CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000274
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Histone-lysine N-methyltransferase 2D 
Protein Synonyms/Alias
 Lysine N-methyltransferase 2D; ALL1-related protein; Myeloid/lymphoid or mixed-lineage leukemia protein 2 
Gene Name
 KMT2D 
Gene Synonyms/Alias
 ALR; MLL2; MLL4 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
1822KELPTSQKGDDGPDIacetylation[1]
2246STPDPFLKPRCPSLDacetylation[2, 3]
2468DPFAPLHKPPRPQPPacetylation[1, 2, 3, 4]
2755LVGLPPSKLSGPILGacetylation[1]
3079LVESANEKAEREALLacetylation[1, 3, 4]
3119ASVLPEVKPKVEEGGacetylation[4]
3121VLPEVKPKVEEGGRHacetylation[1, 2, 3]
3155NSLGLGLKPGQSMMGacetylation[1, 2, 3, 4]
3433KAKMVALKGIKKVMAacetylation[1, 2]
3436MVALKGIKKVMAQGSacetylation[1]
4004LGPGMPAKPLQHFSSacetylation[1, 2]
4465AGHLLLQKLLRAKNVacetylation[2]
4465AGHLLLQKLLRAKNVubiquitination[5]
4494INGHIDSKLAGLEQKacetylation[1]
4516KEDAAARKPLTPKPKacetylation[2, 4]
4653EELGEHPKDAASARDacetylation[1]
4756IPVFPDTKPYGALGLacetylation[1, 3]
4776LPVTTWEKGKGSEVSacetylation[1, 2, 3]
5024GTALRPDKVPRDMRRmethylation[6]
5276EPVAAMRKEADMLRLacetylation[2]
Reference
 [1] 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]
 [2] 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]
 [3] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [4] 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]
 [5] 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]
 [6] Large-scale global identification of protein lysine methylation in vivo.
 Cao XJ, Arnaudo AM, Garcia BA.
 Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510] 
Functional Description
 Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription. 
Sequence Annotation
 REPEAT 442 446 1.
 REPEAT 460 464 2.
 REPEAT 469 473 3.
 REPEAT 496 500 4.
 REPEAT 504 508 5.
 REPEAT 521 525 6.
 REPEAT 555 559 7.
 REPEAT 564 568 8.
 REPEAT 573 577 9.
 REPEAT 582 586 10.
 REPEAT 609 613 11.
 REPEAT 618 622 12.
 REPEAT 627 631 13.
 REPEAT 645 649 14.
 REPEAT 663 667 15.
 DOMAIN 5175 5235 FYR N-terminal.
 DOMAIN 5236 5321 FYR C-terminal.
 DOMAIN 5397 5513 SET.
 DOMAIN 5521 5537 Post-SET.
 ZN_FING 226 276 PHD-type 1.
 ZN_FING 229 274 RING-type 1; atypical.
 ZN_FING 273 323 PHD-type 2.
 ZN_FING 276 321 RING-type 2; degenerate.
 ZN_FING 1377 1430 PHD-type 3.
 ZN_FING 1427 1477 PHD-type 4.
 ZN_FING 1504 1559 PHD-type 5.
 ZN_FING 1507 1557 RING-type 3; atypical.
 ZN_FING 5092 5137 RING-type 4; degenerate.
 REGION 439 668 15 X 5 AA repeats of S/P-P-P-E/P-E/A.
 REGION 5474 5475 S-adenosyl-L-methionine binding (By
 MOTIF 2686 2690 LXXLL motif 1.
 MOTIF 3038 3042 LXXLL motif 2.
 MOTIF 4222 4236 LXXLL motif 3.
 MOTIF 4253 4257 LXXLL motif 4.
 MOTIF 4463 4467 LXXLL motif 5.
 MOTIF 4990 4994 LXXLL motif 6.
 METAL 5477 5477 Zinc (By similarity).
 METAL 5525 5525 Zinc (By similarity).
 METAL 5527 5527 Zinc (By similarity).
 METAL 5532 5532 Zinc (By similarity).
 BINDING 5451 5451 S-adenosyl-L-methionine (By similarity).
 MOD_RES 27 27 Phosphoserine.
 MOD_RES 1606 1606 Phosphoserine.
 MOD_RES 1671 1671 Phosphoserine.
 MOD_RES 2246 2246 N6-acetyllysine.
 MOD_RES 2274 2274 Phosphoserine.
 MOD_RES 2309 2309 Phosphoserine.
 MOD_RES 2311 2311 Phosphoserine.
 MOD_RES 3079 3079 N6-acetyllysine.
 MOD_RES 3130 3130 Phosphoserine.
 MOD_RES 3197 3197 Phosphothreonine.
 MOD_RES 3199 3199 Phosphoserine.
 MOD_RES 3433 3433 N6-acetyllysine.
 MOD_RES 4215 4215 Phosphoserine.
 MOD_RES 4359 4359 Phosphoserine.
 MOD_RES 4465 4465 N6-acetyllysine.
 MOD_RES 4738 4738 Phosphoserine.
 MOD_RES 4776 4776 N6-acetyllysine.
 MOD_RES 4822 4822 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Chromatin regulator; Coiled coil; Complete proteome; Disease mutation; Mental retardation; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 5537 AA 
Protein Sequence
MDSQKLAGED KDSEPAADGP AASEDPSATE SDLPNPHVGE VSVLSSGSPR LQETPQDCSG 60
GPVRRCALCN CGEPSLHGQR ELRRFELPFD WPRCPVVSPG GSPGPNEAVL PSEDLSQIGF 120
PEGLTPAHLG EPGGSCWAHH WCAAWSAGVW GQEGPELCGV DKAIFSGISQ RCSHCTRLGA 180
SIPCRSPGCP RLYHFPCATA SGSFLSMKTL QLLCPEHSEG AAYLEEARCA VCEGPGELCD 240
LFFCTSCGHH YHGACLDTAL TARKRAGWQC PECKVCQACR KPGNDSKMLV CETCDKGYHT 300
FCLKPPMEEL PAHSWKCKAC RVCRACGAGS AELNPNSEWF ENYSLCHRCH KAQGGQTIRS 360
VAEQHTPVCS RFSPPEPGDT PTDEPDALYV ACQGQPKGGH VTSMQPKEPG PLQCEAKPLG 420
KAGVQLEPQL EAPLNEEMPL LPPPEESPLS PPPEESPTSP PPEASRLSPP PEELPASPLP 480
EALHLSRPLE ESPLSPPPEE SPLSPPPESS PFSPLEESPL SPPEESPPSP ALETPLSPPP 540
EASPLSPPFE ESPLSPPPEE LPTSPPPEAS RLSPPPEESP MSPPPEESPM SPPPEASRLF 600
PPFEESPLSP PPEESPLSPP PEASRLSPPP EDSPMSPPPE ESPMSPPPEV SRLSPLPVVS 660
RLSPPPEESP LSPPPEESPT SPPPEASRLS PPPEDSPTSP PPEDSPASPP PEDSLMSLPL 720
EESPLLPLPE EPQLCPRSEG PHLSPRPEEP HLSPRPEEPH LSPQAEEPHL SPQPEEPCLC 780
AVPEEPHLSP QAEGPHLSPQ PEELHLSPQT EEPHLSPVPE EPCLSPQPEE SHLSPQSEEP 840
CLSPRPEESH LSPELEKPPL SPRPEKPPEE PGQCPAPEEL PLFPPPGEPS LSPLLGEPAL 900
SEPGEPPLSP LPEELPLSPS GEPSLSPQLM PPDPLPPPLS PIITAAAPPA LSPLGELEYP 960
FGAKGDSDPE SPLAAPILET PISPPPEANC TDPEPVPPMI LPPSPGSPVG PASPILMEPL 1020
PPQCSPLLQH SLVPQNSPPS QCSPPALPLS VPSPLSPIGK VVGVSDEAEL HEMETEKVSE 1080
PECPALEPSA TSPLPSPMGD LSCPAPSPAP ALDDFSGLGE DTAPLDGIDA PGSQPEPGQT 1140
