SETVS_PLAF7
ID SETVS_PLAF7 Reviewed; 2548 AA.
AC Q8IE95;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Variant-silencing SET domain-containing protein;
DE Short=PfSETvs;
DE EC=2.1.1.359 {ECO:0000305|PubMed:23823717};
DE AltName: Full=SET domain-containing protein 2;
DE Short=PfSET2;
GN Name=SETVS; Synonyms=SET2; ORFNames=MAL13P1.122;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=18299133; DOI=10.1016/j.ijpara.2008.01.002;
RA Cui L., Fan Q., Cui L., Miao J.;
RT "Histone lysine methyltransferases and demethylases in Plasmodium
RT falciparum.";
RL Int. J. Parasitol. 38:1083-1097(2008).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RC STRAIN=3D7;
RX PubMed=23823717; DOI=10.1038/nature12361;
RA Jiang L., Mu J., Zhang Q., Ni T., Srinivasan P., Rayavara K., Yang W.,
RA Turner L., Lavstsen T., Theander T.G., Peng W., Wei G., Jing Q.,
RA Wakabayashi Y., Bansal A., Luo Y., Ribeiro J.M., Scherf A., Aravind L.,
RA Zhu J., Zhao K., Miller L.H.;
RT "PfSETvs methylation of histone H3K36 represses virulence genes in
RT Plasmodium falciparum.";
RL Nature 499:223-227(2013).
CC -!- FUNCTION: Histone methyltransferase that specifically represses
CC expression of the surface antigen-coding var genes by mediating
CC trimethylation of 'Lys-36' of histone H3 (H3K36me3) on var genes.
CC SETVS-dependent H3K36me3 is specifically involved in var genes
CC silencing, a central step malaria pathogenesis: each parasite contains
CC 60 distinct var genes that each code for a different PfEMP1 protein.
CC During infection, the clonal parasite population expresses only 1 gene
CC at a time, while the 59 other var genes are silenced. The parasite then
CC switches to the expression of a new variant antigen as an immune-
CC evasion mechanism to avoid the host antibody response. Represses
CC expression of both var mRNA and antisense long non-coding RNA.
CC {ECO:0000269|PubMed:23823717}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359;
CC Evidence={ECO:0000305|PubMed:23823717};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23823717}. Chromosome
CC {ECO:0000269|PubMed:23823717}. Note=Localizes along the entire gene
CC body of silent var genes, including the transcription start site of var
CC genes and the respective intronic antisense promoter.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in early trophozoite stages.
CC Expression is then reduced in late trophozoites and elevated again in
CC schizonts. {ECO:0000269|PubMed:18299133}.
CC -!- DISRUPTION PHENOTYPE: Leads to expression of all var genes in the ring
CC stage. {ECO:0000269|PubMed:23823717}.
CC -!- MISCELLANEOUS: Parasites lacking SETVS could be used as an antimalarial
CC vaccine because of its ability to express all PfEMP1 proteins, to which
CC the antibody would provide efficient protective immunity against
CC malaria. {ECO:0000305|PubMed:23823717}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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; AL844509; CAD52368.1; -; Genomic_DNA.
DR RefSeq; XP_001349960.1; XM_001349924.1.
DR AlphaFoldDB; Q8IE95; -.
DR SMR; Q8IE95; -.
DR BioGRID; 1208944; 1.
DR IntAct; Q8IE95; 1.
DR STRING; 5833.MAL13P1.122; -.
DR PRIDE; Q8IE95; -.
DR EnsemblProtists; CAD52368; CAD52368; PF3D7_1322100.
DR GeneID; 813672; -.
DR KEGG; pfa:PF3D7_1322100; -.
DR VEuPathDB; PlasmoDB:PF3D7_1322100; -.
DR HOGENOM; CLU_228197_0_0_1; -.
DR InParanoid; Q8IE95; -.
DR OMA; SINNPKH; -.
DR PhylomeDB; Q8IE95; -.
DR Reactome; R-PFA-3214841; PKMTs methylate histone lysines.
DR Proteomes; UP000001450; Chromosome 13.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0034399; C:nuclear periphery; IDA:GeneDB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:GeneDB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0020033; P:antigenic variation; IMP:GeneDB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010452; P:histone H3-K36 methylation; IDA:GeneDB.
DR GO; GO:0097198; P:histone H3-K36 trimethylation; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:GeneDB.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR006560; AWS_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR001965; Znf_PHD.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00249; PHD; 4.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51215; AWS; 1.
DR PROSITE; PS50280; SET; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Chromosome; Malaria; Metal-binding; Methyltransferase;
KW Nucleus; Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase;
KW Zinc; Zinc-finger.
