ID POLG_BVDVN STANDARD; PRT; 3988 AA. AC P19711; DT 01-FEB-1991 (Rel. 17, Created) DT 01-FEB-1996 (Rel. 33, Last sequence update) DT 10-MAY-2005 (Rel. 47, Last annotation update) DE Genome polyprotein [Contains: N-terminal protease (EC 3.4.22.-) (N- DE pro) (Autoprotease p20); Capsid protein C; E(rns) glycoprotein DE (gp44/48); Envelope glycoprotein E1 (gp33); Envelope glycoprotein E2 DE (gp55); p7; Nonstructural protein 2 (NS2); Protease/helicase NS3 DE (EC 3.4.21.-) (NTPase); Nonstructural protein 4A (NS4A); Nonstructural DE protein 4B (NS4B); Nonstructural protein 5A (NS5A); RNA-directed RNA DE polymerase (EC 2.7.7.48) (NS5B)]. OS Bovine viral diarrhea virus (isolate NADL) (BVDV) (Mucosal disease OS virus). OC Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; OC Pestivirus. OX NCBI_TaxID=11100; RN [1] RP NUCLEOTIDE SEQUENCE. RX MEDLINE=88265858; PubMed=2838957; RA Collett M.S., Larson R., Gold C., Strick D., Anderson D.K., RA Purchio A.F.; RT "Molecular cloning and nucleotide sequence of the pestivirus bovine RT viral diarrhea virus."; RL Virology 165:191-199(1988). RN [2] RP GENOMIC ORGANIZATION. RX MEDLINE=88265859; PubMed=2838958; RA Collett M.S., Larson R., Belzer S.K., Retzel E.; RT "Proteins encoded by bovine viral diarrhea virus: the genomic RT organization of a pestivirus."; RL Virology 165:200-208(1988). RN [3] RP PROCESSING OF POLYPROTEIN, AND PROTEIN SEQUENCE OF 2363-2376; RP 2427-2441; 2774-2788 AND 3270-3284. RX PubMed=9188600; RA Xu J., Mendez E., Caron P.R., Lin C., Murcko M.A., Collett M.S., RA Rice C.M.; RT "Bovine viral diarrhea virus NS3 serine proteinase: polyprotein RT cleavage sites, cofactor requirements, and molecular model of an RT enzyme essential for pestivirus replication."; RL J. Virol. 71:5312-5322(1997). RN [4] RP SUBCELLULAR LOCATION. RX PubMed=10355762; RA Weiland F., Weiland E., Unger G., Saalmuller A., Thiel H.-J.; RT "Localization of pestiviral envelope proteins E(rns) and E2 at the RT cell surface and on isolated particles."; RL J. Gen. Virol. 80:1157-1165(1999). RN [5] RP FUNCTION OF NS2-3. RC STRAIN=Isolate NADL Jiv 90(-); RX PubMed=14963137; DOI=10.1128/JVI.78.5.2414-2425.2004; RA Agapov E.V., Murray C.L., Frolov I., Qu L., Myers T.M., Rice C.M.; RT "Uncleaved NS2-3 is required for production of infectious bovine viral RT diarrhea virus."; RL J. Virol. 78:2414-2425(2004). CC -!- FUNCTION: Uncleaved NS2-3 is required for production of infectious CC virus. NS3 is a multifunctional protein with helicase, NTPase and CC protease activity. NS4A is a cofactor for the NS3 protease CC activity. CC -!- FUNCTION: P7 forms a leader sequence to properly orient NS2 in the CC membrane. CC -!- CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate CC + RNA(n+1). CC -!- SUBCELLULAR LOCATION: E(rns) and E2 glycoproteins are located at CC the surface of infected cells. NS2 is a membrane protein. CC -!- PTM: The E(rns) glycoprotein is heavily glycosylated. Forms CC disulfide-linked homodimers (By similarity). CC -!- PTM: The E1 and E2 envelope glycoproteins form disulfide-linked CC homodimers as well as heterodimers (By similarity). CC -!- PTM: The viral RNA of pestiviruses is expressed as a single CC polyprotein which undergoes post-translational proteolytic CC processing resulting in the production of at least eleven CC individual proteins. The N-terminal protease cleaves itself from CC the nascent polyprotein autocatalytically and thereby generates CC the N-terminus of the adjacent viral capsid protein C (By CC similarity). CC -!- PTM: Cleavage between E2 and p7 is partial (By similarity). CC -!- PTM: Cleavage between NS2 and NS3 is partial. CC -!- MISCELLANEOUS: BVDV is divided in two types: cytopathic and CC noncytopathic. Both type of viruses can be found in animals CC suffering from mucosal disease, as a cytopathic BVDV can develop CC from a noncytopathic virus within the infected animal by CC deletions, mutations or insertions. Both types express uncleaved CC NS2-3, but cytopathic also express NS3. The cytopathic NADL strain CC contains an insertion (Jiv 90) that potentiate the partial CC cleavage of NS2-3. Removal of this insertion in the NADL Jiv 90(-) CC strain results in a noncytopathic strain in which NS2-3 remains CC uncleaved. CC -!- SIMILARITY: Belongs to the pestiviruses polyprotein family. CC -!- SIMILARITY: Contains 1 peptidase C53 domain. CC -!- SIMILARITY: Contains 1 peptidase S31 domain. 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; M31182; AAA42854.1; -; Genomic_RNA. DR PIR; A29198; GNWVBV. DR PDB; 1S48; X-ray; A=3340-3948. DR PDB; 1S49; X-ray; A=3340-3948. DR PDB; 1S4F; X-ray; A/B/C/D=3348-3948. DR MEROPS; C53.001; -. DR MEROPS; S31.001; -. DR InterPro; IPR001410; DEAD. DR InterPro; IPR002166; HCV_RdRP. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR008751; Peptidase_C53. DR InterPro; IPR000280; Peptidase_S31. DR InterPro; IPR007095; RNA_pol_DS_PS. DR InterPro; IPR007094; RNA_pol_PSvir. DR InterPro; IPR001568; RNase_T2. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF05550; Peptidase_C53; 1. DR Pfam; PF05578; Peptidase_S31; 1. DR Pfam; PF00998; Viral_RdRP; 1. DR PRINTS; PR00729; CDVENDOPTASE. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR PROSITE; PS00531; RNASE_T2_2; UNKNOWN_1. KW 3D-structure; ATP-binding; Direct protein sequencing; Glycoprotein; KW Helicase; Hydrolase; Nucleotidyltransferase; Polyprotein; Protease; KW RNA-directed RNA polymerase; Serine protease; Thiol protease; KW Transferase; Transmembrane. FT CHAIN 1 168 N-terminal protease (By similarity). FT CHAIN 169 270 Capsid protein C (By similarity). FT CHAIN 271 497 E(rns) glycoprotein (By similarity). FT CHAIN 498 659 Envelope glycoprotein E1 (By similarity). FT CHAIN 660 1066 Envelope glycoprotein E2 (By similarity). FT CHAIN 1067 1136 p7 (By similarity). FT CHAIN 1137 2362 Nonstructural protein 2-3. FT CHAIN 1137 1679 Nonstructural protein 2. FT CHAIN 1680 2362 Protease/helicase NS3. FT CHAIN 2363 2426 Nonstructural protein 4A (By similarity). FT CHAIN 2427 2773 Nonstructural protein 4B (By similarity). FT CHAIN 2774 3269 Nonstructural protein 5A (By similarity). FT CHAIN 3270 3988 RNA-directed RNA polymerase (By FT similarity). FT TRANSMEM 1144 1164 Potential. FT TRANSMEM 1189 1209 Potential. FT TRANSMEM 1217 1237 Potential. FT TRANSMEM 1247 1267 Potential. FT TRANSMEM 1281 1301 Potential. FT TRANSMEM 1360 1380 Potential. FT TRANSMEM 1658 1678 Potential. FT ACT_SITE 22 22 N-terminal protease (By similarity). FT ACT_SITE 49 49 N-terminal protease (By similarity). FT ACT_SITE 69 69 N-terminal protease (By similarity). FT ACT_SITE 1748 1748 Charge relay system; protease NS3 (By FT similarity). FT ACT_SITE 1785 1785 Charge relay system; protease NS3 (By FT similarity). FT ACT_SITE 1842 1842 Charge relay system; protease NS3 (By FT similarity). FT SITE 168 169 Cleavage (auto-) (By similarity). FT SITE 270 271 Cleavage (by host signal peptidase) (By FT similarity). FT SITE 497 498 Cleavage. FT SITE 659 660 Cleavage (by host signal peptidase) (By FT similarity). FT SITE 1066 1067 Cleavage; partial (by host signal FT peptidase) (By similarity). FT SITE 1136 1137 Cleavage (by host signal peptidase) (By FT similarity). FT SITE 1679 1680 Cleavage; partial (in cytopathic FT strains). FT SITE 2362 2363 Cleavage (by NS3) (By similarity). FT SITE 2426 2427 Cleavage (by NS3) (By similarity). FT SITE 2773 2774 Cleavage (by NS3) (By similarity). FT SITE 3269 3270 Cleavage (by NS3) (By similarity). FT CARBOHYD 272 272 N-linked (GlcNAc...) (Potential). FT CARBOHYD 281 281 N-linked (GlcNAc...) (Potential). FT CARBOHYD 296 296 N-linked (GlcNAc...) (Potential). FT CARBOHYD 335 335 N-linked (GlcNAc...) (Potential). FT CARBOHYD 365 365 N-linked (GlcNAc...) (Potential). FT CARBOHYD 370 370 N-linked (GlcNAc...) (Potential). FT CARBOHYD 413 413 N-linked (GlcNAc...) (Potential). FT CARBOHYD 487 487 N-linked (GlcNAc...) (Potential). FT CARBOHYD 597 597 N-linked (GlcNAc...) (Potential). FT CARBOHYD 809 809 N-linked (GlcNAc...) (Potential). FT