SMYD4_DANRE
ID SMYD4_DANRE Reviewed; 753 AA.
AC Q08C84; A5XCC8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=SET and MYND domain-containing protein 4;
DE EC=2.1.1.-;
GN Name=smyd4;
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 GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 575-753.
RX PubMed=18231586; DOI=10.1371/journal.pone.0001499;
RA Sun X.-J., Xu P.-F., Zhou T., Hu M., Fu C.-T., Zhang Y., Jin Y., Chen Y.,
RA Chen S.-J., Huang Q.-H., Liu T.X., Chen Z.;
RT "Genome-wide survey and developmental expression mapping of zebrafish SET
RT domain-containing genes.";
RL PLoS ONE 3:E1499-E1499(2008).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=30110327; DOI=10.1371/journal.pgen.1007578;
RA Xiao D., Wang H., Hao L., Guo X., Ma X., Qian Y., Chen H., Ma J., Zhang J.,
RA Sheng W., Shou W., Huang G., Ma D.;
RT "The roles of SMYD4 in epigenetic regulation of cardiac development in
RT zebrafish.";
RL PLoS Genet. 14:e1007578-e1007578(2018).
CC -!- FUNCTION: Plays a critical role in cardiac development
CC (PubMed:30110327). Acts as a key epigenetic regulator of gene
CC expression during cardiac development via its dual activities as a
CC methyltransferase and negative regulator of HDAC1 (PubMed:30110327).
CC {ECO:0000269|PubMed:30110327}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BTK5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BTK5}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early embryos and
CC becomes enriched in the developing heart at 48 hours post-
CC fertilization. {ECO:0000269|PubMed:30110327}.
CC -!- DISRUPTION PHENOTYPE: Mutants generated by CRISPR-Cas9-mediated gene
CC editing exhibit severe cardiac malformations, including defects in
CC left-right patterning and looping and hypoplastic ventricles.
CC {ECO:0000269|PubMed:30110327}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; CABZ01017683; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01017684; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC124341; AAI24342.1; -; mRNA.
DR EMBL; DQ851818; ABI34489.1; -; mRNA.
DR RefSeq; NP_001070062.1; NM_001076594.1.
DR AlphaFoldDB; Q08C84; -.
DR SMR; Q08C84; -.
DR STRING; 7955.ENSDARP00000080925; -.
DR PaxDb; Q08C84; -.
DR Ensembl; ENSDART00000086490; ENSDARP00000080925; ENSDARG00000060983.
DR GeneID; 767654; -.
DR KEGG; dre:767654; -.
DR CTD; 114826; -.
DR ZFIN; ZDB-GENE-060929-248; smyd4.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00730000111079; -.
DR HOGENOM; CLU_021727_0_0_1; -.
DR InParanoid; Q08C84; -.
DR OMA; FDCTCPA; -.
DR OrthoDB; 1278034at2759; -.
DR PhylomeDB; Q08C84; -.
DR TreeFam; TF106441; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 10.
DR Bgee; ENSDARG00000060983; Expressed in presomitic mesoderm and 28 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; IMP:ZFIN.
DR GO; GO:0003007; P:heart morphogenesis; IMP:ZFIN.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1901726; P:negative regulation of histone deacetylase activity; IMP:ZFIN.
DR CDD; cd10536; SET_SMYD4; 1.
DR Gene3D; 1.25.40.10; -; 2.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR044421; SMYD4_SET.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR002893; Znf_MYND.
DR Pfam; PF00856; SET; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Metal-binding; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..753
FT /note="SET and MYND domain-containing protein 4"
FT /id="PRO_0000453152"
FT DOMAIN 186..528
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 246..285
FT /note="MYND-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 112..114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 246
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 281
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 285
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 467..468
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT BINDING 527
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT CONFLICT 587
FT /note="H -> C (in Ref. 3; ABI34489)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 753 AA; 83677 MW; F5F817B884F64B1E CRC64;
MDLPCQDWVC HVEQKWAELR SEETERFSLL TDIDAIFNYG LSLICPEDLN ILSRISEKFS
VKKSPETASE FRQQGNLSFK VKDYPAAVLH YSKGVCHADK NTDELSLCYA NRSAALFYQG
LYQACLEDIR RSLEAGYPSH LQDKLQTRQT ACQNQLRKAE KPNIPHTDHQ LSPCQKTVNS
TGHLSDGVSV YFSSDKGRHM LVMENKPAGE VVLEDEAYCS VLIPANIFNT GTNKAVETFG
TEDRHCHHCL SQSLSFVPCP KCSYARYCGE SCQKDAWDQW HQWECPVGAD LLAIGVLGHL
ALRVVLKAGQ TEVQMGIKNT KDHVTTYKND SPVQLSLGGD CGKSLDHTDC FHGSSYMGIY
SLLPHVAQHS PASRFLMAIT MAVIYGKLQG GPPPNKWMSF KDEGVKASWQ PEMSMLGATA
LRHMMQLRCN AQAITAVRVK EESGMAVQSS SEIRIATAIF PVLSLLNHSC SPNTSISFTT
GFQPDPHNQL GCSEGHFDHP KGSRSGVTVT VRASKDLTAG QEILHCYGPH RSRMEVKERQ
RLLLEQYFFQ CVCQACQRDL SEGSPNAKEH TAPGMKCVKC GKPLQSHTDG YTCSWSSCGH
QISSADVQNR LQGFQLLLDE AVHLMEQDRL NEALHILQSA FSQANSILTE THPFQGELAD
ALARLYASTG EWSLAASHLK RSLVAIQAQF GEDSIELGRQ LFKLAQLHFN GRDGVASLSV
IPRARRLLSL HCSPRCEELQ ELSEMEHCLQ GLL
