GP_PUUMP
ID GP_PUUMP Reviewed; 1148 AA.
AC P41266;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 103.
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 Puumala virus (strain P360).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=39001;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=447135; Myodes glareolus (Bank vole) (Clethrionomys glareolus).
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8266723; DOI=10.1016/0168-1702(93)90019-j;
RA Xiao S.Y., Spik K.W., Li D., Schmaljohn C.S.;
RT "Nucleotide and deduced amino acid sequences of the M and S genome segments
RT of two Puumala virus isolates from Russia.";
RL Virus Res. 30:97-103(1993).
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] {ECO:0007744|PDB:5J81, ECO:0007744|PDB:5J9H}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 659-1106, GLYCOSYLATION AT
RP ASN-937, AND ABSENCE OF GLYCOSYLATION AT ASN-898.
RX PubMed=27783673; DOI=10.1371/journal.ppat.1005948;
RA Willensky S., Bar-Rogovsky H., Bignon E.A., Tischler N.D., Modis Y.,
RA Dessau M.;
RT "Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion
RT Conformation.";
RL PLoS Pathog. 12:e1005948-e1005948(2016).
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). 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}.
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 (By
CC similarity). Homotrimer; forms homotrimer in the post-fusion
CC conformation at acidic pH (PubMed:27783673). Interacts (via C-terminus)
CC with the nucleoprotein (By similarity). {ECO:0000250|UniProtKB:P08668,
CC ECO:0000250|UniProtKB:P27312, ECO:0000269|PubMed:27783673}.
CC -!- SUBCELLULAR LOCATION: [Glycoprotein N]: Virion membrane
CC {ECO:0000250|UniProtKB:P08668}; 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:0000250|UniProtKB:P08668}; 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 (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; L08755; AAC37848.1; -; Unassigned_RNA.
DR PDB; 5J81; X-ray; 1.80 A; A=659-1106.
DR PDB; 5J9H; X-ray; 2.50 A; A=659-1106.
DR PDBsum; 5J81; -.
DR PDBsum; 5J9H; -.
DR SMR; P41266; -.
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:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; 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:0039547; P:suppression by virus of host TRAF activity; 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 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 3D-structure; 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 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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1148
FT /note="Envelopment polyprotein"
FT /id="PRO_0000036828"
FT CHAIN 24..658
FT /note="Glycoprotein N"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036829"
FT CHAIN 659..1148
FT /note="Glycoprotein C"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036830"
FT TOPO_DOM 24..496
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..637
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..1115
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1116..1136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1137..1148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 621..644
FT /note="ITAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00379"
FT ZN_FING 555..575
FT /note="CCHC-type 1"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT ZN_FING 580..601
FT /note="CCHC-type 2"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 526..543
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 598..615
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT REGION 602..613
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT REGION 621..635
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT REGION 767..787
FT /note="Fusion loop"
FT /evidence="ECO:0000269|PubMed:27783673"
FT REGION 1131..1148
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT REGION 1131..1143
FT /note="Binding to the ribonucleoprotein"
FT /evidence="ECO:0000250|UniProtKB:P27312"
FT MOTIF 625..628
FT /note="YxxL"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT SITE 658..659
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 937
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:27783673"
FT DISULFID 34..159
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 68..165
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 117..136
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 141..146
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 183..193
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 218..257
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 386..445
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 390..399
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 415..434
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 462..485
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT DISULFID 745..780
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 749..787
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 761..894
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 775..905
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 790..913
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 816..825
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 833..842
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 873..877
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 979..1009
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1002..1054
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1019..1024
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1055..1060
FT /evidence="ECO:0000250|UniProtKB:P08668"
FT DISULFID 1094..1098
FT /evidence="ECO:0000250|UniProtKB:Q9E006"
FT STRAND 667..669
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 673..675
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 678..680
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 682..690
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 695..701
FT /evidence="ECO:0007829|PDB:5J81"
FT TURN 704..706
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 707..709
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 711..717
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 721..747
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 749..751
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 755..758
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 759..769
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 773..776
FT /evidence="ECO:0007829|PDB:5J9H"
FT STRAND 786..819
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 822..829
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 833..835
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 837..844
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 855..860
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 862..864
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 866..870
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 885..888
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 891..893
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 901..904
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 912..915
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 922..928
FT /evidence="ECO:0007829|PDB:5J81"
FT HELIX 929..932
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 933..936
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 939..943
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 945..951
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 958..965
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 980..993
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 998..1019
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 1024..1043
FT /evidence="ECO:0007829|PDB:5J81"
FT STRAND 1052..1056
FT /evidence="ECO:0007829|PDB:5J81"
SQ SEQUENCE 1148 AA; 126574 MW; 8AC5C727B5087BE4 CRC64;
MGELSPVCLC LLLQGLLLCN TGAARNLNEL KMECPHTIRL GQGLVVGSVE LPSLPIQQVE
TLKLESSCNF DLHTSTAGQQ SFTKWTWEIK GDLAENTQAS STSFQTKSSE VNLRGLCLIP
TLVVETAARM RKTIACYDLS CNQTVCQPTV YLMGPIQTCI TTKSCLLSLG DQRIQVNYEK
TYCVSGQLVE GICFNPIHTM ALSQPSHTYD IMTMMVRCFL VIKKVTSGDS MKIEKNFETL
VQKNGCTANN FQGYYICLIG SSSEPLYVPA LDDYRSAEVL SRMAFAPHGE DHDIEKNAVS
AMRIAGKVTG KAPSTESSDT VQGIAFSGSP LYTSTGVLTS KDDPVYIWAP GIIMEGNHSI
CEKKTLPLTW TGFISLPGEI EKTTQCTVFC TLAGPGADCE AYSETGIFNI SSPTCLINRV
QRFRGSEQQI KFVCQRVDMD ITVYCNGMKK VILTKTLVIG QCIYTFTSIF SLIPGVAHSL
AVELCVPGLH GWATMLLLLT FCFGWVLIPT ITMILLKILI AFAYLCSKYN TDSKFRILIE
KVKREYQKTM GSMVCEVCQY ECETAKELES HRKSCSIGSC PYCLNPSEAT TSALQAHFKV
CKLTSRFQEN LRKSLTVYEP MQGCYRTLSL FRYRSRFFVG LVWCVLLVLE LIVWAASAET
QNLNAGWTDT AHGSGIIPMK TDLELDFSLP SSASYTYRRQ LQNPANEQEK IPFHLQLSKQ
VIHAEIQHLG HWMDATFNLK TAFHCYGSCE KYAYPWQTAG CFIEKDYEYE TGWGCNPPDC
PGVGTGCTAC GVYLDKLKSV GKVFKIVSLR YTRKVCIQLG TEQTCKTVDS NDCLITTSVK
VCLIGTISKF QPSDTLLFLG PLQQGGLIFK QWCTTTCQFG DPGDIMSTPT GMKCPELNGS
FRKKCAFATT PVCQFDGNTI SGYKRMIATK DSFQSFNVTE PHISTSALEW IDPDSSLRDH
INVIVSRDLS FQDLSETPCQ IDLATASIDG AWGSGVGFNL VCTVSLTECS AFLTSIKACD
AAMCYGSTTA NLVRGQNTIH IVGKGGHSGS KFMCCHDTKC SSTGLVAAAP HLDRVTGYNQ
ADSDKIFDDG APECGMSCWF KKSGEWILGV LNGNWMVVAV LVVLLILSIL LFTLCCPRRP
SYRKEHKP
