GP_TULV
ID GP_TULV Reviewed; 1141 AA.
AC P0DTJ1;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=Envelopment polyprotein;
DE AltName: Full=Glycoprotein precursor {ECO:0000250|UniProtKB:P08668};
DE AltName: Full=M polyprotein;
DE Contains:
DE RecName: Full=Glycoprotein N {ECO:0000250|UniProtKB:P08668};
DE Short=Gn;
DE AltName: Full=Glycoprotein G1;
DE Contains:
DE RecName: Full=Glycoprotein C {ECO:0000250|UniProtKB:P08668};
DE Short=Gc;
DE AltName: Full=Glycoprotein G2;
DE Flags: Precursor;
GN Name=GP;
OS Tula orthohantavirus (TULV) (Tula virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980494;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=47230; Microtus arvalis (Common vole) (Field vole).
OH NCBI_TaxID=523745; Microtus obscurus.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Tula/Moravia/5302v/95;
RX PubMed=9000098; DOI=10.1099/0022-1317-77-12-3063;
RA Vapalahti O., Lundkvist A., Kukkonen S.K., Cheng Y., Gilljam M.,
RA Kanerva M., Manni T., Pejcoch M., Niemimaa J., Kaikusalo A., Henttonen H.,
RA Vaheri A., Plyusnin A.;
RT "Isolation and characterization of Tula virus, a distinct serotype in the
RT genus Hantavirus, family Bunyaviridae.";
RL J. Gen. Virol. 77:3063-3067(1996).
RN [2]
RP DOMAIN (GLYCOPROTEIN N), AND FUNCTION (GLYCOPROTEIN N).
RX PubMed=16973572; DOI=10.1128/jvi.00508-06;
RA Alff P.J., Gavrilovskaya I.N., Gorbunova E., Endriss K., Chong Y.,
RA Geimonen E., Sen N., Reich N.C., Mackow E.R.;
RT "The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and
RT TBK-1-directed interferon responses.";
RL J. Virol. 80:9676-9686(2006).
RN [3]
RP INTERACTION WITH THE NUCLEOPROTEIN (GLYCOPROTEIN N), AND DOMAIN
RP (GLYCOPROTEIN N).
RC STRAIN=Moravia;
RX PubMed=20566401; DOI=10.1016/j.virusres.2010.05.008;
RA Wang H., Alminaite A., Vaheri A., Plyusnin A.;
RT "Interaction between hantaviral nucleocapsid protein and the cytoplasmic
RT tail of surface glycoprotein Gn.";
RL Virus Res. 151:205-212(2010).
RN [4]
RP FUNCTION (GLYCOPROTEIN N), AND DOMAIN (GLYCOPROTEIN N).
RX PubMed=21807393; DOI=10.1016/j.virol.2011.06.030;
RA Strandin T., Hepojoki J., Wang H., Vaheri A., Lankinen H.;
RT "The cytoplasmic tail of hantavirus Gn glycoprotein interacts with RNA.";
RL Virology 418:12-20(2011).
RN [5]
RP FUNCTION (GLYCOPROTEIN N), AND DOMAIN (GLYCOPROTEIN N).
RX PubMed=21367904; DOI=10.1128/jvi.01945-10;
RA Matthys V., Gorbunova E.E., Gavrilovskaya I.N., Pepini T., Mackow E.R.;
RT "The C-terminal 42 residues of the Tula virus Gn protein regulate
RT interferon induction.";
RL J. Virol. 85:4752-4760(2011).
RN [6]
RP FUNCTION (GLYCOPROTEIN N).
RX PubMed=24390324; DOI=10.1128/jvi.02647-13;
RA Matthys V.S., Cimica V., Dalrymple N.A., Glennon N.B., Bianco C.,
RA Mackow E.R.;
RT "Hantavirus GnT elements mediate TRAF3 binding and inhibit RIG-I/TBK1-
RT directed beta interferon transcription by blocking IRF3 phosphorylation.";
RL J. Virol. 88:2246-2259(2014).
RN [7]
RP REVIEW.
RX PubMed=24755564; DOI=10.3390/v6041801;
RA Cifuentes-Munoz N., Salazar-Quiroz N., Tischler N.D.;
RT "Hantavirus Gn and Gc envelope glycoproteins: key structural units for
RT virus cell entry and virus assembly.";
RL Viruses 6:1801-1822(2014).
RN [8]
RP STRUCTURE BY ELECTRON MICROSCOPY (36 ANGSTROMS), SUBUNIT (GLYCOPROTEIN N),
RP SUBUNIT (GLYCOPROTEIN C), SUBCELLULAR LOCATION (GLYCOPROTEIN N), AND
RP SUBCELLULAR LOCATION (GLYCOPROTEIN C).
RX PubMed=20219926; DOI=10.1128/jvi.00057-10;
RA Huiskonen J.T., Hepojoki J., Laurinmaeki P., Vaheri A., Lankinen H.,
RA Butcher S.J., Gruenewald K.;
RT "Electron cryotomography of Tula hantavirus suggests a unique assembly
RT paradigm for enveloped viruses.";
RL J. Virol. 84:4889-4897(2010).
CC -!- FUNCTION: [Glycoprotein N]: Forms homotetramers with glycoprotein C at
CC the surface of the virion (By similarity). Attaches the virion to host
CC cell receptors including integrin alpha5/ITGB1 (Probable). This
CC attachment induces virion internalization predominantly through
CC clathrin-dependent endocytosis (By similarity). Mediates the assembly
CC and budding of infectious virus particles through its interaction with
CC the nucleocapsid protein and the viral genome (PubMed:21807393). May
CC dysregulate normal immune and endothelial cell responses through an
CC ITAM motif. Translocates to mitochondria, binds to host TUFM and
CC recruits MAP1LC3B (By similarity). These interactions induce
CC mitochondrial autophagy and therefore destruction of host MAVS leading
CC to inhibition of type I interferon (IFN) responses (By similarity).
CC Concomitant breakdown of glycoprotein N is apparently prevented by the
CC nucleoprotein that may inhibit Gn-stimulated autophagosome-lysosome
CC fusion (By similarity). Interacts with the viral genomic RNA
CC (PubMed:21807393). Inhibits the host RIG-I/TBK1 pathway by disrupting
CC the formation of TBK1-TRAF3 complexes and downstream signaling
CC responses required for IFN-beta transcription (PubMed:24390324,
CC PubMed:21367904, PubMed:16973572). {ECO:0000250|UniProtKB:P08668,
CC ECO:0000269|PubMed:16973572, ECO:0000269|PubMed:21367904,
CC ECO:0000269|PubMed:21807393, ECO:0000269|PubMed:24390324, ECO:0000305}.
CC -!- FUNCTION: [Glycoprotein C]: Forms homotetramers with glycoprotein N at
CC the surface of the virion. Attaches the virion to host cell receptors
CC including integrin ITGAV/ITGB3. This attachment induces virion
CC internalization predominantly through clathrin-dependent endocytosis.
CC Class II fusion protein that promotes fusion of viral membrane with
CC host endosomal membrane after endocytosis of the virion.
CC {ECO:0000250|UniProtKB:P08668}.
CC -!- SUBUNIT: [Glycoprotein N]: Homodimer (By similarity). Homotetramer;
CC forms heterotetrameric Gn-Gc spikes in the pre-fusion conformation
CC (PubMed:20219926). Interacts (via C-terminus) with the nucleoprotein
CC (PubMed:20566401). Interacts with host TUFM; this interaction
CC contributes to the virus-induced degradation of mitochondria by
CC autophagy, which leads to degradation of host MAVS and inhibition of
CC type I interferon (IFN) responses (By similarity). Interacts with host
CC MAP1LC3B; this interaction contributes to the virus-induced degradation
CC of mitochondria by autophagy, which leads to degradation of host MAVS
CC and inhibition of type I interferon (IFN) responses (By similarity).
CC {ECO:0000250|UniProtKB:P08668, ECO:0000269|PubMed:20219926,
CC ECO:0000269|PubMed:20566401}.
CC -!- SUBUNIT: [Glycoprotein C]: Homodimer (By similarity). Homotetramer;
CC forms heterotetrameric Gn-Gc spikes in the pre-fusion conformation
CC (PubMed:20219926). Homotrimer; forms homotrimer in the post-fusion
CC conformation at acidic pH (By similarity). Interacts (via C-terminus)
CC with the nucleoprotein (By similarity). {ECO:0000250|UniProtKB:P08668,
CC ECO:0000250|UniProtKB:P27312, ECO:0000269|PubMed:20219926}.
