DMRT2_MOUSE
ID DMRT2_MOUSE Reviewed; 561 AA.
AC Q8BG36; Q3USI4; Q3USI7; Q8K185; Q9JJU0; Q9JJU3; Q9WVM0;
DT 24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Doublesex- and mab-3-related transcription factor 2 {ECO:0000250|UniProtKB:Q9Y5R5, ECO:0000312|EMBL:AAN77205.1};
DE AltName: Full=Doublesex-like 2 protein {ECO:0000250|UniProtKB:Q9Y5R5};
DE AltName: Full=Terra {ECO:0000303|PubMed:10021344, ECO:0000312|EMBL:AAD38425.1};
GN Name=Dmrt2 {ECO:0000312|EMBL:AAN77205.1,
GN ECO:0000312|Ensembl:ENSMUSP00000059654, ECO:0000312|MGI:MGI:1330307};
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] {ECO:0000305, ECO:0000312|EMBL:AAN77205.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=CD-1 {ECO:0000269|PubMed:12609607};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAN77205.1};
RX PubMed=12609607; DOI=10.1016/s1567-133x(02)00071-6;
RA Kim S., Kettlewell J.R., Anderson R.C., Bardwell V.J., Zarkower D.;
RT "Sexually dimorphic expression of multiple doublesex-related genes in the
RT embryonic mouse gonad.";
RL Gene Expr. Patterns 3:77-82(2003).
RN [2] {ECO:0000312|EMBL:BAC32130.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC32130.1};
RC TISSUE=Adipose tissue {ECO:0000312|EMBL:BAE24344.1}, and
RC Embryo {ECO:0000312|EMBL:BAC32130.1};
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 [3] {ECO:0000312|Ensembl:ENSMUSP00000059654}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000059654};
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 [4] {ECO:0000312|EMBL:EDL41636.1}
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 [5] {ECO:0000305, ECO:0000312|EMBL:CAB93343.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-176 AND 213-455.
RX PubMed=10857744; DOI=10.1006/geno.2000.6160;
RA Calvari V., Bertini V., De Grandi A., Peverali G., Zuffardi O.,
RA Ferguson-Smith M., Knudtzon J., Camerino G., Borsani G., Guioli S.;
RT "A new submicroscopic deletion that refines the 9p region for sex
RT reversal.";
RL Genomics 65:203-212(2000).
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAD38425.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 224-561, FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=10021344; DOI=10.1242/dev.126.6.1259;
RA Meng A., Moore B., Tang H., Yuan B., Lin S.;
RT "A Drosophila doublesex-related gene, terra, is involved in somitogenesis
RT in vertebrates.";
RL Development 126:1259-1268(1999).
RN [7] {ECO:0000305, ECO:0000312|EMBL:AAH27669.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 224-561.
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH27669.1};
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 [8] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16387292; DOI=10.1016/j.ydbio.2005.11.027;
RA Seo K.W., Wang Y., Kokubo H., Kettlewell J.R., Zarkower D.A., Johnson R.L.;
RT "Targeted disruption of the DM domain containing transcription factor Dmrt2
RT reveals an essential role in somite patterning.";
RL Dev. Biol. 290:200-210(2006).
RN [9] {ECO:0000305}
RP FUNCTION, DNA-BINDING, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17605809; DOI=10.1186/1471-2199-8-58;
RA Murphy M.W., Zarkower D., Bardwell V.J.;
RT "Vertebrate DM domain proteins bind similar DNA sequences and can
RT heterodimerize on DNA.";
RL BMC Mol. Biol. 8:58-58(2007).
RN [10] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=17974128;
RA Seo K.W.;
RT "Dmrt2 and Pax3 double-knockout mice show severe defects in embryonic
RT myogenesis.";
RL Comp. Med. 57:460-468(2007).
RN [11] {ECO:0000305}
RP FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION
RP BY PAX3, AND DISRUPTION PHENOTYPE.
RX PubMed=20368965; DOI=10.1371/journal.pgen.1000897;
RA Sato T., Rocancourt D., Marques L., Thorsteinsdottir S., Buckingham M.;
RT "A Pax3/Dmrt2/Myf5 regulatory cascade functions at the onset of
RT myogenesis.";
RL PLoS Genet. 6:E1000897-E1000897(2010).
RN [12] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21203428; DOI=10.1371/journal.pone.0014438;
RA Lourenco R., Lopes S.S., Saude L.;
RT "Left-right function of dmrt2 genes is not conserved between zebrafish and
RT mouse.";
RL PLoS ONE 5:E14438-E14438(2010).
CC -!- FUNCTION: Transcriptional activator that directly regulates early
CC activation of the myogenic determination gene MYF5 by binding in a
CC sequence-specific manner to the early epaxial enhancer element of it.
CC Involved in somitogenesis during embryogenesis and somite development
CC and differentiation into sclerotome and dermomyotome. Required for the
CC initiation and/or maintenance of proper organization of the sclerotome,
CC dermomyotome and myotome. Is not required for sex determination and/or
CC differentiation in embryonic development. Also not involved in
CC symmetric somite formation and hence does not regulate the laterality
CC pathway that controls left-right asymmetric organ positioning.
CC {ECO:0000269|PubMed:10021344, ECO:0000269|PubMed:16387292,
CC ECO:0000269|PubMed:17605809, ECO:0000269|PubMed:20368965,
CC ECO:0000269|PubMed:21203428}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17605809}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00070,
CC ECO:0000269|PubMed:17605809}.
CC -!- TISSUE SPECIFICITY: Expressed in testis. {ECO:0000269|PubMed:12609607,
CC ECO:0000269|PubMed:20368965}.
CC -!- DEVELOPMENTAL STAGE: Expressed in presomitic mesoderm and developing
CC somites at 8.5 dpc, accumulating in the epaxial domain at 9.5 dpc in
CC the immature caudal somites. At 10.5 dpc expressed in the dermomyotome
CC of somites. By 11.5 dpc, only detectable in caudal somites. In mature
CC somites, expression is confined to the dermomyotome of the somite where
CC Pax3 is also expressed and in the epaxial domain of the most immature
CC caudal somites. At this stage, the most mature anterior somites are
CC beginning to lose the expression at the epaxial and hypaxial
CC extremities of the dermomyotome. At 14.5 dpc expressed in testis, heart
CC and brain. Expression is also detected in proximal forelimb buds and
CC branchial arches of the developing embryo.
CC {ECO:0000269|PubMed:10021344, ECO:0000269|PubMed:12609607,
CC ECO:0000269|PubMed:16387292, ECO:0000269|PubMed:20368965}.
CC -!- INDUCTION: Transcriptionally up-regulated by PAX3 within the
CC dermomyotome. {ECO:0000269|PubMed:20368965}.
CC -!- DISRUPTION PHENOTYPE: Mice heterozygous for Dmrt2 mutation exhibit no
CC visible phenotype. Homozygotes are perinatally lethal due to signs of
CC respiratory distress. They have rib, sternal, vertebral and skull base
CC malformations. Expression of myogenic growth factors, such as Pax3 and
CC Myog, the growth factor Pdgfa, cadherin Cdh2, and the filament protein
CC Des is abnormal. Mutants lack most or all of the epithelial
CC organization seen in wild-type somites, sclerotome and dermomyotome.
CC Mutants have disrupted production of matrix components including
CC laminin-1 in the dermomyotome. Arrangement of the myogenic cells of the
CC inter-limb somites is abnormal. Myf5 activation in the epaxial domain
CC is retarded thus having consequences in the myogenesis by delaying
CC expression of Myog. Mutants do not have left-right defects regarding
CC internal organs positioning. Dmrt2 and Pax3 double null mutant embryos
CC exhibit suspended development and Myog expression is markedly decreased
CC and its expression pattern dramatically distorted.
CC {ECO:0000269|PubMed:16387292, ECO:0000269|PubMed:17974128,
CC ECO:0000269|PubMed:20368965, ECO:0000269|PubMed:21203428}.
CC -!- SIMILARITY: Belongs to the DMRT family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD38425.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC Sequence=AAH27669.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE24347.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB93343.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF539811; AAN77205.1; -; mRNA.
DR EMBL; AK044891; BAC32130.1; -; mRNA.
DR EMBL; AK140337; BAE24344.1; -; mRNA.
DR EMBL; AK140347; BAE24347.1; ALT_FRAME; mRNA.
DR EMBL; AC124540; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC132140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466534; EDL41636.1; -; Genomic_DNA.
DR EMBL; AJ276456; CAB93343.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AJ276459; CAB93346.1; -; Genomic_DNA.
DR EMBL; AF080623; AAD38425.1; ALT_SEQ; mRNA.
DR EMBL; BC027669; AAH27669.1; ALT_INIT; mRNA.
DR CCDS; CCDS29719.1; -.
DR RefSeq; NP_665830.1; NM_145831.3.
DR AlphaFoldDB; Q8BG36; -.
DR SMR; Q8BG36; -.
DR BioGRID; 230465; 25.
DR STRING; 10090.ENSMUSP00000059654; -.
DR PhosphoSitePlus; Q8BG36; -.
DR PaxDb; Q8BG36; -.
DR PRIDE; Q8BG36; -.
DR ProteomicsDB; 279439; -.
DR Antibodypedia; 9092; 73 antibodies from 19 providers.
DR DNASU; 226049; -.
DR Ensembl; ENSMUST00000053068; ENSMUSP00000059654; ENSMUSG00000048138.
DR GeneID; 226049; -.
DR KEGG; mmu:226049; -.
DR UCSC; uc008hbm.1; mouse.
DR CTD; 10655; -.
DR MGI; MGI:1330307; Dmrt2.
DR VEuPathDB; HostDB:ENSMUSG00000048138; -.
DR eggNOG; KOG3815; Eukaryota.
DR GeneTree; ENSGT00940000156282; -.
DR HOGENOM; CLU_030932_0_0_1; -.
DR InParanoid; Q8BG36; -.
DR OMA; YKFTIDR; -.
DR OrthoDB; 897429at2759; -.
DR PhylomeDB; Q8BG36; -.
DR TreeFam; TF317837; -.
DR BioGRID-ORCS; 226049; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Dmrt2; mouse.
DR PRO; PR:Q8BG36; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8BG36; protein.
DR Bgee; ENSMUSG00000048138; Expressed in tail connective tissue and 81 other tissues.
DR Genevisible; Q8BG36; MM.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP: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:0048706; P:embryonic skeletal system development; IMP:MGI.
DR GO; GO:0061055; P:myotome development; IMP:MGI.
DR GO; GO:2000287; P:positive regulation of myotome development; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB.
DR GO; GO:0014807; P:regulation of somitogenesis; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007548; P:sex differentiation; IBA:GO_Central.
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 PANTHER; PTHR12322; PTHR12322; 1.
DR Pfam; PF00751; DM; 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 DNA-binding; Metal-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..561
FT /note="Doublesex- and mab-3-related transcription factor 2"
FT /id="PRO_0000423010"
FT DNA_BIND 123..170
FT /note="DM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00070"
FT REGION 1..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..68
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..95
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 19
FT /note="S -> I (in Ref. 2; BAE24344/BAE24347)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="P -> A (in Ref. 5; CAB93343)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="D -> V (in Ref. 5; CAB93343)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="M -> K (in Ref. 6; AAD38425)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="R -> Q (in Ref. 2; BAE24344/BAE24347)"
FT /evidence="ECO:0000305"
FT CONFLICT 524
FT /note="D -> E (in Ref. 2; BAE24344/BAE24347)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="S -> L (in Ref. 2; BAE24347)"
FT /evidence="ECO:0000305"
SQ 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
