SMYD4_HUMAN
ID SMYD4_HUMAN Reviewed; 804 AA.
AC Q8IYR2; Q8N1P2; Q8NAT0; Q96LV4; Q96PV2;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=SET and MYND domain-containing protein 4;
DE EC=2.1.1.-;
GN Name=SMYD4; Synonyms=KIAA1936;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-131 AND CYS-727.
RC TISSUE=Cerebellum, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-131 AND CYS-727.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 197-754, AND VARIANTS TRP-562 AND
RP CYS-727.
RC TISSUE=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [4]
RP VARIANTS ASP-345 AND GLN-579, CHARACTERIZATION OF VARIANT ASP-345,
RP FUNCTION, AND INTERACTION WITH HDAC1.
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).
RN [5]
RP VARIANT PRO-601.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q08C84, ECO:0000269|PubMed:30110327}.
CC -!- SUBUNIT: Interacts (via MYND-type zinc finger) with HDAC1.
CC {ECO:0000269|PubMed:30110327}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BTK5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BTK5}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; AK057769; BAB71564.1; -; mRNA.
DR EMBL; AK095369; BAC04538.1; -; mRNA.
DR EMBL; BC035077; AAH35077.1; -; mRNA.
DR EMBL; AB067523; BAB67829.1; -; mRNA.
DR CCDS; CCDS11013.1; -.
DR RefSeq; NP_443160.2; NM_052928.2.
DR AlphaFoldDB; Q8IYR2; -.
DR SMR; Q8IYR2; -.
DR BioGRID; 125376; 42.
DR IntAct; Q8IYR2; 7.
DR MINT; Q8IYR2; -.
DR STRING; 9606.ENSP00000304360; -.
DR iPTMnet; Q8IYR2; -.
DR PhosphoSitePlus; Q8IYR2; -.
DR BioMuta; SMYD4; -.
DR DMDM; 296452956; -.
DR EPD; Q8IYR2; -.
DR jPOST; Q8IYR2; -.
DR MassIVE; Q8IYR2; -.
DR MaxQB; Q8IYR2; -.
DR PaxDb; Q8IYR2; -.
DR PeptideAtlas; Q8IYR2; -.
DR PRIDE; Q8IYR2; -.
DR ProteomicsDB; 71215; -.
DR Antibodypedia; 22811; 222 antibodies from 28 providers.
DR DNASU; 114826; -.
DR Ensembl; ENST00000305513.12; ENSP00000304360.7; ENSG00000186532.12.
DR GeneID; 114826; -.
DR KEGG; hsa:114826; -.
DR MANE-Select; ENST00000305513.12; ENSP00000304360.7; NM_052928.3; NP_443160.2.
DR UCSC; uc002ftm.5; human.
DR CTD; 114826; -.
DR DisGeNET; 114826; -.
DR GeneCards; SMYD4; -.
DR HGNC; HGNC:21067; SMYD4.
DR HPA; ENSG00000186532; Low tissue specificity.
DR MIM; 619134; gene.
DR neXtProt; NX_Q8IYR2; -.
DR OpenTargets; ENSG00000186532; -.
DR PharmGKB; PA134925431; -.
DR VEuPathDB; HostDB:ENSG00000186532; -.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00730000111079; -.
DR HOGENOM; CLU_021727_0_0_1; -.
DR InParanoid; Q8IYR2; -.
DR OMA; FDCTCPA; -.
DR OrthoDB; 1278034at2759; -.
DR PhylomeDB; Q8IYR2; -.
DR TreeFam; TF106441; -.
DR PathwayCommons; Q8IYR2; -.
DR SignaLink; Q8IYR2; -.
DR BioGRID-ORCS; 114826; 15 hits in 1092 CRISPR screens.
DR ChiTaRS; SMYD4; human.
DR GeneWiki; SMYD4; -.
DR GenomeRNAi; 114826; -.
DR Pharos; Q8IYR2; Tbio.
DR PRO; PR:Q8IYR2; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IYR2; protein.
DR Bgee; ENSG00000186532; Expressed in gastrocnemius and 121 other tissues.
DR ExpressionAtlas; Q8IYR2; baseline and differential.
DR Genevisible; Q8IYR2; HS.
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:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Disease variant; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..804
FT /note="SET and MYND domain-containing protein 4"
FT /id="PRO_0000227784"
FT DOMAIN 233..574
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 296..335
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 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 335
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 427
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 539..540
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT BINDING 573
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 595
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT VARIANT 101
FT /note="N -> D (in dbSNP:rs9907701)"
FT /id="VAR_057495"
FT VARIANT 131
FT /note="R -> I (in dbSNP:rs7224496)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_025626"
FT VARIANT 236
FT /note="G -> S (in dbSNP:rs9913923)"
FT /id="VAR_057496"
FT VARIANT 345
FT /note="G -> D (probable disease-associated variant found in
FT a patient with congenital heart defect; significant loss of
FT interaction with HDAC1; fails to rescue the abnormal
FT cardiac phenotypes defects in zebrafish morphants;
FT dbSNP:rs759042432)"
FT /evidence="ECO:0000269|PubMed:30110327"
FT /id="VAR_084711"
FT VARIANT 374
FT /note="I -> M (in dbSNP:rs9890631)"
FT /id="VAR_057497"
FT VARIANT 382
FT /note="P -> R (in dbSNP:rs3809875)"
FT /id="VAR_057498"
FT VARIANT 562
FT /note="R -> W (in dbSNP:rs11549830)"
FT /evidence="ECO:0000269|PubMed:11572484"
FT /id="VAR_025628"
FT VARIANT 579
FT /note="R -> Q (found in a patient with congenital heart
FT defect; dbSNP:rs766983285)"
FT /evidence="ECO:0000269|PubMed:30110327"
FT /id="VAR_084712"
FT VARIANT 601
FT /note="A -> P (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064755"
FT VARIANT 727
FT /note="Y -> C (in dbSNP:rs9902398)"
FT /evidence="ECO:0000269|PubMed:11572484,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_025627"
FT CONFLICT 326
FT /note="A -> V (in Ref. 2; AAH35077)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="H -> R (in Ref. 1; BAC04538)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="P -> S (in Ref. 1; BAC04538)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 804 AA; 89225 MW; 982F8BFEF40A49A2 CRC64;
MDLPVDEWKS YLLQKWASLP TSVQVTISTA ETLRDIFLHS SSLLQPEDEL FLKRLSKGYL
VGKDSDAPLF YREEGNKKFQ EKDYTGAAVL YSKGVSHSRP NTEDMSLCHA NRSAALFHLG
QYETCLKDIN RAQTHGYPER LQPKIMLRKA ECLVALGRLQ EASQTISDLE RNFTATPALA
DVLPQTLQRN LHRLKMKMQE KDSLTESFPA ALAKTLEDAA LREENEQLSN ASSSIGLCVD
PLKGRCLVAT KDILPGELLV QEDAFVSVLN PGELPPPHHG LDSKWDTRVT NGDLYCHRCL
KHTLATVPCD GCSYAKYCSQ ECLQQAWELY HRTECPLGGL LLTLGVFCHI ALRLTLLVGF
EDVRKIITKL CDKISNKDIC LPESNNQVKT LNYGLGESEK NGNIVETPIP GCDINGKYEN
NYNAVFNLLP HTENHSPEHK FLCALCVSAL CRQLEAASLQ AIPTERIVNS SQLKAAVTPE
LCPDVTIWGV AMLRHMLQLQ CNAQAMTTIQ HTGPKGSIVT DSRQVRLATG IFPVISLLNH
SCSPNTSVSF ISTVATIRAS QRIRKGQEIL HCYGPHKSRM GVAERQQKLR SQYFFDCACP
ACQTEAHRMA AGPRWEAFCC NSCGAPMQGD DVLRCGSRSC AESAVSRDHL VSRLQDLQQQ
VRVAQKLLRD GELERAVQRL SGCQRDAESF LWAEHAVVGE IADGLARACA ALGDWQKSAT
HLQRSLYVVE VRHGPSSVEM GHELFKLAQI FFNGFAVPEA LSTIQKAEEV LSLHCGPWDD
EIQELQKMKS CLLDLPPTPV GPAL
