#=GF ID Flavi_NS5
#=GF AC PF00972.24
#=GF DE Flavivirus RNA-directed RNA polymerase, fingers and palm domains
#=GF AU Finn RD;0000-0001-8626-2148
#=GF AU Bateman A;0000-0002-6982-4660
#=GF AU Chuguransky S;0000-0002-0520-0736
#=GF SE Pfam-B_200 (release 3.0)
#=GF GA 25.00 25.00;
#=GF TC 30.00 29.80;
#=GF NC 24.60 19.80;
#=GF BM hmmbuild HMM.ann SEED.ann
#=GF SM hmmsearch -Z 75585367 --cpu 4 -E 1000 HMM pfamseq
#=GF TP Domain
#=GF WK RNA-dependent_RNA_polymerase
#=GF CL CL0027
#=GF RN [1]
#=GF RM 7856087
#=GF RT Phylogeny of TYU, SRE, and CFA virus: different evolutionary
#=GF RT rates in the genus Flavivirus.
#=GF RA Marin MS, Zanotto PM, Gritsun TS, Gould EA;
#=GF RL Virology 1995;206:1133-1139.
#=GF RN [2]
#=GF RM 8607261
#=GF RT Recombinant dengue type 1 virus NS5 protein expressed in
#=GF RT Escherichia coli exhibits RNA-dependent RNA polymerase activity.
#=GF RA Tan BH, Fu J, Sugrue RJ, Yap EH, Chan YC, Tan YH;
#=GF RL Virology 1996;216:317-325.
#=GF RN [3]
#=GF RM 8385698
#=GF RT Computer-assisted identification of a putative methyltransferase
#=GF RT domain in NS5 protein of flaviviruses and lambda 2 protein of
#=GF RT reovirus.
#=GF RA Koonin EV;
#=GF RL J Gen Virol 1993;74:733-740.
#=GF RN [4]
#=GF RM 8269709
#=GF RT Evolution and taxonomy of positive-strand RNA viruses:
#=GF RT implications of comparative analysis of amino acid sequences.
#=GF RA Koonin EV, Dolja VV;
#=GF RL Crit Rev Biochem Mol Biol 1993;28:375-430.
#=GF RN [5]
#=GF RM 28345656
#=GF RT Structure and function of the Zika virus full-length NS5
#=GF RT protein.
#=GF RA Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC,
#=GF RA Li P;
#=GF RL Nat Commun. 2017;8:14762.
#=GF RN [6]
#=GF RM 32313955
#=GF RT The flavivirus polymerase NS5 regulates translation of viral
#=GF RT genomic RNA.
#=GF RA Fajardo T, Sanford TJ, Mears HV, Jasper A, Storrie S, Mansur DS,
#=GF RA Sweeney TR;
#=GF RL Nucleic Acids Res. 2020;48:5081-5093.
#=GF DR INTERPRO; IPR000208;
#=GF DR SCOP; 1l9k; fa;
#=GF DR SO; 0000417; polypeptide_domain;
#=GF CC Flaviviruses produce a large polyprotein from the ssRNA genome,
#=GF CC encoding structural proteins required for virus assembly and
#=GF CC non-structural (NS1-5) proteins involved in replication of the
#=GF CC viral genome [1-6]. This polyprotein is cleaved by viral and
#=GF CC cellular proteases to produce mature viral proteins. NS5 is the
#=GF CC largest mature viral protein and contains a N-terminal
#=GF CC methyltransferase (MTase) domain separated by a short linker
#=GF CC from the C-terminal RNA-directed RNA polymerase domain (RdRp)
#=GF CC that adopts a characteristic right-handed fingers-palm-thumb
#=GF CC fold and possesses a number of short regions and motifs
#=GF CC homologous to other RNA-directed RNA polymerases [2,5,6]. This
#=GF CC entry covers the fingers and palm domains of RNA-directed RNA
#=GF CC polymerase (RdRp) from Flavivirus NS5. NS5 binds to a the stem
#=GF CC loop A (SLA) at the 5' extremity of Flavivirus genome and
#=GF CC regulates translation of the viral genome [5,6].