PGSLASELKG SPVLLDPEEL APVTPMEVYP ECKQTAGQGS PCEEQEEPRA PVAPTPPTLI 1200
KSDIVNEISN LSQGDASASF PGSEPLLGSP DPEGGGSLSM ELGVSTDVSP ARDEGSLRLC 1260
TDSLPETDDS LLCDAGTAIS GGKAEGEKGR RRSSPARSRI KQGRSSSFPG RRRPRGGAHG 1320
GRGRGRARLK STASSIETLV VADIDSSPSK EEEEEDDDTM QNTVVLFSNT DKFVLMQDMC 1380
VVCGSFGRGA EGHLLACSQC SQCYHPYCVN SKITKVMLLK GWRCVECIVC EVCGQASDPS 1440
RLLLCDDCDI SYHTYCLDPP LLTVPKGGWK CKWCVSCMQC GAASPGFHCE WQNSYTHCGP 1500
CASLVTCPIC HAPYVEEDLL IQCRHCERWM HAGCESLFTE DDVEQAADEG FDCVSCQPYV 1560
VKPVAPVAPP ELVPMKVKEP EPQYFRFEGV WLTETGMALL RNLTMSPLHK RRQRRGRLGL 1620
PGEAGLEGSE PSDALGPDDK KDGDLDTDEL LKGEGGVEHM ECEIKLEGPV SPDVEPGKEE 1680
TEESKKRKRK PYRPGIGGFM VRQRKSHTRT KKGPAAQAEV LSGDGQPDEV IPADLPAEGA 1740
VEQSLAEGDE KKKQQRRGRK KSKLEDMFPA YLQEAFFGKE LLDLSRKALF AVGVGRPSFG 1800
LGTPKAKGDG GSERKELPTS QKGDDGPDIA DEESRGLEGK ADTPGPEDGG VKASPVPSDP 1860
EKPGTPGEGM LSSDLDRIST EELPKMESKD LQQLFKDVLG SEREQHLGCG TPGLEGSRTP 1920
LQRPFLQGGL PLGNLPSSSP MDSYPGLCQS PFLDSRERGG FFSPEPGEPD SPWTGSGGTT 1980
PSTPTTPTTE GEGDGLSYNQ RSLQRWEKDE ELGQLSTISP VLYANINFPN LKQDYPDWSS 2040
RCKQIMKLWR KVPAADKAPY LQKAKDNRAA HRINKVQKQA ESQINKQTKV GDIARKTDRP 2100
ALHLRIPPQP GALGSPPPAA APTIFIGSPT TPAGLSTSAD GFLKPPAGSV PGPDSPGELF 2160
LKLPPQVPAQ VPSQDPFGLA PAYPLEPRFP TAPPTYPPYP SPTGAPAQPP MLGASSRPGA 2220
GQPGEFHTTP PGTPRHQPST PDPFLKPRCP SLDNLAVPES PGVGGGKASE PLLSPPPFGE 2280
SRKALEVKKE ELGASSPSYG PPNLGFVDSP SSGTHLGGLE LKTPDVFKAP LTPRASQVEP 2340
QSPGLGLRPQ EPPPAQALAP SPPSHPDIFR PGSYTDPYAQ PPLTPRPQPP PPESCCALPP 2400
RSLPSDPFSR VPASPQSQSS SQSPLTPRPL SAEAFCPSPV TPRFQSPDPY SRPPSRPQSR 2460
DPFAPLHKPP RPQPPEVAFK AGSLAHTSLG AGGFPAALPA GPAGELHAKV PSGQPPNFVR 2520
SPGTGAFVGT PSPMRFTFPQ AVGEPSLKPP VPQPGLPPPH GINSHFGPGP TLGKPQSTNY 2580
TVATGNFHPS GSPLGPSSGS TGESYGLSPL RPPSVLPPPA PDGSLPYLSH GASQRSGITS 2640
PVEKREDPGT GMGSSLATAE LPGTQDPGMS GLSQTELEKQ RQRQRLRELL IRQQIQRNTL 2700
RQEKETAAAA AGAVGPPGSW GAEPSSPAFE QLSRGQTPFA GTQDKSSLVG LPPSKLSGPI 2760
LGPGSFPSDD RLSRPPPPAT PSSMDVNSRQ LVGGSQAFYQ RAPYPGSLPL QQQQQQLWQQ 2820
QQATAATSMR FAMSARFPST PGPELGRQAL GSPLAGISTR LPGPGEPVPG PAGPAQFIEL 2880
RHNVQKGLGP GGTPFPGQGP PQRPRFYPVS EDPHRLAPEG LRGLAVSGLP PQKPSAPPAP 2940
