Q9Y5R6 (DMRT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
DM domain expressed in testis protein 1

Gene names

Name:	DMRT1
Synonyms:	DMT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	373 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 By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Testis-specific. Ref.2
Developmental stage	Expressed in the genital ridges of six-week-old male embryos. Becomes confined to the forming seminiferous tubules (probably Sertoli cells) at seven weeks. Not detected in female embryos.
Involvement in disease	Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.10 46,XY sex reversal 4 (SRXY4) [MIM:154230]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients display complete or partial gonadal dysgenesis and a chromosome 9p deletion. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11
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 Polymorphism
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB cell morphogenesis Inferred from electronic annotation. Source: Compara germ cell migration Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: Compara male germ cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB male sex determination Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of meiosis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitosis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	core promoter proximal region sequence-specific DNA binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y5R6-1)

Also known as: DMRT1a;

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: Q9Y5R6-2)

Also known as: DMRT1b;

The sequence of this isoform differs from the canonical sequence as follows:
     275-275: M → V
     276-373: Missing.

Isoform 3 (identifier: Q9Y5R6-3)

Also known as: DMRT1c;

The sequence of this isoform differs from the canonical sequence as follows:
     120-175: ALRRQQAQEE...SQPPPASVPT → GAGVREPGFS...QAILLPQPPK
     176-373: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 373	373	Doublesex- and mab-3-related transcription factor 1		PRO_0000207042
Regions
	DNA binding	72 – 118	47	DM
	Compositional bias	322 – 347	26	Pro/Ser-rich
Natural variations
	Alternative sequence	120 – 175	56	ALRRQ…ASVPT → GAGVREPGFSLSFFFFFFFF RWSLARLPRLQCSGAILAHC NSASRVQAILLPQPPK in isoform 3.		VSP_042959
	Alternative sequence	176 – 373	198	Missing in isoform 3.		VSP_042960
	Alternative sequence	275	1	M → V in isoform 2.		VSP_042961
	Alternative sequence	276 – 373	98	Missing in isoform 2.		VSP_042962
	Natural variant	45	1	S → T. Ref.1 Ref.2 Ref.3 Corresponds to variant rs3739583 [ dbSNP | Ensembl ].		VAR_009954
	Natural variant	221	1	Y → S. Ref.1		VAR_009955
	Natural variant	281	1	R → S. Ref.1		VAR_009956
	Natural variant	295	1	P → L. Ref.1		VAR_009957

