Uniprot ID:Q03164	Protein name: Histone-lysine N-methyltransferase 2A	Gene : KMT2A ALL1 CXXC7 HRX HTRX MLL MLL1 TRX1
Protein Family:"Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, TRX/MLL subfamily"	Squence Length : 3969

Sequnce	>Q03164 3970 MAHSCRWRFPARPGTTGGGGGGGRRGLGGAPRQRVPALLLPPGPPVGGGGPGAPPSPPAVAAAAAAAGSSGAGVPGGAAAASAASSSSASSSSSSSSSASSGPALLRVGPGFDAALQVSAAIGTNLRRFRAVFGESGGGGGSGEDEQFLGFGSDEEVRVRSPTRSPSVKTSPRKPRGRPRSGSDRNSAILSDPSVFSPLNKSETKSGDKIKKKDSKSIEKKRGRPPTFPGVKIKITHGKDISELPKGNKEDSLKKIKRTPSATFQQATKIKKLRAGKLSPLKSKFKTGKLQIGRKGVQIVRRRGRPPSTERIKTPSGLLINSELEKPQKVRKDKEGTPPLTKEDKTVVRQSPRRIKPVRIIPSSKRTDATIAKQLLQRAKKGAQKKIEKEAAQLQGRKVKTQVKNIRQFIMPVVSAISSRIIKTPRRFIEDEDYDPPIKIARLESTPNSRFSAPSCGSSEKSSAASQHSSQMSSDSSRSSSPSVDTSTDSQASEEIQVLPEERSDTPEVHPPLPISQSPENESNDRRSRRYSVSERSFGSRTTKKLSTLQSAPQQQTSSSPPPPLLTPPPPLQPASSISDHTPWLMPPTIPLASPFLPASTAPMQGKRKSILREPTFRWTSLKHSRSEPQYFSSAKYAKEGLIRKPIFDNFRPPPLTPEDVGFASGFSASGTAASARLFSPLHSGTRFDMHKRSPLLRAPRFTPSEAHSRIFESVTLPSNRTSAGTSSSGVSNRKRKRKVFSPIRSEPRSPSHSMRTRSGRLSSSELSPLTPPSSVSSSLSISVSPLATSALNPTFTFPSHSLTQSGESAEKNQRPRKQTSAPAEPFSSSSPTPLFPWFTPGSQTERGRNKDKAPEELSKDRDADKSVEKDKSRERDREREKENKRESRKEKRKKGSEIQSSSALYPVGRVSKEKVVGEDVATSSSAKKATGRKKSSSHDSGTDITSVTLGDTTAVKTKILIKKGRGNLEKTNLDLGPTAPSLEKEKTLCLSTPSSSTVKHSTSSIGSMLAQADKLPMTDKRVASLLKKAKAQLCKIEKSKSLKQTDQPKAQGQESDSSETSVRGPRIKHVCRRAAVALGRKRAVFPDDMPTLSALPWEEREKILSSMGNDDKSSIAGSEDAEPLAPPIKPIKPVTRNKAPQEPPVKKGRRSRRCGQCPGCQVPEDCGVCTNCLDKPKFGGRNIKKQCCKMRKCQNLQWMPSKAYLQKQAKAVKKKEKKSKTSEKKDSKESSVVKNVVDSSQKPTPSAREDPAPKKSSSEPPPRKPVEEKSEEGNVSAPGPESKQATTPASRKSSKQVSQPALVIPPQPPTTGPPRKEVPKTTPSEPKKKQPPPPESGPEQSKQKKVAPRPSIPVKQKPKEKEKPPPVNKQENAGTLNILSTLSNGNSSKQKIPADGVHRIRVDFKEDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCRRCKFCHVCGRQHQATKQLLECNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDAQWSHDFSLCHDCAKLFAKGNFCPLCDKCYDDDDYESKMMQCGKCDRWVHSKCENLSDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISLKQVLTALLNSRTTSHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVLTEVSKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQPEIKKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVLPPSLDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGEPDSPTPLHPPTPPILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIGQNEWTHVNCALWSAEVFEDDDGSLKNVHMAVIRGKQLRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVFRRVFVDFEGISLRRKFLNGLEPENIHMMIGSMTIDCLGILNDLSDCEDKLFPIGYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRTIAHSPTSFTESSSKESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPRIRTPSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRRHSTSSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVDHVLGPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSSSSEMKQSSASDLVSKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELNVSKIGSFAEPSSVSFSSKEALSFPHLHLRGQRNDRDQHTDSTQSANSSPDEDTEVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSKSFLEPGQVTTGEEGNLKPEFMDEVLTPEYMGQRPCNNVSSDKIGDKGLSMPGVPKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSPASPLQIESTSPTEPISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQDRNLMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEEDIPFYSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGEERLASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATTRKSSQIPKRNGKENGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQDSLEAQLSSLESSRRVHTSTPSDKNLLDTYNTELLKSDSDNNNSDDCGNILPSDIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLFEVFSQQLPTTEPVDSSVSSSISAEEQFELPLELPSDLSVLTTRSPTVPSQNPSRLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHFIQGHMDADHISSPPCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQKYVPNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTLPNGVTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQSLFPSASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGLLIGVQPPPDPQLLVSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIAPSDVVSNMTLINFTPSQLPNHPSLLDLGSLNTSSHRTVPNIIKRSKSSIMYFEPAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVVSMQTTTTPTSSASVPGHVTLTNPRLLGTPDIGSISNLLIKASQQSLGIQDQPVALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSGEADEHYQLQHVNQLLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMGLEQNKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQLPLDKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTASVEQSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKTVEEEESNFSSPLMLWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLTDKVQEARSNARLKQLSFAGVNGLRMLGILHDAVVFLIEQLSGAKHCRNYKFRFHKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPNDEEEEEVQLKSARRATSMDLPMPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVDATMHGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDYKFPIEDASNKLPCNCGAKKCRKFLN
PHD-type domains repeats	ZN_FING 1147 1195 CXXC-type ZN_FING 1431 1482 PHD-type 1 ZN_FING 1479 1533 PHD-type 2 ZN_FING 1566 1627 PHD-type 3 ZN_FING 1870 1910 C2HC pre-PHD-type ZN_FING 1931 1978 PHD-type 4
Domin repeated regions	1431 - 1482 RVVCFLCASSGHVEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCRRCKFC 1479 - 1533 CKFCHVCGRQHQATKQLLECNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRC 1566 - 1627 GNFCPLCDKCYDDDDYESKMMQCGKCDRWVHSKCENLSDEMYEILSNLPESVAYTCVNCTER 1870 - 1910 NRQCALCLTYGDDSANDAGRLLYIGQNEWTHVNCALWSAEV 1931 - 1978 LRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHR
Function	"Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (PubMed:12453419, PubMed:20677832, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis. Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity)"
Motifs	MOTIF 2847 2855 9aaTAD
Binding Site	BINDING 3839 3839 S-adenosyl-L-methionine. BINDING 3841 3841 S-adenosyl-L-methionine. BINDING 3883 3883 S-adenosyl-L-methionine. BINDING 3958 3958 S-adenosyl-L-methionine
Mutation	"1150 1150 R->A: Impairs DNA-binding 1151 1151 R->A: Impairs DNA-binding 1153 1153 R->A: No effect on stability or DNA-binding 1154 1154 R->A: Impairs DNA-binding 1155 1155 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1158 1158 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1161 1161 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1162 1162 Q->A: No effect on stability or DNA-binding 1166 1166 D->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1167 1167 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1170 1170 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1172 1172 N->A: No effect on stability or DNA-binding 1173 1173 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1175 1175 D->A: Impairs DNA-binding 1176 1176 K->A: Impairs DNA-binding 1178 1181 KFGG->AAAA: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1178 1178 K->A: Impairs DNA-binding 1179 1179 F->A: Impairs DNA-binding 1183 1183 N->A: Impairs DNA-binding 1185 1185 K->A: Impairs DNA-binding 1186 1186 K->A: Impairs DNA-binding 1187 1187 Q->A: Impairs DNA-binding 1188 1188 C->A: No effect on stability or DNA-binding 1188 1188 C->D: Abolishes DNA-binding and increases CpG methylation of the HOXA9 promoter region 1189 1189 C->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1192 1192 R->A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1193 1193 K->A: Impairs DNA-binding 1194 1194 C->A: Impairs zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding 1195 1195 Q->A: No effect on stability or DNA-binding 1196 1196 N->A: No effect on stability or DNA-binding 1197 1197 L->A: Mildly decreases DNA-binding 1200 1200 M->A: No effect on DNA-binding 1581 1581 Y->A: Decreases affinity for histone H3K4me3 1587 1587 Q->A: Decreases affinity for histone H3K4me3 1594 1594 W->A: Abolishes interaction with histone H3K4me3 1594 1594 W->E: Decreases affinity for histone H3K4me3 1617 1617 V->A: Decreases binding affinity for PPIE 1619 1619 Y->A: May perturb protein folding and thereby decrease binding affinity for PPIE 2666 2667 DG->AA: Reduces cleavage without abolishing it when associated with 2718-A--A-2720 2718 2720 DGV->AAA: Abolishes cleavage by TASP1 when associated with 2666-A-A-2667 3858 3858 Y->A: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me 3858 3858 Y->F: Slightly affects methyltransferase activity toward unmodified or monomethylated H3K4me 3861 3861 N->I: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5 when associated with L-3867 3861 3861 N->T: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5 when associated with V-3867 3864 3864 R->A: Disrupts interaction with ASH2L and RBBP5 and nearly abolishes histone methyltransferase activity 3867 3867 Q->A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex when associated with A-3871 3867 3867 Q->L: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5 when associated with I-3861 3867 3867 Q->V: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5 when associated with T-3861 3869 3869 D->A: Does not affect methyltransferase activity of the enzyme alone or in complex when associated with A-3872 3871 3871 R->A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex when associated with A-3867 3872 3872 E->A: Does not affect methyltransferase activity of the enzyme alone or in complex when associated with A-3869 3874 3874 Y->A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex when associated with A-3878 3878 3878 K->A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex when associated with A-3874 3906 3906 N->A: Loss of the histone H3 methyltransferase activity 3942 3942 Y->A,F: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me 3942 3942 Y->F: Shifts from a specific monomethyltransferase to a di- and trimethyltransferase activity"
Disease	"DISEASE: Wiedemann-Steiner syndrome (WDSTS) [MIM:605130]: A syndrome characterized by hairy elbows (hypertrichosis cubiti), intellectual disability, a distinctive facial appearance, and short stature Facial characteristics include long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Note=Chromosomal aberrations involving KMT2A are a cause of acute leukemias Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11 2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13 3) with ELL; translocation t(11;19)(q23;p13 3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1 Translocation t(3;11)(q28;q23) with LPP Translocation t(10;11)(q22;q23) with TET1 Translocation t(9;11)(q34;q23) with DAB2IP Translocation t(4;11)(p12;q23) with FRYL Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis ; DISEASE: Note=A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia Translocation t(4;11)(q21;q23) with SEPT11"

Q03164 of Proteins PHD-type domain repeats