ELNNSLHPTP HTKGPTLPTG LELVNRPPSS TELGRPNPLA LEAGKLPCED PELDDDFDAH 3000
KALEDDEELA HLGLGVDVAK GDDELGTLEN LETNDPHLDD LLNGDEFDLL AYTDPELDTG 3060
DKKDIFNEHL RLVESANEKA EREALLRGVE PGPLGPEERP PPAADASEPR LASVLPEVKP 3120
KVEEGGRHPS PCQFTIATPK VEPAPAANSL GLGLKPGQSM MGSRDTRMGT GPFSSSGHTA 3180
EKASFGATGG PPAHLLTPSP LSGPGGSSLL EKFELESGAL TLPGGPAASG DELDKMESSL 3240
VASELPLLIE DLLEHEKKEL QKKQQLSAQL QPAQQQQQQQ QQHSLLSAPG PAQAMSLPHE 3300
GSSPSLAGSQ QQLSLGLAGA RQPGLPQPLM PTQPPAHALQ QRLAPSMAMV SNQGHMLSGQ 3360
HGGQAGLVPQ QSSQPVLSQK PMGTMPPSMC MKPQQLAMQQ QLANSFFPDT DLDKFAAEDI 3420
IDPIAKAKMV ALKGIKKVMA QGSIGVAPGM NRQQVSLLAQ RLSGGPSSDL QNHVAAGSGQ 3480
ERSAGDPSQP RPNPPTFAQG VINEADQRQY EEWLFHTQQL LQMQLKVLEE QIGVHRKSRK 3540
ALCAKQRTAK KAGREFPEAD AEKLKLVTEQ QSKIQKQLDQ VRKQQKEHTN LMAEYRNKQQ 3600
QQQQQQQQQQ QQHSAVLALS PSQSPRLLTK LPGQLLPGHG LQPPQGPPGG QAGGLRLTPG 3660
GMALPGQPGG PFLNTALAQQ QQQQHSGGAG SLAGPSGGFF PGNLALRSLG PDSRLLQERQ 3720
LQLQQQRMQL AQKLQQQQQQ QQQQQHLLGQ VAIQQQQQQG PGVQTNQALG PKPQGLMPPS 3780
SHQGLLVQQL SPQPPQGPQG MLGPAQVAVL QQQHPGALGP QGPHRQVLMT QSRVLSSPQL 3840
AQQGQGLMGH RLVTAQQQQQ QQQHQQQGSM AGLSHLQQSL MSHSGQPKLS AQPMGSLQQL 3900
QQQQQLQQQQ QLQQQQQQQL QQQQQLQQQQ LQQQQQQQQL QQQQQQQLQQ QQQQLQQQQQ 3960
QQQQQFQQQQ QQQQMGLLNQ SRTLLSPQQQ QQQQVALGPG MPAKPLQHFS SPGALGPTLL 4020
LTGKEQNTVD PAVSSEATEG PSTHQGGPLA IGTTPESMAT EPGEVKPSLS GDSQLLLVQP 4080
QPQPQPSSLQ LQPPLRLPGQ QQQQVSLLHT AGGGSHGQLG SGSSSEASSV PHLLAQPSVS 4140
LGDQPGSMTQ NLLGPQQPML ERPMQNNTGP QPPKPGPVLQ SGQGLPGVGI MPTVGQLRAQ 4200
LQGVLAKNPQ LRHLSPQQQQ QLQALLMQRQ LQQSQAVRQT PPYQEPGTQT SPLQGLLGCQ 4260
PQLGGFPGPQ TGPLQELGAG PRPQGPPRLP APPGALSTGP VLGPVHPTPP PSSPQEPKRP 4320
SQLPSPSSQL PTEAQLPPTH PGTPKPQGPT LEPPPGRVSP AAAQLADTLF SKGLGPWDPP 4380
DNLAETQKPE QSSLVPGHLD QVNGQVVPEA SQLSIKQEPR EEPCALGAQS VKREANGEPI 4440
GAPGTSNHLL LAGPRSEAGH LLLQKLLRAK NVQLSTGRGS EGLRAEINGH IDSKLAGLEQ 4500
KLQGTPSNKE DAAARKPLTP KPKRVQKASD RLVSSRKKLR KEDGVRASEA LLKQLKQELS 4560
LLPLTEPAIT ANFSLFAPFG SGCPVNGQSQ LRGAFGSGAL PTGPDYYSQL LTKNNLSNPP 4620
TPPSSLPPTP PPSVQQKMVN GVTPSEELGE HPKDAASARD SERALRDTSE VKSLDLLAAL 4680
PTPPHNQTED VRMESDEDSD SPDSIVPASS PESILGEEAP RFPHLGSGRW EQEDRALSPV 4740
