UniProtKB - Q6Q783 (KMT5C_MOUSE)
Protein
Histone-lysine N-methyltransferase KMT5C
Gene
Kmt5c
Organism
Mus musculus (Mouse)
Status
Functioni
Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:15145825, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By similarity). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression (PubMed:15145825). Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions (PubMed:15145825). KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (PubMed:15750587, PubMed:16612004). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273).By similarity4 Publications
Catalytic activityi
- N6-methyl-L-lysyl20-[histone H4] + S-adenosyl-L-methionine = H+ + N6,N6-dimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-homocysteine3 PublicationsEC:2.1.1.3623 PublicationsThis reaction proceeds in the forward1 Publication direction.
- N6,N6-dimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-methionine = H+ + N6,N6,N6-trimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-homocysteine2 PublicationsThis reaction proceeds in the forward1 Publication direction.
- L-lysyl20-[histone H4] + S-adenosyl-L-methionine = H+ + N6-methyl-L-lysyl20-[histone H4] + S-adenosyl-L-homocysteineBy similarityEC:2.1.1.361By similarity
Activity regulationi
Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196).By similarity
Kineticsi
- KM=510 µM for histone H4K20me1 peptide1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 32 | S-adenosyl-L-methionineCombined sources1 Publication | 1 | |
Metal bindingi | 92 | Zinc 1; via pros nitrogenCombined sources | 1 | |
Metal bindingi | 95 | Zinc 1Combined sources1 Publication | 1 | |
Binding sitei | 121 | S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 141 | Zinc 1Combined sources1 Publication | 1 | |
Binding sitei | 160 | S-adenosyl-L-methionine; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 169 | S-adenosyl-L-methionineBy similarity | 1 | |
Metal bindingi | 185 | ZincBy similarity | 1 | |
Metal bindingi | 185 | Zinc 2Combined sources1 Publication | 1 | |
Sitei | 217 | Histone H4 binding; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 229 | ZincBy similarity | 1 | |
Metal bindingi | 229 | Zinc 2Combined sources1 Publication | 1 | |
Binding sitei | 230 | S-adenosyl-L-methionine; via amide nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 231 | ZincBy similarity | 1 | |
Metal bindingi | 231 | Zinc 2Combined sources1 Publication | 1 | |
Metal bindingi | 234 | ZincBy similarity | 1 | |
Metal bindingi | 234 | Zinc 2Combined sources1 Publication | 1 |
GO - Molecular functioni
- chromatin binding Source: UniProtKB
- histone binding Source: UniProtKB
- histone methyltransferase activity (H4-K20 specific) Source: MGI
- metal ion binding Source: UniProtKB-KW
- S-adenosyl-L-methionine binding Source: UniProtKB
GO - Biological processi
- DNA repair Source: UniProtKB
- histone H4-K20 dimethylation Source: InterPro
- histone H4-K20 trimethylation Source: MGI
- histone methylation Source: MGI
- positive regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
- positive regulation of isotype switching Source: UniProtKB
Keywordsi
Molecular function | Chromatin regulator, Methyltransferase, Repressor, Transferase |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-3214841, PKMTs methylate histone lysines |
Names & Taxonomyi
Protein namesi | Recommended name: Histone-lysine N-methyltransferase KMT5CCuratedAlternative name(s): Lysine-specific methyltransferase 5CBy similarity Suppressor of variegation 4-20 homolog 2 Short name: Su(var)4-20 homolog 2 Short name: Suv4-20h2 [histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5BCurated (EC:2.1.1.3623 Publications) [histone H4]-lysine20 N-methyltransferase KMT5BCurated (EC:2.1.1.361By similarity) |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2385262, Kmt5c |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Other locations
- Chromosome 1 Publication
Note: Associated with pericentric heterochromatin. CBX1 and CBX5 are required for the localization to pericentric heterochromatin.
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: GO_Central
Other locations
- condensed chromosome, centromeric region Source: MGI
- heterochromatin Source: MGI
- pericentric heterochromatin Source: MGI
Keywords - Cellular componenti
Chromosome, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 116 | M → S: Does not affect affinity for S-adenosyl-L-methionine. 1 Publication | 1 | |
Mutagenesisi | 161 | S → A: Does not methylates either an unmodified or monomethylated H4K20 substrate. Methylates a di-methylated H4K20 peptide. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000281794 | 1 – 468 | Histone-lysine N-methyltransferase KMT5CAdd BLAST | 468 |
Proteomic databases
EPDi | Q6Q783 |
jPOSTi | Q6Q783 |
MaxQBi | Q6Q783 |
PaxDbi | Q6Q783 |
PeptideAtlasi | Q6Q783 |
PRIDEi | Q6Q783 |
ProteomicsDBi | 264788 |
PTM databases
iPTMneti | Q6Q783 |
PhosphoSitePlusi | Q6Q783 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000059851, Expressed in retinal neural layer and 288 other tissues |
Genevisiblei | Q6Q783, MM |
Interactioni
Subunit structurei
Homodimer (PubMed:24049080).
Interacts with HP1 proteins CBX1, CBX3 and CBX5.
Interacts with RB1 family proteins RB1, RBL1 and RBL2.
4 PublicationsGO - Molecular functioni
- histone binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 231299, 3 interactors |
STRINGi | 10090.ENSMUSP00000104223 |
Miscellaneous databases
RNActi | Q6Q783, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6Q783 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 104 – 218 | SETPROSITE-ProRule annotationAdd BLAST | 115 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 114 – 117 | S-adenosyl-L-methionine bindingBy similarity | 4 | |
Regioni | 150 – 166 | Histone H4 bindingCombined sources1 PublicationAdd BLAST | 17 | |
Regioni | 182 – 183 | S-adenosyl-L-methionine bindingCombined sources1 Publication | 2 | |
Regioni | 348 – 441 | Required for heterochromatin localizationAdd BLAST | 94 |
Sequence similaritiesi
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.PROSITE-ProRule annotation
Phylogenomic databases
eggNOGi | KOG2589, Eukaryota |
GeneTreei | ENSGT00940000161700 |
HOGENOMi | CLU_040002_0_0_1 |
InParanoidi | Q6Q783 |
OMAi | LHRWGGC |
OrthoDBi | 236983at2759 |
PhylomeDBi | Q6Q783 |
TreeFami | TF106433 |
Family and domain databases
CDDi | cd19185, SET_KMT5C, 1 hit |
Gene3Di | 1.10.10.1700, 1 hit |
InterProi | View protein in InterPro IPR041938, Hist-Lys_N-MTase_N IPR044425, KMT5C_SET IPR001214, SET_dom IPR039977, Suv4-20/Set9 IPR025790, Suv4-20_animal |
PANTHERi | PTHR12977, PTHR12977, 1 hit |
Pfami | View protein in Pfam PF00856, SET, 1 hit |
SMARTi | View protein in SMART SM00317, SET, 1 hit |
PROSITEi | View protein in PROSITE PS51570, SAM_MT43_SUVAR420_2, 1 hit PS50280, SET, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q6Q783-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGPDRVTARE LCENDDLATS LVLDPYLGFR THKMNVSPVP TLRRQHHLRS
60 70 80 90 100
ALEAFLRQRD LEAAFRALTL GGWMAHYFQS RAPRQEAALK THIFCYLRAF
110 120 130 140 150
LPESGFTILP CTRYSMETNG AKIVSTRAWK KNEKLELLVG CIAELREEDE
160 170 180 190 200
DLLRAGENDF SIMYSTRKRS AQLWLGPAAF INHDCKPNCK FVPSDGNTAC
210 220 230 240 250
VKVLRDIEPG DEVTCFYGEG FFGEKNEHCE CYTCERKGEG AFRLQPREPE
260 270 280 290 300
LRPKPLDKYE LRETKRRLQQ GLVSSQQSLM SRWACSHLSP LRPDPFCAAC
310 320 330 340 350
QPSCLLPASP HMDYLPLWLQ RAPQPQPIVP PRKRHRRRRP RIRQASLPPV
360 370 380 390 400
LRTACVPLHR WGGCGPHCQL RAEAMVTLHL RPQTRWTPQQ DWYWARRYGL
410 420 430 440 450
PSVGRVELTR LAPALPAAPA PAGNPGPVPT PDFIPKQALA FAPFCPPKRL
460
RLVVSHGSID LDINSGEP
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z2F5 | D3Z2F5_MOUSE | Histone-lysine N-methyltransferase ... | Kmt5c | 164 | Annotation score: | ||
E0CXW4 | E0CXW4_MOUSE | Histone-lysine N-methyltransferase ... | Kmt5c | 145 | Annotation score: | ||
F6XZN9 | F6XZN9_MOUSE | Histone-lysine N-methyltransferase ... | Kmt5c | 147 | Annotation score: |
Sequence cautioni
The sequence AAH24816 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH85473 differs from that shown. Reason: Erroneous initiation.Curated
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY555193 mRNA Translation: AAT00540.1 AK154848 mRNA Translation: BAE32874.1 BC024816 mRNA Translation: AAH24816.1 Different initiation. BC085473 mRNA Translation: AAH85473.2 Different initiation. |
