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Q2YDW7

- SETD8_MOUSE

UniProt

Q2YDW7 - SETD8_MOUSE

Protein

N-lysine methyltransferase SETD8

Gene

Setd8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 78 (01 Oct 2014)
      Sequence version 1 (20 Dec 2005)
      Previous versions | rss
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    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

    1. histone-lysine N-methyltransferase activity Source: UniProtKB
    2. p53 binding Source: UniProtKB
    3. protein-lysine N-methyltransferase activity Source: UniProtKB

    GO - Biological processi

    1. histone lysine methylation Source: GOC
    2. mitotic nuclear division Source: UniProtKB-KW
    3. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    4. peptidyl-lysine monomethylation Source: UniProtKB
    5. regulation of DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
    6. transcription, DNA-templated Source: UniProtKB-KW

    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: Unplaced

    Organism-specific databases

    MGIiMGI:1915206. Setd8.

    Subcellular locationi

    Nucleus By similarity. Chromosome 1 Publication
    Note: Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin By similarity. Colocalized with SIRT2 at mitotic foci. Associates with chromosomes during mitosis; association is increased in a H2O(2)-induced oxidative stress-dependent manner.By similarity

    GO - Cellular componenti

    1. chromosome Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    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.
    KOiK11428.

    Family and domain databases

    InterProiIPR016858. Hist_H4-K20_MeTrfase.
    IPR001214. SET_dom.
    [Graphical view]
    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

    MARGRKMCKP RAVEAAAAAV AATAPGPEMV EQRGPGRPRS DGENVFAGQS    50
    KIYAYMSPNK CSAMRSPLQE ENSVAHHEVK CPGKPLAGIY RKREEKRNTG 100
    NVIRSAVKSD EQKSKDTRRG PLAPFPNQKS EAAEPPKTPP PSCDSTNVAV 150
    AKQALKKSLK GKQAPRKKSQ GKTQQNRKLT DFYPVRRSSR KSKAELQSEE 200
    RKKNELIESG KEEGMKIDLI DGKGRGVIAT KQFSRGDFVV EYHGDLIEIT 250
    DAKKREALYV QDPSTGCYMY YFQYLSKTYC VDATQETNRL GRLINHSKCG 300
    NCQTKLHDID GVPHLILIAS RDIAAGEELL YDYGDRSKAS IEAYPWLKH 349
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK030904 mRNA. Translation: BAC27178.1 . Frameshift.
    BC108333 mRNA. Translation: AAI08334.1 .
    RefSeqi NP_084517.2. NM_030241.2.
    UniGenei Mm.137966.

    3D structure databases

    ProteinModelPortali Q2YDW7.
    SMRi Q2YDW7. Positions 190-349.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 212564. 1 interaction.
    IntActi Q2YDW7. 2 interactions.
    MINTi MINT-4113899.

    PTM databases

    PhosphoSitei Q2YDW7.

    Proteomic databases

    PaxDbi Q2YDW7.
    PRIDEi Q2YDW7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 67956.
    KEGGi mmu:67956.

    Organism-specific databases

    CTDi 387893.
    MGIi MGI:1915206. Setd8.

    Phylogenomic databases

    eggNOGi COG2940.
    HOGENOMi HOG000020818.
    HOVERGENi HBG067546.
    KOi K11428.

    Miscellaneous databases

    ChiTaRSi SETD8. mouse.
    NextBioi 326066.
    PROi Q2YDW7.
    SOURCEi Search...

    Gene expression databases

    Genevestigatori Q2YDW7.

    Family and domain databases

    InterProi IPR016858. Hist_H4-K20_MeTrfase.
    IPR001214. SET_dom.
    [Graphical view ]
    Pfami PF00856. SET. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF027717. Histone_H4-K20_mtfrase. 1 hit.
    SMARTi SM00317. SET. 1 hit.
    [Graphical view ]
    PROSITEi PS51571. SAM_MT43_PR_SET. 1 hit.
    PS50280. SET. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 78 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