ID SETD7_HUMAN Reviewed; 366 AA. AC Q8WTS6; Q0VAH3; Q4W5A9; Q9C0E6; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 24-NOV-2009, entry version 83. DE RecName: Full=Histone-lysine N-methyltransferase SETD7; DE EC=2.1.1.43; DE AltName: Full=Histone H3-K4 methyltransferase SETD7; DE AltName: Full=H3-K4-HMTase SETD7; DE AltName: Full=SET domain-containing protein 7; DE AltName: Full=SET7/9; DE AltName: Full=Lysine N-methyltransferase 7; GN Name=SETD7; Synonyms=KIAA1717, KMT7, SET7, SET9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 35-44; 108-115; RP 144-152; 234-258 AND 345-358, AND MUTAGENESIS OF HIS-297. RC TISSUE=Brain; RX MEDLINE=21638669; PubMed=11779497; DOI=10.1016/S1097-2765(01)00405-1; RA Wang H., Cao R., Xia L., Erdjument-Bromage H., Borchers C., Tempst P., RA Zhang Y.; RT "Purification and functional characterization of a histone H3-lysine RT 4-specific methyltransferase."; RL Mol. Cell 8:1207-1217(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 36-45; 104-115; RP 144-152; 159-169; 201-250 AND 324-358, AND MUTAGENESIS OF HIS-297. RC TISSUE=Cervix carcinoma; RX MEDLINE=21838688; PubMed=11850410; DOI=10.1101/gad.967202; RA Nishioka K., Chuikov S., Sarma K., Erdjument-Bromage H., Allis C.D., RA Tempst P., Reinberg D.; RT "Set9, a novel histone H3 methyltransferase that facilitates RT transcription by precluding histone tail modifications required for RT heterochromatin formation."; RL Genes Dev. 16:479-489(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX MEDLINE=21082932; PubMed=11214970; DOI=10.1093/dnares/7.6.347; RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIX. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=12588998; DOI=10.1128/MCB.23.5.1808-1816.2003; RA Martens J.H., Verlaan M., Kalkhoven E., Zantema A.; RT "Cascade of distinct histone modifications during collagenase gene RT activation."; RL Mol. Cell. Biol. 23:1808-1816(2003). RN [7] RP FUNCTION, AND MUTAGENESIS OF HIS-297. RX PubMed=15099517; DOI=10.1016/S1097-2765(04)00182-0; RA Kouskouti A., Scheer E., Staub A., Tora L., Talianidis I.; RT "Gene-specific modulation of TAF10 function by SET9-mediated RT methylation."; RL Mol. Cell 14:175-182(2004). RN [8] RP FUNCTION, INTERACTION WITH IPF1, AND MUTAGENESIS OF HIS-297. RX PubMed=16141209; DOI=10.1074/jbc.M505741200; RA Francis J., Chakrabarti S.K., Garmey J.C., Mirmira R.G.; RT "Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II RT elongation during activation of insulin transcription."; RL J. Biol. Chem. 280:36244-36253(2005). RN [9] RP FUNCTION. RX PubMed=17108971; DOI=10.1038/nature05287; RA Huang J., Perez-Burgos L., Placek B.J., Sengupta R., Richter M., RA Dorsey J.A., Kubicek S., Opravil S., Jenuwein T., Berger S.L.; RT "Repression of p53 activity by Smyd2-mediated methylation."; RL Nature 444:629-632(2006). RN [10] RP MUTAGENESIS OF GLU-220; GLU-228; TYR-245 AND LYS-294. RX PubMed=16433545; DOI=10.1021/ja056153+; RA Hu P., Zhang Y.; RT "Catalytic mechanism and product specificity of the histone lysine RT methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple RT initial structures."; RL J. Am. Chem. Soc. 128:1272-1278(2006). RN [11] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [12] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 52-344. RX MEDLINE=22259601; PubMed=12372304; DOI=10.1016/S0092-8674(02)00964-9; RA Wilson J., Jing C., Walker P., Martin S., Howell S., Blackburn G., RA Gamblin S., Xiao B.; RT "Crystal structure and functional analysis of the histone RT methyltransferase SET7/9."; RL Cell 111:105-115(2002). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX MEDLINE=22289682; PubMed=12389038; DOI=10.1038/nsb861; RA Jacobs S.A., Harp J.M., Devarakonda S., Kim Y., Rastinejad F., RA Khorasanizadeh S.; RT "The active site of the SET domain is constructed on a knot."; RL Nat. Struct. Biol. 9:833-838(2002). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 108-366 IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE AND HISTONE PEPTIDE, FUNCTION, AND MUTAGENESIS RP OF TYR-245. RX MEDLINE=22459284; PubMed=12540855; DOI=10.1038/nature01378; RA Xiao B., Jing C., Wilson J.R., Walker P.A., Vasisht N., Kelly G., RA Howell S., Taylor I.A., Blackburn G.M., Gamblin S.J.; RT "Structure and catalytic mechanism of the human histone RT methyltransferase SET7/9."; RL Nature 421:652-656(2003). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 70-366 IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE. RX MEDLINE=22401621; PubMed=12514135; DOI=10.1093/emboj/cdg025; RA Kwon T., Chang J.H., Kwak E., Lee C.W., Joachimiak A., Kim Y.C., RA Lee J., Cho Y.; RT "Mechanism of histone lysine methyl transfer revealed by the structure RT of SET7/9-AdoMet."; RL EMBO J. 22:292-303(2003). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 108-366, FUNCTION, AND RP MUTAGENESIS OF HIS-297. RX PubMed=15525938; DOI=10.1038/nature03117; RA Chuikov S., Kurash J.K., Wilson J.R., Xiao B., Justin N., Ivanov G.S., RA McKinney K., Tempst P., Prives C., Gamblin S.J., Barlev N.A., RA Reinberg D.; RT "Regulation of p53 activity through lysine methylation."; RL Nature 432:353-360(2004). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 110-366, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MUTAGENESIS OF LYS-317. RX PubMed=16415881; DOI=10.1038/nsmb1045; RA Couture J.-F., Collazo E., Hauk G., Trievel R.C.; RT "Structural basis for the methylation site specificity of SET7/9."; RL Nat. Struct. Mol. Biol. 13:140-146(2006). CC -!- FUNCTION: Histone methyltransferase that specifically CC monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation CC represents a specific tag for epigenetic transcriptional CC activation. Plays a central role in the transcriptional activation CC of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 CC to the insulin promoter, leading to activate transcription. Has CC also methyltransferase activity toward non-histone proteins such CC as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding CC the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' CC of TAF10, leading to increase the affinity of TAF10 for RNA CC polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing CC p53/TP53 and increasing p53/TP53-mediated transcriptional CC activation. Also able to demethylated 'Lys-372' of p53/TP53 in CC vitro. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + histone L-lysine = CC S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=29 uM for histone H3; CC KM=12 uM for TAF10; CC KM=69 uM for TP/p53; CC -!- SUBUNIT: Interacts with IPF1/PDX-1. CC -!- INTERACTION: CC P68431:HIST1H3A; NbExp=4; IntAct=EBI-1268586, EBI-79722; CC P68433:Hist1h3a (xeno); NbExp=2; IntAct=EBI-1268586, EBI-79743; CC Q12962:TAF10; NbExp=2; IntAct=EBI-1268586, EBI-708376; CC P04637:TP53; NbExp=3; IntAct=EBI-1268586, EBI-366083; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in pancreatic CC islets. CC -!- DOMAIN: The SET domain is necessary but not sufficient for histone CC methyltransferase activity. CC -!- MISCELLANEOUS: Monomethyltransferase activity is achieved by CC disrupting the formation at near-attack conformations for the CC dimethylation reaction. CC -!- SIMILARITY: Belongs to the histone-lysine methyltransferase CC family. SET7 subfamily. CC -!- SIMILARITY: Contains 3 MORN repeats. CC -!- SIMILARITY: Contains 1 SET domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF462150; AAL69901.1; -; mRNA. DR EMBL; AB051504; BAB21808.1; ALT_INIT; mRNA. DR EMBL; AC112236; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC114743; AAY40937.1; -; Genomic_DNA. DR EMBL; BC121055; AAI21056.1; -; mRNA. DR EMBL; BC121056; AAI21057.1; -; mRNA. DR IPI; IPI00028366; -. DR RefSeq; NP_085151.1; -. DR UniGene; Hs.480792; -. DR PDB; 1H3I; X-ray; 2.10 A; A/B=52-344. DR PDB; 1MT6; X-ray; 2.20 A; A=58-337. DR PDB; 1MUF; X-ray; 2.26 A; A=81-337. DR PDB; 1N6A; X-ray; 1.70 A; A=108-366. DR PDB; 1N6C; X-ray; 