SETD3_RAT
ID SETD3_RAT Reviewed; 596 AA.
AC G3V6U9; Q5FWY6;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Actin-histidine N-methyltransferase {ECO:0000305};
DE EC=2.1.1.85 {ECO:0000269|PubMed:30526847};
DE AltName: Full=Protein-L-histidine N-tele-methyltransferase {ECO:0000305};
DE AltName: Full=SET domain-containing protein 3 {ECO:0000305};
GN Name=Setd3 {ECO:0000303|PubMed:30526847, ECO:0000312|RGD:1309550};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 147-596.
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30526847; DOI=10.7554/elife.37921;
RA Kwiatkowski S., Seliga A.K., Vertommen D., Terreri M., Ishikawa T.,
RA Grabowska I., Tiebe M., Teleman A.A., Jagielski A.K., Veiga-da-Cunha M.,
RA Drozak J.;
RT "SETD3 protein is the actin-specific histidine N-methyltransferase.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Protein-histidine N-methyltransferase that specifically
CC mediates 3-methylhistidine (tele-methylhistidine) methylation of actin
CC at 'His-73' (PubMed:30526847). Histidine methylation of actin is
CC required for smooth muscle contraction of the laboring uterus during
CC delivery (By similarity). Does not have protein-lysine N-
CC methyltransferase activity and probably only catalyzes histidine
CC methylation of actin (By similarity). {ECO:0000250|UniProtKB:Q86TU7,
CC ECO:0000269|PubMed:30526847}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidyl-[protein] + S-adenosyl-L-methionine = H(+) +
CC N(tele)-methyl-L-histidyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:19369, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:11600,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16367, ChEBI:CHEBI:29979,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.85;
CC Evidence={ECO:0000269|PubMed:30526847};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19370;
CC Evidence={ECO:0000269|PubMed:30526847};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.996 uM for beta-actin {ECO:0000269|PubMed:30526847};
CC KM=0.109 uM for S-adenosyl-L-methionine
CC {ECO:0000269|PubMed:30526847};
CC Vmax=11.28 nmol/min/mg enzyme with beta-actin as substrate
CC {ECO:0000269|PubMed:30526847};
CC Vmax=8.053 nmol/min/mg enzyme with S-adenosyl-L-methionine as
CC substrate {ECO:0000269|PubMed:30526847};
CC Note=kcat is 0.8 min(-1) with beta-actin as substrate
CC (PubMed:30526847). kcat is 0.57 min(-1) with S-adenosyl-L-methionine
CC as substrate (PubMed:30526847). {ECO:0000269|PubMed:30526847};
CC -!- SUBUNIT: Interacts with MYOD1. {ECO:0000250|UniProtKB:Q91WC0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86TU7}. Nucleus
CC {ECO:0000250|UniProtKB:Q91WC0}. Note=Localizes mainly in the cytoplasm.
CC {ECO:0000250|UniProtKB:Q86TU7}.
CC -!- DOMAIN: The SET domain specifically recognizes and binds actin,
CC suggesting that it does not accommodate substrates diverging from
CC actin. {ECO:0000250|UniProtKB:Q86TU7}.
CC -!- PTM: Phosphorylated by GSK3B, which is required for recognition by the
CC SCF(FBXW7) complex and subsequent degradation.
CC {ECO:0000250|UniProtKB:Q86TU7}.
CC -!- PTM: Ubiquitinated by the SCF(FBXW7) complex following phosphorylation
CC by GSK3B, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q86TU7}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. SETD3 actin-histidine methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00898}.
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DR EMBL; AABR07065498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474034; EDL97577.1; -; Genomic_DNA.
DR EMBL; BC089108; AAH89108.1; -; mRNA.
DR RefSeq; NP_001333399.1; NM_001346470.1.
DR RefSeq; XP_002726820.2; XM_002726774.2.
DR AlphaFoldDB; G3V6U9; -.
DR SMR; G3V6U9; -.
DR STRING; 10116.ENSRNOP00000009121; -.
DR jPOST; G3V6U9; -.
DR PaxDb; G3V6U9; -.
DR PRIDE; G3V6U9; -.
