POLG_YEFV8
ID POLG_YEFV8 Reviewed; 1163 AA.
AC P29165;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 29-SEP-2021, entry version 132.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C;
DE AltName: Full=Core protein;
DE Contains:
DE RecName: Full=Protein prM;
DE Contains:
DE RecName: Full=Peptide pr;
DE Contains:
DE RecName: Full=Small envelope protein M;
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE Contains:
DE RecName: Full=Non-structural protein 2A;
DE Short=NS2A;
DE Flags: Fragment;
OS Yellow fever virus (isolate Peru/1899/1981) (YFV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=31641;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=299629; Aedes luteocephalus (Mosquito).
OH NCBI_TaxID=7161; Aedes simpsoni.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=314293; Simiiformes.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2145394; DOI=10.1099/0022-1317-71-9-2115;
RA Ballinger-Crabtree M.E., Miller B.R.;
RT "Partial nucleotide sequence of South American yellow fever virus strain
RT 1899/81: structural proteins and NS1.";
RL J. Gen. Virol. 71:2115-2121(1990).
CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding
CC to the cell membrane and gathering the viral RNA into a nucleocapsid
CC that forms the core of a mature virus particle. During virus entry, may
CC induce genome penetration into the host cytoplasm after hemifusion
CC induced by the surface proteins. Can migrate to the cell nucleus where
CC it modulates host functions. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering
CC with host Dicer. {ECO:0000250|UniProtKB:P03314}.
CC -!- FUNCTION: [Peptide pr]: Prevents premature fusion activity of envelope
CC proteins in trans-Golgi by binding to envelope protein E at pH6.0.
CC After virion release in extracellular space, gets dissociated from E
CC dimers. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Protein prM]: Acts as a chaperone for envelope protein E
CC during intracellular virion assembly by masking and inactivating
CC envelope protein E fusion peptide. prM is the only viral peptide
CC matured by host furin in the trans-Golgi network probably to avoid
CC catastrophic activation of the viral fusion activity in acidic Golgi
CC compartment prior to virion release. prM-E cleavage is inefficient, and
CC many virions are only partially matured. These uncleaved prM would play
CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding.
CC Exerts cytotoxic effects by activating a mitochondrial apoptotic
CC pathway through M ectodomain. May display a viroporin activity.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and
CC mediates fusion between viral and cellular membranes. Envelope protein
CC is synthesized in the endoplasmic reticulum in the form of heterodimer
CC with protein prM. They play a role in virion budding in the ER, and the
CC newly formed immature particle is covered with 60 spikes composed of
CC heterodimer between precursor prM and envelope protein E. The virion is
CC transported to the Golgi apparatus where the low pH causes dissociation
CC of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is
CC inefficient, and many virions are only partially matured. These
CC uncleaved prM would play a role in immune evasion.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host immune response. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Capsid protein C]: Homodimer (By similarity). Interacts (via
CC N-terminus) with host EXOC1 (via C-terminus); this interaction results
CC in EXOC1 degradation through the proteasome degradation pathway (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane;
CC Peripheral membrane protein; Lumenal side
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: The transmembrane domains of the small envelope protein M and
CC envelope protein E contain an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC mature proteins. The nascent capsid protein C contains a C-terminal
CC hydrophobic domain that act as a signal sequence for translocation of
CC prM into the lumen of the ER. Mature capsid protein C is cleaved at a
CC site upstream of this hydrophobic domain by NS3. prM is cleaved in
CC post-Golgi vesicles by a host furin, releasing the mature small
CC envelope protein M, and peptide pr. Non-structural protein 2A-alpha, a
CC C-terminally truncated form of non-structural protein 2A, results from
CC partial cleavage by NS3. Specific enzymatic cleavages in vivo yield
CC mature proteins peptide 2K acts as a signal sequence and is removed
CC from the N-terminus of NS4B by the host signal peptidase in the ER
CC lumen. Signal cleavage at the 2K-4B site requires a prior NS3 protease-
CC mediated cleavage at the 4A-2K site. {ECO:0000250|UniProtKB:P03314}.
CC -!- PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin,
CC releasing the mature small envelope protein M, and peptide pr. This
CC cleavage is incomplete as up to 30% of viral particles still carry
CC uncleaved prM. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Envelope protein E]: N-glycosylated.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is
CC glycosylated and this is required for efficient secretion of the
CC protein from infected cells. {ECO:0000250|UniProtKB:P17763}.
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; D14458; BAA03355.1; -; Genomic_RNA.
DR PIR; JU0374; GNWVY8.
DR SMR; P29165; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd12149; Flavi_E_C; 1.
DR Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.60.260.50; -; 1.
DR Gene3D; 2.60.40.350; -; 1.
DR Gene3D; 2.60.98.10; -; 1.
DR Gene3D; 3.30.387.10; -; 1.
DR Gene3D; 3.30.67.10; -; 1.
