ID   GP_PHV                  Reviewed;        1142 AA.
AC   P27315;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   24-JAN-2024, entry version 104.
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   Prospect Hill virus (PHV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC   Orthohantavirus.
OX   NCBI_TaxID=3052492;
OH   NCBI_TaxID=10058; Microtus pennsylvanicus (Meadow vole).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1840609; DOI=10.1099/0022-1317-72-8-1845;
RA   Parrington M.A., Lee P.W., Kang C.Y.;
RT   "Molecular characterization of the Prospect Hill virus M RNA segment: a
RT   comparison with the M RNA segments of other hantaviruses.";
RL   J. Gen. Virol. 72:1845-1854(1991).
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).
RN   [3]
RP   STRUCTURE BY NMR OF 548-602, AND DOMAIN (GLYCOPROTEIN N).
RX   PubMed=22203819; DOI=10.3389/fmicb.2011.00251;
RA   Estrada D.F., Conner M., Jeor S.C., Guzman R.N.;
RT   "The Structure of the Hantavirus Zinc Finger Domain is Conserved and
RT   Represents the Only Natively Folded Region of the Gn Cytoplasmic Tail.";
RL   Front. Microbiol. 2:251-251(2011).
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 (By similarity). May
CC       dysregulate normal immune and endothelial cell responses through an
CC       ITAM motif (By similarity). Translocates to mitochondria, binds to host
CC       TUFM and 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 (By
CC       similarity). {ECO:0000250|UniProtKB:P08668,
CC       ECO:0000250|UniProtKB:P27312, 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 (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 (PubMed:22203819).
CC       {ECO:0000250|UniProtKB:P08668, ECO:0000250|UniProtKB:P0DTJ1,
CC       ECO:0000250|UniProtKB:P27312, ECO:0000269|PubMed:22203819}.
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: This virus is non-pathogenic. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the hantavirus envelope glycoprotein family.
CC       {ECO:0000305}.
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DR   EMBL; X55129; CAA38922.1; -; mRNA.
DR   PIR; JQ1380; GNVUPH.
DR   SMR; P27315; -.
DR   GlyCosmos; P27315; 4 sites, No reported glycans.
DR   Proteomes; UP000242194; 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:0016020; C:membrane; 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: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:0046718; P:viral entry into host cell; 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   1: Evidence at protein 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 immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus entry into host cell;
KW   Zinc; Zinc-finger.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..1142
FT                   /note="Envelopment polyprotein"
FT                   /id="PRO_0000036818"
FT   CHAIN           22..654
FT                   /note="Glycoprotein N"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036819"
FT   CHAIN           655..1142
FT                   /note="Glycoprotein C"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000036820"
FT   TOPO_DOM        22..489
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        490..510
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        511..633
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        634..654
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        655..1110
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1111..1131
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1132..1142
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          617..640
FT                   /note="ITAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT   ZN_FING         551..571
FT                   /note="CCHC-type 1"
FT                   /evidence="ECO:0000269|PubMed:22203819"
FT   ZN_FING         576..597
FT                   /note="CCHC-type 2"
FT                   /evidence="ECO:0000269|PubMed:22203819"
FT   REGION          522..539
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   REGION          594..611
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   REGION          598..609
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   REGION          617..631
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   REGION          763..783
FT                   /note="Fusion loop"
FT                   /evidence="ECO:0000250|UniProtKB:P41266"
FT   REGION          1127..1142
FT                   /note="Binding to the ribonucleoprotein"
FT                   /evidence="ECO:0000250|UniProtKB:P27312"
FT   MOTIF           621..624
FT                   /note="YxxL"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   SITE            654..655
FT                   /note="Cleavage; by host signal peptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        933
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        31..156
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        65..162
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        114..133
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        138..143
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        180..190
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        215..253
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        382..441
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        386..395
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        411..430
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        458..481
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
FT   DISULFID        741..776
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        745..783
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        757..890
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        771..901
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        786..909
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        812..821
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        829..838
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        869..873
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        975..1005
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        998..1050
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1015..1020
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1051..1056
FT                   /evidence="ECO:0000250|UniProtKB:P08668"
FT   DISULFID        1090..1094
FT                   /evidence="ECO:0000250|UniProtKB:Q9E006"
SQ   SEQUENCE   1142 AA;  125686 MW;  CD3BAD69F078C8B9 CRC64;
     MSKFCLCLSL LGVLLLQVCD TRSLLELKIE CPHTVGLGQG LVIGTVDLNP VPVESVSTLK
     LESSCNFDVH TSSATQQAVT KWTWEKKADT AETAKAASTT FQSKSTELNL RGLCVIPTLV
     LETANKLRKT VTCYDLSCNQ TACIPTVYLI APIHTCVTTK SCLLGLGTQR IQVTYEKTYC
     VSGQLVEGTC FNPIHTMALS QPSHTYDIVT IPVRCFFIAK KTNDDTLKIE KQFETILEKS
     GCTAANIKGY YVCFLGATSE PIFVPTMDDF RASQILSDMA ISPHGEDHDS ALSSVSTFRI
     AGKLSGKAPS TESSDTVQGV AFSGHPLYTS LSVLASKEDP VYIWSPGIIP ERNHTVCDKK
     TLPLTWTGYL PLPGGIEKTT QCTIFCTLAG PGADCEAYSD TGIFNISSPT CLINRVQRFR
     GAEQQIKFVC QRVDLDIVVY CNGMKKVILT KTLVIGQCIY TFTSVFSLMP GIAHSLAVEL
     CVPGIHGWST IALLATFCFG WLLIPIISLV SIKIMLLFAY MCSKYSNDSK FRLLIEKVKQ
     EYQKTMGSMV CEVCQQECEM AKELESHKKS CPNGMCPYCM NPTESTESAL QAHFKVCKLT
     TRFQENLRKS LNPYEPKRGC YRTLSVFRYR SRCFVGLVWC ILLVLELVIW AASADTVEIK
     TGWTDTAHGA GVIPLKSDLE LDFSLPSSAT YIYRRDLQNP ANEQERIPFH FQLQRQVIHA
     EIQNLGHWMD GTFNLKTSFH CYGACEKYAY PWQTAKCFLE KDYEFETGWG CNPGDCPGVG
     TGCTACGVYL DKLRSVGKVF KVISLKFTRR VCIQLGSEQS CKTIDSNDCL MTTSVKVCMI
     GTVSKFQPGD TLLFLGPLEE GGIIFKQWCT TTCHFGDPGD IMSTPQGMQC PEHTGAFRKK
     CAFATMPTCE YDGNTLSGYQ RMLATRDSFQ SFNITEPHIT SNSLEWVDPD SSLKDHINLV
     VNRDVSFQDL SENPCQVGVA VSSIDGAWGS GVGFNLVCSV SLTECASFLT SIKACDAAMC
     YGATTANLVR GQNTVHILGK GGHSGSKFMC CHSTECSSTG LTAAAPHLDR VTGYNVIDND
     KVFDDGSPEC GVHCWFKKSG EWLMGILSGN WMVVAVLVVL LILSIFLFSL CCPRRVVHKK
     SS
//