Search Results

Overview

Uniprot IDQ8NFU7
Protein NameMethylcytosine dioxygenase TET1
Gene NameTET1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
50 TLSPGKLKQLIQERD

Function

Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) (PubMed:19372391, PubMed:21496894, PubMed:21778364, PubMed:35798741). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression (PubMed:33833093). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair (PubMed:31278917). Involved in the balance between pluripotency and lineage commitment of cells and plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation (PubMed:33833093). May play a role in pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment (PubMed:35798741). Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters (By similarity). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (By similarity). 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 MSRSRHARPS 20 RLVRKEDVNK 30 KKKNSQLRKT 40 TKGANKNVAS 50 VKTLSPGKLK 60 QLIQERDVKK 70 KTEPKPPVPV 80 RSLLTRAGAA 90 RMNLDRTEVL 100 FQNPESLTCN 110 GFTMALRSTS 120 LSRRLSQPPL 130 VVAKSKKVPL 140 SKGLEKQHDC 150 DYKILPALGV 160 KHSENDSVPM 170 QDTQVLPDIE 180 TLIGVQNPSL 190 LKGKSQETTQ 200 FWSQRVEDSK 210 INIPTHSGPA 220 AEILPGPLEG 230 TRCGEGLFSE 240 ETLNDTSGSP 250 KMFAQDTVCA 260 PFPQRATPKV 270 TSQGNPSIQL 280 EELGSRVESL 290 KLSDSYLDPI 300 KSEHDCYPTS 310 SLNKVIPDLN 320 LRNCLALGGS 330 TSPTSVIKFL 340 LAGSKQATLG 350 AKPDHQEAFE 360 ATANQQEVSD 370 TTSFLGQAFG 380 AIPHQWELPG 390 ADPVHGEALG 400 ETPDLPEIPG 410 AIPVQGEVFG 420 TILDQQETLG 430 MSGSVVPDLP 440 VFLPVPPNPI 450 ATFNAPSKWP 460 EPQSTVSYGL 470 AVQGAIQILP 480 LGSGHTPQSS 490 SNSEKNSLPP 500 VMAISNVENE 510 KQVHISFLPA 520 NTQGFPLAPE 530 RGLFHASLGI 540 AQLSQAGPSK 550 SDRGSSQVSV 560 TSTVHVVNTT 570 VVTMPVPMVS 580 TSSSSYTTLL 590 PTLEKKKRKR 600 CGVCEPCQQK 610 TNCGECTYCK 620 NRKNSHQICK 630 KRKCEELKKK 640 PSVVVPLEVI 650 KENKRPQREK 660 KPKVLKADFD 670 NKPVNGPKSE 680 SMDYSRCGHG 690 EEQKLELNPH 700 TVENVTKNED 710 SMTGIEVEKW 720 TQNKKSQLTD 730 HVKGDFSANV 740 PEAEKSKNSE 750 VDKKRTKSPK 760 LFVQTVRNGI 770 KHVHCLPAET 780 NVSFKKFNIE 790 EFGKTLENNS 800 YKFLKDTANH 810 KNAMSSVATD 820 MSCDHLKGRS 830 NVLVFQQPGF 840 NCSSIPHSSH 850 SIINHHASIH 860 NEGDQPKTPE 870 NIPSKEPKDG 880 SPVQPSLLSL 890 MKDRRLTLEQ 900 VVAIEALTQL 910 SEAPSENSSP 920 SKSEKDEESE 930 QRTASLLNSC 940 KAILYTVRKD 950 LQDPNLQGEP 960 PKLNHCPSLE 970 KQSSCNTVVF 980 NGQTTTLSNS 990 HINSATNQAS 1000 TKSHEYSKVT 1010 NSLSLFIPKS 1020 NSSKIDTNKS 1030 IAQGIITLDN 1040 CSNDLHQLPP 1050 RNNEVEYCNQ 1060 LLDSSKKLDS 1070 DDLSCQDATH 1080 TQIEEDVATQ 1090 LTQLASIIKI 1100 NYIKPEDKKV 1110 ESTPTSLVTC 1120 NVQQKYNQEK 1130 GTIQQKPPSS 1140 VHNNHGSSLT 1150 KQKNPTQKKT 1160 KSTPSRDRRK 1170 