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MEI4_MOUSE
ID   MEI4_MOUSE              Reviewed;         389 AA.
AC   Q8BRM6; Q4V9Z7; Q8C4E8;
DT   22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   03-AUG-2022, entry version 103.
DE   RecName: Full=Meiosis-specific protein MEI4 {ECO:0000305};
GN   Name=Mei4 {ECO:0000303|PubMed:20551173, ECO:0000312|MGI:MGI:1922283};
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]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Brain cortex, and Cerebellum;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Eye;
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   [4]
RP   FUNCTION, INTERACTION WITH REC114, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=20551173; DOI=10.1101/gad.571710;
RA   Kumar R., Bourbon H.M., de Massy B.;
RT   "Functional conservation of Mei4 for meiotic DNA double-strand break
RT   formation from yeasts to mice.";
RL   Genes Dev. 24:1266-1280(2010).
RN   [5]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=25795304; DOI=10.1242/jcs.165464;
RA   Kumar R., Ghyselinck N., Ishiguro K., Watanabe Y., Kouznetsova A.,
RA   Hoeoeg C., Strong E., Schimenti J., Daniel K., Toth A., de Massy B.;
RT   "MEI4 - a central player in the regulation of meiotic DNA double-strand
RT   break formation in the mouse.";
RL   J. Cell Sci. 128:1800-1811(2015).
RN   [6]
RP   IDENTIFICATION IN THE MCD RECOMBINOSOME COMPLEX, AND SUBCELLULAR LOCATION.
RX   PubMed=27723721; DOI=10.1038/ncb3417;
RA   Stanzione M., Baumann M., Papanikos F., Dereli I., Lange J., Ramlal A.,
RA   Traenkner D., Shibuya H., de Massy B., Watanabe Y., Jasin M., Keeney S.,
RA   Toth A.;
RT   "Meiotic DNA break formation requires the unsynapsed chromosome axis-
RT   binding protein IHO1 (CCDC36) in mice.";
RL   Nat. Cell Biol. 18:1208-1220(2016).
CC   -!- FUNCTION: Required for DNA double-strand breaks (DSBs) formation in
CC       unsynapsed regions during meiotic recombination (PubMed:20551173,
CC       PubMed:25795304, PubMed:27723721). Probably acts by forming a complex
CC       with IHO1 and REC114, which activates DSBs formation in unsynapsed
CC       regions, an essential step to ensure completion of synapsis
CC       (PubMed:27723721). {ECO:0000269|PubMed:20551173,
CC       ECO:0000269|PubMed:25795304, ECO:0000269|PubMed:27723721}.
CC   -!- SUBUNIT: Interacts with REC114 (PubMed:20551173). Part of the MCD
CC       recombinosome complex, at least composed of IHO1, REC114 and MEI4
CC       (PubMed:27723721). {ECO:0000269|PubMed:20551173,
CC       ECO:0000269|PubMed:27723721}.
CC   -!- INTERACTION:
CC       Q8BRM6; Q9CWH4: Rec114; NbExp=5; IntAct=EBI-9548252, EBI-9548270;
CC   -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:20551173,
CC       ECO:0000269|PubMed:25795304}. Note=Specifically localizes to unsynapsed
CC       chromosomal regions during meiosis (PubMed:25795304, PubMed:27723721).
CC       Located in discrete foci on the axes of meiotic chromosomes. The number
CC       of foci is highest at leptonema, decreases at zygonema and is strongly
CC       reduced in pachynema and subsequent stages (PubMed:20551173).
CC       {ECO:0000269|PubMed:20551173, ECO:0000269|PubMed:25795304,
CC       ECO:0000269|PubMed:27723721}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8BRM6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8BRM6-2; Sequence=VSP_034675;
CC   -!- TISSUE SPECIFICITY: Expressed in adult testis and brain and in
CC       embryonic ovary. {ECO:0000269|PubMed:20551173}.
CC   -!- DEVELOPMENTAL STAGE: In the testis, expression is detected at 4 days
CC       postpartum (dpp) with a peak between days 10 and 14. Levels decrease by
CC       18 dpp with a further decrease in the adult.
CC       {ECO:0000269|PubMed:20551173}.
CC   -!- DISRUPTION PHENOTYPE: Deficient DNA double-strand break formation
CC       during meiotic recombination. {ECO:0000269|PubMed:20551173}.
CC   -!- SIMILARITY: Belongs to the MEI4L family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC38486.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AK043929; BAC31705.1; -; mRNA.
DR   EMBL; AK082395; BAC38486.1; ALT_FRAME; mRNA.
DR   EMBL; AC122931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC132430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC096613; AAH96613.1; -; mRNA.
