TRIM17

UniProt ID: Q9Y577
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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)

Core Functions

Functions as a RING-type E3 ubiquitin ligase that regulates neuronal apoptosis by ubiquitinating and degrading the anti-apoptotic protein MCL1 to initiate neuronal death, and undergoes RING-dependent autoubiquitination.

Molecular Function:
ubiquitin protein ligase activity
Directly Involved In:
protein autoubiquitination
Cellular Locations:
cytoplasm
Supporting Evidence:
  • file:human/TRIM17/TRIM17-uniprot.txt
    ubiquitination and degradation of MCL1 to initiate neuronal death.
  • PMID:19358823
    TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase.

Modulates selective autophagy in a target-selective manner - inhibiting autophagic degradation of diverse substrates while contributing to autophagy of midbodies - acting as an adaptor/scaffold that assembles MCL1 with BECN1 and engages autophagy machinery.

Molecular Function:
protein-macromolecule adaptor activity
Directly Involved In:
autophagy
Cellular Locations:
cytoplasm lysosome
Supporting Evidence:
  • file:human/TRIM17/TRIM17-uniprot.txt
    degradation of diverse known targets while contributing to autophagy of
  • PMID:27562068
    TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000003
Gene Ontology annotation based on Enzyme Commission mapping
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000041
Gene Ontology annotation based on UniPathway vocabulary mapping
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:16189514
Towards a proteome-scale map of the human protein-protein interaction network.
PMID:19358823
TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase.
  • TRIM17/terf is a TRIM ubiquitin E3 ligase that is autoubiquitinated; TRIM44 interacts with (via coiled coil) and stabilizes TRIM17.
PMID:22023800
Terf/TRIM17 stimulates degradation of kinetochore protein ZWINT and regulates cell proliferation.
  • TRIM17/terf interacts with ZWINT, down-regulates ZWINT protein levels, and negatively regulates cell proliferation.
PMID:22493164
Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks.
PMID:25127057
TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
  • TRIM17 is among TRIMs that regulate autophagy; it interacts with autophagy machinery and acts as an adaptor/scaffold, regulating protein localization.
PMID:26871637
Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
PMID:27562068
TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation.
  • TRIM17 contributes to autophagy of midbodies while inhibiting autophagic degradation of other targets (via MCL1 assembled with BECN1); it localizes to the cytoplasm and lysosome.
PMID:29892012
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:32296183
A reference map of the human binary protein interactome.

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(TRIM17-notes.md)

TRIM17 (terf, testis RING finger protein, RNF16) review notes

UniProt: Q9Y577 (TRIM17_HUMAN). EC=2.3.2.27. RING-type E3 ubiquitin transferase. TRIM/RBCC family.
Has a genuine RING-HC domain (CDD: RING-HC_TRIM17_C-IV; InterPro Znf-RING), B-box, coiled-coil, B30.2/SPRY.
Tissue: almost exclusively testis.

Core functions (UniProt FUNCTION + experimental)

  1. RING-type E3 ubiquitin ligase; autoubiquitinated. [PMID:19358823; UniProt EC; RING-HC]
  2. GO:0004842 ubiquitin-protein transferase (IDA PMID:19358823), GO:0051865 protein autoubiquitination (IDA PMID:19358823), GO:0061630 (IBA, IEA EC), ARBA IEA transferase/autoubiq.
  3. Regulator of neuronal apoptosis: ubiquitinates and degrades the anti-apoptotic MCL1 to initiate neuronal death. Also regulates NFAT transcription factors NFATC3/NFATC4 by preventing their nuclear localization (inhibiting their transcriptional activity). [UniProt FUNCTION; PMID:22023800 (MCL1/neuronal apoptosis) - not in stub]
  4. Selective autophagy modulation: inhibits autophagic degradation of diverse targets while contributing to autophagy of midbodies; autophagy-inhibitory activity involves MCL1 which TRIM17 assembles into complexes with BECN1. PMID:27562068
  5. GO:0006914 autophagy (IDA PMID:25127057), GO:0032880 regulation of protein localization (IMP PMID:25127057), GO:0030674 protein-macromolecule adaptor activity (IPI PMID:25127057 with O75385=ULK1, Q8IYI6? - actually O75385 = ULK1; Q8IYI6 = ?). Adaptor activity captures scaffold role.
  6. Prevents TRIM28 E3 ligase activity / its ubiquitination of anti-apoptotic BCL2A1, by interacting with TRIM28. [PMID:19358823? actually PMID:30042493 per UniProt; the BCL2A1 finding cited to PubMed:19358823 in FUNCTION]. TRIM44 stabilizes TRIM17/terf (PMID:19358823).
  7. Stimulates degradation of ZWINT -> negative regulation of cell proliferation (PMID:22023800).
  8. Decreases TRIM41-mediated degradation of ZSCAN2 -> stimulates alpha-synuclein/SNCA transcription in neurons (By similarity). [Note: task mentions ZSCAN21; UniProt says ZSCAN2 for human via similarity to mouse Q7TPM3 where it's Zscan21/Zipro1.]

