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Doublesex- and mab-3-related transcription factor 1 (DM domain expressed in testis protein 1)

 DMRT1_HUMAN             Reviewed;         373 AA.
Q9Y5R6; B2R913; Q6T1H8; Q6T1H9; Q8IW77;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
10-MAY-2005, sequence version 2.
25-OCT-2017, entry version 142.
RecName: Full=Doublesex- and mab-3-related transcription factor 1;
AltName: Full=DM domain expressed in testis protein 1;
Name=DMRT1; Synonyms=DMT1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-45; SER-221;
SER-281 AND LEU-295.
TISSUE=Testis;
PubMed=10332030; DOI=10.1093/hmg/8.6.989;
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.;
"A region of human chromosome 9p required for testis development
contains two genes related to known sexual regulators.";
Hum. Mol. Genet. 8:989-996(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-45, AND TISSUE
SPECIFICITY.
TISSUE=Testis;
PubMed=10857744; DOI=10.1006/geno.2000.6160;
Calvari V., Bertini V., De Grandi A., Peverali G., Zuffardi O.,
Ferguson-Smith M., Knudtzon J., Camerino G., Borsani G., Guioli S.;
"A new submicroscopic deletion that refines the 9p region for sex
reversal.";
Genomics 65:203-212(2000).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT THR-45.
PubMed=16617334; DOI=10.1038/sj.cr.7310050;
Cheng H.H., Ying M., Tian Y.H., Guo Y., McElreavey K., Zhou R.J.;
"Transcriptional diversity of DMRT1 (dsx- and mab3-related
transcription factor 1) in human testis.";
Cell Res. 16:389-393(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Testis;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164053; DOI=10.1038/nature02465;
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.;
"DNA sequence and analysis of human chromosome 9.";
Nature 429:369-374(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
POSSIBLE INVOLVEMENT IN SRXY4.
PubMed=9718346; DOI=10.1086/302016;
Flejter W.L., Fergestad J., Gorski J., Varvill T.,
Chandrasekharappa S.;
"A gene involved in XY sex reversal is located on chromosome 9, distal
to marker D9S1779.";
Am. J. Hum. Genet. 63:794-802(1998).
[9]
POSSIBLE INVOLVEMENT IN SRXY4.
PubMed=9490411; DOI=10.1038/35618;
Raymond C.S., Shamu C.E., Shen M.M., Seifert K.J., Hirsch B.,
Hodgkin J., Zarkower D.;
"Evidence for evolutionary conservation of sex-determining genes.";
Nature 391:691-695(1998).
[10]
POSSIBLE INVOLVEMENT IN TGCT.
PubMed=20543847; DOI=10.1038/ng.607;
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.;
"Variants near DMRT1, TERT and ATF7IP are associated with testicular
germ cell cancer.";
Nat. Genet. 42:604-607(2010).
[11]
POSSIBLE INVOLVEMENT IN SRXY4.
PubMed=21048976; DOI=10.1371/journal.pone.0015392;
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.;
"Identification of de novo copy number variants associated with human
disorders of sexual development.";
PLoS ONE 5:E15392-E15392(2010).
[12]
TISSUE SPECIFICITY.
PubMed=23436708; DOI=10.1002/pmic.201200489;
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.;
"Scanning of novel cancer/testis proteins by human testis proteomic
analysis.";
Proteomics 13:1200-1210(2013).
-!- 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). {ECO:0000250}.
-!- INTERACTION:
Self; NbExp=4; IntAct=EBI-7963304, EBI-7963304;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00070}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1; Synonyms=DMRT1a;
IsoId=Q9Y5R6-1; Sequence=Displayed;
Name=2; Synonyms=DMRT1b;
IsoId=Q9Y5R6-2; Sequence=VSP_042961, VSP_042962;
Name=3; Synonyms=DMRT1c;
IsoId=Q9Y5R6-3; Sequence=VSP_042959, VSP_042960;
-!- TISSUE SPECIFICITY: Testis-specific. Expressed in prostate cancer
(at protein level). {ECO:0000269|PubMed:10857744,
ECO:0000269|PubMed:23436708}.
-!- 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.
-!- 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.
{ECO:0000269|PubMed:20543847}. Note=The disease may be caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: 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.
{ECO:0000269|PubMed:21048976, ECO:0000269|PubMed:9490411,
ECO:0000269|PubMed:9718346}. Note=The disease may be caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the DMRT family. {ECO:0000305}.
