P03316

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003723 RNA binding	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven (KW-0694 RNA-binding) transfer of RNA binding. The claim belongs to the capsid chain (PRO_0000041321), which binds the genomic RNA and packages it into the T=4 nucleocapsid. Correct and central to the capsid's structural role. Reason: Genome binding by the alphavirus capsid protein is a curated, publication-supported activity in the UniProt record, and the crystal structure of the Sindbis core protein was solved precisely as "the coat surrounding the genomic RNA". The term is the right level: no source available here establishes a selectivity (e.g. single-stranded vs duplex, or a defined packaging signal) that would license a more specific child, and the GO term is not merely an uninformative ancestor of anything else annotated on this entry. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation PMID:1944569 protein comprising the coat surrounding the genomic RNA has been determined
GO:0004252 serine-type endopeptidase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO assignment of serine-type endopeptidase activity from the peptidase S3 signature. This is the capsid protein's C-terminal chymotrypsin-like protease domain, which cleaves the Trp-\|-Ser bond releasing the capsid from the nascent polyprotein (EC 3.4.21.90). Reason: The activity is independently established by the crystal structure of the Sindbis core protein, which resolves a chymotrypsin-like fold with a canonical His/Asp/Ser triad and the C-terminal tryptophan still occupying the P1 site after cis cleavage, and by the curated catalytic-activity statement in UniProt. Both the catalytic class (serine-type) and the endopeptidase mode (internal peptide-bond cleavage in cis) are supported, so this is the right term rather than a broader peptidase term. Supporting Evidence: PMID:1944569 chymotrypsin-like serine proteinases with catalytic residues His 141, Asp 163 PMID:1944569 autocatalytic cis cleavage of the capsid protein, thus rendering the proteinase file:SINDV/P03316/P03316-uniprot.txt Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-\|- Ser- bond.
GO:0005198 structural molecule activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO assignment of the generic structural-molecule term from the alphavirus core protein signature. The claim is true of the capsid, E2 and E1 chains, all of which are stoichiometric building blocks of the virion, but the term sits two levels above what the evidence supports. Reason: The evidence is specifically that these chains are constituents of a virus particle - 240 copies of the capsid protein in a T=4 shell, and 240 copies each of E1 and E2 in the complementary envelope lattice resolved by cryo-electron microscopy. GO:0039660 structural constituent of virion is the descendant that says this, and it is supported for three of the five chains, so refine rather than keep the uninformative parent. Proposed replacements: structural constituent of virion Supporting Evidence: PMID:3829124 appear as columnar trimers arranged on a T=4 lattice. The lipid bilayer of the file:SINDV/P03316/P03316-uniprot.txt Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers
GO:0005515 protein binding	IPI PMID:33673546 The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR S...	MODIFY	Summary: Bare protein binding recorded from the capsid-IRAK1 interaction identified by BioID2 proximity labelling and confirmed biochemically. The interaction is real and functionally consequential, but GO:0005515 conveys nothing about it. Reason: Per the protein-binding policy, a GO:0005515 row whose cited paper supports a more informative molecular function should be modified rather than removed. The partner P51617 is IRAK1, a serine/threonine kinase, and the paper's point is that capsid binding to that kinase blocks its signalling output; GO:0019901 protein kinase binding states what was shown and keeps the molecular function informative without inventing an activity the interaction data do not establish. Proposed replacements: protein kinase binding Supporting Evidence: PMID:33673546 between the alphaviral capsid protein and the host IRAK1 protein file:SINDV/P03316/P03316-uniprot.txt Interacts with host IRAK1; the interaction leads to inhibition of IRAK1-dependent signaling (PubMed:33673546)
GO:0006508 proteolysis	IEA GO_REF:0000120	MODIFY	Summary: Generic proteolysis, from the peptidase signature plus the Protease keyword. True, but the proteolysis this protein performs is of a very particular kind: a single cis cleavage of its own nascent chain, after which the protease is left inactive with its C-terminal tryptophan in the P1 pocket. Reason: Two descendants say what GO:0006508 leaves unsaid and are both directly supported: GO:0016540 protein autoprocessing (the capsid cleaves itself out of the polyprotein, in cis, and is then catalytically dead) and GO:0019082 viral protein processing (the substrate is the viral structural polyprotein). Keeping the bare parent would be keeping a term less precise than the evidence allows. Proposed replacements: protein autoprocessing viral protein processing Supporting Evidence: PMID:1944569 autocatalytic cis cleavage of the capsid protein, thus rendering the proteinase file:SINDV/P03316/P03316-uniprot.txt The C-terminus functions as a protease during translation to cleave itself from the translating structural polyprotein (PubMed:1944569)
GO:0006811 monoatomic ion transport	IEA GO_REF:0000043	TOO GENERAL	Summary: Keyword-driven ion transport from KW-0406, reflecting the 6K viroporin. The claim is sound but this row is the bare ancestor of the monoatomic ion transmembrane transport row annotated on the same entry from the paired keyword KW-0407. Reason: GO:0034220 monoatomic ion transmembrane transport, accepted elsewhere in this review, is a descendant of GO:0006811 and entails it. Nothing about 6K's activity is captured by "ion transport" that the transmembrane term does not already capture - all of the evidence is about conductance across a membrane - so the parent row adds no information. This judges the term, not the keyword mapping or the underlying biology. Supporting Evidence: PMID:36191050 6K has been shown to form cation-selective ion channels when inserted into planar lipid bilayers
GO:0008233 peptidase activity	IEA GO_REF:0000043	TOO GENERAL	Summary: Keyword-driven peptidase activity from KW-0645 (Protease). True of the capsid chain, but a strict ancestor of the accepted serine-type endopeptidase activity. Reason: GO:0004252 serine-type endopeptidase activity is accepted in this review and entails peptidase activity. The catalytic class and mechanism are both known from the crystal structure, so there is no residual uncertainty that the broad term would be recording. Supporting Evidence: PMID:1944569 chymotrypsin-like serine proteinases with catalytic residues His 141, Asp 163
GO:0008236 serine-type peptidase activity	IEA GO_REF:0000043	TOO GENERAL	Summary: Keyword-driven serine-type peptidase activity from KW-0720 (Serine protease). Correct catalytic class, but an ancestor of the accepted serine-type endopeptidase activity term. Reason: GO:0004252 serine-type endopeptidase activity, accepted here, entails this term. The endopeptidase mode is established (internal Trp-\|-Ser bond cleaved in cis), so the parent carries no additional claim. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-\|- Ser- bond.
