dbPTM

DNMT1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DNMT1_MOUSE
UniProt AC	P13864
Protein Name	DNA (cytosine-5)-methyltransferase 1
Gene Name	Dnmt1
Organism	Mus musculus (Mouse).
Sequence Length	1620
Subcellular Localization	Nucleus . Cytoplasm . It is nucleoplasmic through most of the cell cycle and associates with replication foci during S-phase. In germ cells, spermatogonia, preleptotene and leptotene spermatocytes all express high levels of nuclear protein, while the
Protein Description	Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (By similarity). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity). Promotes tumor growth (By similarity)..
Protein Sequence	MPARTAPARVPALASPAGSLPDHVRRRLKDLERDGLTEKECVREKLNLLHEFLQTEIKSQLCDLETKLHKEELSEEGYLAKVKSLLNKDLSLENGTHTLTQKANGCPANGSRPTWRAEMADSNRSPRSRPKPRGPRRSKSDSDTLSVETSPSSVATRRTTRQTTITAHFTKGPTKRKPKEESEEGNSAESAAEERDQDKKRRVVDTESGAAAAVEKLEEVTAGTQLGPEEPCEQEDDNRSLRRHTRELSLRRKSKEDPDREARPETHLDEDEDGKKDKRSSRPRSQPRDPAAKRRPKEAEPEQVAPETPEDRDEDEREEKRRKTTRKKLESHTVPVQSRSERKAAQSKSVIPKINSPKCPECGQHLDDPNLKYQQHPEDAVDEPQMLTSEKLSIYDSTSTWFDTYEDSPMHRFTSFSVYCSRGHLCPVDTGLIEKNVELYFSGCAKAIHDENPSMEGGINGKNLGPINQWWLSGFDGGEKVLIGFSTAFAEYILMEPSKEYEPIFGLMQEKIYISKIVVEFLQNNPDAVYEDLINKIETTVPPSTINVNRFTEDSLLRHAQFVVSQVESYDEAKDDDETPIFLSPCMRALIHLAGVSLGQRRATRRVMGATKEKDKAPTKATTTKLVYQIFDTFFSEQIEKYDKEDKENAMKRRRCGVCEVCQQPECGKCKACKDMVKFGGTGRSKQACLKRRCPNLAVKEADDDEEADDDVSEMPSPKKLHQGKKKKQNKDRISWLGQPMKIEENRTYYQKVSIDEEMLEVGDCVSVIPDDSSKPLYLARVTALWEDKNGQMMFHAHWFCAGTDTVLGATSDPLELFLVGECENMQLSYIHSKVKVIYKAPSENWAMEGGTDPETTLPGAEDGKTYFFQLWYNQEYARFESPPKTQPTEDNKHKFCLSCIRLAELRQKEMPKVLEQIEEVDGRVYCSSITKNGVVYRLGDSVYLPPEAFTFNIKVASPVKRPKKDPVNETLYPEHYRKYSDYIKGSNLDAPEPYRIGRIKEIHCGKKKGKVNEADIKLRLYKFYRPENTHRSYNGSYHTDINMLYWSDEEAVVNFSDVQGRCTVEYGEDLLESIQDYSQGGPDRFYFLEAYNSKTKNFEDPPNHARSPGNKGKGKGKGKGKGKHQVSEPKEPEAAIKLPKLRTLDVFSGCGGLSEGFHQAGISETLWAIEMWDPAAQAFRLNNPGTTVFTEDCNVLLKLVMAGEVTNSLGQRLPQKGDVEMLCGGPPCQGFSGMNRFNSRTYSKFKNSLVVSFLSYCDYYRPRFFLLENVRNFVSYRRSMVLKLTLRCLVRMGYQCTFGVLQAGQYGVAQTRRRAIILAAAPGEKLPLFPEPLHVFAPRACQLSVVVDDKKFVSNITRLSSGPFRTITVRDTMSDLPEIQNGASNSEIPYNGEPLSWFQRQLRGSHYQPILRDHICKDMSPLVAARMRHIPLFPGSDWRDLPNIQVRLGDGVIAHKLQYTFHDVKNGYSSTGALRGVCSCAEGKACDPESRQFSTLIPWCLPHTGNRHNHWAGLYGRLEWDGFFSTTVTNPEPMGKQGRVLHPEQHRVVSVRECARSQGFPDSYRFFGNILDRHRQVGNAVPPPLAKAIGLEIKLCLLSSARESASAAVKAKEEAATKD

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Phosphorylation	---MPARTAPARVPA ---CCCCCCCCCCCC	38.81	29514104
15	Phosphorylation	ARVPALASPAGSLPD CCCCCCCCCCCCCCH	19.01	26824392
19	Phosphorylation	ALASPAGSLPDHVRR CCCCCCCCCCHHHHH	38.54	25168779
59	Phosphorylation	FLQTEIKSQLCDLET HHHHHHHHHHCHHHH	33.76	-
70	"N6,N6-dimethyllysine"	DLETKLHKEELSEEG HHHHHHCHHHHCHHC	64.42	-
70	Methylation	DLETKLHKEELSEEG HHHHHHCHHHHCHHC	64.42	-
81	Acetylation	SEEGYLAKVKSLLNK CHHCHHHHHHHHHCC	47.83	22826441
84	Phosphorylation	GYLAKVKSLLNKDLS CHHHHHHHHHCCCCC	40.87	22817900
