ID   MAEL_MOUSE              Reviewed;         434 AA.
AC   Q8BVN9;
DT   18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Protein maelstrom homolog {ECO:0000305};
GN   Name=Mael {ECO:0000312|MGI:MGI:2138453};
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].
RC   STRAIN=C57BL/6J; TISSUE=Testis;
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 MRNA].
RC   TISSUE=Testis;
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   [3]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP   INTERACTION WITH SMARCB1; SIN3B; DDX4; PIWIL1; PIWIL2 AND TDRD1.
RX   PubMed=16787967; DOI=10.1093/hmg/ddl158;
RA   Costa Y., Speed R.M., Gautier P., Semple C.A., Maratou K., Turner J.M.A.,
RA   Cooke H.J.;
RT   "Mouse MAELSTROM: the link between meiotic silencing of unsynapsed
RT   chromatin and microRNA pathway?";
RL   Hum. Mol. Genet. 15:2324-2334(2006).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=18694567; DOI=10.1016/j.devcel.2008.05.015;
RA   Soper S.F.C., van der Heijden G.W., Hardiman T.C., Goodheart M.,
RA   Martin S.L., de Boer P., Bortvin A.;
RT   "Mouse maelstrom, a component of nuage, is essential for spermatogenesis
RT   and transposon repression in meiosis.";
RL   Dev. Cell 15:285-297(2008).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20011505; DOI=10.1371/journal.pgen.1000764;
RA   Aravin A.A., van der Heijden G.W., Castaneda J., Vagin V.V., Hannon G.J.,
RA   Bortvin A.;
RT   "Cytoplasmic compartmentalization of the fetal piRNA pathway in mice.";
RL   PLoS Genet. 5:E1000764-E1000764(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   INTERACTION WITH TEX19.1.
RX   PubMed=28254886; DOI=10.1242/jcs.188763;
RA   Tarabay Y., Achour M., Teletin M., Ye T., Teissandier A., Mark M.,
RA   Bourc'his D., Viville S.;
RT   "Tex19 paralogs are new members of the piRNA pathway controlling
RT   retrotransposon suppression.";
RL   J. Cell Sci. 130:1463-1474(2017).
CC   -!- FUNCTION: Plays a central role during spermatogenesis by repressing
CC       transposable elements and preventing their mobilization, which is
CC       essential for the germline integrity. Acts via the piRNA metabolic
CC       process, which mediates the repression of transposable elements during
CC       meiosis by forming complexes composed of piRNAs and Piwi proteins and
CC       governs the methylation and subsequent repression of transposons. Its
CC       association with piP-bodies suggests a participation in the secondary
CC       piRNAs metabolic process. Required for the localization of germ-cell
CC       factors to the meiotic nuage. {ECO:0000269|PubMed:18694567,
CC       ECO:0000269|PubMed:20011505}.
CC   -!- SUBUNIT: Interacts with SMARCB1, SIN3B and DDX4. Interacts with piRNA-
CC       associated proteins TDRD1, PIWIL1 and PIWIL2. Interacts with Tex19.1
CC       and, probably, Tex19.2 (PubMed:28254886). {ECO:0000269|PubMed:16787967,
CC       ECO:0000269|PubMed:28254886}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18694567,
CC       ECO:0000269|PubMed:20011505}. Nucleus {ECO:0000269|PubMed:16787967,
CC       ECO:0000269|PubMed:18694567}. Note=Component of the meiotic nuage, also
CC       named P granule, a germ-cell-specific organelle required to repress
CC       transposon activity during meiosis. Recruited to perinuclear nuage
CC       during spermatogenesis. Specifically localizes to piP-bodies, a subset
CC       of the nuage which contains secondary piRNAs. PIWIL2 is required for
CC       its localization to piP-bodies. PubMed:16787967, reported an
CC       association with the nuclear XY body, however, PubMed:18694567 showed
CC       that it is not the case because the antibody used by PubMed:16787967
CC       still stains the nuclear XY body in spermatocytes lacking Mael.
CC       Moreover other antibodies raized against the same epitope used in
CC       PubMed:16787967 do not recognize any epitopes on XY chromosomes but
CC       show a clear localization to the meiotic nuage.