#=GF SQ 13
#=GS POLG_ZIKV/2768-3218 AC Q32ZE1.1
#=GS POLG_YEFV1/2758-3210 AC P03314.1
#=GS A0A0P0QKR4_9VIRU/322-712 AC A0A0P0QKR4.1
#=GS A0A0P0QKQ7_9VIRU/333-729 AC A0A0P0QKQ7.1
#=GS A0A0P0QKK1_9VIRU/324-709 AC A0A0P0QKK1.1
#=GS A0A164NVM4_9CRUS/1378-1628 AC A0A164NVM4.1
#=GS A0A164KMQ3_9CRUS/243-353 AC A0A164KMQ3.1
#=GS POLG_DEN1W/2743-3192 AC P17763.2
#=GS A0A2G9UTS9_TELCI/22-223 AC A0A2G9UTS9.1
#=GS A0A0P0QKK6_9VIRU/322-709 AC A0A0P0QKK6.1
#=GS A0A164KMQ3_9CRUS/63-252 AC A0A164KMQ3.1
#=GS A0A0B2UNM1_TOXCA/1-108 AC A0A0B2UNM1.1
#=GS A0A0N7JQI7_9VIRU/323-704 AC A0A0N7JQI7.1
POLG_ZIKV/2768-3218 ......................................................................KYEEDVNLGSGTRAVASCAEAPNMKIIGRRIERIRNEHAETWFLDENHPYRTWAYHGSYEAPTQGSASSLVNG.V.VRLLSKPWDVVTGVTGIAMTDTTPYGQQRVFKEKVDTRVPDPQEGTRQVMNIVSS..WLWKELGK.R.KRPRVCTKEEFINKVRSNAA.LGAIFEEEKEWKTAVEAVNDPRFWALVDR.ER.E.HHLRGECHSCVYNMMGKREKKQGEFGKAKGSRAIWYMWLGARFLEFEALGFLNEDHWMGRENSGGGVEGLGLQRLGYILEEMNRAPGGKMYADDTAGWDTRISKFDLENEALITNQMEE..GHRTLALAVIKYTYQN.KVVKVLRPAEGGKTVMDIISRQDQRGSGQVVTYALNTFTNLVVQLIRNMEAEEVLEMQDLWLLRKP......EKVTRWLQS..NGWDRLKRMAVSGDDCVVKP...IDDRF.A..HALRFLNDMGKVRKDTQEWKPSTGW.....................................................................
POLG_YEFV1/2758-3210 ......................................................................TLEADVILPIGTRSVETDKGPLDKEAIEERVERIKSEYMTSWFYDNDNPYRTWHYCGSYVTKTSGSAASMVNG.V.IKILTYPWDRIEEVTRMAMTDTTPFGQQRVFKEKVDTRAKDPPAGTRKIMKVVNR..WLFRHLAR.E.KNPRLCTKEEFIAKVRSHAA.IGAYLEEQEQWKTANEAVQDPKFWELVDE.ER.K.LHQQGRCRTCVYNMMGKREKKLSEFGKAKGSRAIWYMWLGARYLEFEALGFLNEDHWASRENSGGGVEGIGLQYLGYVIRDLAAMDGGGFYADDTAGWDTRITEADLDDEQEILNYMSP..HHKKLAQAVMEMTYKN.KVVKVLRPAPGGKAYMDVISRRDQRGSGQVVTYALNTITNLKVQLIRMAEAEMVIHHQHVQDCDESv....lTRLEAWLTE..HGCDRLKRMAVSGDDCVVRP...IDDRF.G..LALSHLNAMSKVRKDISEWQPSKGW.....................................................................
A0A0P0QKR4_9VIRU/322-712 ................................................................rvpeqg-----------------------------------------------RNYNHWENMGVYPVGIEGNAGMKYNR.YgLKCAHRLIPSLRGFDDWKLTDTTPKGFIEVFNRKVDVPPKENHKYHRELRTIYQGlaKYFRKIGY.V.HK--EMGWEELMKNANPAGA.PGCI----DKAQSVKEFMEQPGWCKEVEK.IR.K.SLREGKPVGCVFNTMGKREKKESK--HVKGSRMIAFLPIATRLLEMKIFGNLLK--LTKPTVNRFGVGGMGLHDLGE---RIAETWLGKGVSNDIAGFDTRVGLVIQSLECEFIRELCN..N-ENLKEDVENLYRIY.AYPHILIPIPSEFRRSELLAGRGQRMSGTNPTYSMNTITRLAIFLLELGV-----SLGERITVDWV......VDV--MQGS..KGWNKRIAGCISGDDATFTT...-----.-..-------------------------qsdqqqlsmtgeileevgfprknmhagqra.......................................