Localization

  • Cytoplasm (IBA, IEA, EXP PMID:27562068). Core.
  • Lysosome (IEA SubCell, EXP PMID:27562068): consistent with autophagy role.

Notes on specific annotations

  • GO:0045087 innate immune response (IBA): family-level phylogenetic inference; TRIM17's documented roles are apoptosis/autophagy/proliferation, not innate immunity. Weakly supported for TRIM17 specifically. KEEP_AS_NON_CORE (or MARK_AS_OVER_ANNOTATED). I'll KEEP_AS_NON_CORE per guideline not to overrule IBA without strong grounds, but note it's not a documented TRIM17 function. Actually it's an over-propagated family IBA -> MARK_AS_OVER_ANNOTATED is defensible. Use KEEP_AS_NON_CORE to be conservative.
  • GO:0010468 regulation of gene expression (IBA): TRIM17 regulates NFAT/transcription indirectly (via localization/degradation). KEEP_AS_NON_CORE.
  • GO:0004842/GO:0061630 ubiquitin ligase/transferase: core. ACCEPT.
  • protein binding (GO:0005515) IPI: TRIM39 (Q9HCM9 x several), TRIM41 (Q8WV44), HGS (O14964), MEOX2 (Q6FHY5), MCL1 (Q07820? no), BECN1 (O75385? no - O75385=ULK1), and PMID:25127057 set (O75385, Q8IYI6, O95166=LC3B, Q13501=SQSTM1, Q14457=BECN1, Q9H492=MAP1LC3A). Bare protein binding -> KEEP_AS_NON_CORE.
  • PMID:25127057 IPI Q14457 = BECN1; O75385 = ULK1; Q13501 = SQSTM1; O95166 = GABARAPL2/LC3? ; Q9H492 = MAP1LC3A; Q8IYI6 = ? These are autophagy machinery.
  • GO:0030674 protein-macromolecule adaptor activity (IPI PMID:25127057): scaffold linking MCL1/BECN1/autophagy machinery. ACCEPT (informative MF for the autophagy-regulatory scaffold).
  • GO:0008270 zinc ion binding (IEA): RING/B-box. KEEP_AS_NON_CORE.

GO IDs verified relevant

  • GO:0061630 / GO:0004842 ubiquitin ligase/transferase (core MF)
  • GO:0051865 protein autoubiquitination
  • GO:0006914 autophagy (core BP - regulation of selective autophagy)
  • GO:0030674 protein-macromolecule adaptor activity
  • GO:0005737 cytoplasm / GO:0005764 lysosome (CC)

Pn Notes

(TRIM17-pn-notes.md)

TRIM17 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y577
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-14
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: 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.
  • Existing/core annotation action counts: ACCEPT: 13; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 1; NEW: 1

PN Consistency Summary

  • Consistency: Consistent. PN (selective-autophagy receptor for midbodies + genuine RING E3), review and notes agree: TRIM17 has a real RING-HC domain, autoubiquitinates (PMID:19358823), degrades MCL1 to drive neuronal apoptosis, and acts in target-selective autophagy — broadly INHIBITING autophagic degradation while contributing to midbody autophagy via MCL1/BECN1 scaffolding (PMID:27562068). Functional RING → catalytic ligase MF correct. No contradictions; the nuance that TRIM17 is mostly an autophagy inhibitor is captured in both.
  • PN story / NEW pressure: PN routes midbody autophagy through the cargo-adaptor MF GO:0160247 (verified real) because GO has NO dedicated "midbody autophagy" process term (confirmed — searchClasses returns nothing). The review already captures this MF as GO:0030674 protein-macromolecule adaptor activity (ACCEPT, IPI PMID:25127057) and GO:0006914 autophagy (ACCEPT) — so the role IS in GOA at the generic level, and GO:0160247 is the more specific upgrade (hence PN's "more_specific_than_existing_goa"). Defensible refinement, not a brand-new role. No new GO process term mintable for midbody autophagy.
  • Evidence alignment: Strong overlap. PN cites the LIR/cargo-receptor review and the midbody paper (= PMID:27562068, review HIGH) and 33791238/19489725 (TRIM/E3 reviews). Review refs (PMID:27562068, 25127057, 19358823) cover the autophagy + ligase arms; the MCL1/neuronal-apoptosis primary paper (PMID:22023800, in notes) is not a cited reference in the review.
  • Verdict: Consistent; cargo-adaptor MF upgrade warranted; RING ligase already captured. Recommended edits: [YAML] upgrade the GO:0030674 adaptor MF to the more specific GO:0160247 autophagy cargo adaptor activity (supported by PMID:27562068/25127057), scoped to midbody autophagy. [REF] consider adding PMID:22023800 (MCL1/ZWINT, neuronal apoptosis) to references to support the core MCL1-degradation function.

Full Consistency Review

  • UniProt: Q9Y577 (terf/RNF16) · batch: proteostasis-batch-2026-06-14 · review status: COMPLETE
  • PN placement: 2 rows — ALP|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy; UPS|E3 ubiquitin and UBL ligases|RING|TRIM / class IV|SPRY. PN-node mapping: Midbody-autophagy type → mapped/ok GO:0160247 autophagy cargo adaptor activity (more_specific_than_existing_goa); RING group → mapped/ok GO:0061630 ubiquitin protein ligase activity (already_in_goa_exact); E3-ligase ancestors = no_mapping/context_only.
  • Consistency: Consistent. PN (selective-autophagy receptor for midbodies + genuine RING E3), review and notes agree: TRIM17 has a real RING-HC domain, autoubiquitinates (PMID:19358823), degrades MCL1 to drive neuronal apoptosis, and acts in target-selective autophagy — broadly INHIBITING autophagic degradation while contributing to midbody autophagy via MCL1/BECN1 scaffolding (PMID:27562068). Functional RING → catalytic ligase MF correct. No contradictions; the nuance that TRIM17 is mostly an autophagy inhibitor is captured in both.
  • PN story / NEW pressure: PN routes midbody autophagy through the cargo-adaptor MF GO:0160247 (verified real) because GO has NO dedicated "midbody autophagy" process term (confirmed — searchClasses returns nothing). The review already captures this MF as GO:0030674 protein-macromolecule adaptor activity (ACCEPT, IPI PMID:25127057) and GO:0006914 autophagy (ACCEPT) — so the role IS in GOA at the generic level, and GO:0160247 is the more specific upgrade (hence PN's "more_specific_than_existing_goa"). Defensible refinement, not a brand-new role. No new GO process term mintable for midbody autophagy.
  • Mapping strategy: No node change needed. Cargo-adaptor MF over bare protein binding is the prescribed pattern and matches the review. Genuine RING → GO:0061630 already_in_goa_exact, correctly retained. Caution: TRIM17's autophagy role is predominantly inhibitory/selective; the cargo-adaptor MF should be scoped to the midbody-autophagy contribution, not read as a general pro-autophagy receptor.
  • Evidence alignment: Strong overlap. PN cites the LIR/cargo-receptor review and the midbody paper (= PMID:27562068, review HIGH) and 33791238/19489725 (TRIM/E3 reviews). Review refs (PMID:27562068, 25127057, 19358823) cover the autophagy + ligase arms; the MCL1/neuronal-apoptosis primary paper (PMID:22023800, in notes) is not a cited reference in the review.
  • Verdict: Consistent; cargo-adaptor MF upgrade warranted; RING ligase already captured. Recommended edits: [YAML] upgrade the GO:0030674 adaptor MF to the more specific GO:0160247 autophagy cargo adaptor activity (supported by PMID:27562068/25127057), scoped to midbody autophagy. [REF] consider adding PMID:22023800 (MCL1/ZWINT, neuronal apoptosis) to references to support the core MCL1-degradation function.
  • 2026-06-18 follow-up: Implemented the scoped YAML recommendation by adding GO:0160247 as a NEW midbody-selective autophagy cargo-adaptor recommendation, but retained GO:0030674 as the core MF after review feedback because TRIM17's dominant autophagy role is inhibitory/context-dependent. PMID:22023800 was added as a medium-relevance ZWINT/proliferation reference with an explicit caveat that the cached abstract does not support the MCL1 apoptosis claim.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-14
  • review_yaml: genes/human/TRIM17/TRIM17-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Midbody autophagy

  • UniProt: Q9Y577
  • In branches: ALP, UPS
  • Notes: Receptor for selective autophagy. Normally acts as a prominent inhibitor of bulk autophagy via stabilizing interactions between autophagy factor Beclin1 and anti-autophagy Mcl-1. TRIM17 is specifically required for the promotion and the removal of midbodies, remnants of the cell division machinery that are known autophagy targets via its interaction with p62/SQSTM1 and LC3B.
  • PN references (titles):
    • Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
    • TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0160247 autophagy cargo adaptor activity]
      rationale: Midbody-autophagy receptors such as SQSTM1 link ubiquitinated midbody material to the autophagy machinery. GO does not currently expose a dedicated midbody-autophagy process term in the local ontology cache, so the receptor activity term is the best available mapping target.
    • [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | RING | TRIM / class IV | SPRY

  • UniProt: Q9Y577
  • In branches: ALP, UPS
  • Signature domains: IPR001841
  • Auxiliary domains: IPR003877, IPR006574
  • PN references (titles):
    • 33791238 / rev
    • 19489725 / rev
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING|TRIM / class IV|SPRY
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING|TRIM / class IV
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower E3-ligase architecture, component, or domain subdivision already covered by the curated parent E3 mapping. No additional direct GO mapping is needed at this node.
    • [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This PN group is a catalytic ubiquitin E3 ligase bucket. The shared GO molecular-function target is ubiquitin protein ligase activity.
    • [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
      status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
    • [branch] Ubiquitin Proteasome System
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (2)