CC       {ECO:0000269|PubMed:16787967, ECO:0000269|PubMed:18694567,
CC       ECO:0000269|PubMed:20011505}.
CC   -!- TISSUE SPECIFICITY: Testis-specific. Present in spermatocytes and round
CC       and early elongating spermatids. {ECO:0000269|PubMed:16787967,
CC       ECO:0000269|PubMed:18694567}.
CC   -!- DEVELOPMENTAL STAGE: Present from 12.5 dpc, although at this stage,
CC       protein levels are low. In the male, from 12.5 until 14.5 cpc, it
CC       localizes to the cytoplasm of germ cells, but from 15.5-16.5 dpc, it
CC       localizes to the nucleus as well. In the female, it is cytoplasmic in
CC       germ cells throughout embryonic gonad development (at protein level).
CC       In testis, low levels are observed in the early stages of meiotic
CC       prophase I (leptonema to midpachynema). Starts to accumulate throughout
CC       the cytoplasm and in prominent perinuclear nuage in late pachytene and
CC       diplotene spermatocytes. Meiotic metaphases and secondary spermatocytes
CC       show a high level in the cytoplasm as well as in nuage. Present in the
CC       chromatoid body and in a second smaller nuage in round spermatids (at
CC       protein level). {ECO:0000269|PubMed:16787967}.
CC   -!- DISRUPTION PHENOTYPE: Mice are viable but show profound defect in
CC       synapsis of homologous chromosomes in male meiosis, piRNA production
CC       defects, DNA demethylation of LINE-1 (L1) transposable elements and a
CC       100-fold increase in L1 expression in the adult testis. In the adult
CC       testes, L1 transposon derepression occurs at the onset of meiosis. As a
CC       result, spermatocytes are flooded with L1 ribonucleoproteins (RNPs)
CC       that accumulates in large cytoplasmic enclaves and nuclei.
CC       Spermatocytes with nuclear L1 RNPs exhibit massive DNA damage and
CC       severe chromosome asynapsis. In gonocytes, PIWIL4, TDRD9, and DDX4 are
CC       lost from piP-bodies, whereas no effects on pi-body composition are
CC       observed. {ECO:0000269|PubMed:18694567, ECO:0000269|PubMed:20011505}.
CC   -!- SIMILARITY: Belongs to the maelstrom family. {ECO:0000305}.
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DR   EMBL; AK077103; BAC36612.1; -; mRNA.
DR   EMBL; AK165801; BAE38386.1; -; mRNA.
DR   EMBL; BC050800; AAH50800.1; -; mRNA.
DR   CCDS; CCDS15448.1; -.
DR   RefSeq; NP_780505.1; NM_175296.4.
DR   AlphaFoldDB; Q8BVN9; -.
DR   SMR; Q8BVN9; -.
DR   BioGRID; 221084; 7.
DR   STRING; 10090.ENSMUSP00000045828; -.
DR   PhosphoSitePlus; Q8BVN9; -.
DR   SwissPalm; Q8BVN9; -.
DR   PaxDb; 10090-ENSMUSP00000045828; -.
DR   ProteomicsDB; 252712; -.
DR   Antibodypedia; 34338; 82 antibodies from 21 providers.
DR   DNASU; 98558; -.
DR   Ensembl; ENSMUST00000038782.4; ENSMUSP00000045828.4; ENSMUSG00000040629.9.
DR   GeneID; 98558; -.
DR   KEGG; mmu:98558; -.
DR   UCSC; uc007dkk.1; mouse.
DR   AGR; MGI:2138453; -.
DR   CTD; 84944; -.
DR   MGI; MGI:2138453; Mael.
DR   VEuPathDB; HostDB:ENSMUSG00000040629; -.
DR   eggNOG; ENOG502QTQB; Eukaryota.
DR   GeneTree; ENSGT00390000003645; -.
DR   HOGENOM; CLU_051692_0_0_1; -.
DR   InParanoid; Q8BVN9; -.
DR   OMA; GARNAYY; -.
DR   OrthoDB; 5394659at2759; -.
DR   PhylomeDB; Q8BVN9; -.
DR   TreeFam; TF323573; -.
