AC   MF_04084;
DC   Protein; auto
TR   HAMAP; MF_04084; -; 1; level=0
XX
Names: ARENA_GPC
XX
ID   GLYC
DE   RecName: Full=Pre-glycoprotein polyprotein GP complex;
DE            Short=Pre-GP-C;
DE   Contains:
DE     RecName: Full=Stable signal peptide;
DE              Short=SSP;
DE   Contains:
DE     RecName: Full=Glycoprotein G1;
DE              Short=GP1;
DE   Contains:
DE     RecName: Full=Glycoprotein G2;
DE              Short=GP2;
GN   Name=GPC;
XX
CC   -!- FUNCTION: [Stable signal peptide]: Functions as a cleaved signal
CC       peptide that is retained as the third component of the GP complex (GP-
CC       C). Helps to stabilize the spike complex in its native conformation.
CC       The SSP is required for efficient glycoprotein expression, post-
CC       translational maturation cleavage of G1 and G2, glycoprotein transport
CC       to the cell surface plasma membrane, formation of infectious virus
CC       particles, and acid pH-dependent glycoprotein-mediated cell fusion.
case <OS:Mammarenavirus lassaense>
CC   -!- FUNCTION: [Glycoprotein G1]: Forms the virion spikes together with
CC       glycoprotein G2. The glycoprotein spike trimers are connected to the
CC       underlying matrix. Interacts with the host receptor. Mediates virus
CC       attachment to the host primary receptor alpha-dystroglycan DAG1 (alpha-
CC       DG) at the cell surface. This attachment induces virion internalization
CC       apparently through macropinocytosis. Following endocytosis, there is a
CC       pH-dependent switch from binding DAG1 to the host lysosomal receptor
CC       LAMP1. This latter binding triggers the dissociation of GP1, exposing
CC       the fusion subunit, GP2, such that fusion can occur. Down-modulates
CC       host DAG1.
else
CC   -!- FUNCTION: [Glycoprotein G1]: Forms the virion spikes together with
CC       glycoprotein G2. The glycoprotein spike trimers are connected to the
CC       underlying matrix. Interacts with the host receptor leading to virus
CC       endocytosis.
end case
CC   -!- FUNCTION: [Glycoprotein G2]: Forms the virion spikes together with
CC       glycoprotein G1. The glycoprotein spike trimers are connected to the
CC       underlying matrix. Class I viral fusion protein that directs fusion of
CC       viral and host endosomal membranes, leading to delivery of the
CC       nucleocapsid into the cytoplasm. Membrane fusion is mediated by
CC       irreversible conformational changes induced by acidification.
CC   -!- SUBUNIT: [Stable signal peptide]: Interacts with glycoprotein G2. Part
CC       of the GP complex (GP-C) together with glycoprotein G1 and glycoprotein
CC       G2. The GP-complex interacts with protein Z, which interacts with
CC       ribonucleocapsid; these interactions may induce virion budding.
case <OS:Mammarenavirus lassaense>
CC   -!- SUBUNIT: [Glycoprotein G1]: Homotrimer; disulfide-linked. In pre-fusion
CC       state, G1 homotrimers bind G2 homotrimers via ionic interactions. Part
CC       of the GP complex (GP-C) together with glycoprotein G2 and the stable
CC       signal peptide. Interacts with the primary host receptor DAG1 on the
CC       cell surface; this interaction occurs at pH 8.0 but not at pH 6.0 and
CC       below. Upon virus internalization and at endosomal pH, interacts with
CC       the host lysosomal protein LAMP1; this interaction mediates G1
CC       dissociation from GP-C and membrane fusion. The GP-complex interacts
CC       with protein Z, which interacts with ribonucleocapsid; these
CC       interactions may induce virion budding.
else
CC   -!- SUBUNIT: [Glycoprotein G1]: Homotrimer; disulfide-linked. In pre-fusion
CC       state, G1 homotrimers bind G2 homotrimers via ionic interactions. Part
CC       of the GP complex (GP-C) together with glycoprotein G2 and the stable
CC       signal peptide. The GP-complex interacts with protein Z, which
CC       interacts with ribonucleocapsid; these interactions may induce virion
CC       budding.
end case
CC   -!- SUBUNIT: [Glycoprotein G2]: Homotrimer. Interacts with the stable
CC       signal peptide. In pre-fusion state, G2 homotrimers bind G1 homotrimers
CC       via ionic interactions. Part of the GP complex (GP-C) together with
CC       glycoprotein G1 and the stable signal peptide. Acidification in the
CC       endosome triggers rearrangements, which ultimately leads to a 6 helix
CC       bundle formed by the two heptad repeat domains (HR1 and HR2) in post-
CC       fusion state. The GP-complex interacts with protein Z, which interacts
CC       with ribonucleocapsid; these interactions may induce virion budding.
CC   -!- SUBCELLULAR LOCATION: [Stable signal peptide]: Virion membrane; Single-
CC       pass type II membrane protein. Host endoplasmic reticulum membrane;
CC       Single-pass type II membrane protein. Host Golgi apparatus membrane;
CC       Single-pass type II membrane protein. Host cell membrane ; Single-pass
CC       type II membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Glycoprotein G1]: Virion membrane; Peripheral
CC       membrane protein. Host endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Host Golgi apparatus membrane; Peripheral membrane
CC       protein. Host cell membrane; Peripheral membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Glycoprotein G2]: Virion membrane; Single-pass
CC       membrane protein. Host endoplasmic reticulum membrane; Single-pass
CC       membrane protein. Host Golgi apparatus membrane; Single-pass membrane
CC       protein. Host cell membrane; Single-pass membrane protein. Note=Binding
CC       to the stable signal peptide masks endogenous ER localization signals
CC       in the cytoplasmic domain of G2 to ensure that only the fully
CC       assembled, tripartite GP complex is transported for virion assembly.
CC   -!- DOMAIN: [Stable signal peptide]: The N-terminus is localized at the
CC       extracellular side of the GP-C, with a part embedded in the membrane
CC       probably.
case <OS:Mammarenavirus lassaense> and <FTGroup:1>
CC   -!- DOMAIN: [Glycoprotein G1]: Upon protonation in a weak acidic
CC       environment, the histidine triad involved in host LAMP1 binding
CC       inhibits pre-mature triggering of the spike, an inhibition that LAMP1
CC       overrides.
end case
CC   -!- DOMAIN: [Glycoprotein G2]: Contains 1 fusion peptide at the N-terminus,
CC       2 heptad repeats domains HR1 and HR2 and, at the C-terminus, a
CC       cytoplasmic domain that plays a role in ER location. Also contains a
CC       zinc-binding domain that allows SSP retention in the GPC complex by
CC       accepting a cysteine from SSP as the fourth ligand.
CC   -!- PTM: [Pre-glycoprotein polyprotein GP complex]: Specific enzymatic
CC       cleavages in vivo yield mature proteins. GP-C polyprotein is cleaved in
CC       the endoplasmic reticulum by the host protease MBTPS1. Only cleaved
CC       glycoprotein is incorporated into virions. The SSP remains stably
CC       associated with the GP complex following cleavage by signal peptidase.
CC   -!- SIMILARITY: Belongs to the arenaviridae GPC protein family.
XX
DR   Pfam; PF00798; Arena_glycoprot; 1; trigger=no
DR   PIRSF; PIRSF004028; GPC_ArenaV; 1; trigger=no
DR   General; Transmembrane; -; 3; trigger=no
XX
KW   Disulfide bond
KW   Fusion of virus membrane with host endosomal membrane
KW   Fusion of virus membrane with host membrane
KW   Glycoprotein
KW   Host cell membrane
KW   Host endoplasmic reticulum
KW   Host Golgi apparatus
KW   Host membrane
KW   Host-virus interaction
KW   Lipoprotein
KW   Membrane
KW   Metal-binding
KW   Myristate
KW   Transmembrane
KW   Transmembrane helix
KW   Viral attachment to host cell
KW   Viral envelope protein
KW   Viral penetration into host cytoplasm
KW   Virion
KW   Virus endocytosis by host
KW   Virus entry into host cell
KW   Zinc
XX
GO   GO:0020002; C:host cell plasma membrane
GO   GO:0016020; C:membrane
GO   GO:0019031; C:viral envelope
GO   GO:0055036; C:virion membrane
GO   GO:0039654; P:fusion of virus membrane with host endosome membrane
GO   GO:0019065; P:receptor-mediated endocytosis of virus by host cell
GO   GO:0019062; P:virion attachment to host cell
XX
FT   From: GLYC_LASSJ (P08669)
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT   Condition: M
FT   CHAIN           2..Cter
FT                   /note="Pre-glycoprotein polyprotein GP complex"
FT   CHAIN           2..58
FT                   /note="Stable signal peptide"
FT   CHAIN           59..259
FT                   /note="Glycoprotein G1"
FT   CHAIN           260..Cter
FT                   /note="Glycoprotein G2"
FT   TOPO_DOM        2..17
FT                   /note="Extracellular"
FT   TRANSMEM        18..33
FT                   /note="Helical"
FT   TOPO_DOM        34..58
FT                   /note="Cytoplasmic"
FT   TOPO_DOM        59..432
FT                   /note="Extracellular"
FT   TRANSMEM        433..453
FT                   /note="Helical"
FT   TOPO_DOM        454..Cter
FT                   /note="Cytoplasmic"
FT   SITE            58..59
FT                   /note="Cleavage; by host signal peptidase"
FT   SITE            259..260
FT                   /note="Cleavage; by host MBTPS1"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT   Condition: G
FT   REGION          258..294
FT                   /note="Fusion"
FT                   /evidence="ECO:0000269|PubMed:28572385,
FT   REGION          295..363
FT                   /note="HR1"
FT   REGION          368..431
FT                   /note="HR2"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        89
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        99
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        109
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        224
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        373
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   Condition: N
FT   DISULFID        86..231
FT   Condition: C-x*-C
FT   DISULFID        118..155
FT   Condition: C-x*-C
FT   DISULFID        180..212
FT   Condition: C-x*-C
FT   DISULFID        180..212
FT   Condition: C-x*-C
FT   DISULFID        279..292
FT   Condition: C-x*-C
FT   DISULFID        301..310
FT   Condition: C-x*-C
FT   DISULFID        364..385
FT   Condition: C-x*-C
case <OS:Mammarenavirus lassaense>
FT   REGION          188..216
FT                   /note="Binding to the host receptor LAMP1"
FT   SITE            92
FT                   /note="Binding to the host receptor LAMP1"
FT   Group: 1; Condition: H
FT   SITE            93
FT                   /note="Binding to the host receptor LAMP1"
FT   Group: 1; Condition: H
FT   SITE            230
FT                   /note="Binding to the host receptor LAMP1"
FT   Group: 1; Condition: H
end case
FT   From: GLYC_JUNIN (P26313)
FT   BINDING         57
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   Condition: C
FT   BINDING         447
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   Condition: H
FT   BINDING         449
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   Condition: H
FT   BINDING         455
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   Condition: C
FT   BINDING         459
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   Condition: H
FT   BINDING         467
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   Condition: C
FT   BINDING         469
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   Condition: C
FT   BINDING         485
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   Condition: H
XX
Size: 479-518;
Related: None;
Template: P19240; P08669; P26313; P09991;
Scope:
 Viruses; Arenaviridae
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.10 2023/07/04
//