TRIM5 (tripartite motif-containing protein 5; the antiviral isoform is TRIM5alpha) is a cytoplasmic RING-type E3 ubiquitin ligase of the TRIM/RBCC family that functions both as a capsid-specific retroviral restriction factor and as an innate immune pattern-recognition receptor. Its RBCC architecture comprises an N-terminal RING-type zinc finger that confers E3 ubiquitin ligase activity (EC 2.3.2.27), a B-box-type zinc finger and a coiled-coil that drive the higher- and lower-order self-multimerization required for activity, and a C-terminal B30.2/PRYSPRY (SPRY) domain that directly recognizes the assembled retroviral capsid lattice. Through the PRYSPRY domain TRIM5alpha binds the hexameric capsid lattice of incoming non-host-adapted retroviruses and blocks infection at an early post-entry step, before reverse transcription; polymorphisms in the PRYSPRY domain account for the species-specific spectrum of restriction (human TRIM5alpha restricts N-tropic MLV, EIAV, SIVmac, FIV and BIV but only weakly HIV-1). Capsid lattice binding also triggers TRIM5's RING E3 ligase activity: together with the UBE2V1-UBE2N (UBC13-UEV1A) E2 complex it synthesizes unanchored Lys63-linked polyubiquitin chains that activate the TAK1 (MAP3K7)-TAB2-TAB3 kinase complex by autophosphorylation, inducing NF-kappaB- and AP-1/MAPK-responsive inflammatory genes and thereby acting as a sensor that links capsid detection to innate immune signaling. TRIM5alpha is itself regulated by ubiquitination (RING/UBE2D2-dependent autoubiquitination, monoubiquitination by TRIM21) and undergoes rapid proteasome-dependent turnover upon engaging restriction-sensitive virus. It additionally functions in selective ("precision") autophagy: it acts as a platform that assembles and activates the autophagy regulators ULK1 and BECN1 (Beclin-1, by dissociating it from BCL2 and TAB2) and as a selective autophagy receptor that directly recognizes the HIV-1 capsid protein p24 and delivers it for autophagic degradation, interacting with SQSTM1/p62 and the ATG8 family proteins GABARAP/GABARAPL1/GABARAPL2 and MAP1LC3A/C. TRIM5alpha localizes predominantly to cytoplasmic bodies, where it can form homodimers and homotrimers and colocalizes with proteasomal subunits and SQSTM1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cytoplasmic localization, where TRIM5alpha acts in cytoplasmic bodies. Reason: TRIM5alpha is predominantly cytoplasmic and acts there (capsid recognition, signaling, autophagy); strongly supported experimentally. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0045087 innate immune response | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of involvement in innate immunity; TRIM5alpha both restricts retroviruses and activates innate immune signaling. Reason: Core biological process; TRIM5alpha is an innate immune sensor of the retroviral capsid lattice that activates NF-kB/MAPK signaling. Supporting Evidence: PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid lattice |
| GO:0010468 regulation of gene expression | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Generic regulation-of-gene-expression term inherited phylogenetically; downstream consequence of TRIM5-driven NF-kB/MAPK activation. Reason: Correct but overly generic; the specific positive regulation of NF-kB signaling and MAPK cascade annotations better capture the mechanism. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Activation of the MAP3K7/TAK1 complex by autophosphorylation |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of RING E3 ubiquitin ligase activity, consistent with the experimentally demonstrated RING-dependent ligase activity. Reason: Core molecular function; the RING domain confers E3 ligase activity essential for restriction, autoubiquitination and signaling. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination |
| GO:0046596 regulation of viral entry into host cell | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of regulation of viral entry; TRIM5alpha restricts retroviruses but acts after entry, before reverse transcription. Reason: TRIM5alpha blocks an early post-entry (uncoating/pre-reverse-transcription) step rather than viral entry itself; the restriction role is better captured by host-mediated suppression of symbiont invasion and defense response to virus. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Blocks viral replication early in the life cycle, after viral entry but before reverse transcription |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of protein kinase binding; TRIM5alpha binds the TAK1 kinase complex and ULK1. Reason: Real and functionally relevant (TAK1/MAP3K7, ULK1) but the informative functions are the downstream signaling activation and autophagy regulation. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt MAP3K7/TAK1, TAB2 and TAB3 |
| GO:0032880 regulation of protein localization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of regulation of protein localization, consistent with the IMP annotation from the autophagy study. Reason: Supported but a broad process term; reflects TRIM5's autophagy-platform role rather than a core dedicated function. Supporting Evidence: PMID:25127057 TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition |
| GO:0042803 protein homodimerization activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of homodimerization; TRIM5alpha forms homodimers and homotrimers essential for restriction activity. Reason: Core molecular function; self-association (coiled-coil-mediated dimerization plus B-box-driven higher-order multimerization) is essential for capsid-lattice recognition and restriction. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Can form homodimers and homotrimers |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of positive regulation of NF-kB signaling, consistent with the experimental IMP/IDA evidence. Reason: Core biological process; capsid sensing triggers TRIM5-mediated K63-Ub/TAK1 activation that induces NF-kB. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Activation of the MAP3K7/TAK1 complex by autophosphorylation |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Electronic transfer of a nuclear localization that is only "By similarity" in UniProt (partial nuclear pool seen with TRIM22/TRIM27 coexpression). Reason: Human TRIM5alpha is predominantly cytoplasmic; nuclear localization is only by similarity (UniProtKB:Q0PF16) and context-dependent, not a core or robustly supported localization. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt partial nuclear localization is observed in the presence of TRIM22 or TRIM27 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of cytoplasmic localization from the UniProt subcellular location; the core compartment. Reason: Correct core localization; redundant with experimental IDA cytoplasm annotations. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic assignment of zinc ion binding by the RING and B-box zinc fingers. Reason: Correct (RING and B-box coordinate Zn2+) and underpins ligase/multimerization, but generic; the informative MF is ubiquitin ligase activity. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt /note="RING-type" |
| GO:0042802 identical protein binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning assignment of identical protein binding, reflecting TRIM5 self-association. Reason: Correct (TRIM5 self-associates) but redundant with and less informative than the protein homodimerization activity annotation. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Can form homodimers and homotrimers |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Inter-ontology electronic inference from the transcription coactivator activity annotation. Reason: Derived from the over-interpreted transcription coactivator annotation; TRIM5 acts upstream in NF-kB/MAPK signaling rather than as a direct DNA-templated transcriptional activator. Supporting Evidence: PMID:23077300 to induce NF-ΞΊB and MAP kinase (MAPK) signaling |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.3.2.27-based electronic assignment of ubiquitin protein ligase activity; core function. Reason: Core molecular function corroborated by experimental RING-dependent ligase activity. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt EC=2.3.2.27 |
| GO:0005515 protein binding | IPI PMID:22493164 Systematic analysis of dimeric E3-RING interactions reveals ... | KEEP AS NON CORE | Summary: Interaction from a systematic dimeric E3-RING interaction screen. Bare protein binding is uninformative. Reason: Records a real RING-RING interaction but bare protein binding is uninformative per curation guidelines. Supporting Evidence: PMID:22493164 Systematic analysis of dimeric E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:25203322 PKD1 phosphorylation-dependent degradation of SNAIL by SCF-F... | KEEP AS NON CORE | Summary: Interaction reported in an SCF-FBXO11/SNAIL study (TRIM5 appears as an interactor). Bare protein binding is uninformative. Reason: Bare protein binding is uninformative; not a core TRIM5 function. Supporting Evidence: PMID:25203322 PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 |
| GO:0005515 protein binding | IPI PMID:26618866 βF508 CFTR interactome remodelling promotes rescue of cystic... | KEEP AS NON CORE | Summary: Interaction from a CFTR interactome remodeling study (TRIM5 interacts with CFTR per IntAct). Bare protein binding is uninformative. Reason: High-throughput interactome interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Q9C035; P13569: CFTR; NbExp=3 |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | KEEP AS NON CORE | Summary: Interaction from a CFTR mammalian-membrane-two-hybrid screen. Bare protein binding is uninformative. Reason: High-throughput interactome interaction; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Q9C035; P13569: CFTR; NbExp=3 |
| GO:0042802 identical protein binding | IPI PMID:22493164 Systematic analysis of dimeric E3-RING interactions reveals ... | KEEP AS NON CORE | Summary: TRIM5-TRIM5 self-interaction detected in the E3-RING dimer screen. Reason: Correct self-association but redundant with and less informative than protein homodimerization activity. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Q9C035; Q9C035: TRIM5; NbExp=3 |
