CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011046
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Histone-lysine N-methyltransferase 2A 
Protein Synonyms/Alias
 Lysine N-methyltransferase 2A; ALL-1; CXXC-type zinc finger protein 7; Myeloid/lymphoid or mixed-lineage leukemia; Myeloid/lymphoid or mixed-lineage leukemia protein 1; Trithorax-like protein; Zinc finger protein HRX; MLL cleavage product N320; N-terminal cleavage product of 320 kDa; p320; MLL cleavage product C180; C-terminal cleavage product of 180 kDa; p180 
Gene Name
 KMT2A 
Gene Synonyms/Alias
 ALL1; CXXC7; HRX; HTRX; MLL; MLL1; TRX1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
216KIKKKDSKSIEKKRGubiquitination[1]
220KDSKSIEKKRGRPPTubiquitination[1]
221DSKSIEKKRGRPPTFubiquitination[1]
277IKKLRAGKLSPLKSKubiquitination[2]
289KSKFKTGKLQIGRKGubiquitination[2]
636PQYFSSAKYAKEGLIacetylation[3]
645AKEGLIRKPIFDNFRubiquitination[1, 4]
1130EPLAPPIKPIKPVTRacetylation[3]
1235SKESSVVKNVVDSSQacetylation[3]
2299SASDLVSKSSSLKGEacetylation[5]
2613PQEDGSFKRRYPRRSubiquitination[6]
2754ENGTENLKIDRPEDAacetylation[5]
2958VISDSGEKRVTITEKacetylation[7]
3287RTVPNIIKRSKSSIMubiquitination[2]
3290PNIIKRSKSSIMYFEubiquitination[2]
3696AWKSLTDKVQEARSNubiquitination[2]
3707ARSNARLKQLSFAGVubiquitination[1, 4, 7, 8]
3749NYKFRFHKPEEANEPacetylation[9]
3784MFNFLASKHRQPPEYubiquitination[1, 4]
Reference
 [1] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786
Functional Description
 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. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. 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'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis. 
Sequence Annotation
 DOMAIN 1703 1748 Bromo; divergent.
 DOMAIN 2018 2074 FYR N-terminal.
 DOMAIN 3666 3747 FYR C-terminal.
 DOMAIN 3829 3945 SET.
 DOMAIN 3953 3969 Post-SET.
 DNA_BIND 169 180 A.T hook 1.
 DNA_BIND 217 227 A.T hook 2.
 DNA_BIND 301 309 A.T hook 3.
 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.
 REGION 3906 3907 S-adenosyl-L-methionine binding.
 MOTIF 2847 2855 9aaTAD.
 METAL 3909 3909 Zinc.
 METAL 3957 3957 Zinc.
 METAL 3959 3959 Zinc.
 METAL 3964 3964 Zinc.
 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.
 MOD_RES 153 153 Phosphoserine.
 MOD_RES 197 197 Phosphoserine.
 MOD_RES 518 518 Phosphoserine.
 MOD_RES 636 636 N6-acetyllysine.
 MOD_RES 680 680 Phosphoserine.
 MOD_RES 840 840 Phosphothreonine.
 MOD_RES 926 926 Phosphoserine.
 MOD_RES 1056 1056 Phosphoserine.
 MOD_RES 1130 1130 N6-acetyllysine.
 MOD_RES 1235 1235 N6-acetyllysine.
 MOD_RES 1845 1845 Phosphothreonine.
 MOD_RES 1858 1858 Phosphoserine.
 MOD_RES 2098 2098 Phosphoserine.
 MOD_RES 2147 2147 Phosphothreonine.
 MOD_RES 2151 2151 Phosphoserine.
 MOD_RES 2201 2201 Phosphoserine.
 MOD_RES 2525 2525 Phosphothreonine.
 MOD_RES 2955 2955 Phosphoserine.
 MOD_RES 3036 3036 Phosphoserine.
 MOD_RES 3372 3372 Phosphothreonine.
 MOD_RES 3511 3511 Phosphoserine.
 MOD_RES 3515 3515 Phosphoserine.
