Q96T68 (SETB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase SETDB2
EC=2.1.1.43

Alternative name(s):
Chronic lymphocytic leukemia deletion region gene 8 protein
Lysine N-methyltransferase 1F
SET domain bifurcated 2

Gene names

Name:	SETDB2
Synonyms:	C13orf4, CLLD8, KMT1F

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	719 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone methyltransferase involved in left-right axis specification in early development and mitosis. Specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 is a specific tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. Plays a role in chromosome condensation and segregation during mitosis. Ref.5
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
Subcellular location	Nucleus. Chromosome Probable Ref.5.
Tissue specificity	Ubiquitous. Highest expression in heart, testis and ovary.
Sequence similarities	Belongs to the histone-lysine methyltransferase family. Contains 1 MBD (methyl-CpG-binding) domain. Contains 1 pre-SET domain. Contains 1 SET domain.
Sequence caution	The sequence CAH56265.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. The sequence CAI10818.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Chromosome Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Chromatin regulator Developmental protein Methyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Inferred from mutant phenotype Ref.5. Source: UniProtKB heart looping Inferred from sequence or structural similarity. Source: UniProtKB left/right axis specification Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from mutant phenotype Ref.5. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro histone methyltransferase activity (H3-K9 specific) Inferred from direct assay Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96T68-1)

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: Q96T68-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-81: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q96T68-3)

The sequence of this isoform differs from the canonical sequence as follows:
     523-523: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 719	719	Histone-lysine N-methyltransferase SETDB2		PRO_0000186088
Regions
	Domain	157 – 229	73	MBD
	Domain	291 – 364	74	Pre-SET
	Domain	366 – 698	333	SET
Sites
	Metal binding	293	1	Zinc 1 By similarity
	Metal binding	293	1	Zinc 2 By similarity
	Metal binding	295	1	Zinc 1 By similarity
	Metal binding	299	1	Zinc 1 By similarity
	Metal binding	299	1	Zinc 3 By similarity
	Metal binding	305	1	Zinc 1 By similarity
	Metal binding	307	1	Zinc 2 By similarity
	Metal binding	345	1	Zinc 2 By similarity
	Metal binding	345	1	Zinc 3 By similarity
	Metal binding	349	1	Zinc 2 By similarity
	Metal binding	351	1	Zinc 3 By similarity
	Metal binding	356	1	Zinc 3 By similarity
Natural variations
	Alternative sequence	70 – 81	12	Missing in isoform 2.		VSP_008413
	Alternative sequence	523	1	Missing in isoform 3.		VSP_024034
	Natural variant	117	1	E → G. Ref.1 Ref.6 Corresponds to variant rs7998427 [ dbSNP | Ensembl ].		VAR_031282
	Natural variant	473	1	V → M. Ref.3 Ref.4 Ref.6 Corresponds to variant rs2057413 [ dbSNP | Ensembl ].		VAR_016976

