ID   GP_HANTB                Reviewed;        1133 AA.
AC   P28728;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-1992, sequence version 1.
DT   24-JAN-2024, entry version 101.
DE   RecName: Full=Envelopment polyprotein;
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   Hantaan virus (strain B-1) (Korean hemorrhagic fever virus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC   Orthohantavirus; Orthohantavirus hantanense.
OX   NCBI_TaxID=31617;
OH   NCBI_TaxID=39030; Apodemus agrarius (Eurasian field mouse).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2118626; DOI=10.1093/nar/18.16.4936;
RA   Isegawa Y., Fujiwara Y., Ohshima A., Fukunaga R., Murakami H.,
RA   Yamanishi K., Sokawa Y.;
RT   "Nucleotide sequence of the M genome segment of hemorrhagic fever with
RT   renal syndrome virus strain B-1.";
RL   Nucleic Acids Res. 18:4936-4936(1990).
RN   [2]
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).
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 ITGAV/ITGB3 (By similarity). This
CC       attachment induces virion internalization predominantly through
CC       clathrin-dependent endocytosis (By similarity). May also bind to host
CC       C1QBP for virus entry into the host cell (By similarity). Mediates the
CC       assembly and budding of infectious virus particles through its
CC       interaction with the nucleocapsid protein and the viral genome (By
CC       similarity). May dysregulate normal immune and endothelial cell
CC       responses through an ITAM motif (By similarity). Translocates to
CC       mitochondria, binds to host TUFM and recruits MAP1LC3B (By similarity).
CC       These interactions induce mitochondrial autophagy and therefore
CC       destruction of host MAVS leading to inhibition of type I interferon
CC       (IFN) responses (By similarity). Concomitant breakdown of glycoprotein
CC       N is apparently prevented by the nucleoprotein that may inhibit Gn-
CC       stimulated autophagosome-lysosome fusion (By similarity). Interacts
CC       with the viral genomic RNA (By similarity).
CC       {ECO:0000250|UniProtKB:P08668, ECO:0000250|UniProtKB:P27312}.
CC   -!- FUNCTION: [Glycoprotein C]: Forms homotetramers with glycoprotein N at
CC       the surface of the virion (By similarity). Attaches the virion to host
CC       cell receptors including integrin ITGAV/ITGB3 (By similarity). This
CC       attachment induces virion internalization predominantly through
CC       clathrin-dependent endocytosis (By similarity). May also bind to host
CC       C1QBP for virus entry into the host cell (By similarity). Class II
CC       fusion protein that promotes fusion of viral membrane with host
CC       endosomal membrane after endocytosis of the virion (By similarity).
CC       {ECO:0000250|UniProtKB:P08668}.
CC   -!- SUBUNIT: [Glycoprotein N]: Homodimer (By similarity). Homotetramer;
CC       forms heterotetrameric Gn-Gc spikes in the pre-fusion conformation (By
CC       similarity). Interacts (via C-terminus) with the nucleoprotein (By
CC       similarity). Interacts with host TUFM; this interaction contributes to
CC       the virus-induced degradation of mitochondria by autophagy, which leads
CC       to degradation of host MAVS and inhibition of type I interferon (IFN)
CC       responses (By similarity). Interacts with host MAP1LC3B; this
CC       interaction contributes to the virus-induced degradation of
CC       mitochondria by autophagy, which leads to degradation of host MAVS and
CC       inhibition of type I interferon (IFN) responses (By similarity).
CC       {ECO:0000250|UniProtKB:P08668, ECO:0000250|UniProtKB:P0DTJ1}.
CC   -!- SUBUNIT: [Glycoprotein C]: Homodimer. Homotetramer; forms
CC       heterotetrameric Gn-Gc spikes in the pre-fusion conformation.
CC       Homotrimer; forms homotrimer in the post-fusion conformation at acidic
CC       pH (By similarity). Interacts (via C-terminus) with the nucleoprotein
CC       (By similarity). {ECO:0000250|UniProtKB:P08668,
CC       ECO:0000250|UniProtKB:P27312}.
CC   -!- SUBCELLULAR LOCATION: [Glycoprotein N]: Virion membrane
CC       {ECO:0000250|UniProtKB:P08668}; Multi-pass membrane protein. Host cell
CC       surface {ECO:0000250|UniProtKB:P08668}. Host Golgi apparatus membrane
CC       {ECO:0000250|UniProtKB:P08668}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P08668}. Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P08668}; Multi-pass membrane protein
CC       {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:0000250|UniProtKB:P08668}; Single-pass type I membrane protein.
CC       Host cell surface {ECO:0000250|UniProtKB:P08668}. Host Golgi apparatus
CC       membrane {ECO:0000250|UniProtKB:P08668}; Single-pass type I membrane
CC       protein {ECO:0000250|UniProtKB:P08668}. Host endoplasmic reticulum
CC       membrane {ECO:0000250|UniProtKB:P08668}; Single-pass type I membrane
CC       protein {ECO:0000250|UniProtKB:P08668}. Note=Budding probably takes
CC       place at the host Golgi (Probable). Glycoprotein C cytoplasmic tail is
CC       important for efficient Golgi localization (By similarity).
CC       {ECO:0000250|UniProtKB:P08668, 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       (By similarity). The C-terminus of the cytoplasmic tail is involved in
CC       binding to the viral genome and the nucleocapsid (By similarity).
CC       Contains 2 contiguous zinc-fingers (By similarity).
CC       {ECO:0000250|UniProtKB:P08668, ECO:0000250|UniProtKB:P0DTJ1,
CC       ECO:0000250|UniProtKB:P27312, ECO:0000250|UniProtKB:Q9E006}.
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   -!- SIMILARITY: Belongs to the hantavirus envelope glycoprotein family.
CC       {ECO:0000305}.
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DR   EMBL; X53861; CAA37854.1; -; mRNA.
DR   PIR; S12597; S12597.
DR   SMR; P28728; -.
DR   GlyCosmos; P28728; 5 sites, No reported glycans.
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:0016020; C: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:0039527; P:disruption by virus of host TRAF-mediated signal transduction; 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:0007165; P:signal transduction; IEA:InterPro.
DR   GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.8.1320; -; 1.
DR   InterPro; IPR016402; Envelope_glycoprot_Hantavirus.
DR   InterPro; IPR048791; Gc_C_bunya.
DR   InterPro; IPR048790; Gn-B_hanta.
DR   InterPro; IPR002532; Hanta_Gc_N.
DR   InterPro; IPR002534; Hanta_Gn-H.
DR   InterPro; IPR012316; ITAM_motif_hantavir-typ.
DR   Pfam; PF20682; Hanta_Gc_C; 1.
DR   Pfam; PF01561; Hanta_Gc_N; 1.
DR   Pfam; PF20679; Hanta_Gn-B; 1.
DR   Pfam; PF01567; Hanta_Gn-H; 1.
DR   Pfam; PF10538; ITAM_Cys-rich; 1.
DR   PIRSF; PIRSF003945; M_poly_HantaV; 1.
DR   PROSITE; PS51056; ITAM_2; 1.
PE   2: Evidence at transcript level;
KW   Disulfide bond; 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 RLR pathway by virus; Inhibition of host TRAFs by virus;
KW   Membrane; Metal-binding; Phosphoprotein; Repeat; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell; Zinc; Zinc-finger.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..1133
FT                   /note="Envelopment polyprotein"
FT                   /id="PRO_0000036806"
FT   CHAIN           17..646
FT                   /note="Glycoprotein N"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036807"
FT   CHAIN           647..1133
FT                   /note="Glycoprotein C"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036808"
FT   TOPO_DOM        17..485
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        486..506
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        507..626
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        627..647
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        648..1103
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1104..1124
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1125..1133
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          609..632
FT                   /note="ITAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT   ZN_FING         543..563
FT                   /note="CCHC-type 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   ZN_FING         568..589
FT                   /note="CCHC-type 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   REGION          514..531
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   REGION          586..603
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   REGION          590..601
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   REGION          609..623
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   REGION          755..775
FT                   /note="Fusion loop"
FT                   /evidence="ECO:0000250|UniProtKB:P41266"
FT   REGION          1120..1133
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   MOTIF           613..616
FT                   /note="YxxL"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   SITE            646..647
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        233
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        345
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        926
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        27..149
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        61..155
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        173..183
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        208..245
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        232..349
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        374..433
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        378..387
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        403..422
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        450..473
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        733..768
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        737..775
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        749..883
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        763..894
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        778..902
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        804..813
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        821..830
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        861..865
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        968..998
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        991..1043
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1008..1013
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1044..1049
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1083..1087
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
SQ   SEQUENCE   1133 AA;  125909 MW;  0A25160A32862FD6 CRC64;
     MWSLLLLAAL VGQGFALKNV FDMRIQCPHS VNFGETSVSG YTELPPLSLQ EAEQLVPESS
     CNMDNHQSLS TINKLTKVIW RKKANQESAN QNSFEVVESE VSFKGLCMLK HRMVEESYRN
     RRSVIYYDLA GNSTFCKPTV YMIVPIHACN MMKSCLIGLG PYRIQVVYER TYCTTGILTE
     GKCFVPDKAV VSALKRGMYA IASIETICFF IHQKWNKYKI VTAITSAMGS KCNNTDTKVQ
     GYYICIIGGN SAPVYAPAGE DFRAMEVFSG IITSPHGEDH DLPGEEIATY HISGQIEAKI
     PHTVSSKNLR LAAFAGIPSY SSTSILAASE DGRFIFSPGL FPNLNQSVCD NNALPLIWRG
     LIDLTGYYEA VHPCNVFCVL SGPGASCEAF SEGGIFNITS PMCLVSKQNR FRAAEQQISF
     VCQRVDMDII VYCNGQKKTI LTKTLVIGQC IYTITSLFSL LPGVAHSIAI ELCVPGFHGW
     ATAALLITFC FGWVLIPACT LAILLVLKFF ANILHTSNQE NRFKAILRKI KEEFEKRKGS
     MVCEICKYEC ETLKELKAHN LSCVQGECPY CFTHCEPTET AIQAHYKVCQ ATHRFREDLK
     KTVTPQNIGP GCYRTLNLFR YKSRCYILTM WTLLLIIESI LWAASAAEIP LVPLWTDNAH
     GVGSVPMHTD LELDFSLPSS SKYTYKRHLT NPVNDQQSVS LHIEIESQGI GADVHHLGHW
     YDARLNLKTS FHCYGACTKY QYPWHTAKCH FEKDYEYENS WACNPPDCPG VGTGCTACGL
     YLDQLKPVGT AFKIISVRYS RKVCVQFGEE HLCKTIDMND CFVTRHAKIC IIGTVSKFSQ
     GDTLLFLGPM EGGGIIFKHW CTSTCHFGDP RDVMGPKDKP FICPEFPGQF RKKCNFATTP
     VCEYDGNIIS GYKKVLATID SFQSFNTSNI HFTDERIEWR DPDGMLRDHI NIVISKDIDF
     ENLAENPCKV GLQAANIEGA WGSGVGFTLT CQVSLTECPT FLTSIKACDM AICYGAESVT
     LSRGQNTVKI TGKGGHSGSS FKCCHGKECS STGLQASAPH LDKVNGISEL ENEKVYDDGA
     PECGVTCWFK KSGEWVMGII NGNWVVLIVL CVLLLFSLIL LSILCPVRKH KKS
//