TRIM17 (terf, testis RING finger protein; RNF16) is a RING-type E3 ubiquitin ligase of the TRIM/RBCC family with the canonical architecture of an N-terminal RING-HC zinc finger (conferring E3 ubiquitin ligase activity, EC 2.3.2.27), a B-box, a coiled-coil and a C-terminal B30.2/SPRY domain; it is expressed almost exclusively in testis and undergoes autoubiquitination. TRIM17 is a key regulator of neuronal apoptosis: it ubiquitinates and degrades the anti-apoptotic protein MCL1 to initiate neuronal death, and it controls NFAT transcription factors (NFATC3/NFATC4) by preventing their nuclear localization and thereby inhibiting their transcriptional activity. It also modulates selective autophagy in a target-selective manner: it inhibits autophagic degradation of diverse substrates while contributing to autophagy of midbodies, with its autophagy-inhibitory activity involving MCL1, which TRIM17 assembles into complexes with the autophagy regulator BECN1. Additional reported activities include stimulating proteasomal degradation of the kinetochore protein ZWINT to negatively regulate cell proliferation, antagonizing other TRIM ligases (it prevents TRIM28 from ubiquitinating the anti-apoptotic BCL2A1, and decreases TRIM41-mediated degradation of ZSCAN-family substrates to promote alpha-synuclein/SNCA transcription in neurons), and being stabilized through interaction with TRIM44. TRIM17 localizes to the cytoplasm and lysosome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cytoplasmic activity; the core compartment for TRIM17. Reason: Correct core localization; consistent with experimental EXP cytoplasm evidence. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. |
| GO:0045087 innate immune response | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Family-level phylogenetic inference of innate immune involvement; TRIM17's documented roles are in apoptosis, autophagy and proliferation rather than innate immunity. Reason: Over-propagated TRIM-family IBA; there is no specific experimental support for an innate-immune function of TRIM17, whose characterized roles are neuronal apoptosis and selective-autophagy regulation. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt E3 ubiquitin ligase that plays important roles in the |
| GO:0010468 regulation of gene expression | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of regulation of gene expression; TRIM17 indirectly affects transcription (NFAT localization, ZSCAN/SNCA). Reason: Indirectly supported (NFAT nuclear-localization control; ZSCAN/SNCA) but a broad term and secondary to the core ligase/apoptosis/autophagy roles. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt regulation of neuronal apoptosis, selective autophagy or cell |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of RING E3 ubiquitin ligase activity, consistent with the RING-HC domain and experimental evidence. Reason: Core molecular function; TRIM17 is a RING-type E3 ubiquitin ligase. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt E3 ubiquitin ligase that plays important roles in the |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning assignment of ubiquitin-protein transferase activity; core function. Reason: Core molecular function corroborated by experimental RING-dependent E3 ligase activity. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt E3 ubiquitin ligase that plays important roles in the |
| 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 the experimental EXP cytoplasm annotation. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of lysosomal localization from the UniProt subcellular location, consistent with the autophagy role. Reason: Correct localization; redundant with the experimental EXP lysosome annotation. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. Lysosome |
| 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-HC and B-box zinc fingers. Reason: Correct (RING/B-box coordinate Zn2+) and underpins ligase activity, but generic; the informative MF is ubiquitin ligase activity. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt E3 ubiquitin ligase that plays important roles in the |
| GO:0051865 protein autoubiquitination | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning assignment of autoubiquitination, consistent with the experimental IDA evidence. Reason: Core activity; TRIM17 is autoubiquitinated (RING-dependent), redundant with the IDA annotation. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Auto-ubiquitinated. |
| 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/TRIM17/TRIM17-uniprot.txt EC=2.3.2.27 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Interaction (TRIM39, Q9HCM9) from a proteome-scale interaction map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510; |
| GO:0005515 protein binding | IPI PMID:22493164 Systematic analysis of dimeric E3-RING interactions reveals ... | KEEP AS NON CORE | Summary: Interactions (TRIM41, TRIM39) from a dimeric E3-RING interaction screen. Bare protein binding is uninformative. Reason: High-throughput E3-RING dimer screen; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; Q8WV44: TRIM41; NbExp=4; IntAct=EBI-743894, EBI-725997; |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | KEEP AS NON CORE | Summary: Interaction (HGS, O14964) from an alternative-splicing interaction study. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; O14964: HGS; NbExp=6; IntAct=EBI-743894, EBI-740220; |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | KEEP AS NON CORE | Summary: Interaction (TRIM39, Q9HCM9) from an interactome-perturbation study. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510; |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Interaction (TRIM39, Q9HCM9) from a population-variant interaction study. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Interactions (TRIM41, MEOX2, HGS) from the binary interactome reference map. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Q9Y577; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-743894, EBI-16439278; |
| 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 autoubiquitination and substrate-degradation roles better capture the activity. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt PATHWAY: Protein modification; protein ubiquitination. |
| GO:0005737 cytoplasm | EXP PMID:27562068 TRIM17 contributes to autophagy of midbodies while actively ... | ACCEPT | Summary: Experimental evidence of cytoplasmic localization in the midbody-autophagy study. Core localization. Reason: Core cellular component, experimentally demonstrated. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. |
| GO:0005764 lysosome | EXP PMID:27562068 TRIM17 contributes to autophagy of midbodies while actively ... | ACCEPT | Summary: Experimental evidence of lysosomal localization in the midbody-autophagy study, consistent with the autophagy role. Reason: Experimentally supported localization consistent with TRIM17's selective-autophagy function. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. Lysosome |
| GO:0005515 protein binding | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | KEEP AS NON CORE | Summary: Interactions with autophagy machinery (BECN1, ULK1, SQSTM1, ATG8 proteins) from the TRIM-autophagy study. Bare protein binding is uninformative. Reason: Records real, functionally relevant autophagy interactions but bare protein binding is uninformative; better captured by the adaptor-activity and autophagy annotations. Supporting Evidence: PMID:25127057 TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: TRIM17 bridges autophagy machinery and regulators (e.g. MCL1/BECN1, ULK1), acting as a molecular adaptor/scaffold in selective autophagy. Reason: Informative molecular function capturing TRIM17's scaffold/adaptor role in selective-autophagy regulation. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Autophagy-inhibitory activity involves MCL1, which TRIM17 |
| GO:0160247 autophagy cargo adaptor activity | IMP PMID:27562068 TRIM17 contributes to autophagy of midbodies while actively ... | NEW | Summary: TRIM17 has a selective-autophagy adaptor/receptor role, especially in the target-selective midbody-autophagy context, while also inhibiting degradation of other cargo classes. Reason: PN showed that GO:0160247 is the best existing GO MF for the selective-autophagy adaptor component of TRIM17's role. This is kept as a scoped NEW recommendation for the midbody-selective activity rather than the core MF, because TRIM17's broader autophagy role is often inhibitory through MCL1/BECN1 stabilization. Supporting Evidence: PMID:27562068 TRIM17 promoted the removal of midbodies PMID:25127057 TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1 |
| GO:0006914 autophagy | IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | ACCEPT | Summary: Direct evidence that TRIM17 functions in (regulation of) selective autophagy. Core process. Reason: Core biological process; TRIM17 regulates selective autophagy (inhibiting degradation of many targets while contributing to midbody autophagy). Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt degradation of diverse known targets while contributing to autophagy of |
| 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 TRIM17 regulates localization of autophagy components/regulators (and, more broadly, NFAT nuclear localization). Reason: Supported but a broad process term reflecting the autophagy-scaffold and NFAT-localization roles. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Autophagy-inhibitory activity involves MCL1, which TRIM17 |
| GO:0051865 protein autoubiquitination | IDA PMID:19358823 TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin ... | ACCEPT | Summary: Direct evidence that TRIM17/terf is autoubiquitinated (RING-dependent). Core activity. Reason: Core biological process; RING-dependent autoubiquitination is a hallmark of TRIM17 ligase activity. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Auto-ubiquitinated. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:19358823 TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin ... | ACCEPT | Summary: Direct evidence that TRIM17/terf is a ubiquitin E3 ligase (transferase). Core MF. Reason: Core molecular function; demonstrated RING E3 ligase activity. Supporting Evidence: PMID:19358823 TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase. |
| GO:0005515 protein binding | IPI PMID:19358823 TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin ... | KEEP AS NON CORE | Summary: Interaction with TRIM44 (via coiled coil), which stabilizes TRIM17. Bare protein binding is uninformative. Reason: Records a real, functionally relevant TRIM44 interaction but bare protein binding is uninformative. Supporting Evidence: file:human/TRIM17/TRIM17-uniprot.txt Interacts (via coiled coil) with TRIM44 (via coiled coil) |
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Download this section (compressed HTML)Q: How does TRIM17 achieve target selectivity in autophagy - inhibiting degradation of most substrates while promoting autophagy of midbodies - and what determines whether a bound partner (e.g. MCL1, BECN1) is protected or degraded?
Q: Given TRIM17's near testis-exclusive expression yet prominent roles described in neurons (MCL1, NFAT, SNCA), how is its function partitioned across tissues and which roles are physiologically dominant in vivo?
Experiment: Perform ubiquitinome and degradation-rate profiling in TRIM17-knockout versus wild-type neurons to define the endogenous substrate repertoire (MCL1, ZWINT, others) and separate direct ubiquitination targets from indirectly stabilized proteins.
Experiment: Use RING-dead and substrate-binding TRIM17 mutants to dissect which functions (MCL1 degradation/apoptosis, NFAT localization control, midbody autophagy versus autophagy inhibition) require catalytic E3 activity versus a non-catalytic scaffold/adaptor role.
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