2.30 A; A=70-366. DR PDB; 1O9S; X-ray; 1.75 A; A/B=108-366. DR PDB; 1XQH; X-ray; 1.75 A; A/E=108-366. DR PDB; 2F69; X-ray; 1.30 A; A=110-366. DR PDB; 3CBM; X-ray; 1.69 A; A=111-366. DR PDB; 3CBO; X-ray; 1.65 A; A=111-366. DR PDB; 3CBP; X-ray; 1.42 A; A=111-366. DR PDBsum; 1H3I; -. DR PDBsum; 1MT6; -. DR PDBsum; 1MUF; -. DR PDBsum; 1N6A; -. DR PDBsum; 1N6C; -. DR PDBsum; 1O9S; -. DR PDBsum; 1XQH; -. DR PDBsum; 2F69; -. DR PDBsum; 3CBM; -. DR PDBsum; 3CBO; -. DR PDBsum; 3CBP; -. DR DIP; DIP:29045N; -. DR IntAct; Q8WTS6; 4. DR STRING; Q8WTS6; -. DR PeptideAtlas; Q8WTS6; -. DR PRIDE; Q8WTS6; -. DR Ensembl; ENST00000274031; ENSP00000274031; ENSG00000145391; Homo sapiens. DR GeneID; 80854; -. DR KEGG; hsa:80854; -. DR UCSC; uc003ihw.1; human. DR CTD; 80854; -. DR GeneCards; GC04M140646; -. DR H-InvDB; HIX0004511; -. DR HGNC; HGNC:30412; SETD7. DR MIM; 606594; gene. DR HOGENOM; Q8WTS6; -. DR HOVERGEN; Q8WTS6; -. DR OMA; GSSVYHF; -. DR OrthoDB; EOG9NKFFK; -. DR BRENDA; 2.1.1.43; 247. DR NextBio; 71300; -. DR ArrayExpress; Q8WTS6; -. DR Bgee; Q8WTS6; -. DR CleanEx; HS_SETD7; -. DR Genevestigator; Q8WTS6; -. DR GermOnline; ENSG00000145391; Homo sapiens. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0016568; P:chromatin modification; NAS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:InterPro. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR017155; Hist-Lys_N-MeTrfase_SET. DR InterPro; IPR003409; MORN. DR InterPro; IPR001214; SET. DR Pfam; PF02493; MORN; 3. DR Pfam; PF00856; SET; 1. DR PIRSF; PIRSF037249; Histone_Lys_mtfrase_SET; 1. DR SMART; SM00317; SET; 1. DR PROSITE; PS50280; SET; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Chromatin regulator; Chromosomal protein; KW Complete proteome; Direct protein sequencing; Methyltransferase; KW Nucleus; Repeat; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase. FT CHAIN 1 366 Histone-lysine N-methyltransferase SETD7. FT /FTId=PRO_0000186054. FT REPEAT 36 58 MORN 1. FT REPEAT 59 81 MORN 2. FT REPEAT 106 128 MORN 3. FT DOMAIN 215 340 SET. FT REGION 226 228 S-adenosyl-L-methionine binding. FT REGION 256 258 Substrate binding. FT REGION 266 268 Substrate binding. FT REGION 296 297 S-adenosyl-L-methionine binding. FT COMPBIAS 51 54 Poly-Phe. FT BINDING 245 245 Substrate. FT BINDING 317 317 Substrate. FT BINDING 335 335 Substrate; via carbonyl oxygen. FT BINDING 356 356 S-adenosyl-L-methionine; via carbonyl FT oxygen. FT MUTAGEN 220 220 E->A: Increases near-attack FT conformations. FT MUTAGEN 228 228 E->A: Increases near-attack FT conformations. FT MUTAGEN 245 245 Y->A: Significantly reduces the FT monomethyltransferase activity but FT increases the dimethyltransferase FT activity. FT MUTAGEN 294 294 K->A: Significantly reduces the catalytic FT activity. FT MUTAGEN 297 297 H->A,G: Abolishes methyltransferase FT activity. FT MUTAGEN 317 317 K->A: Induces a reduction in FT methyltransferase activity toward TAF10 FT but an increased methyltransferase FT activity for H3 and p53/TP53. FT STRAND 54 56 FT STRAND 61 64 FT STRAND 67 75 FT STRAND 81 87 FT STRAND 90 98 FT STRAND 100 102 FT STRAND 119 122 FT STRAND 128 131 FT STRAND 141 147 FT STRAND 151 160 FT STRAND 163 176 FT STRAND 179 184 FT HELIX 210 213 FT STRAND 216 220 FT STRAND 228 234 FT STRAND 241 245 FT STRAND 248 250 FT HELIX 252 256 FT HELIX 260 262 FT STRAND 270 272 FT STRAND 274 276 FT TURN 279 282 FT TURN 284 286 FT HELIX 292 294 FT STRAND 302 310 FT TURN 311 313 FT STRAND 314 323 FT STRAND 330 333 FT HELIX 351 363 SQ SEQUENCE 366 AA; 40721 MW; 73A1217079E3BA13 CRC64; MDSDDEMVEE AVEGHLDDDG LPHGFCTVTY SSTDRFEGNF VHGEKNGRGK FFFFDGSTLE GYYVDDALQG QGVYTYEDGG VLQGTYVDGE LNGPAQEYDT DGRLIFKGQY KDNIRHGVCW IYYPDGGSLV GEVNEDGEMT GEKIAYVYPD ERTALYGKFI DGEMIEGKLA TLMSTEEGRP HFELMPGNSV YHFDKSTSSC ISTNALLPDP YESERVYVAE SLISSAGEGL FSKVAVGPNT VMSFYNGVRI THQEVDSRDW ALNGNTLSLD EETVIDVPEP YNHVSKYCAS LGHKANHSFT PNCIYDMFVH PRFGPIKCIR TLRAVEADEE LTVAYGYDHS PPGKSGPEAP EWYQVELKAF QATQQK //