Search Results

Overview

Uniprot IDQ9BYW2
Protein NameHistone-lysine N-methyltransferase SETD2
Gene NameSETD2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1135 TDKFFLHKGTEKNPE
1191 PNSEETVKAKIPSRQ
1193 SEETVKAKIPSRQQE
141 KSRVELGKIHFKKHL
2027 KEVYRIPKKSQTEKE
303 SKISLSCKKTGSKKK
340 SQRSHDLKFSASIEK
359 KKSSAPLKSEDLGKP
37 AKIENVQKTGFIKGP
382 DKYFSYSKLERDTRY
42 VQKTGFIKGPMFKGV
47 FIKGPMFKGVASSRF
490 LRTSSYSKSDRDCKT
513 RRGKYSSKLERESKR
556 DSSASRYKSTLSKPI
561 RYKSTLSKPIPKSDK
596 SLQTPCSKGSELRMI
605 SELRMINKNPEREKA
922 KKSSEFLKHAGKETI

Function

Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426)

Protein Sequence

10 MKQLQPQPPP 20 KMGDFYDPEH 30 PTPEEEENEA 40 KIENVQKTGF 50 IKGPMFKGVA 60 SSRFLPKGTK 70 TKVNLEEQGR 80 QKVSFSFSLT 90 KKTLQNRFLT 100 ALGNEKQSDT 110 PNPPAVPLQV 120 DSTPKMKMEI 130 GDTLSTAEES 140 SPPKSRVELG 150 KIHFKKHLLH 160 VTSRPLLATT 170 TAVASPPTHA 180 APLPAVIAES 190 TTVDSPPSSP 200 PPPPPPAQAT 210 TLSSPAPVTE 220 PVALPHTPIT 230 VLMAAPVPLP 240 VDVAVRSLKE 250 PPIIIVPESL 260 EADTKQDTIS 270 NSLEEHVTQI 280 LNEQADISSK 290 KEDSHIGKDE 300 EIPDSSKISL 310 SCKKTGSKKK 320 SSQSEGIFLG 330 SESDEDSVRT 340 SSSQRSHDLK 350 FSASIEKERD 360 FKKSSAPLKS 370 EDLGKPSRSK 380 TDRDDKYFSY 390 SKLERDTRYV 400 SSRCRSERER 410 RRSRSHSRSE 420 RGSRTNLSYS 430 RSERSHYYDS 440 DRRYHRSSPY 450 RERTRYSRPY 460 TDNRARESSD 470 SEEEYKKTYS 480 RRTSSHSSSY 490 RDLRTSSYSK 500 SDRDCKTETS 510 YLEMERRGKY 520 SSKLERESKR 530 TSENEAIKRC 540 CSPPNELGFR 550 RGSSYSKHDS 560 SASRYKSTLS 570 KPIPKSDKFK 580 NSFCCTELNE 590 EIKQSHSFSL 600 QTPCSKGSEL 610 RMINKNPERE 620 KAGSPAPSNR 630 LNDSPTLKKL 640 DELPIFKSEF 650 ITHDSHDSIK 660 ELDSLSKVKN 670 DQLRSFCPIE 680 LNINGSPGAE 690 SDLATFCTSK 700 TDAVLMTSDD 710 SVTGSELSPL 720 VKACMLSSNG 730 FQNISRCKEK 740 DLDDTCMLHK 750 KSESPFRETE 760 PLVSPHQDKL 770 MSMPVMTVDY 780 SKTVVKEPVD 790 TRVSCCKTKD 800 SDIYCTLNDS 810 NPSLCNSEAE 820 NIEPSVMKIS 830 SNSFMNVHLE 840 SKPVICDSRN 850 LTDHSKFACE 860 EYKQSIGSTS 870 SASVNHFDDL 880 YQPIGSSGIA 890 SSLQSLPPGI 900 KVDSLTLLKC 910 GENTSPVLDA 920 VLKSKKSSEF 930 LKHAGKETIV 940 EVGSDLPDSG 950 KGFASRENRR 960 NNGLSGKCLQ 970 EAQEEGNSIL 980 PERRGRPEIS 990 LDERGEGGHV 1000 HTSDDSEVVF 1010 SSCDLNLTME 1020 DSDGVTYALK 1030 CDSSGHAPEI 1040 VSTVHEDYSG 1050 SSESSNDESD 1060 SEDTDSDDSS 1070 IPRNRLQSVV 1080 VVPKNSTLPM 1090 EETSPCSSRS 1100 SQSYRHYSDH 1110 WEDERLESRR 1120 HLYEEKFESI 1130 ASKACPQTDK 1140 FFLHKGTEKN 1150 PEISFTQSSR 1160 KQIDNRLPEL 1170 SHPQSDGVDS 1180 TSHTDVKSDP 1190 LGHPNSEETV 1200 KAKIPSRQQE 1210 ELPIYSSDFE 1220 DVPNKSWQQT 1230 TFQNRPDSRL 1240 GKTELSFSSS 1250 CEIPHVDGLH 1260 SSEELRNLGW 1270 DFSQEKPSTT 1280 YQQPDSSYGA 1290 CGGHKYQQNA 1300 EQYGGTRDYW 1310 QGNGYWDPRS 1320 GRPPGTGVVY 1330 DRTQGQVPDS 1340 LTDDREEEEN 1350 WDQQDGSHFS 1360 DQSDKFLLSL 1370 QKDKGSVQAP 1380 EISSNSIKDT 1390 LAVNEKKDFS 1400 KNLEKNDIKD 1410 RGPLKKRRQE 1420 IESDSESDGE 1430 LQDRKKVRVE 1440 VEQGETSVPP 1450 GSALVGPSCV 1460 MDDFRDPQRW 1470 KECAKQGKMP 1480 CYFDLIEENV 1490 YLTERKKNKS 1500 HRDIKRMQCE 1510 CTPLSKDERA 1520 QGEIACGEDC 1530 LNRLLMIECS 1540 SRCPNGDYCS 1550 NRRFQRKQHA 1560 DVEVILTEKK 1570 GWGLRAAKDL 1580 PSNTFVLEYC 1590 GEVLDHKEFK 1600 ARVKEYARNK 1610 NIHYYFMALK 1620 NDEIIDATQK 1630 GNCSRFMNHS 1640 CEPNCETQKW 1650 TVNGQLRVGF 1660 FTTKLVPSGS 1670 ELTFDYQFQR 1680 YGKEAQKCFC 1690 GSANCRGYLG 1700 GENRVSIRAA 1710 GGKMKKERSR 1720 KKDSVDGELE 1730 ALMENGEGLS 1740 DKNQVLSLSR 1750 LMVRIETLEQ 1760 KLTCLELIQN 1770 THSQSCLKSF 1780 LERHGLSLLW 1790 IWMAELGDGR 1800 ESNQKLQEEI 1810 IKTLEHLPIP 1820 TKNMLEESKV 1830 LPIIQRWSQT 1840 KTAVPPLSEG 1850 DGYSSENTSR 1860 AHTPLNTPDP 1870 STKLSTEADT 1880 DTPKKLMFRR 1890 LKIISENSMD 1900 SAISDATSEL 1910 EGKDGKEDLD 1920 QLENVPVEEE 1930 EELQSQQLLP 1940 QQLPECKVDS 1950 ETNIEASKLP 1960 TSEPEADAEI 1970 EPKESNGTKL 1980 EEPINEETPS 1990 QDEEEGVSDV 2000 ESERSQEQPD 2010 KTVDISDLAT 2020 KLLDSWKDLK 2030 EVYRIPKKSQ 2040 TEKENTTTER 2050 GRDAVGFRDQ 2060 TPAPKTPNRS 2070 RERDPDKQTQ 2080 NKEKRKRRSS 2090 LSPPSSAYER 2100 GTKRPDDRYD 2110 TPTSKKKVRI 2120 KDRNKLSTEE 2130 RRKLFEQEVA 2140 QREAQKQQQQ 2150 MQNLGMTSPL 2160 PYDSLGYNAP 2170 HHPFAGYPPG 2180 YPMQAYVDPS 2190 NPNAGKVLLP 2200 TPSMDPVCSP 2210 APYDHAQPLV 2220 GHSTEPLSAP 2230 PPVPVVPHVA 2240 APVEVSSSQY 2250 VAQSDGVVHQ 2260 DSSVAVLPVP 2270 APGPVQGQNY 2280 SVWDSNQQSV 2290 SVQQQYSPAQ 2300 SQATIYYQGQ 2310 TCPTVYGVTS 2320 PYSQTTPPIV 2330 QSYAQPSLQY 2340 IQGQQIFTAH 2350 PQGVVVQPAA 2360 AVTTIVAPGQ 2370 PQPLQPSEMV 2380 VTNNLLDLPP 2390 PSPPKPKTIV 2400 LPPNWKTARD 2410 PEGKIYYYHV 2420 ITRQTQWDPP 2430 TWESPGDDAS 2440 LEHEAEMDLG 2450 TPTYDENPMK 2460 ASKKPKTAEA 2470 DTSSELAKKS 2480 KEVFRKEMSQ 2490 FIVQCLNPYR 2500 KPDCKVGRIT 2510 TTEDFKHLAR 2520 KLTHGVMNKE 2530 LKYCKNPEDL 2540 ECNENVKHKT 2550 KEYIKKYMQK 2560 FGAVYKPKED TELE

Gene Ontology

Classification GO ID Description
Biological Process GO:0010508 positive regulation of autophagy
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0043014 alpha-tubulin binding
Molecular Function GO:0140938 histone H3 methyltransferase activity
Molecular Function GO:0046975 histone H3K36 methyltransferase activity
Molecular Function GO:0140955 histone H3K36 trimethyltransferase activity
Molecular Function GO:0046872 metal ion binding
Molecular Function GO:0016279 protein-lysine N-methyltransferase activity
Biological Process GO:0051607 defense response to virus
Biological Process GO:0035987 endodermal cell differentiation
Biological Process GO:1902850 microtubule cytoskeleton organization involved in mitosis
Biological Process GO:0006298 mismatch repair
Biological Process GO:0034728 nucleosome organization
Biological Process GO:0018023 peptidyl-lysine trimethylation
Biological Process GO:0032727 positive regulation of interferon-alpha production
Biological Process GO:0045778 positive regulation of ossification
Biological Process GO:0032465 regulation of cytokinesis
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0010569 regulation of double-strand break repair via homologous recombination
Biological Process GO:0010468 regulation of gene expression
Biological Process GO:0010793 regulation of mRNA export from nucleus
Biological Process GO:1905634 regulation of protein localization to chromatin
Biological Process GO:0043279 response to alkaloid
Biological Process GO:0010038 response to metal ion
Biological Process GO:0034340 response to type I interferon
Biological Process GO:0048863 stem cell differentiation
Biological Process GO:0006368 transcription elongation by RNA polymerase II

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] 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.

[3] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.