91	Phosphorylation	SLLNKDLSLENGTHT HHHCCCCCCCCCCEE	43.71	29899451
122	Phosphorylation	WRAEMADSNRSPRSR CCHHHCCCCCCCCCC	25.30	26824392
125	Phosphorylation	EMADSNRSPRSRPKP HHCCCCCCCCCCCCC	28.99	27087446
128	Phosphorylation	DSNRSPRSRPKPRGP CCCCCCCCCCCCCCC	57.21	22817900
138	Phosphorylation	KPRGPRRSKSDSDTL CCCCCCCCCCCCCCC	37.48	27087446
139	Methylation	PRGPRRSKSDSDTLS CCCCCCCCCCCCCCE	57.37	-
140	Phosphorylation	RGPRRSKSDSDTLSV CCCCCCCCCCCCCEE	43.52	25521595
142	Phosphorylation	PRRSKSDSDTLSVET CCCCCCCCCCCEEEC	39.32	22942356
144	Phosphorylation	RSKSDSDTLSVETSP CCCCCCCCCEEECCC	25.53	22942356
146	Phosphorylation	KSDSDTLSVETSPSS CCCCCCCEEECCCCH	21.72	22942356
149	Phosphorylation	SDTLSVETSPSSVAT CCCCEEECCCCHHHC	43.72	22942356
150	Phosphorylation	DTLSVETSPSSVATR CCCEEECCCCHHHCC	14.85	22942356
152	Phosphorylation	LSVETSPSSVATRRT CEEECCCCHHHCCCC	36.89	22942356
153	Phosphorylation	SVETSPSSVATRRTT EEECCCCHHHCCCCC	21.10	23984901
156	Phosphorylation	TSPSSVATRRTTRQT CCCCHHHCCCCCCCE	20.66	25619855
163	Phosphorylation	TRRTTRQTTITAHFT CCCCCCCEEEEEEEC	19.51	25338131
164	Phosphorylation	RRTTRQTTITAHFTK CCCCCCEEEEEEECC	14.16	29514104
166	Phosphorylation	TTRQTTITAHFTKGP CCCCEEEEEEECCCC	16.40	22871156
171	Acetylation	TITAHFTKGPTKRKP EEEEEECCCCCCCCC	63.05	-
182	Phosphorylation	KRKPKEESEEGNSAE CCCCHHHCCCCCCHH	41.88	25619855
187	Phosphorylation	EESEEGNSAESAAEE HHCCCCCCHHHHHHH	44.25	25521595
190	Phosphorylation	EEGNSAESAAEERDQ CCCCCHHHHHHHHHH	32.28	27087446
206	Phosphorylation	KKRRVVDTESGAAAA HCCCEEECHHHHHHH	22.05	28066266
208	Phosphorylation	RRVVDTESGAAAAVE CCEEECHHHHHHHHH	35.51	28066266
224	Phosphorylation	LEEVTAGTQLGPEEP HHHHCCCCCCCCCCC	20.39	25266776
240	Phosphorylation	EQEDDNRSLRRHTRE CCCCCCHHHHHHHHH	32.27	21149613
245	Phosphorylation	NRSLRRHTRELSLRR CHHHHHHHHHHHHHH	24.83	25338131
248	Phosphorylation	LRRHTRELSLRRKSK HHHHHHHHHHHHHCC	5.42	24719451
249	Phosphorylation	RRHTRELSLRRKSKE HHHHHHHHHHHHCCC	18.31	25159016
254	Phosphorylation	ELSLRRKSKEDPDRE HHHHHHHCCCCCCCC	39.19	17965600
255	Acetylation	LSLRRKSKEDPDREA HHHHHHCCCCCCCCC	69.99	-
280	Phosphorylation	DGKKDKRSSRPRSQP CCCCCCCCCCCCCCC	36.12	20450229
281	Phosphorylation	GKKDKRSSRPRSQPR CCCCCCCCCCCCCCC	50.79	20450229
285	Phosphorylation	KRSSRPRSQPRDPAA CCCCCCCCCCCCHHH	47.41	25266776
308	Phosphorylation	PEQVAPETPEDRDED HHHCCCCCCCCCCHH	30.80	25521595
331	Phosphorylation	TTRKKLESHTVPVQS HHHHHHHHCCCCCCC	34.59	24759943
333	Phosphorylation	RKKLESHTVPVQSRS HHHHHHCCCCCCCHH	35.47	24759943
338	Phosphorylation	SHTVPVQSRSERKAA HCCCCCCCHHHHHHH	37.70	24759943
340	Phosphorylation	TVPVQSRSERKAAQS CCCCCCHHHHHHHHC	47.18	24759943
356	Phosphorylation	SVIPKINSPKCPECG CCCCCCCCCCCCCCC	29.25	26745281
372	Acetylation	HLDDPNLKYQQHPED CCCCCCCCCCCCCCC	47.88	-
397	Phosphorylation	EKLSIYDSTSTWFDT CEEEEECCCCCCEEC	13.79	-
498	Phosphorylation	EYILMEPSKEYEPIF HHHHCCCCCCCCCCC	25.47	17965600
515	Phosphorylation	MQEKIYISKIVVEFL HHCHHHHHHHHHHHH	10.19	17965600
