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Doublesex- and mab-3-related transcription factor 1

 DMRT1_MOUSE             Reviewed;         374 AA.
Q9QZ59; Q19AV2; Q2TDQ9; Q6Y951; Q6Y953; Q9QZ37; Q9QZA4;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
18-APR-2012, sequence version 2.
10-MAY-2017, entry version 132.
RecName: Full=Doublesex- and mab-3-related transcription factor 1;
Name=Dmrt1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
STRAIN=C57BL/6J; TISSUE=Testis;
PubMed=10545231; DOI=10.1006/dbio.1999.9461;
Raymond C.S., Kettlewell J.R., Hirsch B., Bardwell V.J., Zarkower D.;
"Expression of Dmrt1 in the genital ridge of mouse and chicken embryos
suggests a role in vertebrate sexual development.";
Dev. Biol. 215:208-220(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
STRAIN=BALB/cJ; TISSUE=Testis;
PubMed=10640721; DOI=10.1016/S0925-4773(99)00282-8;
De Grandi A., Calvari V., Bertini V., Bulfone A., Peverali G.,
Camerino G., Borsani G., Guioli S.;
"The expression pattern of a mouse doublesex-related gene is
consistent with a role in gonadal differentiation.";
Mech. Dev. 90:323-326(2000).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
STRAIN=Kunming;
PubMed=17141192; DOI=10.1016/j.bbrc.2006.11.066;
Lu H., Huang X., Zhang L., Guo Y., Cheng H., Zhou R.;
"Multiple alternative splicing of mouse Dmrt1 during gonadal
differentiation.";
Biochem. Biophys. Res. Commun. 352:630-634(2007).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 104-203 (ISOFORM 1).
TISSUE=Embryonic testis;
PubMed=10604464; DOI=10.1038/45130;
Smith C.A., McClive P.J., Western P.S., Reed K.J., Sinclair A.H.;
"Conservation of a sex-determining gene.";
Nature 402:601-602(1999).
[8]
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL
STAGE, AND DISRUPTION PHENOTYPE.
PubMed=11040213; DOI=10.1101/gad.834100;
Raymond C.S., Murphy M.W., O'Sullivan M.G., Bardwell V.J.,
Zarkower D.;
"Dmrt1, a gene related to worm and fly sexual regulators, is required
for mammalian testis differentiation.";
Genes Dev. 14:2587-2595(2000).
[9]
FUNCTION.
PubMed=17540358; DOI=10.1016/j.ydbio.2007.04.046;
Kim S., Bardwell V.J., Zarkower D.;
"Cell type-autonomous and non-autonomous requirements for Dmrt1 in
postnatal testis differentiation.";
Dev. Biol. 307:314-327(2007).
[10]
FUNCTION, AND DISRUPTION PHENOTYPE.
STRAIN=129/Sv;
PubMed=20007774; DOI=10.1073/pnas.0905431106;
Krentz A.D., Murphy M.W., Kim S., Cook M.S., Capel B., Zhu R.,
Matin A., Sarver A.L., Parker K.L., Griswold M.D., Looijenga L.H.,
Bardwell V.J., Zarkower D.;
"The DM domain protein DMRT1 is a dose-sensitive regulator of fetal
germ cell proliferation and pluripotency.";
Proc. Natl. Acad. Sci. U.S.A. 106:22323-22328(2009).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[12]
FUNCTION, AND DNA-BINDING.
PubMed=20616082; DOI=10.1073/pnas.1006243107;
Murphy M.W., Sarver A.L., Rice D., Hatzi K., Ye K., Melnick A.,
Heckert L.L., Zarkower D., Bardwell V.J.;
"Genome-wide analysis of DNA binding and transcriptional regulation by
the mammalian Doublesex homolog DMRT1 in the juvenile testis.";
Proc. Natl. Acad. Sci. U.S.A. 107:13360-13365(2010).
[13]
FUNCTION, DNA-BINDING, AND TISSUE SPECIFICITY.
PubMed=20951351; DOI=10.1016/j.devcel.2010.09.010;
Matson C.K., Murphy M.W., Griswold M.D., Yoshida S., Bardwell V.J.,
Zarkower D.;
"The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper
that controls the mitosis versus meiosis decision in male germ
cells.";
Dev. Cell 19:612-624(2010).
[14]
FUNCTION.
PubMed=21621532; DOI=10.1016/j.ydbio.2011.05.658;
Krentz A.D., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
Zarkower D.;
"DMRT1 promotes oogenesis by transcriptional activation of Stra8 in
the mammalian fetal ovary.";
Dev. Biol. 356:63-70(2011).
[15]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=21775990; DOI=10.1038/nature10239;
Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
Zarkower D.;
"DMRT1 prevents female reprogramming in the postnatal mammalian
testis.";
Nature 476:101-104(2011).
[16]
ERRATUM.
Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J.,
Zarkower D.;
Nature 477:238-238(2011).
