Q2YDW7 (SETD8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Setd8

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	349 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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 By similarity.
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
Subunit structure	Interacts with L3MBTL1 By similarity.
Subcellular location	Nucleus By similarity. Chromosome By similarity. Note: Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin By similarity.
Domain	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 similarities	Belongs to the histone-lysine methyltransferase family. PR/SET subfamily. Contains 1 SET domain.
Sequence caution	The sequence BAC27178.1 differs from that shown. Reason: Frameshift at position 20.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-lysine monomethylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of DNA damage response, signal transduction by p53 class mediator Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	histone-lysine N-methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB p53 binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 349	349	N-lysine methyltransferase SETD8		PRO_0000228689
Regions
	Domain	212 – 338	127	SET
	Region	223 – 225	3	S-adenosyl-L-methionine binding By similarity
	Region	295 – 296	2	S-adenosyl-L-methionine binding By similarity
	Compositional bias	12 – 24	13	Ala-rich
Sites
	Binding site	268	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	57	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	204	1	N → ID in BAC27178. Ref.1
	Sequence conflict	260	1	V → A in BAC27178. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q2YDW7 [UniParc]. Last modified December 20, 2005. Version 1. Checksum: C89BAE59660DA5AF	FASTA	349	38,845
	10 20 30 40 50 60 MARGRKMCKP RAVEAAAAAV AATAPGPEMV EQRGPGRPRS DGENVFAGQS KIYAYMSPNK 70 80 90 100 110 120 CSAMRSPLQE ENSVAHHEVK CPGKPLAGIY RKREEKRNTG NVIRSAVKSD EQKSKDTRRG 130 140 150 160 170 180 PLAPFPNQKS EAAEPPKTPP PSCDSTNVAV AKQALKKSLK GKQAPRKKSQ GKTQQNRKLT 190 200 210 220 230 240 DFYPVRRSSR KSKAELQSEE RKKNELIESG KEEGMKIDLI DGKGRGVIAT KQFSRGDFVV 250 260 270 280 290 300 EYHGDLIEIT DAKKREALYV QDPSTGCYMY YFQYLSKTYC VDATQETNRL GRLINHSKCG 310 320 330 340 NCQTKLHDID GVPHLILIAS RDIAAGEELL YDYGDRSKAS IEAYPWLKH

References

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK030904 mRNA. Translation: BAC27178.1. Frameshift. BC108333 mRNA. Translation: AAI08334.1.
IPI	IPI00409777.
RefSeq	NP_084517.2. NM_030241.2.
UniGene	Mm.137966.
3D structure databases
ProteinModelPortal	Q2YDW7.
SMR	Q2YDW7. Positions 190-349.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q2YDW7. 1 interaction.
MINT	MINT-4113899.
PTM databases
PhosphoSite	Q2YDW7.
Proteomic databases
PaxDb	Q2YDW7.
PRIDE	Q2YDW7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	67956.
KEGG	mmu:67956.
Organism-specific databases
CTD	387893.
MGI	MGI:1915206. Setd8.
Phylogenomic databases
eggNOG	COG2940.
HOGENOM	HOG000020818.
HOVERGEN	HBG067546.
KO	K11428.
OrthoDB	EOG415GFP.
Gene expression databases
Genevestigator	Q2YDW7.
GermOnline	ENSMUSG00000049327. Mus musculus.
Family and domain databases
InterPro	IPR016858. Hist_H4-K20_MeTrfase. IPR001214. SET_dom. [Graphical view]
Pfam	PF00856. SET. 1 hit. [Graphical view]
PIRSF	PIRSF027717. Histone_H4-K20_mtfrase. 1 hit.
SMART	SM00317. SET. 1 hit. [Graphical view]
PROSITE	PS50280. SET. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SETD8. mouse.
NextBio	326066.
SOURCE	Search...

Entry information

Entry name

SETD8_MOUSE

Accession

Primary (citable) accession number: Q2YDW7
Secondary accession number(s): Q8C0J9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	December 20, 2005
Last modified:	May 29, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program