GO:0015267 channel activity	IEA GO_REF:0000043	MODIFY	Summary: Keyword-driven channel activity from KW-1182 (Viral ion channel), belonging to the 6K chain (PRO_0000041324). The underlying claim is that 6K is a viroporin; the evidence is permeabilization of bacterial and mammalian membranes, cation-selective channels in planar bilayers, functional complementation by the HIV-1 Vpu channel helix, and inhibition of virus release by the Vpu channel blocker HMA. Reason: The keyword mapping stops at the branch root, but every line of evidence is about ion conductance specifically, so GO:0005216 monoatomic ion channel activity is the supported descendant and matches the monoatomic ion transmembrane transport process row on the same entry. A caveat belongs on the record rather than on the action: direct expression of 6K cRNA in Xenopus oocytes found no intrinsic channel conductance, the measured currents being endogenous oocyte channels upregulated downstream of ER calcium-store depletion, and the oligomeric state and conduction mechanism of 6K are still unresolved. The planar-bilayer and pharmacological evidence nevertheless support a channel, and ion selectivity is reported as weak, so a selectivity-specific child would overreach. Proposed replacements: monoatomic ion channel activity Supporting Evidence: PMID:36191050 6K has been shown to form cation-selective ion channels when inserted into planar lipid bilayers PMID:36191050 significantly reduces SINV release, suggesting that the ion channel activity of file:SINDV/P03316/P03316-uniprot.txt The channel activity is blocked by 5-N, N- PMID:17483865 Although no intrinsic channel
GO:0016787 hydrolase activity	IEA GO_REF:0000043	TOO GENERAL	Summary: Keyword-driven hydrolase activity from KW-0378. True of the capsid protease but the most distant ancestor of the accepted serine-type endopeptidase activity. Reason: Entailed by GO:0004252, which is accepted in this review. "Hydrolase activity" on a protein whose only known catalytic event is a single autoproteolytic cleavage conveys nothing additional. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-\|- Ser- bond.
GO:0019028 viral capsid	IEA GO_REF:0000120	ACCEPT	Summary: Viral capsid location for the capsid chain, from the alphavirus core protein signature plus KW-0167. Correct: 240 copies of the capsid protein form the nucleocapsid shell enclosing the genome. Reason: Although the more specific GO:0039619 T=4 icosahedral viral capsid is also annotated on this entry and is a descendant of this term, "viral capsid" is not a contentless ancestor: it asserts that the protein is part of the proteinaceous genome shell, which is the central structural claim about this chain and is what distinguishes it from the envelope chains of the same polyprotein. Keeping both is redundancy of the harmless kind rather than a defect. Supporting Evidence: PMID:1944569 protein comprising the coat surrounding the genomic RNA has been determined file:SINDV/P03316/P03316-uniprot.txt Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein
GO:0019031 viral envelope	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven viral envelope location from KW-0261 (Viral envelope protein), belonging to the E1, E2 and 6K chains, which are the integral components of the virion's lipid bilayer and its 80 trimeric spikes. Reason: Directly supported by the cryo-EM organization of the particle, in which the spike trimers sit on a polyhedral lipid bilayer surrounding the nucleocapsid, and by the detection of 6K in purified virions. GO:0055036 virion membrane, also annotated here, is not a descendant of this term in GO, so the two rows are complementary rather than parent and child. Supporting Evidence: PMID:3829124 virus envelope is polyhedral and surrounds a smooth T=3 nucleocapsid. PMID:2408229 that the 6K protein can be detected in
GO:0019062 virion attachment to host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven attachment term from KW-1161 (Viral attachment to host cell). The claim belongs to E2 (PRO_0000041323), the receptor-binding subunit of the spike, and is independently supported by both the binding-defective E2 insertion mutants and the later identification of VLDLR/ApoER2 as receptors for the Sindbis E2-E1 spike. Reason: Attachment is one of the two entry functions this polyprotein performs (the other being E1-mediated fusion), and the keyword mapping lands on exactly the right process. The more specific GO:0098670 is also annotated and accepted, but "virion attachment to host cell" remains a substantive claim about E2 rather than an empty ancestor. Supporting Evidence: PMID:7684466 NB2 were defective for binding to CEF and BHK-21 cells. PMID:34929721 eastern equine encephalitis virus and Sindbis virus interact with the
GO:0019062 virion attachment to host cell	IMP PMID:7684466 Sindbis virus attachment: isolation and characterization of ...	ACCEPT	Summary: CACAO row. Dubuisson and Rice built random-insertion libraries across the PE2 and E1 genes of a full-length Sindbis cDNA clone, depleted binding-competent virus by serial adsorption to chicken embryo fibroblast monolayers at 4 degrees C, and recovered binding-defective mutants. Three were characterized: NB1 and NB12 carry insertions near the PE2 cleavage site (blocking pE2 cleavage completely and partially, respectively) and NB2 carries an insertion between E2 residues 69 and 74. NB1 and NB2 are defective for binding to CEF and BHK-21 cells while assembling and releasing particles normally, and mild trypsin digestion of NB1 virions cleaves pE2 and partially restores binding. Reason: This is a CACAO annotation and it holds up on every axis. The protein is right (the mutations are in pE2/E2, chains of this entry); the assay is a direct cell-binding measurement, not a downstream phenotype, so the evidence code IMP fits the mutant-based design; and the granularity is exactly right - the paper establishes that attachment requires pE2 cleavage and the E2 N-terminal region but does not identify a receptor, and the row correspondingly stops at GO:0019062 rather than claiming the receptor-mediated child. The trypsin-rescue experiment rules out a general assembly defect as the explanation, which is the usual way an attachment phenotype turns out to be something else. Note that the cached publication is abstract-only (full_text_available: false), so figure-level detail could not be checked, and the GONUTS wiki page that would record the student's evidence is offline; the abstract alone is nevertheless explicit about the binding defect. Supporting Evidence: PMID:7684466 NB2 were defective for binding to CEF and BHK-21 cells. PMID:7684466 Consistent with previous work, these results implicate PE2 cleavage PMID:7684466 Insertion mutations for NB1 and NB12 were found