DR   CCDS; CCDS23371.1; -. [Q8BRM6-1]
DR   CCDS; CCDS90635.1; -. [Q8BRM6-2]
DR   RefSeq; NP_780422.1; NM_175213.3. [Q8BRM6-1]
DR   RefSeq; XP_006511584.1; XM_006511521.1.
DR   AlphaFoldDB; Q8BRM6; -.
DR   SMR; Q8BRM6; -.
DR   BioGRID; 217167; 1.
DR   IntAct; Q8BRM6; 1.
DR   STRING; 10090.ENSMUSP00000061341; -.
DR   iPTMnet; Q8BRM6; -.
DR   PhosphoSitePlus; Q8BRM6; -.
DR   PaxDb; Q8BRM6; -.
DR   PRIDE; Q8BRM6; -.
DR   ProteomicsDB; 295996; -. [Q8BRM6-1]
DR   Antibodypedia; 77185; 25 antibodies from 5 providers.
DR   DNASU; 75033; -.
DR   Ensembl; ENSMUST00000057067; ENSMUSP00000061341; ENSMUSG00000043289. [Q8BRM6-1]
DR   Ensembl; ENSMUST00000189832; ENSMUSP00000140647; ENSMUSG00000043289. [Q8BRM6-2]
DR   GeneID; 75033; -.
DR   KEGG; mmu:75033; -.
DR   UCSC; uc009qvp.1; mouse. [Q8BRM6-1]
DR   CTD; 101928601; -.
DR   MGI; MGI:1922283; Mei4.
DR   VEuPathDB; HostDB:ENSMUSG00000043289; -.
DR   eggNOG; ENOG502S31K; Eukaryota.
DR   GeneTree; ENSGT00390000013856; -.
DR   HOGENOM; CLU_055456_0_0_1; -.
DR   InParanoid; Q8BRM6; -.
DR   OMA; GNNHINR; -.
DR   OrthoDB; 1116097at2759; -.
DR   PhylomeDB; Q8BRM6; -.
DR   TreeFam; TF335485; -.
DR   BioGRID-ORCS; 75033; 1 hit in 71 CRISPR screens.
DR   ChiTaRS; Mei4; mouse.
DR   PRO; PR:Q8BRM6; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q8BRM6; protein.
DR   Bgee; ENSMUSG00000043289; Expressed in primary oocyte and 71 other tissues.
DR   ExpressionAtlas; Q8BRM6; baseline and differential.
DR   Genevisible; Q8BRM6; MM.
DR   GO; GO:0000800; C:lateral element; IDA:MGI.
DR   GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR   GO; GO:0007129; P:homologous chromosome pairing at meiosis; IMP:MGI.
DR   GO; GO:0042138; P:meiotic DNA double-strand break formation; IMP:UniProtKB.
DR   GO; GO:0048477; P:oogenesis; IMP:MGI.
DR   GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR   InterPro; IPR025888; MEI4.
DR   PANTHER; PTHR28575; PTHR28575; 1.
DR   Pfam; PF13971; Mei4; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromosome; DNA recombination; Meiosis;
KW   Reference proteome.
FT   CHAIN           1..389
FT                   /note="Meiosis-specific protein MEI4"
FT                   /id="PRO_0000343704"
FT   VAR_SEQ         301..389
FT                   /note="DQGIYDVTRYENIFSLFWILEQVLQQAPQGDRTAHMDHSIPEMQTFLQKHDE
FT                   VIFRLSDAFPLFAFYLWRLGVLLNSAEMETVKNESLP -> ALPVELADSIQA (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_034675"
FT   CONFLICT        44
FT                   /note="E -> D (in Ref. 3; AAH96613)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   389 AA;  44471 MW;  04B41F13A4A3FCD1 CRC64;
     MDIQPWYLKT SKLALALAII HSKPADRSSR EYTEYLASLV TQKESTWKSK LEALEAEVLQ
     LRQKLLLSRI SSGLFKNGPD VLPTLSDQEP TSSENTLTLM DDSGCVLSNE QRNEPAELSQ
     HFVESTDPPL LPLPLEKRPR TTLENPLSSH MQFFQHLLEL KKWTESSSLK VYLTHFEKDS
     STVSDSVSQL LDALITFYRN PKLPFSSFWT EAVGTLARLA SDFNLSNHIF KRCSKKLEEF
     EKTLLQAILE NNSINRFQVQ RYVSQSLVTL GSCSLLRKSI ISLLLSEVNS FVDDLGAIDQ
     DQGIYDVTRY ENIFSLFWIL EQVLQQAPQG DRTAHMDHSI PEMQTFLQKH DEVIFRLSDA
     FPLFAFYLWR LGVLLNSAEM ETVKNESLP
 
 
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