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Q9Y5R6 (DMRT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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
Alternative name(s):
DM domain expressed in testis protein 1
Gene names
Name:DMRT1
Synonyms:DMT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length373 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 By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Testis-specific. Expressed in prostate cancer (at protein level). Ref.2 Ref.12

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 processDifferentiation
Sexual differentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from electronic annotation. Source: Ensembl

Sertoli cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

germ cell migration

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

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

oocyte development

Inferred from electronic annotation. Source: Ensembl

positive regulation of male gonad development

Inferred from electronic annotation. Source: Ensembl

positive regulation of meiosis I

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncore 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 373373Doublesex- and mab-3-related transcription factor 1
PRO_0000207042

Regions

DNA binding72 – 11847DM
Compositional bias322 – 34726Pro/Ser-rich

Natural variations

Alternative sequence120 – 17556ALRRQ…ASVPT → GAGVREPGFSLSFFFFFFFF RWSLARLPRLQCSGAILAHC NSASRVQAILLPQPPK in isoform 3.
VSP_042959
Alternative sequence176 – 373198Missing in isoform 3.
VSP_042960
Alternative sequence2751M → V in isoform 2.
VSP_042961
Alternative sequence276 – 37398Missing in isoform 2.
VSP_042962
Natural variant451S → T. Ref.1 Ref.2 Ref.3
Corresponds to variant rs3739583 [ dbSNP | Ensembl ].
VAR_009954
Natural variant2211Y → S. Ref.1
VAR_009955
Natural variant2811R → S. Ref.1
VAR_009956
Natural variant2951P → L. Ref.1
VAR_009957

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (DMRT1a) [UniParc].

Last modified May 10, 2005. Version 2.
Checksum: 23348B2C4A4733A1

FASTA37339,473
        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 

« Hide

Isoform 2 (DMRT1b) [UniParc].

Checksum: E5ED8B07861609D9
Show »

FASTA27528,690
Isoform 3 (DMRT1c) [UniParc].

Checksum: 9CFD6F98F5F9B54C
Show »

FASTA17518,325

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
[12]"Scanning of novel cancer/testis proteins by human testis proteomic analysis."
Liu M., Hu Z., Qi L., Wang J., Zhou T., Guo Y., Zeng Y., Zheng B., Wu Y., Zhang P., Chen X., Tu W., Zhang T., Zhou Q., Jiang M., Guo X., Zhou Z., Sha J.
Proteomics 13:1200-1210(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+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.
RefSeqNP_068770.2. NM_021951.2.
UniGeneHs.98586.

3D structure databases

ProteinModelPortalQ9Y5R6.
SMRQ9Y5R6. Positions 70-118.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108101. 2 interactions.
IntActQ9Y5R6. 1 interaction.
MINTMINT-7969865.
STRING9606.ENSP00000371711.

PTM databases

PhosphoSiteQ9Y5R6.

Polymorphism databases

DMDM83305820.

Proteomic databases

PaxDbQ9Y5R6.
PeptideAtlasQ9Y5R6.
PRIDEQ9Y5R6.

Protocols and materials databases

DNASU1761.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382276; ENSP00000371711; ENSG00000137090. [Q9Y5R6-1]
GeneID1761.
KEGGhsa:1761.
UCSCuc003zgu.1. human. [Q9Y5R6-2]
uc003zgv.3. human. [Q9Y5R6-1]

Organism-specific databases

CTD1761.
GeneCardsGC09P000831.
HGNCHGNC:2934. DMRT1.
HPAHPA027850.
MIM154230. phenotype.
273300. phenotype.
602424. gene.
neXtProtNX_Q9Y5R6.
Orphanet242. 46,XY complete gonadal dysgenesis.
PharmGKBPA27381.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG271390.
HOGENOMHOG000059585.
HOVERGENHBG055845.
InParanoidQ9Y5R6.
OMAECEPASE.
OrthoDBEOG7K3TMG.
PhylomeDBQ9Y5R6.
TreeFamTF317837.

Gene expression databases

ArrayExpressQ9Y5R6.
BgeeQ9Y5R6.
CleanExHS_DMRT1.
GenevestigatorQ9Y5R6.

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

GeneWikiDMRT1.
GenomeRNAi1761.
NextBio7179.
PROQ9Y5R6.
SOURCESearch...

Entry information

Entry nameDMRT1_HUMAN
AccessionPrimary (citable) accession number: Q9Y5R6
Secondary accession number(s): B2R913 expand/collapse secondary AC list , Q6T1H8, Q6T1H9, Q8IW77
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2005
Last modified: March 19, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM