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Protein

Histone-lysine N-methyltransferase 2E

Gene

Kmt2e

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone methyltransferase that specifically mono- and dimethylates 'Lys-4' of histone H3 (H3K4me1 and H3K4me2). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation. Plays an essential role in retinoic-acid-induced granulopoiesis by acting as a coactivator of RAR-alpha (RARA) in target gene promoters. Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages. Required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. Overexpression inhibits cell cycle progression, while knockdown induces cell cycle arrest at both the G1 and G2/M phases.4 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri118 – 166PHD-typePROSITE-ProRule annotationAdd BLAST49

GO - Molecular functioni

GO - Biological processi

  • cell cycle arrest Source: UniProtKB-KW
  • cellular response to retinoic acid Source: BHF-UCL
  • DNA methylation Source: UniProtKB
  • erythrocyte differentiation Source: UniProtKB
  • histone H3-K4 methylation Source: BHF-UCL
  • neutrophil activation Source: UniProtKB
  • neutrophil mediated immunity Source: UniProtKB
  • positive regulation of granulocyte differentiation Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • retinoic acid receptor signaling pathway Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

Cell cycle, Growth arrest, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-3214841. PKMTs methylate histone lysines.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase 2E (EC:2.1.1.43)
Short name:
Lysine N-methyltransferase 2E
Alternative name(s):
Myeloid/lymphoid or mixed-lineage leukemia protein 5 homolog
Gene namesi
Name:Kmt2e
Synonyms:Mll5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1924825. Kmt2e.

Subcellular locationi

  • Nucleus speckle By similarity

  • Note: Absent from the nucleolus.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Defects in immunity and hematopoiesis. Adult homozygous mice are obtained at reduced frequency because of postnatal lethality. Surviving animals display a variety of abnormalities, including male infertility, retarded growth and defects in multiple hematopoietic lineages. They also show increased susceptibility to spontaneous eye infections associated with a cell-autonomous impairment of neutrophil function. They exhibit a mild impairment of erythropoiesis and hematopoietic stem cells (HSCs) have impaired competitive repopulating capacity both under normal conditions and when subjected to self-renewal stimulation by NUP98-HOXA10. Homozygous HSCs show a dramatic sensitivity to DNA demethylation-induced differentiation (5-azadeoxycytidine).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi411C → A: Unable to repress cell-cycle-regulated element. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003414201 – 1868Histone-lysine N-methyltransferase 2EAdd BLAST1868

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi440O-linked (GlcNAc)By similarity1
Modified residuei837PhosphoserineBy similarity1
Modified residuei845PhosphoserineCombined sources1
Modified residuei1070PhosphoserineBy similarity1
Modified residuei1282PhosphoserineBy similarity1
Modified residuei1364PhosphoserineBy similarity1

Post-translational modificationi

O-glycosylation at Thr-440 in the SET domain by OGT is essential for the histone methyltransferase and the coactivator activity toward RARA in granulopoiesis (By similarity). The absence of Thr-440 glycosylation in assays done in vitro may explain why PubMed:18952892 and PubMed:19264965 did not detected any histone methyltransferase activity for this protein.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ3UG20.
PeptideAtlasiQ3UG20.
PRIDEiQ3UG20.

PTM databases

iPTMnetiQ3UG20.
PhosphoSitePlusiQ3UG20.

Expressioni

Inductioni

Up-regulated in reversibly arrested C2C12 myoblasts.1 Publication

Gene expression databases

BgeeiENSMUSG00000029004.
ExpressionAtlasiQ3UG20. baseline and differential.
GenevisibleiQ3UG20. MM.

Interactioni

Subunit structurei

Component of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with RARA (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi213280. 1 interactor.
IntActiQ3UG20. 1 interactor.
STRINGi10090.ENSMUSP00000092569.

Structurei

3D structure databases

ProteinModelPortaliQ3UG20.
SMRiQ3UG20.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini330 – 447SETPROSITE-ProRule annotationAdd BLAST118

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili559 – 613Sequence analysisAdd BLAST55

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1549 – 1856Pro-richSequence analysisAdd BLAST308

Sequence similaritiesi

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.PROSITE-ProRule annotation
Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
Contains 1 SET domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri118 – 166PHD-typePROSITE-ProRule annotationAdd BLAST49

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG1844. Eukaryota.
COG2940. LUCA.
GeneTreeiENSGT00520000055602.
HOVERGENiHBG105683.
InParanoidiQ3UG20.
KOiK09189.
OMAiNQEGYDR.
OrthoDBiEOG091G00UT.
TreeFamiTF106417.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001214. SET_dom.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50280. SET. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 12 Publications (identifier: Q3UG20-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSIAIPLGVD TTETSYLEMA AGSEPESVEA SPVVVEKSNS FPHQLYTSSS
60 70 80 90 100
HHSHSYIGLP YADHNYGARP PPTPPASPPP SGLISKNEVG IFTTPNFDET
110 120 130 140 150
SSATTISTSE DGSYGTDVTR CICGFTHDDG YMICCDKCSV WQHIDCMGID
160 170 180 190 200
RQHIPDTYLC ERCQPRSLDK ERAVLLQRRK RENMSDGDTS ATESGDEVPV
210 220 230 240 250
ELYTAFQHTP TSITLTASRV PKVTDKRRKK SGEKEQNFSK CKKAFREGSR
260 270 280 290 300
KSSRVKGSAP EIDPSSDSSN FVWETKIKAW MDRYEEANNN QYSEGVQREA
310 320 330 340 350
QRLAQRLGSG NDSKDMNKSE LSTNNSLFRP PVESHIQKNK KILKSAKDLP
360 370 380 390 400
PDALIIEYRG KFMLREQFEA NGYFFKRPYP FVLFYSKFHG LEMCVDARTF
410 420 430 440 450
GNEARFIRRS CTPNAEVRHE IEEGTIHLYI YSIQSIPKGT EITIAFDFDY
460 470 480 490 500
GNCKYKVDCA CLKENPECPV LKRSSESTEN INSGYETRRK KGKKEKDTSK
510 520 530 540 550
EKDIQNQNMT LDCEGTNNKI RSPETKQRKL SPLRLSVSNN QEPDFIDDME
560 570 580 590 600
EKTPISNEVE MESEEQIAER KRKMTREERK MEAILQAFAR LEKREKRREQ
610 620 630 640 650
ALERISTAKT EVKPECKESQ VIADAEVVQE QVKEETAIKP AAAKVNRTKQ
660 670 680 690 700
RKSFSRSRTH IGQQRRRHRT VSMCSDIPPS SPDIEVLSQQ NEIENTVLAI
710 720 730 740 750
EPETETAVAE IIPEAEVPAL NKCPTKYPKT KKHLVNEWLS EKNEKTGKPS
760 770 780 790 800
DSLSERPLRI TTDPEVLATQ LNSLPGLTYS PHVYSTPKHY IRFTSPFLSE
810 820 830 840 850
KKRRKETTEN ISGSCKKRWL KQALEEENST ILHRYHSPCQ ERSRSPTVNG
860 870 880 890 900
ENKSPLLLSD SCSLPDLTTP LKKRRLYQLL DTAYSESSTP TPSPYATPTH
910 920 930 940 950
TDITPTDPAF ATPPRIKSDD ETYRNGYKPI YSPVTPVTPG TPGNTMHFEN
960 970 980 990 1000
ISSPESSPEI KRCTYNQEGY DRPSNMLTLG PFRNSNLTEL GLQEIKTIGY
1010 1020 1030 1040 1050
TSPRSRTEVN RPCPGEKESV SDLQLGLDAV EPAALQKSME TPAHDRTEPS
1060 1070 1080 1090 1100
NQLDSTHSGR GTMYSSWVKS PDRTGVNFSV NSNLRDLTPS HQLETGGGFR
1110 1120 1130 1140 1150
VSESKCLIQQ DDTRGMFLGA AVFCTSEDGL ASGFGRTVND NLIDGSCTPQ
1160 1170 1180 1190 1200
NPPQKKKVSL LEYRKRQREA RKSGSKPENF ALISVSPHPS GSLSSSGDGC
1210 1220 1230 1240 1250
VHSSENGEQA ENQASLPLPP PAAAAAATAA AAYSASSEEG SSNCPVKDAN
1260 1270 1280 1290 1300
SSEKKDPEVQ WTASTSVEQV RERSYQRALL LSDHRKDKDS GGESPCVSCS
1310 1320 1330 1340 1350
PSHVQSPPSS HSNHIPQVHA QSLAPSLSEL MADPDAEGTE ATSTSECPSP
1360 1370 1380 1390 1400
DTSQSPSKTS KPGSPGPINP AQSHGKILTK PDSHWEATAT VSEADNSVHQ
1410 1420 1430 1440 1450
NPEPQHRQLS SNTPALSQNH APQAHALSAN DQLPQKLPSA PTKLHCPPSP
1460 1470 1480 1490 1500
HTENPPKSST PHTPVQHGYL SPKPPSQHLG SPFRPHHSQS PQVGTPQRET
1510 1520 1530 1540 1550
QRNFYAAAQN LQANPQQATS GALFTQTPSG QSSATYSQFN QQSLNSTAPP
1560 1570 1580 1590 1600
PPPPPPPSSY YQNQQPSANF QNYNQLKGSL SQQTVFTSGP NQALPGSTSQ
1610 1620 1630 1640 1650
QSVPGHHVTP GHFLPSQNPT IHHQPAAAAV VPPPPPPPPA PGPHLIQQPS
1660 1670 1680 1690 1700
SHQQHSVAHG VGPVHAVTPG SHIHSQTAGH HLPPPPPPPG PAPHHHPPPH
1710 1720 1730 1740 1750
PTTGLQSLQA QHQHVVNSAP PPPPPPPPPP PASVLVSGHH SASGQALHHP
1760 1770 1780 1790 1800
PHQGPPLFPA SAHPAVPPYP SQATHHTTLG PGPQHQPSGT GPHCPLPVAG
1810 1820 1830 1840 1850
PHLQPQGPNS IPTPTASGFC PHPHPGSVAL PHGVQGPQQA SPVPAQIPIH
1860
RAQVPPTFQN NYHGSGWH
Note: No experimental confirmation available.Curated
Length:1,868
Mass (Da):204,543
Last modified:June 10, 2008 - v2
Checksum:iB676F509E965415C
GO
Isoform 21 Publication (identifier: Q3UG20-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-580: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:1,288
Mass (Da):138,681
Checksum:i2166B0C437DBCC75
GO

Sequence cautioni

The sequence AAH36286 differs from that shown. Contaminating sequence. Potential poly-A sequence starting in position 486.Curated
The sequence AAH64079 differs from that shown. Contaminating sequence. Potential poly-A sequence starting in position 803.Curated
The sequence AAH89356 differs from that shown. Contaminating sequence. Potential poly-A sequence starting in position 495.Curated
The sequence AAI03802 differs from that shown. Contaminating sequence. Potential poly-A sequence starting in position 492.Curated
The sequence BAB25186 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC28936 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAE28389 differs from that shown. Reason: Frameshift at position 12.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62A → S in BAE43262 (PubMed:16141072).Curated1
Sequence conflicti181R → I in BAE28389 (PubMed:16141072).Curated1
Sequence conflicti320E → G in BAE28389 (PubMed:16141072).Curated1
Sequence conflicti489R → S in BAB25186 (PubMed:16141072).Curated1
Sequence conflicti512D → Y in BAC28936 (PubMed:16141072).Curated1
Sequence conflicti550E → G in BAE35839 (PubMed:16141072).Curated1
Sequence conflicti562E → G in BAE28389 (PubMed:16141072).Curated1
Sequence conflicti1005S → R in BAC28936 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0528131 – 580Missing in isoform 2. 2 PublicationsAdd BLAST580

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC122022 Genomic DNA. No translation available.
AK007682 mRNA. Translation: BAB25186.1. Different initiation.
AK021284 mRNA. Translation: BAE43262.1.
AK035078 mRNA. Translation: BAC28936.2. Different initiation.
AK148169 mRNA. Translation: BAE28389.1. Frameshift.
AK160519 mRNA. Translation: BAE35839.1.
BC036286 mRNA. Translation: AAH36286.1. Sequence problems.
BC064079 mRNA. Translation: AAH64079.1. Sequence problems.
BC089356 mRNA. Translation: AAH89356.1. Sequence problems.
BC103801 mRNA. Translation: AAI03802.1. Sequence problems.
CCDSiCCDS51430.1. [Q3UG20-1]
RefSeqiNP_081260.1. NM_026984.1. [Q3UG20-1]
XP_006535868.1. XM_006535805.3. [Q3UG20-1]
UniGeneiMm.205190.
Mm.403814.

Genome annotation databases

EnsembliENSMUST00000094962; ENSMUSP00000092569; ENSMUSG00000029004. [Q3UG20-1]
ENSMUST00000115128; ENSMUSP00000110781; ENSMUSG00000029004. [Q3UG20-1]
GeneIDi69188.
KEGGimmu:69188.
UCSCiuc008wqa.2. mouse. [Q3UG20-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC122022 Genomic DNA. No translation available.
AK007682 mRNA. Translation: BAB25186.1. Different initiation.
AK021284 mRNA. Translation: BAE43262.1.
AK035078 mRNA. Translation: BAC28936.2. Different initiation.
AK148169 mRNA. Translation: BAE28389.1. Frameshift.
AK160519 mRNA. Translation: BAE35839.1.
BC036286 mRNA. Translation: AAH36286.1. Sequence problems.
BC064079 mRNA. Translation: AAH64079.1. Sequence problems.
BC089356 mRNA. Translation: AAH89356.1. Sequence problems.
BC103801 mRNA. Translation: AAI03802.1. Sequence problems.
CCDSiCCDS51430.1. [Q3UG20-1]
RefSeqiNP_081260.1. NM_026984.1. [Q3UG20-1]
XP_006535868.1. XM_006535805.3. [Q3UG20-1]
UniGeneiMm.205190.
Mm.403814.

3D structure databases

ProteinModelPortaliQ3UG20.
SMRiQ3UG20.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi213280. 1 interactor.
IntActiQ3UG20. 1 interactor.
STRINGi10090.ENSMUSP00000092569.

PTM databases

iPTMnetiQ3UG20.
PhosphoSitePlusiQ3UG20.

Proteomic databases

PaxDbiQ3UG20.
PeptideAtlasiQ3UG20.
PRIDEiQ3UG20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000094962; ENSMUSP00000092569; ENSMUSG00000029004. [Q3UG20-1]
ENSMUST00000115128; ENSMUSP00000110781; ENSMUSG00000029004. [Q3UG20-1]
GeneIDi69188.
KEGGimmu:69188.
UCSCiuc008wqa.2. mouse. [Q3UG20-1]

Organism-specific databases

CTDi55904.
MGIiMGI:1924825. Kmt2e.

Phylogenomic databases

eggNOGiKOG1844. Eukaryota.
COG2940. LUCA.
GeneTreeiENSGT00520000055602.
HOVERGENiHBG105683.
InParanoidiQ3UG20.
KOiK09189.
OMAiNQEGYDR.
OrthoDBiEOG091G00UT.
TreeFamiTF106417.

Enzyme and pathway databases

ReactomeiR-MMU-3214841. PKMTs methylate histone lysines.

Miscellaneous databases

PROiQ3UG20.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029004.
ExpressionAtlasiQ3UG20. baseline and differential.
GenevisibleiQ3UG20. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001214. SET_dom.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiPS50280. SET. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKMT2E_MOUSE
AccessioniPrimary (citable) accession number: Q3UG20
Secondary accession number(s): Q3SYI5
, Q3TUY2, Q3V410, Q5FWI1, Q6P3B3, Q8BS65, Q8CFX7, Q9CVK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: November 2, 2016
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.