UniProtKB - Q96T68 (SETB2_HUMAN)
Histone-lysine N-methyltransferase SETDB2
SETDB2
Functioni
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.
1 PublicationCatalytic activityi
- N6,N6-dimethyl-L-lysyl9-[histone H3] + S-adenosyl-L-methionine = H+ + N6,N6,N6-trimethyl-L-lysyl9-[histone H3] + S-adenosyl-L-homocysteine1 PublicationEC:2.1.1.3661 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 293 | Zinc 1By similarity | 1 | |
Metal bindingi | 293 | Zinc 2By similarity | 1 | |
Metal bindingi | 295 | Zinc 1By similarity | 1 | |
Metal bindingi | 299 | Zinc 1By similarity | 1 | |
Metal bindingi | 299 | Zinc 3By similarity | 1 | |
Metal bindingi | 305 | Zinc 1By similarity | 1 | |
Metal bindingi | 307 | Zinc 2By similarity | 1 | |
Metal bindingi | 345 | Zinc 2By similarity | 1 | |
Metal bindingi | 345 | Zinc 3By similarity | 1 | |
Metal bindingi | 349 | Zinc 2By similarity | 1 | |
Metal bindingi | 351 | Zinc 3By similarity | 1 | |
Metal bindingi | 356 | Zinc 3By similarity | 1 | |
Binding sitei | 418 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 648 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Metal bindingi | 654 | Zinc 4By similarity | 1 | |
Metal bindingi | 707 | Zinc 4By similarity | 1 | |
Metal bindingi | 709 | Zinc 4By similarity | 1 | |
Metal bindingi | 714 | Zinc 4By similarity | 1 |
GO - Molecular functioni
- DNA binding Source: InterPro
- histone-lysine N-methyltransferase activity Source: Reactome
- histone methyltransferase activity (H3-K9 specific) Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- cell division Source: UniProtKB-KW
- chromosome segregation Source: UniProtKB
- heart looping Source: UniProtKB
- heterochromatin organization Source: GO_Central
- histone H3-K9 methylation Source: UniProtKB
- left/right axis specification Source: UniProtKB
- mitotic cell cycle Source: UniProtKB
- negative regulation of gene expression Source: GO_Central
- negative regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of DNA methylation-dependent heterochromatin assembly Source: GO_Central
Keywordsi
Molecular function | Chromatin regulator, Developmental protein, Methyltransferase, Transferase |
Biological process | Cell cycle, Cell division, Mitosis |
Ligand | Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96T68 |
Reactomei | R-HSA-3214841, PKMTs methylate histone lysines |
SignaLinki | Q96T68 |
SIGNORi | Q96T68 |
Names & Taxonomyi
Protein namesi | Recommended name: Histone-lysine N-methyltransferase SETDB2 (EC:2.1.1.3661 Publication)Alternative name(s): Chronic lymphocytic leukemia deletion region gene 8 protein Lysine N-methyltransferase 1F SET domain bifurcated 2 |
Gene namesi | Name:SETDB2 Synonyms:C13orf4, CLLD8, KMT1F |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20263, SETDB2 |
MIMi | 607865, gene |
neXtProti | NX_Q96T68 |
VEuPathDBi | HostDB:ENSG00000136169 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Other locations
- Chromosome 1 Publication
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- chromosome Source: UniProtKB-SubCell
Keywords - Cellular componenti
Chromosome, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 83852 |
OpenTargetsi | ENSG00000136169 |
PharmGKBi | PA134956285 |
Miscellaneous databases
Pharosi | Q96T68, Tbio |
Genetic variation databases
BioMutai | SETDB2 |
DMDMi | 143811459 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186088 | 1 – 719 | Histone-lysine N-methyltransferase SETDB2Add BLAST | 719 |
Proteomic databases
jPOSTi | Q96T68 |
MassIVEi | Q96T68 |
PaxDbi | Q96T68 |
PeptideAtlasi | Q96T68 |
PRIDEi | Q96T68 |
ProteomicsDBi | 78203 [Q96T68-1] 78204 [Q96T68-2] 78205 [Q96T68-3] |
PTM databases
iPTMneti | Q96T68 |
PhosphoSitePlusi | Q96T68 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000136169, Expressed in sperm and 211 other tissues |
ExpressionAtlasi | Q96T68, baseline and differential |
Genevisiblei | Q96T68, HS |
Organism-specific databases
HPAi | ENSG00000136169, Low tissue specificity |
Interactioni
Binary interactionsi
Q96T68
With | #Exp. | IntAct |
---|---|---|
ARL14EP [Q8N8R7] | 4 | EBI-1222089,EBI-2807994 |
Isoform 2 [Q96T68-2]
With | #Exp. | IntAct |
---|---|---|
ARL14EP [Q8N8R7] | 6 | EBI-12346707,EBI-2807994 |
Protein-protein interaction databases
BioGRIDi | 123768, 15 interactors |
IntActi | Q96T68, 12 interactors |
STRINGi | 9606.ENSP00000346175 |
Miscellaneous databases
RNActi | Q96T68, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96T68 |
SMRi | Q96T68 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 157 – 229 | MBDPROSITE-ProRule annotationAdd BLAST | 73 | |
Domaini | 291 – 364 | Pre-SETPROSITE-ProRule annotationAdd BLAST | 74 | |
Domaini | 367 – 694 | SETPROSITE-ProRule annotationAdd BLAST | 328 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 72 – 102 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 377 – 379 | S-adenosyl-L-methionine bindingBy similarity | 3 | |
Regioni | 508 – 547 | DisorderedSequence analysisAdd BLAST | 40 | |
Regioni | 651 – 652 | S-adenosyl-L-methionine bindingBy similarity | 2 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 519 – 547 | Basic and acidic residuesSequence analysisAdd BLAST | 29 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1141, Eukaryota |
GeneTreei | ENSGT00940000158209 |
HOGENOMi | CLU_003279_2_0_1 |
InParanoidi | Q96T68 |
OMAi | NQQVFCD |
OrthoDBi | 183716at2759 |
PhylomeDBi | Q96T68 |
TreeFami | TF106411 |
Family and domain databases
Gene3Di | 2.170.270.10, 2 hits |
InterProi | View protein in InterPro IPR016177, DNA-bd_dom_sf IPR001739, Methyl_CpG_DNA-bd IPR007728, Pre-SET_dom IPR001214, SET_dom IPR046341, SET_dom_sf |
Pfami | View protein in Pfam PF01429, MBD, 1 hit PF05033, Pre-SET, 1 hit PF00856, SET, 1 hit |
SMARTi | View protein in SMART SM00391, MBD, 1 hit SM00468, PreSET, 1 hit SM00317, SET, 1 hit |
SUPFAMi | SSF54171, SSF54171, 1 hit SSF82199, SSF82199, 1 hit |
PROSITEi | View protein in PROSITE PS50982, MBD, 1 hit PS50867, PRE_SET, 1 hit PS50280, SET, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGEKNGDAKT FWMELEDDGK VDFIFEQVQN VLQSLKQKIK DGSATNKEYI
60 70 80 90 100
QAMILVNEAT IINSSTSIKG ASQKEVNAQS SDPMPVTQKE QENKSNAFPS
110 120 130 140 150
TSCENSFPED CTFLTTENKE ILSLEDKVVD FREKDSSSNL SYQSHDCSGA
160 170 180 190 200
CLMKMPLNLK GENPLQLPIK CHFQRRHAKT NSHSSALHVS YKTPCGRSLR
210 220 230 240 250
NVEEVFRYLL ETECNFLFTD NFSFNTYVQL ARNYPKQKEV VSDVDISNGV
260 270 280 290 300
ESVPISFCNE IDSRKLPQFK YRKTVWPRAY NLTNFSSMFT DSCDCSEGCI
310 320 330 340 350
DITKCACLQL TARNAKTSPL SSDKITTGYK YKRLQRQIPT GIYECSLLCK
360 370 380 390 400
CNRQLCQNRV VQHGPQVRLQ VFKTEQKGWG VRCLDDIDRG TFVCIYSGRL
410 420 430 440 450
LSRANTEKSY GIDENGRDEN TMKNIFSKKR KLEVACSDCE VEVLPLGLET
460 470 480 490 500
HPRTAKTEKC PPKFSNNPKE LTVETKYDNI SRIQYHSVIR DPESKTAIFQ
510 520 530 540 550
HNGKKMEFVS SESVTPEDND GFKPPREHLN SKTKGAQKDS SSNHVDEFED
560 570 580 590 600
NLLIESDVID ITKYREETPP RSRCNQATTL DNQNIKKAIE VQIQKPQEGR
610 620 630 640 650
STACQRQQVF CDEELLSETK NTSSDSLTKF NKGNVFLLDA TKEGNVGRFL
660 670 680 690 700
NHSCCPNLLV QNVFVETHNR NFPLVAFFTN RYVKARTELT WDYGYEAGTV
710
PEKEIFCQCG VNKCRKKIL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A087WYZ9 | A0A087WYZ9_HUMAN | Histone-lysine N-methyltransferase ... | SETDB2 | 719 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031282 | 117 | E → G2 PublicationsCorresponds to variant dbSNP:rs7998427Ensembl. | 1 | |
Natural variantiVAR_016976 | 473 | V → M3 PublicationsCorresponds to variant dbSNP:rs2057413Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008413 | 70 – 81 | Missing in isoform 2. 1 PublicationAdd BLAST | 12 | |
Alternative sequenceiVSP_024034 | 523 | Missing in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF334407 mRNA Translation: AAK38373.1 AL136218 Genomic DNA No translation available. AL139321 Genomic DNA No translation available. BC017078 mRNA Translation: AAH17078.1 BC047434 mRNA Translation: AAH47434.1 AL831937 mRNA Translation: CAH56265.1 Sequence problems. |
CCDSi | CCDS53868.1 [Q96T68-2] CCDS9417.1 [Q96T68-1] |
RefSeqi | NP_001153780.1, NM_001160308.2 [Q96T68-2] NP_114121.2, NM_031915.2 [Q96T68-1] |
Genome annotation databases
Ensembli | ENST00000317257.12; ENSP00000326477.9; ENSG00000136169.17 [Q96T68-2] ENST00000354234.8; ENSP00000346175.5; ENSG00000136169.17 ENST00000611815.2; ENSP00000482240.2; ENSG00000136169.17 [Q96T68-2] |
GeneIDi | 83852 |
KEGGi | hsa:83852 |
MANE-Selecti | ENST00000611815.2; ENSP00000482240.2; NM_001160308.3; NP_001153780.1 [Q96T68-2] |
UCSCi | uc001vcz.4, human [Q96T68-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF334407 mRNA Translation: AAK38373.1 AL136218 Genomic DNA No translation available. AL139321 Genomic DNA No translation available. BC017078 mRNA Translation: AAH17078.1 BC047434 mRNA Translation: AAH47434.1 AL831937 mRNA Translation: CAH56265.1 Sequence problems. |
CCDSi | CCDS53868.1 [Q96T68-2] CCDS9417.1 [Q96T68-1] |
RefSeqi | NP_001153780.1, NM_001160308.2 [Q96T68-2] NP_114121.2, NM_031915.2 [Q96T68-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5TFP | X-ray | 2.00 | A/B | 1-64 | [»] | |
AlphaFoldDBi | Q96T68 | |||||
SMRi | Q96T68 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123768, 15 interactors |
IntActi | Q96T68, 12 interactors |
STRINGi | 9606.ENSP00000346175 |
PTM databases
iPTMneti | Q96T68 |
PhosphoSitePlusi | Q96T68 |
Genetic variation databases
BioMutai | SETDB2 |
DMDMi | 143811459 |
Proteomic databases
jPOSTi | Q96T68 |
MassIVEi | Q96T68 |
PaxDbi | Q96T68 |
PeptideAtlasi | Q96T68 |
PRIDEi | Q96T68 |
ProteomicsDBi | 78203 [Q96T68-1] 78204 [Q96T68-2] 78205 [Q96T68-3] |
Protocols and materials databases
Antibodypediai | 23922, 233 antibodies from 36 providers |
DNASUi | 83852 |
Genome annotation databases
Ensembli | ENST00000317257.12; ENSP00000326477.9; ENSG00000136169.17 [Q96T68-2] ENST00000354234.8; ENSP00000346175.5; ENSG00000136169.17 ENST00000611815.2; ENSP00000482240.2; ENSG00000136169.17 [Q96T68-2] |
GeneIDi | 83852 |
KEGGi | hsa:83852 |
MANE-Selecti | ENST00000611815.2; ENSP00000482240.2; NM_001160308.3; NP_001153780.1 [Q96T68-2] |
UCSCi | uc001vcz.4, human [Q96T68-1] |
Organism-specific databases
CTDi | 83852 |
DisGeNETi | 83852 |
GeneCardsi | SETDB2 |
HGNCi | HGNC:20263, SETDB2 |
HPAi | ENSG00000136169, Low tissue specificity |
MIMi | 607865, gene |
neXtProti | NX_Q96T68 |
OpenTargetsi | ENSG00000136169 |
PharmGKBi | PA134956285 |
VEuPathDBi | HostDB:ENSG00000136169 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1141, Eukaryota |
GeneTreei | ENSGT00940000158209 |
HOGENOMi | CLU_003279_2_0_1 |
InParanoidi | Q96T68 |
OMAi | NQQVFCD |
OrthoDBi | 183716at2759 |
PhylomeDBi | Q96T68 |
TreeFami | TF106411 |
Enzyme and pathway databases
PathwayCommonsi | Q96T68 |
Reactomei | R-HSA-3214841, PKMTs methylate histone lysines |
SignaLinki | Q96T68 |
SIGNORi | Q96T68 |
Miscellaneous databases
BioGRID-ORCSi | 83852, 22 hits in 1117 CRISPR screens |
GenomeRNAii | 83852 |
Pharosi | Q96T68, Tbio |
PROi | PR:Q96T68 |
RNActi | Q96T68, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136169, Expressed in sperm and 211 other tissues |
ExpressionAtlasi | Q96T68, baseline and differential |
Genevisiblei | Q96T68, HS |
Family and domain databases
Gene3Di | 2.170.270.10, 2 hits |
InterProi | View protein in InterPro IPR016177, DNA-bd_dom_sf IPR001739, Methyl_CpG_DNA-bd IPR007728, Pre-SET_dom IPR001214, SET_dom IPR046341, SET_dom_sf |
Pfami | View protein in Pfam PF01429, MBD, 1 hit PF05033, Pre-SET, 1 hit PF00856, SET, 1 hit |
SMARTi | View protein in SMART SM00391, MBD, 1 hit SM00468, PreSET, 1 hit SM00317, SET, 1 hit |
SUPFAMi | SSF54171, SSF54171, 1 hit SSF82199, SSF82199, 1 hit |
PROSITEi | View protein in PROSITE PS50982, MBD, 1 hit PS50867, PRE_SET, 1 hit PS50280, SET, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SETB2_HUMAN | |
Accessioni | Q96T68Primary (citable) accession number: Q96T68 Secondary accession number(s): Q5TC65 Q96AI6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 3, 2003 |
Last sequence update: | April 3, 2007 | |
Last modified: | May 25, 2022 | |
This is version 168 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families