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (DMRT1a) [UniParc]. Last modified May 10, 2005. Version 2. Checksum: 23348B2C4A4733A1	FASTA	373	39,473
	10 20 30 40 50 60 MPNDEAFSKP STPSEAPHAP GVPPQGRAGG FGKASGALVG AASGSSAGGS SRGGGSGSGA 70 80 90 100 110 120 SDLGAGSKKS PRLPKCARCR NHGYASPLKG HKRFCMWRDC QCKKCNLIAE RQRVMAAQVA 130 140 150 160 170 180 LRRQQAQEEE LGISHPIPLP SAAELLVKRE NNGSNPCLMT ECSGTSQPPP ASVPTTAASE 190 200 210 220 230 240 GRMVIQDIPA VTSRGHVENT PDLVSDSTYY SSFYQPSLFP YYNNLYNCPQ YSMALAADSA 250 260 270 280 290 300 SGEVGNPLGG SPVKNSLRGL PGPYVPGQTG NQWQMKNMEN RHAMSSQYRM HSYYPPPSYL 310 320 330 340 350 360 GQSVPQFFTF EDAPSYPEAR ASVFSPPSSQ DSGLVSLSSS SPISNKSTKA VLECEPASEP 370 SSFTVTPVIE EDE
	Isoform 2 (DMRT1b) [UniParc]. Checksum: E5ED8B07861609D9	FASTA	275	28,690
	10 20 30 40 50 60 MPNDEAFSKP STPSEAPHAP GVPPQGRAGG FGKASGALVG AASGSSAGGS SRGGGSGSGA 70 80 90 100 110 120 SDLGAGSKKS PRLPKCARCR NHGYASPLKG HKRFCMWRDC QCKKCNLIAE RQRVMAAQVA 130 140 150 160 170 180 LRRQQAQEEE LGISHPIPLP SAAELLVKRE NNGSNPCLMT ECSGTSQPPP ASVPTTAASE 190 200 210 220 230 240 GRMVIQDIPA VTSRGHVENT PDLVSDSTYY SSFYQPSLFP YYNNLYNCPQ YSMALAADSA 250 260 270 SGEVGNPLGG SPVKNSLRGL PGPYVPGQTG NQWQV
	Isoform 3 (DMRT1c) [UniParc]. Checksum: 9CFD6F98F5F9B54C	FASTA	175	18,325
	10 20 30 40 50 60 MPNDEAFSKP STPSEAPHAP GVPPQGRAGG FGKASGALVG AASGSSAGGS SRGGGSGSGA 70 80 90 100 110 120 SDLGAGSKKS PRLPKCARCR NHGYASPLKG HKRFCMWRDC QCKKCNLIAE RQRVMAAQVG 130 140 150 160 170 AGVREPGFSL SFFFFFFFFR WSLARLPRLQ CSGAILAHCN SASRVQAILL PQPPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators." Raymond C.S., Parker E.D., Kettlewell J.R., Brown L.G., Page D.C., Kusz K., Jaruzelska J., Reinberg Y., Flejter W.L., Bardwell V.J., Hirsch B., Zarkower D. Hum. Mol. Genet. 8:989-996(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-45; SER-221; SER-281 AND LEU-295. Tissue: Testis.
[2]	"A new submicroscopic deletion that refines the 9p region for sex reversal." Calvari V., Bertini V., De Grandi A., Peverali G., Zuffardi O., Ferguson-Smith M., Knudtzon J., Camerino G., Borsani G., Guioli S. Genomics 65:203-212(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-45, TISSUE SPECIFICITY. Tissue: Testis.
[3]	"Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1) in human testis." Cheng H.H., Ying M., Tian Y.H., Guo Y., McElreavey K., Zhou R.J. Cell Res. 16:389-393(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), VARIANT THR-45.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779." Flejter W.L., Fergestad J., Gorski J., Varvill T., Chandrasekharappa S. Am. J. Hum. Genet. 63:794-802(1998) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SRXY4.
[9]	"Evidence for evolutionary conservation of sex-determining genes." Raymond C.S., Shamu C.E., Shen M.M., Seifert K.J., Hirsch B., Hodgkin J., Zarkower D. Nature 391:691-695(1998) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SRXY4.
[10]	"Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer." Turnbull C., Rapley E.A., Seal S., Pernet D., Renwick A., Hughes D., Ricketts M., Linger R., Nsengimana J., Deloukas P., Huddart R.A., Bishop D.T., Easton D.F., Stratton M.R., Rahman N. Nat. Genet. 42:604-607(2010) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN TGCT.
[11]	"Identification of de novo copy number variants associated with human disorders of sexual development." Tannour-Louet M., Han S., Corbett S.T., Louet J.F., Yatsenko S., Meyers L., Shaw C.A., Kang S.H., Cheung S.W., Lamb D.J. PLoS ONE 5:E15392-E15392(2010) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SRXY4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF130728 mRNA. Translation: AAD40474.1. AL162131 mRNA. Translation: CAB82427.1. AY442914 mRNA. Translation: AAR89619.1. AY442915 mRNA. Translation: AAR89620.1. AK313594 mRNA. Translation: BAG36360.1. AJ276801 mRNA. Translation: CAB82851.1. AL136365 Genomic DNA. Translation: CAB99335.1. CH471071 Genomic DNA. Translation: EAW58820.1. BC040847 mRNA. Translation: AAH40847.1.
IPI	IPI00001733.
RefSeq	NP_068770.2. NM_021951.2.
UniGene	Hs.98586.
3D structure databases
ProteinModelPortal	Q9Y5R6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000371711.
PTM databases
PhosphoSite	Q9Y5R6.
Polymorphism databases
DMDM	83305820.
Proteomic databases
PaxDb	Q9Y5R6.
PeptideAtlas	Q9Y5R6.
PRIDE	Q9Y5R6.
Protocols and materials databases
DNASU	1761.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000382276; ENSP00000371711; ENSG00000137090.
GeneID	1761.
KEGG	hsa:1761.
UCSC	uc003zgu.1. human.
Organism-specific databases
CTD	1761.
GeneCards	GC09P000831.
HGNC	HGNC:2934. DMRT1.
HPA	HPA027850.
MIM	154230. phenotype. 273300. phenotype. 602424. gene.
neXtProt	NX_Q9Y5R6.
Orphanet	242. 46,XY complete gonadal dysgenesis.
PharmGKB	PA27381.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG271390.
HOGENOM	HOG000059585.
HOVERGEN	HBG055845.
InParanoid	Q9Y5R6.
OMA	ECEPASE.
OrthoDB	EOG441QBZ.
PhylomeDB	Q9Y5R6.
Gene expression databases
ArrayExpress	Q9Y5R6.
Bgee	Q9Y5R6.
CleanEx	HS_DMRT1.
Genevestigator	Q9Y5R6.
GermOnline	ENSG00000137090. Homo sapiens.
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
GenomeRNAi	1761.
NextBio	7179.
SOURCE	Search...

Entry information

Entry name

DMRT1_HUMAN

Accession

Primary (citable) accession number: Q9Y5R6
Secondary accession number(s): B2R913 , Q6T1H8, Q6T1H9, Q8IW77

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 10, 2005
Last modified:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.