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Database: UniProt
Entry: Q8IE95
LinkDB: Q8IE95
Original site: Q8IE95 
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   16-JAN-2019, entry version 91.
DE   RecName: Full=Variant-silencing SET domain-containing protein;
DE            Short=PfSETvs;
DE            EC=2.1.1.43;
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; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX   NCBI_TaxID=36329;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Isolate 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.,
RA   James K.D., Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A.,
RA   Kyes S., Chan M.-S., Nene V., Shallom S.J., Suh B., Peterson J.,
RA   Angiuoli S., Pertea M., Allen J., Selengut J., Haft D., Mather M.W.,
RA   Vaidya A.B., Martin D.M.A., Fairlamb A.H., Fraunholz M.J., Roos D.S.,
RA   Ralph S.A., McFadden G.I., Cummings L.M., Subramanian G.M.,
RA   Mungall C., Venter J.C., Carucci D.J., Hoffman S.L., Newbold C.,
RA   Davis R.W., Fraser C.M., Barrell B.G.;
RT   "Genome sequence of the human malaria parasite Plasmodium
RT   falciparum.";
RL   Nature 419:498-511(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Isolate 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.,
RA   Chillingworth T., Christodoulou Z., Clark L., Clark R., Corton C.,
RA   Cronin A., Davies R.M., Davis P., Dear P., Dearden F., Doggett J.,
RA   Feltwell T., Goble A., Goodhead I., Gwilliam R., Hamlin N., Hance Z.,
RA   Harper D., Hauser H., Hornsby T., Holroyd S., Horrocks P.,
RA   Humphray S., Jagels K., James K.D., Johnson D., Kerhornou A.,
RA   Knights A., Konfortov B., Kyes S., Larke N., Lawson D., Lennard N.,
RA   Line A., Maddison M., Mclean J., Mooney P., Moule S., Murphy L.,
RA   Oliver K., Ormond D., Price C., Quail M.A., Rabbinowitsch E.,
RA   Rajandream M.A., Rutter S., Rutherford K.M., Sanders M., Simmonds M.,
RA   Seeger K., Sharp S., Smith R., Squares R., Squares S., Stevens K.,
RA   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=Isolate 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.,
RA   Aravind L., 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
CC       contains 60 distinct var genes that each code for a different
CC       PfEMP1 protein. During infection, the clonal parasite population
CC       expresses only 1 gene at a time, while the 59 other var genes are
CC       silenced. The parasite then switches to the expression of a new
CC       variant antigen as an immune-evasion mechanism to avoid the host
CC       antibody response. Represses expression of both var mRNA and
CC       antisense long non-coding RNA. {ECO:0000269|PubMed:23823717}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23823717}.
CC       Chromosome {ECO:0000269|PubMed:23823717}. Note=Localizes along the
CC       entire gene body of silent var genes, including the transcription
CC       start site of var genes and the respective intronic antisense
CC       promoter.
CC   -!- DEVELOPMENTAL STAGE: Highly expressed in early trophozoite stages.
CC       Expression is then reduced in late trophozoites and elevated again
CC       in schizonts. {ECO:0000269|PubMed:18299133}.
CC   -!- DISRUPTION PHENOTYPE: Leads to expression of all var genes in the
CC       ring stage. {ECO:0000269|PubMed:23823717}.
CC   -!- MISCELLANEOUS: Parasites lacking SETVS could be used as an
CC       antimalarial vaccine because of its ability to express all PfEMP1
CC       proteins, to which the antibody would provide efficient protective
CC       immunity against malaria. {ECO:0000305|PubMed:23823717}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00190}.
DR   EMBL; AL844509; CAD52368.1; -; Genomic_DNA.
DR   RefSeq; XP_001349960.1; XM_001349924.1.
DR   ProteinModelPortal; Q8IE95; -.
DR   SMR; Q8IE95; -.
DR   BioGrid; 1208944; 1.
DR   IntAct; Q8IE95; 1.
DR   PRIDE; Q8IE95; -.
DR   EnsemblProtists; CAD52368; CAD52368; PF3D7_1322100.
DR   GeneDB; PF3D7_1322100.1:pep; -.
DR   GeneID; 813672; -.
DR   KEGG; pfa:PF3D7_1322100; -.
DR   EuPathDB; PlasmoDB:PF3D7_1322100; -.
DR   InParanoid; Q8IE95; -.
DR   OMA; HNEQDSI; -.
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:0020012; P:evasion or tolerance of host immune response; IDA:UniProtKB.
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; 3.30.40.10; -; 1.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR001965; Znf_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00249; PHD; 4.
DR   SMART; SM00317; SET; 1.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS50280; SET; 1.
PE   2: Evidence at transcript level;
KW   Chromatin regulator; Chromosome; Complete proteome; Malaria;
KW   Metal-binding; Methyltransferase; Nucleus; Reference proteome; Repeat;
KW   S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger.
FT   CHAIN         1   2548       Variant-silencing SET domain-containing
FT                                protein.
FT                                /FTId=PRO_0000424016.
FT   DOMAIN     2067   2117       AWS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00562}.
FT   DOMAIN     2119   2240       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   ZN_FING     787    846       PHD-type 1.
FT   ZN_FING    2423   2471       PHD-type 2.
FT   COMPBIAS     45   1989       Asn-rich.
FT   COMPBIAS    357    396       Asp-rich.
FT   BINDING    2239   2239       S-adenosyl-L-methionine.
FT                                {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
//
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