ID PRDM7_HUMAN Reviewed; 492 AA. AC Q9NQW5; A4Q9G8; Q08EM4; Q9NQW4; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 2. DT 03-MAY-2023, entry version 172. DE RecName: Full=Histone-lysine N-methyltransferase PRDM7; DE EC=2.1.1.- {ECO:0000269|PubMed:27129774}; DE AltName: Full=PR domain zinc finger protein 7; DE AltName: Full=PR domain-containing protein 7; DE AltName: Full=[histone H3]-lysine4 N-methyltransferase PRDM7; GN Name=PRDM7 {ECO:0000303|PubMed:27129774, ECO:0000312|HGNC:HGNC:9351}; GN Synonyms=PFM4; 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 [MRNA] (ISOFORM 1), AND VARIANT GLU-90. RX PubMed=17916234; DOI=10.1186/1471-2148-7-187; RA Fumasoni I., Meani N., Rambaldi D., Scafetta G., Alcalay M., RA Ciccarelli F.D.; RT "Family expansion and gene rearrangements contributed to the functional RT specialization of PRDM genes in vertebrates."; RL BMC Evol. Biol. 7:187-187(2007). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). RX PubMed=10668202; DOI=10.14670/hh-15.109; RA Jiang G.L., Huang S.; RT "The yin-yang of PR-domain family genes in tumorigenesis."; RL Histol. Histopathol. 15:109-117(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [5] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF SER-289; SER-312 AND SER-357. RX PubMed=27129774; DOI=10.1074/jbc.m116.721472; RA Blazer L.L., Lima-Fernandes E., Gibson E., Eram M.S., Loppnau P., RA Arrowsmith C.H., Schapira M., Vedadi M.; RT "PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 RT Trimethyltransferase."; RL J. Biol. Chem. 291:13509-13519(2016). CC -!- FUNCTION: Histone methyltransferase that selectively methylates 'Lys-4' CC of dimethylated histone H3 (H3K4me2) to produce trimethylated 'Lys-4' CC histone H3 (H3K4me3). May play a role in epigenetic regulation of gene CC expression by defining an active chromatin state. CC {ECO:0000269|PubMed:27129774}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L- CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60272, Rhea:RHEA- CC COMP:15537, Rhea:RHEA-COMP:15540, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:27129774}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60273; CC Evidence={ECO:0000269|PubMed:27129774}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=900 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:27129774}; CC KM=0.8 uM for H3K4me0 {ECO:0000269|PubMed:27129774}; CC KM=0.7 uM for H3K4me1 {ECO:0000269|PubMed:27129774}; CC KM=3.5 uM for H3K4me2 {ECO:0000269|PubMed:27129774}; CC Note=kcat is 190 h(-1) with S-adenosyl-L-methionine as substrate. CC kcat is 9 h(-1) with H3K4me0 as substrate. kcat is 8 h(-1) with CC H3K4me1 as substrate. kcat is 190 h(-1) with H3K4me2 as substrate. CC {ECO:0000269|PubMed:27129774}; CC -!- INTERACTION: CC Q9NQW5; Q13077: TRAF1; NbExp=3; IntAct=EBI-10312471, EBI-359224; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Chromosome {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9NQW5-3; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q9NQW5-2; Sequence=VSP_036349, VSP_006930, VSP_006931; CC Name=3; Synonyms=A; CC IsoId=Q9NQW5-1; Sequence=VSP_036349, VSP_036350; CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. 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; AM690991; CAM84449.1; -; mRNA. DR EMBL; AF274347; AAF78084.1; -; mRNA. DR EMBL; AF274348; AAF78085.1; -; mRNA. DR EMBL; CH471184; EAW66654.1; -; Genomic_DNA. DR EMBL; BC107033; AAI07034.1; -; mRNA. DR CCDS; CCDS45557.1; -. [Q9NQW5-3] DR RefSeq; NP_001091643.1; NM_001098173.1. [Q9NQW5-3] DR RefSeq; XP_005256331.1; XM_005256274.3. DR AlphaFoldDB; Q9NQW5; -. DR SMR; Q9NQW5; -. DR BioGRID; 116286; 11. DR IntAct; Q9NQW5; 9. DR MINT; Q9NQW5; -. DR STRING; 9606.ENSP00000396732; -. DR iPTMnet; Q9NQW5; -. DR PhosphoSitePlus; Q9NQW5; -. DR BioMuta; PRDM7; -. DR DMDM; 223590134; -. DR jPOST; Q9NQW5; -. DR MassIVE; Q9NQW5; -. DR PaxDb; Q9NQW5; -. DR PeptideAtlas; Q9NQW5; -. DR ProteomicsDB; 82207; -. [Q9NQW5-1] DR ProteomicsDB; 82208; -. [Q9NQW5-2] DR Antibodypedia; 67566; 68 antibodies from 16 providers. DR DNASU; 11105; -. DR Ensembl; ENST00000449207.8; ENSP00000396732.2; ENSG00000126856.16. [Q9NQW5-3] DR GeneID; 11105; -. DR KEGG; hsa:11105; -. DR MANE-Select; ENST00000449207.8; ENSP00000396732.2; NM_001098173.2; NP_001091643.1. DR UCSC; uc010cje.4; human. [Q9NQW5-3] DR AGR; HGNC:9351; -. DR CTD; 11105; -. DR DisGeNET; 11105; -. DR GeneCards; PRDM7; -. DR HGNC; HGNC:9351; PRDM7. DR HPA; ENSG00000126856; Tissue enriched (testis). DR MIM; 609759; gene. DR neXtProt; NX_Q9NQW5; -. DR OpenTargets; ENSG00000126856; -. DR PharmGKB; PA33719; -. DR VEuPathDB; HostDB:ENSG00000126856; -. DR eggNOG; KOG2461; Eukaryota. DR GeneTree; ENSGT00940000158211; -. DR HOGENOM; CLU_042879_1_0_1; -. DR InParanoid; Q9NQW5; -. DR OMA; PFQVRNF; -. DR OrthoDB; 3470369at2759; -. DR PhylomeDB; Q9NQW5; -. DR TreeFam; TF337915; -. DR BioCyc; MetaCyc:HS13221-MON; -. DR BRENDA; 2.1.1.354; 2681. DR PathwayCommons; Q9NQW5; -. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR SignaLink; Q9NQW5; -. DR BioGRID-ORCS; 11105; 14 hits in 1107 CRISPR screens. DR GenomeRNAi; 11105; -. DR Pharos; Q9NQW5; Tdark. DR PRO; PR:Q9NQW5; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9NQW5; protein. DR Bgee; ENSG00000126856; Expressed in right testis and 59 other tissues. DR ExpressionAtlas; Q9NQW5; baseline and differential. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; IBA:GO_Central. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; IDA:ARUK-UCL. DR GO; GO:0010844; F:recombination hotspot binding; IBA:GO_Central. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0080182; P:histone H3-K4 trimethylation; IDA:ARUK-UCL. DR GO; GO:0010845; P:positive regulation of reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro. DR CDD; cd07765; KRAB_A-box; 1. DR CDD; cd19193; PR-SET_PRDM7_9; 1. DR Gene3D; 6.10.140.140; -; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR InterPro; IPR003655; aKRAB. DR InterPro; IPR001909; KRAB. DR InterPro; IPR036051; KRAB_dom_sf. DR InterPro; IPR044417; PRDM7_9_PR-SET. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR019041; SSXRD_motif. DR PANTHER; PTHR16515; PR DOMAIN ZINC FINGER PROTEIN; 1. DR PANTHER; PTHR16515:SF18; ZINC FINGER PROTEIN 711-RELATED; 1. DR Pfam; PF01352; KRAB; 1. DR Pfam; PF09514; SSXRD; 1. DR SMART; SM00349; KRAB; 1. DR SUPFAM; SSF109640; KRAB domain (Kruppel-associated box); 1. DR PROSITE; PS50806; KRAB_RELATED; 1. DR PROSITE; PS50280; SET; 1. PE 1: Evidence at protein level; KW Alternative splicing; Chromatin regulator; Chromosome; Methyltransferase; KW Nucleus; Reference proteome; S-adenosyl-L-methionine; Transferase. FT CHAIN 1..492 FT /note="Histone-lysine N-methyltransferase PRDM7" FT /id="PRO_0000047763" FT DOMAIN 23..86 FT /note="KRAB-related" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00120" FT DOMAIN 244..358 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 111..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 118..165 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..206 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10668202, FT ECO:0000303|PubMed:15489334" FT /id="VSP_036349" FT VAR_SEQ 318..377 FT /note="YVNCARDDEEQNLVAFQYHRQIFYRTCRVIRPGCELLVWSGDEYGQELGIRS FT SIEPAESL -> TKARDPSMSLMLSGLFKSKISQSTCGTQSLLSELPRTICKKTSPTRE FT SLPRGSESGAAIF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10668202, FT ECO:0000303|PubMed:15489334" FT /id="VSP_006930" FT VAR_SEQ 368..492 FT /note="RSSIEPAESLGQAVNCWSGMGMSMARNWASSGAASGRKSSWQGENQSQRSIH FT VPHAVWPFQVKNFSVNMWNAITPLRTSQDHLQENFSNQRIPAQGIRIRSGNILIHAAVM FT TKPKVKRSKKGPNS -> KWGSKWKKELMAGREPKPEIHPCPSCCLAFSSQKFLSQHVE FT RNHSSQNFPGPSARKLLQPENPCPGDQNQERQYSDPRCCNDKTKGQEIKERSKLLNKRT FT WQREISRAFSSPPKGQMGSSRVGERMMEEESRTGQKVNPGNTGKLFVGVGISRIAKVKY FT GECGQGFSDKSDVITHQRTHTGGKPYVCRECGEGFSRKSDLLSHQRTHTGEKPYVCREC FT ERGFSRKSVLLIHQRTHRGEAPVCRKDE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10668202" FT /id="VSP_036350" FT VAR_SEQ 378..492 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10668202, FT ECO:0000303|PubMed:15489334" FT /id="VSP_006931" FT VARIANT 90 FT /note="D -> E (in dbSNP:rs12925933)" FT /evidence="ECO:0000269|PubMed:17916234" FT /id="VAR_057461" FT VARIANT 131 FT /note="R -> K (in dbSNP:rs2078478)" FT /id="VAR_057462" FT VARIANT 435 FT /note="N -> K (in dbSNP:rs7206111)" FT /id="VAR_057463" FT MUTAGEN 289 FT /note="S->N: Gains the ability to sequentially mono-, di-, FT and tri-methylate both 'Lys-4' and 'Lys-36' of histone H3, FT albeit with lower efficiency when compared to PRDM9." FT /evidence="ECO:0000269|PubMed:27129774" FT MUTAGEN 312 FT /note="S->W: Gains the ability to sequentially mono-, di-, FT and tri-methylate both 'Lys-4' and 'Lys-36' of histone H3, FT albeit with lower efficiency when compared to PRDM9." FT /evidence="ECO:0000269|PubMed:27129774" FT MUTAGEN 357 FT /note="S->Y: Substantially increases histone-lysine N- FT methyltransferase activity. Gains the catalytic competency FT of PRDM9. Sequentially mono-, di-, and tri-methylates both FT 'Lys-4' and 'Lys-36' of histone H3." FT /evidence="ECO:0000269|PubMed:27129774" FT CONFLICT 357 FT /note="S -> Y (in Ref. 2; AAF78084)" FT /evidence="ECO:0000305" SQ SEQUENCE 492 AA; 55777 MW; 0C80D8DE8BA65DC5 CRC64; MSPERSQEES PEGDTERTER KPMVKDAFKD ISIYFTKEEW AEMGDWEKTR YRNVKMNYNA LITVGLRATR PAFMCHRRQA IKLQVDDTED SDEEWTPRQQ VKPPWMAFRG EQSKHQKGMP KASFNNESSL RELSGTPNLL NTSDSEQAQK PVSPPGEAST SGQHSRLKLE LRRKETEGKM YSLRERKGHA YKEISEPQDD DYLYCEMCQN FFIDSCAAHG PPTFVKDSAV DKGHPNRSAL SLPPGLRIGP SGIPQAGLGV WNEASDLPLG LHFGPYEGRI TEDEEAANSG YSWLITKGRN CYEYVDGKDK SSANWMRYVN CARDDEEQNL VAFQYHRQIF YRTCRVIRPG CELLVWSGDE YGQELGIRSS IEPAESLGQA VNCWSGMGMS MARNWASSGA ASGRKSSWQG ENQSQRSIHV PHAVWPFQVK NFSVNMWNAI TPLRTSQDHL QENFSNQRIP AQGIRIRSGN ILIHAAVMTK PKVKRSKKGP NS //