Lipid Modification Database
Tag Content
LipidDB ID
LipidDB-11033-00874
Entry Name
UniProt Accession
Theoretical PI
8.25
Molecular Weight
269512.16
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
RNA-directed RNA polymerase nsP4
Protein Synonyms/Alias
Polyprotein nsP1234; P1234; 2.1.1.-; 2.7.7.-; Non-structural protein 1; 3.1.3.33; 3.4.22.-; 3.6.1.15; 3.6.4.13; Non-structural protein 2; nsP2; nsP3; 2.7.7.48; Non-structural protein 4; nsP4;
Gene Name
Gene Synonyms/Alias
Created Date
01-AUG-1988
 Lipid Modification Sites 
 Position   Sequence Form   Peptide   References   Modification Type 
418
Canonical
VRERSLTCCCLWAFK
[1]
S-Palmitoylation
419
Canonical
RERSLTCCCLWAFKT
[1]
S-Palmitoylation
420
Canonical
ERSLTCCCLWAFKTR
[1]
S-Palmitoylation
Organism
Semliki forest virus (SFV)
NCBI Taxa ID
11033
Reference
[1] Zusinaite E, Tints K, Kiiver K, Spuul P, Karo-Astover L, Merits A, Sarand I.Mutations at the palmitoylation site of non-structural protein nsP1 of SemlikiForest virus attenuate virus replication and cause accumulation of compensatorymutations. J Gen Virol. 2007 Jul;88(Pt 7):1977-85.[PMID:17554031]
Functional Description
P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex.nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins.
Sequence Annotation
Domain: 692 844 (+)RNA virus helicase ATP-binding.
Domain: 845 993 (+)RNA virus helicase C-terminal.
Domain: 1006 1329 Peptidase C9.
Domain: 1337 1495 Macro.
Domain: 2182 2297 RdRp catalytic.
Nucleotide-binding: 723 730 ATP.
Region: 245 264 nsP1 membrane-binding.
Region: 1007 1026 Nucleolus localization signal.
Motif: 1184 1188 Nuclear localization signal.
Active site: 1015 1015 For cysteine protease nsP2 activity.
Active site: 1085 1085 For cysteine protease nsP2 activity.
Functional site: 537 538 Cleavage; by nsP2.
Functional site: 1336 1337 Cleavage; by nsP2.
Functional site: 1818 1819 Cleavage; by nsP2.
Modified residue: 1680 1680 Phosphothreonine; by host.
Modified residue: 1681 1681 Phosphothreonine; by host.
Protein Length
2432 AA.
Protein Sequence
(Canonical)
MAAKVHVDIE ADSPFIKSLQ KAFPSFEVES LQVTPNDHAN ARAFSHLATK LIEQETDKDT  60
LILDIGSAPS RRMMSTHKYH CVCPMRSAED PERLVCYAKK LAAASGKVLD REIAGKITDL  120
QTVMATPDAE SPTFCLHTDV TCRTAAEVAV YQDVYAVHAP TSLYHQAMKG VRTAYWIGFD  180