KKPTVVSYQE 1180 NDRQKWEKLS 1190 YMYGTICDIW 1200 IASKFQNFGQ 1210 FCPHDFPTVF 1220 GKISSSTKIW 1230 KPLAQTRSIM 1240 QPKTVFPPLT 1250 QIKLQRYPES 1260 AEEKVKVEPL 1270 DSLSLFHLKT 1280 ESNGKAFTDK 1290 AYNSQVQLTV 1300 NANQKAHPLT 1310 QPSSPPNQCA 1320 NVMAGDDQIR 1330 FQQVVKEQLM 1340 HQRLPTLPGI 1350 SHETPLPESA 1360 LTLRNVNVVC 1370 SGGITVVSTK 1380 SEEEVCSSSF 1390 GTSEFSTVDS 1400 AQKNFNDYAM 1410 NFFTNPTKNL 1420 VSITKDSELP 1430 TCSCLDRVIQ 1440 KDKGPYYTHL 1450 GAGPSVAAVR 1460 EIMENRYGQK 1470 GNAIRIEIVV 1480 YTGKEGKSSH 1490 GCPIAKWVLR 1500 RSSDEEKVLC 1510 LVRQRTGHHC 1520 PTAVMVVLIM 1530 VWDGIPLPMA 1540 DRLYTELTEN 1550 LKSYNGHPTD 1560 RRCTLNENRT 1570 CTCQGIDPET 1580 CGASFSFGCS 1590 WSMYFNGCKF 1600 GRSPSPRRFR 1610 IDPSSPLHEK 1620 NLEDNLQSLA 1630 TRLAPIYKQY 1640 APVAYQNQVE 1650 YENVARECRL 1660 GSKEGRPFSG 1670 VTACLDFCAH 1680 PHRDIHNMNN 1690 GSTVVCTLTR 1700 EDNRSLGVIP 1710 QDEQLHVLPL 1720 YKLSDTDEFG 1730 SKEGMEAKIK 1740 SGAIEVLAPR 1750 RKKRTCFTQP 1760 VPRSGKKRAA 1770 MMTEVLAHKI 1780 RAVEKKPIPR 1790 IKRKNNSTTT 1800 NNSKPSSLPT 1810 LGSNTETVQP 1820 EVKSETEPHF 1830 ILKSSDNTKT 1840 YSLMPSAPHP 1850 VKEASPGFSW 1860 SPKTASATPA 1870 PLKNDATASC 1880 GFSERSSTPH 1890 CTMPSGRLSG 1900 ANAAAADGPG 1910 ISQLGEVAPL 1920 PTLSAPVMEP 1930 LINSEPSTGV 1940 TEPLTPHQPN 1950 HQPSFLTSPQ 1960 DLASSPMEED 1970 EQHSEADEPP 1980 SDEPLSDDPL 1990 SPAEEKLPHI 2000 DEYWSDSEHI 2010 FLDANIGGVA 2020 IAPAHGSVLI 2030 ECARRELHAT 2040 TPVEHPNRNH 2050 PTRLSLVFYQ 2060 HKNLNKPQHG 2070 FELNKIKFEA 2080 KEAKNKKMKA 2090 SEQKDQAANE 2100 GPEQSSEVNE 2110 LNQIPSHKAL 2120 TLTHDNVVTV 2130 SPYALTHVAG PYNHWV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Biological Process GO:1902455 negative regulation of stem cell population maintenance
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
Biological Process GO:0044029 positive regulation of gene expression via chromosomal CpG island demethylation
Biological Process GO:1902459 positive regulation of stem cell population maintenance
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0006493 protein O-linked glycosylation
Biological Process GO:0019827 stem cell population maintenance
Cellular Component GO:0031965 nuclear membrane
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0070579 DNA 5-methylcytosine dioxygenase activity
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0005506 iron ion binding
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:0034614 cellular response to reactive oxygen species
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0001826 inner cell mass cell differentiation
Biological Process GO:0030336 negative regulation of cell migration

Reference

[1] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.