-!- FUNCTION: Transcription factor that plays a key role in male sex
determination and differentiation by controlling testis
development and male germ cell proliferation. Plays a central role
in spermatogonia by inhibiting meiosis in undifferentiated
spermatogonia and promoting mitosis, leading to spermatogonial
development and allowing abundant and continuous production of
sperm. Acts both as a transcription repressor and activator:
prevents meiosis by restricting retinoic acid (RA)-dependent
transcription and repressing STRA8 expression and promotes
spermatogonial development by activating spermatogonial
differentiation genes, such as SOHLH1. Also plays a key role in
postnatal sex maintenance by maintaining testis determination and
preventing feminization: represses transcription of female
promoting genes such as FOXL2 and activates male-specific genes.
May act as a tumor suppressor. May also play a minor role in
oogenesis. {ECO:0000269|PubMed:11040213,
ECO:0000269|PubMed:17540358, ECO:0000269|PubMed:20007774,
ECO:0000269|PubMed:20616082, ECO:0000269|PubMed:20951351,
ECO:0000269|PubMed:21621532, ECO:0000269|PubMed:21775990}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00070, ECO:0000269|PubMed:11040213}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1; Synonyms=Dmrt1a, Dmrt1a1, Dmrt1a2, Dmrt1a3;
IsoId=Q9QZ59-1; Sequence=Displayed;
Name=2; Synonyms=Dmrt1b, DMR1g, Dmrt1g;
IsoId=Q9QZ59-2; Sequence=VSP_042965;
Name=3; Synonyms=Dmrt1d;
IsoId=Q9QZ59-3; Sequence=VSP_042963;
Name=4; Synonyms=Dmrt1c;
IsoId=Q9QZ59-4; Sequence=VSP_042964;
-!- TISSUE SPECIFICITY: Testis-specific. In adult testis, expressed in
Sertoli cells in all regions of the seminiferous tubules.
Expressed dynamically in premeiotic germ cells (spermatogonia),
with high expression only in regions of the seminiferous tubule
that are early in the spermatogenic cycle (at protein level).
Expressed in all mitotic spermatogonia. Expression decreases with
the onset of spermatogonial differentiation and disappears at the
initiation of meiosis. {ECO:0000269|PubMed:11040213,
ECO:0000269|PubMed:20951351}.
-!- DEVELOPMENTAL STAGE: Detected already at 9.5 dpc. At 10.5 dpc,
expressed in the genital ridges of both sexes. At 14.5 dpc, during
gonadal sexual differentiation, expression declines in the ovary,
but is maintained in the testis, where it becomes restricted to
Sertoli and germ cells in the developing seminiferous tubules of
the testis. Accumulates primarily in Sertoli cells. From P1,
appears in germ cells and reach high levels by P7, just before
meiosis begins. From P7 through adult stage, present in Sertoli
cells and undifferentiated germ cells, but not in differentiating
germ cells. {ECO:0000269|PubMed:10545231,
ECO:0000269|PubMed:11040213}.
-!- DISRUPTION PHENOTYPE: Severe defects in the adult testis with
hypoplastic testes and disorganization of seminiferous tubules and
absence of germ cells, due to pre-meiotic germ cell death in
testes. Sertoli cell fail to differentiate. Female mutant mice
have normal ovaries and are fertile. Depending on the strain
background mice also show testis teratomas: deletion in 129/Sv
strain causes a high incidence of teratomas, whereas these tumors
do not form in C57BL/6J mutant mice. Deletion of Dmrt1 during
fetal development causes postnatal Sertoli cells to lose male-
promoting Sox9 and instead activation of female-promoting genes
such as Foxl2, leading to reprogrammation of Sertoli cells into
granulosa cells. As a consequence, theca cells form, estrogen is
produced and germ cells appear feminized.
{ECO:0000269|PubMed:11040213, ECO:0000269|PubMed:20007774,
ECO:0000269|PubMed:21775990}.
-!- SIMILARITY: Belongs to the DMRT family. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AF202778; AAF12826.1; -; mRNA.
EMBL; AL133300; CAB62040.1; -; mRNA.
EMBL; AY169785; AAO41733.1; -; mRNA.
EMBL; AY169786; AAO41734.1; -; mRNA.
EMBL; AY169787; AAO41735.1; -; mRNA.
EMBL; AY943925; AAY20941.1; -; mRNA.
EMBL; DQ530630; ABF83854.1; -; mRNA.
EMBL; AC132140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH466534; EDL41631.1; -; Genomic_DNA.
EMBL; BC125474; AAI25475.1; -; mRNA.
EMBL; AF192561; AAF05764.1; -; mRNA.
CCDS; CCDS29717.1; -. [Q9QZ59-1]
RefSeq; NP_056641.2; NM_015826.5. [Q9QZ59-1]
UniGene; Mm.391208; -.
ProteinModelPortal; Q9QZ59; -.
SMR; Q9QZ59; -.
IntAct; Q9QZ59; 1.
STRING; 10090.ENSMUSP00000025755; -.
iPTMnet; Q9QZ59; -.
PhosphoSitePlus; Q9QZ59; -.
PaxDb; Q9QZ59; -.
PRIDE; Q9QZ59; -.