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EMBL; AF130728; AAD40474.1; -; mRNA.
EMBL; AL162131; CAB82427.1; -; mRNA.
EMBL; AY442914; AAR89619.1; -; mRNA.
EMBL; AY442915; AAR89620.1; -; mRNA.
EMBL; AK313594; BAG36360.1; -; mRNA.
EMBL; AJ276801; CAB82851.1; -; mRNA.
EMBL; AL136365; CAB99335.1; -; Genomic_DNA.
EMBL; CH471071; EAW58820.1; -; Genomic_DNA.
EMBL; BC040847; AAH40847.1; -; mRNA.
CCDS; CCDS6442.1; -. [Q9Y5R6-1]
RefSeq; NP_068770.2; NM_021951.2. [Q9Y5R6-1]
UniGene; Hs.98586; -.
PDB; 4YJ0; X-ray; 3.81 A; A/B/C=70-131.
PDBsum; 4YJ0; -.
ProteinModelPortal; Q9Y5R6; -.
SMR; Q9Y5R6; -.
BioGrid; 108101; 2.
DIP; DIP-58084N; -.
IntAct; Q9Y5R6; 1.
MINT; MINT-7969865; -.
STRING; 9606.ENSP00000371711; -.
iPTMnet; Q9Y5R6; -.
PhosphoSitePlus; Q9Y5R6; -.
BioMuta; DMRT1; -.
DMDM; 83305820; -.
PaxDb; Q9Y5R6; -.
PeptideAtlas; Q9Y5R6; -.
PRIDE; Q9Y5R6; -.
DNASU; 1761; -.
Ensembl; ENST00000382276; ENSP00000371711; ENSG00000137090. [Q9Y5R6-1]
GeneID; 1761; -.
KEGG; hsa:1761; -.
UCSC; uc003zgv.5; human. [Q9Y5R6-1]
CTD; 1761; -.
DisGeNET; 1761; -.
EuPathDB; HostDB:ENSG00000137090.11; -.
GeneCards; DMRT1; -.
HGNC; HGNC:2934; DMRT1.
HPA; HPA027850; -.
MalaCards; DMRT1; -.
MIM; 154230; phenotype.
MIM; 273300; phenotype.
MIM; 602424; gene.
neXtProt; NX_Q9Y5R6; -.
OpenTargets; ENSG00000137090; -.
Orphanet; 242; 46,XY complete gonadal dysgenesis.
PharmGKB; PA27381; -.
eggNOG; KOG3815; Eukaryota.
eggNOG; ENOG410XSK9; LUCA.
GeneTree; ENSGT00550000074486; -.
HOGENOM; HOG000059585; -.
HOVERGEN; HBG055845; -.
InParanoid; Q9Y5R6; -.
KO; K19488; -.
OMA; NMENRHA; -.
OrthoDB; EOG091G0PWB; -.
PhylomeDB; Q9Y5R6; -.
TreeFam; TF317837; -.
GeneWiki; DMRT1; -.
GenomeRNAi; 1761; -.
PRO; PR:Q9Y5R6; -.
Proteomes; UP000005640; Chromosome 9.
Bgee; ENSG00000137090; -.
CleanEx; HS_DMRT1; -.
ExpressionAtlas; Q9Y5R6; baseline and differential.
Genevisible; Q9Y5R6; HS.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
GO; GO:0000987; F:core promoter proximal region sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IEA:Ensembl.
GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
GO; GO:0008354; P:germ cell migration; IEA:Ensembl.
GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
GO; GO:0002176; P:male germ cell proliferation; ISS:UniProtKB.
GO; GO:0030238; P:male sex determination; ISS:UniProtKB.
GO; GO:0046661; P:male sex differentiation; ISS:UniProtKB.
GO; GO:0045835; P:negative regulation of meiotic nuclear division; ISS:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
GO; GO:0048599; P:oocyte development; IEA:Ensembl.
GO; GO:2000020; P:positive regulation of male gonad development; IEA:Ensembl.
GO; GO:0060903; P:positive regulation of meiosis I; IEA:Ensembl.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
GO; GO:1900107; P:regulation of nodal signaling pathway; IEA:Ensembl.
GO; GO:0060009; P:Sertoli cell development; IEA:Ensembl.
GO; GO:0060008; P:Sertoli cell differentiation; ISS:UniProtKB.
GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
Gene3D; 4.10.1040.10; -; 1.
InterPro; IPR001275; DM_DNA-bd.
InterPro; IPR036407; DM_DNA-bd_sf.
InterPro; IPR026607; DMRT/dsx/mab-3.
InterPro; IPR022114; DMRT1-like.
PANTHER; PTHR12322; PTHR12322; 1.
Pfam; PF00751; DM; 1.
Pfam; PF12374; Dmrt1; 1.
SMART; SM00301; DM; 1.
SUPFAM; SSF82927; SSF82927; 1.
PROSITE; PS40000; DM_1; 1.
PROSITE; PS50809; DM_2; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Developmental protein; Differentiation; DNA-binding; Metal-binding;
Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
Sexual differentiation; Transcription; Transcription regulation; Zinc.
CHAIN 1 373 Doublesex- and mab-3-related
transcription factor 1.
/FTId=PRO_0000207042.
DNA_BIND 72 118 DM. {ECO:0000255|PROSITE-
ProRule:PRU00070}.
COMPBIAS 322 347 Pro/Ser-rich.
MOD_RES 339 339 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZ59}.
VAR_SEQ 120 175 ALRRQQAQEEELGISHPIPLPSAAELLVKRENNGSNPCLMT
ECSGTSQPPPASVPT -> GAGVREPGFSLSFFFFFFFFRW
SLARLPRLQCSGAILAHCNSASRVQAILLPQPPK (in
isoform 3).
{ECO:0000303|PubMed:16617334}.
/FTId=VSP_042959.
VAR_SEQ 176 373 Missing (in isoform 3).
{ECO:0000303|PubMed:16617334}.
/FTId=VSP_042960.
VAR_SEQ 275 275 M -> V (in isoform 2).
{ECO:0000303|PubMed:16617334}.
/FTId=VSP_042961.
VAR_SEQ 276 373 Missing (in isoform 2).
{ECO:0000303|PubMed:16617334}.
/FTId=VSP_042962.
VARIANT 45 45 S -> T (in dbSNP:rs3739583).
{ECO:0000269|PubMed:10332030,
ECO:0000269|PubMed:10857744,
ECO:0000269|PubMed:16617334}.
/FTId=VAR_009954.
VARIANT 221 221 Y -> S. {ECO:0000269|PubMed:10332030}.
/FTId=VAR_009955.
VARIANT 281 281 R -> S. {ECO:0000269|PubMed:10332030}.
/FTId=VAR_009956.
VARIANT 295 295 P -> L. {ECO:0000269|PubMed:10332030}.
/FTId=VAR_009957.
SEQUENCE 373 AA; 39473 MW; 23348B2C4A4733A1 CRC64;
MPNDEAFSKP STPSEAPHAP GVPPQGRAGG FGKASGALVG AASGSSAGGS SRGGGSGSGA
SDLGAGSKKS PRLPKCARCR NHGYASPLKG HKRFCMWRDC QCKKCNLIAE RQRVMAAQVA
LRRQQAQEEE LGISHPIPLP SAAELLVKRE NNGSNPCLMT ECSGTSQPPP ASVPTTAASE
GRMVIQDIPA VTSRGHVENT PDLVSDSTYY SSFYQPSLFP YYNNLYNCPQ YSMALAADSA
SGEVGNPLGG SPVKNSLRGL PGPYVPGQTG NQWQMKNMEN RHAMSSQYRM HSYYPPPSYL
GQSVPQFFTF EDAPSYPEAR ASVFSPPSSQ DSGLVSLSSS SPISNKSTKA VLECEPASEP
SSFTVTPVIE EDE


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DMRTD_BOVIN Bovine ELISA Kit FOR Doublesex- and mab-3-related transcription factor C2 96T
DMRTA2 DMRT3 Gene doublesex and mab-3 related transcription factor 3
E1313m Human ELISA Kit FOR Doublesex- and mab-3-related transcription factor A1 96T
DMRT3_HUMAN Human ELISA Kit FOR Doublesex- and mab-3-related transcription factor 3 96T
CSB-EL006975RA Rat Doublesex- and mab-3-related transcription factor C1(DMRTC1) ELISA kit 96T
DMTA2_HUMAN Human ELISA Kit FOR Doublesex- and mab-3-related transcription factor A2 96T


 

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