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Q9Z148 (EHMT2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Histone-lysine N-methyltransferase EHMT2
EC=2.1.1.-
EC=2.1.1.43
Alternative name(s):
Euchromatic histone-lysine N-methyltransferase 2
HLA-B-associated transcript 8
Histone H3-K9 methyltransferase 3
Short name=H3-K9-HMTase 3
Protein G9a
Gene names
Name:Ehmt2
Synonyms:Bat8, G9a, Ng36
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1263 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. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. Ref.1 Ref.7 Ref.10

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.6 Ref.7

Subunit structure

Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, GFI1B, L3MBTL2 and YAF2 By similarity. Heterodimer; heterodimerizes with EHMT1. Interacts with WIZ. Ref.7 Ref.8

Subcellular location

Nucleus. Chromosome Probable. Note: Almost excluded form nucleoli. Associates with euchromatic regions. Does not associate with heterochromatin. Ref.6 Ref.7

Tissue specificity

Ubiquitous. Ref.7

Domain

The ANK repeats bind H3K9me1 and H3K9me2 By similarity.

The SET domain mediates interaction with WIZ.

Post-translational modification

Methylated at Lys-239; automethylated By similarity.

Disruption phenotype

Mice show a higher level of histone H3 with acetylated 'Lys-9' (H3K9ac) and/or methylated 'Lys-4' (H3K4me), display severe developmental defects and die within E9.5-E12.5 stages. Ref.1

Sequence similarities

Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily.

Contains 7 ANK repeats.

Contains 1 post-SET domain.

Contains 1 pre-SET domain.

Contains 1 SET domain.

Caution

NG36 and G9a were originally thought to derive from two separate genes.

Sequence caution

The sequence AAC84164.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAC84165.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAH25539.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH58357.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Z148-1)

Also known as: G9a-L;

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: Q9Z148-2)

Also known as: G9a-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.
     58-71: AGLTGPPVPCLPSQ → MAAAAGAAAAAAAE
     426-459: Missing.
Isoform 3 (identifier: Q9Z148-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.
     58-71: AGLTGPPVPCLPSQ → MAAAAGAAAAAAAE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12631263Histone-lysine N-methyltransferase EHMT2
PRO_0000186069

Regions

Repeat702 – 73130ANK 1
Repeat737 – 76630ANK 2
Repeat770 – 79930ANK 3
Repeat803 – 83331ANK 4
Repeat837 – 86630ANK 5
Repeat870 – 89930ANK 6
Repeat903 – 93230ANK 7
Domain1025 – 108864Pre-SET
Domain1090 – 1212123SET
Domain1217 – 123317Post-SET
Region870 – 8723Histone H3K9me binding By similarity
Region1101 – 11033S-adenosyl-L-methionine binding By similarity
Region1127 – 114620Interaction with histone H3 By similarity
Region1165 – 11662S-adenosyl-L-methionine binding By similarity
Region1207 – 12104Interaction with histone H3 By similarity
Compositional bias352 – 37928Poly-Glu

Sites

Metal binding10271Zinc 1 By similarity
Metal binding10271Zinc 2 By similarity
Metal binding10291Zinc 1 By similarity
Metal binding10331Zinc 1 By similarity
Metal binding10331Zinc 3 By similarity
Metal binding10381Zinc 1 By similarity
Metal binding10401Zinc 2 By similarity
Metal binding10701Zinc 2 By similarity
Metal binding10701Zinc 3 By similarity
Metal binding10741Zinc 2 By similarity
Metal binding10761Zinc 3 By similarity
Metal binding10801Zinc 3 By similarity
Metal binding11681Zinc 4 By similarity
Metal binding12211Zinc 4 By similarity
Metal binding12231Zinc 4 By similarity
Metal binding12281Zinc 4 By similarity
Binding site11201Histone H3K9me By similarity
Binding site11381S-adenosyl-L-methionine By similarity

Amino acid modifications

Modified residue1931Phosphoserine By similarity
Modified residue2391N6,N6,N6-trimethyllysine; by EHMT2; alternate By similarity
Modified residue2391N6,N6-dimethyllysine; by EHMT2; alternate By similarity
Modified residue2851Phosphoserine By similarity
Modified residue2981Phosphoserine By similarity
Modified residue6081Phosphothreonine Ref.9
Modified residue12631Phosphothreonine By similarity

Natural variations

Alternative sequence1 – 5757Missing in isoform 2 and isoform 3.
VSP_002214
Alternative sequence58 – 7114AGLTG…CLPSQ → MAAAAGAAAAAAAE in isoform 2 and isoform 3.
VSP_002215
Alternative sequence426 – 45934Missing in isoform 2.
VSP_002216

Experimental info

Mutagenesis11201Y → V in GM7; defective in methyltransferase activity without affecting DNA methylation; when associated with F-1207. Ref.10
Mutagenesis11621R → H: Strongly reduces histone methyltransferase activity. Ref.6
Mutagenesis1165 – 11684Missing: Abolishes histone methyltransferase activity and subsequent repression. Ref.1 Ref.10
Mutagenesis1165 – 11684Missing in GM3; does not form heterodimer with EHMT1 and is defective in mediating both H3K9me and DNA methylation. Ref.1 Ref.10
Mutagenesis1165 – 11662NH → LE in GM6; does not form heterodimer with EHMT1 and is defective in mediating H3K9me.
Mutagenesis11681C → A in GM4; defective in methyltransferase activity without affecting DNA methylation. Ref.10
Mutagenesis12071Y → F in GM7; defective in methyltransferase activity without affecting DNA methylation; when associated with V-1120. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (G9a-L) [UniParc].

Last modified November 15, 2002. Version 2.
Checksum: 74DBFF9A36769589

FASTA1,263138,039
        10         20         30         40         50         60 
MRGLPRGRGL MRARGRGRAA PTGGRGRGRG GAHRGRGRPR SLLSLPRAQA SWAPQLPAGL 

        70         80         90        100        110        120 
TGPPVPCLPS QGEAPAEMGA LLLEKEPRGA AERVHSSLGD TPQSEETLPK ANPDSLEPAG 

       130        140        150        160        170        180 
PSSPASVTVT VGDEGADTPV GAASLIGDEP ESLEGDGGRI VLGHATKSFP SSPSKGGACP 

       190        200        210        220        230        240 
SRAKMSMTGA GKSPPSVQSL AMRLLSMPGA QGAATAGPEP SPATTAAQEG QPKVHRARKT 

       250        260        270        280        290        300 
MSKPSNGQPP IPEKRPPEVQ HFRMSDDMHL GKVTSDVAKR RKLNSGSLSE DLGSAGGSGD 

       310        320        330        340        350        360 
IILEKGEPRP LEEWETVVGD DFSLYYDAYS VDERVDSDSK SEVEALAEQL SEEEEEEEEE 

       370        380        390        400        410        420 
EEEEEEEEEE EEEEEEDEES GNQSDRSGSS GRRKAKKKWR KDSPWVKPSR KRRKREPPRA 

       430        440        450        460        470        480 
KEPRGVNGVG SSGPSEYMEV PLGSLELPSE GTLSPNHAGV SNDTSSLETE RGFEELPLCS 

       490        500        510        520        530        540 
CRMEAPKIDR ISERAGHKCM ATESVDGELL GCNAAILKRE TMRPSSRVAL MVLCEAHRAR 

       550        560        570        580        590        600 
MVKHHCCPGC GYFCTAGTFL ECHPDFRVAH RFHKACVSQL NGMVFCPHCG EDASEAQEVT 

       610        620        630        640        650        660 
IPRGDGGTPP IGTAAPALPP LAHDAPGRAD TSQPSARMRG HGEPRRPPCD PLADTIDSSG 

       670        680        690        700        710        720 
PSLTLPNGGC LSAVGLPPGP GREALEKALV IQESERRKKL RFHPRQLYLS VKQGELQKVI 

       730        740        750        760        770        780 
LMLLDNLDPN FQSDQQSKRT PLHAAAQKGS VEICHVLLQA GANINAVDKQ QRTPLMEAVV 

       790        800        810        820        830        840 
NNHLEVARYM VQLGGCVYSK EEDGSTCLHH AAKIGNLEMV SLLLSTGQVD VNAQDSGGWT 

       850        860        870        880        890        900 
PIIWAAEHKH IDVIRMLLTR GADVTLTDNE ENICLHWASF TGSAAIAEVL LNAQCDLHAV 

       910        920        930        940        950        960 
NYHGDTPLHI AARESYHDCV LLFLSRGANP ELRNKEGDTA WDLTPERSDV WFALQLNRKL 

       970        980        990       1000       1010       1020 
RLGVGNRAVR TEKIICRDVA RGYENVPIPC VNGVDGEPCP EDYKYISENC ETSTMNIDRN 

      1030       1040       1050       1060       1070       1080 
ITHLQHCTCV DDCSSSNCLC GQLSIRCWYD KDGRLLQEFN KIEPPLIFEC NQACSCWRSC 

      1090       1100       1110       1120       1130       1140 
KNRVVQSGIK VRLQLYRTAK MGWGVRALQT IPQGTFICEY VGELISDAEA DVREDDSYLF 

      1150       1160       1170       1180       1190       1200 
DLDNKDGEVY CIDARYYGNI SRFINHLCDP NIIPVRVFML HQDLRFPRIA FFSSRDIRTG 

      1210       1220       1230       1240       1250       1260 
EELGFDYGDR FWDIKSKYFT CQCGSEKCKH SAEAIALEQS RLARLDPHPE LLPDLSSLPP 


INT

« Hide

Isoform 2 (G9a-S) [UniParc].

Checksum: 52D345057AFCF200
Show »

FASTA1,172128,420
Isoform 3 [UniParc].

Checksum: 5DFF4CBADB784977
Show »

FASTA1,206131,772

References

« Hide 'large scale' references
[1]"G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis."
Tachibana M., Sugimoto K., Nozaki M., Ueda J., Ohta T., Ohki M., Fukuda M., Takeda N., Niida H., Kato H., Shinkai Y.
Genes Dev. 16:1779-1791(2002) [PubMed: 12130538] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF 1165-ASN--CYS-1168, DISRUPTION PHENOTYPE, FUNCTION.
[2]"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse."
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.
Genome Res. 13:2621-2636(2003) [PubMed: 14656967] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 129.
[3]"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: 19468303] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Mammary tumor.
[5]"Novel NG36/G9a gene products encoded within the human and mouse MHC class III regions."
Brown S.E., Campbell R.D., Sanderson C.M.
Mamm. Genome 12:916-924(2001) [PubMed: 11707778] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2).
[6]"Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3."
Tachibana M., Sugimoto K., Fukushima T., Shinkai Y.
J. Biol. Chem. 276:25309-25317(2001) [PubMed: 11316813] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-1162.
[7]"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: 15774718] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH EHMT1, TISSUE SPECIFICITY.
[8]"Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP."
Ueda J., Tachibana M., Ikura T., Shinkai Y.
J. Biol. Chem. 281:20120-20128(2006) [PubMed: 16702210] [Abstract]
Cited for: INTERACTION WITH WIZ AND EHMT1.
[9]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-608, MASS SPECTROMETRY.
Tissue: Liver.
[10]"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: 18818694] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF TYR-1120; 1165-ASN--CYS-1168; 1165-ASN-HIS-1166; CYS-1168 AND TYR-1207.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF109906 Genomic DNA. Translation: AAC84164.1. Sequence problems.
AF109906 Genomic DNA. Translation: AAC84165.1. Sequence problems.
AB077209 mRNA. Translation: BAC05482.1.
AB077210 mRNA. Translation: BAC05483.1.
CT025759 Genomic DNA. Translation: CAM27791.1.
BC025539 mRNA. Translation: AAH25539.1. Different initiation.
BC058357 mRNA. Translation: AAH58357.1. Different initiation.
IPIIPI00170261.
IPI00230523.
IPI00515297.
RefSeqNP_665829.1. NM_145830.1.
NP_671493.1. NM_147151.1.
UniGeneMm.35345.

3D structure databases

ProteinModelPortalQ9Z148.
SMRQ9Z148. Positions 670-1245.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-31916N.
IntActQ9Z148. 3 interactions.
MINTMINT-2736375.
STRINGQ9Z148.

PTM databases

PhosphoSiteQ9Z148.

Proteomic databases

PRIDEQ9Z148.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000013931; ENSMUSP00000013931; ENSMUSG00000013787.
ENSMUST00000078061; ENSMUSP00000077208; ENSMUSG00000013787.
ENSMUST00000114033; ENSMUSP00000109667; ENSMUSG00000013787.
GeneID110147.
KEGGmmu:110147.
UCSCuc008ced.1. mouse.

Organism-specific databases

CTD10919.
MGIMGI:2148922. Ehmt2.

Phylogenomic databases

GeneTreeENSGT00600000084355.
HOVERGENHBG028394.
PhylomeDBQ9Z148.

Gene expression databases

ArrayExpressQ9Z148.
BgeeQ9Z148.
CleanExMM_EHMT2.
GenevestigatorQ9Z148.
GermOnlineENSMUSG00000013787. Mus musculus.

Family and domain databases

InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR003616. Post-SET_dom.
IPR007728. Pre-SET_dom.
IPR003606. Pre-SET_Zn-bd_sub.
IPR001214. SET_dom.
[Graphical view]
Gene3DG3DSA:1.25.40.20. ANK. 1 hit.
KOK11420.
PfamPF12796. Ank_2. 3 hits.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 6 hits.
SM00508. PostSET. 1 hit.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMSSF48403. ANK. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS50868. POST_SET. False negative.
PS50867. PRE_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio363413.
SOURCESearch...

Entry information

Entry nameEHMT2_MOUSE
AccessionPrimary (citable) accession number: Q9Z148
Secondary accession number(s): A2CG75 expand/collapse secondary AC list , Q6PE08, Q8K4R6, Q8K4R7, Q9Z149
Entry history
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: January 25, 2012
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

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