 CROSSLNK 216 216 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 220 220 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 221 221 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; Bromodomain; Chromatin regulator; Chromosomal rearrangement; Complete proteome; Direct protein sequencing; DNA-binding; Isopeptide bond; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 3969 AA 
Protein Sequence
MAHSCRWRFP ARPGTTGGGG GGGRRGLGGA PRQRVPALLL PPGPPVGGGG PGAPPSPPAV 60
AAAAAAAGSS GAGVPGGAAA ASAASSSSAS SSSSSSSSAS SGPALLRVGP GFDAALQVSA 120
AIGTNLRRFR AVFGESGGGG GSGEDEQFLG FGSDEEVRVR SPTRSPSVKT SPRKPRGRPR 180
SGSDRNSAIL SDPSVFSPLN KSETKSGDKI KKKDSKSIEK KRGRPPTFPG VKIKITHGKD 240
ISELPKGNKE DSLKKIKRTP SATFQQATKI KKLRAGKLSP LKSKFKTGKL QIGRKGVQIV 300
RRRGRPPSTE RIKTPSGLLI NSELEKPQKV RKDKEGTPPL TKEDKTVVRQ SPRRIKPVRI 360
IPSSKRTDAT IAKQLLQRAK KGAQKKIEKE AAQLQGRKVK TQVKNIRQFI MPVVSAISSR 420
IIKTPRRFIE DEDYDPPIKI ARLESTPNSR FSAPSCGSSE KSSAASQHSS QMSSDSSRSS 480
SPSVDTSTDS QASEEIQVLP EERSDTPEVH PPLPISQSPE NESNDRRSRR YSVSERSFGS 540
RTTKKLSTLQ SAPQQQTSSS PPPPLLTPPP PLQPASSISD HTPWLMPPTI PLASPFLPAS 600
TAPMQGKRKS ILREPTFRWT SLKHSRSEPQ YFSSAKYAKE GLIRKPIFDN FRPPPLTPED 660
VGFASGFSAS GTAASARLFS PLHSGTRFDM HKRSPLLRAP RFTPSEAHSR IFESVTLPSN 720
RTSAGTSSSG VSNRKRKRKV FSPIRSEPRS PSHSMRTRSG RLSSSELSPL TPPSSVSSSL 780
SISVSPLATS ALNPTFTFPS HSLTQSGESA EKNQRPRKQT SAPAEPFSSS SPTPLFPWFT 840
PGSQTERGRN KDKAPEELSK DRDADKSVEK DKSRERDRER EKENKRESRK EKRKKGSEIQ 900
SSSALYPVGR VSKEKVVGED VATSSSAKKA TGRKKSSSHD SGTDITSVTL GDTTAVKTKI 960
LIKKGRGNLE KTNLDLGPTA PSLEKEKTLC LSTPSSSTVK HSTSSIGSML AQADKLPMTD 1020
KRVASLLKKA KAQLCKIEKS KSLKQTDQPK AQGQESDSSE TSVRGPRIKH VCRRAAVALG 1080
RKRAVFPDDM PTLSALPWEE REKILSSMGN DDKSSIAGSE DAEPLAPPIK PIKPVTRNKA 1140
PQEPPVKKGR RSRRCGQCPG CQVPEDCGVC TNCLDKPKFG GRNIKKQCCK MRKCQNLQWM 1200
PSKAYLQKQA KAVKKKEKKS KTSEKKDSKE SSVVKNVVDS SQKPTPSARE DPAPKKSSSE 1260
PPPRKPVEEK SEEGNVSAPG PESKQATTPA SRKSSKQVSQ PALVIPPQPP TTGPPRKEVP 1320
KTTPSEPKKK QPPPPESGPE QSKQKKVAPR PSIPVKQKPK EKEKPPPVNK QENAGTLNIL 1380
STLSNGNSSK QKIPADGVHR IRVDFKEDCE AENVWEMGGL GILTSVPITP RVVCFLCASS 1440
GHVEFVYCQV CCEPFHKFCL EENERPLEDQ LENWCCRRCK FCHVCGRQHQ ATKQLLECNK 1500
