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Q5DW34 (EHMT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone-lysine N-methyltransferase EHMT1

EC=2.1.1.-
EC=2.1.1.43
Alternative name(s):
Euchromatic histone-lysine N-methyltransferase 1
Short name=Eu-HMTase1
G9a-like protein 1
Short name=GLP
Short name=GLP1
Lysine N-methyltransferase 1D
Gene names
Name:Ehmt1
Synonyms:Euhmtase1, Glp, Kmt1d
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1296 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Ref.1 Ref.4

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.1

Enzyme regulation

Methyltransferase activity is inhibited by BIX-01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively By similarity.

Subunit structure

Interacts with WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts with MPHOSPH8 By similarity. Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 By similarity. Heterodimer; heterodimerizes with EHMT2. Interacts (via ANK repeats) with RELA (when monomethylated at 'Lys-310'). Ref.1 Ref.5

Subcellular location

Nucleus. Chromosome. Note: Associates with euchromatic regions. Ref.1

Tissue specificity

Ubiquitous. Ref.1

Domain

The ANK repeats specifically recognize and bind H3K9me1 and H3K9me2 By similarity. They also specifically recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310'. Ref.5

The SET domain mediates interaction with WIZ By similarity. Ref.5

Disruption phenotype

Embryos die around E9.5. Levels of H3K9me1 and H3K9me2 are drastically reduced. Ref.1

Sequence similarities

Belongs to the class V-like SAM-binding methyltransferase superfamily.

Contains 8 ANK repeats.

Contains 1 pre-SET domain.

Contains 1 SET domain.

Sequence caution

The sequence CAM22112.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentChromosome
Nucleus
   Coding sequence diversityAlternative splicing
   DomainANK repeat
Repeat
   LigandMetal-binding
S-adenosyl-L-methionine
Zinc
   Molecular functionChromatin regulator
Methyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation

Inferred from direct assay Ref.4. Source: UniProtKB

embryo development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

histone H3-K27 methylation

Inferred from direct assay Ref.1. Source: GOC

histone H3-K9 methylation

Inferred from direct assay Ref.1. Source: GOC

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 17392792. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.5. Source: UniProtKB

peptidyl-lysine dimethylation

Inferred from mutant phenotype Ref.1. Source: UniProtKB

peptidyl-lysine monomethylation

Inferred from mutant phenotype Ref.1. Source: UniProtKB

   Cellular_componentchromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionC2H2 zinc finger domain binding

Inferred from physical interaction PubMed 16702210. Source: UniProt

histone methyltransferase activity (H3-K27 specific)

Inferred from direct assay Ref.1. Source: UniProtKB

histone methyltransferase activity (H3-K9 specific)

Inferred from direct assay Ref.1. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5DW34-1)

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.
Isoform 2 (identifier: Q5DW34-2)

The sequence of this isoform differs from the canonical sequence as follows:
     273-279: Missing.
     455-500: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q5DW34-3)

The sequence of this isoform differs from the canonical sequence as follows:
     550-597: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12961296Histone-lysine N-methyltransferase EHMT1
PRO_0000405844

Regions

Repeat735 – 76430ANK 1
Repeat770 – 79930ANK 2
Repeat803 – 83230ANK 3
Repeat836 – 86631ANK 4
Repeat870 – 89930ANK 5
Repeat903 – 93230ANK 6
Repeat936 – 96530ANK 7
Repeat969 – 100234ANK 8
Domain1058 – 112164Pre-SET
Domain1124 – 1241118SET
Region903 – 9053Histone H3K9me binding By similarity
Region1134 – 11363S-adenosyl-L-methionine binding By similarity
Region1160 – 117920Interaction with histone H3 By similarity
Region1198 – 11992S-adenosyl-L-methionine binding By similarity
Region1240 – 12434Interaction with histone H3 By similarity
Compositional bias440 – 4478Poly-Arg
Compositional bias1290 – 12934Poly-Ala

Sites

Metal binding10601Zinc 1 By similarity
Metal binding10601Zinc 2 By similarity
Metal binding10621Zinc 1 By similarity
Metal binding10661Zinc 1 By similarity
Metal binding10661Zinc 3 By similarity
Metal binding10711Zinc 1 By similarity
Metal binding10731Zinc 2 By similarity
Metal binding11031Zinc 2 By similarity
Metal binding11031Zinc 3 By similarity
Metal binding11071Zinc 2 By similarity
Metal binding11091Zinc 3 By similarity
Metal binding11131Zinc 3 By similarity
Metal binding12011Zinc 4 By similarity
Metal binding12541Zinc 4 By similarity
Metal binding12561Zinc 4 By similarity
Metal binding12611Zinc 4 By similarity
Binding site11531Histone H3K9me By similarity
Binding site11711S-adenosyl-L-methionine By similarity
Binding site12551S-adenosyl-L-methionine; via amide nitrogen By similarity

Natural variations

Alternative sequence273 – 2797Missing in isoform 2.
VSP_040724
Alternative sequence455 – 50046Missing in isoform 2.
VSP_040725
Alternative sequence550 – 59748Missing in isoform 3.
VSP_040726

Experimental info

Mutagenesis11531Y → V in LM7; does not prevent methyltransferase activity; when associated with F-1240. Ref.4
Mutagenesis1198 – 12014Missing in LM3; does not form heterodimer with EHMT2 and is defective in mediating both H3K9me and DNA methylation. Ref.4
Mutagenesis12011C → A in LM4; does not prevent methyltransferase activity. Ref.4
Mutagenesis12401Y → F in LM7; does not prevent methyltransferase activity; when associated with V-1153. Ref.4
Sequence conflict4111E → D in BAD90007. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 8, 2011. Version 2.
Checksum: B7783B6F38D3C7CB

FASTA1,296141,999
        10         20         30         40         50         60 
MAAADAEQAV LAKQETKQDC CMKTELLRED TPMAADEGST EKQEGETPMA ADGETNGSCE 

        70         80         90        100        110        120 
KSGDPSHLNA PKHTQENTRA SPQEGTNRVS RVAENGVSER DTEVGKQNHV TADDFMQTSV 

       130        140        150        160        170        180 
IGSNGYFLNK PALQGQPLRT PNILTSSLPG HAAKTLPGGA SKCRTLSALP QTPTTAPTVP 

       190        200        210        220        230        240 
GEGSADTEDR KPTASGTDVR VHRARKTMPK SILGLHAASK DHREVQDHKE PKEDINRNIS 

       250        260        270        280        290        300 
ECGRQQLLPT FPALHQSLPQ NQCYMATTKS QTACLPFVLA AAVSRKKKRR MGTYSLVPKK 

       310        320        330        340        350        360 
KTKVLKQRTV IEMFKSITHS TVGAKGEKAL DDSALHVNGE SLEMDSEDED SDELEDDEDH 

       370        380        390        400        410        420 
GAEQAAAFPT EDSRTSKESM SETDRAAKMD GDSEEEQESP DTGEDEDGGD ESDLSSESSI 

       430        440        450        460        470        480 
KKKFLKRRGK TDSPWIKPAR KRRRRSRKKP SSMLGSEACK SSPGSMEQAA LGDSAGYMEV 

       490        500        510        520        530        540 
SLDSLDLRVR GILSSQTENE GLASGPDVLG TDGLQEVPLC SCRMETPKSR EISTLANNQC 

       550        560        570        580        590        600 
MATESVDHEL GRCTNSVVKY ELMRPSNKAP LLVLCEDHRG RMVKHQCCPG CGYFCTAGNF 

       610        620        630        640        650        660 
MECQPESSIS HRFHKDCASR VNNASYCPHC GEEASKAKEV TIAKADTTST VTLAPGQEKS 

       670        680        690        700        710        720 
LAAEGRADTT TGSIAGAPED ERSQSTAPQA PECFDPAGPA GLVRPTSGLS QGPGKETLES 

       730        740        750        760        770        780 
ALIALDSEKP KKLRFHPKQL YFSARQGELQ KVLLMLVDGI DPNFKMEHQS KRSPLHAAAE 

       790        800        810        820        830        840 
AGHVDICHML VQAGANIDTC SEDQRTPLME AAENNHLDAV KYLIKAGAQV DPKDAEGSTC 

       850        860        870        880        890        900 
LHLAAKKGHY DVVQYLLSNG QMDVNCQDDG GWTPMIWATE YKHVELVKLL LSKGSDINIR 

       910        920        930        940        950        960 
DNEENICLHW AAFSGCVDIA EILLAAKCDL HAVNIHGDSP LHIAARENRY DCVVLFLSRD 

       970        980        990       1000       1010       1020 
SDVTLKNKEG ETPLQCASLS SQVWSALQMS KALRDSAPDK PVAVEKTVSR DIARGYERIP 

      1030       1040       1050       1060       1070       1080 
IPCVNAVDSE LCPTNYKYVS QNCVTSPMNI DRNITHLQYC VCVDDCSSST CMCGQLSMRC 

      1090       1100       1110       1120       1130       1140 
WYDKDGRLLP EFNMAEPPLI FECNHACSCW RNCRNRVVQN GLRARLQLYR TQDMGWGVRS 

      1150       1160       1170       1180       1190       1200 
LQDIPLGTFV CEYVGELISD SEADVREEDS YLFDLDNKDG EVYCIDARFY GNVSRFINHH 

      1210       1220       1230       1240       1250       1260 
CEPNLVPVRV FMSHQDLRFP RIAFFSTRLI QAGEQLGFDY GERFWDVKGK LFSCRCGSSK 

      1270       1280       1290 
CRHSSAALAQ RQASAAQEPQ ENGLPDTSSA AAADPL 

« Hide

Isoform 2 [UniParc].

Checksum: AB666EE7F3CE9EC3
Show »

FASTA1,243136,496
Isoform 3 [UniParc].

Checksum: 6D881B82F181F36E
Show »

FASTA1,248136,631

References

« Hide 'large scale' references
[1]"Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9."
Tachibana M., Ueda J., Fukuda M., Takeda N., Ohta T., Iwanari H., Sakihama T., Kodama T., Hamakubo T., Shinkai Y.
Genes Dev. 19:815-826(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH EHMT2, TISSUE SPECIFICITY.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-1296 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-1296 (ISOFORM 3).
Strain: C57BL/6.
Tissue: Brain.
[4]"G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription."
Tachibana M., Matsumura Y., Fukuda M., Kimura H., Shinkai Y.
EMBO J. 27:2681-2690(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-1153; 1198-ASN--CYS-1201; CYS-1201 AND TYR-1240.
[5]"Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling."
Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K. expand/collapse author list , Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X., Gozani O.
Nat. Immunol. 12:29-36(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN ANK REPEATS, INTERACTION WITH RELA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB205007 mRNA. Translation: BAD90007.1.
AL732525 Genomic DNA. Translation: CAM22112.1. Different initiation.
AL732525 Genomic DNA. Translation: CAM22113.1.
AL732525 Genomic DNA. Translation: CAM22114.1.
BC056938 mRNA. Translation: AAH56938.1.
BC089302 mRNA. Translation: AAH89302.1.
RefSeqNP_001012536.2. NM_001012518.3.
NP_001103156.1. NM_001109686.2.
NP_001103157.1. NM_001109687.2.
UniGeneMm.24176.

3D structure databases

ProteinModelPortalQ5DW34.
SMRQ5DW34. Positions 717-1264.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid218847. 6 interactions.
DIPDIP-49000N.
DIP-59572N.
IntActQ5DW34. 3 interactions.

PTM databases

PhosphoSiteQ5DW34.

Proteomic databases

PaxDbQ5DW34.
PRIDEQ5DW34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000046227; ENSMUSP00000046077; ENSMUSG00000036893. [Q5DW34-3]
ENSMUST00000102938; ENSMUSP00000100002; ENSMUSG00000036893. [Q5DW34-1]
ENSMUST00000114432; ENSMUSP00000110075; ENSMUSG00000036893. [Q5DW34-2]
ENSMUST00000147147; ENSMUSP00000119057; ENSMUSG00000036893.
GeneID77683.
KEGGmmu:77683.
UCSCuc008iph.3. mouse. [Q5DW34-3]
uc008ipi.3. mouse. [Q5DW34-1]
uc012brr.2. mouse. [Q5DW34-2]

Organism-specific databases

CTD79813.
MGIMGI:1924933. Ehmt1.

Phylogenomic databases

eggNOGCOG0666.
GeneTreeENSGT00750000117632.
HOGENOMHOG000231216.
HOVERGENHBG028394.
InParanoidQ5DW34.
KOK11420.
OMASDFGRQQ.
OrthoDBEOG744T8D.
PhylomeDBQ5DW34.
TreeFamTF106443.

Gene expression databases

BgeeQ5DW34.
GenevestigatorQ5DW34.

Family and domain databases

Gene3D1.25.40.20. 3 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR007728. Pre-SET_dom.
IPR003606. Pre-SET_Zn-bd_sub.
IPR001214. SET_dom.
[Graphical view]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 7 hits.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS50867. PRE_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio347359.
PROQ5DW34.
SOURCESearch...

Entry information

Entry nameEHMT1_MOUSE
AccessionPrimary (citable) accession number: Q5DW34
Secondary accession number(s): A2AIS3 expand/collapse secondary AC list , A2AIS4, Q5EBR1, Q6PGM0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 8, 2011
Last sequence update: March 8, 2011
Last modified: April 16, 2014
This is version 88 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot