional roles for these proteins that may underlie the microcephaly phenotype and advocate for the use of flies as a relevant model for human MCPH. - Source: PubMed
Publication date: 2025/10/11
Chakraborty ShaliniFlorez StevenSchoborg Todd - - Source: PubMed
Publication date: 2025/09/12
Barsh Gabrielle RSmith Carly MMatalon Dena RSoares Bruno P