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UniProtKB/Swiss-Prot entry Q9NQR1


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name SETD8_HUMAN
Primary accession number Q9NQR1
Secondary accession numbers Q86W83 Q8TD09
Integrated into Swiss-Prot on November 15, 2002
Sequence was last modified on November 15, 2002 (Sequence version 3)
Annotations were last modified on    July 22, 2008 (Entry version 69)
Name and origin of the protein
Protein name Histone-lysine N-methyltransferase SETD8
Synonyms EC 2.1.1.43
H4-K20-HMTase SETD8
SET domain-containing protein 8
PR/SET domain-containing protein 07
PR/SET07
PR-Set7
Lysine N-methyltransferase 5A
Gene name
Name: SETD8
Synonyms: KMT5A, PRSET7, SET07, SET8
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 108-131; 220-231 AND 349-393, CHARACTERIZATION, AND MUTAGENESIS OF ARG-336.
TISSUE=Cervix carcinoma;
DOI=10.1016/S1097-2765(02)00548-8; PubMed=12086618 [NCBI, ExPASy, EBI, Israel, Japan]
Nishioka K., Rice J.C., Sarma K., Erdjument-Bromage H., Werner J., Wang Y., Chuikov S., Valenzuela P., Tempst P., Steward R., Lis J.T., Allis C.D., Reinberg D.;
"PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin.";
Mol. Cell 9:1201-1213(2002).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 83-103; 109-134; 141-151; 162-172; 221-230; 245-260; 280-297 AND 350-393, CHARACTERIZATION, AND MUTAGENESIS OF HIS-340 AND 385-ILE--HIS-393.
DOI=10.1016/S0960-9822(02)00924-7; PubMed=12121615 [NCBI, ExPASy, EBI, Israel, Japan]
Fang J., Feng Q., Ketel C.S., Wang H., Cao R., Xia L., Erdjument-Bromage H., Tempst P., Simon J.A., Zhang Y.;
"Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase.";
Curr. Biol. 12:1086-1099(2002).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tain F., Huang S.;
"A novel PR/SET domain-containing gene, SET07, as a candidate tumor suppressor.";
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Testis;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
DOI=10.1101/gad.1014902; PubMed=12208845 [NCBI, ExPASy, EBI, Israel, Japan]
Rice J.C., Nishioka K., Sarma K., Steward R., Reinberg D., Allis C.D.;
"Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes.";
Genes Dev. 16:2225-2230(2002).
[6]
FUNCTION, AND INDUCTION.
DOI=10.1016/j.molcel.2004.06.008; PubMed=15200950 [NCBI, ExPASy, EBI, Israel, Japan]
Julien E., Herr W.;
"A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1.";
Mol. Cell 14:713-725(2004).
[7]
CATALYTIC ACTIVITY.
DOI=10.1074/jbc.M501691200; PubMed=15964846 [NCBI, ExPASy, EBI, Israel, Japan]
Yin Y., Liu C., Tsai S.N., Zhou B., Ngai S.M., Zhu G.;
"SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and mono-methylates lysine 20.";
J. Biol. Chem. 280:30025-30031(2005).
[8]
FUNCTION.
DOI=10.1074/jbc.M513462200; PubMed=16517599 [NCBI, ExPASy, EBI, Israel, Japan]
Sims J.K., Houston S.I., Magazinnik T., Rice J.C.;
"A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin.";
J. Biol. Chem. 281:12760-12766(2006).
[9]
X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 233-393 IN COMPLEX WITH HISTONE H4 AND S-ADENOSYLMETHIONINE, AND FUNCTION.
DOI=10.1101/gad.1315905; PubMed=15933069 [NCBI, ExPASy, EBI, Israel, Japan]
Xiao B., Jing C., Kelly G., Walker P.A., Muskett F.W., Frenkiel T.A., Martin S.R., Sarma K., Reinberg D., Gamblin S.J., Wilson J.R.;
"Specificity and mechanism of the histone methyltransferase Pr-Set7.";
