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O88974 (SETB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone-lysine N-methyltransferase SETDB1

EC=2.1.1.43
Alternative name(s):
ERG-associated protein with SET domain
Short name=ESET
SET domain bifurcated 1
Gene names
Name:Setdb1
Synonyms:Eset, Kiaa0067
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1307 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins By similarity.

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.1

Subunit structure

Interacts with MBD1; interaction is abolished when MBD1 is sumoylated. Interacts with ATF7IP and ATF7IP2; the interaction with ATF7IP is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 'Lys-9'. During DNA replication, it is recruited by SETDB1 to form a S phase-specific complex that facilitates methylation of H3 'Lys-9' during replication-coupled chromatin assembly and is at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1. Interacts with TRIM28/TIF1B, CBX1, CBX5, CHD7, DNMT3A, DNMT3B, NLK, PPARG and SUMO2. Interacts with MPHOSPH8 By similarity. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 By similarity. Interacts with ERG, HDAC1, HDAC2, SIN3A, SIN3B. Ref.1 Ref.6

Subcellular location

Nucleus By similarity. Chromosome By similarity. Note: Associated with non-pericentromeric regions of chromatin By similarity.

Tissue specificity

Ubiquitously expressed. Strong expression in liver and testis. Ref.2

Domain

The pre-SET, SET and post-SET domains are all required for methyltransferase activity. The 347-amino-acid insertion in the SET domain has no effect on the catalytic activity.

In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster By similarity.

Sequence similarities

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

Contains 1 MBD (methyl-CpG-binding) domain.

Contains 1 post-SET domain.

Contains 1 pre-SET domain.

Contains 1 SET domain.

Contains 2 Tudor domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ErgP812703EBI-79658,EBI-79647

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: O88974-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O88974-2)

The sequence of this isoform differs from the canonical sequence as follows:
     482-486: SRKQV → AQSQK
     489-1307: Missing.
Isoform 3 (identifier: O88974-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-807: Missing.
Isoform 4 (identifier: O88974-4)

The sequence of this isoform differs from the canonical sequence as follows:
     474-474: D → ES
Isoform 5 (identifier: O88974-5)

The sequence of this isoform differs from the canonical sequence as follows:
     527-1307: Missing.
Isoform 6 (identifier: O88974-6)

The sequence of this isoform differs from the canonical sequence as follows:
     474-474: D → ES
     527-1307: Missing.
Isoform 7 (identifier: O88974-7)

The sequence of this isoform differs from the canonical sequence as follows:
     756-1307: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13071307Histone-lysine N-methyltransferase SETDB1
PRO_0000186065

Regions

Domain257 – 32064Tudor 1
Domain347 – 40357Tudor 2
Domain611 – 68272MBD
Domain744 – 81774Pre-SET
Domain820 – 1282463SET
Domain1291 – 130717Post-SET
Region830 – 8323S-adenosyl-L-methionine binding By similarity
Region1239 – 12402S-adenosyl-L-methionine binding By similarity
Coiled coil30 – 6536 Potential

Sites

Metal binding7461Zinc 1 By similarity
Metal binding7461Zinc 2 By similarity
Metal binding7481Zinc 1 By similarity
Metal binding7521Zinc 1 By similarity
Metal binding7521Zinc 3 By similarity
Metal binding7581Zinc 1 By similarity
Metal binding7601Zinc 2 By similarity
Metal binding7981Zinc 2 By similarity
Metal binding7981Zinc 3 By similarity
Metal binding8021Zinc 2 By similarity
Metal binding8041Zinc 3 By similarity
Metal binding8091Zinc 3 By similarity
Metal binding12421Zinc 4 By similarity
Metal binding12951Zinc 4 By similarity
Metal binding12971Zinc 4 By similarity
Metal binding13021Zinc 4 By similarity
Binding site8681S-adenosyl-L-methionine By similarity
Binding site8701S-adenosyl-L-methionine By similarity
Binding site12361S-adenosyl-L-methionine By similarity

Amino acid modifications

Modified residue9931Phosphothreonine; by NLK By similarity
Cross-link182Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence1 – 807807Missing in isoform 3.
VSP_002221
Alternative sequence4741D → ES in isoform 4 and isoform 6.
VSP_024031
Alternative sequence482 – 4865SRKQV → AQSQK in isoform 2.
VSP_002219
Alternative sequence489 – 1307819Missing in isoform 2.
VSP_002220
Alternative sequence527 – 1307781Missing in isoform 5 and isoform 6.
VSP_024032
Alternative sequence756 – 1307552Missing in isoform 7.
VSP_024033