  • GO:0160247 autophagy cargo adaptor activity | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy
  • GO:0061630 ubiquitin protein ligase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q9Y577
gene_symbol: TRIM17
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q9Y577-1
- name: '2'
  id: Q9Y577-2
  sequence_note: VSP_040994, VSP_040995
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic inference of cytoplasmic activity; the core compartment for TRIM17.
    action: ACCEPT
    reason: Correct core localization; consistent with experimental EXP cytoplasm evidence.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}.'
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Family-level phylogenetic inference of innate immune involvement; TRIM17's documented roles are in apoptosis, autophagy and proliferation rather than innate immunity.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: E3 ubiquitin ligase that plays important roles in the
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of regulation of gene expression; TRIM17 indirectly affects transcription (NFAT localization, ZSCAN/SNCA).
    action: KEEP_AS_NON_CORE
    reason: Indirectly supported (NFAT nuclear-localization control; ZSCAN/SNCA) but a broad term and secondary to the core ligase/apoptosis/autophagy roles.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: regulation of neuronal apoptosis, selective autophagy or cell
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic inference of RING E3 ubiquitin ligase activity, consistent with the RING-HC domain and experimental evidence.
    action: ACCEPT
    reason: Core molecular function; TRIM17 is a RING-type E3 ubiquitin ligase.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: E3 ubiquitin ligase that plays important roles in the
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: ARBA machine-learning assignment of ubiquitin-protein transferase activity; core function.
    action: ACCEPT
    reason: Core molecular function corroborated by experimental RING-dependent E3 ligase activity.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: E3 ubiquitin ligase that plays important roles in the
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of cytoplasmic localization from the UniProt subcellular location; the core compartment.
    action: ACCEPT
    reason: Correct core localization; redundant with the experimental EXP cytoplasm annotation.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}.'
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of lysosomal localization from the UniProt subcellular location, consistent with the autophagy role.
    action: ACCEPT
    reason: Correct localization; redundant with the experimental EXP lysosome annotation.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. Lysosome'
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic assignment of zinc ion binding by the RING-HC and B-box zinc fingers.
    action: KEEP_AS_NON_CORE
    reason: Correct (RING/B-box coordinate Zn2+) and underpins ligase activity, but generic; the informative MF is ubiquitin ligase activity.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: E3 ubiquitin ligase that plays important roles in the
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning assignment of autoubiquitination, consistent with the experimental IDA evidence.
    action: ACCEPT
    reason: Core activity; TRIM17 is autoubiquitinated (RING-dependent), redundant with the IDA annotation.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: Auto-ubiquitinated.
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: EC 2.3.2.27-based electronic assignment of ubiquitin protein ligase activity; core function.
    action: ACCEPT
    reason: Core molecular function corroborated by experimental RING-dependent ligase activity.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: EC=2.3.2.27
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Interaction (TRIM39, Q9HCM9) from a proteome-scale interaction map. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22493164
  qualifier: enables
  review:
    summary: Interactions (TRIM41, TRIM39) from a dimeric E3-RING interaction screen. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput E3-RING dimer screen; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; Q8WV44: TRIM41; NbExp=4; IntAct=EBI-743894, EBI-725997;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: Interaction (HGS, O14964) from an alternative-splicing interaction study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; O14964: HGS; NbExp=6; IntAct=EBI-743894, EBI-740220;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29892012
  qualifier: enables
  review:
    summary: Interaction (TRIM39, Q9HCM9) from an interactome-perturbation study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Interaction (TRIM39, Q9HCM9) from a population-variant interaction study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; Q9HCM9: TRIM39; NbExp=8; IntAct=EBI-743894, EBI-739510;'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Interactions (TRIM41, MEOX2, HGS) from the binary interactome reference map. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'Q9Y577; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-743894, EBI-16439278;'
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway-derived general protein ubiquitination process.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific autoubiquitination and substrate-degradation roles better capture the activity.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'PATHWAY: Protein modification; protein ubiquitination.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:27562068
  qualifier: located_in
  review:
    summary: Experimental evidence of cytoplasmic localization in the midbody-autophagy study. Core localization.
    action: ACCEPT
    reason: Core cellular component, experimentally demonstrated.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}.'
- term:
    id: GO:0005764
    label: lysosome
  evidence_type: EXP
  original_reference_id: PMID:27562068
  qualifier: located_in
  review:
    summary: Experimental evidence of lysosomal localization in the midbody-autophagy study, consistent with the autophagy role.
    action: ACCEPT
    reason: Experimentally supported localization consistent with TRIM17's selective-autophagy function.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27562068}. Lysosome'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25127057
  qualifier: enables
  review:
    summary: Interactions with autophagy machinery (BECN1, ULK1, SQSTM1, ATG8 proteins) from the TRIM-autophagy study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real, functionally relevant autophagy interactions but bare protein binding is uninformative; better captured by the adaptor-activity and autophagy annotations.
    supported_by:
    - reference_id: PMID:25127057
      supporting_text: TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
- term:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  evidence_type: IPI
  original_reference_id: PMID:25127057
  qualifier: enables
  review:
    summary: TRIM17 bridges autophagy machinery and regulators (e.g. MCL1/BECN1, ULK1), acting as a molecular adaptor/scaffold in selective autophagy.
    action: ACCEPT
    reason: Informative molecular function capturing TRIM17's scaffold/adaptor role in selective-autophagy regulation.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: Autophagy-inhibitory activity involves MCL1, which TRIM17
- term:
    id: GO:0160247
    label: autophagy cargo adaptor activity
  evidence_type: IMP
  original_reference_id: PMID:27562068
  qualifier: enables
  review:
    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.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:27562068
      supporting_text: TRIM17 promoted the removal of midbodies
      reference_section_type: ABSTRACT
    - reference_id: PMID:25127057
      supporting_text: TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1
      reference_section_type: ABSTRACT
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IDA
  original_reference_id: PMID:25127057
  qualifier: involved_in
  review:
    summary: Direct evidence that TRIM17 functions in (regulation of) selective autophagy. Core process.
    action: ACCEPT
    reason: Core biological process; TRIM17 regulates selective autophagy (inhibiting degradation of many targets while contributing to midbody autophagy).
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: degradation of diverse known targets while contributing to autophagy of
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IMP
  original_reference_id: PMID:25127057
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that TRIM17 regulates localization of autophagy components/regulators (and, more broadly, NFAT nuclear localization).
    action: KEEP_AS_NON_CORE
    reason: Supported but a broad process term reflecting the autophagy-scaffold and NFAT-localization roles.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: Autophagy-inhibitory activity involves MCL1, which TRIM17
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IDA
  original_reference_id: PMID:19358823
  qualifier: involved_in
  review:
    summary: Direct evidence that TRIM17/terf is autoubiquitinated (RING-dependent). Core activity.
    action: ACCEPT
    reason: Core biological process; RING-dependent autoubiquitination is a hallmark of TRIM17 ligase activity.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: Auto-ubiquitinated.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:19358823
  qualifier: enables
  review:
    summary: Direct evidence that TRIM17/terf is a ubiquitin E3 ligase (transferase). Core MF.
    action: ACCEPT
    reason: Core molecular function; demonstrated RING E3 ligase activity.
    supported_by:
    - reference_id: PMID:19358823
      supporting_text: TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19358823
  qualifier: enables
  review:
    summary: Interaction with TRIM44 (via coiled coil), which stabilizes TRIM17. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real, functionally relevant TRIM44 interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
      supporting_text: Interacts (via coiled coil) with TRIM44 (via coiled coil)
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding (TRIM39) annotation.
- id: PMID:19358823
  title: TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase.
  findings:
  - statement: TRIM17/terf is a TRIM ubiquitin E3 ligase that is autoubiquitinated; TRIM44 interacts with (via coiled coil) and stabilizes TRIM17.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available. Establishes TRIM17/terf as an E3 ligase (transferase, autoubiquitination) and the TRIM44 interaction. "terf" is testis RING finger = TRIM17.
- id: PMID:22023800
  title: Terf/TRIM17 stimulates degradation of kinetochore protein ZWINT and regulates
    cell proliferation.
  findings:
  - statement: TRIM17/terf interacts with ZWINT, down-regulates ZWINT protein levels,
      and negatively regulates cell proliferation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-cached abstract supports the ZWINT/proliferation activity in the description; it does not directly support the MCL1 apoptosis claim.
- id: PMID:22493164
  title: Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput E3-RING dimer screen; source of bare protein binding (TRIM41/TRIM39) annotations.
- id: PMID:25127057
  title: TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
  findings:
  - statement: TRIM17 is among TRIMs that regulate autophagy; it interacts with autophagy machinery and acts as an adaptor/scaffold, regulating protein localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract-only. Supports TRIM17 autophagy involvement, adaptor activity and regulation of protein localization.
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome (alternative splicing); source of a bare protein binding (HGS) annotation.
- id: PMID:27562068
  title: TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation.
  findings:
  - statement: TRIM17 contributes to autophagy of midbodies while inhibiting autophagic degradation of other targets (via MCL1 assembled with BECN1); it localizes to the cytoplasm and lysosome.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available. Establishes TRIM17's target-selective autophagy role and cytoplasm/lysosome localization.
- id: PMID:29892012
  title: An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding (TRIM39) annotation.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of a bare protein binding (TRIM39) annotation.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Binary interactome reference map; source of bare protein binding (TRIM41, MEOX2, HGS) annotations.
core_functions:
- description: Functions as a RING-type E3 ubiquitin ligase that regulates neuronal apoptosis by ubiquitinating and degrading the anti-apoptotic protein MCL1 to initiate neuronal death, and undergoes RING-dependent autoubiquitination.
  molecular_function:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
    supporting_text: ubiquitination and degradation of MCL1 to initiate neuronal death.
  - reference_id: PMID:19358823
    supporting_text: TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase.
  directly_involved_in:
  - id: GO:0051865
    label: protein autoubiquitination
- description: Modulates selective autophagy in a target-selective manner - inhibiting autophagic degradation of diverse substrates while contributing to autophagy of midbodies - acting as an adaptor/scaffold that assembles MCL1 with BECN1 and engages autophagy machinery.
  molecular_function:
    id: GO:0030674
    label: protein-macromolecule adaptor activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005764
    label: lysosome
  supported_by:
  - reference_id: file:human/TRIM17/TRIM17-uniprot.txt
    supporting_text: degradation of diverse known targets while contributing to autophagy of
  - reference_id: PMID:27562068
    supporting_text: TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation.
  directly_involved_in:
  - id: GO:0006914
    label: autophagy
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.