CC -!- SUBCELLULAR LOCATION: [Glycoprotein N]: Virion membrane
CC {ECO:0000269|PubMed:20219926}; Multi-pass membrane protein
CC {ECO:0000305}. Host cell surface {ECO:0000250|UniProtKB:P08668}. Host
CC Golgi apparatus membrane {ECO:0000250|UniProtKB:P08668}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P08668}. Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P08668}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P08668}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P08668}. Note=Interaction between glycoprotein N
CC and glycoprotein C is essential for proper targeting of glycoprotein N
CC to the host Golgi complex, where virion budding occurs.
CC {ECO:0000250|UniProtKB:P27312}.
CC -!- SUBCELLULAR LOCATION: [Glycoprotein C]: Virion membrane
CC {ECO:0000269|PubMed:20219926}; Single-pass type I membrane protein
CC {ECO:0000305}. Host cell surface {ECO:0000250|UniProtKB:P08668}. Host
CC Golgi apparatus membrane {ECO:0000250|UniProtKB:P08668}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:P08668}. Host
CC endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P08668}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:P08668}.
CC Note=Budding probably takes place at the host Golgi (Probable).
CC Glycoprotein C cytoplasmic tail is important for efficient Golgi
CC localization (By similarity). {ECO:0000250|UniProtKB:P08668,
CC ECO:0000305}.
CC -!- DOMAIN: [Glycoprotein N]: The YxxL motif at the C-terminus is
CC indispensable for the interaction with MAP1LC3B and for the Gn-mediated
CC induction of mitochondrial autophagy (By similarity). The cytoplasmic
CC tail is involved in the inhibition of the host innate immune response
CC (PubMed:21367904, PubMed:16973572). The C-terminus of the cytoplasmic
CC tail is involved in binding to the viral genome and the nucleoprotein
CC (PubMed:20566401, PubMed:21807393). Contains 2 contiguous zinc-fingers
CC (By similarity). {ECO:0000250|UniProtKB:P08668,
CC ECO:0000250|UniProtKB:Q9E006, ECO:0000269|PubMed:16973572,
CC ECO:0000269|PubMed:20566401, ECO:0000269|PubMed:21367904,
CC ECO:0000269|PubMed:21807393}.
CC -!- DOMAIN: [Glycoprotein C]: The C-terminus is necessary for proper
CC localization in the Golgi (By similarity). The cytoplasmic tail is
CC involved in binding to the nucleocapsid (By similarity).
CC {ECO:0000250|UniProtKB:P27312}.
CC -!- PTM: [Envelopment polyprotein]: Envelope polyprotein precursor is
CC quickly cleaved in vivo just after synthesis, presumably by host signal
CC peptidase. {ECO:0000250|UniProtKB:P08668}.
CC -!- MISCELLANEOUS: TULV has the ability to regulate IFN induction although
CC it is not pathogenic. {ECO:0000269|PubMed:21367904}.
CC -!- SIMILARITY: Belongs to the hantavirus envelope glycoprotein family.
CC {ECO:0000305}.
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; Z69993; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR Proteomes; UP000243699; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0044228; C:host cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0039547; P:suppression by virus of host TRAF activity; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR InterPro; IPR016402; Envelope_glycoprot_Hantavirus.
DR InterPro; IPR002532; Hanta_Gc.
DR InterPro; IPR002534; Hanta_Gn.
DR InterPro; IPR012316; ITAM_motif_hantavir-typ.
DR Pfam; PF01567; Hanta_G1; 1.
DR Pfam; PF01561; Hanta_G2; 1.
DR Pfam; PF10538; ITAM_Cys-rich; 1.
DR PIRSF; PIRSF003945; M_poly_HantaV; 1.
DR PROSITE; PS51056; ITAM_2; 1.
