SETD6_MOUSE
ID SETD6_MOUSE Reviewed; 473 AA.
AC Q9CWY3; B2RTA7; Q8C6I1;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=N-lysine methyltransferase SETD6;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q8TBK2};
DE AltName: Full=SET domain-containing protein 6;
GN Name=Setd6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-22, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION.
RX PubMed=23324626; DOI=10.4161/epi.23416;
RA Binda O., Sevilla A., LeRoy G., Lemischka I.R., Garcia B.A., Richard S.;
RT "SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance
RT of embryonic stem cell self-renewal.";
RL Epigenetics 8:177-183(2013).
CC -!- FUNCTION: Protein-lysine N-methyltransferase. Monomethylates 'Lys-310'
CC of the RELA subunit of NF-kappa-B complex, leading to down-regulation
CC of NF-kappa-B transcription factor activity. Monomethylates 'Lys-8' of
CC H2AZ (H2AZK8me1) (By similarity). Required for the maintenance of
CC embryonic stem cell self-renewal (PubMed:23324626). Methylates PAK4.
CC {ECO:0000250|UniProtKB:Q8TBK2, ECO:0000269|PubMed:23324626}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000250|UniProtKB:Q8TBK2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51737;
CC Evidence={ECO:0000250|UniProtKB:Q8TBK2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(8)-[histone H2AZ] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(8)-[histone H2AZ] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:67808, Rhea:RHEA-COMP:17357, Rhea:RHEA-COMP:17358,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000250|UniProtKB:Q8TBK2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67809;
CC Evidence={ECO:0000250|UniProtKB:Q8TBK2};
CC -!- SUBUNIT: Monomer, homodimer and homotrimer; these structures are
CC stabilized in the presence of S-adenosyl-L-methionine (SAM).
CC {ECO:0000250|UniProtKB:Q8TBK2}.
CC -!- INTERACTION:
CC Q9CWY3; Q9UHL9: GTF2IRD1; Xeno; NbExp=3; IntAct=EBI-10768425, EBI-372530;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8TBK2}.
CC -!- PTM: Automethylated. {ECO:0000250|UniProtKB:Q8TBK2}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC35846.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK010304; BAB26837.1; -; mRNA.
DR EMBL; AK075597; BAC35846.1; ALT_FRAME; mRNA.
DR EMBL; AK167753; BAE39788.1; -; mRNA.
DR EMBL; CH466525; EDL11181.1; -; Genomic_DNA.
DR EMBL; BC139198; AAI39199.1; -; mRNA.
DR EMBL; BC139199; AAI39200.1; -; mRNA.
DR CCDS; CCDS22566.1; -.
DR RefSeq; NP_001030295.1; NM_001035123.3.
DR AlphaFoldDB; Q9CWY3; -.
DR SMR; Q9CWY3; -.
DR BioGRID; 426098; 1.
DR IntAct; Q9CWY3; 2.
DR MINT; Q9CWY3; -.
DR STRING; 10090.ENSMUSP00000034096; -.
DR iPTMnet; Q9CWY3; -.
DR PhosphoSitePlus; Q9CWY3; -.
DR EPD; Q9CWY3; -.
DR MaxQB; Q9CWY3; -.
DR PaxDb; Q9CWY3; -.
DR PeptideAtlas; Q9CWY3; -.
DR PRIDE; Q9CWY3; -.
DR ProteomicsDB; 257127; -.
DR Antibodypedia; 48742; 145 antibodies from 26 providers.
DR DNASU; 66083; -.
DR Ensembl; ENSMUST00000034096; ENSMUSP00000034096; ENSMUSG00000031671.
DR GeneID; 66083; -.
DR KEGG; mmu:66083; -.
DR UCSC; uc009myv.1; mouse.
DR CTD; 79918; -.
DR MGI; MGI:1913333; Setd6.
DR VEuPathDB; HostDB:ENSMUSG00000031671; -.
DR eggNOG; KOG1338; Eukaryota.
DR GeneTree; ENSGT00940000153577; -.
DR HOGENOM; CLU_017135_2_0_1; -.
DR InParanoid; Q9CWY3; -.
DR OMA; EYSADYL; -.
DR OrthoDB; 490654at2759; -.
DR PhylomeDB; Q9CWY3; -.
DR TreeFam; TF106399; -.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR BioGRID-ORCS; 66083; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Setd6; mouse.
DR PRO; PR:Q9CWY3; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9CWY3; protein.
DR Bgee; ENSMUSG00000031671; Expressed in otic placode and 258 other tissues.
DR ExpressionAtlas; Q9CWY3; baseline and differential.
DR Genevisible; Q9CWY3; MM.
DR GO; GO:0005694; C:chromosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISS:UniProtKB.
DR GO; GO:0034968; P:histone lysine methylation; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IDA:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; IDA:UniProtKB.
DR CDD; cd19178; SET_SETD6; 1.
DR Gene3D; 3.90.1420.10; -; 1.
DR InterPro; IPR011383; N-lys_methylase_SETD6.
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; IPR044430; SETD6_SET.
DR Pfam; PF09273; Rubis-subs-bind; 1.
DR Pfam; PF00856; SET; 1.
DR PIRSF; PIRSF011771; RMS1_SET; 1.
DR SUPFAM; SSF81822; SSF81822; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Methylation; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..473
FT /note="N-lysine methyltransferase SETD6"
FT /id="PRO_0000281890"
FT DOMAIN 62..286
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 73..75
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 251..252
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT BINDING 297
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 63
FT /note="N6-methylated lysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT MOD_RES 179
FT /note="N6-methylated lysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT MOD_RES 372
FT /note="N6-methylated lysine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q8TBK2"
FT CONFLICT 87
FT /note="E -> T (in Ref. 1; BAC35846)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 52960 MW; 36B10A092DF43ECF CRC64;
MAAPAKRARV SGGSPLVAPC PSPRAARAPL PLPAGSSGGE PEGDAVAGFL RWCRRVGLEL
SPKVTVSRQG TVAGYGMVAR ESVRAGELLF AVPRSALLSP HTCSISGLLE RERGALQSLS
GWVPLLLALL HELQAPASPW SPYFALWPEL GRLEHPMFWP EEERLRLLKG TGVPEAVEKD
LVNIRSEYYS IVLPFMEAHS DLFSPSVRSL ELYQQLVALV MAYSFQEPLE EDDDEKEPNS
PLMVPAADIL NHIANHNANL EYSADYLRMV ATQPILEGHE IFNTYGQMAN WQLIHMYGFA
EPYPNNTDDT ADIQMVTVRD AALQGTKDET EKLLVCERWD FLCKQEMVGE EGAFVIGCEE
VLTEEELATT LKVLCMPAEE FRDYKERAGW GEEETEDDSL AITDIPKLQE SWKRLLRNSV
LLTLQTYTTD LKTDQDLLSN KEAYATLSWR EQQALQVRYG QKMILHRVLE LTN