Experimental info

Mutagenesis7981C → T: Abolishes methyltransferase activity. Ref.1
Mutagenesis12421C → T: Abolishes methyltransferase activity. Ref.1
Sequence conflict4631I → M in BAC40439. Ref.5
Sequence conflict10921P → S in BAC65480. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 326AED6371D156C2

FASTA1,307144,549
        10         20         30         40         50         60 
MSSLPGCMSL AAAPAAADSA EIAELQQAVV EELGISMEEL RQYIDEELEK MDCIQQRKKQ 

        70         80         90        100        110        120 
LAELETWVLQ KESEVAYVDR LFDDASREVT NCESLVKDFY SKLGLQYHDS SSEDEASRPT 

       130        140        150        160        170        180 
EIIEIPDEDD DVLSIDSGDA GSRTPKDQKL REAMAALRKS AQDVQKFMDA VNKKSSSQDL 

       190        200        210        220        230        240 
HKGTLGQVSG ELSKDGDLIV SMRILGKKRT KTWHKGTLIA IQTVGLGKKY KVKFDNKGKS 

       250        260        270        280        290        300 
LLSGNHIAYD YHPPADKLFV GSRVVAKYKD GNQVWLYAGI VAETPNVKNK LRFLIFFDDG 

       310        320        330        340        350        360 
YASYVTQSEL YPICRPLKKT WEDIEDSSCR DFIEEYITAY PNRPMVLLKS GQLIKTEWEG 

       370        380        390        400        410        420 
TWWKSRVEEV DGSLVRILFL DDKRCEWIYR GSTRLEPMFS MKTSSASAME KKQGGQLRTR 

       430        440        450        460        470        480 
PNMGAVRSKG PVVQYTQDLT GTGIQFKPME PLQPIAPPAP LPIPPLSPQA ADTDLESQLA 

       490        500        510        520        530        540 
QSRKQVAKKS TSFRPGSVGS GHSSPTSSTL SENVSAGKLG INQTYRSPLA SVTSTPASAA 

       550        560        570        580        590        600 
PPVPPVPPGP PTPPGPPAPP GPLAPPAFHG MLERAPAEPS YRAPMEKLFY LPHVCSYTCL 

       610        620        630        640        650        660 
SRIRPMRNEQ YRGKNPLLVP LLYDFRRMTA RRRVNRKMGF HVIYKTPCGL CLRTMQEIER 

       670        680        690        700        710        720 
YLFETGCDFL FLEMFCLDPY VLVDRKFQPF KPFYYILDIT YGKEDVPLSC VNEIDTTPPP 

       730        740        750        760        770        780 
QVAYSKERIP GKGVFINTGP EFLVGCDCKD GCRDKSKCAC HQLTIQATAC TPGGQVNPNS 

       790        800        810        820        830        840 
GYQYKRLEEC LPTGVYECNK RCNCDPNMCT NRLVQHGLQV RLQLFKTQNK GWGIRCLDDI 

       850        860        870        880        890        900 
AKGSFVCIYA GKILTDDFAD KEGLEMGDEY FANLDHIESV ENFKEGYESD VPTSSDSSGV 

       910        920        930        940        950        960 
DMKDQEDGNS GSEDPEESND DSSDDNFCKD EDFSTSSVWR SYATRRQTRG QKENELSEMT 

       970        980        990       1000       1010       1020 
SKDSRPPDLG PPHVPIPSSV SVGGCNPPSS EETPKNKVAS WLSCNSVSEG GFADSDSRSS 

      1030       1040       1050       1060       1070       1080 
FKTSEGGDGR AGGGRGEAER ASTSGLSFKD EGDNKQPKKE DPENRNKMPV VTEGSQNHGH 

      1090       1100       1110       1120       1130       1140 
NPPMKSEGLR RPASKMSVLQ SQRVVTSTQS NPDDILTLSS STESEGESGT SRKPTAGHTS 

      1150       1160       1170       1180       1190       1200 
ATAVDSDDIQ TISSGSDGDD FEDKKNLSGP TKRQVAVKST RGFALKSTHG IAIKSTNMAS 

      1210       1220       1230       1240       1250       1260 
VDKGESAPVR KNTRQFYDGE ESCYIIDAKL EGNLGRYLNH SCSPNLFVQN VFVDTHDLRF 

      1270       1280       1290       1300 
PWVAFFASKR IRAGTELTWD YNYEVGSVEG KELLCCCGAI ECRGRLL 

« Hide

Isoform 2 [UniParc].

Checksum: 8874BF6A963B5415
Show »

FASTA48854,696
Isoform 3 [UniParc].

Checksum: 164B400024020B2F
Show »

FASTA50054,477
Isoform 4 [UniParc].

Checksum: E224818F50D56E25
Show »

FASTA1,308144,650
Isoform 5 [UniParc].

Checksum: F5B6903C06D91D11
Show »

FASTA52658,617
Isoform 6 [UniParc].

Checksum: F2B3561EAA10EC06
Show »

FASTA52758,719
Isoform 7 [UniParc].

Checksum: 3AE0FFE5C3542A60
Show »

FASTA75584,400

References

« Hide 'large scale' references
[1]"Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor."
Yang L., Xia L., Wu D.Y., Wang H., Chansky H.A., Schubach W.H., Hickstein D.D., Zhang Y.
Oncogene 21:148-152(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ENZYME ACTIVITY, INTERACTION WITH ERG, MUTAGENESIS OF CYS-798 AND CYS-1242.
Strain: BDF1.
Tissue: Blood.
[2]"Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain."
Blackburn M.L., Chansky H.A., Zielinska-Kwiatkowska A., Matsui Y., Yang L.
Biochim. Biophys. Acta 1629:8-14(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 6), TISSUE SPECIFICITY.
Strain: BDF1 and C57BL/6J X DBA/2.
[3]"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] (ISOFORMS 3 AND 7).
Strain: C57BL/6.
Tissue: Brain.
[4]"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 145-1307 (ISOFORM 4).
Tissue: Brain.
[5]"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. expand/collapse author list , 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] OF 289-1307 (ISOFORM 4).
Strain: NOD.
Tissue: Thymus.
[6]"An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B."
Yang L., Mei Q., Zielinska-Kwiatkowska A., Matsui Y., Blackburn M.L., Benedetti D., Krumm A.A., Taborsky G.J. Jr., Chansky H.A.
Biochem. J. 369:651-657(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC1; HDAC2; SIN3A AND SIN3B.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF091628 mRNA. Translation: AAC43039.1.
AY091600 mRNA. Translation: AAM13922.1.
AF546078 mRNA. Translation: AAN52358.1.
AY226577 Genomic DNA. Translation: AAO73535.2.
AY226577 Genomic DNA. Translation: AAO73536.2.
BC007176 mRNA. Translation: AAH07176.1.
BC079537 mRNA. Translation: AAH79537.1.
AK122198 Transcribed RNA. Translation: BAC65480.3.
AK088590 mRNA. Translation: BAC40439.1.
CCDSCCDS17613.1. [O88974-4]
CCDS50991.1. [O88974-1]
PIRT17453.
UniGeneMm.490259.

3D structure databases

ProteinModelPortalO88974.
SMRO88974. Positions 196-397, 698-903, 1181-1306.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO88974. 9 interactions.
MINTMINT-1753431.
STRING10090.ENSMUSP00000102788.

PTM databases

PhosphoSiteO88974.

Proteomic databases

MaxQBO88974.
PaxDbO88974.
PRIDEO88974.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCuc008qjo.2. mouse. [O88974-5]

Organism-specific databases

MGIMGI:1934229. Setdb1.
RougeSearch...

Phylogenomic databases

eggNOGCOG2940.
HOVERGENHBG061013.

Gene expression databases

CleanExMM_SETDB1.
GenevestigatorO88974.

Family and domain databases

InterProIPR016177. DNA-bd_dom.
IPR025796. Hist-Lys_N-MeTrfase_SETDB1.
IPR001739. Methyl_CpG_DNA-bd.
IPR003616. Post-SET_dom.
IPR007728. Pre-SET_dom.
IPR003606. Pre-SET_Zn-bd_sub.
IPR001214. SET_dom.
IPR002999. Tudor.
[Graphical view]
PfamPF01429. MBD. 1 hit.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
SMARTSM00391. MBD. 1 hit.
SM00508. PostSET. 1 hit.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
SM00333. TUDOR. 2 hits.
[Graphical view]
SUPFAMSSF54171. SSF54171. 1 hit.
PROSITEPS50982. MBD. 1 hit.
PS50868. POST_SET. 1 hit.
PS50867. PRE_SET. 1 hit.
PS51573. SAM_MT43_SUVAR39_1. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSETDB1. mouse.
PROO88974.
SOURCESearch...

Entry information

Entry nameSETB1_MOUSE
AccessionPrimary (citable) accession number: O88974
Secondary accession number(s): Q6AXH8 expand/collapse secondary AC list , Q78N64, Q78N65, Q80U84, Q8BTV6, Q8CIX7, Q922K1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot