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Q9QZ59 (DMRT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Doublesex- and mab-3-related transcription factor 1
Gene names
Name:Dmrt1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length374 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Subcellular location

Nucleus Ref.8.

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. Ref.8 Ref.12

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. Ref.1 Ref.8

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. Dpedending on the strain backgroundm ice 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. Ref.8 Ref.10 Ref.14

Sequence similarities

Belongs to the DMRT family.

Contains 1 DM DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Sexual differentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseTumor suppressor
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Developmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from mutant phenotype Ref.14. Source: MGI

Sertoli cell differentiation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

cell morphogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

developmental process involved in reproduction

Inferred from genetic interaction Ref.9. Source: MGI

germ cell migration

Inferred from mutant phenotype Ref.9. Source: MGI

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

male germ cell proliferation

Inferred from mutant phenotype Ref.10Ref.12. Source: UniProtKB

male gonad development

Inferred from mutant phenotype Ref.9. Source: MGI

male sex determination

Inferred from mutant phenotype Ref.8Ref.10Ref.12. Source: UniProtKB

male sex differentiation

Inferred from mutant phenotype Ref.8Ref.10Ref.12. Source: UniProtKB

negative regulation of meiosis

Inferred from mutant phenotype Ref.12. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.10Ref.11Ref.12. Source: UniProtKB

oocyte development

Inferred from mutant phenotype Ref.13. Source: MGI

positive regulation of male gonad development

Inferred from mutant phenotype Ref.14. Source: MGI

positive regulation of meiosis I

Inferred from mutant phenotype Ref.13. Source: MGI

positive regulation of mitosis

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.11Ref.12. Source: UniProtKB

regulation of nodal signaling pathway

Inferred from mutant phenotype PubMed 23473982. Source: MGI

spermatogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.13. Source: MGI

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from direct assay PubMed 23473982. Source: MGI

core promoter proximal region sequence-specific DNA binding

Inferred from direct assay Ref.11Ref.12. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein heterodimerization activity

Inferred from physical interaction PubMed 17605809. Source: MGI

protein homodimerization activity

Inferred from direct assay PubMed 17605809. Source: MGI

sequence-specific DNA binding

Inferred from direct assay PubMed 17605809. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QZ59-1)

Also known as: Dmrt1a; Dmrt1a1; Dmrt1a2; Dmrt1a3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9QZ59-2)

Also known as: Dmrt1b; DMR1g; Dmrt1g;

The sequence of this isoform differs from the canonical sequence as follows:
     213-374: Missing.
Isoform 3 (identifier: Q9QZ59-3)

Also known as: Dmrt1d;

The sequence of this isoform differs from the canonical sequence as follows:
     1-180: Missing.
Isoform 4 (identifier: Q9QZ59-4)

Also known as: Dmrt1c;

The sequence of this isoform differs from the canonical sequence as follows:
     178-374: EGRMVIQDIP...NQVLEEDEDE → DEDLREPPPS...QRELEGSSGM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 374374Doublesex- and mab-3-related transcription factor 1
PRO_0000207043

Regions

DNA binding70 – 11647DM Ref.11 Ref.12
Compositional bias323 – 34624Pro/Ser-rich

Natural variations

Alternative sequence1 – 180180Missing in isoform 3.
VSP_042963
Alternative sequence178 – 374197EGRMV…EDEDE → DEDLREPPPSELPVPDALIL RASLLPGPEHVPDLYLRGRP LLLRSQSQCVLAPQQSRFWL GLPLQQLSDEQRELEGSSGM in isoform 4.
VSP_042964
Alternative sequence213 – 374162Missing in isoform 2.
VSP_042965

Experimental info

Sequence conflict251Q → K in AAF12826. Ref.1
Sequence conflict3061F → L in CAB62040. Ref.2
Sequence conflict3651N → S in CAB62040. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Dmrt1a) (Dmrt1a1) (Dmrt1a2) (Dmrt1a3) [UniParc].

Last modified April 18, 2012. Version 2.
Checksum: B6C4601432007C35

FASTA37439,444
        10         20         30         40         50         60 
MPNDDTFGKP STPTEVPHAP GAPPQGKAGG YSKAAGAMAG AAGGSGAGGS GGASGSGPSG 

        70         80         90        100        110        120 
LGSGSKKSPR LPKCARCRNH GYASPLKGHK RFCMWRDCQC KKCSLIAERQ RVMAAQVALR 

       130        140        150        160        170        180 
RQQAQEEELG ISHPIPLPSA AELLVKRENN ASNPCLMAEN SSSAQPPPAS TPTPAASEGR 

       190        200        210        220        230        240 
MVIQDIPAVT SRGHMENTSD LVSDPAYYSS FYQPSLFPYY NNLYNYPQYS MALSAESSSG 

       250        260        270        280        290        300 
EVGNSLGGSP VKNSLRSLPA PYVPAQTGNQ WQMKTSESRH PVSSQYRMHS YYGPPSYLGQ 

       310        320        330        340        350        360 
SMSQIFTFEE GPSYSEAKAS VFSPPSSQDS GLVSLSSSSP MSNESSKGVL ECESASSEPS 

       370 
SYAVNQVLEE DEDE 

« Hide

Isoform 2 (Dmrt1b) (DMR1g) (Dmrt1g) [UniParc].

Checksum: 995A1A053EFC8840
Show »

FASTA21221,891
Isoform 3 (Dmrt1d) [UniParc].

Checksum: 69A02CDAABC2DE47
Show »

FASTA19421,148
Isoform 4 (Dmrt1c) [UniParc].

Checksum: ED63F763E109DB2B
Show »

FASTA25726,906

References

« Hide 'large scale' references
[1]"Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development."
Raymond C.S., Kettlewell J.R., Hirsch B., Bardwell V.J., Zarkower D.
Dev. Biol. 215:208-220(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE.
Strain: C57BL/6.
Tissue: Testis.
[2]"The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation."
De Grandi A., Calvari V., Bertini V., Bulfone A., Peverali G., Camerino G., Borsani G., Guioli S.
Mech. Dev. 90:323-326(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
Tissue: Testis.
[3]"Multiple alternative splicing of mouse Dmrt1 during gonadal differentiation."
Lu H., Huang X., Zhang L., Guo Y., Cheng H., Zhou R.
Biochem. Biophys. Res. Commun. 352:630-634(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
Strain: Kunming.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
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. expand/collapse author list , 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.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Conservation of a sex-determining gene."
Smith C.A., McClive P.J., Western P.S., Reed K.J., Sinclair A.H.
Nature 402:601-602(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 104-203 (ISOFORM 1).
Tissue: Embryonic testis.
[8]"Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation."
Raymond C.S., Murphy M.W., O'Sullivan M.G., Bardwell V.J., Zarkower D.
Genes Dev. 14:2587-2595(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[9]"Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation."
Kim S., Bardwell V.J., Zarkower D.
Dev. Biol. 307:314-327(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ cell proliferation and pluripotency."
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.
Proc. Natl. Acad. Sci. U.S.A. 106:22323-22328(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
Strain: 129/Sv.
[11]"Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis."
Murphy M.W., Sarver A.L., Rice D., Hatzi K., Ye K., Melnick A., Heckert L.L., Zarkower D., Bardwell V.J.
Proc. Natl. Acad. Sci. U.S.A. 107:13360-13365(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[12]"The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells."
Matson C.K., Murphy M.W., Griswold M.D., Yoshida S., Bardwell V.J., Zarkower D.
Dev. Cell 19:612-624(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, TISSUE SPECIFICITY.
[13]"DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary."
Krentz A.D., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J., Zarkower D.
Dev. Biol. 356:63-70(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"DMRT1 prevents female reprogramming in the postnatal mammalian testis."
Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J., Zarkower D.
Nature 476:101-104(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[15]Erratum
Matson C.K., Murphy M.W., Sarver A.L., Griswold M.D., Bardwell V.J., Zarkower D.
Nature 477:238-238(2011)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF202778 mRNA. Translation: AAF12826.1.
AL133300 mRNA. Translation: CAB62040.1.
AY169785 mRNA. Translation: AAO41733.1.
AY169786 mRNA. Translation: AAO41734.1.
AY169787 mRNA. Translation: AAO41735.1.
AY943925 mRNA. Translation: AAY20941.1.
DQ530630 mRNA. Translation: ABF83854.1.
AC132140 Genomic DNA. No translation available.
CH466534 Genomic DNA. Translation: EDL41631.1.
BC125474 mRNA. Translation: AAI25475.1.
AF192561 mRNA. Translation: AAF05764.1.
RefSeqNP_056641.2. NM_015826.5.
UniGeneMm.391208.

3D structure databases

ProteinModelPortalQ9QZ59.
SMRQ9QZ59. Positions 68-116.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9QZ59. 1 interaction.

PTM databases

PhosphoSiteQ9QZ59.

Proteomic databases

PaxDbQ9QZ59.
PRIDEQ9QZ59.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025755; ENSMUSP00000025755; ENSMUSG00000024837. [Q9QZ59-1]
ENSMUST00000087525; ENSMUSP00000084803; ENSMUSG00000024837. [Q9QZ59-4]
GeneID50796.
KEGGmmu:50796.
UCSCuc008hbi.1. mouse.
uc012bjv.1. mouse.

Organism-specific databases

CTD1761.
MGIMGI:1354733. Dmrt1.

Phylogenomic databases

eggNOGNOG271390.
GeneTreeENSGT00550000074486.
HOGENOMHOG000059585.
HOVERGENHBG055845.
InParanoidQ9QZ59.
OMAECEPASE.
OrthoDBEOG7K3TMG.
TreeFamTF317837.

Gene expression databases

BgeeQ9QZ59.
GenevestigatorQ9QZ59.

Family and domain databases

Gene3D4.10.1040.10. 1 hit.
InterProIPR001275. DM_DNA-bd.
IPR026607. DMRT/dsx/mab-3.
IPR022114. DMRT1-like.
[Graphical view]
PANTHERPTHR12322. PTHR12322. 1 hit.
PfamPF00751. DM. 1 hit.
PF12374. Dmrt1. 1 hit.
[Graphical view]
SMARTSM00301. DM. 1 hit.
[Graphical view]
SUPFAMSSF82927. SSF82927. 1 hit.
PROSITEPS40000. DM_1. 1 hit.
PS50809. DM_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDMRT1. mouse.
NextBio307801.
PROQ9QZ59.
SOURCESearch...

Entry information

Entry nameDMRT1_MOUSE
AccessionPrimary (citable) accession number: Q9QZ59
Secondary accession number(s): Q19AV2 expand/collapse secondary AC list , Q2TDQ9, Q6Y951, Q6Y953, Q9QZ37, Q9QZA4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: April 18, 2012
Last modified: April 16, 2014
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot