SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000508 
UniProt Accession
Theoretical PI
7.99  
Molecular Weight
183165 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
DNMT1 
Gene Synonyms/Alias
AIM, CXXC9, DNMT 
Protein Name
DNA (cytosine-5)-methyltransferase 1 
Protein Synonyms/Alias
Dnmt1EC=2.1.1.37 CXXC-type zinc finger protein 9; DNA methyltransferase HsaI;DNA MTase HsaIM.HsaI MCMT; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:19;10244023-10305755;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene spermatocytes and round spermatids) and protein (in round spermatids).  
The information of related literatures
1. O. A. Omisanjo, K. Biermann, S. Hartmann, L. C. Heukamp, V. Sonnack, A. Hild, R. Brehm, M. Bergmann, W. Weidner and K. Steger (2007) DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer. Histochem Cell Biol 127(2): 175-81. 

Abstract
DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone deacetylation catalyzed by histone deacetylases (HDACs) play an important role for the regulation of gene expression during carcinogenesis and spermatogenesis. We therefore studied the cell-specific expression of DNMT1 and HDAC1 for the first time in human testicular cancer and impaired human spermatogenesis. During normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of spermatogonia. While HDAC1 was additionally present in nuclei of Sertoli cells, DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene spermatocytes and round spermatids) and protein (in round spermatids). Interestingly, in infertile patients revealing round spermatid maturation arrest, round spermatids lack DNMT1 protein, while pachytene spermatocytes became immunopositive for DNMT1. In contrast, no changes in the expression pattern could be observed for HDAC1. This holds true also in testicular tumors, where HDAC1 has been demonstrated in embryonal carcinoma, seminoma and teratoma. Interestingly, DNMT1 was not expressed in seminoma, but upregulated in embryonal carcinoma. PMID: [16960727] 

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Figures for illustrating the function of this protein/gene
Function
Methylates CpG residues. Preferentially methylateshemimethylated DNA. Associates with DNA replication sites in Sphase maintaining the methylation pattern in the newly synthesizedstrand, that is essential for epigenetic inheritance. Associateswith chromatin during G2 and M phases to maintain DNA methylationindependently of replication. It is responsible for maintainingmethylation patterns established in development. DNA methylationis coordinated with methylation of histones. Mediatestranscriptional repression by direct binding to HDAC2. Inassociation with DNMT3B and via the recruitment of CTCFL/BORIS,involved in activation of BAG1 gene expression by modulatingdimethylation of promoter histone H3 at H3K4 and H3K9. 
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Subcellular Location
Nucleus. 
Tissue Specificity
Ubiquitous; highly expressed in fetal tissues,heart, kidney, placenta, peripheral blood mononuclear cells, andexpressed at lower levels in spleen, lung, brain, small intestine,colon, liver, and skeletal muscle. Isoform 2 is less expressedthan isoform 1. 
Gene Ontology
GO IDGO termEvidence
GO:0005721 C:centromeric heterochromatin IEA:Compara.
GO:0005634 C:nucleus TAS:ProtInc.
GO:0005657 C:replication fork IEA:Compara.
GO:0003886 F:DNA (cytosine-5-)-methyltransferase activity TAS:ProtInc.
GO:0003677 F:DNA binding IDA:UniProtKB.
GO:0008327 F:methyl-CpG binding IEA:Compara.
GO:0003723 F:RNA binding IEA:Compara.
GO:0008270 F:zinc ion binding IEA:Compara.
GO:0071230 P:cellular response to amino acid stimulus IEA:Compara.
GO:0016568 P:chromatin modification IEA:UniProtKB-KW.
GO:0016458 P:gene silencing IEA:Compara.
GO:0010216 P:maintenance of DNA methylation IDA:UniProtKB.
GO:0051573 P:negative regulation of histone H3-K9 methylation IMP:UniProtKB.
GO:0000122 P:negative regulation of transcription from RNA polymerase II promoter TAS:ProtInc.
GO:0010628 P:positive regulation of gene expression IMP:UniProtKB.
GO:0051571 P:positive regulation of histone H3-K4 methylation IMP:UniProtKB.
GO:0042127 P:regulation of cell proliferation IEA:Compara.
GO:0006351 P:transcription, DNA-dependent IEA:UniProtKB-KW.
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Interpro
IPR001025;    BAH_dom.
IPR018117;    C5_DNA_meth_AS.
IPR001525;    C5_MeTfrase.
IPR022702;    Cytosine_MeTrfase1_RFD.
IPR010506;    DMAP1-bd.
IPR017198;    DNA_C5-MeTrfase_1_euk.
IPR002857;    Znf_CXXC.
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Pfam
PF01426;    BAH;    2.
PF06464;    DMAP_binding;    1.
PF00145;    DNA_methylase;    1.
PF12047;    DNMT1-RFD;    1.
PF02008;    zf-CXXC;    1.
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SMART
SM00439;    BAH;    2.
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PROSITE
PS51038;    BAH;    2.
PS00094;    C5_MTASE_1;    1.
PS00095;    C5_MTASE_2;    1.
PS51058;    ZF_CXXC;    1.
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PRINTS
PR00105;    C5METTRFRASE.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1   1616       DNA (cytosine-5)-methyltransferase 1.
                             /FTId=PRO_0000088034.
DOMAIN      755    880       BAH 1.
DOMAIN      972   1100       BAH 2.
REPEAT     1109   1110       1.
REPEAT     1111   1112       2.
REPEAT     1113   1114       3.
REPEAT     1115   1116       4.
REPEAT     1117   1118       5.
REPEAT     1119   1120       6; approximate.
ZN_FING     646    692       CXXC-type.
REGION        1    336       Interaction with the PRC2/EED-EZH2
                             complex (By similarity).
REGION        1    148       Interaction with DNMT3A.
REGION        1    120       Interaction with DMAP1.
REGION      149    217       Interaction with DNMT3B.
REGION      163    174       Interaction with PCNA.
REGION      308    606       Interaction with the PRC2/EED-EZH2
                             complex (By similarity).
REGION      310    502       Homodimerization.
REGION      331    550       DNA replication foci-targeting sequence
                             (By similarity).
REGION      651    697       Required for activity.
REGION      693    754       Autoinhibitory linker.
REGION     1109   1120       6 X 2 AA tandem repeats of K-G.
REGION     1121   1616       Interaction with the PRC2/EED-EZH2
                             complex (By similarity).
REGION     1139   1616       Catalytic.
MOTIF       177    205       Nuclear localization signal (Potential).
ACT_SITE   1226   1226
METAL       353    353       Zinc.
METAL       356    356       Zinc.
METAL       414    414       Zinc.
METAL       418    418       Zinc.
SITE        509    509       Important for activity (By similarity).
MOD_RES      70     70       N6,N6-dimethyllysine.
MOD_RES     127    127       Phosphoserine.
MOD_RES     137    137       Phosphothreonine.
MOD_RES     142    142       N6-methyllysine; by SETD7.
MOD_RES     143    143       Phosphoserine; by PKB/AKT1.
MOD_RES     152    152       Phosphoserine.
MOD_RES     154    154       Phosphoserine.
MOD_RES     160    160       N6-acetyllysine.
MOD_RES     173    173       N6-acetyllysine.
MOD_RES     188    188       N6-acetyllysine.
MOD_RES     259    259       N6-acetyllysine.
MOD_RES     288    288       Phosphoserine (By similarity).
MOD_RES     366    366       N6-acetyllysine.
MOD_RES     394    394       Phosphoserine.
MOD_RES     509    509       Phosphoserine (By similarity).
MOD_RES     714    714       Phosphoserine.
MOD_RES     732    732       Phosphoserine.
MOD_RES     749    749       N6-acetyllysine.
MOD_RES     891    891       N6-acetyllysine.
MOD_RES     954    954       Phosphoserine.
MOD_RES     957    957       N6-acetyllysine.
MOD_RES     961    961       N6-acetyllysine.
MOD_RES     969    969       Phosphotyrosine.
MOD_RES     975    975       N6-acetyllysine.
MOD_RES    1054   1054       N6-acetyllysine.
MOD_RES    1105   1105       Phosphoserine.
MOD_RES    1111   1111       N6-acetyllysine.