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 01CD2CFE5C1D9067	FASTA	719	81,894
	10 20 30 40 50 60 MGEKNGDAKT FWMELEDDGK VDFIFEQVQN VLQSLKQKIK DGSATNKEYI QAMILVNEAT 70 80 90 100 110 120 IINSSTSIKG ASQKEVNAQS SDPMPVTQKE QENKSNAFPS TSCENSFPED CTFLTTENKE 130 140 150 160 170 180 ILSLEDKVVD FREKDSSSNL SYQSHDCSGA CLMKMPLNLK GENPLQLPIK CHFQRRHAKT 190 200 210 220 230 240 NSHSSALHVS YKTPCGRSLR NVEEVFRYLL ETECNFLFTD NFSFNTYVQL ARNYPKQKEV 250 260 270 280 290 300 VSDVDISNGV ESVPISFCNE IDSRKLPQFK YRKTVWPRAY NLTNFSSMFT DSCDCSEGCI 310 320 330 340 350 360 DITKCACLQL TARNAKTSPL SSDKITTGYK YKRLQRQIPT GIYECSLLCK CNRQLCQNRV 370 380 390 400 410 420 VQHGPQVRLQ VFKTEQKGWG VRCLDDIDRG TFVCIYSGRL LSRANTEKSY GIDENGRDEN 430 440 450 460 470 480 TMKNIFSKKR KLEVACSDCE VEVLPLGLET HPRTAKTEKC PPKFSNNPKE LTVETKYDNI 490 500 510 520 530 540 SRIQYHSVIR DPESKTAIFQ HNGKKMEFVS SESVTPEDND GFKPPREHLN SKTKGAQKDS 550 560 570 580 590 600 SSNHVDEFED NLLIESDVID ITKYREETPP RSRCNQATTL DNQNIKKAIE VQIQKPQEGR 610 620 630 640 650 660 STACQRQQVF CDEELLSETK NTSSDSLTKF NKGNVFLLDA TKEGNVGRFL NHSCCPNLLV 670 680 690 700 710 QNVFVETHNR NFPLVAFFTN RYVKARTELT WDYGYEAGTV PEKEIFCQCG VNKCRKKIL
	Isoform 2 [UniParc]. Checksum: 631679B2687F6FBD	FASTA	707	80,707
	10 20 30 40 50 60 MGEKNGDAKT FWMELEDDGK VDFIFEQVQN VLQSLKQKIK DGSATNKEYI QAMILVNEAT 70 80 90 100 110 120 IINSSTSIKD PMPVTQKEQE NKSNAFPSTS CENSFPEDCT FLTTENKEIL SLEDKVVDFR 130 140 150 160 170 180 EKDSSSNLSY QSHDCSGACL MKMPLNLKGE NPLQLPIKCH FQRRHAKTNS HSSALHVSYK 190 200 210 220 230 240 TPCGRSLRNV EEVFRYLLET ECNFLFTDNF SFNTYVQLAR NYPKQKEVVS DVDISNGVES 250 260 270 280 290 300 VPISFCNEID SRKLPQFKYR KTVWPRAYNL TNFSSMFTDS CDCSEGCIDI TKCACLQLTA 310 320 330 340 350 360 RNAKTSPLSS DKITTGYKYK RLQRQIPTGI YECSLLCKCN RQLCQNRVVQ HGPQVRLQVF 370 380 390 400 410 420 KTEQKGWGVR CLDDIDRGTF VCIYSGRLLS RANTEKSYGI DENGRDENTM KNIFSKKRKL 430 440 450 460 470 480 EVACSDCEVE VLPLGLETHP RTAKTEKCPP KFSNNPKELT VETKYDNISR IQYHSVIRDP 490 500 510 520 530 540 ESKTAIFQHN GKKMEFVSSE SVTPEDNDGF KPPREHLNSK TKGAQKDSSS NHVDEFEDNL 550 560 570 580 590 600 LIESDVIDIT KYREETPPRS RCNQATTLDN QNIKKAIEVQ IQKPQEGRST ACQRQQVFCD 610 620 630 640 650 660 EELLSETKNT SSDSLTKFNK GNVFLLDATK EGNVGRFLNH SCCPNLLVQN VFVETHNRNF 670 680 690 700 PLVAFFTNRY VKARTELTWD YGYEAGTVPE KEIFCQCGVN KCRKKIL
	Isoform 3 [UniParc]. Checksum: FCBD4B8D5A1A3506	FASTA	718	81,766
	10 20 30 40 50 60 MGEKNGDAKT FWMELEDDGK VDFIFEQVQN VLQSLKQKIK DGSATNKEYI QAMILVNEAT 70 80 90 100 110 120 IINSSTSIKG ASQKEVNAQS SDPMPVTQKE QENKSNAFPS TSCENSFPED CTFLTTENKE 130 140 150 160 170 180 ILSLEDKVVD FREKDSSSNL SYQSHDCSGA CLMKMPLNLK GENPLQLPIK CHFQRRHAKT 190 200 210 220 230 240 NSHSSALHVS YKTPCGRSLR NVEEVFRYLL ETECNFLFTD NFSFNTYVQL ARNYPKQKEV 250 260 270 280 290 300 VSDVDISNGV ESVPISFCNE IDSRKLPQFK YRKTVWPRAY NLTNFSSMFT DSCDCSEGCI 310 320 330 340 350 360 DITKCACLQL TARNAKTSPL SSDKITTGYK YKRLQRQIPT GIYECSLLCK CNRQLCQNRV 370 380 390 400 410 420 VQHGPQVRLQ VFKTEQKGWG VRCLDDIDRG TFVCIYSGRL LSRANTEKSY GIDENGRDEN 430 440 450 460 470 480 TMKNIFSKKR KLEVACSDCE VEVLPLGLET HPRTAKTEKC PPKFSNNPKE LTVETKYDNI 490 500 510 520 530 540 SRIQYHSVIR DPESKTAIFQ HNGKKMEFVS SESVTPEDND GFPPREHLNS KTKGAQKDSS 550 560 570 580 590 600 SNHVDEFEDN LLIESDVIDI TKYREETPPR SRCNQATTLD NQNIKKAIEV QIQKPQEGRS 610 620 630 640 650 660 TACQRQQVFC DEELLSETKN TSSDSLTKFN KGNVFLLDAT KEGNVGRFLN HSCCPNLLVQ 670 680 690 700 710 NVFVETHNRN FPLVAFFTNR YVKARTELTW DYGYEAGTVP EKEIFCQCGV NKCRKKIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell chronic lymphocytic leukemia." Mabuchi H., Fujii H., Calin G., Alder H., Negrini M., Rassenti L., Kipps T.J., Bullrich F., Croce C.M. Cancer Res. 61:2870-2877(2001) [PubMed: 11306461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-117.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT MET-473. Tissue: Colon and Testis.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-719 (ISOFORM 3), VARIANT MET-473. Tissue: Amygdala.
