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Doublesex- and mab-3-related transcription factor 2 (Doublesex-like 2 protein) (Terra)

 DMRT2_MOUSE             Reviewed;         561 AA.
Q8BG36; Q3USI4; Q3USI7; Q8K185; Q9JJU0; Q9JJU3; Q9WVM0;
24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
01-MAR-2003, sequence version 1.
25-OCT-2017, entry version 104.
RecName: Full=Doublesex- and mab-3-related transcription factor 2 {ECO:0000250|UniProtKB:Q9Y5R5, ECO:0000312|EMBL:AAN77205.1};
AltName: Full=Doublesex-like 2 protein {ECO:0000250|UniProtKB:Q9Y5R5};
AltName: Full=Terra {ECO:0000303|PubMed:10021344, ECO:0000312|EMBL:AAD38425.1};
Name=Dmrt2 {ECO:0000312|EMBL:AAN77205.1,
ECO:0000312|Ensembl:ENSMUSP00000059654, ECO:0000312|MGI:MGI:1330307};
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1] {ECO:0000305, ECO:0000312|EMBL:AAN77205.1}
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
STAGE.
STRAIN=CD-1 {ECO:0000269|PubMed:12609607};
TISSUE=Embryo {ECO:0000312|EMBL:AAN77205.1};
PubMed=12609607; DOI=10.1016/S1567-133X(02)00071-6;
Kim S., Kettlewell J.R., Anderson R.C., Bardwell V.J., Zarkower D.;
"Sexually dimorphic expression of multiple doublesex-related genes in
the embryonic mouse gonad.";
Gene Expr. Patterns 3:77-82(2003).
[2] {ECO:0000312|EMBL:BAC32130.1}
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC32130.1};
TISSUE=Adipose tissue {ECO:0000312|EMBL:BAE24344.1}, and
Embryo {ECO:0000312|EMBL:BAC32130.1};
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[3] {ECO:0000312|Ensembl:ENSMUSP00000059654}
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000059654};
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).
[4] {ECO:0000312|EMBL:EDL41636.1}
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.
[5] {ECO:0000305, ECO:0000312|EMBL:CAB93343.1}
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-176 AND 213-455.
PubMed=10857744; DOI=10.1006/geno.2000.6160;
Calvari V., Bertini V., De Grandi A., Peverali G., Zuffardi O.,
Ferguson-Smith M., Knudtzon J., Camerino G., Borsani G., Guioli S.;
"A new submicroscopic deletion that refines the 9p region for sex
reversal.";
Genomics 65:203-212(2000).
[6] {ECO:0000305, ECO:0000312|EMBL:AAD38425.1}
NUCLEOTIDE SEQUENCE [MRNA] OF 224-561, FUNCTION, AND DEVELOPMENTAL
STAGE.
PubMed=10021344;
Meng A., Moore B., Tang H., Yuan B., Lin S.;
"A Drosophila doublesex-related gene, terra, is involved in
somitogenesis in vertebrates.";
Development 126:1259-1268(1999).
[7] {ECO:0000305, ECO:0000312|EMBL:AAH27669.1}
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 224-561.
TISSUE=Mammary gland {ECO:0000312|EMBL:AAH27669.1};
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).
[8] {ECO:0000305}
FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
PubMed=16387292; DOI=10.1016/j.ydbio.2005.11.027;
Seo K.W., Wang Y., Kokubo H., Kettlewell J.R., Zarkower D.A.,
Johnson R.L.;
"Targeted disruption of the DM domain containing transcription factor
Dmrt2 reveals an essential role in somite patterning.";
Dev. Biol. 290:200-210(2006).
[9] {ECO:0000305}
FUNCTION, DNA-BINDING, SUBUNIT, AND SUBCELLULAR LOCATION.
PubMed=17605809; DOI=10.1186/1471-2199-8-58;
Murphy M.W., Zarkower D., Bardwell V.J.;
"Vertebrate DM domain proteins bind similar DNA sequences and can
heterodimerize on DNA.";
BMC Mol. Biol. 8:58-58(2007).
[10] {ECO:0000305}
DISRUPTION PHENOTYPE.
PubMed=17974128;
Seo K.W.;
"Dmrt2 and Pax3 double-knockout mice show severe defects in embryonic
myogenesis.";
Comp. Med. 57:460-468(2007).
[11] {ECO:0000305}
FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
INDUCTION BY PAX3, AND DISRUPTION PHENOTYPE.
PubMed=20368965; DOI=10.1371/journal.pgen.1000897;
Sato T., Rocancourt D., Marques L., Thorsteinsdottir S.,
Buckingham M.;
"A Pax3/Dmrt2/Myf5 regulatory cascade functions at the onset of
myogenesis.";
PLoS Genet. 6:E1000897-E1000897(2010).
[12] {ECO:0000305}
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=21203428; DOI=10.1371/journal.pone.0014438;
Lourenco R., Lopes S.S., Saude L.;
"Left-right function of dmrt2 genes is not conserved between zebrafish
and mouse.";
PLoS ONE 5:E14438-E14438(2010).
-!- FUNCTION: Transcriptional activator that directly regulates early
activation of the myogenic determination gene MYF5 by binding in a
sequence-specific manner to the early epaxial enhancer element of
it. Involved in somitogenesis during embryogenesis and somite
development and differentiation into sclerotome and dermomyotome.
Required for the initiation and/or maintenance of proper
organization of the sclerotome, dermomyotome and myotome. Is not
required for sex determination and/or differentiation in embryonic
development. Also not involved in symmetric somite formation and
hence does not regulate the laterality pathway that controls left-
right asymmetric organ positioning. {ECO:0000269|PubMed:10021344,
ECO:0000269|PubMed:16387292, ECO:0000269|PubMed:17605809,
ECO:0000269|PubMed:20368965, ECO:0000269|PubMed:21203428}.
-!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17605809}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00070, ECO:0000269|PubMed:17605809}.
-!- TISSUE SPECIFICITY: Expressed in testis.
{ECO:0000269|PubMed:12609607, ECO:0000269|PubMed:20368965}.
-!- DEVELOPMENTAL STAGE: Expressed in presomitic mesoderm and
developing somites at embryonic day 8.5 (E8.5) accumulating in the
epaxial domain at E9.5 in the immature caudal somites. At E10.5
expressed in the dermomyotome of somites. By E11.5, only
detectable in caudal somites. In mature somites, expression is
confined to the dermomyotome of the somite where Pax3 is also
expressed and in the epaxial domain of the most immature caudal
somites. At this stage, the most mature anterior somites are
beginning to lose the expression at the epaxial and hypaxial
extremities of the dermomyotome. At E14.5 expressed in testis,
heart and brain. Expression is also detected in proximal forelimb
buds and branchial arches of the developing embryo.
{ECO:0000269|PubMed:10021344, ECO:0000269|PubMed:12609607,
ECO:0000269|PubMed:16387292, ECO:0000269|PubMed:20368965}.
-!- INDUCTION: Transcriptionally up-regulated by PAX3 within the
dermomyotome. {ECO:0000269|PubMed:20368965}.
-!- DISRUPTION PHENOTYPE: Mice heterozygous for Dmrt2 mutation exhibit
no visible phenotype. Homozygotes are perinatally lethal due to
signs of respiratory distress. They have rib, sternal, vertebral
and skull base malformations. Expression of myogenic growth
factors, such as Pax3 and Myog, the growth factor Pdgfa, cadherin
Cdh2, and the filament protein Des is abnormal. Mutants lack most
or all of the epithelial organization seen in wild-type somites,
sclerotome and dermomyotome. Mutants have disrupted production of
matrix components including laminin-1 in the dermomyotome.
Arrangement of the myogenic cells of the inter-limb somites is
abnormal. Myf5 activation in the epaxial domain is retarded thus
having consequences in the myogenesis by delaying expression of
Myog. Mutants do not have left-right defects regarding internal
organs positioning. Dmrt2 and Pax3 double null mutant embryos
exhibit suspended development and Myog expression is markedly
decreased and its expression pattern dramatically distorted.
{ECO:0000269|PubMed:16387292, ECO:0000269|PubMed:17974128,
ECO:0000269|PubMed:20368965, ECO:0000269|PubMed:21203428}.
-!- SIMILARITY: Belongs to the DMRT family. {ECO:0000255}.
-!- SEQUENCE CAUTION:
Sequence=AAD38425.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
Sequence=AAH27669.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=BAE24347.1; Type=Frameshift; Positions=548; Evidence={ECO:0000305};
Sequence=CAB93343.1; Type=Frameshift; Positions=90, 114; Evidence={ECO:0000305};
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EMBL; AF539811; AAN77205.1; -; mRNA.
EMBL; AK044891; BAC32130.1; -; mRNA.
EMBL; AK140337; BAE24344.1; -; mRNA.
EMBL; AK140347; BAE24347.1; ALT_FRAME; mRNA.
EMBL; AC124540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC132140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH466534; EDL41636.1; -; Genomic_DNA.
EMBL; AJ276456; CAB93343.1; ALT_FRAME; Genomic_DNA.
EMBL; AJ276459; CAB93346.1; -; Genomic_DNA.
EMBL; AF080623; AAD38425.1; ALT_SEQ; mRNA.
EMBL; BC027669; AAH27669.1; ALT_INIT; mRNA.
CCDS; CCDS29719.1; -.
RefSeq; NP_665830.1; NM_145831.3.
UniGene; Mm.275572; -.
ProteinModelPortal; Q8BG36; -.
SMR; Q8BG36; -.
BioGrid; 230465; 25.
STRING; 10090.ENSMUSP00000059654; -.
PhosphoSitePlus; Q8BG36; -.
PaxDb; Q8BG36; -.
PRIDE; Q8BG36; -.
Ensembl; ENSMUST00000053068; ENSMUSP00000059654; ENSMUSG00000048138.
GeneID; 226049; -.
KEGG; mmu:226049; -.
UCSC; uc008hbm.1; mouse.
CTD; 10655; -.
MGI; MGI:1330307; Dmrt2.
eggNOG; KOG3815; Eukaryota.
eggNOG; ENOG410XSK9; LUCA.
GeneTree; ENSGT00550000074486; -.
HOGENOM; HOG000049088; -.
HOVERGEN; HBG055968; -.
InParanoid; Q8BG36; -.
KO; K19489; -.
OMA; PKKHREC; -.
OrthoDB; EOG091G0R96; -.
PhylomeDB; Q8BG36; -.
TreeFam; TF317837; -.
PRO; PR:Q8BG36; -.
Proteomes; UP000000589; Chromosome 19.
Bgee; ENSMUSG00000048138; -.
Genevisible; Q8BG36; MM.
GO; GO:0005634; C:nucleus; ISO:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IC:NTNU_SB.
GO; GO:0048706; P:embryonic skeletal system development; IMP:MGI.
GO; GO:2000287; P:positive regulation of myotome development; IMP:MGI.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:NTNU_SB.
GO; GO:0014807; P:regulation of somitogenesis; IMP:MGI.
Gene3D; 4.10.1040.10; -; 1.
InterPro; IPR001275; DM_DNA-bd.
InterPro; IPR036407; DM_DNA-bd_sf.
InterPro; IPR026607; DMRT/dsx/mab-3.
PANTHER; PTHR12322; PTHR12322; 1.
Pfam; PF00751; DM; 1.
SMART; SM00301; DM; 1.
SUPFAM; SSF82927; SSF82927; 1.
PROSITE; PS40000; DM_1; 1.
PROSITE; PS50809; DM_2; 1.
1: Evidence at protein level;
Complete proteome; DNA-binding; Metal-binding; Nucleus;
Reference proteome; Transcription; Transcription regulation; Zinc.
CHAIN 1 561 Doublesex- and mab-3-related
transcription factor 2.
/FTId=PRO_0000423010.
DNA_BIND 123 170 DM. {ECO:0000255|PROSITE-
ProRule:PRU00070}.
COMPBIAS 47 57 Poly-Glu. {ECO:0000255}.
CONFLICT 19 19 S -> I (in Ref. 2; BAE24344/BAE24347).
{ECO:0000305}.
CONFLICT 90 90 P -> A (in Ref. 5; CAB93343).
{ECO:0000305}.
CONFLICT 176 176 D -> V (in Ref. 5; CAB93343).
{ECO:0000305}.
CONFLICT 274 274 M -> K (in Ref. 6; AAD38425).
{ECO:0000305}.
CONFLICT 434 434 R -> Q (in Ref. 2; BAE24344/BAE24347).
{ECO:0000305}.
CONFLICT 524 524 D -> E (in Ref. 2; BAE24344/BAE24347).
{ECO:0000305}.
CONFLICT 547 547 S -> L (in Ref. 2; BAE24347).
{ECO:0000305}.
SEQUENCE 561 AA; 61641 MW; CC4430D9F9EC4D68 CRC64;
MTEGQAVPGV GDWEIDVESL DLEEDSCGTP LRATPPQEPS PAAADGEEDE DEEEEDEDVE
DEGDGEEPGV SSEVPGRPEQ PGGLAPRPPP AAQALPAAAA APERGATAGG GAEPRKLSRT
PKCARCRNHG VVSCLKGHKR FCRWRDCQCA NCLLVVERQR VMAAQVALRR QQATEDKKGL
SGKQNNFDRK AVYQRQVRAP SLLAKSILEG YRPMTAETYL GGTLPLPPPV SDRMRKRRAF
ADKELENIML EREYKEREML ETSQAAALFL PNRMVPGPEY SSYKGTYSPT AGELPSKDFC
NFLPTCLDLT MQYSGSGNME LISSNVSVAT TYRQYPLSSR FLVWPKCGPI SDTLLYQQYL
LNATTSVQAL KPGTGWDLKG TRVQDGLSAE QDMMPPKLEG SLVLPHLPEV PASRTDLQVH
QVVPERSAFS PPGRNFSPIV DMDCLAAQGH VLTKLSKENT RPSLPLKTNP FHSVFQQTLS
DKSGPELNAP FVKEAFEETP KKHRECLVKE SQKYTFTIDR CAKDLFVAKQ VGTKLSANEP
LSFSVESILK RPSSAVTHVS Q


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