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Q2YDJ8

- SETD8_BOVIN

UniProt

Q2YDJ8 - SETD8_BOVIN

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Protein

N-lysine methyltransferase SETD8

Gene

SETD8

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 4 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 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
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
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-KW
  2. nucleus Source: UniProtKB-KW
Complete GO annotation...

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

« Hide

        10         20         30         40         50
MARGRKMSKP RAVEAAAAAA AVAATAPGPE MVERRGPGRP RTNGENVFTG
60 70 80 90 100
QSKIYTYMSP NKCSGMRSPL QEENSVAQYE VKCQGKPLAG IYRKRDEKRN
110 120 130 140 150
SGNAIRSSMK AEEQKIKDAR RGPLAPFPNQ KSEAAEPPKT PTSSCDTPNA
160 170 180 190 200
AAAKQGLKKP VRGKQAPRKK AQGKTQQNRK LTDFYPVRRS SRKSKAELQS
210 220 230 240 250
EERKRIDELI ESGKEEGMKI DLIDGKGRGV IATKQFSRGE FVVEYHGDLI
260 270 280 290 300
EITDAKKREA LYAQDPSTGC YMYYFQYLSK TYCVDATRET NRLGRLINHS
310 320 330 340 350
KCGNCQTKLH DIDGVPHLIL IASRDIEAGE ELLYDYGDRS RASIEAYPWL

KH
Length:352
Mass (Da):39,277
Last modified:December 20, 2005 - v1
Checksum:i98BBD07941AAE9BE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 29, 2014
This is version 76 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