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Protein

N-lysine methyltransferase SETD8

Gene

Setd8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 + N(6)-methyl-L-lysine-[histone].PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei268 – 2681S-adenosyl-L-methioninePROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis, Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
N-lysine methyltransferase SETD8 (EC:2.1.1.-)
Alternative name(s):
H4-K20-HMTase SETD8
Histone-lysine N-methyltransferase SETD8 (EC:2.1.1.43)
PR/SET domain-containing protein 07
Short name:
PR-Set7
Short name:
PR/SET07
SET domain-containing protein 8
Gene namesi
Name:Setd8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1915206. Setd8.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 349349N-lysine methyltransferase SETD8PRO_0000228689Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei57 – 571PhosphoserineBy similarity
Modified residuei129 – 1291N6-acetyllysineBy similarity

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

PaxDbiQ2YDW7.
PRIDEiQ2YDW7.

PTM databases

PhosphoSiteiQ2YDW7.

Expressioni

Gene expression databases

GenevestigatoriQ2YDW7.

Interactioni

Subunit structurei

Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates SETD8-mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H2O(2)-induced oxidative stress-dependent manner (By similarity).By similarity

Protein-protein interaction databases

BioGridi212564. 1 interaction.
IntActiQ2YDW7. 2 interactions.
MINTiMINT-4113899.

Structurei

3D structure databases

ProteinModelPortaliQ2YDW7.
SMRiQ2YDW7. Positions 190-349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini213 – 334122SETPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni223 – 2253S-adenosyl-L-methionine bindingPROSITE-ProRule annotation
Regioni295 – 2962S-adenosyl-L-methionine bindingPROSITE-ProRule annotation

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi12 – 2413Ala-richAdd
BLAST

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
Contains 1 SET domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG2940.
HOGENOMiHOG000020818.
HOVERGENiHBG067546.
InParanoidiQ2YDW7.
KOiK11428.

Family and domain databases

InterProiIPR016858. Hist_H4-K20_MeTrfase.
IPR001214. SET_dom.
[Graphical view]
PANTHERiPTHR22884:SF11. PTHR22884:SF11. 1 hit.
PfamiPF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF027717. Histone_H4-K20_mtfrase. 1 hit.
SMARTiSM00317. SET. 1 hit.
[Graphical view]
PROSITEiPS51571. SAM_MT43_PR_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]

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 BAC27178.1 differs from that shown. Reason: Frameshift at position 20. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti204 – 2041N → ID in BAC27178 (PubMed:16141072).Curated
Sequence conflicti260 – 2601V → A in BAC27178 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK030904 mRNA. Translation: BAC27178.1. Frameshift.
BC108333 mRNA. Translation: AAI08334.1.
RefSeqiNP_084517.2. NM_030241.2.
UniGeneiMm.137966.

Genome annotation databases

GeneIDi67956.
KEGGimmu:67956.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK030904 mRNA. Translation: BAC27178.1. Frameshift.
BC108333 mRNA. Translation: AAI08334.1.
RefSeqiNP_084517.2. NM_030241.2.
UniGeneiMm.137966.

3D structure databases

ProteinModelPortaliQ2YDW7.
SMRiQ2YDW7. Positions 190-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi212564. 1 interaction.
IntActiQ2YDW7. 2 interactions.
MINTiMINT-4113899.

PTM databases

PhosphoSiteiQ2YDW7.

Proteomic databases

PaxDbiQ2YDW7.
PRIDEiQ2YDW7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi67956.
KEGGimmu:67956.

Organism-specific databases

CTDi387893.
MGIiMGI:1915206. Setd8.

Phylogenomic databases

eggNOGiCOG2940.
HOGENOMiHOG000020818.
HOVERGENiHBG067546.
InParanoidiQ2YDW7.
KOiK11428.

Miscellaneous databases

ChiTaRSiSetd8. mouse.
NextBioi326066.
PROiQ2YDW7.
SOURCEiSearch...

Gene expression databases

GenevestigatoriQ2YDW7.

Family and domain databases

InterProiIPR016858. Hist_H4-K20_MeTrfase.
IPR001214. SET_dom.
[Graphical view]
PANTHERiPTHR22884:SF11. PTHR22884:SF11. 1 hit.
PfamiPF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF027717. Histone_H4-K20_mtfrase. 1 hit.
SMARTiSM00317. SET. 1 hit.
[Graphical view]
PROSITEiPS51571. SAM_MT43_PR_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Thymus.
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NMRI.
    Tissue: Mammary tumor.
  3. "The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation."
    Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N., Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q., Rabanal R.M., Fondevila D., Munoz P., Kruger M., Tischfield J.A., Vaquero A.
    Genes Dev. 27:639-653(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiSETD8_MOUSE
AccessioniPrimary (citable) accession number: Q2YDW7
Secondary accession number(s): Q8C0J9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: December 20, 2005
Last modified: April 1, 2015
This is version 84 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

External Data

Dasty 3

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 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.