KHDC3_MOUSE
ID KHDC3_MOUSE Reviewed; 440 AA.
AC Q9CWU5; A7YIL2; Q9CRD6;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=KH domain-containing protein 3;
DE AltName: Full=Protein Filia {ECO:0000303|PubMed:18057100};
GN Name=Khdc3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH NLRP5,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovary {ECO:0000269|PubMed:18057100};
RX PubMed=18057100; DOI=10.1242/dev.011445;
RA Ohsugi M., Zheng P., Baibakov B., Li L., Dean J.;
RT "Maternally derived FILIA-MATER complex localizes asymmetrically in
RT cleavage-stage mouse embryos.";
RL Development 135:259-269(2008).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAD95487.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Yamanaka S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAD95487.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Ovary {ECO:0000312|EMBL:ABK91524.1};
RA Sachdev M., Mandal A., Chertihin O., Digilio L., Flickinger C.J.,
RA Herr J.C.;
RT "OEEP, an egg and embryo specific protein, predominantly restricted to the
RT periphery of the oocyte and early embryonic stages.";
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:BAB26895.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB26895.1};
RC TISSUE=Embryonic stem cell {ECO:0000312|EMBL:BAB26895.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAD95487.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAI37809.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION.
RX PubMed=17913455; DOI=10.1016/j.ygeno.2007.06.003;
RA Pierre A., Gautier M., Callebaut I., Bontoux M., Jeanpierre E.,
RA Pontarotti P., Monget P.;
RT "Atypical structure and phylogenomic evolution of the new eutherian
RT oocyte- and embryo-expressed KHDC1/DPPA5/ECAT1/OOEP gene family.";
RL Genomics 90:583-594(2007).
RN [8] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE SCMC COMPLEX, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH NLRP5.
RX PubMed=18804437; DOI=10.1016/j.devcel.2008.07.010;
RA Li L., Baibakov B., Dean J.;
RT "A subcortical maternal complex essential for preimplantation mouse
RT embryogenesis.";
RL Dev. Cell 15:416-425(2008).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19376971; DOI=10.1073/pnas.0900519106;
RA Zheng P., Dean J.;
RT "Role of Filia, a maternal effect gene, in maintaining euploidy during
RT cleavage-stage mouse embryogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:7473-7478(2009).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25208553; DOI=10.1038/ncomms5887;
RA Yu X.J., Yi Z., Gao Z., Qin D., Zhai Y., Chen X., Ou-Yang Y., Wang Z.B.,
RA Zheng P., Zhu M.S., Wang H., Sun Q.Y., Dean J., Li L.;
RT "The subcortical maternal complex controls symmetric division of mouse
RT zygotes by regulating F-actin dynamics.";
RL Nat. Commun. 5:4887-4887(2014).
RN [11]
RP FUNCTION, INTERACTION WITH PARP1 AND NUMA1, SUBCELLULAR LOCATION,
RP INDUCTION, PHOSPHORYLATION AT SER-349, AND MUTAGENESIS OF SER-349.
RX PubMed=25936915; DOI=10.1016/j.stem.2015.03.017;
RA Zhao B., Zhang W.D., Duan Y.L., Lu Y.Q., Cun Y.X., Li C.H., Guo K.,
RA Nie W.H., Li L., Zhang R., Zheng P.;
RT "Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards
RT Genomic Stability.";
RL Cell Stem Cell 16:684-698(2015).
RN [12]
RP FUNCTION, INTERACTION WITH OOEP; BLM AND TRIM25, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-151, AND MUTAGENESIS OF
RP SER-151 AND SER-349.
RX PubMed=29125140; DOI=10.1038/cr.2017.139;
RA Zhao B., Zhang W., Cun Y., Li J., Liu Y., Gao J., Zhu H., Zhou H.,
RA Zhang R., Zheng P.;
RT "Mouse embryonic stem cells have increased capacity for replication fork
RT restart driven by the specific Filia-Floped protein complex.";
RL Cell Res. 28:69-89(2018).
RN [13]
RP FUNCTION, AND IDENTIFICATION IN THE SCMC COMPLEX.