TTPFMFDALA GAYPTYATNW ADEQVLQARN IGLCAASLTE GRLGKLSILR KKQLKPCDTV  240
MFSVGSTLYT ESRKLLRSWH LPSVFHLKGK QSFTCRCDTI VSCEGYVVKK ITMCPGLYGK  300
TVGYAVTYHA EGFLVCKTTD TVKGERVSFP VCTYVPSTIC DQMTGILATD VTPEDAQKLL  360
VGLNQRIVVN GRTQRNTNTM KNYLLPIVAV AFSKWAREYK ADLDDEKPLG VRERSLTCCC  420
LWAFKTRKMH TMYKKPDTQT IVKVPSEFNS FVIPSLWSTG LAIPVRSRIK MLLAKKTKRE  480
LIPVLDASSA RDAEQEEKER LEAELTREAL PPLVPIAPAE TGVVDVDVEE LEYHAGAGVV  540
ETPRSALKVT AQPNDVLLGN YVVLSPQTVL KSSKLAPVHP LAEQVKIITH NGRAGRYQVD  600
GYDGRVLLPC GSAIPVPEFQ ALSESATMVY NEREFVNRKL YHIAVHGPSL NTDEENYEKV  660
RAERTDAEYV FDVDKKCCVK REEASGLVLV GELTNPPFHE FAYEGLKIRP SAPYKTTVVG  720
VFGVPGSGKS AIIKSLVTKH DLVTSGKKEN CQEIVNDVKK HRGLDIQAKT VDSILLNGCR  780
RAVDILYVDE AFACHSGTLL ALIALVKPRS KVVLCGDPKQ CGFFNMMQLK VNFNHNICTE  840
VCHKSISRRC TRPVTAIVST LHYGGKMRTT NPCNKPIIID TTGQTKPKPG DIVLTCFRGW  900
VKQLQLDYRG HEVMTAAASQ GLTRKGVYAV RQKVNENPLY APASEHVNVL LTRTEDRLVW  960
KTLAGDPWIK VLSNIPQGNF TATLEEWQEE HDKIMKVIEG PAAPVDAFQN KANVCWAKSL  1020
VPVLDTAGIR LTAEEWSTII TAFKEDRAYS PVVALNEICT KYYGVDLDSG LFSAPKVSLY  1080
YENNHWDNRP GGRMYGFNAA TAARLEARHT FLKGQWHTGK QAVIAERKIQ PLSVLDNVIP  1140
INRRLPHALV AEYKTVKGSR VEWLVNKVRG YHVLLVSEYN LALPRRRVTW LSPLNVTGAD  1200
RCYDLSLGLP ADAGRFDLVF VNIHTEFRIH HYQQCVDHAM KLQMLGGDAL RLLKPGGSLL  1260
MRAYGYADKI SEAVVSSLSR KFSSARVLRP DCVTSNTEVF LLFSNFDNGK RPSTLHQMNT  1320
KLSAVYAGEA MHTAGCAPSY RVKRADIATC TEAAVVNAAN ARGTVGDGVC RAVAKKWPSA  1380
FKGAATPVGT IKTVMCGSYP VIHAVAPNFS ATTEAEGDRE LAAVYRAVAA EVNRLSLSSV  1440
AIPLLSTGVF SGGRDRLQQS LNHLFTAMDA TDADVTIYCR DKSWEKKIQE AIDMRTAVEL  1500
LNDDVELTTD LVRVHPDSSL VGRKGYSTTD GSLYSYFEGT KFNQAAIDMA EILTLWPRLQ  1560
EANEQICLYA LGETMDNIRS KCPVNDSDSS TPPRTVPCLC RYAMTAERIA RLRSHQVKSM  1620
VVCSSFPLPK YHVDGVQKVK CEKGLLFDPT VPSVVSPRKY AASTTDHSDR SLRGFDLDWT  1680
TDSSSTASDT MSLPSLQSCD IDSIYEPMAP IVVTADVHPE PAGIADLAAD VHPEPADHVD  1740
LENPIPPPRP KRAAYLASRA AERPVPAPRK PTPAPRTAFR NKLPLTFGDF DEHEVDALAS  1800
GITFGDFDDV LRLGRAGAYI FSSDTGSGHL QQKSVRQHNL QCAQLDAVEE EKMYPPKLDT  1860
EREKLLLLKM QMHPSEANKS RYQSRKVENM KATVVDRLTS GARLYTGADV GRIPTYAVRY  1920
PRPVYSPTVI ERFSSPDVAI AACNEYLSRN YPTVASYQIT DEYDAYLDMV DGSDSCLDRA  1980
TFCPAKLRCY PKHHAYHQPT VRSAVPSPFQ NTLQNVLAAA TKRNCNVTQM RELPTMDSAV  2040
FNVECFKRYA CSGEYWEEYA KQPIRITTEN ITTYVTKLKG PKAAALFAKT HNLVPLQEVP  2100
