Molecule Information

General Information of the Molecule (ID: Mol04295)

• Name: Histone-lysine N-methyltransferase 2D (KMT2D) ,Homo sapiens
• Synonyms: ALL1-related protein; Myeloid/lymphoid or mixed-lineage leukemia protein 2
• Molecule Type: Protein
• Gene Name: KMT2D
• Gene ID: 8085
• Sequence:
  MDSQKLAGEDKDSEPAADGPAASEDPSATESDLPNPHVGEVSVLSSGSPRLQETPQDCSG
  GPVRRCALCNCGEPSLHGQRELRRFELPFDWPRCPVVSPGGSPGPNEAVLPSEDLSQIG
  F PEGLTPAHLGEPGGSCWAHHWCAAWSAGVWGQEGPELCGVDKAIFSGISQRCSHCTRL
  GA SIPCRSPGCPRLYHFPCATASGSFLSMKTLQLLCPEHSEGAAYLEEARCAVCEGPGE
  LCD LFFCTSCGHHYHGACLDTALTARKRAGWQCPECKVCQACRKPGNDSKMLVCETCDK
  GYHT FCLKPPMEELPAHSWKCKACRVCRACGAGSAELNPNSEWFENYSLCHRCHKAQGG
  QTIRS VAEQHTPVCSRFSPPEPGDTPTDEPDALYVACQGQPKGGHVTSMQPKEPGPLQC
  EAKPLG KAGVQLEPQLEAPLNEEMPLLPPPEESPLSPPPEESPTSPPPEASRLSPPPEE
  LPASPLP EALHLSRPLEESPLSPPPEESPLSPPPESSPFSPLEESPLSPPEESPPSPAL
  ETPLSPPP EASPLSPPFEESPLSPPPEELPTSPPPEASRLSPPPEESPMSPPPEESPMS
  PPPEASRLF PPFEESPLSPPPEESPLSPPPEASRLSPPPEDSPMSPPPEESPMSPPPEV
  SRLSPLPVVS RLSPPPEESPLSPPPEESPTSPPPEASRLSPPPEDSPTSPPPEDSPASP
  PPEDSLMSLPL EESPLLPLPEEPQLCPRSEGPHLSPRPEEPHLSPRPEEPHLSPQAEEP
  HLSPQPEEPCLC AVPEEPHLSPQAEGPHLSPQPEELHLSPQTEEPHLSPVPEEPCLSPQ
  PEESHLSPQSEEP CLSPRPEESHLSPELEKPPLSPRPEKPPEEPGQCPAPEELPLFPPP
  GEPSLSPLLGEPAL SEPGEPPLSPLPEELPLSPSGEPSLSPQLMPPDPLPPPLSPIITA
  AAPPALSPLGELEYP FGAKGDSDPESPLAAPILETPISPPPEANCTDPEPVPPMILPPS
  PGSPVGPASPILMEPL PPQCSPLLQHSLVPQNSPPSQCSPPALPLSVPSPLSPIGKVVG
  VSDEAELHEMETEKVSE PECPALEPSATSPLPSPMGDLSCPAPSPAPALDDFSGLGEDT
  APLDGIDAPGSQPEPGQT PGSLASELKGSPVLLDPEELAPVTPMEVYPECKQTAGQGSP
  CEEQEEPRAPVAPTPPTLI KSDIVNEISNLSQGDASASFPGSEPLLGSPDPEGGGSLSM
  ELGVSTDVSPARDEGSLRLC TDSLPETDDSLLCDAGTAISGGKAEGEKGRRRSSPARSR
  IKQGRSSSFPGRRRPRGGAHG GRGRGRARLKSTASSIETLVVADIDSSPSKEEEEEDDD
  TMQNTVVLFSNTDKFVLMQDMC VVCGSFGRGAEGHLLACSQCSQCYHPYCVNSKITKVM
  LLKGWRCVECIVCEVCGQASDPS RLLLCDDCDISYHTYCLDPPLLTVPKGGWKCKWCVS
  CMQCGAASPGFHCEWQNSYTHCGP CASLVTCPICHAPYVEEDLLIQCRHCERWMHAGCE
  SLFTEDDVEQAADEGFDCVSCQPYV VKPVAPVAPPELVPMKVKEPEPQYFRFEGVWLTE
  TGMALLRNLTMSPLHKRRQRRGRLGL PGEAGLEGSEPSDALGPDDKKDGDLDTDELLKG
  EGGVEHMECEIKLEGPVSPDVEPGKEE TEESKKRKRKPYRPGIGGFMVRQRKSHTRTKK
  GPAAQAEVLSGDGQPDEVIPADLPAEGA VEQSLAEGDEKKKQQRRGRKKSKLEDMFPAY
  LQEAFFGKELLDLSRKALFAVGVGRPSFG LGTPKAKGDGGSERKELPTSQKGDDGPDIA
  DEESRGLEGKADTPGPEDGGVKASPVPSDP EKPGTPGEGMLSSDLDRISTEELPKMESK
  DLQQLFKDVLGSEREQHLGCGTPGLEGSRTP LQRPFLQGGLPLGNLPSSSPMDSYPGLC
  QSPFLDSRERGGFFSPEPGEPDSPWTGSGGTT PSTPTTPTTEGEGDGLSYNQRSLQRWE
  KDEELGQLSTISPVLYANINFPNLKQDYPDWSS RCKQIMKLWRKVPAADKAPYLQKAKD
  NRAAHRINKVQKQAESQINKQTKVGDIARKTDRP ALHLRIPPQPGALGSPPPAAAPTIF
  IGSPTTPAGLSTSADGFLKPPAGSVPGPDSPGELF LKLPPQVPAQVPSQDPFGLAPAYP
  LEPRFPTAPPTYPPYPSPTGAPAQPPMLGASSRPGA GQPGEFHTTPPGTPRHQPSTPDP
  FLKPRCPSLDNLAVPESPGVGGGKASEPLLSPPPFGE SRKALEVKKEELGASSPSYGPP
  NLGFVDSPSSGTHLGGLELKTPDVFKAPLTPRASQVEP QSPGLGLRPQEPPPAQALAPS
  PPSHPDIFRPGSYTDPYAQPPLTPRPQPPPPESCCALPP RSLPSDPFSRVPASPQSQSS
  SQSPLTPRPLSAEAFCPSPVTPRFQSPDPYSRPPSRPQSR DPFAPLHKPPRPQPPEVAF
  KAGSLAHTSLGAGGFPAALPAGPAGELHAKVPSGQPPNFVR SPGTGAFVGTPSPMRFTF
  PQAVGEPSLKPPVPQPGLPPPHGINSHFGPGPTLGKPQSTNY TVATGNFHPSGSPLGPS
  SGSTGESYGLSPLRPPSVLPPPAPDGSLPYLSHGASQRSGITS PVEKREDPGTGMGSSL
  ATAELPGTQDPGMSGLSQTELEKQRQRQRLRELLIRQQIQRNTL RQEKETAAAAAGAVG
  PPGSWGAEPSSPAFEQLSRGQTPFAGTQDKSSLVGLPPSKLSGPI LGPGSFPSDDRLSR
  PPPPATPSSMDVNSRQLVGGSQAFYQRAPYPGSLPLQQQQQQLWQQ QQATAATSMRFAM
  SARFPSTPGPELGRQALGSPLAGISTRLPGPGEPVPGPAGPAQFIEL RHNVQKGLGPGG
  TPFPGQGPPQRPRFYPVSEDPHRLAPEGLRGLAVSGLPPQKPSAPPAP ELNNSLHPTPH
  TKGPTLPTGLELVNRPPSSTELGRPNPLALEAGKLPCEDPELDDDFDAH KALEDDEELA
  HLGLGVDVAKGDDELGTLENLETNDPHLDDLLNGDEFDLLAYTDPELDTG DKKDIFNEH
  LRLVESANEKAEREALLRGVEPGPLGPEERPPPAADASEPRLASVLPEVKP KVEEGGRH
  PSPCQFTIATPKVEPAPAANSLGLGLKPGQSMMGSRDTRMGTGPFSSSGHTA EKASFGA
  TGGPPAHLLTPSPLSGPGGSSLLEKFELESGALTLPGGPAASGDELDKMESSL VASELP
  LLIEDLLEHEKKELQKKQQLSAQLQPAQQQQQQQQQHSLLSAPGPAQAMSLPHE GSSPS
  LAGSQQQLSLGLAGARQPGLPQPLMPTQPPAHALQQRLAPSMAMVSNQGHMLSGQ HGGQ
  AGLVPQQSSQPVLSQKPMGTMPPSMCMKPQQLAMQQQLANSFFPDTDLDKFAAEDI IDP
  IAKAKMVALKGIKKVMAQGSIGVAPGMNRQQVSLLAQRLSGGPSSDLQNHVAAGSGQ ER
  SAGDPSQPRPNPPTFAQGVINEADQRQYEEWLFHTQQLLQMQLKVLEEQIGVHRKSRK A
  LCAKQRTAKKAGREFPEADAEKLKLVTEQQSKIQKQLDQVRKQQKEHTNLMAEYRNKQQ
  QQQQQQQQQQQQHSAVLALSPSQSPRLLTKLPGQLLPGHGLQPPQGPPGGQAGGLRLTPG
  GMALPGQPGGPFLNTALAQQQQQQHSGGAGSLAGPSGGFFPGNLALRSLGPDSRLLQER
  Q LQLQQQRMQLAQKLQQQQQQQQQQQHLLGQVAIQQQQQQGPGVQTNQALGPKPQGLMP
  PS SHQGLLVQQLSPQPPQGPQGMLGPAQVAVLQQQHPGALGPQGPHRQVLMTQSRVLSS
  PQL AQQGQGLMGHRLVTAQQQQQQQQHQQQGSMAGLSHLQQSLMSHSGQPKLSAQPMGS
  LQQL QQQQQLQQQQQLQQQQQQQLQQQQQLQQQQLQQQQQQQQLQQQQQQQLQQQQQQL
  QQQQQ QQQQQFQQQQQQQQMGLLNQSRTLLSPQQQQQQQVALGPGMPAKPLQHFSSPGA
  LGPTLL LTGKEQNTVDPAVSSEATEGPSTHQGGPLAIGTTPESMATEPGEVKPSLSGDS
  QLLLVQP QPQPQPSSLQLQPPLRLPGQQQQQVSLLHTAGGGSHGQLGSGSSSEASSVPH
  LLAQPSVS LGDQPGSMTQNLLGPQQPMLERPMQNNTGPQPPKPGPVLQSGQGLPGVGIM