A0A0P0QKQ7_9VIRU/333-729 ................................................................pihvsk-----------------------------------------------REFRHWESLGVYPVGSKGSKATQRNPyA.IKVTSRLRDTLTEYEDWKATDTTPEGFMQVFNTKIDTTPIENSPYDEMLFH-VYN..WKAKHYLKkG.IRLKPLSWD----EVRELANkQGAAGHTDFGIRNMADFFMNPKWKEECEKvEN.ElLGEDPRPIKAIFNTMGKREKKKSK--GVKGSRMVAYLPIPMRLIELKYLYRCMEMTKM--KNNPFAVGGLGLHDLGERIREVWK---GAATSSDIAGFDTRIGIRIRELEHHLVQNLMR..DESVQSQQIVRNLFRVyAYPHLLIPYPGENVRSELIHGRGQRMSGEFGTYSLNTETRSNLAAIQFLV----------------......---------..--------------------...-----.-..-------------------------tmgidgsspnlkeriyqlmdhlyhsgkygggvsgddefftsdekfiehfrrqsgcldimgfprkdvppt
A0A0P0QKK1_9VIRU/324-709 .................................................................eqgle-------------------------------------------------FNHWETAGVYPFGSQGSTAMKYNRyA.MCVLRRLLSTVPGFDHWKTTDTTPTGFLGVFNKKVDTAPKENHKYEQHLVQIYEG..LAHHFLKM.G.FSFRELDWTEVMHQANKQGA.PGII---DTQFENVGQFLSQPNWVKKVIY.TR.Q.ALEKGRPVGGVFNTIGKREKKLSPH-EMKGSRMVAYLPIATRLLELKLFGKLLELTKPA--INHFGVGGLGLHDLGMRVEEIW---QGHAVSDDIAGFDTRIGLFFLSLENHFIRLLGG..NETH---TLMYRLYAY.--PHILVPLASEFTRSQLLKGRGQRMSGTNVTYSMNTITRICICLLQYAVANNI-PVQELHQWTI-......----KMMKQ..NA--EL-QGVVSGDDASFSG...PQDKItAlsNTAHVLEEVGMPRKDIPL-------nipsp................................................................
A0A164NVM4_9CRUS/1378-1628 ...........................................ktswvikilnpteslpnlevlwvirhk--------------------------------------------------------------TPAGRCGCVNG.V.INYVFSLWAEEHAVNQYSMTDISPRMIQKLFTEKVDTRVPPRPLGTRVISRTIAT..WMWDRARK.RgMKPRICTKDEFLQKLRNDAG.VG-VWNDYLMWENANKAVADPRFWKMVDE.ER.E.LHLRGECRLCLYNTMGKRDKKPREFGNAKGSRVIWYMWLGSRFLEFEALGFLNEDGWAKREKTGFGVSGLGVNYLGYVLD---------------------------------------..----------------.------------------------------------------------------------------......---------..--------------------...-----.-..-------------------------vrieemlsrmgnasif.....................................................
A0A164KMQ3_9CRUS/243-353 .................................................................sfywn-------------------------------------------------------------------------.-.-------------------------------------------------------..--------.-.--------------------.-----------------------------.--.-.-----------------------------------------------------------------------------------------------------------------------..----------------.--------ADTG-MVMDLIGREDSRGSGQNVTYVCNTFINAKNLIGRQLEADGVITEGDINTEDATradrvrEKVEEALRE..AGEKLCSQMAVSGDDSVVAN...NNKEY.G..RALHYINA-----------------.....................................................................
POLG_DEN1W/2743-3192 ......................................................................TYERDVDLGAGTRHVAVEPEVANLDIIGQRIENIKNGHKSTWHYDEDNPYKTWAYHGSYEVKPSGSASSMVNG.V.VRLLTKPWDVIPMVTQIAMTDTTPFGQQRVFKEKVDTRTPKAKRGTAQIMEVTAR..WLWGFLSR.N.KKPRICTREEFTRKVRSNAA.IGAVFVDENQWNSAKEAVEDERFWDLVHR.ER.E.LHKQGKCATCVYNMMGKREKKLGEFGKAKGSRAIWYMWLGARFLEFEALGFMNEDHWFSRENSLSGVEGEGLHKLGYILRDISKIPGGNMYADDTAGWDTRITEDDLQNEAKITDIMEP..EHALLATSIFKLTYQN.KVVRVQRPAKNG-TVMDVISRRDQRGSGQVGTYGLNTFTNMEAQLIRQMESEGIFSPSELETPNLA......ERVLDWLKK..HGTERLKRMAISGDDCVVKP...IDDRF.A..TALTALNDMGKVRKDIPQWEPSKGW.....................................................................