| GO:0042802 identical protein binding | IPI PMID:22829933 TRIM27 negatively regulates NOD2 by ubiquitination and prote... | KEEP AS NON CORE | Summary: Self-interaction / TRIM-TRIM interaction reported in a TRIM27/NOD2 study. Reason: Correct self-association but redundant with the homodimerization annotation. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Can form homodimers and homotrimers |
| GO:0140374 antiviral innate immune response | IDA PMID:18248090 TRIM E3 ligases interfere with early and late stages of the ... | ACCEPT | Summary: Direct evidence that TRIM5 functions in the antiviral innate immune response (retroviral restriction screen). Core process. Reason: Core biological process; TRIM5alpha is an antiviral restriction factor and innate immune effector. Supporting Evidence: PMID:18248090 Members of the TRIpartite interaction Motif (TRIM) family of E3 ligases have been shown to exhibit antiviral activities |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IDA PMID:20357094 p62/sequestosome-1 associates with and sustains the expressi... | KEEP AS NON CORE | Summary: Localization to cytoplasmic RNP granules/P-bodies reported in the SQSTM1/p62 study. Reason: Experimentally observed but a specialized sub-compartment; the core localization is cytoplasmic bodies. Defer to curator who read the full text. Supporting Evidence: PMID:20357094 p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: UniPathway-derived general protein ubiquitination process. Reason: Correct but generic; the specific K63-linked ubiquitination annotation better captures the activity. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt PATHWAY: Protein modification; protein ubiquitination. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based (HPA) cytosolic localization, consistent with the core cytoplasmic site of action. Reason: Correct cytosolic localization; consistent with cytoplasmic body localization. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0005634 nucleus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence-similarity transfer of nuclear localization, matching the "By similarity" nuclear note in UniProt. Reason: Nuclear localization for human TRIM5alpha is only by similarity and context-dependent (TRIM22/TRIM27 coexpression); the protein is predominantly cytoplasmic. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt partial nuclear localization is observed in the presence of TRIM22 or TRIM27 |
| GO:0003713 transcription coactivator activity | IDA PMID:23077300 TRIM protein-mediated regulation of inflammatory and innate ... | MARK AS OVER ANNOTATED | Summary: Assigned from a TRIM-family NF-kB/AP-1/IFN activation screen; reflects TRIM5-driven TAK1/NF-kB signaling rather than direct transcriptional coactivation. Reason: TRIM5 acts upstream as a signaling activator (TAK1->NF-kB/MAPK), not as a DNA-associated transcription coactivator; this MF over-interprets the signaling phenotype. Supporting Evidence: PMID:23077300 to induce NF-ΞΊB and MAP kinase (MAPK) signaling |
| GO:0044790 suppression of viral release by host | IDA PMID:18248090 TRIM E3 ligases interfere with early and late stages of the ... | MARK AS OVER ANNOTATED | Summary: Late-stage (viral release) suppression assigned from a broad TRIM screen; for TRIM5alpha the validated dominant activity is early post-entry restriction. Reason: The screen found late-stage effects for several TRIMs (e.g. TRIM25/31/62); TRIM5alpha's well-established mechanism is early post-entry capsid restriction, so a "viral release" role is weakly supported for TRIM5. Supporting Evidence: PMID:18248090 many TRIM proteins affected late stages of the viral life cycle |
| GO:0046597 host-mediated suppression of symbiont invasion | IDA PMID:18248090 TRIM E3 ligases interfere with early and late stages of the ... | ACCEPT | Summary: Direct evidence that TRIM5 suppresses retroviral invasion (early restriction). Core restriction process. Reason: Core biological process; captures the capsid-dependent post-entry restriction of incoming retroviruses. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Capsid-specific restriction factor that prevents infection |
| GO:0005515 protein binding | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | KEEP AS NON CORE | Summary: Autophagy-machinery interactions (ULK1, BECN1, SQSTM1, ATG8 proteins) from the precision-autophagy study. Bare protein binding is uninformative. Reason: Records real, functionally important autophagy interactions but bare protein binding is uninformative; better captured by the adaptor-activity and autophagy annotations. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Interacts with ULK1 (phosphorylated form), GABARAP, GABARAPL1, GABARAPL2, |
| GO:0005737 cytoplasm | IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: Direct evidence of cytoplasmic localization from the autophagy study. Core localization. Reason: Correct core localization, experimentally demonstrated. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0006914 autophagy | IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: Direct evidence that TRIM5alpha functions in autophagy, as a selective autophagy receptor and as a platform activating ULK1/BECN1. Core process. Reason: Core biological process; TRIM5alpha regulates autophagy and acts as a selective autophagy receptor for the HIV-1 capsid. Supporting Evidence: PMID:25127057 TRIM5Ξ± acts as a selective autophagy receptor |
| GO:0098792 xenophagy | IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | NEW | Summary: TRIM5alpha delivers the HIV-1 capsid, a foreign cytosolic viral cargo, for selective autophagic degradation. Reason: PN correctly flagged that the existing autophagy annotation is generic for this role. Xenophagy is the more specific process term for autophagic degradation of a cytosolic viral capsid. Supporting Evidence: PMID:25127057 TRIM5Ξ± delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation |
| GO:0019901 protein kinase binding | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | KEEP AS NON CORE | Summary: Direct interaction with the kinase ULK1 (phosphorylated form) in the autophagy study. Reason: Real and functionally relevant (ULK1) but the informative function is the autophagy-platform/adaptor role. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Interacts with ULK1 (phosphorylated form) |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: TRIM5alpha bridges autophagy machinery (ULK1, BECN1, ATG8s) and substrate, acting as a molecular adaptor/scaffold. Reason: Informative molecular function capturing TRIM5alpha's role as a selective-autophagy receptor/adaptor that links cargo to the autophagy apparatus. Supporting Evidence: PMID:25127057 act as platforms assembling ULK1 and Beclin 1 in their |
| GO:0160247 autophagy cargo adaptor activity | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | NEW | Summary: TRIM5alpha acts as a selective-autophagy cargo adaptor/receptor that recognizes viral capsid cargo and couples it to autophagic degradation. Reason: PN showed that the accepted GO:0030674 adaptor annotation can be made more precise with existing GO:0160247. This is an upgrade to an existing GO term, not a new term request. Supporting Evidence: PMID:25127057 TRIM5Ξ± acts as a selective autophagy receptor PMID:25127057 TRIM5Ξ± delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation |
| GO:0032880 regulation of protein localization | IMP PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence that TRIM5alpha regulates localization of autophagy components/cargo. Reason: Supported but a broad process term reflecting the autophagy-platform role. Supporting Evidence: PMID:25127057 TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition |
| GO:1990462 omegasome | IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: Colocalization with the omegasome (autophagosome-formation site), consistent with TRIM5alpha's autophagy-platform role. Reason: Experimentally supported colocalization at autophagosome biogenesis sites, consistent with the autophagy function. Supporting Evidence: PMID:25127057 act as platforms assembling ULK1 and Beclin 1 in their |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1031716 | ACCEPT | Summary: Reactome curation of cytosolic localization in the interferon-gamma-stimulated gene context. Reason: Correct cytosolic localization, consistent with the core cytoplasmic site of action. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:23077300 TRIM protein-mediated regulation of inflammatory and innate ... | ACCEPT | Summary: Direct evidence (TRIM-family NF-kB activation screen) that TRIM5 positively regulates NF-kB signaling via TAK1. Reason: Core biological process; TRIM5-driven TAK1 activation induces NF-kB. Supporting Evidence: PMID:23077300 to induce NF-ΞΊB and MAP kinase (MAPK) signaling |
| GO:0005737 cytoplasm | IDA PMID:18248090 TRIM E3 ligases interfere with early and late stages of the ... | ACCEPT | Summary: Direct evidence of cytoplasmic localization in the retroviral restriction screen. Core localization. Reason: Correct core localization, experimentally demonstrated. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Predominantly localizes in cytoplasmic bodies |
| GO:0005515 protein binding | IPI PMID:20357094 p62/sequestosome-1 associates with and sustains the expressi... | KEEP AS NON CORE | Summary: Interaction with SQSTM1/p62 that sustains TRIM5alpha expression. Bare protein binding is uninformative. Reason: Records a real, functionally relevant SQSTM1 interaction but bare protein binding is uninformative. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Interacts with SQSTM1 |
| GO:0005515 protein binding | IPI PMID:22078707 TRIM5alpha associates with proteasomal subunits in cells whi... | KEEP AS NON CORE | Summary: Interaction with proteasome subunit PSMC2 (and other proteasome subunits) in cytoplasmic bodies. Bare protein binding is uninformative. Reason: Records a real proteasome-subunit interaction relevant to TRIM5 turnover/restriction but bare protein binding is uninformative. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Interacts with PSMC2 |
| GO:0051607 defense response to virus | TAS PMID:22291694 TRIM5alpha and Species Tropism of HIV/SIV. | ACCEPT | Summary: Author-statement (review) that TRIM5alpha defends against retroviruses. Core process. Reason: Core biological process; TRIM5alpha is a retroviral restriction factor. Supporting Evidence: PMID:22291694 TRIM5Ξ± recognizes the multimerized capsid proteins (viral core) of an incoming virus by its PRYSPRY domain |
| GO:0002218 activation of innate immune response | IDA PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Direct evidence that capsid-lattice sensing by TRIM5 activates the innate immune response. Core process. Reason: Core biological process; capsid recognition triggers TRIM5 ligase activity and innate immune signaling. Supporting Evidence: PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid lattice |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Direct evidence that capsid binding triggers TRIM5 E3 ubiquitin transferase activity (with UBE2V1-UBE2N). Core MF. Reason: Core molecular function; TRIM5 catalyzes ubiquitin transfer to generate K63-linked chains upon capsid sensing. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Binding to the viral capsid triggers its E3 ubiquitin ligase activity |
| GO:0005515 protein binding | IPI PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | KEEP AS NON CORE | Summary: Interactions with the TAK1 complex (MAP3K7, TAB2, TAB3) from the innate-sensor study. Bare protein binding is uninformative. Reason: Records real, functionally central interactions (TAK1 complex) but bare protein binding is uninformative. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt MAP3K7/TAK1, TAB2 and TAB3 |
| GO:0031664 regulation of lipopolysaccharide-mediated signaling pathway | IMP PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | KEEP AS NON CORE | Summary: Mutant-phenotype evidence linking TRIM5-mediated TAK1 activation to LPS/innate signaling pathways. Reason: Supported but a specific signaling-context process; the core mechanism is capsid-triggered TAK1/NF-kB activation. Defer to curator. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt autophosphorylation of the MAP3K7/TAK1 complex |
| GO:0038187 pattern recognition receptor activity | IDA PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Direct evidence that TRIM5 acts as a pattern recognition receptor for the retroviral capsid lattice. Core molecular function. Reason: Core molecular function; TRIM5 is a cytosolic PRR sensing the capsid lattice PAMP. Supporting Evidence: PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid lattice |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Mutant-phenotype evidence that TRIM5 positively regulates NF-kB signaling. Core process. Reason: Core biological process; redundant with the IDA/IBA NF-kB annotations. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Activation of the MAP3K7/TAK1 complex by autophosphorylation |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Mutant-phenotype evidence that TRIM5-mediated TAK1 activation positively regulates the MAPK cascade. Core process. Reason: Core biological process; capsid-triggered TAK1 activation induces MAPK-responsive genes. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt autophosphorylation of the MAP3K7/TAK1 complex |
| GO:0051607 defense response to virus | TAS PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Author-statement that TRIM5 defends against retroviruses. Core process. Reason: Core biological process; redundant with the antiviral/restriction annotations. Supporting Evidence: PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid lattice |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:21512573 TRIM5 is an innate immune sensor for the retrovirus capsid l... | ACCEPT | Summary: Direct evidence that TRIM5, with UBE2V1-UBE2N, generates K63-linked polyubiquitin chains. Core activity. Reason: Core biological process; the K63-chain synthesis is the mechanistic link between capsid sensing and TAK1/NF-kB activation. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt generates 'Lys-63'-linked |
| GO:0042803 protein homodimerization activity | IPI PMID:11331580 The tripartite motif family identifies cell compartments. | ACCEPT | Summary: Self-association reported in the foundational TRIM-family paper; homodimerization/multimerization essential for restriction. Core MF. Reason: Core molecular function; self-multimerization underlies capsid-lattice avidity and restriction. Supporting Evidence: file:human/TRIM5/TRIM5-uniprot.txt Can form homodimers and homotrimers |
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Download this section (compressed HTML)Q: How is the balance between TRIM5alpha's two effector outcomes after capsid recognition - proteasome-dependent restriction versus selective autophagic delivery of the capsid - controlled in a given cell type?
Q: To what extent does the innate immune signaling (PRR/TAK1/NF-kB) function of TRIM5alpha contribute to antiviral protection in vivo independently of direct capsid restriction?
Experiment: Reconstitute capsid-triggered TRIM5alpha E3 ligase activity in vitro with purified TRIM5alpha (wild-type vs RING C15A and PRYSPRY mutants), UBE2V1-UBE2N, ubiquitin and assembled capsid tubes, to map how lattice binding stimulates unanchored K63-chain synthesis and TAK1 activation.
Experiment: Use separation-of-function TRIM5alpha mutants (restriction-competent/signaling-dead and signaling-competent/restriction-dead) in primary human cells to dissect the relative contributions of capsid restriction, NF-kB/MAPK signaling, and selective autophagy to antiretroviral defense.
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