Protein: KH domain-containing protein 3 (Protein Filia) (Q9CWU5)
Organism: Mus musculus (Mouse)
Function: As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart. Regulates homologous recombination-mediated DNA repair via recruitment of RAD51 to sites of DNA double-strand breaks, and sustainment of PARP1 activity, which in turn modulates downstream ATM or ATR activation. Activation of ATM or ATR in response to DNA double-strand breaks may be cell-type specific. Its role in DNA double-strand break repair is independent of its role in restarting stalled replication forks. As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics. Required for maintenance of euploidy during cleavage-stage embryogenesis. Required for the formation of F-actin cytoplasmic lattices in oocytes which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning. Ensures proper spindle assembly by regulating the localization of AURKA via RHOA signaling and of PLK1 via a RHOA-independent process. Required for the localization of MAD2L1 to kinetochores to enable spindle assembly checkpoint function. Promotes neural stem cell neurogenesis and neuronal differentiation in the hippocampus. May regulate normal development of learning, memory and anxiety. Capable of binding RNA.
Subcellular location: Cytoplasm, cell cortex {ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:25936915}. Nucleus {ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:29125140, ECO:0000269|PubMed:33115731}. Mitochondrion {ECO:0000269|PubMed:25936915}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:25936915}. Chromosome {ECO:0000250|UniProtKB:Q587J8}. Note=Localized to centrosomes during interphase and mitosis (PubMed:25936915). Localizes to sites of DNA double-strand break repair (By similarity). Localization to the mitochondrion during apoptosis following phosphorylation of Ser-349 (PubMed:25936915). Expressed in the subcortex of oocytes (PubMed:25208553). Located throughout the cell cortex of ovulated eggs in a complex with NLRP5 (PubMed:18057100). After fertilization, restricted to the apical cortex and excluded from regions of cell-cell contact (PubMed:18057100). {ECO:0000250|UniProtKB:Q587J8, ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:25208553, ECO:0000269|PubMed:25936915}.
Interaction partners:
- Transducin-like enhancer protein 6
- Oocyte-expressed protein homolog
- NACHT, LRR and PYD domains-containing protein 5
- RNA polymerase-associated protein LEO1
- Predicted gene 20509
- Inactive protein-arginine deiminase type-6
- DNA-directed RNA polymerase II subunit RPB2
- FACT complex subunit SPT16
- Transcription elongation factor SPT6
- DNA-directed RNA polymerase II subunit RPB4
Sequence:
MASLKRFQTLVPLDHKQGTLFEIIGEPKLPKWFHVECLEDPKRLYVEPRLLEIMFGKDGEHIPHLESMLHTLIHVNVWGPERRAEIWIFGPPPFRRDVDRMLTDLAHYCRMKLMEIEALEAGVERRRMAAHKAATQPAPVKVREAAPRPASVKVPETATQPAPVKVREAAPQPAPVQEVREAAPQQASVQEEVREAATEQAPVQEVREAATEQAPVQEVSEAATEQAPVQEVNEAATEQASVQAVREAATRPAPGKVRKAATQPAPVQVCQEATQLAPVKVREAATQPASGKVREAATQLAPVKVRKAATQLAPVKVHEAATQPAPGKVSDAATQSASVQVREAATQLSPVEATDTSQLAQVKADEAFAQHTSGEAHQVANGQSPIEVCETATGQHSLDVSRALSQKCPEVFEWETQSCLDGSYVIVQPPRDAWESFIIL