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Protein

N-lysine methyltransferase KMT5A

Gene

Kmt5a

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

Functioni

Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei268S-adenosyl-L-methioninePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Methyltransferase, Repressor, Transferase
Biological processCell cycle, Cell division, Mitosis, Transcription, Transcription regulation
LigandS-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
N-lysine methyltransferase KMT5ACurated (EC:2.1.1.-)
Alternative name(s):
H4-K20-HMTase KMT5A
Histone-lysine N-methyltransferase KMT5A (EC:2.1.1.43)
Lysine-specific methylase 5ABy similarity
PR/SET domain-containing protein 07
Short name:
PR-Set7
Short name:
PR/SET07
SET domain-containing protein 8
Gene namesi
Name:Kmt5aBy similarity
Synonyms:Setd8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1915206 Kmt5a

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

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002286891 – 349N-lysine methyltransferase KMT5AAdd BLAST349

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphoserineBy similarity1
Modified residuei129N6-acetyllysineBy similarity1
Modified residuei138PhosphothreonineCombined sources1

Post-translational modificationi

Acetylated at Lys-129; does not change methyltransferase activity. Deacetylated at Lys-129 by SIRT2; does not change methyltransferase activity (By similarity).By similarity
Ubiquitinated and degraded by the DCX(DTL) complex.Curated

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ2YDW7
PaxDbiQ2YDW7
PRIDEiQ2YDW7

PTM databases

iPTMnetiQ2YDW7
PhosphoSitePlusiQ2YDW7

Interactioni

Subunit structurei

Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A-mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H2O2-induced oxidative stress-dependent manner (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi212564, 2 interactors
IntActiQ2YDW7, 2 interactors
MINTiQ2YDW7
STRINGi10090.ENSMUSP00000052953

Structurei

3D structure databases

ProteinModelPortaliQ2YDW7
SMRiQ2YDW7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini213 – 334SETPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni223 – 225S-adenosyl-L-methionine bindingPROSITE-ProRule annotation3
Regioni295 – 296S-adenosyl-L-methionine bindingPROSITE-ProRule annotation2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi12 – 24Ala-richAdd BLAST13

Domaini

Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.By similarity

Sequence similaritiesi

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1085 Eukaryota
COG2940 LUCA
HOGENOMiHOG000020818
HOVERGENiHBG067546
InParanoidiQ2YDW7
KOiK11428

Family and domain databases

InterProiView protein in InterPro
IPR016858 Hist_H4-K20_MeTrfase
IPR001214 SET_dom
PfamiView protein in Pfam
PF00856 SET, 1 hit
PIRSFiPIRSF027717 Histone_H4-K20_mtfrase, 1 hit
SMARTiView protein in SMART
SM00317 SET, 1 hit
PROSITEiView protein in PROSITE
PS51571 SAM_MT43_PR_SET, 1 hit
PS50280 SET, 1 hit

Sequencei

Sequence statusi: Complete.

Q2YDW7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARGRKMCKP RAVEAAAAAV AATAPGPEMV EQRGPGRPRS DGENVFAGQS
60 70 80 90 100
KIYAYMSPNK CSAMRSPLQE ENSVAHHEVK CPGKPLAGIY RKREEKRNTG
110 120 130 140 150
NVIRSAVKSD EQKSKDTRRG PLAPFPNQKS EAAEPPKTPP PSCDSTNVAV
160 170 180 190 200
AKQALKKSLK GKQAPRKKSQ GKTQQNRKLT DFYPVRRSSR KSKAELQSEE
210 220 230 240 250
RKKNELIESG KEEGMKIDLI DGKGRGVIAT KQFSRGDFVV EYHGDLIEIT
260 270 280 290 300
DAKKREALYV QDPSTGCYMY YFQYLSKTYC VDATQETNRL GRLINHSKCG
310 320 330 340
NCQTKLHDID GVPHLILIAS RDIAAGEELL YDYGDRSKAS IEAYPWLKH
Length:349
Mass (Da):38,845
Last modified:December 20, 2005 - v1
Checksum:iC89BAE59660DA5AF
GO

Sequence cautioni

The sequence BAC27178 differs from that shown. Reason: Frameshift at position 20.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204N → ID in BAC27178 (PubMed:16141072).Curated1
Sequence conflicti260V → A in BAC27178 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK030904 mRNA Translation: BAC27178.1 Frameshift.
BC108333 mRNA Translation: AAI08334.1
RefSeqiNP_001297652.1, NM_001310723.1
NP_001297656.1, NM_001310727.1
NP_084517.2, NM_030241.3
UniGeneiMm.137966
Mm.472072

Genome annotation databases

GeneIDi67956
KEGGimmu:67956

Similar proteinsi

Entry informationi

Entry nameiKMT5A_MOUSE
AccessioniPrimary (citable) accession number: Q2YDW7
Secondary accession number(s): Q8C0J9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: December 20, 2005
Last modified: March 28, 2018
This is version 103 of the entry and version 1 of the sequence. See 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

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