555	Phosphorylation	VNRFTEDSLLRHAQF CCCCCHHHHHHHHHH	24.07	-
597	Phosphorylation	LIHLAGVSLGQRRAT HHHHHCCCHHHHHHH	26.34	17965600
599 (in isoform 2)	Phosphorylation	-	16.08	19144319
604	Phosphorylation	SLGQRRATRRVMGAT CHHHHHHHHHHCCCC	19.73	-
611	Phosphorylation	TRRVMGATKEKDKAP HHHHCCCCCCCCCCC	33.72	-
612	Ubiquitination	RRVMGATKEKDKAPT HHHCCCCCCCCCCCC	63.33	-
625	Ubiquitination	PTKATTTKLVYQIFD CCCHHHHHHHHHHHH	33.59	-
669	Ubiquitination	CQQPECGKCKACKDM HCCCCCCCCCHHHHH	44.19	-
671	Ubiquitination	QPECGKCKACKDMVK CCCCCCCCHHHHHHH	61.37	-
674	Ubiquitination	CGKCKACKDMVKFGG CCCCCHHHHHHHCCC	54.43	-
678	Ubiquitination	KACKDMVKFGGTGRS CHHHHHHHCCCCCHH	31.49	-
713	Phosphorylation	EEADDDVSEMPSPKK CCCCCCHHHCCCHHH	34.86	27149854
716	Phosphorylation	DDDVSEMPSPKKLHQ CCCHHHCCCHHHCCC	43.35	24719451
717	Phosphorylation	DDVSEMPSPKKLHQG CCHHHCCCHHHCCCC	48.30	27087446
735	Phosphorylation	KQNKDRISWLGQPMK CCCCCCCCCCCCCCC	19.69	-
752	Acetylation	ENRTYYQKVSIDEEM CCCCEEEECCCCHHH	23.10	-
843	Phosphorylation	KVIYKAPSENWAMEG EEEEECCCCCCCCCC	48.71	25338131
882	Phosphorylation	QEYARFESPPKTQPT CCCEECCCCCCCCCC	43.73	-
895	Acetylation	PTEDNKHKFCLSCIR CCCCCCCCHHHHHHH	39.11	-
957	Phosphorylation	FTFNIKVASPVKRPK EEEEEEECCCCCCCC	11.78	24719451
958	Phosphorylation	TFNIKVASPVKRPKK EEEEEECCCCCCCCC	32.96	26824392
961	Acetylation	IKVASPVKRPKKDPV EEECCCCCCCCCCCC	67.38	-
965	Acetylation	SPVKRPKKDPVNETL CCCCCCCCCCCCCCC	70.69	-
979	Acetylation	LYPEHYRKYSDYIKG CCHHHHHHHHHHHCC	41.77	-
981	Phosphorylation	PEHYRKYSDYIKGSN HHHHHHHHHHHCCCC	27.29	24759943
985	Ubiquitination	RKYSDYIKGSNLDAP HHHHHHHCCCCCCCC	50.48	-
1108	Phosphorylation	DPPNHARSPGNKGKG CCCCCCCCCCCCCCC	37.63	25266776
1114	Acetylation	RSPGNKGKGKGKGKG CCCCCCCCCCCCCCC	60.09	22826441
1116	Acetylation	PGNKGKGKGKGKGKG CCCCCCCCCCCCCCC	62.02	22826441
1118	Acetylation	NKGKGKGKGKGKGKH CCCCCCCCCCCCCCC	62.02	22826441
1120	Acetylation	GKGKGKGKGKGKHQV CCCCCCCCCCCCCCC	62.02	-
1122	Acetylation	GKGKGKGKGKHQVSE CCCCCCCCCCCCCCC	69.17	23806337
1124	Acetylation	GKGKGKGKHQVSEPK CCCCCCCCCCCCCCC	34.06	23806337
1128	Phosphorylation	GKGKHQVSEPKEPEA CCCCCCCCCCCCCHH	41.43	29109428
1249	Phosphorylation	TYSKFKNSLVVSFLS HHHHHCCHHHHHHHH	24.11	17965600
1253	Phosphorylation	FKNSLVVSFLSYCDY HCCHHHHHHHHHCCC	17.00	17965600
1326	Ubiquitination	LAAAPGEKLPLFPEP EEECCCCCCCCCCCC	62.41	-
1352	Acetylation	SVVVDDKKFVSNITR EEEECCHHHHHHHHH	58.97	-
1418	Acetylation	ILRDHICKDMSPLVA HHHHHHCCCCHHHHH	56.73	-
1421	Phosphorylation	DHICKDMSPLVAARM HHHCCCCHHHHHHHH	25.80	17965600
1460	Phosphorylation	VIAHKLQYTFHDVKN EEEEEEEEEEEECCC	23.08	25177544
1471	Phosphorylation	DVKNGYSSTGALRGV ECCCCCCCCCHHHHH	23.52	25177544
1495	Phosphorylation	DPESRQFSTLIPWCL CHHHCCHHHHHHHHC	17.61	17965600
1550	Phosphorylation	HPEQHRVVSVRECAR CHHHCCEEEHHHHHH	4.40	24719451
1600	Phosphorylation	EIKLCLLSSARESAS HHHHHHHHHHHHHHH	14.70	29895711

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
