SETB2_DANRE
ID SETB2_DANRE Reviewed; 551 AA.
AC Q06ZW3; Q6NZ23;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Histone-lysine N-methyltransferase SETDB2;
DE EC=2.1.1.366 {ECO:0000250|UniProtKB:Q96T68};
DE AltName: Full=SET domain bifurcated 2;
GN Name=setdb2; ORFNames=zgc:77298;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney marrow;
RX PubMed=15520368; DOI=10.1073/pnas.0407241101;
RA Song H.-D., Sun X.-J., Deng M., Zhang G.-W., Zhou Y., Wu X.-Y., Sheng Y.,
RA Chen Y., Ruan Z., Jiang C.-L., Fan H.-Y., Zon L.I., Kanki J.P., Liu T.X.,
RA Look A.T., Chen Z.;
RT "Hematopoietic gene expression profile in zebrafish kidney marrow.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16240-16245(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=20133783; DOI=10.1073/pnas.0914396107;
RA Xu P.F., Zhu K.Y., Jin Y., Chen Y., Sun X.J., Deng M., Chen S.J., Chen Z.,
RA Liu T.X.;
RT "Setdb2 restricts dorsal organizer territory and regulates left-right
RT asymmetry through suppressing fgf8 activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2521-2526(2010).
CC -!- FUNCTION: Histone methyltransferase involved in left-right axis
CC specification in early development and mitosis. Specifically
CC trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 represents a
CC specific tag for epigenetic transcriptional repression by recruiting
CC HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones.
CC Contributes to H3K9me3 in both the interspersed repetitive elements and
CC centromere-associated repeats. Plays a role in chromosome condensation
CC and segregation during mitosis. During early development, required to
CC specify the left-right axis by repressing expression of FGF8, leading
CC to negatively regulate the dorsal organizer formation.
CC {ECO:0000269|PubMed:20133783}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-
CC COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; EC=2.1.1.366;
CC Evidence={ECO:0000250|UniProtKB:Q96T68};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed throughout embryogenesis. {ECO:0000269|PubMed:20133783}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Randomization of left-right asymmetry, including
CC heart and visceral organs. {ECO:0000269|PubMed:20133783}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; DQ358104; ABC88479.1; -; mRNA.
DR EMBL; BC066376; AAH66376.1; -; mRNA.
DR RefSeq; NP_996941.1; NM_207058.1.
DR AlphaFoldDB; Q06ZW3; -.
DR GeneID; 335153; -.
DR KEGG; dre:335153; -.
DR CTD; 83852; -.
DR ZFIN; ZDB-GENE-030131-7093; setdb2.
DR InParanoid; Q06ZW3; -.
DR OrthoDB; 183716at2759; -.
DR PhylomeDB; Q06ZW3; -.
DR PRO; PR:Q06ZW3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0060027; P:convergent extension involved in gastrulation; IMP:ZFIN.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:UniProtKB.
DR GO; GO:0070828; P:heterochromatin organization; IBA:GO_Central.
DR GO; GO:0051567; P:histone H3-K9 methylation; IMP:UniProtKB.
DR GO; GO:0070986; P:left/right axis specification; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IBA:GO_Central.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR016177; DNA-bd_dom_sf.
DR InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF01429; MBD; 1.
DR Pfam; PF05033; Pre-SET; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00391; MBD; 1.
DR SMART; SM00468; PreSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54171; SSF54171; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50867; PRE_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Chromatin regulator; Chromosome;
KW Developmental protein; Metal-binding; Methyltransferase; Mitosis; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..551
FT /note="Histone-lysine N-methyltransferase SETDB2"
FT /id="PRO_0000398646"
FT DOMAIN 146..210
FT /note="MBD"
FT DOMAIN 269..329
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 332..537
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 426..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 271
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 271
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 342..344
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 491
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 494..495
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT CONFLICT 166
FT /note="D -> E (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="S -> I (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="R -> H (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 281..282
FT /note="HS -> QR (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="R -> C (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="M -> R (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 445..446
FT /note="NR -> DQ (in Ref. 1; ABC88479)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 551 AA; 62424 MW; 080D6827516499CA CRC64;
METEADTAKT FWSEVDVDGV FDELMEVLRR LRHTLRHNTA TDREYVQAMR IVQESKLIRT
ETEDVLLDED ILTVTVSEPQ CSPESLQNGI EPEDPQHSTA RLYSDVGVVC SHMSSSRPDP
AAPLVFQPHV CSSACVPHLP AHTHHLLGHN PLRAPLLCHF QRVCDDAGVV YKAPCGRSLS
CMQEVLHFLL QTQSVCVLQT DRFSFSTQVC VERQVCAAPL LERDLSRGLE PVPVALVNTV
DGARPREFRY RRERWPHGCF LSAEPLYSVC CDCTDGCTDA HSCACVRRTA GAAYTHQRLT
HTLRTGLFEC GPWCGCERSR CENRVVQKGL RVRLQVFRTP EHMWAVRCRD DLDAGTFICI
YAGVVLRLQQ SSECPAERSG EPAVSDDEVQ LVEEWRIPEE THTHTHTLDS SPPLHVPVIQ
RPAEHSLAQR RDQQQFSISS ETEDNRCEQA LRKKPRLMES NGLQDSRTHT LTHTHDGVYY
LDASREGNVA RFFTHSDDPN LFIQNVFTDT HDPQFPLIAF FTCRPVKAGT ELTWSCTNTE
QQKTEEKHCS V