IPLIPRASIP VFPDTKPYGA LGLEVPGKLP VTTWEKGKGS EVSVMLTVSA AAAKNLNGVM 4800
VAVAELLSMK IPNSYEVLFP ESPARAGTEP KKGEAEGPGG KEKGLEGKSP DTGPDWLKQF 4860
DAVLPGYTLK SQLDILSLLK QESPAPEPPT QHSYTYNVSN LDVRQLSAPP PEEPSPPPSP 4920
LAPSPASPPT EPLVELPTEP LAEPPVPSPL PLASSPESAR PKPRARPPEE GEDSRPPRLK 4980
KWKGVRWKRL RLLLTIQKGS GRQEDEREVA EFMEQLGTAL RPDKVPRDMR RCCFCHEEGD 5040
GATDGPARLL NLDLDLWVHL NCALWSTEVY ETQGGALMNV EVALHRGLLT KCSLCQRTGA 5100
TSSCNRMRCP NVYHFACAIR AKCMFFKDKT MLCPMHKIKG PCEQELSSFA VFRRVYIERD 5160
EVKQIASIIQ RGERLHMFRV GGLVFHAIGQ LLPHQMADFH SATALYPVGY EATRIYWSLR 5220
TNNRRCCYRC SIGENNGRPE FVIKVIEQGL EDLVFTDASP QAVWNRIIEP VAAMRKEADM 5280
LRLFPEYLKG EELFGLTVHA VLRIAESLPG VESCQNYLFR YGRHPLMELP LMINPTGCAR 5340
SEPKILTHYK RPHTLNSTSM SKAYQSTFTG ETNTPYSKQF VHSKSSQYRR LRTEWKNNVY 5400
LARSRIQGLG LYAAKDLEKH TMVIEYIGTI IRNEVANRRE KIYEEQNRGI YMFRINNEHV 5460
IDATLTGGPA RYINHSCAPN CVAEVVTFDK EDKIIIISSR RIPKGEELTY DYQFDFEDDQ 5520
HKIPCHCGAW NCRKWMN 5537 
Gene Ontology
 GO:0035097; C:histone methyltransferase complex; IPI:MGI.
 GO:0018024; F:histone-lysine N-methyltransferase activity; IEA:EC.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006342; P:chromatin silencing; ISS:UniProtKB.
 GO:0051568; P:histone H3-K4 methylation; ISS:UniProtKB.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0001555; P:oocyte growth; ISS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
 GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IMP:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0043627; P:response to estrogen stimulus; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR003889; FYrich_C.
 IPR003888; FYrich_N.
 IPR009071; HMG_box_dom.
 IPR003616; Post-SET_dom.
 IPR001214; SET_dom.
 IPR011011; Znf_FYVE_PHD.
 IPR001965; Znf_PHD.
 IPR019787; Znf_PHD-finger.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD. 
Pfam
 PF05965; FYRC
 PF05964; FYRN
 PF00628; PHD
 PF00856; SET 
SMART
 SM00542; FYRC
 SM00541; FYRN
 SM00398; HMG
 SM00249; PHD
 SM00508; PostSET
 SM00184; RING
 SM00317; SET 
PROSITE
 PS51543; FYRC
 PS51542; FYRN
 PS50868; POST_SET
 PS50280; SET
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS