Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Histone-lysine N-methyltransferase SUV39H1

Gene

Suv39h1

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

Functioni

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.7 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].PROSITE-ProRule annotation1 Publication

Enzyme regulationi

Negatively regulated by CCAR2.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi181Zinc 1By similarity1
Metal bindingi181Zinc 2By similarity1
Metal bindingi183Zinc 1By similarity1
Metal bindingi186Zinc 1By similarity1
Metal bindingi186Zinc 3By similarity1
Metal bindingi194Zinc 1By similarity1
Metal bindingi195Zinc 1By similarity1
Metal bindingi195Zinc 2By similarity1
Metal bindingi222Zinc 2By similarity1
Metal bindingi222Zinc 3By similarity1
Metal bindingi226Zinc 2By similarity1
Metal bindingi228Zinc 3By similarity1
Metal bindingi232Zinc 3By similarity1
Binding sitei297S-adenosyl-L-methioninePROSITE-ProRule annotation1
Metal bindingi326Zinc 4By similarity1
Metal bindingi400Zinc 4By similarity1
Metal bindingi402Zinc 4By similarity1
Metal bindingi407Zinc 4By similarity1

GO - Molecular functioni

  • histone-lysine N-methyltransferase activity Source: UniProtKB
  • histone methyltransferase activity Source: MGI
  • histone methyltransferase activity (H3-K9 specific) Source: UniProtKB
  • methyltransferase activity Source: UniProtKB
  • protein methyltransferase activity Source: MGI
  • protein N-terminus binding Source: MGI
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • S-adenosylmethionine-dependent methyltransferase activity Source: MGI
  • transcription regulatory region sequence-specific DNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to hypoxia Source: MGI
  • chromatin silencing Source: UniProtKB
  • chromatin silencing at rDNA Source: MGI
  • DNA packaging Source: MGI
  • histone H3-K9 dimethylation Source: UniProtKB
  • histone H3-K9 methylation Source: MGI
  • histone H3-K9 trimethylation Source: UniProtKB
  • histone lysine methylation Source: MGI
  • negative regulation of circadian rhythm Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • rhythmic process Source: UniProtKB-KW
  • rRNA processing Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Biological rhythms, Cell cycle, Differentiation, rRNA processing, Transcription, Transcription regulation

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiR-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-427359. SIRT1 negatively regulates rRNA Expression.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase SUV39H1 (EC:2.1.1.43)
Alternative name(s):
Histone H3-K9 methyltransferase 1
Short name:
H3-K9-HMTase 1
Position-effect variegation 3-9 homolog
Suppressor of variegation 3-9 homolog 1
Short name:
Su(var)3-9 homolog 1
Gene namesi
Name:Suv39h1
Synonyms:Suv39h
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1099440. Suv39h1.

Subcellular locationi

GO - Cellular componenti

  • chromatin silencing complex Source: UniProtKB
  • chromosome, centromeric region Source: UniProtKB-SubCell
  • heterochromatin Source: UniProtKB
  • nuclear heterochromatin Source: MGI
  • nuclear lamina Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • rDNA heterochromatin Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice lacking Suv39h1 and Suv39h2 display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. They also show a higher level of histone H3 with phosphorylated 'Ser-10' and a reduced number of cells in G1 phase and an increased portion of cells with aberrant nuclear morphologies.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860581 – 412Histone-lysine N-methyltransferase SUV39H1Add BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei266N6-acetyllysineBy similarity1
Modified residuei391PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on serine residues, and to a lesser degree, on threonine residues.By similarity
Acetylated at Lys-266, leading to inhibition of enzyme activity. SIRT1-mediated deacetylation relieves this inhibition (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO54864.
MaxQBiO54864.
PaxDbiO54864.
PeptideAtlasiO54864.
PRIDEiO54864.

PTM databases

iPTMnetiO54864.
PhosphoSitePlusiO54864.

Expressioni

Tissue specificityi

Widely expressed.2 Publications

Developmental stagei

Expression present throughout embryogenesis. Higher expression between E9.5 and E13.

Gene expression databases

BgeeiENSMUSG00000039231.
ExpressionAtlasiO54864. baseline and differential.
GenevisibleiO54864. MM.

Interactioni

Subunit structurei

Interacts with CCAR2 and GFI1B. Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8 (By similarity). Interacts with H3 and H4 histones. Interacts with DNMT3B, CBX1, CBX4, MBD1, RUNX1, RUNX3, MYOD1, SMAD5 and RB1. Interacts with SBF1 through the SET domain. Interacts with HDAC1 and HDAC2 through the N-terminus and associates with the core histone deacetylase complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. Interacts (via SET domain) with MECOM; enhances MECOM transcriptional repression activity. Interacts with LMNA; the interaction increases stability of SUV39H1. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gfi1bO702372EBI-302230,EBI-4287943
Myod1P100853EBI-302230,EBI-4405734
SIRT1Q96EB64EBI-302230,EBI-1802965From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203586. 1 interactor.
DIPiDIP-32590N.
IntActiO54864. 5 interactors.
MINTiMINT-256025.
STRINGi10090.ENSMUSP00000111301.

Structurei

3D structure databases

ProteinModelPortaliO54864.
SMRiO54864.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 101ChromoPROSITE-ProRule annotationAdd BLAST59
Domaini179 – 240Pre-SETPROSITE-ProRule annotationAdd BLAST62
Domaini243 – 366SETPROSITE-ProRule annotationAdd BLAST124
Domaini396 – 412Post-SETPROSITE-ProRule annotationAdd BLAST17

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 89Interaction with SIRT1Add BLAST89
Regioni254 – 256S-adenosyl-L-methionine bindingBy similarity3
Regioni255 – 377Mediates interaction with MECOM1 PublicationAdd BLAST123
Regioni323 – 324S-adenosyl-L-methionine bindingBy similarity2

Domaini

Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin.
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.By similarity

Sequence similaritiesi

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.PROSITE-ProRule annotation
Contains 1 chromo domain.PROSITE-ProRule annotation
Contains 1 post-SET domain.PROSITE-ProRule annotation
Contains 1 pre-SET domain.PROSITE-ProRule annotation
Contains 1 SET domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1082. Eukaryota.
COG2940. LUCA.
GeneTreeiENSGT00780000121845.
HOGENOMiHOG000231244.
HOVERGENiHBG055621.
InParanoidiO54864.
KOiK11419.
TreeFamiTF106452.

Family and domain databases

InterProiIPR000953. Chromo/shadow_dom.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
IPR011381. Histone_H3-K9_MeTrfase.
IPR003616. Post-SET_dom.
IPR007728. Pre-SET_dom.
IPR001214. SET_dom.
[Graphical view]
PfamiPF00385. Chromo. 1 hit.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF009343. SUV39_SET. 1 hit.
SMARTiSM00298. CHROMO. 1 hit.
SM00508. PostSET. 1 hit.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF54160. SSF54160. 1 hit.
PROSITEiPS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
PS50868. POST_SET. 1 hit.
PS50867. PRE_SET. 1 hit.
PS51579. SAM_MT43_SUVAR39_3. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O54864-1) [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
MAENLKGCSV CCKSSWNQLQ DLCRLAKLSC PALGVSKKNL YDFEVEYLCD
60 70 80 90 100
YKKIREQEYY LVKWRGYPDS ENTWEPRQNL KCIRVLKQFH KDLERELVRR
110 120 130 140 150
HRRSKPPRHL DPNLANYLVQ KAKQRRALQR WEQELNAKRS HLGRITVENE
160 170 180 190 200
VDLDGPPRSF VYINEYRVGE GITLNQVAVG CECQDCLLAP TGGCCPGASL
210 220 230 240 250
HKFAYNDQGQ VRLKAGQPIY ECNSRCCCGY DCPNRVVQKG IRYDLCIFRT
260 270 280 290 300
NDGRGWGVRT LEKIRKNSFV MEYVGEIITS EEAERRGQIY DRQGATYLFD
310 320 330 340 350
LDYVEDVYTV DAAYYGNISH FVNHSCDPNL QVYNVFIDNL DERLPRIAFF
360 370 380 390 400
ATRTIWAGEE LTFDYNMQVD PVDMESTRMD SNFGLAGLPG SPKKRVRIEC
410
KCGTTACRKY LF
Length:412
Mass (Da):47,754
Last modified:June 1, 1998 - v1
Checksum:i6B690F4FE7FD997C
GO
Isoform 2 (identifier: O54864-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MAENLK → LKEKVAATRGKRRLSVTVTLSVSTGDAGRGGRSGTDPLLKMGEPATL

Note: Incomplete sequence.Curated
Show »
Length:453
Mass (Da):51,889
Checksum:i64BE15984279410B
GO
Isoform 3 (identifier: O54864-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     277-286: IITSEEAERR → VPPGCYLLGK
     287-412: Missing.

Note: No experimental confirmation available.
Show »
Length:286
Mass (Da):33,111
Checksum:iE1BEB67AD19032E1
GO

Sequence cautioni

Isoform 2 : The sequence AAF60970 differs from that shown. Reason: Frameshift at position 35.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti364D → G in BAC40334 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0022081 – 6MAENLK → LKEKVAATRGKRRLSVTVTL SVSTGDAGRGGRSGTDPLLK MGEPATL in isoform 2. Curated6
Alternative sequenceiVSP_024029277 – 286IITSEEAERR → VPPGCYLLGK in isoform 3. 1 Publication10
Alternative sequenceiVSP_024030287 – 412Missing in isoform 3. 1 PublicationAdd BLAST126

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019969 mRNA. Translation: AAB92225.1.
AF193861 mRNA. Translation: AAF60969.1.
AF193862 mRNA. Translation: AAF60970.1. Frameshift.
AK088405 mRNA. Translation: BAC40334.1.
AK139757 mRNA. Translation: BAE24129.1.
AK169389 mRNA. Translation: BAE41136.1.
AL663032 Genomic DNA. Translation: CAM19494.1.
AL663032 Genomic DNA. Translation: CAM19495.1.
BC023860 mRNA. Translation: AAH23860.1.
AF149203 Genomic DNA. Translation: AAF73151.1.
CCDSiCCDS40846.1. [O54864-1]
RefSeqiNP_001277645.1. NM_001290716.1.
NP_035644.1. NM_011514.2. [O54864-1]
UniGeneiMm.479743.
Mm.9244.

Genome annotation databases

EnsembliENSMUST00000115636; ENSMUSP00000111299; ENSMUSG00000039231. [O54864-3]
ENSMUST00000115638; ENSMUSP00000111301; ENSMUSG00000039231. [O54864-1]
GeneIDi20937.
KEGGimmu:20937.
UCSCiuc009snq.2. mouse. [O54864-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019969 mRNA. Translation: AAB92225.1.
AF193861 mRNA. Translation: AAF60969.1.
AF193862 mRNA. Translation: AAF60970.1. Frameshift.
AK088405 mRNA. Translation: BAC40334.1.
AK139757 mRNA. Translation: BAE24129.1.
AK169389 mRNA. Translation: BAE41136.1.
AL663032 Genomic DNA. Translation: CAM19494.1.
AL663032 Genomic DNA. Translation: CAM19495.1.
BC023860 mRNA. Translation: AAH23860.1.
AF149203 Genomic DNA. Translation: AAF73151.1.
CCDSiCCDS40846.1. [O54864-1]
RefSeqiNP_001277645.1. NM_001290716.1.
NP_035644.1. NM_011514.2. [O54864-1]
UniGeneiMm.479743.
Mm.9244.

3D structure databases

ProteinModelPortaliO54864.
SMRiO54864.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203586. 1 interactor.
DIPiDIP-32590N.
IntActiO54864. 5 interactors.
MINTiMINT-256025.
STRINGi10090.ENSMUSP00000111301.

PTM databases

iPTMnetiO54864.
PhosphoSitePlusiO54864.

Proteomic databases

EPDiO54864.
MaxQBiO54864.
PaxDbiO54864.
PeptideAtlasiO54864.
PRIDEiO54864.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000115636; ENSMUSP00000111299; ENSMUSG00000039231. [O54864-3]
ENSMUST00000115638; ENSMUSP00000111301; ENSMUSG00000039231. [O54864-1]
GeneIDi20937.
KEGGimmu:20937.
UCSCiuc009snq.2. mouse. [O54864-1]

Organism-specific databases

CTDi6839.
MGIiMGI:1099440. Suv39h1.

Phylogenomic databases

eggNOGiKOG1082. Eukaryota.
COG2940. LUCA.
GeneTreeiENSGT00780000121845.
HOGENOMiHOG000231244.
HOVERGENiHBG055621.
InParanoidiO54864.
KOiK11419.
TreeFamiTF106452.

Enzyme and pathway databases

ReactomeiR-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-427359. SIRT1 negatively regulates rRNA Expression.

Miscellaneous databases

PROiO54864.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039231.
ExpressionAtlasiO54864. baseline and differential.
GenevisibleiO54864. MM.

Family and domain databases

InterProiIPR000953. Chromo/shadow_dom.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
IPR011381. Histone_H3-K9_MeTrfase.
IPR003616. Post-SET_dom.
IPR007728. Pre-SET_dom.
IPR001214. SET_dom.
[Graphical view]
PfamiPF00385. Chromo. 1 hit.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF009343. SUV39_SET. 1 hit.
SMARTiSM00298. CHROMO. 1 hit.
SM00508. PostSET. 1 hit.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF54160. SSF54160. 1 hit.
PROSITEiPS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
PS50868. POST_SET. 1 hit.
PS50867. PRE_SET. 1 hit.
PS51579. SAM_MT43_SUVAR39_3. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSUV91_MOUSE
AccessioniPrimary (citable) accession number: O54864
Secondary accession number(s): Q3TEW2
, Q3UT51, Q8C2L3, Q9JLC7, Q9JLP8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: June 1, 1998
Last modified: November 2, 2016
This is version 155 of the entry and version 1 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.