CCDSi | CCDS20743.2 |
RefSeqi | NP_001108490.1, NM_001115018.1 NP_666289.2, NM_146177.2 XP_006539837.1, XM_006539774.1 |
Genome annotation databases
Ensembli | ENSMUST00000098853; ENSMUSP00000096452; ENSMUSG00000059851 ENSMUST00000108582; ENSMUSP00000104223; ENSMUSG00000059851 ENSMUST00000108583; ENSMUSP00000104224; ENSMUSG00000059851 |
GeneIDi | 232811 |
KEGGi | mmu:232811 |
UCSCi | uc009eyi.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY555193 mRNA Translation: AAT00540.1 AK154848 mRNA Translation: BAE32874.1 BC024816 mRNA Translation: AAH24816.1 Different initiation. BC085473 mRNA Translation: AAH85473.2 Different initiation. |
CCDSi | CCDS20743.2 |
RefSeqi | NP_001108490.1, NM_001115018.1 NP_666289.2, NM_146177.2 XP_006539837.1, XM_006539774.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4AU7 | X-ray | 2.07 | A/B | 1-246 | [»] | |
SMRi | Q6Q783 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 231299, 3 interactors |
STRINGi | 10090.ENSMUSP00000104223 |
PTM databases
iPTMneti | Q6Q783 |
PhosphoSitePlusi | Q6Q783 |
Proteomic databases
EPDi | Q6Q783 |
jPOSTi | Q6Q783 |
MaxQBi | Q6Q783 |
PaxDbi | Q6Q783 |
PeptideAtlasi | Q6Q783 |
PRIDEi | Q6Q783 |
ProteomicsDBi | 264788 |
Protocols and materials databases
Antibodypediai | 46420, 64 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000098853; ENSMUSP00000096452; ENSMUSG00000059851 ENSMUST00000108582; ENSMUSP00000104223; ENSMUSG00000059851 ENSMUST00000108583; ENSMUSP00000104224; ENSMUSG00000059851 |
GeneIDi | 232811 |
KEGGi | mmu:232811 |
UCSCi | uc009eyi.2, mouse |
Organism-specific databases
CTDi | 84787 |
MGIi | MGI:2385262, Kmt5c |
Phylogenomic databases
eggNOGi | KOG2589, Eukaryota |
GeneTreei | ENSGT00940000161700 |
HOGENOMi | CLU_040002_0_0_1 |
InParanoidi | Q6Q783 |
OMAi | LHRWGGC |
OrthoDBi | 236983at2759 |
PhylomeDBi | Q6Q783 |
TreeFami | TF106433 |
Enzyme and pathway databases
Reactomei | R-MMU-3214841, PKMTs methylate histone lysines |
Miscellaneous databases
BioGRID-ORCSi | 232811, 1 hit in 54 CRISPR screens |
ChiTaRSi | Suv420h2, mouse |
PROi | PR:Q6Q783 |
RNActi | Q6Q783, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000059851, Expressed in retinal neural layer and 288 other tissues |
Genevisiblei | Q6Q783, MM |
Family and domain databases
CDDi | cd19185, SET_KMT5C, 1 hit |
Gene3Di | 1.10.10.1700, 1 hit |
InterProi | View protein in InterPro IPR041938, Hist-Lys_N-MTase_N IPR044425, KMT5C_SET IPR001214, SET_dom IPR039977, Suv4-20/Set9 IPR025790, Suv4-20_animal |
PANTHERi | PTHR12977, PTHR12977, 1 hit |
Pfami | View protein in Pfam PF00856, SET, 1 hit |
SMARTi | View protein in SMART SM00317, SET, 1 hit |
PROSITEi | View protein in PROSITE PS51570, SAM_MT43_SUVAR420_2, 1 hit PS50280, SET, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KMT5C_MOUSE | |
Accessioni | Q6Q783Primary (citable) accession number: Q6Q783 Secondary accession number(s): Q5RKP6, Q8R1C5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 3, 2007 |
Last sequence update: | July 5, 2004 | |
Last modified: | April 7, 2021 | |
This is version 124 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families