GO:0020002 host cell plasma membrane	EXP PMID:23785213 Imaging of the alphavirus capsid protein during virus replic...	ACCEPT	Summary: Live-cell imaging of a tetracysteine-tagged Sindbis capsid protein (Q94-TC), validated as replication-competent, shows discrete capsid puncta at the plasma membrane that colocalize with E2 and recruit newly synthesized capsid; electron microscopy of the same virus shows particles budding at the plasma membrane. Reason: Direct, well-controlled localization of the capsid chain at the host plasma membrane, which is where alphavirus budding occurs and where the capsid-E2 interaction that drives it takes place. The puncta are shown not to be replication complexes (no colocalization with dsRNA) and to require the E2 cytoplasmic tail, so the assignment is mechanistically anchored rather than incidental. Supporting Evidence: PMID:23785213 Capsid puncta were also observed at the PM. PMID:23785213 Abundant Q94-TC virus particles were observed budding at the plasma membrane
GO:0020002 host cell plasma membrane	EXP PMID:2408229 The Sindbis virus 6K protein can be detected in virions and ...	ACCEPT	Summary: Antiserum raised against the 6K N-terminal 16 residues detected 6K (and an underacylated 4K form) in infected cells and in purified virions; 6K had previously been localized to membranes of infected cells, and UniProt cites this paper for the 6K host cell membrane and virion membrane locations. Reason: The 6K chain is a multi-pass membrane protein that transits the secretory pathway and is incorporated into virions budding from the plasma membrane, so a plasma-membrane assignment is consistent with the whole body of 6K data. The cached record is abstract-only, so the membrane fractionation detail cannot be checked here, and the abstract itself speaks of "membranes" rather than naming the plasma membrane; the curator reading the full text is in a better position to make that call, and independent infected-cell surface data on the same entry (PMID:875134, PMID:2806407) support the location for the other envelope chains. Worth recording that a later live-imaging study did not see 6K accumulate at the plasma membrane, attributing this to its substoichiometric abundance there. Supporting Evidence: PMID:2408229 that the 6K protein can be detected in PMID:2408229 found on membranes in virus-infected cells file:SINDV/P03316/P03316-uniprot.txt SUBCELLULAR LOCATION: [6K protein]: Host cell membrane {ECO:0000269\|PubMed:2408229}
GO:0020002 host cell plasma membrane	EXP PMID:2806407 Biosynthesis, membrane translocation, and surface expression...	ACCEPT	Summary: Deletion analysis of the region upstream of E1, assayed by in vitro transcription/translation and in vivo expression, showed that E1 carries internal signal sequences, is inserted into the ER membrane independently of the pE2 signal sequence, and is efficiently transported to the plasma membrane even without pE2/E2. Reason: Direct evidence that the E1 chain reaches the host plasma membrane, and specifically that it does so autonomously - the point of the experiment. This is the compartment from which Sindbis virions bud, so the location is functionally central for E1 rather than incidental. Supporting Evidence: PMID:2806407 transported to the plasma membrane in the absence of PE2/E2; exit from the
GO:0020002 host cell plasma membrane	EXP PMID:875134 Envelopments of Sindbis virus: synthesis and organization of...	ACCEPT	Summary: Surface-specific labelling of infected BHK cells - ferritin-conjugated antibody and lactoperoxidase-mediated iodination - detected E1 and E2 on the plasma membrane of wild-type-infected cells in the same relative proportions as in iodinated virions, whereas pE2 was present in membranes but never iodinatable at the surface; the maturation-defective mutant ts-20 displayed mainly E1 at the surface. Reason: Two independent surface-restricted methods place the mature E1 and E2 chains at the host plasma membrane in infected cells, with an internal control (pE2) that was not labelled, which is unusually strong for a 1977 localization. The row is the infected-cell anchor for this term on this entry. Supporting Evidence: PMID:875134 Iodine was incorporated into E1 and E2 on the surface PMID:875134 ts-20-infected cells had significant amounts of viral
GO:0020002 host cell plasma membrane	IDA PMID:17483865 The alphavirus 6K protein activates endogenous ionic conduct...	ACCEPT	Summary: CACAO row. Sindbis 6K cRNA was expressed in Xenopus oocytes and voltage-clamped; the authors report that 6K was located at both the plasma membrane and the endoplasmic reticulum membrane, and that it upregulated endogenous hyperpolarization-activated inward and calcium-dependent chloride currents after depleting reticular calcium stores. No intrinsic 6K channel activity was detected in this system. Reason: The CACAO term matches what the paper states for the 6K chain, and the claim is independently carried by infected-cell data on this same entry (PMID:875134, PMID:2806407, PMID:2408229, PMID:23785213), so I accept it. Three caveats belong on the record rather than on the action. First, the assay is heterologous expression of a single chain in Xenopus oocytes, not an infected host cell, so strictly it shows where 6K goes in an amphibian oocyte; "host cell plasma membrane" is an extrapolation that happens to be right. Second, the same sentence reports the endoplasmic reticulum equally, and the student took one of the two compartments from it - the host ER term is annotated on this entry only from a later paper (PMID:36191050), so the CACAO row left half of its own evidence uncaptured. Third, the paper's main conclusion is explicitly that 6K has no intrinsic channel activity in oocytes, which is relevant context for the channel-activity row elsewhere in this review and is not what a localization annotation from this paper would lead a reader to expect. The GONUTS wiki page that would record the student's reasoning is offline, so the cached abstract is all that could be consulted. Supporting Evidence: PMID:17483865 6K was located at both the plasma and the endoplasmic PMID:17483865 6K upregulated endogenous currents
GO:0020002 host cell plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location vocabulary mapping of the curated "Host cell membrane" statements on the capsid, pE2, E2, 6K and E1 chains to GO:0020002. Reason: The electronic mapping reproduces curated, publication-backed location statements for four separate chains of this entry, each of which is independently accepted above from the primary papers. Nothing in the mapping is over-propagated. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Host cell membrane {ECO:0000269\|PubMed:23785213, ECO:0000269\|PubMed:875134}; Single-pass type I membrane protein
GO:0030430 host cell cytoplasm	EXP PMID:23785213 Imaging of the alphavirus capsid protein during virus replic...	ACCEPT	Summary: Live imaging of the tetracysteine-tagged capsid shows a diffuse cytoplasmic pool throughout infection plus three classes of cytoplasmic foci (motile E2-positive puncta, G3BP/nsP3-positive irregular structures, and plasma-membrane puncta). Reason: The capsid chain is released into the cytoplasm by its own autoproteolysis and assembles the nucleocapsid there, so the cytoplasm is where its core activities take place, and this paper images it directly with a tag validated not to perturb replication, morphology or protein distribution. Supporting Evidence: PMID:23785213 distributed diffusely in the cytoplasm as before but also showed distinct foci file:SINDV/P03316/P03316-uniprot.txt Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles
GO:0030430 host cell cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping of the curated "Host cytoplasm" statement for the capsid chain. Reason: Reproduces a curated statement tied to PubMed:23785213, which is accepted above from the primary data. Correct compartment and correct chain. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Host cytoplasm {ECO:0000269\|PubMed:23785213}
GO:0033644 host cell membrane	IEA GO_REF:0000043	TOO GENERAL	Summary: Generic host cell membrane, mapped from the Viral ion channel keyword. True of 6K and of the envelope chains, but it is the direct parent of the host cell plasma membrane term that this entry carries with five experimental rows, and an ancestor of the host ER and host Golgi terms it also carries. Reason: Every host membrane this polyprotein's chains occupy is named specifically elsewhere in this review - plasma membrane (GO:0020002, accepted from four independent experimental papers), endoplasmic reticulum (GO:0044165) and Golgi apparatus (GO:0044177) - and GO:0020002 is a descendant of GO:0033644, so this row adds no information. Note that this is a generic membrane term, not a root organelle term, so the organelle-retention policy does not apply to it. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt SUBCELLULAR LOCATION: [6K protein]: Host cell membrane {ECO:0000269\|PubMed:2408229}; Multi-pass membrane protein
GO:0034220 monoatomic ion transmembrane transport	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven ion transmembrane transport from KW-0407 (Ion channel), belonging to the 6K viroporin chain. 6K forms cation-selective channels in planar lipid bilayers, permeabilizes E. coli and mammalian cells, and its channel function is pharmacologically blockable with HMA. Reason: This is the process counterpart of the 6K channel activity and is the right granularity: conductance across a membrane is what all the evidence measures, while the ion selectivity is reported only as weak, so no narrower cation- or anion-specific child is warranted. Accepting this row is what makes the bare GO:0006811 parent row redundant. Supporting Evidence: PMID:36191050 6K has been shown to form cation-selective ion channels when inserted into planar lipid bilayers PMID:12424249 synthesized both capsid protein and 6K. Transfection of the construct with
GO:0039619 T=4 icosahedral viral capsid	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven T=4 icosahedral capsid location from KW-1144, for the capsid chain. The Sindbis nucleocapsid is built from 240 copies of the capsid protein in T=4 quasisymmetry, complementary to the T=4 envelope lattice. Reason: The triangulation number is an established structural fact for this virus, inferred from the core-protein dimer model in the 1991 crystal structure and consolidated by later cryo-EM; UniProt states it in curated form. This is the most specific correct capsid term available and belongs in core_functions as the capsid's location. Supporting Evidence: PMID:1944569 nucleocapsid is likely to have T = 4 quasisymmetry. file:SINDV/P03316/P03316-uniprot.txt Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein
GO:0039654 fusion of virus membrane with host endosome membrane	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven endosomal fusion term from KW-1170, belonging to the E1 chain. Sindbis fusion is strictly low-pH dependent with a threshold near pH 6.0 and is undetectable at neutral pH, and is preceded by E2-E1 dissociation and E1 homotrimerization. Reason: This is the specific entry step E1 performs, and it is the term the liposome data actually pin down: fusion occurs only in the acidic range characteristic of endosomes, which is why the authors read their result as settling a long-standing controversy in favour of endocytic entry. It is also the correct replacement for the generic GO:0061025 membrane fusion row elsewhere in this review. Supporting Evidence: PMID:10482600 Fusion was optimal at pH 5.0, with a threshold at pH 6.0, and PMID:10482600 the E1 trimer represents the fusion-active conformation of the viral spike
GO:0039663 membrane fusion involved in viral entry into host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven entry-fusion term from KW-1168, the parent of the endosomal fusion term also annotated here. Both describe the E1 chain's fusogenic step in entry. Reason: The claim is correct and is more than a bare restatement: it ties the fusion event to viral entry, which is the biological point of E1's activity, whereas the child term specifies the membrane. The two keywords (KW-1168, KW-1170) are curated as a pair and both land on sound terms, so this is benign redundancy rather than over-annotation. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion (PubMed:21124457)
GO:0039722 symbiont-mediated suppression of host toll-like receptor signaling pathway	IDA PMID:33673546 The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR S...	ACCEPT	Summary: BioID2 proximity labelling from the Sindbis capsid protein identified host IRAK1 among its interactors; the interaction is conserved across arthritogenic and encephalitic alphaviruses, and cellular model systems showed that the capsid protein specifically inhibits IRAK1-dependent signalling, which the authors interpret as innate-immune evasion before viral gene expression. Reason: IRAK1 is the proximal kinase of the MyD88-dependent Toll-like receptor pathway, so capsid-mediated inhibition of IRAK1-dependent signalling is suppression of TLR signalling by the symbiont, exactly what the term denotes. The direction is right (the viral protein does the suppressing), the arm is right (the paper assays signalling downstream of the receptor-proximal kinase, not interferon production), and the activity is a property of the capsid chain, which is also the chain carrying the corresponding kinase-binding row. Supporting Evidence: PMID:33673546 the alphaviral capsid protein specifically inhibits PMID:33673546 this capsid-IRAK1 interaction is conserved across multiple alphavirus species file:SINDV/P03316/P03316-uniprot.txt Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry
GO:0042025 host cell nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Subcellular-location mapping of the capsid chain's "Host nucleus" statement, which in UniProt carries ECO:0000250 (by similarity to the VEEV capsid Q8JUX5) rather than Sindbis-specific evidence. Reason: Nucleocytoplasmic shuttling of the alphavirus capsid, via an N-terminal NLS and an unusually strong supraNES that binds CRM1 without RanGTP, is well established for other alphavirus capsids and the motifs are conserved, so the claim is plausible and should be retained. But no source available here measures it for Sindbis, and the capsid's documented activities - autoproteolysis, genome binding, nucleocapsid assembly, budding at the plasma membrane and IRAK1 inhibition - all take place outside the nucleus. The location is therefore kept as peripheral rather than treated as a core compartment. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Host nucleus {ECO:0000250\|UniProtKB:Q8JUX5}. Note=Shuttles between the cytoplasm and the nucleus.
