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Q2YDJ8

- SETD8_BOVIN

UniProt

Q2YDJ8 - SETD8_BOVIN

Protein

N-lysine methyltransferase SETD8

Gene

SETD8

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 75 (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 sitei271 – 2711S-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
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Unplaced

    Subcellular locationi

    Nucleus By similarity. Chromosome By similarity
    Note: Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Colocalized with SIRT2 at mitotic foci. Associates with chromosomes during mitosis; association is increased in a H2O(2)-induced oxidative stress-dependent manner. Not associated with constitutive heterochromatin By similarity.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 – 352352N-lysine methyltransferase SETD8PRO_0000228688Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei59 – 591PhosphoserineBy similarity
    Modified residuei131 – 1311N6-acetyllysineBy similarity

    Post-translational modificationi

    Acetylated at Lys-131; does not change methyltransferase activity. Deacetylated at Lys-131 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

    PRIDEiQ2YDJ8.

    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

    STRINGi9913.ENSBTAP00000000160.

    Structurei

    3D structure databases

    ProteinModelPortaliQ2YDJ8.
    SMRiQ2YDJ8. Positions 192-352.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini216 – 337122SETPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni226 – 2283S-adenosyl-L-methionine bindingPROSITE-ProRule annotation
    Regioni298 – 2992S-adenosyl-L-methionine bindingPROSITE-ProRule annotation

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi15 – 2612Poly-AlaAdd
    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.
    InParanoidiQ2YDJ8.
    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.

    Q2YDJ8-1 [UniParc]FASTAAdd to Basket

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    MARGRKMSKP RAVEAAAAAA AVAATAPGPE MVERRGPGRP RTNGENVFTG    50
    QSKIYTYMSP NKCSGMRSPL QEENSVAQYE VKCQGKPLAG IYRKRDEKRN 100
    SGNAIRSSMK AEEQKIKDAR RGPLAPFPNQ KSEAAEPPKT PTSSCDTPNA 150
    AAAKQGLKKP VRGKQAPRKK AQGKTQQNRK LTDFYPVRRS SRKSKAELQS 200
    EERKRIDELI ESGKEEGMKI DLIDGKGRGV IATKQFSRGE FVVEYHGDLI 250
    EITDAKKREA LYAQDPSTGC YMYYFQYLSK TYCVDATRET NRLGRLINHS 300
    KCGNCQTKLH DIDGVPHLIL IASRDIEAGE ELLYDYGDRS RASIEAYPWL 350
    KH 352
    Length:352
    Mass (Da):39,277
    Last modified:December 20, 2005 - v1
    Checksum:i98BBD07941AAE9BE
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC110189 mRNA. Translation: AAI10190.1.
    RefSeqiNP_001039795.1. NM_001046330.1.
    UniGeneiBt.65045.

    Genome annotation databases

    GeneIDi532622.
    KEGGibta:532622.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC110189 mRNA. Translation: AAI10190.1 .
    RefSeqi NP_001039795.1. NM_001046330.1.
    UniGenei Bt.65045.

    3D structure databases

    ProteinModelPortali Q2YDJ8.
    SMRi Q2YDJ8. Positions 192-352.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9913.ENSBTAP00000000160.

    Proteomic databases

    PRIDEi Q2YDJ8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 532622.
    KEGGi bta:532622.

    Organism-specific databases

    CTDi 387893.

    Phylogenomic databases

    eggNOGi COG2940.
    HOGENOMi HOG000020818.
    HOVERGENi HBG067546.
    InParanoidi Q2YDJ8.
    KOi K11428.

    Miscellaneous databases

    NextBioi 20875752.

    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. NIH - Mammalian Gene Collection (MGC) project
      Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Crossbred X Angus.
      Tissue: Liver.

    Entry informationi

    Entry nameiSETD8_BOVIN
    AccessioniPrimary (citable) accession number: Q2YDJ8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 21, 2006
    Last sequence update: December 20, 2005
    Last modified: October 1, 2014
    This is version 75 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3