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 27-MAR-2024, entry version 111.
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).
RN [7]
RP IDENTIFICATION IN A COMPLEX WITH REC114 AND IHO1, INTERACTION WITH REC114
RP AND IHO1, AND SUBCELLULAR LOCATION.
RX PubMed=30569039; DOI=10.26508/lsa.201800259;
RA Kumar R., Oliver C., Brun C., Juarez-Martinez A.B., Tarabay Y., Kadlec J.,
RA de Massy B.;
RT "Mouse REC114 is essential for meiotic DNA double-strand break formation
RT and forms a complex with MEI4.";
RL Life. Sci Alliance 1:e201800259-e201800259(2018).
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: Part of the MCD recombinosome complex, at least composed of
CC IHO1, REC114 and MEI4 (PubMed:27723721, PubMed:30569039). Forms a
CC complex with REC114; the interaction is required for MEI4 stability
CC (PubMed:20551173, PubMed:30569039). Interacts (via N-terminal domain)
CC with REC114 (via C-terminal domain) (PubMed:20551173, PubMed:30569039).
CC Interacts with IHO1 (PubMed:30569039). {ECO:0000269|PubMed:20551173,
CC ECO:0000269|PubMed:27723721, ECO:0000269|PubMed:30569039}.
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, ECO:0000269|PubMed:30569039}.
CC Note=Specifically localizes to unsynapsed chromosomal regions during
CC meiosis (PubMed:25795304, PubMed:27723721). Located in discrete foci on
CC the axes of meiotic chromosomes. The number of foci is highest at
CC leptonema, decreases at zygonema and is strongly reduced in pachynema
CC and subsequent stages (PubMed:20551173). {ECO:0000269|PubMed:20551173,
CC ECO:0000269|PubMed:25795304, 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; 10090-ENSMUSP00000061341; -.
DR ProteomicsDB; 295996; -. [Q8BRM6-1]
DR Antibodypedia; 77185; 25 antibodies from 5 providers.
DR DNASU; 75033; -.
DR Ensembl; ENSMUST00000057067.10; ENSMUSP00000061341.3; ENSMUSG00000043289.13. [Q8BRM6-1]
DR Ensembl; ENSMUST00000189832.7; ENSMUSP00000140647.2; ENSMUSG00000043289.13. [Q8BRM6-2]
DR GeneID; 75033; -.
DR KEGG; mmu:75033; -.
DR UCSC; uc009qvp.1; mouse. [Q8BRM6-1]
DR AGR; MGI:1922283; -.
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; MYDITQY; -.
DR OrthoDB; 2966546at2759; -.
DR PhylomeDB; Q8BRM6; -.
DR TreeFam; TF335485; -.
DR BioGRID-ORCS; 75033; 1 hit in 76 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 73 other cell types or tissues.
DR ExpressionAtlas; Q8BRM6; baseline and differential.
DR Genevisible; Q8BRM6; MM.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
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; MEIOSIS-SPECIFIC PROTEIN MEI4; 1.
DR PANTHER; PTHR28575:SF1; MEIOSIS-SPECIFIC PROTEIN MEI4; 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 REGION 1..127
FT /note="Interaction with REC114"
FT /evidence="ECO:0000269|PubMed:30569039"
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
//