Genes Dev. 19:1444-1454(2005).
[10]
X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 231-393 IN COMPLEX WITH HISTONE H4 AND S-ADENOSYLMETHIONINE, FUNCTION, AND MUTAGENESIS OF TYR-286; GLU-300; CYS-311; TYR-375; ASP-379 AND HIS-388.
DOI=10.1101/gad.1318405; PubMed=15933070 [NCBI, ExPASy, EBI, Israel, Japan]
Couture J.-F., Collazo E., Brunzelle J.S., Trievel R.C.;
"Structural and functional analysis of SET8, a histone H4 'Lys-20' methyltransferase.";
Genes Dev. 19:1455-1465(2005).
Comments
  • FUNCTION: Histone methyltransferase that specifically monomethylates 'Lys-20' of histone H4. H4 'Lys-20' monomethylation 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.
  • CATALYTIC ACTIVITY: S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine.
  • INTERACTION:
    P62805:HIST1H4A; NbExp=4; IntAct=EBI-1268946, EBI-302023;
  • SUBCELLULAR LOCATION: Nucleus. Note=Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ9NQR1-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ9NQR1-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_002226, VSP_002227.
  • DEVELOPMENTAL STAGE: Not detected during G1 phase. First detected during S through G2 phases, and peaks during mitosis (at protein level).
  • INDUCTION: By HCFC1 C-terminal chain, independently of HCFC1 N-terminal chain.
  • 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.
  • SIMILARITY: Belongs to the histone-lysine methyltransferase family. PR/SET subfamily.
  • SIMILARITY: Contains 1 SET domain.
  • CAUTION: It is uncertain whether Met-1 or Met-72 is the initiator.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AY064546; AAL40879.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY102937; AAM47033.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF287261; AAF97812.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC050346; AAH50346.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_065115.3; -.
UniGene Hs.572262
3D structure databases
PDB
1ZKK; X-ray; 1.45 A; A/B/C/D=231-393.[ExPASy / RCSB / EBI]
2BQZ; X-ray; 1.50 A; A/E=233-393.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1ZKK; -.
2BQZ; -.
ModBase Q9NQR1.
Protein-protein interaction databases
IntAct Q9NQR1; -.
PTM databases
PhosphoSite Q9NQR1; -.
Organism-specific databases
H-InvDB HIX0020766; -.
HIX0026375; -.
HIX0030601; -.
HIX0037637; -.
HGNC HGNC:29489; SETD8.
GenAtlas SETD8.
MIM 607240; gene. [NCBI / EBI]
GeneCards Q9NQR1.
Gene expression databases
CleanEx HS_SETD8; -.
Ontologies
GO
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
QuickGo view.
Family and domain databases
InterPro IPR016858; Hist_H4-K20_MeTrfase.
IPR001214; SET.
Graphical view of domain structure.
Pfam PF00856; SET; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF027717; Histone_H4-K20_mtfrase; 1.
SMART SM00317; SET; 1.
SMART graphical view of domain structure.
PROSITE PS50280; SET; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q9NQR1.
Genome annotation databases
Ensembl ENSG00000183955; Homo sapiens. [Contig view]
GeneID 387893; -.
KEGG hsa:387893; -.
Phylogenomic databases
HOGENOM Q9NQR1; -.
HOVERGEN Q9NQR1; -.
Other
LinkHub Q9NQR1; -.
SOURCE SETD8; Homo sapiens.
ProtoNet Q9NQR1.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Cell cycle; Cell division; Chromatin regulator; Chromosomal protein; Coiled coil; Direct protein sequencing; Methyltransferase; Mitosis; Nucleus; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   393  393     Histone-lysine N-methyltransferase SETD8. PRO_0000186081