FT CHAIN 1..2548
FT /note="Variant-silencing SET domain-containing protein"
FT /id="PRO_0000424016"
FT DOMAIN 2067..2117
FT /note="AWS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00562"
FT DOMAIN 2119..2240
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 787..846
FT /note="PHD-type 1"
FT ZN_FING 2423..2471
FT /note="PHD-type 2"
FT REGION 37..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..1054
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1546..1575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1713..1732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1772..1822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..360
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..379
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 929..947
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 970..988
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 989..1011
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1012..1054
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1546..1569
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1772..1798
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1805..1822
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2239
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
SQ SEQUENCE 2548 AA; 300714 MW; A0F2BC3015CC4AEE CRC64;
MEYKLFKNKK ILNEKVNELT KKNRQRNTLD HINCIEIDDD DDDDNDNNEE PKEMNINKTN
NNNNDILMKS CNDIRRNTTF YRHNVINEEQ KNFEYLLSRK KKNVDSIDNV NFYDFMKNDF
FNIFNNNIIS EHKKTNQIVN QINNNVDTSK NVVYNINYDE HKGEVVNLSF DKKGKETYPQ
VDIELYNKKM NPRYQNINEQ NTCQTSDDNT TYRNVYSDNC ALNSSYTNFL RNKSLKYKKC
YKQNRQDEST GAEFDYNLDE SVYYDDCNNK LYKRSFLKNN KNIIEKGREE HKQDIYNNIS
DICKSYIKNF DYLNKRIFHN KSKIWKLSNK KVTIHGDPKK RIERNKQEIE DHRREQDGEN
DQEEDNYDDY DDEDDDDDNC HIYDNYDDYL ENDDYDNHNY FYHKNHDVNK IRKIQNKNCS
TDFINYTSIN NRNMECPNKN ADNLKNMDSF LLYMKERKIK KKKNINDHME NQLSDTLNNS
NNYNKDVYDS YYDDMNFCYD KDYNMILKKG VNSNRTKSLD RYPNNISHNY VNNISSEIIK
YCKDNNITLK SDIKNIINHF NKKYANSSLT NSKISMYENG YPQRSVDRIY DSSTNDPKSD
MNGSNNNNSS SNNNNNITHI TNDCDNTQTN KNKHYVNSIV NSIVNIFQKR KNVNEKKENI
NEQNCISFNT NLRNNKLNNN DDLCSNSYVN NINRNKQITN NENKKDNMLM LKGTYHGDSL
NESINIEHNL KNNNSMSDVN FVLNNNDNDK KQNSYDISEV SINCYYDDVI KCYMDYTMHG
MEDETNFYLC EFCEQNIFDM NNMIKKDKAK ECMYRCNISC GRTFHKACVC YIKNNDNYIC
FFCLYDINFC TLCKEVLTND SLLPCYYPLC SVSMHTKCVE KLLLFNSHCL KQYESIILPR
DINIEQQKNT QKSASDGIIE QPLNIKKKIK RRHIYRKRRR RGPRKSQITT SNKKINKSEL
AGGSIINGVD MEQENDQGGN NNNNDDNNDD NNDNNDDNND NNDDNNDNND NNDDNNNDNN
NNNNNDNNDN NNNNNNNNNN NDNDNNNNNN CDENFKNHLL KKDLLRDEPH HNNYDKILEC
NTEIKMENNV NMSEEPIYNK LFNGKEETLN NENDEKIIVL KKFICPLHIC YVCKEFDINN
TESSKKELKN NLFRCIKCYK SVHRKCMNQL KNNDNNDNDN NNNNINIYII SHKHRIICCA
NHMDDYKKEH MEYLKYIKEV KDICKLDEPI HNNNNNNNIL SEKGFYGDEN NLSISKFHNN
SSYEPIKNKE TCIKGKDSNY LSHDNKGITD MNNTNKMNVL NLKSCMVNDM NTSERKKKKS
CESRGSNITN KKVVFDLTDE LNEKEKSPPL DNVQNKIIYG DNEIEKNVNI CQKEDGGLNL
GSMNILSIGK NHMRTNNNNN NDSSCSSNNN IISVENEYIL KNKNLNKSNN SLLDHNNKIK
KNSTLNIKEC TDSCINVDEF INKNQNEKDI SLENIDALCI KRKRNVSHPY NDTLDDTNIL
KDISNNKSYY VNISKKKRNV SFNYKEEFMK GDEQFLLKGN NLESNEKNTK NKLCNNDNNN
NNNNKGKNTK YNTLDRKNNK NKQINDTINK EPENINHNMQ NQQLTDNFVE DNMKYKQEIY
HIKLSHILSI EKGLLSLQEI NIDQMNDECK KHISILCTFR QDFINYVIFL FSKRLHKENQ
IEPVNGVDHK KEGNIYHAER KQEKINHNAK HNEQGSINNA KHNEQGSINN AKHNEQDSIN
NAKQNEQDSI NNAKHNEQDS INNAKHNEQD SINNAKHNED DSLNNAKHNE DDSLNNAKQN
EEDSLNNAKQ NEEDILNNDD HRNQEELHER WKENMVYNFL ANYDKKEKKY ISKKEEDAII
KILSNDIVGI MKKELKISLY DFIMLKKKTI STNENHKDND ESVVYVEDGK HHCNDINKMK
DNVNNDIIPN IKYNNNNYDD VINTKEKESI PDASYMKVTR NQSIMNNDIY NNNIQIIEKE
RIMNNNKKNY YDEEKKREEY NGLFSKGKKK SFKNNKMDLK TFFSLTNNGY KVDISILKKY
SSFLKFEYIS KNIYLNDKNK NLLACKSDDY KCLCQGECNL YTCYNSLSNI QCSKSRCNLP
EKIQDRKCFN RPFRKSFVKD LEIKKTEKTG YGVFCKRDIK NGELICEYVG EVLGKREFEK
RLEVYQEESK KTDMYNWYII QINKDVYIDS GKKGSISRFI NHSCSPNSVS QKWIVRGFYR
IGIFALRDIP SGEEITYNYS YNFLFNNFEC LCKSPNCMNY HLLKKGESSG ASNIIKETEL
LNNTIFNPVE NFHNLHGKMQ DWNIFIEEAH TRLLYEYNKM NAFNLRLMEC YSTWIFYDMN
FQKNQFFSLK SKPYNVSAEF WKVLVSAFSD GEKNIINTFN LFLPSLIKIG QLRRIQQYSY
ILHNIIGLEH DMWNLIDKGF ADDEVCRKCK SCGNLTMCDK CFQSYHQLCG NMHSKMYKNN
ELVLCRFCQK YDYKIQWIKE NHGSKMKTCI EIRSKAFYKL NRDIMTLLEE SVKYTQNQSL
DSIHAHNTKA FKSKKLKLRK FQYKYVKI