CARBOHYD 878 878 N-linked (GlcNAc...) (Potential). FT CARBOHYD 922 922 N-linked (GlcNAc...) (Potential). FT CARBOHYD 990 990 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1357 1357 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1419 1419 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1451 1451 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1803 1803 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2224 2224 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2307 2307 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2584 2584 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2772 2772 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2981 2981 N-linked (GlcNAc...) (Potential). FT CARBOHYD 3778 3778 N-linked (GlcNAc...) (Potential). FT CARBOHYD 3867 3867 N-linked (GlcNAc...) (Potential). FT CARBOHYD 3883 3883 N-linked (GlcNAc...) (Potential). SQ SEQUENCE 3988 AA; 449163 MW; 4474212F338661B8 CRC64; MELITNELLY KTYKQKPVGV EEPVYDQAGD PLFGERGAVH PQSTLKLPHK RGERDVPTNL ASLPKRGDCR SGNSRGPVSG IYLKPGPLFY QDYKGPVYHR APLELFEEGS MCETTKRIGR VTGSDGKLYH IYVCIDGCII IKSATRSYQR VFRWVHNRLD CPLWVTTCSD TKEEGATKKK TQKPDRLERG KMKIVPKESE KDSKTKPPDA TIVVEGVKYQ VRKKGKTKSK NTQDGLYHNK NKPQESRKKL EKALLAWAII AIVLFQVTMG ENITQWNLQD NGTEGIQRAM FQRGVNRSLH GIWPEKICTG VPSHLATDIE LKTIHGMMDA SEKTNYTCCR LQRHEWNKHG WCNWYNIEPW ILVMNRTQAN LTEGQPPREC AVTCRYDRAS DLNVVTQARD SPTPLTGCKK GKNFSFAGIL MRGPCNFEIA ASDVLFKEHE RISMFQDTTL YLVDGLTNSL EGARQGTAKL TTWLGKQLGI LGKKLENKSK TWFGAYAASP YCDVDRKIGY IWYTKNCTPA CLPKNTKIVG PGKFGTNAED GKILHEMGGH LSEVLLLSLV VLSDFAPETA SVMYLILHFS IPQSHVDVMD CDKTQLNLTV ELTTAEVIPG SVWNLGKYVC IRPNWWPYET TVVLAFEEVS QVVKLVLRAL RDLTRIWNAA TTTAFLVCLV KIVRGQMVQG ILWLLLITGV QGHLDCKPEF SYAIAKDERI GQLGAEGLTT TWKEYSPGMK LEDTMVIAWC EDGKLMYLQR CTRETRYLAI LHTRALPTSV VFKKLFDGRK QEDVVEMNDN FEFGLCPCDA KPIVRGKFNT TLLNGPAFQM VCPIGWTGTV SCTSFNMDTL ATTVVRTYRR SKPFPHRQGC ITQKNLGEDL HNCILGGNWT CVPGDQLLYK GGSIESCKWC GYQFKESEGL PHYPIGKCKL ENETGYRLVD STSCNREGVA IVPQGTLKCK IGKTTVQVIA MDTKLGPMPC RPYEIISSEG PVEKTACTFN YTKTLKNKYF EPRDSYFQQY MLKGEYQYWF DLEVTDHHRD YFAESILVVV VALLGGRYVL WLLVTYMVLS EQKALGIQYG SGEVVMMGNL LTHNNIEVVT YFLLLYLLLR EESVKKWVLL LYHILVVHPI KSVIVILLMI GDVVKADSGG QEYLGKIDLC FTTVVLIVIG LIIARRDPTI VPLVTIMAAL RVTELTHQPG VDIAVAVMTI TLLMVSYVTD YFRYKKWLQC ILSLVSAVFL IRSLIYLGRI EMPEVTIPNW RPLTLILLYL ISTTIVTRWK VDVAGLLLQC VPILLLVTTL WADFLTLILI LPTYELVKLY YLKTVRTDTE RSWLGGIDYT RVDSIYDVDE SGEGVYLFPS RQKAQGNFSI LLPLIKATLI SCVSSKWQLI YMSYLTLDFM YYMHRKVIEE ISGGTNIISR LVAALIELNW SMEEEESKGL KKFYLLSGRL RNLIIKHKVR NETVASWYGE EEVYGMPKIM TIIKASTLSK SRHCIICTVC EGREWKGGTC PKCGRHGKPI TCGMSLADFE ERHYKRIFIR EGNFEGMCSR CQGKHRRFEM DREPKSARYC