[5]	"CLLD8/KMT1F is a lysine methyltransferase that is important for chromosome segregation." Falandry C., Fourel G., Galy V., Ristriani T., Horard B., Bensimon E., Salles G., Gilson E., Magdinier F. J. Biol. Chem. 285:20234-20241(2010) [PubMed: 20404330] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma." Zhang Y., Leaves N.I., Anderson G.G., Ponting C.P., Broxholme J., Holt R., Edser P., Bhattacharyya S., Dunham A., Adcock I.M., Pulleyn L., Barnes P.J., Harper J.I., Abecasis G., Cardon L., White M., Burton J., Matthews L. , Mott R., Ross M., Cox R., Moffatt M.F., Cookson W.O.C.M. Nat. Genet. 34:181-186(2003) [PubMed: 12754510] [Abstract] Cited for: VARIANTS GLY-117 AND MET-473.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF334407 mRNA. Translation: AAK38373.1. AL139321, AL136218 Genomic DNA. Translation: CAH71048.1. AL136218, AL139321 Genomic DNA. Translation: CAI10817.1. AL136218 Genomic DNA. Translation: CAI10818.2. Sequence problems. BC017078 mRNA. Translation: AAH17078.1. BC047434 mRNA. Translation: AAH47434.1. AL831937 mRNA. Translation: CAH56265.1. Sequence problems.
IPI	IPI00045922. IPI00375872. IPI00843770.
RefSeq	NP_001153780.1. NM_001160308.1. NP_114121.2. NM_031915.2.
UniGene	Hs.631789.
3D structure databases
ProteinModelPortal	Q96T68.
SMR	Q96T68. Positions 169-230, 636-697.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96T68. 1 interaction.
STRING	Q96T68.
PTM databases
PhosphoSite	Q96T68.
Polymorphism databases
DMDM	143811459.
Proteomic databases
PRIDE	Q96T68.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317257; ENSP00000326477; ENSG00000136169.
GeneID	83852.
KEGG	hsa:83852.
UCSC	uc001vcz.1. human. uc001vda.1. human.
Organism-specific databases
CTD	83852.
GeneCards	GC13P050018.
H-InvDB	HIX0011315.
HGNC	HGNC:20263. SETDB2.
HPA	CAB012190.
MIM	607865. gene.
neXtProt	NX_Q96T68.
PharmGKB	PA134956285.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05243.
GeneTree	ENSGT00600000084326.
HOVERGEN	HBG106688.
InParanoid	Q96T68.
OMA	ACLMKMP.
OrthoDB	EOG47WNN2.
PhylomeDB	Q96T68.
Gene expression databases
ArrayExpress	Q96T68.
Bgee	Q96T68.
CleanEx	HS_SETDB2.
Genevestigator	Q96T68.
GermOnline	ENSG00000136169. Homo sapiens.
Family and domain databases
InterPro	IPR016177. DNA-bd_integrase-typ. IPR001739. Methyl_CpG_DNA-bd. IPR007728. Pre-SET_dom. IPR001214. SET_dom. [Graphical view]
Gene3D	G3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.
KO	K11421.
Pfam	PF01429. MBD. 1 hit. PF05033. Pre-SET. 1 hit. PF00856. SET. 1 hit. [Graphical view]
SMART	SM00317. SET. 1 hit. [Graphical view]
SUPFAM	SSF54171. DNA-binding_integrase-type. 1 hit.
PROSITE	PS50982. MBD. 1 hit. PS50867. PRE_SET. 1 hit. PS50280. SET. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	72831.
SOURCE	Search...

Entry information

Entry name

SETB2_HUMAN

Accession

Primary (citable) accession number: Q96T68
Secondary accession number(s): Q5TC65 , Q5TC66, Q5W0A7, Q659A7, Q86UD6, Q96AI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	April 3, 2007
Last modified:	January 25, 2012
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.