DMRT1_MOUSE
ID DMRT1_MOUSE Reviewed; 374 AA.
AC Q9QZ59; Q19AV2; Q2TDQ9; Q6Y951; Q6Y953; Q9QZ37; Q9QZA4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Doublesex- and mab-3-related transcription factor 1;
GN Name=Dmrt1;
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 [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=10545231; DOI=10.1006/dbio.1999.9461;
RA Raymond C.S., Kettlewell J.R., Hirsch B., Bardwell V.J., Zarkower D.;
RT "Expression of Dmrt1 in the genital ridge of mouse and chicken embryos
RT suggests a role in vertebrate sexual development.";
RL Dev. Biol. 215:208-220(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Testis;
RX PubMed=10640721; DOI=10.1016/s0925-4773(99)00282-8;
RA De Grandi A., Calvari V., Bertini V., Bulfone A., Peverali G., Camerino G.,
RA Borsani G., Guioli S.;
RT "The expression pattern of a mouse doublesex-related gene is consistent
RT with a role in gonadal differentiation.";
RL Mech. Dev. 90:323-326(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=Kunming;
RX PubMed=17141192; DOI=10.1016/j.bbrc.2006.11.066;
RA Lu H., Huang X., Zhang L., Guo Y., Cheng H., Zhou R.;
RT "Multiple alternative splicing of mouse Dmrt1 during gonadal
RT differentiation.";
RL Biochem. Biophys. Res. Commun. 352:630-634(2007).
RN [4]
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 [5]
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 104-203 (ISOFORM 1).
RC TISSUE=Embryonic testis;
RX PubMed=10604464; DOI=10.1038/45130;
RA Smith C.A., McClive P.J., Western P.S., Reed K.J., Sinclair A.H.;
RT "Conservation of a sex-determining gene.";
RL Nature 402:601-602(1999).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=11040213; DOI=10.1101/gad.834100;
RA Raymond C.S., Murphy M.W., O'Sullivan M.G., Bardwell V.J., Zarkower D.;
RT "Dmrt1, a gene related to worm and fly sexual regulators, is required for
RT mammalian testis differentiation.";
RL Genes Dev. 14:2587-2595(2000).
RN [9]
RP FUNCTION.
RX PubMed=17540358; DOI=10.1016/j.ydbio.2007.04.046;
RA Kim S., Bardwell V.J., Zarkower D.;
RT "Cell type-autonomous and non-autonomous requirements for Dmrt1 in
RT postnatal testis differentiation.";
RL Dev. Biol. 307:314-327(2007).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=129/Sv;
RX PubMed=20007774; DOI=10.1073/pnas.0905431106;
RA Krentz A.D., Murphy M.W., Kim S., Cook M.S., Capel B., Zhu R., Matin A.,
RA Sarver A.L., Parker K.L., Griswold M.D., Looijenga L.H., Bardwell V.J.,
RA Zarkower D.;
RT "The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ
RT cell proliferation and pluripotency.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:22323-22328(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337, AND IDENTIFICATION BY
RP 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 [12]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=20616082; DOI=10.1073/pnas.1006243107;
RA Murphy M.W., Sarver A.L., Rice D., Hatzi K., Ye K., Melnick A.,
RA Heckert L.L., Zarkower D., Bardwell V.J.;
RT "Genome-wide analysis of DNA binding and transcriptional regulation by the
RT mammalian Doublesex homolog DMRT1 in the juvenile testis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:13360-13365(2010).
RN [13]
RP FUNCTION, DNA-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=20951351; DOI=10.1016/j.devcel.2010.09.010;
RA Matson C.K., Murphy M.W., Griswold M.D., Yoshida S., Bardwell V.J.,
RA Zarkower D.;
RT "The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that
RT controls the mitosis versus meiosis decision in male germ cells.";
RL Dev. Cell 19:612-624(2010).
RN [14]
RP FUNCTION.
RX PubMed=21621532; DOI=10.1016/j.ydbio.2011.05.658;
RA Krentz A.D., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
RA Zarkower D.;
RT "DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the
RT mammalian fetal ovary.";
RL Dev. Biol. 356:63-70(2011).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21775990; DOI=10.1038/nature10239;
RA Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
RA Zarkower D.;
RT "DMRT1 prevents female reprogramming in the postnatal mammalian testis.";
RL Nature 476:101-104(2011).
RN [16]
RP ERRATUM OF PUBMED:21775990.
RA Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
RA Zarkower D.;
RL Nature 477:238-238(2011).
CC -!- FUNCTION: Transcription factor that plays a key role in male sex
CC determination and differentiation by controlling testis development and
CC male germ cell proliferation. Plays a central role in spermatogonia by
CC inhibiting meiosis in undifferentiated spermatogonia and promoting
CC mitosis, leading to spermatogonial development and allowing abundant
CC and continuous production of sperm. Acts both as a transcription
CC repressor and activator: prevents meiosis by restricting retinoic acid
CC (RA)-dependent transcription and repressing STRA8 expression and
CC promotes spermatogonial development by activating spermatogonial
CC differentiation genes, such as SOHLH1. Also plays a key role in
CC postnatal sex maintenance by maintaining testis determination and
CC preventing feminization: represses transcription of female promoting
CC genes such as FOXL2 and activates male-specific genes. May act as a
CC tumor suppressor. May also play a minor role in oogenesis.
CC {ECO:0000269|PubMed:11040213, ECO:0000269|PubMed:17540358,
CC ECO:0000269|PubMed:20007774, ECO:0000269|PubMed:20616082,
CC ECO:0000269|PubMed:20951351, ECO:0000269|PubMed:21621532,
CC ECO:0000269|PubMed:21775990}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00070,
CC ECO:0000269|PubMed:11040213}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Dmrt1a, Dmrt1a1, Dmrt1a2, Dmrt1a3;
CC IsoId=Q9QZ59-1; Sequence=Displayed;
CC Name=2; Synonyms=Dmrt1b, DMR1g, Dmrt1g;
CC IsoId=Q9QZ59-2; Sequence=VSP_042965;
CC Name=3; Synonyms=Dmrt1d;
CC IsoId=Q9QZ59-3; Sequence=VSP_042963;
CC Name=4; Synonyms=Dmrt1c;
CC IsoId=Q9QZ59-4; Sequence=VSP_042964;
CC -!- TISSUE SPECIFICITY: Testis-specific. In adult testis, expressed in
CC Sertoli cells in all regions of the seminiferous tubules. Expressed
CC dynamically in premeiotic germ cells (spermatogonia), with high
CC expression only in regions of the seminiferous tubule that are early in
CC the spermatogenic cycle (at protein level). Expressed in all mitotic
CC spermatogonia. Expression decreases with the onset of spermatogonial
CC differentiation and disappears at the initiation of meiosis.
CC {ECO:0000269|PubMed:11040213, ECO:0000269|PubMed:20951351}.
CC -!- DEVELOPMENTAL STAGE: Detected already at 9.5 dpc. At 10.5 dpc,
CC expressed in the genital ridges of both sexes. At 14.5 dpc, during
CC gonadal sexual differentiation, expression declines in the ovary, but
CC is maintained in the testis, where it becomes restricted to Sertoli and
CC germ cells in the developing seminiferous tubules of the testis.
CC Accumulates primarily in Sertoli cells. From P1, appears in germ cells
CC and reach high levels by P7, just before meiosis begins. From P7
CC through adult stage, present in Sertoli cells and undifferentiated germ
CC cells, but not in differentiating germ cells.
CC {ECO:0000269|PubMed:10545231, ECO:0000269|PubMed:11040213}.
CC -!- DISRUPTION PHENOTYPE: Severe defects in the adult testis with
CC hypoplastic testes and disorganization of seminiferous tubules and
CC absence of germ cells, due to pre-meiotic germ cell death in testes.
CC Sertoli cell fail to differentiate. Female mutant mice have normal
CC ovaries and are fertile. Depending on the strain background mice also
CC show testis teratomas: deletion in 129/Sv strain causes a high
CC incidence of teratomas, whereas these tumors do not form in C57BL/6J
CC mutant mice. Deletion of Dmrt1 during fetal development causes
CC postnatal Sertoli cells to lose male-promoting Sox9 and instead
CC activation of female-promoting genes such as Foxl2, leading to
CC reprogrammation of Sertoli cells into granulosa cells. As a
CC consequence, theca cells form, estrogen is produced and germ cells
CC appear feminized. {ECO:0000269|PubMed:11040213,
CC ECO:0000269|PubMed:20007774, ECO:0000269|PubMed:21775990}.
CC -!- SIMILARITY: Belongs to the DMRT family. {ECO:0000305}.
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DR EMBL; AF202778; AAF12826.1; -; mRNA.
DR EMBL; AL133300; CAB62040.1; -; mRNA.
DR EMBL; AY169785; AAO41733.1; -; mRNA.
DR EMBL; AY169786; AAO41734.1; -; mRNA.
DR EMBL; AY169787; AAO41735.1; -; mRNA.
DR EMBL; AY943925; AAY20941.1; -; mRNA.
DR EMBL; DQ530630; ABF83854.1; -; mRNA.
DR EMBL; AC132140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466534; EDL41631.1; -; Genomic_DNA.
DR EMBL; BC125474; AAI25475.1; -; mRNA.
DR EMBL; AF192561; AAF05764.1; -; mRNA.
DR CCDS; CCDS29717.1; -. [Q9QZ59-1]
DR RefSeq; NP_056641.2; NM_015826.5. [Q9QZ59-1]
DR AlphaFoldDB; Q9QZ59; -.
DR SMR; Q9QZ59; -.
DR IntAct; Q9QZ59; 1.
DR STRING; 10090.ENSMUSP00000025755; -.
DR iPTMnet; Q9QZ59; -.
DR PhosphoSitePlus; Q9QZ59; -.
DR PaxDb; Q9QZ59; -.
DR PRIDE; Q9QZ59; -.
DR ProteomicsDB; 279730; -. [Q9QZ59-1]
DR ProteomicsDB; 279731; -. [Q9QZ59-2]
DR ProteomicsDB; 279732; -. [Q9QZ59-3]
DR ProteomicsDB; 279733; -. [Q9QZ59-4]
DR Antibodypedia; 23777; 327 antibodies from 26 providers.
DR DNASU; 50796; -.
DR Ensembl; ENSMUST00000025755; ENSMUSP00000025755; ENSMUSG00000024837. [Q9QZ59-1]
DR Ensembl; ENSMUST00000087525; ENSMUSP00000084803; ENSMUSG00000024837. [Q9QZ59-4]
DR GeneID; 50796; -.
DR KEGG; mmu:50796; -.
DR UCSC; uc008hbi.1; mouse. [Q9QZ59-1]
DR UCSC; uc012bjv.1; mouse. [Q9QZ59-4]
DR CTD; 1761; -.
DR MGI; MGI:1354733; Dmrt1.
DR VEuPathDB; HostDB:ENSMUSG00000024837; -.
DR eggNOG; KOG3815; Eukaryota.
DR GeneTree; ENSGT00940000156489; -.
DR HOGENOM; CLU_069148_0_0_1; -.
DR InParanoid; Q9QZ59; -.
DR OMA; CLMTECS; -.
DR OrthoDB; 1209937at2759; -.
DR TreeFam; TF317837; -.
DR BioGRID-ORCS; 50796; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Dmrt1; mouse.
DR PRO; PR:Q9QZ59; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9QZ59; protein.
DR Bgee; ENSMUSG00000024837; Expressed in indifferent gonad and 24 other tissues.
DR Genevisible; Q9QZ59; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0001674; C:female germ cell nucleus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0003006; P:developmental process involved in reproduction; IGI:MGI.
DR GO; GO:0007281; P:germ cell development; IBA:GO_Central.