RX PubMed=28992324; DOI=10.1093/jmcb/mjx035;
RA Gao Z., Zhang X., Yu X., Qin D., Xiao Y., Yu Y., Xiang Y., Nie X., Lu X.,
RA Liu W., Yi Z., Li L.;
RT "Zbed3 participates in the subcortical maternal complex and regulates the
RT distribution of organelles.";
RL J. Mol. Cell Biol. 10:74-88(2018).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31575650; DOI=10.1242/dev.183616;
RA Qin D., Gao Z., Xiao Y., Zhang X., Ma H., Yu X., Nie X., Fan N., Wang X.,
RA Ouyang Y., Sun Q.Y., Yi Z., Li L.;
RT "The subcortical maternal complex protein Nlrp4f is involved in cytoplasmic
RT lattice formation and organelle distribution.";
RL Development 146:0-0(2019).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=33115731; DOI=10.1126/sciadv.aba0682;
RA Li J., Shang Y., Wang L., Zhao B., Sun C., Li J., Liu S., Li C., Tang M.,
RA Meng F.L., Zheng P.;
RT "Genome integrity and neurogenesis of postnatal hippocampal neural
RT stem/progenitor cells require a unique regulator Filia.";
RL Sci. Adv. 6:0-0(2020).
RN [16] {ECO:0000305}
RP PRELIMINARY X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-124.
RX PubMed=20823540; DOI=10.1107/s1744309110031994;
RA Wang J., Zhang T.C., Liu X.;
RT "Preliminary crystallographic analysis of the N-terminal domain of FILIA, a
RT protein essential for embryogenesis.";
RL Acta Crystallogr. F 66:1111-1114(2010).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-124, FUNCTION, AND DOMAIN.
RX PubMed=22276159; DOI=10.1371/journal.pone.0030209;
RA Wang J., Xu M., Zhu K., Li L., Liu X.;
RT "The N-terminus of FILIA forms an atypical KH domain with a unique
RT extension involved in interaction with RNA.";
RL PLoS ONE 7:0-0(2012).
CC -!- FUNCTION: As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25
CC to DNA replication forks, thereby promoting the ubiquitination of BLM
CC by TRIM25, enhancing BLM retainment at replication forks and therefore
CC promoting stalled replication fork restart (PubMed:29125140,
CC PubMed:33115731). Regulates homologous recombination-mediated DNA
CC repair via recruitment of RAD51 to sites of DNA double-strand breaks,
CC and sustainment of PARP1 activity, which in turn modulates downstream
CC ATM or ATR activation (PubMed:25936915, PubMed:33115731). Activation of
CC ATM or ATR in response to DNA double-strand breaks may be cell-type
CC specific (PubMed:25936915, PubMed:33115731). Its role in DNA double-
CC strand break repair is independent of its role in restarting stalled
CC replication forks (PubMed:29125140). As a member of the subcortical
CC maternal complex (SCMC), plays an essential role for zygotes to
CC progress beyond the first embryonic cell divisions via regulation of
CC actin dynamics (PubMed:18804437, PubMed:29125140, PubMed:28992324,
CC PubMed:31575650). Required for maintenance of euploidy during cleavage-
CC stage embryogenesis (PubMed:19376971). Required for the formation of F-
CC actin cytoplasmic lattices in oocytes which in turn are responsible for
CC symmetric division of zygotes via the regulation of mitotic spindle
CC formation and positioning (PubMed:25208553, PubMed:31575650). Ensures
CC proper spindle assembly by regulating the localization of AURKA via
CC RHOA signaling and of PLK1 via a RHOA-independent process
CC (PubMed:19376971). Required for the localization of MAD2L1 to
CC kinetochores to enable spindle assembly checkpoint function
CC (PubMed:19376971). Promotes neural stem cell neurogenesis and neuronal
CC differentiation in the hippocampus (PubMed:33115731). May regulate
CC normal development of learning, memory and anxiety (PubMed:33115731).
CC Capable of binding RNA (PubMed:22276159). {ECO:0000269|PubMed:18804437,
CC ECO:0000269|PubMed:19376971, ECO:0000269|PubMed:22276159,
CC ECO:0000269|PubMed:25208553, ECO:0000269|PubMed:25936915,
CC ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:29125140,
CC ECO:0000269|PubMed:31575650, ECO:0000269|PubMed:33115731}.
CC -!- SUBUNIT: Component of the subcortical maternal complex (SCMC), at least
CC composed of NLRP5, KHDC3, OOEP, and TLE6 (PubMed:18057100,
CC PubMed:18804437, PubMed:28992324). Within the complex, interacts with
CC NLRP5, OOEP and TLE6 (PubMed:18057100, PubMed:18804437). The SCMC may
CC facilitate translocation of its components between the nuclear and
CC cytoplasmic compartments (By similarity). Forms a scaffold complex with
CC OOEP/FLOPED, and interacts with BLM and TRIM25 at DNA replication forks
CC (PubMed:29125140). Interacts with PARP1; the interaction is increased
CC following the formation of DNA double-strand breaks (PubMed:25936915).