CRNSYHPECL GPNYPTKPTK KKKVWICTKC VRCKSCGSTT PGKGWDAQWS HDFSLCHDCA 1560
KLFAKGNFCP LCDKCYDDDD YESKMMQCGK CDRWVHSKCE NLSDEMYEIL SNLPESVAYT 1620
CVNCTERHPA EWRLALEKEL QISLKQVLTA LLNSRTTSHL LRYRQAAKPP DLNPETEESI 1680
PSRSSPEGPD PPVLTEVSKQ DDQQPLDLEG VKRKMDQGNY TSVLEFSDDI VKIIQAAINS 1740
DGGQPEIKKA NSMVKSFFIR QMERVFPWFS VKKSRFWEPN KVSSNSGMLP NAVLPPSLDH 1800
NYAQWQEREE NSHTEQPPLM KKIIPAPKPK GPGEPDSPTP LHPPTPPILS TDRSREDSPE 1860
LNPPPGIEDN RQCALCLTYG DDSANDAGRL LYIGQNEWTH VNCALWSAEV FEDDDGSLKN 1920
VHMAVIRGKQ LRCEFCQKPG ATVGCCLTSC TSNYHFMCSR AKNCVFLDDK KVYCQRHRDL 1980
IKGEVVPENG FEVFRRVFVD FEGISLRRKF LNGLEPENIH MMIGSMTIDC LGILNDLSDC 2040
EDKLFPIGYQ CSRVYWSTTD ARKRCVYTCK IVECRPPVVE PDINSTVEHD ENRTIAHSPT 2100
SFTESSSKES QNTAEIISPP SPDRPPHSQT SGSCYYHVIS KVPRIRTPSY SPTQRSPGCR 2160
PLPSAGSPTP TTHEIVTVGD PLLSSGLRSI GSRRHSTSSL SPQRSKLRIM SPMRTGNTYS 2220
RNNVSSVSTT GTATDLESSA KVVDHVLGPL NSSTSLGQNT STSSNLQRTV VTVGNKNSHL 2280
DGSSSSEMKQ SSASDLVSKS SSLKGEKTKV LSSKSSEGSA HNVAYPGIPK LAPQVHNTTS 2340
RELNVSKIGS FAEPSSVSFS SKEALSFPHL HLRGQRNDRD QHTDSTQSAN SSPDEDTEVK 2400
TLKLSGMSNR SSIINEHMGS SSRDRRQKGK KSCKETFKEK HSSKSFLEPG QVTTGEEGNL 2460
KPEFMDEVLT PEYMGQRPCN NVSSDKIGDK GLSMPGVPKA PPMQVEGSAK ELQAPRKRTV 2520
KVTLTPLKME NESQSKNALK ESSPASPLQI ESTSPTEPIS ASENPGDGPV AQPSPNNTSC 2580
QDSQSNNYQN LPVQDRNLML PDGPKPQEDG SFKRRYPRRS ARARSNMFFG LTPLYGVRSY 2640
GEEDIPFYSS STGKKRGKRS AEGQVDGADD LSTSDEDDLY YYNFTRTVIS SGGEERLASH 2700
NLFREEEQCD LPKISQLDGV DDGTESDTSV TATTRKSSQI PKRNGKENGT ENLKIDRPED 2760
AGEKEHVTKS SVGHKNEPKM DNCHSVSRVK TQGQDSLEAQ LSSLESSRRV HTSTPSDKNL 2820
LDTYNTELLK SDSDNNNSDD CGNILPSDIM DFVLKNTPSM QALGESPESS SSELLNLGEG 2880
LGLDSNREKD MGLFEVFSQQ LPTTEPVDSS VSSSISAEEQ FELPLELPSD LSVLTTRSPT 2940
VPSQNPSRLA VISDSGEKRV TITEKSVASS ESDPALLSPG VDPTPEGHMT PDHFIQGHMD 3000
ADHISSPPCG SVEQGHGNNQ DLTRNSSTPG LQVPVSPTVP IQNQKYVPNS TDSPGPSQIS 3060
NAAVQTTPPH LKPATEKLIV VNQNMQPLYV LQTLPNGVTQ KIQLTSSVSS TPSVMETNTS 3120
VLGPMGGGLT LTTGLNPSLP TSQSLFPSAS KGLLPMSHHQ HLHSFPAATQ SSFPPNISNP 3180
PSGLLIGVQP PPDPQLLVSE SSQRTDLSTT VATPSSGLKK RPISRLQTRK NKKLAPSSTP 3240
SNIAPSDVVS NMTLINFTPS QLPNHPSLLD LGSLNTSSHR TVPNIIKRSK SSIMYFEPAP 3300
LLPQSVGGTA ATAAGTSTIS QDTSHLTSGS VSGLASSSSV LNVVSMQTTT TPTSSASVPG 3360
HVTLTNPRLL GTPDIGSISN LLIKASQQSL GIQDQPVALP PSSGMFPQLG TSQTPSTAAI 3420
TAASSICVLP STQTTGITAA SPSGEADEHY QLQHVNQLLA SKTGIHSSQR DLDSASGPQV 3480
SNFTQTVDAP NSMGLEQNKA LSSAVQASPT SPGGSPSSPS SGQRSASPSV PGPTKPKPKT 3540
KRFQLPLDKG NGKKHKVSHL RTSSSEAHIP DQETTSLTSG TGTPGAEAEQ QDTASVEQSS 3600
QKECGQPAGQ VAVLPEVQVT QNPANEQESA EPKTVEEEES NFSSPLMLWL QQEQKRKESI 3660
TEKKPKKGLV FEISSDDGFQ ICAESIEDAW KSLTDKVQEA RSNARLKQLS FAGVNGLRML 3720
GILHDAVVFL IEQLSGAKHC RNYKFRFHKP EEANEPPLNP HGSARAEVHL RKSAFDMFNF 3780
LASKHRQPPE YNPNDEEEEE VQLKSARRAT SMDLPMPMRF RHLKKTSKEA VGVYRSPIHG 3840
RGLFCKRNID AGEMVIEYAG NVIRSIQTDK REKYYDSKGI GCYMFRIDDS EVVDATMHGN 3900
AARFINHSCE PNCYSRVINI DGQKHIVIFA MRKIYRGEEL TYDYKFPIED ASNKLPCNCG 3960
AKKCRKFLN 3969 
Gene Ontology
 GO:0071339; C:MLL1 complex; IDA:UniProtKB.
 GO:0003680; F:AT DNA binding; NAS:UniProtKB.
 GO:0070577; F:histone acetyl-lysine binding; IDA:UniProtKB.
 GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
 GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0035162; P:embryonic hemopoiesis; TAS:UniProtKB.
 GO:0080182; P:histone H3-K4 trimethylation; IDA:BHF-UCL.
 GO:0043984; P:histone H4-K16 acetylation; IMP:UniProtKB.
 GO:2001040; P:positive regulation of cellular response to drug; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0032411; P:positive regulation of transporter activity; IMP:BHF-UCL.
 GO:0006461; P:protein complex assembly; IDA:UniProtKB.
 GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. 
Interpro
 IPR017956; AT_hook_DNA-bd_motif.
 IPR001487; Bromodomain.
 IPR003889; FYrich_C.
 IPR003888; FYrich_N.
 IPR016569; MeTrfase_trithorax.
 IPR003616; Post-SET_dom.
 IPR001214; SET_dom.
 IPR002857; Znf_CXXC.
 IPR011011; Znf_FYVE_PHD.
 IPR001965; Znf_PHD.
 IPR019787; Znf_PHD-finger.
 IPR013083; Znf_RING/FYVE/PHD. 
Pfam
 PF05965; FYRC
 PF05964; FYRN
 PF00628; PHD
 PF00856; SET
 PF02008; zf-CXXC 
SMART
 SM00384; AT_hook
 SM00297; BROMO
 SM00542; FYRC
 SM00541; FYRN
 SM00249; PHD
 SM00508; PostSET
 SM00317; SET 
PROSITE
 PS50014; BROMODOMAIN_2
 PS51543; FYRC
 PS51542; FYRN
 PS50868; POST_SET
 PS50280; SET
 PS51058; ZF_CXXC
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2 
PRINTS