PE 1: Evidence at protein level;
KW Activation of host autophagy by virus; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host endoplasmic reticulum; Host Golgi apparatus; Host membrane;
KW Host mitochondrion; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host TRAFs by virus; Membrane; Metal-binding; Phosphoprotein;
KW Repeat; Signal; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc; Zinc-finger.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1141
FT /note="Envelopment polyprotein"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT /id="PRO_0000455203"
FT CHAIN 20..653
FT /note="Glycoprotein N"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT /id="PRO_0000455204"
FT CHAIN 654..1141
FT /note="Glycoprotein C"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT /id="PRO_0000455205"
FT TOPO_DOM 20..489
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 633..653
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 654..1109
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1110..1130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1131..1141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 616..639
FT /note="ITAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT ZN_FING 550..570
FT /note="CCHC-type 1"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT ZN_FING 575..596
FT /note="CCHC-type 2"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 521..538
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 593..610
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT REGION 597..608
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 612..653
FT /note="Inhibition of interferon induction"
FT /evidence="ECO:0000269|PubMed:21367904"
FT REGION 616..630
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT REGION 762..782
FT /note="Fusion loop"
FT /evidence="ECO:0000250|UniProtKB:P41266"
FT REGION 1126..1141
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT MOTIF 620..623
FT /note="YxxL"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT SITE 653..654
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT MOD_RES 620
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT MOD_RES 633
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 932
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 29..154
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 63..160
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 112..131
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 136..141
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 178..188
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 213..252
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 381..440
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 385..394
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 410..429
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 457..480
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 740..775
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 744..782
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 756..889
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 770..900
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 785..908
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 811..820
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 828..837
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 868..872
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 974..1004
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 997..1049
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1014..1019
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1050..1055
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1089..1093
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
SQ SEQUENCE 1141 AA; 125905 MW; EC1EA1214985D860 CRC64;
MFCLCLSLLG LLLCWPAATR NLLELKVECP HTIGLGQGIV IGSAELPPVP LAKVESLKLE
SSCNFDLHTS TAAQQAFTKW SWEKKADTAE NAKAASTTFQ SSSKEVQLRG LCVIPTLVLE
TASRTRKTVT CFDLSCNQTV CQPTVYLMAP IQTCVTTKSC LLGLGDQRIQ VVYEKTYCVS
GQLIEGNCFN PLHTIAISQP THTYDIMTLA VHCFFISKKG GTDDTLKIEK QFETLVEKTG
CTENALKGYY ACILGTSSEV VYVPAMDDYR SSEILSRMTT APHGEDHDID PNAISSLRIV
GQLTGKAPST ESSDTVQGIA FAGTPLYTST SILVRKEDPI YLWSPGIIPE GNHSQCDKKT
LPLTWTGFIT LPGEIEKTTQ CTVFCTLSGP GADCEAYSDT GIFNISSPTC LVNRVQRFRG
AEQQVKFVCQ RVDLDITVYC NGVKKVILTK TLVIGQCIYT FTSIFSLMPG VAHSLAVELC
VPGLHGWATI SLLITFCFGW LAIPLLSMII IRFLLIFTYL CSKYSTDSKF KLIIEKVKQE
YQKTMGSMVC EVCQQGCETA KELESHKKSC PHGQCPYCLN PTEATESALQ AHFKVCKLTT
RFQENLKKSL STYEPKRGLY RTLSMFRYKS KCYVGLVWCI LLTMELIVWA ASAETINLEP
GWTDTAHGSG IIPLKTDLEL DFSLPSSATY TYRRELQNPA NEQEKIPFHF QMERQVIHAE
IQHLGHWMDG TFNLKTAFHC YGSCIKYAYP WQTAKCFLEK DFEFETGWGC NPPDCPGVGT
GCTACGVYLD KLRSVGKVYK ILSLKYTRKV CIQLGTEQTC KTIDSNDCLV TTSVKVCMIG
TISKFQPGDT LLFLGPLEEG GMIFKQWCTT TCQFGDPGDI MSTPLGMKCP EHAGSFRKKC
SFATLPSCQY DGNTVSGYQR MIATKDSFQS FNITEPHITT NSLEWVDPDS SLKDHVNLIV
NRDLSFQDLA ENPCQVDLSV SSIDGAWGSG VGFNLVCSVS LTECASFLTS IKACDSAMCY
GSSTANLVRG QNTVHVVGKG GHSGSKFMCC HDKKCSATGL VAAAPHLDRV TGYNQIDTNK
VFDDGAPQCG VHCWFKKSGE WLLGILSGNW MVVAVLIALF IFSLLLFSLC CPRRQNYKKN
K