A0A2G9UTS9_TELCI/22-223 vvpdfsmwsvtdttaretfkmvarkvdvppvenhhhypsllsiakanrksgmglqermlatsmgdyldsg-------------------------------------------------------------------------.-.-------------------------------------------------------..--------.-.--------------------.----------------------LWRERKK.EViE.DLLQGYTDLGFFNSMGKKEKKKV--SGYKGLRLIWYLPATMRLIEHENLGFLMEI---LKEFP-FSVSGYPLYDYGPLM-DIAFQGCECFLADD-----TRITVGDLRIEHWMLQEITQ..D---------------.------------------------------------------------------------------......---------..--------------------...-----.-..-------------------------erqkqlitalsdi........................................................
A0A0P0QKK6_9VIRU/322-709 ................................................................lpeqgl------------------------------------------------EYNHWESLGVYPVGKTGSTAQRYNRyA.LKVLTRLIPSLQGFDHWKTTDTTPSGFQRVFHAKVDTPPKENHQYENKLLSIYEG..MAAHFVAE.G.FVLKELTWEEVYEQANKQGA.AGTI----DMFENVGEFLSNPNWIEKVKM.VR.K.CLDEGKPIHGVFNTIGKREKKKCG-EKQKGSRMVAYLPIAMRLLELKLFGNLL--KLTKPELNHFGVGGLGLHDLGMRINEVWQEHG---VSDDIAGFDTRVGLTTLSLENRFIKLLGG..---NLTHQKMYRLYGH.PLILVPICSE--YNRSELLRGRGQRMSGSNPTYSMNTITRIAVGLLQLSVVEEIP-GDELLTWTME......QMIYDKSKM..KGC-------VSGDDATFMSdehTAKKL.A..CGYDVLDEIGMPRKDIPRG------vptp.................................................................
A0A164KMQ3_9CRUS/63-252 ..................................................................nprm-------------------------------------------------------------------------.-.--------------------------IQKLFTEKVDTWVQPRPLGARVISKTIAK..WMWERASK.KgLKPRFCTKEEFLKKLRNDAA.VGAW-NDTLMWESGNKALADPRFWKIVDE.ER.E.LHLRGECRLCMYNTMGKREMRPREFGNAKGSRVIWYMWLGSIFLEFEALGFLNEDGWAKRENTGFGVSGLGVNYLGYVLEDLR--DHGSFYW---------------------------..----------------.------------------------------------------------------------------......---------..--------------------...-----.-..-------------------------nadtgm...............................................................
A0A0B2UNM1_TOXCA/1-108 ...................................................................mlc-------------------------------------------------------------------------.-.-------------------------------------------------------..--------.-.--------------------.-----------------------------.--.-.-----------------------------------------------------------------------------------------------------------------------..------LELFYQLYAH.KVVMMPRERDGT-EETALVRIRSQRGSGENVTYGMNTITNFRFLFAKYLKSEGVAEN---------......---------..--------------------...-----.-..-------------------------aikahvwsylqgeepvglmvsggdsivmldeqrakvsra..............................
A0A0N7JQI7_9VIRU/323-704 ..................................................................evgr------------------------------------------------AYNHWESLGVYPMGVSGSKGMKYNK.YgMACATRMLSSIDGFDQWKLTDTTPEGFVSVFNTKIDKPPTENHPYEKRLWAVYKG..MSSHFQAR.G.FRLRELSYDEIEKQVNNAGA.P-GYADMMEGVNDIKDYMSRPDWRKKVEK.LR.Q.ALLSGRPKEAIFNTMGKREKKKSG---GKGSRMIAYMSIGMRLLEMKLFGNLM--KLTKPEYMHFGVGGFGLHDLGERLRRVWKGEG---SSDDIAGFDTRVSAKTLAFEAAFVQELGGntGHREM-----YEVYAS.P--HILIPVPSPHRRVQLLVGRGQRMSGCQVTYPMNTLTRVALFLVQASLAEGVDEN---------......-LVQAWVMRvmRGKEDIG-GAVSGDDAVF--...-----.-..-------------------------tsskkmkeiinhsdvledmgfprknmargv.......................................
#=GC seq_cons .....................................................................t.................................................appWt.hGsY.h..pGutu.hhNt.h.hphhpp.hs.l.thsphthTDTTP.G..pVFppKVDT.s.cs..hpp.lhphhtt..hhhchhtc.t.hp.+.hoh-EhhppspptuA..Gsh......hpsstchhtpPpahchVcc.pR.c.hh.pGcshtslaNoMGKREKK.st..psKGSRhIhYh.luhRhLEhchhGhL.E.thht.E.stFGVuGhGLpcLG.hlc-lh...ttthhusDhAGaDTRls.h.hp.Et.hhp.ht...t......th...hat.....hl.hsh.st.th.pllttRsQRhSGpssTYuhNThTphth.llp.h.sp.l.......................h.....tu........lSGDDssh............................................................................................................
//