MDRFTVDMKR DVKVTPGTKH TEERPKVQVI QAAEPLATAY LCGIHRELVR RLNAVLRPNV  2160
HTLFDMSAED FDAIIASHFH PGDPVLETDI ASFDKSQDDS LALTGLMILE DLGVDQYLLD  2220
LIEAAFGEIS SCHLPTGTRF KFGAMMKSGM FLTLFINTVL NITIASRVLE QRLTDSACAA  2280
FIGDDNIVHG VISDKLMAER CASWVNMEVK IIDAVMGEKP PYFCGGFIVF DSVTQTACRV  2340
SDPLKRLFKL GKPLTAEDKQ DEDRRRALSD EVSKWFRTGL GAELEVALTS RYEVEGCKSI  2400
LIAMATLARD IKAFKKLRGP VIHLYGGPRL VR                                2432
FASTA
(Canonical)
>LipidDB-11033-00874|P08411
MAAKVHVDIEADSPFIKSLQKAFPSFEVESLQVTPNDHANARAFSHLATKLIEQETDKDT
LILDIGSAPSRRMMSTHKYHCVCPMRSAEDPERLVCYAKKLAAASGKVLDREIAGKITDL
QTVMATPDAESPTFCLHTDVTCRTAAEVAVYQDVYAVHAPTSLYHQAMKGVRTAYWIGFD
TTPFMFDALAGAYPTYATNWADEQVLQARNIGLCAASLTEGRLGKLSILRKKQLKPCDTV
MFSVGSTLYTESRKLLRSWHLPSVFHLKGKQSFTCRCDTIVSCEGYVVKKITMCPGLYGK
TVGYAVTYHAEGFLVCKTTDTVKGERVSFPVCTYVPSTICDQMTGILATDVTPEDAQKLL
VGLNQRIVVNGRTQRNTNTMKNYLLPIVAVAFSKWAREYKADLDDEKPLGVRERSLTCCC
LWAFKTRKMHTMYKKPDTQTIVKVPSEFNSFVIPSLWSTGLAIPVRSRIKMLLAKKTKRE
LIPVLDASSARDAEQEEKERLEAELTREALPPLVPIAPAETGVVDVDVEELEYHAGAGVV
ETPRSALKVTAQPNDVLLGNYVVLSPQTVLKSSKLAPVHPLAEQVKIITHNGRAGRYQVD
GYDGRVLLPCGSAIPVPEFQALSESATMVYNEREFVNRKLYHIAVHGPSLNTDEENYEKV
RAERTDAEYVFDVDKKCCVKREEASGLVLVGELTNPPFHEFAYEGLKIRPSAPYKTTVVG
VFGVPGSGKSAIIKSLVTKHDLVTSGKKENCQEIVNDVKKHRGLDIQAKTVDSILLNGCR
RAVDILYVDEAFACHSGTLLALIALVKPRSKVVLCGDPKQCGFFNMMQLKVNFNHNICTE
VCHKSISRRCTRPVTAIVSTLHYGGKMRTTNPCNKPIIIDTTGQTKPKPGDIVLTCFRGW
VKQLQLDYRGHEVMTAAASQGLTRKGVYAVRQKVNENPLYAPASEHVNVLLTRTEDRLVW
KTLAGDPWIKVLSNIPQGNFTATLEEWQEEHDKIMKVIEGPAAPVDAFQNKANVCWAKSL
VPVLDTAGIRLTAEEWSTIITAFKEDRAYSPVVALNEICTKYYGVDLDSGLFSAPKVSLY
YENNHWDNRPGGRMYGFNAATAARLEARHTFLKGQWHTGKQAVIAERKIQPLSVLDNVIP
INRRLPHALVAEYKTVKGSRVEWLVNKVRGYHVLLVSEYNLALPRRRVTWLSPLNVTGAD
RCYDLSLGLPADAGRFDLVFVNIHTEFRIHHYQQCVDHAMKLQMLGGDALRLLKPGGSLL
MRAYGYADKISEAVVSSLSRKFSSARVLRPDCVTSNTEVFLLFSNFDNGKRPSTLHQMNT
KLSAVYAGEAMHTAGCAPSYRVKRADIATCTEAAVVNAANARGTVGDGVCRAVAKKWPSA
FKGAATPVGTIKTVMCGSYPVIHAVAPNFSATTEAEGDRELAAVYRAVAAEVNRLSLSSV
AIPLLSTGVFSGGRDRLQQSLNHLFTAMDATDADVTIYCRDKSWEKKIQEAIDMRTAVEL
LNDDVELTTDLVRVHPDSSLVGRKGYSTTDGSLYSYFEGTKFNQAAIDMAEILTLWPRLQ
EANEQICLYALGETMDNIRSKCPVNDSDSSTPPRTVPCLCRYAMTAERIARLRSHQVKSM
VVCSSFPLPKYHVDGVQKVKCEKGLLFDPTVPSVVSPRKYAASTTDHSDRSLRGFDLDWT
TDSSSTASDTMSLPSLQSCDIDSIYEPMAPIVVTADVHPEPAGIADLAADVHPEPADHVD
LENPIPPPRPKRAAYLASRAAERPVPAPRKPTPAPRTAFRNKLPLTFGDFDEHEVDALAS