DOMAIN   256   382  127     SET. 
REGION   267   269  3     S-adenosyl-L-methionine binding. 
REGION   339   340  2     S-adenosyl-L-methionine binding. 
COILED   134   163  30     Potential. 
COMPBIAS   6    67  62     Ala-rich. 
COMPBIAS   29    32  4     Poly-Arg. 
BINDING   312   312        S-adenosyl-L-methionine. 
VAR_SEQ   1    41        Missing (in isoform 2). VSP_002226
VAR_SEQ   42    57        PGRAAGGKMSKPCAVE -> MARGRKMSKPRAVEAA (in isoform 2). VSP_002227
MUTAGEN   286   286        Y->A,F: Strongly reduces affinity for histone H4 and abolishes methyltransferase activity. 
MUTAGEN   300   300        E->A: Strongly reduces affinity for histone H4. 
MUTAGEN   311   311        C->A: Strongly reduces affinity for histone H4. 
MUTAGEN   336   336        R->G: Abolishes methyltransferase activity. 
MUTAGEN   340   340        H->A: Strongly decreases methyltransferase activity. 
MUTAGEN   375   375        Y->A: Strongly reduces affinity for histone H4 and methyltransferase activity. 
MUTAGEN   375   375        Y->F: Alters methyltransferase activity, so that both monomethylation and dimethylation take place. 
MUTAGEN   379   379        D->A,N: Abolishes histone H4 binding and methyltransferase activity. 
MUTAGEN   385   393        Missing: Abolishes methyltransferase activity. 
MUTAGEN   388   388        H->A,E: Strongly reduces affinity for histone H4. 
MUTAGEN   388   388        H->F: Increases affinity for histone H4. 
CONFLICT   162   163        KG -> RR (in Ref. 1; AAF97812). 
CONFLICT   281   281        D -> A (in Ref. 3; AAF97812). 
CONFLICT   343   343        C -> R (in Ref. 3; AAF97812). 
CONFLICT   357   357        P -> R (in Ref. 4; AAH50346). 
CONFLICT   373   373        L -> P (in Ref. 3; AAF97812). 
HELIX   236   253  18      
STRAND   259   264  6      
TURN   265   267  3      
STRAND   268   275  8      
STRAND   282   286  5      
STRAND   288   292  5      
HELIX   293   303  11      
STRAND   313   318  6      
STRAND   321   326  6      
HELIX   335   337  3      
STRAND   345   353  9      
STRAND   356   365  10      
HELIX   382   387  6      
HELIX   389   392  4      
Sequence information
Length: 393 AA [This is the length of the unprocessed precursor] Molecular weight: 42890 Da [This is the MW of the unprocessed precursor] CRC64: 2DCD9B697834B5BD [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGEGGAAAAL VAAAAAAAAA AAAVVAGQRR RRLGRRARCH GPGRAAGGKM SKPCAVEAAA 

        70         80         90        100        110        120 
AAVAATAPGP EMVERRGPGR PRTDGENVFT GQSKIYSYMS PNKCSGMRFP LQEENSVTHH 

       130        140        150        160        170        180 
EVKCQGKPLA GIYRKREEKR NAGNAVRSAM KSEEQKIKDA RKGPLVPFPN QKSEAAEPPK 

       190        200        210        220        230        240 
TPPSSCDSTN AAIAKQALKK PIKGKQAPRK KAQGKTQQNR KLTDFYPVRR SSRKSKAELQ 

       250        260        270        280        290        300 
SEERKRIDEL IESGKEEGMK IDLIDGKGRG VIATKQFSRG DFVVEYHGDL IEITDAKKRE 

       310        320        330        340        350        360 
ALYAQDPSTG CYMYYFQYLS KTYCVDATRE TNRLGRLINH SKCGNCQTKL HDIDGVPHLI 

       370        380        390 
LIASRDIAAG EELLYDYGDR SKASIEAHPW LKH 

Q9NQR1 in FASTA format

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