DR   BioGRID-ORCS; 98558; 2 hits in 81 CRISPR screens.
DR   PRO; PR:Q8BVN9; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q8BVN9; Protein.
DR   Bgee; ENSMUSG00000040629; Expressed in seminiferous tubule of testis and 32 other cell types or tissues.
DR   ExpressionAtlas; Q8BVN9; baseline and differential.
DR   GO; GO:0030849; C:autosome; IDA:MGI.
DR   GO; GO:0000785; C:chromatin; IDA:MGI.
DR   GO; GO:0033391; C:chromatoid body; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0043186; C:P granule; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR   GO; GO:0071547; C:piP-body; IDA:UniProtKB.
DR   GO; GO:0001741; C:XY body; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR   GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR   GO; GO:0006974; P:DNA damage response; IMP:MGI.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; IMP:MGI.
DR   GO; GO:0009566; P:fertilization; IMP:MGI.
DR   GO; GO:0010467; P:gene expression; IMP:MGI.
DR   GO; GO:0007129; P:homologous chromosome pairing at meiosis; IMP:MGI.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR   GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR   GO; GO:0051093; P:negative regulation of developmental process; IMP:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IBA:GO_Central.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR   GO; GO:2000242; P:negative regulation of reproductive process; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR   GO; GO:0034587; P:piRNA processing; IMP:UniProtKB.
DR   GO; GO:0060964; P:regulation of miRNA-mediated gene silencing; IEA:InterPro.
DR   GO; GO:0046620; P:regulation of organ growth; IMP:MGI.
DR   GO; GO:0031047; P:regulatory ncRNA-mediated gene silencing; IMP:UniProtKB.
DR   GO; GO:0141007; P:siRNA-mediated retrotransposon silencing by heterochromatin formation; IMP:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR   CDD; cd21992; HMG-box_MAEL; 1.
DR   Gene3D; 1.10.30.10; High mobility group box domain; 1.
DR   InterPro; IPR009071; HMG_box_dom.
DR   InterPro; IPR036910; HMG_box_dom_sf.
DR   InterPro; IPR024970; Maelstrom.
DR   InterPro; IPR039259; Protein_maelstrom.
DR   PANTHER; PTHR21358; PROTEIN MAELSTROM HOMOLOG; 1.
DR   PANTHER; PTHR21358:SF4; PROTEIN MAELSTROM HOMOLOG; 1.
DR   Pfam; PF09011; HMG_box_2; 1.
DR   Pfam; PF13017; Maelstrom; 1.
DR   SUPFAM; SSF47095; HMG-box; 1.
DR   Genevisible; Q8BVN9; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Developmental protein; Differentiation; DNA-binding; Meiosis;
KW   Nucleus; Reference proteome; RNA-binding; RNA-mediated gene silencing;
KW   Spermatogenesis.
FT   CHAIN           1..434
FT                   /note="Protein maelstrom homolog"
FT                   /id="PRO_0000232503"
FT   DNA_BIND        4..73
FT                   /note="HMG box"
SQ   SEQUENCE   434 AA;  49371 MW;  3007B0DBBB95415C CRC64;
     MPNRRASRNA YYFFVQEKIP ELRRRGLPVA RVADAIPYCS ADWALLREDE KEKYSEMARE
     WRAAQGKDSG PSEKQKLVST PLRRPGMLVP KPSISPPDMS NLSIKSDQAL LGGIFYFLNI
     FSHGELPPHC EQRFLPCEIG CVKYSLQEGI MADFHSFIHP GEIPRGFRFH CQAASDSSHK
     IPISNFEFGH DQATVLQNLY KFIHPNPGNW PPIYCKSDDR ARVNWCLKRM ERASEIRQDL
     ELLTVEDLVV GIYQQKFLKE PSKTWVRSLL DVAMWDYSSN TRCKWHEEND ILFCALAVCK
     KIAYCISNSL ATLFGIQLTG AHVPLQDYEA SNSVTPKMVV LDAGRYQKLR VESPGFCHFN
     SYNQEQRSNT STGYYPSGVK ISGPHSSVRG RGITRLLESI SNSSNNIHRF SSCETSLSPY
     TPQKDGYKPF SSFS
//