GO:0042025 host cell nucleus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Curator-judged sequence-similarity transfer of host nucleus localization from Q8JUX5, the Venezuelan equine encephalitis virus capsid protein, which is documented to shuttle between cytoplasm and nucleus. Reason: The donor is the correct homologue (an alphavirus capsid protein, the same chain of the same polyprotein architecture) and the transferred feature is a short motif pair - NLS plus supraNES - in the conserved capsid N-terminus, so the inference is of the kind ISS is for and should not be overruled. Consistent with the keyword-derived row for the same term: retained, but peripheral to the capsid's core structural and enzymatic functions, and still awaiting a Sindbis-specific measurement. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt The N-terminus also contains a nuclear localization signal and a supra nuclear export signal (supraNES), which is an unusually strong NES that mediates host CRM1 binding in the absence of RanGTP
GO:0044165 host cell endoplasmic reticulum	EXP PMID:36191050 Requirement of a functional ion channel for Sindbis virus gl...	ACCEPT	Summary: Live-cell imaging of a miniSOG-tagged 6K in infected cells, together with mCherry-E2, placed 6K in the ER and in post-Golgi vesicles colocalizing with E2 through the secretory pathway; a chimeric virus in which 6K was replaced by HCV P7, which is retained in the ER, failed to make CPV-II. Reason: The ER is where this polyprotein's membrane chains begin their lives: after capsid autoproteolysis the exposed internal signal sequence targets the remainder to the ER, host signal peptidase carves out pE2, 6K and E1 there, and pE2-E1 heterodimers form there. This row images one of those chains in that compartment during real infection, so the location is functionally central rather than incidental. Supporting Evidence: PMID:36191050 6K localizes to ER and Golgi file:SINDV/P03316/P03316-uniprot.txt As soon as the capsid protein has been autocleaved, an internal uncleaved signal peptide directs the remaining polyprotein to the endoplasmic reticulum.
GO:0044165 host cell endoplasmic reticulum	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping of the curated "Host endoplasmic reticulum" statement for the 6K chain, which is tied to PubMed:36191050. Reason: Reproduces a curated, publication-backed statement that is accepted above from the primary imaging data, and is independently consistent with the oocyte study that also placed 6K at the ER membrane. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Host endoplasmic reticulum {ECO:0000269\|PubMed:36191050}
GO:0044177 host cell Golgi apparatus	EXP PMID:36191050 Requirement of a functional ion channel for Sindbis virus gl...	ACCEPT	Summary: Flag-tagged 6K colocalized with the Golgi marker giantin, and dual-labelled miniSOG-6K/mCherry-E2 virus showed 6K and E2 together on Golgi and post-Golgi vesicles in live infected cells; the localization persisted when the ribosomal slip site was mutated to abolish TF, showing it is 6K itself and not the frameshift product. Reason: Direct localization in infected cells with a marker control and a genetic control for the confounding TF product. The compartment is also where 6K does its job: absence of 6K abolishes type II cytopathic vacuoles, which originate from the Golgi, with a concomitant loss of glycoprotein transport to the plasma membrane. pE2 is likewise cleaved by host furin in trans-Golgi vesicles, so this is a functionally loaded compartment for the entry as a whole. Supporting Evidence: PMID:36191050 6K and E2 colocalize on Golgi in the secretory pathway PMID:36191050 CPV-II, which originates from the Golgi apparatus, is not detected in
GO:0044177 host cell Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: Subcellular-location mapping of the curated "Host Golgi apparatus" (and trans-Golgi network) statement for the 6K chain. Reason: Reproduces a curated statement tied to PubMed:36191050, accepted above from the primary data; the trans-Golgi network refinement in the UniProt note is consistent with the imaging and with the site of furin cleavage of pE2. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt Host Golgi apparatus {ECO:0000269\|PubMed:36191050}. Host Golgi apparatus, host trans-Golgi network.
