Protein: Variant-silencing SET domain-containing protein (PfSETvs) (EC 2.1.1.359) (SET domain-containing protein 2) (PfSET2) (Q8IE95)
Organism: Plasmodium falciparum (isolate 3D7)
Function: Histone methyltransferase that specifically represses expression of the surface antigen-coding var genes by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3) on var genes. SETVS-dependent H3K36me3 is specifically involved in var genes silencing, a central step malaria pathogenesis: each parasite contains 60 distinct var genes that each code for a different PfEMP1 protein. During infection, the clonal parasite population expresses only 1 gene at a time, while the 59 other var genes are silenced. The parasite then switches to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. Represses expression of both var mRNA and antisense long non-coding RNA.
Subcellular location: Nucleus {ECO:0000269|PubMed:23823717}. Chromosome {ECO:0000269|PubMed:23823717}. Note=Localizes along the entire gene body of silent var genes, including the transcription start site of var genes and the respective intronic antisense promoter.
Interaction partners:
- Histone H3
- Histone H3-like centromeric protein CSE4
- Histone H3
- Histone H4
- Heterochromatin protein 1
- RNA helicase, putative
Sequence:
MEYKLFKNKKILNEKVNELTKKNRQRNTLDHINCIEIDDDDDDDNDNNEEPKEMNINKTNNNNNDILMKSCNDIRRNTTFYRHNVINEEQKNFEYLLSRKKKNVDSIDNVNFYDFMKNDFFNIFNNNIISEHKKTNQIVNQINNNVDTSKNVVYNINYDEHKGEVVNLSFDKKGKETYPQVDIELYNKKMNPRYQNINEQNTCQTSDDNTTYRNVYSDNCALNSSYTNFLRNKSLKYKKCYKQNRQDESTGAEFDYNLDESVYYDDCNNKLYKRSFLKNNKNIIEKGREEHKQDIYNNISDICKSYIKNFDYLNKRIFHNKSKIWKLSNKKVTIHGDPKKRIERNKQEIEDHRREQDGENDQEEDNYDDYDDEDDDDDNCHIYDNYDDYLENDDYDNHNYFYHKNHDVNKIRKIQNKNCSTDFINYTSINNRNMECPNKNADNLKNMDSFLLYMKERKIKKKKNINDHMENQLSDTLNNSNNYNKDVYDSYYDDMNFCYDKDYNMILKKGVNSNRTKSLDRYPNNISHNYVNNISSEIIKYCKDNNITLKSDIKNIINHFNKKYANSSLTNSKISMYENGYPQRSVDRIYDSSTNDPKSDMNGSNNNNSSSNNNNNITHITNDCDNTQTNKNKHYVNSIVNSIVNIFQKRKNVNEKKENINEQNCISFNTNLRNNKLNNNDDLCSNSYVNNINRNKQITNNENKKDNMLMLKGTYHGDSLNESINIEHNLKNNNSMSDVNFVLNNNDNDKKQNSYDISEVSINCYYDDVIKCYMDYTMHGMEDETNFYLCEFCEQNIFDMNNMIKKDKAKECMYRCNISCGRTFHKACVCYIKNNDNYICFFCLYDINFCTLCKEVLTNDSLLPCYYPLCSVSMHTKCVEKLLLFNSHCLKQYESIILPRDINIEQQKNTQKSASDGIIEQPLNIKKKIKRRHIYRKRRRRGPRKSQITTSNKKINKSELAGGSIINGVDMEQENDQGGNNNNNDDNNDDNNDNNDDNNDNNDDNNDNNDNNDDNNNDNNNNNNNDNNDNNNNNNNNNNNNDNDNNNNNNCDENFKNHLLKKDLLRDEPHHNNYDKILECNTEIKMENNVNMSEEPIYNKLFNGKEETLNNENDEKIIVLKKFICPLHICYVCKEFDINNTESSKKELKNNLFRCIKCYKSVHRKCMNQLKNNDNNDNDNNNNNINIYIISHKHRIICCANHMDDYKKEHMEYLKYIKEVKDICKLDEPIHNNNNNNNILSEKGFYGDENNLSISKFHNNSSYEPIKNKETCIKGKDSNYLSHDNKGITDMNNTNKMNVLNLKSCMVNDMNTSERKKKKSCESRGSNITNKKVVFDLTDELNEKEKSPPLDNVQNKIIYGDNEIEKNVNICQKEDGGLNLGSMNILSIGKNHMRTNNNNNNDSSCSSNNNIISVENEYILKNKNLNKSNNSLLDHNNKIKKNSTLNIKECTDSCINVDEFINKNQNEKDISLENIDALCIKRKRNVSHPYNDTLDDTNILKDISNNKSYYVNISKKKRNVSFNYKEEFMKGDEQFLLKGNNLESNEKNTKNKLCNNDNNNNNNNKGKNTKYNTLDRKNNKNKQINDTINKEPENINHNMQNQQLTDNFVEDNMKYKQEIYHIKLSHILSIEKGLLSLQEINIDQMNDECKKHISILCTFRQDFINYVIFLFSKRLHKENQIEPVNGVDHKKEGNIYHAERKQEKINHNAKHNEQGSINNAKHNEQGSINNAKHNEQDSINNAKQNEQDSINNAKHNEQDSINNAKHNEQDSINNAKHNEDDSLNNAKHNEDDSLNNAKQNEEDSLNNAKQNEEDILNNDDHRNQEELHERWKENMVYNFLANYDKKEKKYISKKEEDAIIKILSNDIVGIMKKELKISLYDFIMLKKKTISTNENHKDNDESVVYVEDGKHHCNDINKMKDNVNNDIIPNIKYNNNNYDDVINTKEKESIPDASYMKVTRNQSIMNNDIYNNNIQIIEKERIMNNNKKNYYDEEKKREEYNGLFSKGKKKSFKNNKMDLKTFFSLTNNGYKVDISILKKYSSFLKFEYISKNIYLNDKNKNLLACKSDDYKCLCQGECNLYTCYNSLSNIQCSKSRCNLPEKIQDRKCFNRPFRKSFVKDLEIKKTEKTGYGVFCKRDIKNGELICEYVGEVLGKREFEKRLEVYQEESKKTDMYNWYIIQINKDVYIDSGKKGSISRFINHSCSPNSVSQKWIVRGFYRIGIFALRDIPSGEEITYNYSYNFLFNNFECLCKSPNCMNYHLLKKGESSGASNIIKETELLNNTIFNPVENFHNLHGKMQDWNIFIEEAHTRLLYEYNKMNAFNLRLMECYSTWIFYDMNFQKNQFFSLKSKPYNVSAEFWKVLVSAFSDGEKNIINTFNLFLPSLIKIGQLRRIQQYSYILHNIIGLEHDMWNLIDKGFADDEVCRKCKSCGNLTMCDKCFQSYHQLCGNMHSKMYKNNELVLCRFCQKYDYKIQWIKENHGSKMKTCIEIRSKAFYKLNRDIMTLLEESVKYTQNQSLDSIHAHNTKAFKSKKLKLRKFQYKYVKI