AECNRLHPAE EGDFWAESSM LGLKITYFAL MDGKVYDITE WAGCQRVGIS PDTHRVPCHI SFGSRMPFRQ EYNGFVQYTA RGQLFLRNLP VLATKVKMLM VGNLGEEIGN LEHLGWILRG PAVCKKITEH EKCHINILDK LTAFFGIMPR GTTPRAPVRF PTSLLKVRRG LETAWAYTHQ GGISSVDHVT AGKDLLVCDS MGRTRVVCQS NNRLTDETEY GVKTDSGCPD GARCYVLNPE AVNISGSKGA VVHLQKTGGE FTCVTASGTP AFFDLKNLKG WSGLPIFEAS SGRVVGRVKV GKNEESKPTK IMSGIQTVSK NRADLTEMVK KITSMNRGDF KQITLATGAG KTTELPKAVI EEIGRHKRVL VLIPLRAAAE SVYQYMRLKH PSISFNLRIG DMKEGDMATG ITYASYGYFC QMPQPKLRAA MVEYSYIFLD EYHCATPEQL AIIGKIHRFS ESIRVVAMTA TPAGSVTTTG QKHPIEEFIA PEVMKGEDLG SQFLDIAGLK IPVDEMKGNM LVFVPTRNMA VEVAKKLKAK GYNSGYYYSG EDPANLRVVT SQSPYVIVAT NAIESGVTLP DLDTVIDTGL KCEKRVRVSS KIPFIVTGLK RMAVTVGEQA QRRGRVGRVK PGRYYRSQET ATGSKDYHYD LLQAQRYGIE DGINVTKSFR EMNYDWSLYE EDSLLITQLE ILNNLLISED LPAAVKNIMA RTDHPEPIQL AYNSYEVQVP VLFPKIRNGE VTDTYENYSF LNARKLGEDV PVYIYATEDE DLAVDLLGLD WPDPGNQQVV ETGKALKQVT GLSSAENALL VALFGYVGYQ ALSKRHVPMI TDIYTIEDQR LEDTTHLQYA PNAIKTDGTE TELKELASGD VEKIMGAISD YAAGGLEFVK SQAEKIKTAP LFKENAEAAK GYVQKFIDSL IENKEEIIRY GLWGTHTALY KSIAARLGHE TAFATLVLKW LAFGGESVSD HVKQAAVDLV VYYVMNKPSF PGDSETQQEG RRFVASLFIS ALATYTYKTW NYHNLSKVVE PALAYLPYAT SALKMFTPTR LESVVILSTT IYKTYLSIRK GKSDGLLGTG ISAAMEILSQ NPVSVGISVM LGVGAIAAHN AIESSEQKRT LLMKVFVKNF LDQAATDELV KENPEKIIMA LFEAVQTIGN PLRLIYHLYG VYYKGWEAKE LSERTAGRNL FTLIMFEAFE LLGMDSQGKI RNLSGNYILD LIYGLHKQIN RGLKKMVLGW APAPFSCDWT PSDERIRLPT DNYLRVETRC PCGYEMKAFK NVGGKLTKVE ESGPFLCRNR PGRGPVNYRV TKYYDDNLRE IKPVAKLEGQ VEHYYKGVTA KIDYSKGKML LATDKWEVEH GVITRLAKRY TGVGFNGAYL GDEPNHRALV ERDCATITKN TVQFLKMKKG CAFTYDLTIS NLTRLIELVH RNNLEEKEIP TATVTTWLAY TFVNEDVGTI KPVLGERVIP DPVVDINLQP EVQVDTSEVG ITIIGRETLM TTGVTPVLEK VEPDASDNQN SVKIGLDEGN YPGPGIQTHT LTEEIHNRDA RPFIMILGSR NSISNRAKTA RNINLYTGND PREIRDLMAA GRMLVVALRD VDPELSEMVD FKGTFLDREA LEALSLGQPK PKQVTKEAVR NLIEQKKDVE IPNWFASDDP VFLEVALKND KYYLVGDVGE LKDQAKALGA TDQTRIIKEV GSRTYAMKLS SWFLKASNKQ MSLTPLFEEL LLRCPPATKS NKGHMASAYQ LAQGNWEPLG CGVHLGTIPA RRVKIHPYEA YLKLKDFIEE EEKKPRVKDT VIREHNKWIL KKIRFQGNLN TKKMLNPGKL SEQLDREGRK RNIYNHQIGT IMSSAGIRLE KLPIVRAQTD TKTFHEAIRD KIDKSENRQN PELHNKLLEI FHTIAQPTLK HTYGEVTWEQ LEAGVNRKGA AGFLEKKNIG EVLDSEKHLV EQLVRDLKAG RKIKYYETAI PKNEKRDVSD DWQAGDLVVE KRPRVIQYPE AKTRLAITKV MYNWVKQQPV VIPGYEGKTP LFNIFDKVRK EWDSFNEPVA VSFDTKAWDT QVTSKDLQLI GEIQKYYYKK EWHKFIDTIT DHMTEVPVIT ADGEVYIRNG QRGSGQPDTS AGNSMLNVLT MMYGFCESTG VPYKSFNRVA RIHVCGDDGF LITEKGLGLK FANKGMQILH EAGKPQKITE GEKMKVAYRF EDIEFCSHTP VPVRWSDNTS SHMAGRDTAV ILSKMATRLD SSGERGTTAY EKAVAFSFLL MYSWNPLVRR ICLLVLSQQP ETDPSKHATY YYKGDPIGAY KDVIGRNLSE LKRTGFEKLA NLNLSLSTLG VWTKHTSKRI IQDCVAIGKE EGNWLVKPDR LISSKTGHLY IPDKGFTLQG KHYEQLQLRT ETNPVMGVGT ERYKLGPIVN LLLRRLKILL MTAVGVSS //