DR InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR001122; Flavi_capsidC.
DR InterPro; IPR037172; Flavi_capsidC_sf.
DR InterPro; IPR027287; Flavi_E_Ig-like.
DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR InterPro; IPR001157; Flavi_NS1.
DR InterPro; IPR002535; Flavi_propep.
DR InterPro; IPR038688; Flavi_propep_sf.
DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR InterPro; IPR011998; Glycoprot_cen/dimer.
DR InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF01003; Flavi_capsid; 1.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF00948; Flavi_NS1; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
PE 3: Inferred from homology;
KW ATP-binding; Capsid protein;
KW Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein; Helicase;
KW Host cytoplasm; Host endoplasmic reticulum; Host membrane; Host nucleus;
KW Host-virus interaction; Hydrolase; Membrane; Nucleotide-binding; Secreted;
KW Suppressor of RNA silencing; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc.
FT CHAIN 1..>1163
FT /note="Genome polyprotein"
FT /id="PRO_0000405154"
FT CHAIN 1..101
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037776"
FT PROPEP 102..121
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037777"
FT CHAIN 122..285
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000261453"
FT CHAIN 122..210
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000261454"
FT CHAIN 211..285
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037778"
FT CHAIN 286..778
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037779"
FT CHAIN 779..1130
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037780"
FT CHAIN 1131..>1163
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037781"
FT TOPO_DOM 1..104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..285
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 286..730
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 731..751
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 752..757
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 758..778
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 779..>1163
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 38..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 383..396
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT SITE 101..102
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 121..122
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 210..211
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 285..286
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 778..779
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 1130..1131
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 908
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 986
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 288..315
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 345..406
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 359..390
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 377..401
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 467..568
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 585..615
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 782..793
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 833..921
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 957..1002
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1058..1107
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1069..1091
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1090..1094
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT NON_TER 1163
SQ SEQUENCE 1163 AA; 128521 MW; 6BEBDA317D722E01 CRC64;
MSGRKAQGKT LGVNMVRQGV RSLSNKIKQK TKQIGNRPGP SRGVQGFIFF FLFNVLTGRK
ITAHLKKLWR MLDPRQGLAV LKKVKRVVAS LMRGLSSRKR RSYEVLTVQF LILGMLLMTG
GVTLVRKSRW LLLNVTSEDL GKTFSVGTGN CTTNILEAKN WCPDSMEYNC PNLSPREEPD
DIDCWCYGVE NVRVAYGKCD SAGRSRRSRR AIDLPTHENH GLKTRQEKWM TGRMGERQLQ
KIERWLVRNP FFAVTALAIA YLVGSNMTQR VVIALLVLAV GPAYSAHCIG ITDRDFIEGV
HGGTWVSATL EQDKCVTVMA PDKPSLDISL ETVAIDGPAE ARKVCYSAVL THVKINDKCP
STGEAHLAEE NEGDHACKRT YSDRGWGNGC GLFGKGSIVA CAKFTCAKSM SLFEVDQTKI
QYVIRAQLHV GAKQENWNAD IKTLKFDALS GSQEAEFTGY GKATLECQVQ TAVDFSNSYI
AEMEKESWIV DRQWAQDLTL PWQSGSGGVW REMHHLVEFE PPHAATIKVL ALGNQEGSLK
TALTGAMRVT KDTNGSNLYK LHGGHVSCRV KLSALTLKGT SYKMCTDKMS FVKNPTDTGH
GTAVMQVKVP KGAPCRIPVM VADDLTASVN KGILVTVNPI ASTNEDEVLI EVNPPFGDSY
IIVGTGDSRL TYQWHKEGSS IGKLFTQTMK GAERLAVMGD AAWDFSSAGG FFTSVGKGIH
MVFGSAFQGL FGGLSWITKV IMGAVLIWVG INMRNMTMSM SMILVGVIMM FLSLGVGADQ
GCAINFGKRE LKCGDGVFIF RDSDDWLNKY SYYPEDPVKL ASIVKASFEE GKCGLNSVDS
LEHEMWRSRA DEINAILEEN EVDISVVVQD PKNIYQRGTH PFSRIRDGLQ YGWKTWGKNL
VFSPGRKNGS FIIDGKSRKE CPFSNRVWNS LQIEEFGTGV FTTRVYMDAV FEYTMDCDGS
ILGAAVNGKK SAHGSPTFWM GSHEVNGTWM IHTLETLDYK ECEWPLTHTI GTSVEESDMF
MPRSIGGPVS SHNHIPGYKV QTNGPWMQVP LEVKREACPG TSVVVDGGCD GRGKSTRSTT
DSGKIIPEWC CRSCTMPPVS FHGSDGCWYP MEIRPRKTHD NHLVRSWVTA GEVHAVPFGL
VSMMIAMEVF LKKRQGPKQI LVG
