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Protein

Histone-lysine N-methyltransferase SUV39H1

Gene

SUV39H1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). 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 large 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.6 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone].PROSITE-ProRule annotation2 Publications

Activity regulationi

Inhibited by S-adenosyl-L-homocysteine. Negatively regulated by CCAR2.2 Publications

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

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Methyltransferase, Repressor, Transferase
Biological processBiological rhythms, Cell cycle, Differentiation, Host-virus interaction, rRNA processing, Transcription, Transcription regulation
LigandMetal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214841 PKMTs methylate histone lysines
R-HSA-427359 SIRT1 negatively regulates rRNA expression
SIGNORiO43463

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
Lysine N-methyltransferase 1A
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:KMT1A, SUV39H
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101945.16
HGNCiHGNC:11479 SUV39H1
MIMi300254 gene
neXtProtiNX_O43463

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64W → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi67Y → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi266K → A: Loss of SIRT1-mediated up-regulation of enzymatic activity. 1 Publication1
Mutagenesisi266K → Q: Significant loss of enzymatic activity. 1 Publication1
Mutagenesisi320H → R: Strongly increases methylation of histone H3. 1 Publication1
Mutagenesisi324H → L or K: Abolishes methylation of histone H3. 1 Publication1
Mutagenesisi326C → A: Abolishes methylation of histone H3. 1 Publication1

Organism-specific databases

DisGeNETi6839
OpenTargetsiENSG00000101945
PharmGKBiPA36264

Chemistry databases

ChEMBLiCHEMBL1795118
GuidetoPHARMACOLOGYi2715

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860571 – 412Histone-lysine N-methyltransferase SUV39H1Add BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei266N6-acetyllysine1 Publication1
Modified residuei391PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on serine residues, and to a lesser degree, on threonine residues. The phosphorylated form is stabilized by SBF1 and is less active in its transcriptional repressor function.1 Publication
Acetylated at Lys-266, leading to inhibition of enzyme activity. SIRT1-mediated deacetylation relieves this inhibition.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO43463
MaxQBiO43463
PaxDbiO43463
PeptideAtlasiO43463
PRIDEiO43463
ProteomicsDBi48957

PTM databases

iPTMnetiO43463
PhosphoSitePlusiO43463

Expressioni

Developmental stagei

Accumulates during mitosis at centromeres during prometaphase, but dissociates from the centromere at the meta- to anaphase transition.

Gene expression databases

BgeeiENSG00000101945 Expressed in 166 organ(s), highest expression level in right lobe of liver
CleanExiHS_SUV39H1
GenevisibleiO43463 HS

Interactioni

Subunit structurei

Interacts with H3 and H4 histones. Interacts with GFI1B, DNMT3B, CBX1, CBX4, CCAR2, 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. Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. 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.16 Publications
(Microbial infection) Interacts with HTLV-1 Tax protein, leading to abrogate Tax transactivation of HTLV-1 LTR.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112706, 174 interactors
ComplexPortaliCPX-467 eNoSc complex
CORUMiO43463
DIPiDIP-32589N
IntActiO43463, 137 interactors
MINTiO43463
STRINGi9606.ENSP00000365877

Chemistry databases

BindingDBiO43463

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43463
SMRiO43463
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 MECOMBy similarityAdd 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.1 Publication
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.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1082 Eukaryota
COG2940 LUCA
GeneTreeiENSGT00780000121845
HOGENOMiHOG000231244
HOVERGENiHBG055621
InParanoidiO43463
KOiK11419
OMAiFDYKMQI
OrthoDBiEOG091G0Y4N
PhylomeDBiO43463
TreeFamiTF106452

Family and domain databases

CDDicd00024 CHROMO, 1 hit
InterProiView protein in InterPro
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
IPR011381 Histone_H3-K9_MeTrfase
IPR003616 Post-SET_dom
IPR007728 Pre-SET_dom
IPR001214 SET_dom
PfamiView protein in Pfam
PF00385 Chromo, 1 hit
PF05033 Pre-SET, 1 hit
PF00856 SET, 1 hit
PIRSFiPIRSF009343 SUV39_SET, 1 hit
SMARTiView protein in SMART
SM00298 CHROMO, 1 hit
SM00508 PostSET, 1 hit
SM00468 PreSET, 1 hit
SM00317 SET, 1 hit
SUPFAMiSSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS00598 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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O43463-1) [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 PALGISKRNL YDFEVEYLCD
60 70 80 90 100
YKKIREQEYY LVKWRGYPDS ESTWEPRQNL KCVRILKQFH KDLERELLRR
110 120 130 140 150
HHRSKTPRHL DPSLANYLVQ KAKQRRALRR WEQELNAKRS HLGRITVENE
160 170 180 190 200
VDLDGPPRAF VYINEYRVGE GITLNQVAVG CECQDCLWAP TGGCCPGASL
210 220 230 240 250
HKFAYNDQGQ VRLRAGLPIY ECNSRCRCGY DCPNRVVQKG IRYDLCIFRT
260 270 280 290 300
DDGRGWGVRT LEKIRKNSFV MEYVGEIITS EEAERRGQIY DRQGATYLFD
310 320 330 340 350
LDYVEDVYTV DAAYYGNISH FVNHSCDPNL QVYNVFIDNL DERLPRIAFF
360 370 380 390 400
ATRTIRAGEE LTFDYNMQVD PVDMESTRMD SNFGLAGLPG SPKKRVRIEC
410
KCGTESCRKY LF
Length:412
Mass (Da):47,907
Last modified:June 1, 1998 - v1
Checksum:iAF6F959AD20C6C76
GO
Isoform 2 (identifier: O43463-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:423
Mass (Da):49,148
Checksum:i67729933D3ABC7CF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213L → P in BAD96791 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0542861 – 6MAENLK → MVGMSRLRNDRLADPLT in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019968 mRNA Translation: AAB92224.1
CR541746 mRNA Translation: CAG46546.1
AK223071 mRNA Translation: BAD96791.1
AK299900 mRNA Translation: BAG61742.1
AK312547 mRNA Translation: BAG35445.1
AF196970 Genomic DNA No translation available.
CH471224 Genomic DNA Translation: EAW50756.1
CH471224 Genomic DNA Translation: EAW50757.1
BC006238 mRNA Translation: AAH06238.1
CCDSiCCDS14304.1 [O43463-1]
CCDS65252.1 [O43463-2]
RefSeqiNP_001269095.1, NM_001282166.1 [O43463-2]
NP_003164.1, NM_003173.3 [O43463-1]
UniGeneiHs.522639

Genome annotation databases

EnsembliENST00000337852; ENSP00000337976; ENSG00000101945 [O43463-2]
ENST00000376687; ENSP00000365877; ENSG00000101945 [O43463-1]
GeneIDi6839
KEGGihsa:6839
UCSCiuc004dkn.5 human [O43463-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019968 mRNA Translation: AAB92224.1
CR541746 mRNA Translation: CAG46546.1
AK223071 mRNA Translation: BAD96791.1
AK299900 mRNA Translation: BAG61742.1
AK312547 mRNA Translation: BAG35445.1
AF196970 Genomic DNA No translation available.
CH471224 Genomic DNA Translation: EAW50756.1
CH471224 Genomic DNA Translation: EAW50757.1
BC006238 mRNA Translation: AAH06238.1
CCDSiCCDS14304.1 [O43463-1]
CCDS65252.1 [O43463-2]
RefSeqiNP_001269095.1, NM_001282166.1 [O43463-2]
NP_003164.1, NM_003173.3 [O43463-1]
UniGeneiHs.522639

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MTSX-ray2.20A/B/C44-106[»]
ProteinModelPortaliO43463
SMRiO43463
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112706, 174 interactors
ComplexPortaliCPX-467 eNoSc complex
CORUMiO43463
DIPiDIP-32589N
IntActiO43463, 137 interactors
MINTiO43463
STRINGi9606.ENSP00000365877

Chemistry databases

BindingDBiO43463
ChEMBLiCHEMBL1795118
GuidetoPHARMACOLOGYi2715

PTM databases

iPTMnetiO43463
PhosphoSitePlusiO43463

Proteomic databases

EPDiO43463
MaxQBiO43463
PaxDbiO43463
PeptideAtlasiO43463
PRIDEiO43463
ProteomicsDBi48957

Protocols and materials databases

DNASUi6839
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000337852; ENSP00000337976; ENSG00000101945 [O43463-2]
ENST00000376687; ENSP00000365877; ENSG00000101945 [O43463-1]
GeneIDi6839
KEGGihsa:6839
UCSCiuc004dkn.5 human [O43463-1]

Organism-specific databases

CTDi6839
DisGeNETi6839
EuPathDBiHostDB:ENSG00000101945.16
GeneCardsiSUV39H1
HGNCiHGNC:11479 SUV39H1
MIMi300254 gene
neXtProtiNX_O43463
OpenTargetsiENSG00000101945
PharmGKBiPA36264
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1082 Eukaryota
COG2940 LUCA
GeneTreeiENSGT00780000121845
HOGENOMiHOG000231244
HOVERGENiHBG055621
InParanoidiO43463
KOiK11419
OMAiFDYKMQI
OrthoDBiEOG091G0Y4N
PhylomeDBiO43463
TreeFamiTF106452

Enzyme and pathway databases

ReactomeiR-HSA-3214841 PKMTs methylate histone lysines
R-HSA-427359 SIRT1 negatively regulates rRNA expression
SIGNORiO43463

Miscellaneous databases

ChiTaRSiSUV39H1 human
GeneWikiiSUV39H1
GenomeRNAii6839
PROiPR:O43463
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101945 Expressed in 166 organ(s), highest expression level in right lobe of liver
CleanExiHS_SUV39H1
GenevisibleiO43463 HS

Family and domain databases

CDDicd00024 CHROMO, 1 hit
InterProiView protein in InterPro
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
IPR011381 Histone_H3-K9_MeTrfase
IPR003616 Post-SET_dom
IPR007728 Pre-SET_dom
IPR001214 SET_dom
PfamiView protein in Pfam
PF00385 Chromo, 1 hit
PF05033 Pre-SET, 1 hit
PF00856 SET, 1 hit
PIRSFiPIRSF009343 SUV39_SET, 1 hit
SMARTiView protein in SMART
SM00298 CHROMO, 1 hit
SM00508 PostSET, 1 hit
SM00468 PreSET, 1 hit
SM00317 SET, 1 hit
SUPFAMiSSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS00598 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
ProtoNetiSearch...

Entry informationi

Entry nameiSUV91_HUMAN
AccessioniPrimary (citable) accession number: O43463
Secondary accession number(s): B2R6E8
, B4DST0, Q53G60, Q6FHK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 191 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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