DR Ensembl; ENSRNOT00000009120; ENSRNOP00000009121; ENSRNOG00000006587.
DR GeneID; 299295; -.
DR KEGG; rno:299295; -.
DR CTD; 84193; -.
DR RGD; 1309550; Setd3.
DR eggNOG; KOG1337; Eukaryota.
DR GeneTree; ENSGT00940000153577; -.
DR HOGENOM; CLU_028272_0_0_1; -.
DR InParanoid; G3V6U9; -.
DR OMA; DFWMKIP; -.
DR OrthoDB; 489371at2759; -.
DR TreeFam; TF354226; -.
DR Reactome; R-RNO-3214841; PKMTs methylate histone lysines.
DR PRO; PR:G3V6U9; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Proteomes; UP000234681; Chromosome 6.
DR Bgee; ENSRNOG00000006587; Expressed in skeletal muscle tissue and 19 other tissues.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); ISO:RGD.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); ISO:RGD.
DR GO; GO:0018064; F:protein-L-histidine N-tele-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0030047; P:actin modification; IDA:UniProtKB.
DR GO; GO:0008218; P:bioluminescence; IEA:UniProtKB-KW.
DR GO; GO:0018021; P:peptidyl-histidine methylation; IDA:UniProtKB.
DR GO; GO:0018027; P:peptidyl-lysine dimethylation; IBA:GO_Central.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IBA:GO_Central.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IBA:GO_Central.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0070472; P:regulation of uterine smooth muscle contraction; ISS:UniProtKB.
DR CDD; cd19176; SET_SETD3; 1.
DR Gene3D; 3.90.1420.10; -; 1.
DR InterPro; IPR015353; Rubisco_LSMT_subst-bd.
DR InterPro; IPR036464; Rubisco_LSMT_subst-bd_sf.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR025785; SETD3.
DR InterPro; IPR044428; SETD3_SET.
DR Pfam; PF09273; Rubis-subs-bind; 1.
DR Pfam; PF00856; SET; 1.
DR SUPFAM; SSF81822; SSF81822; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51565; SAM_MT85_SETD3; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Cytoplasm; Luminescence; Methyltransferase; Nucleus;
KW Phosphoprotein; Photoprotein; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; Ubl conjugation.
FT CHAIN 1..596
FT /note="Actin-histidine N-methyltransferase"
FT /id="PRO_0000446383"
FT DOMAIN 94..314
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..586
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 75
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86TU7"
FT BINDING 104..106
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86TU7"
FT BINDING 254
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86TU7"
FT BINDING 275..279
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86TU7"
FT BINDING 325..327
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86TU7"
SQ SEQUENCE 596 AA; 67420 MW; 8B6407562CF41AF9 CRC64;
MGKKSRVKTQ KSGTGATATV SPKEILNLTS ELLQKCSSPA PGPGKEWEEY TQIRALVEKI
RKKQKGLSVT FDGKREDYFP DLMKWASENG ASVEGFEMVN FKEEGFGLRA TRDIKAEELF
LWVPRKLLMT VESAKNSILG PLYSQDRILQ AMGNIALAFH LLCERASPNS FWQPYIQTLP
SEYDTPLYFE EEEVRCLQST QAIHDVFSQY KNTARQYAYF YKVIQTHPHA NKLPLKDSFT
YEDYRWAVSS VMTRQNQIPT EDGSRVTLAL IPLWDMCNHT NGLITTGYNL EDDRCECVAL
QDFQAGDQIY IFYGTRSNAE FVIHSGFFFD NNSHDRVKIK LGVSKSDRLY AMKAEVLARA
GIPTSSVFAL HFTEPPISAQ LLAFLRVFCM TEEELKEHLL GDSAIDRIFT LGNSEFPVSW
DNEVKLWTFL EDRASLLLKT YKTTIEEDKT VLKNPDLSVR ATMAIKLRLG EKEILEKAVK
SAAMNREYYR KHMEERAPLP RYEESDLGLL EGGVGDSRLP LVLRKLEEEA GVQESLSLTE
TVSKVKAAEN GLVNGESLIP NGTRSENESL SPEESENTTG DTEESSGSMD AVKERL