  PTVGQLRAQ LQGVLAKNPQLRHLSPQQQQQLQALLMQRQLQQSQAVRQTPPYQEPGTQT
  SPLQGLLGCQ PQLGGFPGPQTGPLQELGAGPRPQGPPRLPAPPGALSTGPVLGPVHPTP
  PPSSPQEPKRP SQLPSPSSQLPTEAQLPPTHPGTPKPQGPTLEPPPGRVSPAAAQLADT
  LFSKGLGPWDPP DNLAETQKPEQSSLVPGHLDQVNGQVVPEASQLSIKQEPREEPCALG
  AQSVKREANGEPI GAPGTSNHLLLAGPRSEAGHLLLQKLLRAKNVQLSTGRGSEGLRAE
  INGHIDSKLAGLEQ KLQGTPSNKEDAAARKPLTPKPKRVQKASDRLVSSRKKLRKEDGV
  RASEALLKQLKQELS LLPLTEPAITANFSLFAPFGSGCPVNGQSQLRGAFGSGALPTGP
  DYYSQLLTKNNLSNPP TPPSSLPPTPPPSVQQKMVNGVTPSEELGEHPKDAASARDSER
  ALRDTSEVKSLDLLAAL PTPPHNQTEDVRMESDEDSDSPDSIVPASSPESILGEEAPRF
  PHLGSGRWEQEDRALSPV IPLIPRASIPVFPDTKPYGALGLEVPGKLPVTTWEKGKGSE
  VSVMLTVSAAAAKNLNGVM VAVAELLSMKIPNSYEVLFPESPARAGTEPKKGEAEGPGG
  KEKGLEGKSPDTGPDWLKQF DAVLPGYTLKSQLDILSLLKQESPAPEPPTQHSYTYNVS
  NLDVRQLSAPPPEEPSPPPSP LAPSPASPPTEPLVELPTEPLAEPPVPSPLPLASSPES
  ARPKPRARPPEEGEDSRPPRLK KWKGVRWKRLRLLLTIQKGSGRQEDEREVAEFMEQLG
  TALRPDKVPRDMRRCCFCHEEGD GATDGPARLLNLDLDLWVHLNCALWSTEVYETQGGA
  LMNVEVALHRGLLTKCSLCQRTGA TSSCNRMRCPNVYHFACAIRAKCMFFKDKTMLCPM
  HKIKGPCEQELSSFAVFRRVYIERD EVKQIASIIQRGERLHMFRVGGLVFHAIGQLLPH
  QMADFHSATALYPVGYEATRIYWSLR TNNRRCCYRCSIGENNGRPEFVIKVIEQGLEDL
  VFTDASPQAVWNRIIEPVAAMRKEADM LRLFPEYLKGEELFGLTVHAVLRIAESLPGVE
  SCQNYLFRYGRHPLMELPLMINPTGCAR SEPKILTHYKRPHTLNSTSMSKAYQSTFTGE
  TNTPYSKQFVHSKSSQYRRLRTEWKNNVY LARSRIQGLGLYAAKDLEKHTMVIEYIGTI
  IRNEVANRREKIYEEQNRGIYMFRINNEHV IDATLTGGPARYINHSCAPNCVAEVVTFD
  KEDKIIIISSRRIPKGEELTYDYQFDFEDDQ HKIPCHCGAWNCRKWMN
• Function: Histone methyltransferase that catalyzes methyl grouptransfer from S-adenosyl-L-methionine to the epsilon-amino group of'Lys-4' of histone H3 . Part of chromatinremodeling machinery predominantly forms H3K4me1 methylation marks atactive chromatin sites where transcription and DNA repair take place. Acts as a coactivator for estrogenreceptor by being recruited by ESR1, thereby activating transcription. {ECO:0000269|PubMed:16603732,ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
• Uniprot ID: KMT2D_HUMAN
• Ensembl ID: ENSG0000016754818
• HGNC ID: HGNC:7133

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Inotuzumab ozogamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Mature B-cell neoplasms [.] [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Loss
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

References

• Ref 1: Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. Blood. 2024 Jul 4;144(1):61-73.