GO:0044389 ubiquitin-like protein ligase binding	IPI PMID:22020285 Image-based genome-wide siRNA screen identifies selective au...	KEEP AS NON CORE	Summary: In a genome-wide siRNA screen for selective-autophagy factors, scored on colocalization of mCherry-tagged Sindbis capsid with GFP-LC3, SMURF1 emerged as a hit; mouse Smurf1 (Q9CUN6) and the Sindbis capsid protein co-immunoprecipitate from infected MEFs and HeLa cells, and Smurf1 is required for delivery of the capsid to autophagosomes and for its proteasome-independent degradation. Reason: The interaction is directly demonstrated by co-immunoprecipitation in infected cells and the term is informative, naming the partner class rather than asserting bare protein binding, so it should be retained. It is non-core because the direction of causation runs the other way from a viral function: SMURF1 is host machinery acting on the capsid as a virophagy cargo, and the consequence (capsid degradation, host cell survival) is a host defence rather than something the capsid does for the virus. The capsid was not detectably ubiquitinated, and the authors show Smurf1's role in selective autophagy is independent of its ligase activity, so no catalytic relationship should be inferred from this row. Supporting Evidence: PMID:22020285 Smurf1 and SIN capsid protein co-immunoprecipitate in SIN-infected MEFs and HeLa cells PMID:22020285 Smurf1 is required for SIN capsid targeting to autophagosomes
GO:0044389 ubiquitin-like protein ligase binding	IPI PMID:22020285 Image-based genome-wide siRNA screen identifies selective au...	KEEP AS NON CORE	Summary: Companion row recording the same capsid-SMURF1 interaction against the human orthologue (Q9HCE7), consistent with the paper's HeLa co-immunoprecipitation and the siRNA knockdown experiments, which were performed in human cells. Reason: Same judgment as the mouse row, with which it must be consistent: a real, informative, directly demonstrated interaction, but one in which the host E3 acts on the capsid as autophagy cargo rather than the capsid exerting a viral function. The human partner is supported by the HeLa co-immunoprecipitation and by the SMURF1 siRNA experiments in HeLa cells, so this is not a bare orthology transfer. Supporting Evidence: PMID:22020285 Smurf1 and SIN capsid protein co-immunoprecipitate in SIN-infected MEFs and HeLa cells
GO:0046718 symbiont entry into host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven entry term from KW-1160 (Viral penetration into host cytoplasm) and KW-1162 (Viral penetration into host cytoplasm/Virus entry into host cell). The polyprotein's E2 and E1 chains together carry out entry: receptor binding, endocytic uptake, low-pH-triggered fusion and release of the nucleocapsid. Reason: Entry is one of the two things this polyprotein exists to do (the other being virion assembly and budding), and both halves of it are experimentally established on this entry - attachment from the E2 insertion mutants and receptor identification, fusion and nucleocapsid delivery from the liposome system. The pathway-level term is the right summary claim and the specific steps are annotated separately. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (PubMed:9707418) PMID:10482600 SIN fused efficiently with receptor-free liposomes
GO:0055036 virion membrane	EXP PMID:2408229 The Sindbis virus 6K protein can be detected in virions and ...	ACCEPT	Summary: Immunoprecipitation with an antiserum against the 6K N-terminal 16 residues detected 6K in purified virion preparations, at roughly 0.08-0.12 copies per E1+E2, establishing that this small acylated membrane protein is a genuine, if minor, virion component. Reason: Direct detection of the chain in purified particles. The quantification matters: it distinguishes a real low-stoichiometry virion component from contamination by infected-cell membranes, and UniProt cites this paper for the 6K virion membrane location. Supporting Evidence: PMID:2408229 that the 6K protein can be detected in PMID:2408229 ratio of 6K to E1 + E2 ranged from 0.08 to 0.12.
GO:0055036 virion membrane	EXP PMID:3829124 The T=4 envelope of Sindbis virus is organized by interactio...	ACCEPT	Summary: Cryo-electron microscopy of vitrified Sindbis particles, reconstructed to 35 A, resolved columnar spike trimers on a T=4 lattice standing on a polyhedral lipid bilayer that surrounds the nucleocapsid, with 240 copies of each spike protein per virion. Reason: Structural evidence placing the E1 and E2 chains in the virion's own lipid membrane, and the clearest demonstration on this entry that the spikes are envelope structures rather than capsid structures. This is the term that should carry the spike localization for this polyprotein. Supporting Evidence: PMID:3829124 virus envelope is polyhedral and surrounds a smooth T=3 nucleocapsid. PMID:3829124 appear as columnar trimers arranged on a T=4 lattice. The lipid bilayer of the
GO:0055036 virion membrane	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated assignment of virion membrane from an ARBA rule, the alphavirus E1 and E2 glycoprotein signatures, and the curated SL-0275 location. Reason: The automated route is uninformative on its own - an ARBA association rule is an unvetted prediction - but the conclusion is independently established by the two experimental rows for the same term on this entry, and the InterPro signatures it rests on are the E1/E2 envelope glycoprotein families, whose membership really does imply an envelope membrane location. Accepted on the strength of the experimental rows rather than the rule. Supporting Evidence: PMID:3829124 virus envelope is polyhedral and surrounds a smooth T=3 nucleocapsid.
GO:0061025 membrane fusion	IDA PMID:10482600 Low-pH-dependent fusion of Sindbis virus with receptor-free ...	MODIFY	Summary: CACAO row. Smit, Bittman and Wilschut measured fusion of pyrene-labelled Sindbis virions with receptor-free liposomes by excimer-fluorescence dequenching in both directions, and independently by trypsin-mediated degradation of the capsid protein after transfer of the nucleocapsid into trypsin-loaded liposomes. Fusion reached 60-85 per cent, was optimal at pH 5.0 with a threshold at pH 6.0 and undetectable at neutral pH, required cholesterol plus sphingolipid in the target membrane, and was preceded by dissociation of the E2-E1 heterodimer and appearance of a trypsin-resistant E1 homotrimer. Reason: The CACAO annotation is on the right paper, the right protein and with the right evidence code - this is a direct, two-assay fusion measurement on virions, not a phenotype read as a process - but it sits at the generic root of the branch while the paper pins down the specific step. The whole point of the study was to settle whether Sindbis fuses at the plasma membrane at neutral pH or from within acidic endosomes, and it answers the latter: fusion is undetectable at neutral pH and optimal at endosomal pH. GO:0039654 fusion of virus membrane with host endosome membrane is therefore the supported descendant, and GO:0039663 membrane fusion involved in viral entry into host cell its parent; both are already carried on this entry as keyword-derived IEA rows, which this experimental row should reinforce at the same granularity rather than restate at the root. This is the parent-level-restatement shape in the CACAO failure taxonomy. Proposed replacements: fusion of virus membrane with host endosome membrane Supporting Evidence: PMID:10482600 Fusion was optimal at pH 5.0, with a threshold at pH 6.0, and PMID:10482600 Fusion of SIN required the presence of both cholesterol and sphingolipid in the target liposomes PMID:10482600 the E1 trimer represents the fusion-active conformation of the viral spike
