PRDM7_HUMAN
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-AUG-2022, entry version 168.
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}.
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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 PRIDE; Q9NQW5; -.
DR ProteomicsDB; 82207; -. [Q9NQW5-1]
DR ProteomicsDB; 82208; -. [Q9NQW5-2]
DR Antibodypedia; 67566; 66 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 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; EDCHELY; -.
DR OrthoDB; 1318335at2759; -.
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; 13 hits in 1030 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 methyltransferase activity (H3-K36 specific); IBA:GO_Central.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); 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:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR CDD; cd07765; KRAB_A-box; 1.
DR CDD; cd19193; PR-SET_PRDM7_9; 1.
DR Gene3D; 2.170.270.10; -; 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 Pfam; PF01352; KRAB; 1.
DR Pfam; PF09514; SSXRD; 1.
DR SMART; SM00349; KRAB; 1.
DR SUPFAM; SSF109640; SSF109640; 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