Ensembl; ENSMUST00000025755; ENSMUSP00000025755; ENSMUSG00000024837. [Q9QZ59-1]
Ensembl; ENSMUST00000087525; ENSMUSP00000084803; ENSMUSG00000024837. [Q9QZ59-4]
GeneID; 50796; -.
KEGG; mmu:50796; -.
UCSC; uc008hbi.1; mouse. [Q9QZ59-1]
UCSC; uc012bjv.1; mouse. [Q9QZ59-4]
CTD; 1761; -.
MGI; MGI:1354733; Dmrt1.
eggNOG; KOG3815; Eukaryota.
eggNOG; ENOG410XSK9; LUCA.
GeneTree; ENSGT00550000074486; -.
HOGENOM; HOG000203592; -.
HOVERGEN; HBG055845; -.
InParanoid; Q9QZ59; -.
KO; K19488; -.
OMA; NMENRHA; -.
OrthoDB; EOG091G0PWB; -.
TreeFam; TF317837; -.
ChiTaRS; Dmrt1; mouse.
PRO; PR:Q9QZ59; -.
Proteomes; UP000000589; Chromosome 19.
Bgee; ENSMUSG00000024837; -.
Genevisible; Q9QZ59; MM.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0046982; F:protein heterodimerization activity; IPI:MGI.
GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:NTNU_SB.
GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
GO; GO:0003006; P:developmental process involved in reproduction; IGI:MGI.
GO; GO:0008354; P:germ cell migration; IMP:MGI.
GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
GO; GO:0002176; P:male germ cell proliferation; IMP:UniProtKB.
GO; GO:0008584; P:male gonad development; IMP:MGI.
GO; GO:0030238; P:male sex determination; IMP:UniProtKB.
GO; GO:0046661; P:male sex differentiation; IMP:UniProtKB.
GO; GO:0045835; P:negative regulation of meiotic nuclear division; IMP:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:0048599; P:oocyte development; IMP:MGI.
GO; GO:2000020; P:positive regulation of male gonad development; IMP:MGI.
GO; GO:0060903; P:positive regulation of meiosis I; IMP:MGI.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:1900107; P:regulation of nodal signaling pathway; IMP:MGI.
GO; GO:0060009; P:Sertoli cell development; IMP:MGI.
GO; GO:0060008; P:Sertoli cell differentiation; IMP:UniProtKB.
GO; GO:0007283; P:spermatogenesis; IMP:MGI.
Gene3D; 4.10.1040.10; -; 1.
InterPro; IPR001275; DM_DNA-bd.
InterPro; IPR026607; DMRT/dsx/mab-3.
InterPro; IPR022114; DMRT1-like.
PANTHER; PTHR12322; PTHR12322; 1.
Pfam; PF00751; DM; 1.
Pfam; PF12374; Dmrt1; 1.
SMART; SM00301; DM; 1.
SUPFAM; SSF82927; SSF82927; 1.
PROSITE; PS40000; DM_1; 1.
PROSITE; PS50809; DM_2; 1.
1: Evidence at protein level;
Activator; Alternative splicing; Complete proteome;
Developmental protein; Differentiation; DNA-binding; Metal-binding;
Nucleus; Phosphoprotein; Reference proteome; Repressor;
Sexual differentiation; Transcription; Transcription regulation;
Tumor suppressor; Zinc.
CHAIN 1 374 Doublesex- and mab-3-related
transcription factor 1.
/FTId=PRO_0000207043.
DNA_BIND 70 116 DM. {ECO:0000255|PROSITE-
ProRule:PRU00070}.
COMPBIAS 323 346 Pro/Ser-rich.
MOD_RES 337 337 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
VAR_SEQ 1 180 Missing (in isoform 3).
{ECO:0000303|PubMed:17141192}.
/FTId=VSP_042963.
VAR_SEQ 178 374 EGRMVIQDIPAVTSRGHMENTSDLVSDPAYYSSFYQPSLFP
YYNNLYNYPQYSMALSAESSSGEVGNSLGGSPVKNSLRSLP
APYVPAQTGNQWQMKTSESRHPVSSQYRMHSYYGPPSYLGQ
SMSQIFTFEEGPSYSEAKASVFSPPSSQDSGLVSLSSSSPM
SNESSKGVLECESASSEPSSYAVNQVLEEDEDE -> DEDL
REPPPSELPVPDALILRASLLPGPEHVPDLYLRGRPLLLRS
QSQCVLAPQQSRFWLGLPLQQLSDEQRELEGSSGM (in
isoform 4).
{ECO:0000303|PubMed:17141192}.
/FTId=VSP_042964.
VAR_SEQ 213 374 Missing (in isoform 2).
{ECO:0000303|PubMed:17141192}.
/FTId=VSP_042965.
CONFLICT 25 25 Q -> K (in Ref. 1; AAF12826).
{ECO:0000305}.
CONFLICT 306 306 F -> L (in Ref. 2; CAB62040).
{ECO:0000305}.
CONFLICT 365 365 N -> S (in Ref. 2; CAB62040).
{ECO:0000305}.
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


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