DR GO; GO:0008354; P:germ cell migration; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0002176; P:male germ cell proliferation; IMP:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0030238; P:male sex determination; IMP:UniProtKB.
DR GO; GO:0046661; P:male sex differentiation; IMP:UniProtKB.
DR GO; GO:0007127; P:meiosis I; IMP:MGI.
DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0048599; P:oocyte development; IMP:MGI.
DR GO; GO:2000020; P:positive regulation of male gonad development; IMP:MGI.
DR GO; GO:0060903; P:positive regulation of meiosis I; IMP:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1900107; P:regulation of nodal signaling pathway; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060009; P:Sertoli cell development; IMP:MGI.
DR GO; GO:0060008; P:Sertoli cell differentiation; IMP:UniProtKB.
DR GO; GO:0007548; P:sex differentiation; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR Gene3D; 4.10.1040.10; -; 1.
DR InterPro; IPR001275; DM_DNA-bd.
DR InterPro; IPR036407; DM_DNA-bd_sf.
DR InterPro; IPR026607; DMRT.
DR InterPro; IPR022114; DMRT1-like.
DR PANTHER; PTHR12322; PTHR12322; 3.
DR Pfam; PF00751; DM; 1.
DR Pfam; PF12374; Dmrt1; 1.
DR SMART; SM00301; DM; 1.
DR SUPFAM; SSF82927; SSF82927; 1.
DR PROSITE; PS40000; DM_1; 1.
DR PROSITE; PS50809; DM_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Developmental protein; Differentiation;
KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Sexual differentiation; Transcription; Transcription regulation;
KW Tumor suppressor; Zinc.
FT CHAIN 1..374
FT /note="Doublesex- and mab-3-related transcription factor 1"
FT /id="PRO_0000207043"
FT DNA_BIND 70..116
FT /note="DM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00070"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 319..364
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..180
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17141192"
FT /id="VSP_042963"
FT VAR_SEQ 178..374
FT /note="EGRMVIQDIPAVTSRGHMENTSDLVSDPAYYSSFYQPSLFPYYNNLYNYPQY
FT SMALSAESSSGEVGNSLGGSPVKNSLRSLPAPYVPAQTGNQWQMKTSESRHPVSSQYRM
FT HSYYGPPSYLGQSMSQIFTFEEGPSYSEAKASVFSPPSSQDSGLVSLSSSSPMSNESSK
FT GVLECESASSEPSSYAVNQVLEEDEDE -> DEDLREPPPSELPVPDALILRASLLPGP
FT EHVPDLYLRGRPLLLRSQSQCVLAPQQSRFWLGLPLQQLSDEQRELEGSSGM (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:17141192"
FT /id="VSP_042964"
FT VAR_SEQ 213..374
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17141192"
FT /id="VSP_042965"
FT CONFLICT 25
FT /note="Q -> K (in Ref. 1; AAF12826)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="F -> L (in Ref. 2; CAB62040)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="N -> S (in Ref. 2; CAB62040)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 374 AA; 39444 MW; B6C4601432007C35 CRC64;
MPNDDTFGKP STPTEVPHAP GAPPQGKAGG YSKAAGAMAG AAGGSGAGGS GGASGSGPSG
LGSGSKKSPR LPKCARCRNH GYASPLKGHK RFCMWRDCQC KKCSLIAERQ RVMAAQVALR
RQQAQEEELG ISHPIPLPSA AELLVKRENN ASNPCLMAEN SSSAQPPPAS TPTPAASEGR
MVIQDIPAVT SRGHMENTSD LVSDPAYYSS FYQPSLFPYY NNLYNYPQYS MALSAESSSG
EVGNSLGGSP VKNSLRSLPA PYVPAQTGNQ WQMKTSESRH PVSSQYRMHS YYGPPSYLGQ
SMSQIFTFEE GPSYSEAKAS VFSPPSSQDS GLVSLSSSSP MSNESSKGVL ECESASSEPS
SYAVNQVLEE DEDE