GO:0075509 endocytosis involved in viral entry into host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven term from KW-1164 (Virus endocytosis by host). Sindbis enters by receptor-mediated endocytosis, the uptake being driven by E2 engagement of VLDLR or LRP8/ApoER2 followed by internalization of the virus-receptor complex. Reason: The spike chains perform the part of endocytic entry that the virus contributes: receptor engagement and delivery of the particle into the endocytic route, after which the acidic lumen triggers E1-mediated fusion. Ectopic expression of VLDLR or ApoER2 was shown to confer attachment and internalization of alphavirus particles, so the internalization step is tied to the spike-receptor interaction rather than merely assumed from the fusion requirement. Supporting Evidence: PMID:34929721 cellular attachment, and internalization of virus-like particles file:SINDV/P03316/P03316-uniprot.txt after virus attachment to target cell via host VLDLR or LRP8/APOER2 and endocytosis, acidification of the endosome induces dissociation of E1/E2 heterodimer
GO:0075512 clathrin-dependent endocytosis of virus by host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven term from KW-1165 (Clathrin-mediated endocytosis of virus by host), specifying the route by which Sindbis virions are taken up. UniProt states the clathrin-mediated route in curated form with a publication reference. Reason: The clathrin route for Sindbis entry is independently established - dominant-negative dynamin, which blocks budding of clathrin-coated pits, inhibits infection, as the liposome-fusion paper notes while reviewing the then-new evidence - and it is the route that delivers the particle to the acidic compartment where E1 fuses. The mechanistic claim rests on host machinery, but the gene product under annotation is what engages the receptor that enters by that route, so the involvement is genuine rather than a property of the host alone. Supporting Evidence: PMID:10482600 thus suggesting that SIN infects its host cells by clathrin-mediated endocytosis file:SINDV/P03316/P03316-uniprot.txt In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (PubMed:9707418)
GO:0075523 viral translational frameshifting	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Keyword-driven process term from KW-0688 (Ribosomal frameshifting), reflecting the fact that a (-1) programmed frameshift at a heptanucleotide slip site inside the 6K coding region generates the alternative product TF (P0DOK0) from this same open reading frame. Reason: The frameshift is real and is correctly recorded on the entry as an alternative product, but the annotation asserts that this gene product is involved in the frameshifting process, and it is not: the work of frameshifting is done by the host ribosome acting on the slip-site and downstream structure of the subgenomic mRNA. The polyprotein is the output of translation, not a participant in the recoding event, and nothing in the available evidence suggests the nascent chain promotes its own frameshift. This is a keyword-to-GO mapping that converts a sequence feature of the coding RNA into a process annotation on the protein; it is not wrong about the biology of the virus, only about which entity performs the step, so it is marked over-annotated rather than removed. Supporting Evidence: file:SINDV/P03316/P03316-uniprot.txt ALTERNATIVE PRODUCTS: Event=Ribosomal frameshifting; Named isoforms=2; PMID:36191050 the TF protein produced by a (−1) programmed ribosomal frameshifting in a heptanucleotide slip site in the 6K coding region
GO:0098029 icosahedral viral capsid, spike	IDA PMID:10482600 Low-pH-dependent fusion of Sindbis virus with receptor-free ...	MODIFY	Summary: CACAO row from the liposome fusion study. That paper describes the Sindbis spike - 80 hetero-oligomeric spikes, each a trimer of E2-E1 heterodimers - and concludes that the trypsin-resistant E1 homotrimer is the fusion-active conformation of the spike. The annotation places the E1/E2 spike in GO:0098029, whose definition is "A short structure attached to an icosahedral virion capsid, and used for attachment to the host cell" and whose only ontology placement is part_of GO:0019030 icosahedral viral capsid (checked against QuickGO, 2026-10-29). Reason: The spike itself is real and these chains are its constituents, so this is a term choice problem rather than a false claim - but the term puts the spike on the wrong structure. Sindbis is an enveloped alphavirus: the spike trimers are anchored in the virion's lipid bilayer, which surrounds the nucleocapsid, and cryo-EM of the particle resolves exactly that arrangement. A term that is part_of icosahedral viral capsid therefore asserts the glycoproteins are part of the proteinaceous genome shell, which they are not; it suits a non-enveloped virus whose spikes protrude from the capsid. The supported cellular component for E1 and E2 is GO:0055036 virion membrane, which this entry already carries with two experimental rows. GO has no envelope-spike component term - a QuickGO text search for "spike" returns only GO:0098029 outside the neuroscience senses - so the spike assembly itself cannot currently be expressed, and this review files a request for one under proposed_new_terms. Note also that the spike architecture in this paper is background citing earlier structural work rather than a result of its own assays, which are fusion measurements. New failure shape for the CACAO taxonomy: the term names the right supramolecular assembly but attaches it to the wrong parent structure, visible only from the term's ontology placement. Proposed replacements: virion membrane Supporting Evidence: PMID:10482600 The glycoproteins are organized in 80 hetero-oligomeric spikes; a single spike consists of a trimer of E2/E1 heterodimers. PMID:3829124 appear as columnar trimers arranged on a T=4 lattice. The lipid bilayer of the PMID:3829124 virus envelope is polyhedral and surrounds a smooth T=3 nucleocapsid.