GITFGDFDDVLRLGRAGAYIFSSDTGSGHLQQKSVRQHNLQCAQLDAVEEEKMYPPKLDT
EREKLLLLKMQMHPSEANKSRYQSRKVENMKATVVDRLTSGARLYTGADVGRIPTYAVRY
PRPVYSPTVIERFSSPDVAIAACNEYLSRNYPTVASYQITDEYDAYLDMVDGSDSCLDRA
TFCPAKLRCYPKHHAYHQPTVRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTMDSAV
FNVECFKRYACSGEYWEEYAKQPIRITTENITTYVTKLKGPKAAALFAKTHNLVPLQEVP
MDRFTVDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLRPNV
HTLFDMSAEDFDAIIASHFHPGDPVLETDIASFDKSQDDSLALTGLMILEDLGVDQYLLD
LIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFINTVLNITIASRVLEQRLTDSACAA
FIGDDNIVHGVISDKLMAERCASWVNMEVKIIDAVMGEKPPYFCGGFIVFDSVTQTACRV
SDPLKRLFKLGKPLTAEDKQDEDRRRALSDEVSKWFRTGLGAELEVALTSRYEVEGCKSI
LIAMATLARDIKAFKKLRGPVIHLYGGPRLVR
Gene Ontology
GO:0044174; C:host cell endosome; IEA:UniProtKB-KW
GO:0044187; C:host cell lysosome; IEA:UniProtKB-KW
GO:0042025; C:host cell nucleus; IEA:UniProtKB-KW
GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-KW
GO:0044157; C:host cell projection; IEA:UniProtKB-KW
GO:0016020; C:membrane; IEA:UniProtKB-KW
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW
GO:0005525; F:GTP binding; IEA:UniProtKB-KW
GO:0004386; F:helicase activity; IEA:UniProtKB-KW
GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro
GO:0004651; F:polynucleotide 5'-phosphatase activity; IEA:UniProtKB-EC
GO:0003723; F:RNA binding; IEA:UniProtKB-KW
GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW
GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW
GO:0039523; P:suppression by virus of host RNA polymerase II activity; IEA:UniProtKB-KW
GO:0006351; P:transcription, DNA-templated; IEA:InterPro
GO:0039694; P:viral RNA genome replication; IEA:InterPro
Interpro
InterPro; IPR027351; (+)RNA_virus_helicase_core_dom
InterPro; IPR002620; Alphavirus_nsp2pro
InterPro; IPR002589; Macro_dom
InterPro; IPR027417; P-loop_NTPase
InterPro; IPR007094; RNA-dir_pol_PSvirus
InterPro; IPR002588; Tymovirus_MeTrfase
InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol
Pfam
Pfam; PF01661; Macro;
Pfam; PF01707; Peptidase_C9;
Pfam; PF00978; RdRP_2;
Pfam; PF01443; Viral_helicase1;
Pfam; PF01660; Vmethyltransf;
SMART
SMART; SM00506; A1pp;
PROSITE
PROSITE; PS51154; MACRO;
PROSITE; PS51520; NSP2PRO;
PROSITE; PS51657; PSRV_HELICASE;
PROSITE; PS50507; RDRP_SSRNA_POS;
PRINTS