CC Interacts (via C-terminus) with NUMA1 (PubMed:25936915).
CC {ECO:0000250|UniProtKB:Q587J8, ECO:0000269|PubMed:18057100,
CC ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:25936915,
CC ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:29125140}.
CC -!- INTERACTION:
CC Q9CWU5; Q9R1M5: Nlrp5; NbExp=3; IntAct=EBI-2905804, EBI-2905719;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:18804437,
CC ECO:0000269|PubMed:25936915}. Nucleus {ECO:0000269|PubMed:25936915,
CC ECO:0000269|PubMed:29125140, ECO:0000269|PubMed:33115731}.
CC Mitochondrion {ECO:0000269|PubMed:25936915}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:25936915}. Chromosome
CC {ECO:0000250|UniProtKB:Q587J8}. Note=Localized to centrosomes during
CC interphase and mitosis (PubMed:25936915). Localizes to sites of DNA
CC double-strand break repair (By similarity). Localization to the
CC mitochondrion during apoptosis following phosphorylation of Ser-349
CC (PubMed:25936915). Expressed in the subcortex of oocytes
CC (PubMed:25208553). Located throughout the cell cortex of ovulated eggs
CC in a complex with NLRP5 (PubMed:18057100). After fertilization,
CC restricted to the apical cortex and excluded from regions of cell-cell
CC contact (PubMed:18057100). {ECO:0000250|UniProtKB:Q587J8,
CC ECO:0000269|PubMed:18057100, ECO:0000269|PubMed:25208553,
CC ECO:0000269|PubMed:25936915}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:18057100}; Synonyms=Filia 1.6
CC {ECO:0000269|PubMed:18057100};
CC IsoId=Q9CWU5-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:18057100}; Synonyms=Filia 1.2
CC {ECO:0000269|PubMed:18057100};
CC IsoId=Q9CWU5-2; Sequence=VSP_040951, VSP_040952;
CC Name=3 {ECO:0000269|Ref.3};
CC IsoId=Q9CWU5-3; Sequence=VSP_040950;
CC -!- TISSUE SPECIFICITY: Detected in ovary, but not in testis or somatic
CC tissues. In the ovary, expressed in growing oocytes.
CC {ECO:0000269|PubMed:18057100}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain at low levels during fetal
CC development, from 13.5 dpc to 18.5 dpc, however significantly increased
CC after birth from P1 to P60 (PubMed:33115731). Highly expressed in
CC neural stem progenitor cells in the hippocampus after birth
CC (PubMed:33115731). {ECO:0000269|PubMed:33115731}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Expressed in growing oocytes but
CC diminishes in fully grown oocytes (PubMed:18057100). Detected at very
CC low levels in morula and early blastocyst (PubMed:18057100).
CC {ECO:0000269|PubMed:18057100}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Expressed in growing oocytes,
CC ovulated eggs and preimplantation embryos up to the morula stage and
CC decreases markedly at the blastocyst stage (at protein level).
CC {ECO:0000269|PubMed:18057100}.
CC -!- INDUCTION: Induced by ultraviolet light, etoposide, doxorubicin,
CC camptothecin and hydroxyl urea in embryonic stem cells
CC (PubMed:25936915). Induced by etoposide and hydroxy urea in neural stem
CC cells (PubMed:33115731). {ECO:0000269|PubMed:25936915,
CC ECO:0000269|PubMed:33115731}.
CC -!- DOMAIN: Contains 1 atypical KH domain, which is still capable of
CC binding RNA. {ECO:0000269|PubMed:22276159}.
CC -!- PTM: Phosphorylation at Ser-151 is required to promote stalled fork
CC restart. {ECO:0000269|PubMed:29125140}.
CC -!- DISRUPTION PHENOTYPE: Reduced fecundity and impaired preimplantation
CC embryo development with a high incidence of aneuploidy due to abnormal
CC spindle assembly, chromosomal misalignment and spindle assembly
CC checkpoint inactivation (PubMed:19376971). Loss of cytoplasmic lattices
CC and aberrant organelle distribution in oocytes (PubMed:31575650).
CC Increase in abnormal embryonic structure and loss of the embryo
CC following compromised post-implantation embryo development
CC (PubMed:29125140). Knockout mice show normal brain structure and weight
CC (PubMed:33115731). Increased DNA double-strand breaks in hippocampus
CC neural stem cells at P1 to 1 year of age (PubMed:33115731). Reduced
CC hippocampal neural stem cell proliferation from P7 to P60
CC (PubMed:33115731). Reduced differentiation of neurons and dendritic
CC spines formation in the dentate gyrus from P13 to P66
CC (PubMed:33115731). Impaired hippocampus-dependent spatial learning,
CC memory and anxiety from 2 months to 1 year of age (PubMed:33115731).
CC {ECO:0000269|PubMed:19376971, ECO:0000269|PubMed:29125140,
CC ECO:0000269|PubMed:31575650, ECO:0000269|PubMed:33115731}.
CC -!- SIMILARITY: Belongs to the KHDC1 family. {ECO:0000305}.
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DR EMBL; AB211060; BAD95487.1; -; mRNA.
DR EMBL; DQ917421; ABK91524.1; -; mRNA.
DR EMBL; DQ917422; ABK91525.1; -; mRNA.
DR EMBL; AK010377; BAB26895.1; -; mRNA.
DR EMBL; AK021223; BAB32334.1; -; mRNA.
DR EMBL; CH466522; EDL26289.1; -; Genomic_DNA.
DR EMBL; BC137808; AAI37809.1; -; mRNA.
DR EMBL; BC137809; AAI37810.1; -; mRNA.
DR CCDS; CCDS23336.1; -. [Q9CWU5-1]
DR CCDS; CCDS81036.1; -. [Q9CWU5-2]
DR RefSeq; NP_001298035.1; NM_001311106.1. [Q9CWU5-2]
DR RefSeq; NP_080166.1; NM_025890.3. [Q9CWU5-1]
DR PDB; 3V69; X-ray; 2.20 A; A/B=1-124.
DR PDBsum; 3V69; -.
DR AlphaFoldDB; Q9CWU5; -.
DR SMR; Q9CWU5; -.
DR BioGRID; 211859; 1.
DR CORUM; Q9CWU5; -.
DR IntAct; Q9CWU5; 3.
DR STRING; 10090.ENSMUSP00000034737; -.
DR iPTMnet; Q9CWU5; -.
DR PhosphoSitePlus; Q9CWU5; -.
DR REPRODUCTION-2DPAGE; Q9CWU5; -.
DR CPTAC; non-CPTAC-3979; -.
DR PaxDb; Q9CWU5; -.
DR PRIDE; Q9CWU5; -.
DR ProteomicsDB; 263434; -. [Q9CWU5-1]
DR ProteomicsDB; 263435; -. [Q9CWU5-2]
DR ProteomicsDB; 263436; -. [Q9CWU5-3]
DR DNASU; 66991; -.
DR Ensembl; ENSMUST00000034737; ENSMUSP00000034737; ENSMUSG00000092622. [Q9CWU5-1]
DR Ensembl; ENSMUST00000167514; ENSMUSP00000132527; ENSMUSG00000092622. [Q9CWU5-3]
DR Ensembl; ENSMUST00000173734; ENSMUSP00000133915; ENSMUSG00000092622. [Q9CWU5-2]
DR GeneID; 66991; -.
DR KEGG; mmu:66991; -.
DR UCSC; uc009qqy.2; mouse. [Q9CWU5-1]
DR UCSC; uc009qqz.2; mouse. [Q9CWU5-2]
DR CTD; 66991; -.
DR MGI; MGI:1914241; Khdc3.
DR VEuPathDB; HostDB:ENSMUSG00000092622; -.
DR eggNOG; ENOG502QQIF; Eukaryota.
DR GeneTree; ENSGT00940000162601; -.
DR HOGENOM; CLU_050702_0_0_1; -.
DR InParanoid; Q9CWU5; -.
DR OMA; AVWRADY; -.
DR OrthoDB; 913590at2759; -.
DR PhylomeDB; Q9CWU5; -.
DR TreeFam; TF338690; -.
DR BioGRID-ORCS; 66991; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q9CWU5; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9CWU5; protein.
DR Bgee; ENSMUSG00000092622; Expressed in morula and 35 other tissues.
DR ExpressionAtlas; Q9CWU5; baseline and differential.
DR Genevisible; Q9CWU5; MM.
DR GO; GO:0045179; C:apical cortex; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0106333; C:subcortical maternal complex; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0051656; P:establishment of organelle localization; IMP:UniProtKB.
DR GO; GO:0090307; P:mitotic spindle assembly; IMP:MGI.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; IMP:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR CDD; cd12795; FILIA_N_like; 1.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR031952; MOEP19_KH-like.
DR Pfam; PF16005; MOEP19; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell cycle; Chromosome; Cytoplasm;
KW Cytoskeleton; Developmental protein; Mitochondrion; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding.
FT CHAIN 1..440
FT /note="KH domain-containing protein 3"
FT /id="PRO_0000407378"
FT DOMAIN 40..118
FT /note="KH; atypical"
FT REGION 1..39
FT /note="Involved in RNA binding"
FT /evidence="ECO:0000269|PubMed:22276159"
FT REGION 132..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..440
FT /note="Required for interaction with NUMA1 and regulation
FT of apoptosis in response to DNA damage"
FT /evidence="ECO:0000269|PubMed:25936915"
FT SITE 151
FT /note="Not required for interaction with OOEP"
FT /evidence="ECO:0000269|PubMed:29125140"
FT MOD_RES 151
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:29125140"
FT MOD_RES 274
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q587J8"
FT MOD_RES 286
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q587J8"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25936915"
FT VAR_SEQ 148..171
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_040950"
FT VAR_SEQ 341..346
FT /note="VREAAT -> ESGRTE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18057100"
FT /id="VSP_040951"
FT VAR_SEQ 347..440
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18057100"
FT /id="VSP_040952"
FT MUTAGEN 151
FT /note="S->A: Reduces restart of stalled replication forks
FT and cells show an increase in DNA double strand breaks.
FT Decreases phosphorylation of ATR at 'S-428'. Reduces TRIM25
FT ubiquitination of BLM and subsequent localization to DNA
FT replication forks. Reduces phosphorylation and activation
FT of ATR. No effect on Filia distribution at replication
FT forks or nascent DNA degradation following DNA damage. Not
FT effect on interaction with OOEP."
FT /evidence="ECO:0000269|PubMed:29125140"
FT MUTAGEN 151
FT /note="S->D: No effect on localization at replication
FT forks, nascent DNA degradation following DNA damage,
FT restart of stalled replication forks or levels of DNA
FT damage."
FT /evidence="ECO:0000269|PubMed:29125140"
FT MUTAGEN 349
FT /note="S->A: Abolishes localization to the nucleus and
FT enhances localization to the mitochondrion. Reduces stalled
FT replication fork restart. Abolishes ATR-mediated
FT phosphorylation of S-151. No effect on phosphorylation and
FT activation of ATR. No effect on localization to centrosomes
FT or centrosome integrity."
FT /evidence="ECO:0000269|PubMed:25936915,
FT ECO:0000269|PubMed:29125140"
FT MUTAGEN 349
FT /note="S->D: Abolishes DNA double-strand break repair and
FT subsequent regulation of apoptosis. Abolishes localization
FT to the mitochondrion. No effect on localization to
FT centrosomes or centrosome integrity."
FT /evidence="ECO:0000269|PubMed:25936915"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:3V69"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:3V69"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:3V69"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:3V69"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:3V69"
FT HELIX 92..116
FT /evidence="ECO:0007829|PDB:3V69"
SQ SEQUENCE 440 AA; 47995 MW; 19C1B93DACC42851 CRC64;
MASLKRFQTL VPLDHKQGTL FEIIGEPKLP KWFHVECLED PKRLYVEPRL LEIMFGKDGE
HIPHLESMLH TLIHVNVWGP ERRAEIWIFG PPPFRRDVDR MLTDLAHYCR MKLMEIEALE
AGVERRRMAA HKAATQPAPV KVREAAPRPA SVKVPETATQ PAPVKVREAA PQPAPVQEVR
EAAPQQASVQ EEVREAATEQ APVQEVREAA TEQAPVQEVS EAATEQAPVQ EVNEAATEQA
SVQAVREAAT RPAPGKVRKA ATQPAPVQVC QEATQLAPVK VREAATQPAS GKVREAATQL
APVKVRKAAT QLAPVKVHEA ATQPAPGKVS DAATQSASVQ VREAATQLSP VEATDTSQLA
QVKADEAFAQ HTSGEAHQVA NGQSPIEVCE TATGQHSLDV SRALSQKCPE VFEWETQSCL
DGSYVIVQPP RDAWESFIIL