GO:0098670 entry receptor-mediated virion attachment to host cell	IEA GO_REF:0000043	ACCEPT	Summary: Keyword-driven term from KW-1234 (Viral attachment to host entry receptor), reflecting the identification of VLDLR and LRP8/ApoER2 as receptors engaged by the Sindbis E2-E1 spike. Reason: The receptor-mediated specialization of attachment is now experimentally grounded for Sindbis: the E2-E1 glycoproteins of Sindbis virus, along with those of Semliki Forest and eastern equine encephalitis viruses, were shown to interact with the ligand-binding domains of VLDLR and ApoER2, and ectopic expression of either receptor confers attachment and internalization. This is the most specific correct attachment term for the E2 chain. Supporting Evidence: PMID:34929721 eastern equine encephalitis virus and Sindbis virus interact with the file:SINDV/P03316/P03316-uniprot.txt Plays a role in viral attachment to target host cell, by binding to the cell receptors VLDLR or LRP8/APOER2 (PubMed:34929721)
GO:0019068 virion assembly	IDA PMID:23785213 Imaging of the alphavirus capsid protein during virus replic...	NEW	Summary: Proposed new annotation. Assembly of the Sindbis particle is performed by the chains of this polyprotein and by nothing else: 240 capsid proteins build the nucleocapsid around the genome, the E2 cytoplasmic tail binds the capsid to nucleate budding, and 6K is required for the Golgi-derived structures that deliver spikes to the assembly site. Live imaging of tagged capsid shows plasma-membrane puncta containing capsid and E2 that recruit newly made capsid and are abolished by the E2 Y400K substitution, which blocks the E2-capsid interaction. Reason: GOA has no assembly or budding annotation for this entry, which is a striking gap for a structural polyprotein. The participation test is clearly met: the capsid and E2 chains are the entities that perform the assembly steps - capsid-capsid lattice formation, capsid-E2 engagement at the membrane - rather than being merely required for or acted on by a process another protein executes. The comparator check was run against the other alphavirus structural polyproteins, which stand in exactly this role, and its result is patchy curation rather than a convention either way: Semliki Forest virus P03315 POLS_SFV does carry GO:0019068, by IMP, and the annotation is itself a CACAO row; chikungunya Q8JUX5 POLS_CHIKS and Q5XXP3 POLS_CHIK3 carry no assembly or budding term at all (checked GO:0019068, GO:0019069, GO:0019076, GO:0046755 and GO:0039702 by QuickGO query on 2026-10-31). A systematic absence across the comparators would have meant a convention to identify; one comparator carrying the term and two lacking it, on entries whose rows are dominated by keyword mappings, means the term is accepted for this role and simply unannotated here. Sindbis virus's own non-structural polyprotein P03317 lacks it correctly, since assembly is not its job. GO:0019068 is neither an ancestor nor a descendant of any other term proposed or accepted in this review. Supporting Evidence: PMID:23785213 Capsid puncta were also observed at the PM. PMID:23785213 Abundant Q94-TC virus particles were observed budding at the plasma membrane file:SINDV/P03316/P03316-uniprot.txt The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (PubMed:9143274)
GO:0046761 viral budding from plasma membrane	IMP PMID:36191050 Requirement of a functional ion channel for Sindbis virus gl...	NEW	Summary: Proposed new annotation. Sindbis buds at the host plasma membrane, and this entry's chains carry out the budding reaction: the capsid-E2 interaction drives envelopment, and the 6K chain's ion-channel function is required for the Golgi-derived CPV-II structures and for glycoprotein delivery to the plasma membrane, with a 6K deletion and channel-blocker treatment both reducing virus release. Reason: The site-specific budding term is absent from GOA for this entry even though budding is one of the two things the polyprotein exists to do. Participation is satisfied by the viral chains themselves: alphavirus budding is driven by lateral glycoprotein interactions and by capsid engagement of the E2 cytoplasmic tail, without a host ESCRT requirement, so the work of the process is done by E2, capsid and 6K rather than by host machinery that merely permits it. The mutant evidence is of the right kind for IMP - an in-frame 6K deletion reduces particle production, functional complementation by the Vpu channel helix restores it, and the channel blocker HMA reduces release from wild-type-infected cells - and the plasma-membrane site is independently imaged. The term is not an ancestor or descendant of GO:0019068, which is proposed alongside it. Supporting Evidence: PMID:36191050 significantly reduces SINV release, suggesting that the ion channel activity of PMID:23785213 Abundant Q94-TC virus particles were observed budding at the plasma membrane file:SINDV/P03316/P03316-uniprot.txt This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins.
GO:0046789 host cell surface receptor binding	IPI PMID:34929721 VLDLR and ApoER2 are receptors for multiple alphaviruses.	NEW	Summary: Proposed new annotation. The E2-E1 spike of Sindbis virus binds the ligand-binding domains of the host surface receptors VLDLR and LRP8/ApoER2, and ectopic expression of either receptor confers attachment and internalization of alphavirus particles. GOA records the resulting attachment processes but no molecular function for the binding event itself. Reason: The entry carries the attachment processes (GO:0019062, GO:0098670) with no molecular function underneath them, so the activity that executes those processes is unannotated. GO:0046789 host cell surface receptor binding states exactly what was measured - a viral protein binding a receptor on the host cell surface - and the binding was shown directly for the Sindbis E2-E1 glycoproteins rather than inferred from the Semliki Forest result. This is not a process term, so the participation test does not arise; the comparator check is also satisfied, since GO:0046789 is the standard molecular function for viral attachment proteins. The term is neither an ancestor nor a descendant of anything else accepted or proposed in this review. Supporting Evidence: PMID:34929721 eastern equine encephalitis virus and Sindbis virus interact with the PMID:34929721 cellular attachment, and internalization of virus-like particles file:SINDV/P03316/P03316-uniprot.txt E2-E1 heterodimers interact with host VLDLR or LRP8/APOER2 to mediate viral entry (PubMed:34929721)
GO:0140522 fusogenic activity	IDA PMID:10482600 Low-pH-dependent fusion of Sindbis virus with receptor-free ...	NEW	Summary: Proposed new annotation. E1 is a class II viral fusion protein: in a receptor-free liposome system, low pH dissociates the E2-E1 heterodimer, E1 forms a trypsin-resistant homotrimer that kinetically precedes fusion, and 60-85 per cent of virions fuse, with nucleocapsid transfer confirmed independently by trypsin encapsulated in the target liposomes. GOA records the fusion processes on this entry but no fusogenic molecular function. Reason: The entry carries two fusion process terms (GO:0039654, GO:0039663) and, after this review, a third experimental row modified onto GO:0039654, but no molecular function for the activity that performs them. GO:0140522 fusogenic activity - "The activity of joining two lipid bilayers to form a single membrane" - is precisely what the liposome assays measure, in a receptor-free system in which the only protein present is the viral spike, so the entity performing the step is unambiguous. The term is neither an ancestor nor a descendant of any other term accepted or proposed here. Supporting Evidence: PMID:10482600 SIN fused efficiently with receptor-free liposomes PMID:10482600 the E1 trimer represents the fusion-active conformation of the viral spike file:SINDV/P03316/P03316-uniprot.txt FUNCTION: [Spike glycoprotein E1]: Class II viral fusion protein.

Gene Description

Functional Isoforms

Proposed New Ontology Terms

viral envelope spike

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

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