146	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
146	S	Phosphorylation	Kinase	CSNK1E	Q9JMK2	GPS
146	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
146	S	Phosphorylation	Kinase	CK1	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Fzr1	Q9R1K5	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
139	K	Methylation	-
Methylation at Lys-139 by SETD7 promotes DNMT1 proteasomal degradation.
140	S	Methylation	21183079
Phosphorylation of Ser-140 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability (By similarity).
140	S	Phosphorylation	21183079
Phosphorylation of Ser-140 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability (By similarity).
146	S	Phosphorylation	21183079
Phosphorylation at Ser-146 by CK1 reduces DNA-binding activity.
152	S	Phosphorylation	17242355
Phosphorylation of Ser-152 by CDKs is important for enzymatic activity and protein stability.
1352	K	Acetylation	-
Deacetylation of Lys-1352 and Lys-1418 by SIRT1 increases methyltransferase activity (By similarity).
1418	K	Acetylation	-
Deacetylation of Lys-1352 and Lys-1418 by SIRT1 increases methyltransferase activity (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of DNMT1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HDAC1_HUMAN	HDAC1	physical	10615135
TF65_MOUSE	Rela	physical	20211142
TOX3_MOUSE	Tox3	physical	20211142
PA2GA_MOUSE	Pla2g2a	genetic	10919675
DNMT1_MOUSE	Dnmt1	physical	21311766
CADH1_MOUSE	Cdh1	physical	15899874
HESX1_MOUSE	Hesx1	physical	17931718
ATM_MOUSE	Atm	physical	23754744
KAT5_MOUSE	Kat5	physical	23754744
UHRF1_MOUSE	Uhrf1	physical	23754744
UHRF1_MOUSE	Uhrf1	physical	24013172
BRAP_MOUSE	Brap	physical	25820252

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of DNMT1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"The DNA-binding activity of mouse DNA methyltransferase 1 isregulated by phosphorylation with casein kinase 1delta/epsilon."; Sugiyama Y., Hatano N., Sueyoshi N., Suetake I., Tajima S.,Kinoshita E., Kinoshita-Kikuta E., Koike T., Kameshita I.; Biochem. J. 427:489-497(2010). Cited for: PHOSPHORYLATION AT SER-146 BY CSNK1D/CK1, AND INTERACTION WITH CSNK1D.	20192920 [Abstract]
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-285, AND MASSSPECTROMETRY.	19367708 [Abstract]
"Phosphorylation of serine-515 activates the mammalian maintenancemethyltransferase Dnmt1."; Goyal R., Rathert P., Laser H., Gowher H., Jeltsch A.; Epigenetics 2:155-160(2007). Cited for: PHOSPHORYLATION AT SER-515, AND MUTAGENESIS OF SER-515.	17965600 [Abstract]
"Peptide mapping of the murine DNA methyltransferase reveals a majorphosphorylation site and the start of translation."; Glickman J.F., Pavlovich J.G., Reich N.O.; J. Biol. Chem. 272:17851-17857(1997). Cited for: PHOSPHORYLATION AT SER-515, AND MASS SPECTROMETRY.	9211941 [Abstract]

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