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Overview

Uniprot IDO43151
Protein NameMethylcytosine dioxygenase TET3
Gene NameTET3
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1012 RLAGDNPKEEEVLRK

Function

Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization (PubMed:31928709). Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation (By similarity). Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes (PubMed:23217707). In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin (By similarity). In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT (PubMed:23353889). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034)

Protein Sequence

10 MSQFQVPLAV 20 QPDLPGLYDF 30 PQRQVMVGSF 40 PGSGLSMAGS 50 ESQLRGGGDG 60 RKKRKRCGTC 70 EPCRRLENCG 80 ACTSCTNRRT 90 HQICKLRKCE 100 VLKKKVGLLK 110 EVEIKAGEGA 120 GPWGQGAAVK 130 TGSELSPVDG 140 PVPGQMDSGP 150 VYHGDSRQLS 160 ASGVPVNGAR 170 EPAGPSLLGT 180 GGPWRVDQKP 190 DWEAAPGPAH 200 TARLEDAHDL 210 VAFSAVAEAV 220 SSYGALSTRL 230 YETFNREMSR 240 EAGNNSRGPR 250 PGPEGCSAGS 260 EDLDTLQTAL 270 ALARHGMKPP 280 NCNCDGPECP 290 DYLEWLEGKI 300 KSVVMEGGEE 310 RPRLPGPLPP 320 GEAGLPAPST 330 RPLLSSEVPQ 340 ISPQEGLPLS 350 QSALSIAKEK 360 NISLQTAIAI 370 EALTQLSSAL 380 PQPSHSTPQA 390 SCPLPEALSP 400 PAPFRSPQSY 410 LRAPSWPVVP 420 PEEHSSFAPD 430 SSAFPPATPR 440 TEFPEAWGTD 450 TPPATPRSSW 460 PMPRPSPDPM 470 AELEQLLGSA 480 SDYIQSVFKR 490 PEALPTKPKV 500 KVEAPSSSPA 510 PAPSPVLQRE 520 APTPSSEPDT 530 HQKAQTALQQ 540 HLHHKRSLFL 550 EQVHDTSFPA 560 PSEPSAPGWW 570 PPPSSPVPRL 580 PDRPPKEKKK 590 KLPTPAGGPV 600 GTEKAAPGIK 610 PSVRKPIQIK 620 KSRPREAQPL 630 FPPVRQIVLE 640 GLRSPASQEV 650 QAHPPAPLPA 660 SQGSAVPLPP 670 EPSLALFAPS 680 PSRDSLLPPT 690 QEMRSPSPMT 700 ALQPGSTGPL 710 PPADDKLEEL 720 IRQFEAEFGD 730 SFGLPGPPSV 740 PIQDPENQQT 750 CLPAPESPFA 760 TRSPKQIKIE 770 SSGAVTVLST 780 TCFHSEEGGQ 790 EATPTKAENP 800 LTPTLSGFLE 810 SPLKYLDTPT 820 KSLLDTPAKR 830 AQAEFPTCDC 840 VEQIVEKDEG 850 PYYTHLGSGP 860 TVASIRELME 870 ERYGEKGKAI 880 RIEKVIYTGK 890 EGKSSRGCPI 900 AKWVIRRHTL 910 EEKLLCLVRH 920 RAGHHCQNAV 930 IVILILAWEG 940 IPRSLGDTLY 950 QELTDTLRKY 960 GNPTSRRCGL 970 NDDRTCACQG 980 KDPNTCGASF 990 SFGCSWSMYF 1000 NGCKYARSKT 1010 PRKFRLAGDN 1020 PKEEEVLRKS 1030 FQDLATEVAP 1040 LYKRLAPQAY 1050 QNQVTNEEIA 1060 IDCRLGLKEG 1070 RPFAGVTACM 1080 DFCAHAHKDQ 1090 HNLYNGCTVV 1100 CTLTKEDNRC 1110 VGKIPEDEQL 1120 HVLPLYKMAN 1130 TDEFGSEENQ 1140 NAKVGSGAIQ 1150 VLTAFPREVR 1160 RLPEPAKSCR 1170 QRQLEARKAA 1180 AEKKKIQKEK 1190 LSTPEKIKQE 1200 ALELAGITSD 1210 PGLSLKGGLS 1220 QQGLKPSLKV 1230 EPQNHFSSFK 1240 YSGNAVVESY 1250 SVLGNCRPSD 1260 PYSMNSVYSY 1270 HSYYAQPSLT 1280 SVNGFHSKYA 1290 LPSFSYYGFP 1300 SSNPVFPSQF 1310 LGPGAWGHSG 1320 SSGSFEKKPD 1330 LHALHNSLSP 1340 AYGGAEFAEL 1350 PSQAVPTDAH 1360 HPTPHHQQPA 1370 YPGPKEYLLP 1380 KAPLLHSVSR 1390 DPSPFAQSSN 1400 CYNRSIKQEP 1410 VDPLTQAEPV 1420 PRDAGKMGKT 1430 PLSEVSQNGG 1440 PSHLWGQYSG 1450 GPSMSPKRTN 1460 GVGGSWGVFS 1470 SGESPAIVPD 1480 KLSSFGASCL 1490 APSHFTDGQW 1500 GLFPGEGQQA 1510 ASHSGGRLRG 1520 KPWSPCKFGN 1530 STSALAGPSL 1540 TEKPWALGAG 1550 DFNSALKGSP 1560 GFQDKLWNPM 1570 KGEEGRIPAA 1580 GASQLDRAWQ 1590 SFGLPLGSSE 1600 KLFGALKSEE 1610 KLWDPFSLEE 1620 GPAEEPPSKG 1630 AVKEEKGGGG 1640 AEEEEEELWS 1650 DSEHNFLDEN 1660 IGGVAVAPAH 1670 GSILIECARR 1680 ELHATTPLKK 1690 PNRCHPTRIS 1700 LVFYQHKNLN 1710 QPNHGLALWE 1720 AKMKQLAERA 1730 RARQEEAARL 1740 GLGQQEAKLY 1750 GKKRKWGGTV 1760 VAEPQQKEKK 1770 GVVPTRQALA 1780 VPTDSAVTVS 1790 SYAYTKVTGP YSRWI

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0001939 female pronucleus
Cellular Component GO:0001940 male pronucleus
Cellular Component GO:0005634 nucleus
Molecular Function GO:0070579 DNA 5-methylcytosine dioxygenase activity
Molecular Function GO:0008327 methyl-CpG binding
Molecular Function GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0044727 epigenetic programing of male pronucleus
Biological Process GO:0044029 positive regulation of gene expression via chromosomal CpG island demethylation
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0006493 protein O-linked glycosylation

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.