Q9QZ59 (DMRT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Doublesex- and mab-3-related transcription factor 1

Gene names

Name:

Dmrt1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Sexual differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell differentiation Inferred from mutant phenotype Ref.8. Source: UniProtKB cell morphogenesis Inferred from mutant phenotype Ref.9. Source: MGI germ cell migration Inferred from mutant phenotype Ref.9. Source: MGI intracellular signal transduction Inferred from electronic annotation. Source: Compara male germ cell proliferation Inferred from mutant phenotype Ref.10Ref.12. Source: UniProtKB male sex determination 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 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 spermatogenesis Inferred from mutant phenotype Ref.9. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	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
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 374	374	Doublesex- and mab-3-related transcription factor 1		PRO_0000207043
Regions
	DNA binding	70 – 116	47	DM Ref.11 Ref.12
	Compositional bias	323 – 346	24	Pro/Ser-rich
Natural variations
	Alternative sequence	1 – 180	180	Missing in isoform 3.		VSP_042963
	Alternative sequence	178 – 374	197	EGRMV…EDEDE → DEDLREPPPSELPVPDALIL RASLLPGPEHVPDLYLRGRP LLLRSQSQCVLAPQQSRFWL GLPLQQLSDEQRELEGSSGM in isoform 4.		VSP_042964
	Alternative sequence	213 – 374	162	Missing in isoform 2.		VSP_042965
Experimental info
	Sequence conflict	25	1	Q → K in AAF12826. Ref.1
	Sequence conflict	306	1	F → L in CAB62040. Ref.2
	Sequence conflict	365	1	N → S in CAB62040. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Dmrt1a) (Dmrt1a1) (Dmrt1a2) (Dmrt1a3) [UniParc]. Last modified April 18, 2012. Version 2. Checksum: B6C4601432007C35	FASTA	374	39,444
	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
	Isoform 2 (Dmrt1b) (DMR1g) (Dmrt1g) [UniParc]. Checksum: 995A1A053EFC8840	FASTA	212	21,891
	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 MVIQDIPAVT SRGHMENTSD LVSDPAYYSS FY
	Isoform 3 (Dmrt1d) [UniParc]. Checksum: 69A02CDAABC2DE47	FASTA	194	21,148
	10 20 30 40 50 60 MVIQDIPAVT SRGHMENTSD LVSDPAYYSS FYQPSLFPYY NNLYNYPQYS MALSAESSSG 70 80 90 100 110 120 EVGNSLGGSP VKNSLRSLPA PYVPAQTGNQ WQMKTSESRH PVSSQYRMHS YYGPPSYLGQ 130 140 150 160 170 180 SMSQIFTFEE GPSYSEAKAS VFSPPSSQDS GLVSLSSSSP MSNESSKGVL ECESASSEPS 190 SYAVNQVLEE DEDE
	Isoform 4 (Dmrt1c) [UniParc]. Checksum: ED63F763E109DB2B	FASTA	257	26,906
	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 TPTPAASDED 190 200 210 220 230 240 LREPPPSELP VPDALILRAS LLPGPEHVPD LYLRGRPLLL RSQSQCVLAP QQSRFWLGLP 250 LQQLSDEQRE LEGSSGM

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00136866.
RefSeq	NP_056641.2. NM_015826.5.
UniGene	Mm.391208.
3D structure databases
ProteinModelPortal	Q9QZ59.
SMR	Q9QZ59. Positions 68-116.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9QZ59. 1 interaction.
PTM databases
PhosphoSite	Q9QZ59.
Proteomic databases
PaxDb	Q9QZ59.
PRIDE	Q9QZ59.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025755; ENSMUSP00000025755; ENSMUSG00000024837. ENSMUST00000087525; ENSMUSP00000084803; ENSMUSG00000024837.
GeneID	50796.
KEGG	mmu:50796.
Organism-specific databases
CTD	1761.
MGI	MGI:1354733. Dmrt1.
Phylogenomic databases
eggNOG	NOG271390.
GeneTree	ENSGT00550000074486.
HOGENOM	HOG000059585.
HOVERGEN	HBG055845.
InParanoid	Q9QZ59.
OMA	ECEPASE.
OrthoDB	EOG441QBZ.
Gene expression databases
ArrayExpress	Q9QZ59.
Bgee	Q9QZ59.
Genevestigator	Q9QZ59.
GermOnline	ENSMUSG00000024837. Mus musculus.
Family and domain databases
Gene3D	4.10.1040.10. 1 hit.
InterPro	IPR001275. DM_DNA-bd. IPR026607. DMRT/dsx/mab-3. IPR022114. DMRT1-like. [Graphical view]
PANTHER	PTHR12322. PTHR12322. 1 hit.
Pfam	PF00751. DM. 1 hit. PF12374. Dmrt1. 1 hit. [Graphical view]
SMART	SM00301. DM. 1 hit. [Graphical view]
SUPFAM	SSF82927. DM_DNA_bd. 1 hit.
PROSITE	PS40000. DM_1. 1 hit. PS50809. DM_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DMRT1. mouse.
NextBio	307801.
SOURCE	Search...

Entry information

Entry name

DMRT1_MOUSE

Accession

Primary (citable) accession number: Q9QZ59
Secondary accession number(s): Q19AV2 , Q2TDQ9, Q6Y951, Q6Y953, Q9QZ37, Q9QZA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	April 18, 2012
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program