MOD_RES    1113   1113       N6-acetyllysine.
MOD_RES    1115   1115       N6-acetyllysine.
MOD_RES    1117   1117       N6-acetyllysine; by EHMT2.
MOD_RES    1349   1349       N6-acetyllysine.
MOD_RES    1415   1415       N6-acetyllysine.
VAR_SEQ       1    336       Missing (in isoform 3).
                             /FTId=VSP_005617.
VAR_SEQ     149    149       P -> RSRDPPASASQVTGIRA (in isoform 2).
                             /FTId=VSP_005618.
VARIANT      97     97       H -> R (in dbSNP:rs16999593).
                             /FTId=VAR_024605.
VARIANT     311    311       I -> V (in dbSNP:rs2228612).
                             /FTId=VAR_051960.
VARIANT     490    491       DP -> EY (in HSN1E; unstable protein with
                             decreased enzymatic activity and impaired
                             heterochromatin binding ability after the
                             S phase).
                             /FTId=VAR_065965.
VARIANT     495    495       Y -> C (in HSN1E; unstable protein with
                             decreased enzymatic activity and impaired
                             heterochromatin binding ability after the
                             S phase).
                             /FTId=VAR_065966.
MUTAGEN     163    163       R->A: Abolishes interaction with PCNA.
MUTAGEN     164    164       Q->A: Abolishes interaction with PCNA.
MUTAGEN     166    166       T->A: Abolishes interaction with PCNA.
MUTAGEN     167    167       I->A: Abolishes interaction with PCNA.
MUTAGEN     169    169       S->A: No loss of interaction with PCNA.
MUTAGEN     170    170       H->V: Abolishes interaction with PCNA.
MUTAGEN     171    171       F->V: Abolishes interaction with PCNA.
MUTAGEN     172    172       A->S: No loss of interaction with PCNA.
MUTAGEN     173    173       K->A: No loss of interaction with PCNA.
MUTAGEN     653    653       C->G: Reduces activity about 10-fold;
                             when associated with G-656; G-659; G-664;
                             G-667 and G-670.
MUTAGEN     656    656       C->G: Reduces activity about 10-fold;
                             when associated with G-653; G-659; G-664;
                             G-667 and G-670.
MUTAGEN     659    659       C->G: Reduces activity about 10-fold;
                             when associated with G-653; G-656; G-664;
                             G-667 and G-670.
MUTAGEN     664    664       C->F: Reduces activity about 10-fold;
                             when associated with G-653; G-656; G-659;
                             G-667 and G-670.
MUTAGEN     667    667       C->G: Reduces activity about 10-fold;
                             when associated with G-653; G-656; G-659;
                             G-664 and G-670.
MUTAGEN     670    670       C->G: Reduces activity about 10-fold;
                             when associated with G-653; G-656; G-659;
                             G-664 and G-667.
MUTAGEN    1226   1226       C->A: Loss of activity.
TURN        354    356
HELIX       377    389
STRAND      405    413
STRAND      422    425
TURN        426    430
STRAND      434    441
STRAND      453    458
STRAND      462    467
STRAND      476    480
STRAND      485    488
TURN        493    495
HELIX       496    499
HELIX       504    518
HELIX       524    533
HELIX       538    540
HELIX       547    551
HELIX       554    567
HELIX       575    577
HELIX       579    587
HELIX       592    598
HELIX       622    629
TURN        657    659
HELIX       670    672
HELIX       687    689
STRAND      731    735
STRAND      744    746
STRAND      748    752
STRAND      755    758
STRAND      762    765
STRAND      767    769
STRAND      775    785
TURN        786    788
STRAND      789    799
HELIX       800    802
HELIX       806    808
STRAND      813    824
HELIX       825    827
STRAND      828    832
STRAND      834    836
HELIX       843    845
HELIX       856    860
STRAND      862    870
TURN        871    874
STRAND      875    877
TURN        889    891
HELIX       894    905
STRAND      912    916
STRAND      921    928
STRAND      931    934
STRAND      938    941
TURN        966    968
HELIX       973    975
HELIX       976    980
STRAND      992   1001
STRAND     1005   1008
STRAND     1015   1020
HELIX      1024   1026
HELIX      1031   1034
STRAND     1035   1037
STRAND     1041   1044
STRAND     1048   1052
HELIX      1053   1055
STRAND     1058   1064
HELIX      1065   1067
HELIX      1072   1077
STRAND     1079   1090
TURN       1091   1094
STRAND     1095   1097
STRAND     1139   1145
HELIX      1150   1158
STRAND     1160   1167
HELIX      1171   1180
STRAND     1184   1187
HELIX      1191   1200
TURN       1214   1216
STRAND     1218   1222
STRAND     1231   1233
HELIX      1237   1243
HELIX      1247   1258
STRAND     1261   1268
HELIX      1269   1272
HELIX      1275   1277
HELIX      1278   1289
STRAND     1293   1300
HELIX      1301   1304
STRAND     1311   1318
HELIX      1336   1338
STRAND     1343   1345
STRAND     1348   1350
HELIX      1367   1371
STRAND     1384   1386
HELIX      1395   1401
HELIX      1419   1426
HELIX      1436   1438
STRAND     1451   1453
TURN       1462   1464
HELIX      1477   1479
STRAND     1480   1482
HELIX      1487   1489
STRAND     1493   1496
HELIX      1499   1503
HELIX      1504   1506
HELIX      1508   1510
TURN       1511   1514
STRAND     1523   1525
STRAND     1542   1547
HELIX      1550   1556
HELIX      1569   1578
HELIX      1582   1598
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Nucleotide Sequence
Length: 5434 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 1616 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
YWHAZMINT 
hNp95BioGRID 
SSX2IPString 
_HPRD 
_BioGRID 
_BioGRID 
SP3BioGRID 
BAZ2ABioGRID 
CBX1HPRD 
CHEK1BioGRID 
CXXC1BioGRID 
MECP2BioGRID 
DMAP1HPRD 
DNMT3AHPRD 
DNMT3BHPRD 
hNp95BioGRID 
SSX2IPString 
_IntAct 
SP3BioGRID 
BMPR1BIntAct 
CBX1BioGRID 
CBX5BioGRID 
CHEK1BioGRID 
CXXC1BioGRID 
BMPR1BIntAct 
BMPR1BIntAct 
Dlg4MINT 
DMAP1BioGRID 
DNMT3ABioGRID 
DNMT3BBioGRID 
DNMT1HPRD 
DNMT1HPRD 
E2F1BioGRID 
DNMT3ABioGRID 
EEDHPRD 
EHMT2BioGRID 
EZH2HPRD 
HHT1BioGRID 
HDAC1BioGRID 
HDAC2BioGRID 
SPENString 
PCNABioGRID 
UHRF1BioGRID 
_BioGRID 
CBX1BioGRID 
HDAC1BioGRID 
SP3BioGRID 
DNMT3ABioGRID 
_BioGRID 
RB1BioGRID 
SETD7BioGRID 
SMARCA5BioGRID 
SP1BioGRID 
SP3BioGRID 
STAT3BioGRID 
SUV39H1BioGRID 
TRIM27HPRD 
UHRF1BioGRID 
DYNLL1HPRD 
EEDBioGRID 
EHMT2BioGRID 
EZH2BioGRID 
HDAC1HPRD 
HDAC2BioGRID 
HELLSBioGRID 
HMGB1HPRD 
MBD2BioGRID 
MECP2BioGRID 
SPENString 
mltFIntAct 
NRIP1MINT 
TP53BioGRID 
PCNAHPRD 
UHRF1BioGRID 
RGS6BioGRID 
_BioGRID 
_BioGRID 
_BioGRID 
DNCL1HPRD 
CBX1HPRD 
HDAC1HPRD 
_BioGRID 
SP3BioGRID 
RB1HPRD 
RGS6BioGRID 
SETD7BioGRID 
SMARCA5BioGRID 
SP1BioGRID 
SP3BioGRID 
STAT3BioGRID 
SUV39H1HPRD 
TRIM27IntAct 
TSG101HPRD 
USP7BioGRID 
UHRF1BioGRID 
ureGIntAct 
YPO2697IntAct 
Other Protein-Protein interaction resources
String database  
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