LTN1

UniProt ID: O94822
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

LTN1 (Listerin, also RNF160/ZNF294) is a large (1766 aa) cytosolic RING-type E3 ubiquitin-protein ligase (EC 2.3.2.27) that is the catalytic core of the ribosome-associated quality control (RQC) complex. Its N-terminal HEAT/ARM-repeat solenoid wraps around the 60S large ribosomal subunit while its C-terminal RING-CH (RING-type zinc finger) domain catalyzes ubiquitin transfer. When an elongating 80S ribosome stalls and is split into subunits by the rescue factors PELO/HBS1L/ABCE1, the incomplete nascent polypeptide remains attached to a peptidyl-tRNA housed in the 60S subunit; LTN1 is recruited to these 60S-nascent chain complexes by NEMF, which senses the exposed P-site tRNA, and poly-ubiquitinates the trapped nascent chain. This commits aberrant translation products to extraction by the VCP/p97 AAA-ATPase and degradation by the proteasome, preventing accumulation of potentially toxic incomplete proteins. LTN1 thus functions in nascent-chain surveillance and rescue of stalled ribosomes; it is broadly expressed and acts in the cytosol in association with the 60S subunit.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: LTN1 acts in the cytosol in association with the 60S subunit and the RQC complex. The phylogenetic (IBA) cytosolic localization is consistent with direct experimental evidence and the documented cytoplasmic site of action.
Reason: Cytosol is the correct site of action; supported by experimental IDA (PMID:25578875, PMID:28757607) and the UniProt subcellular location.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: LTN1 ubiquitinates 60S-stalled nascent chains to commit them to proteasomal degradation; this is its defining biological process and is well supported across the LTN1/Rkr1 family.
Reason: Directly supported experimentally; the RQC pathway degrades incompletely synthesized nascent chains via LTN1-mediated ubiquitination.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation
GO:0061630 ubiquitin protein ligase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: The core molecular function of Listerin is RING-type ubiquitin ligase activity, transferring ubiquitin to nascent-chain lysines. Conserved across the LTN1/Rkr1 family.
Reason: Core molecular function; corroborated by IDA (PMID:25578875), EC 2.3.2.27, and the C-terminal RING-CH domain.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
E3 ubiquitin-protein ligase component of the ribosome quality control complex
GO:0072344 rescue of stalled cytosolic ribosome
IBA
GO_REF:0000033 		ACCEPT
Summary: By clearing the nascent chain from 60S-stalled complexes, LTN1 participates in resolving stalled ribosomes. Conserved RQC role.
Reason: Phylogenetically and experimentally supported; LTN1 is a defining factor of the stalled-ribosome rescue/RQC pathway.
Supporting Evidence:
PMID:25578875
the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
GO:1990112 RQC complex
IBA
GO_REF:0000033 		ACCEPT
Summary: LTN1 is a constitutive component of the RQC complex (LTN1 + NEMF + TCF25) on the 60S subunit.
Reason: Directly demonstrated; LTN1 is one of the three defining RQC complex subunits.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit
GO:0043023 ribosomal large subunit binding
IBA
GO_REF:0000033 		ACCEPT
Summary: LTN1's HEAT/ARM-repeat solenoid wraps the 60S large subunit, and its C-terminal RWD domain contacts the ribosome; binding the 60S subunit is integral to its function.
Reason: Structurally and biochemically demonstrated; LTN1 cofractionates with and binds 60S-nascent chain complexes.
Supporting Evidence:
PMID:25578875
Listerin's C-terminal RWD domain directly contacts the ribosome to position the adjacent ligase domain near the nascent polypeptide exit tunnel
GO:0005829 cytosol
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic transfer of the cytosol localization from the UniProt subcellular location, consistent with stronger experimental evidence.
Reason: Redundant with IDA cytosol annotations; correct compartment.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0008270 zinc ion binding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: The C-terminal RING-type zinc finger coordinates zinc as a structural requirement for the ligase fold. This is a structural attribute supporting, but not equal to, the ligase activity.
Reason: Accurate structural feature of the RING domain (residues 1715-1762) but subsidiary to the informative ubiquitin ligase activity; not a standalone core function.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
RING-type
GO:0061630 ubiquitin protein ligase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment of the core RING E3 ligase activity, consistent with the experimental IDA evidence and EC 2.3.2.27.
Reason: Correct core molecular function; redundant with IDA/IBA evidence.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
EC=2.3.2.27
GO:1990112 RQC complex
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based electronic assignment to the RQC complex, consistent with the experimental IDA annotation.
Reason: Correct; LTN1 is a defining RQC complex subunit.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
Component of the ribosome quality control complex (RQC)
GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro-based electronic assignment of the RQC catabolic process, consistent with experimental evidence.
Reason: Correct defining biological process; redundant with IDA/IBA.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation
GO:0005515 protein binding
IPI
PMID:21903422
Mapping a dynamic innate immunity protein interaction networ... 		KEEP AS NON CORE
Summary: High-throughput innate-immunity interactome capturing LTN1 interactions with IRF7, STING1 and TIRAP. The bare protein binding term is uninformative and the partners are unrelated to LTN1's RQC ligase function.
Reason: Records real IntAct interactions (IRF7/STING1/TIRAP) from an innate-immunity screen, but bare protein binding is uninformative and these partners do not reflect the core RQC ligase function; per guidelines not elevated to core.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
O94822; Q92985: IRF7
GO:0004842 ubiquitin-protein transferase activity
IEA
GO_REF:0000107 		ACCEPT
Summary: Ortholog-based electronic transfer of ubiquitin-protein transferase activity, a parent/sibling of the more precise ubiquitin protein ligase activity that LTN1 enables.
Reason: Correct general molecular function; the more specific GO:0061630 captures the core RING E3 ligase activity.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
RING-type E3 ubiquitin transferase listerin
GO:0051865 protein autoubiquitination
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: LTN1 is autoubiquitinated, a common property of RING E3 ligases reflecting their catalytic activity on themselves. Peripheral to the substrate-directed function.
Reason: Supported by the UniProt PTM (autoubiquitinated) but a secondary property of the ligase, not its core nascent-chain-directed function.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
Autoubiquitinated
GO:0072344 rescue of stalled cytosolic ribosome
TAS
Reactome:R-HSA-9948299 		ACCEPT
Summary: Reactome curation of LTN1 in stalled-ribosome rescue, consistent with experimental evidence and the IBA/IDA annotations.
Reason: Correct; redundant with experimentally supported RQC role.
Supporting Evidence:
PMID:25578875
the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
GO:0016567 protein ubiquitination
IEA
GO_REF:0000041 		KEEP AS NON CORE
Summary: General protein ubiquitination process annotation derived from the UniPathway ubiquitination pathway; a parent of the specific RQC catabolic process.
Reason: Correct but generic; the specific GO:1990116 (RQC ubiquitin-dependent catabolism) better captures LTN1's biological role.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
PATHWAY: Protein modification; protein ubiquitination.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-9948362 		ACCEPT
Summary: Reactome curation of the core RING E3 ligase activity of LTN1, consistent with experimental evidence.
Reason: Correct core molecular function.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
E3 ubiquitin-protein ligase component of the ribosome quality control complex
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with LTN1's site of action.
Reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0072344 rescue of stalled cytosolic ribosome
NAS
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria... 		ACCEPT
Summary: Review-based (NAS, ComplexPortal) assertion of LTN1's role in stalled-ribosome rescue, drawn from the RQC review by Filbeck et al.
Reason: Consistent with the experimentally supported RQC role; the cited review summarizes RQC mechanisms from bacteria to humans.
Supporting Evidence:
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria to humans
GO:1990112 RQC complex
NAS
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria... 		ACCEPT
Summary: Review-based (NAS, ComplexPortal) assertion of LTN1 as an RQC complex component.
Reason: Consistent with experimentally demonstrated RQC complex membership.
Supporting Evidence:
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria to humans
GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
NAS
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria... 		ACCEPT
Summary: Review-based (NAS, ComplexPortal) assertion of LTN1's RQC ubiquitin-dependent catabolic role.
Reason: Consistent with the experimentally supported defining process.
Supporting Evidence:
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria to humans
GO:0022626 cytosolic ribosome
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: LTN1 acts on the cytosolic (60S) ribosome; the cryo-EM RQC complex study places Listerin directly on the 60S subunit.
Reason: Directly demonstrated; LTN1 functions while bound to the cytosolic ribosome.
Supporting Evidence:
PMID:25578875
the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
GO:0072344 rescue of stalled cytosolic ribosome
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: Direct experimental evidence that Listerin acts on stalled 60S-nascent chain complexes within the RQC pathway.
Reason: Core, experimentally supported RQC/rescue function.
Supporting Evidence:
PMID:25578875
its mammalian homolog Listerin was both necessary and sufficient for ubiquitination of stalled translation products
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: Direct experimental demonstration that Listerin is the E3 ubiquitin ligase that poly-ubiquitinates 60S-housed nascent chains. This is LTN1's core molecular function.
Reason: Core molecular function with direct experimental (IDA) support and structural basis (C-terminal RING-CH domain).
Supporting Evidence:
PMID:25578875
the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
GO:0005829 cytosol
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: Direct evidence for cytosolic localization of Listerin.
Reason: Correct compartment; LTN1 acts in the cytosol on ribosomes.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:1990112 RQC complex
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: The cryo-EM structure resolves Listerin as part of the RQC complex bound to the 60S-nascent chain, with NEMF bridging.
Reason: Directly demonstrated structurally; LTN1 is a defining RQC complex subunit.
Supporting Evidence:
PMID:25578875
ribosome-bound NEMF recruits and stabilizes Listerin's N-terminal domain
GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
IDA
PMID:25578875
Structure and assembly pathway of the ribosome quality contr... 		ACCEPT
Summary: Direct evidence that Listerin ubiquitinates 60S-stalled nascent chains, committing them to proteasomal degradation.
Reason: Core, experimentally supported defining biological process.
Supporting Evidence:
PMID:25578875
the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
GO:0005829 cytosol
IDA
PMID:28757607
Ubiquitination of stalled ribosome triggers ribosome-associa... 		ACCEPT
Summary: Cytosolic localization annotation derived from an RQC study (Matsuo et al. focused on Hel2/uS10 ubiquitination); consistent with LTN1's cytosolic site of action.
Reason: Correct compartment, consistent with stronger LTN1-specific evidence; the source paper primarily concerns the 40S/Hel2 branch but the localization is accurate.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol
TAS
Reactome:R-HSA-9948318 		ACCEPT
Summary: Reactome curation of LTN1 cytosolic localization.
Reason: Correct compartment; redundant with experimental cytosol annotations.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol
TAS
Reactome:R-HSA-9948362 		ACCEPT
Summary: Reactome curation of LTN1 cytosolic localization.
Reason: Correct compartment; redundant with experimental cytosol annotations.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol
TAS
Reactome:R-HSA-9948427 		ACCEPT
Summary: Reactome curation of LTN1 cytosolic localization.
Reason: Correct compartment; redundant with experimental cytosol annotations.
Supporting Evidence:
file:human/LTN1/LTN1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytosol

Core Functions

RING-type E3 ubiquitin ligase that poly-ubiquitinates incompletely synthesized nascent polypeptides housed in the stalled 60S ribosomal subunit, marking them for VCP/p97 extraction and proteasomal degradation.

Molecular Function:
ubiquitin protein ligase activity
Cellular Locations:
cytosolic ribosome
Supporting Evidence:
  • PMID:25578875
    the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
  • file:human/LTN1/LTN1-uniprot.txt
    E3 ubiquitin-protein ligase component of the ribosome quality control complex

Catalytic component of the ribosome quality control (RQC) complex that, recruited to 60S-nascent chain complexes by NEMF, mediates ribosome-associated ubiquitin-dependent degradation of stalled translation products and contributes to rescue of stalled ribosomes.

Molecular Function:
ubiquitin protein ligase activity
Directly Involved In:
ribosome-associated ubiquitin-dependent protein catabolic process
In Complex:
RQC complex
Supporting Evidence:
  • file:human/LTN1/LTN1-uniprot.txt
    Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit
  • PMID:25578875
    ribosome-bound NEMF recruits and stabilizes Listerin's N-terminal domain

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
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 Subcellular Location vocabulary mapping
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic Assertion of Orthology
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:21903422
Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
PMID:25578875
Structure and assembly pathway of the ribosome quality control complex.
  • Listerin is the E3 ligase that poly-ubiquitinates 60S-housed nascent polypeptides during RQC, and its specificity for nascent chain-60S complexes depends on NEMF.
  • NEMF recruits and stabilizes Listerin's N-terminal domain on the 60S while Listerin's C-terminal RWD domain contacts the ribosome to position the RING ligase domain near the nascent polypeptide exit tunnel.
PMID:28757607
Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
  • Establishes the upstream RQC trigger in which Hel2/RQT1 ubiquitinates the 40S protein uS10; provides the cytosolic RQC context in which LTN1 acts on the 60S branch.
PMID:35452614
Ribosome-associated quality-control mechanisms from bacteria to humans.
  • Review summarizing RQC, including LTN1/Listerin as the RQC complex E3 ligase that ubiquitinates stalled nascent chains for degradation.
Reactome:R-HSA-9948299
Reactome: rescue of stalled ribosome (LTN1)
Reactome:R-HSA-9948318
Reactome: LTN1 cytosol localization
Reactome:R-HSA-9948362
Reactome: LTN1 ubiquitin ligase activity
Reactome:R-HSA-9948427
Reactome: LTN1 cytosol localization
file:human/LTN1/LTN1-uniprot.txt
UniProt entry O94822 (LTN1_HUMAN), E3 ubiquitin-protein ligase listerin
  • E3 ubiquitin-protein ligase component of the RQC complex (LTN1, TCF25, NEMF) on the 60S subunit; recruited to stalled 60S by NEMF and ubiquitinates stalled nascent chains for proteasomal extraction/degradation via VCP/p97; RING-type ligase, EC 2.3.2.27; cytosolic.

Suggested Questions for Experts

Q: How is LTN1 RING ligase activity spatially coordinated with NEMF-mediated CAT-tailing on the same 60S-nascent chain complex, and what determines the order of these events?

Q: Do the innate-immunity interactions (IRF7/STING1/TIRAP) reflect a genuine moonlighting role for LTN1 or are they incidental high-throughput captures?

Suggested Experiments

Experiment: Reconstitute ubiquitination of defined 60S-nascent chain complexes with purified LTN1, NEMF and an E2 to map the lysine sites and ubiquitin chain topology Listerin builds on stalled nascent chains.

Experiment: CRISPR knockout of LTN1 in human cells followed by proteomics of stabilized, CAT-tailed aggregation-prone nascent chains to define the endogenous substrate repertoire.

📚 Additional Documentation

Notes

(LTN1-notes.md)

LTN1 (Listerin) research notes

UniProt: O94822 (LTN1_HUMAN). Gene synonyms: RNF160, ZNF294, C21orf10. 1766 aa.
EC 2.3.2.27 (RING-type E3 ubiquitin transferase). HGNC:13082.

Core function

LTN1/Listerin is the RING-type E3 ubiquitin ligase of the ribosome-associated quality
control (RQC) complex. It poly-ubiquitinates nascent polypeptides that remain housed in
the 60S large ribosomal subunit after a stalled 80S ribosome is split, marking them for
proteasomal degradation (via VCP/p97 extraction).

  • PMID:25578875
  • PMID:25578875
  • UniProt FUNCTION: "E3 ubiquitin-protein ligase component of the ribosome quality control complex (RQC) ... mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation"
  • CATALYTIC ACTIVITY EC=2.3.2.27.

Mechanism / NEMF dependence

Listerin's specificity for nascent-chain–60S complexes depends on NEMF. The 3.6 Å cryo-EM
structure of a nascent chain–60S–Listerin–NEMF complex shows NEMF contacts 60S and
peptidyl-tRNA to sense nascent-chain occupancy; ribosome-bound NEMF recruits and stabilizes
Listerin's N-terminal domain, and Listerin's C-terminal RWD domain contacts the ribosome to
position the ligase (RING) domain near the nascent polypeptide exit tunnel.
- PMID:25578875
- PMID:25578875

Domain architecture

N-terminal HEAT/ARM repeats (16 HEAT repeats) form a ring that wraps the 60S; C-terminal
RING-CH / RING-type zinc finger (residues 1715–1762) is the catalytic ligase domain. The
RING coordinates zinc (zinc ion binding is a structural feature of the RING).

Subunit / complex

Component of the RQC complex (LTN1 + NEMF + TCF25), associated with the 60S ribosomal
subunit; the complex probably also contains VCP/p97.
- UniProt SUBUNIT: "Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit"
- GO term GO:1990112 RQC complex (IDA, PMID:25578875).

Localization

Cytoplasm/cytosol; associated with cytosolic ribosomes (60S). PMID:28757607 used for
cytosol IDA in GOA.

PMID:28757607 caveat

This paper (Matsuo et al. 2017) is about Hel2/RQT1 ubiquitination of 40S uS10 (the ZNF598
ortholog branch), not Listerin catalysis per se. It is cited in LTN1 GOA only for cytosol
localization (located_in GO:0005829). Relevance to LTN1 = LOW/contextual.

PMID:21903422 caveat

Li et al. 2011 Immunity — innate immunity interactome (IRF7, STING1/TMEM173, TIRAP). These
are the IntAct "protein binding" partners (Q92985 IRF7, Q86WV6 STING1, P58753 TIRAP). High-
throughput innate-immunity interactome; not part of LTN1's core RQC ligase function.

Autoubiquitination

LTN1 is autoubiquitinated (UniProt PTM, by similarity to mouse Q6A009). Supports
GO:0051865 protein autoubiquitination (Ensembl IEA).

Actions summary

  • Core MF: GO:0061630 ubiquitin protein ligase activity (IDA PMID:25578875) -> ACCEPT (core).
  • GO:0072344 rescue of stalled cytosolic ribosome, GO:1990116 ribosome-associated ubiquitin-
    dependent protein catabolic process, GO:1990112 RQC complex -> ACCEPT.
  • GO:0043023 ribosomal large subunit binding -> ACCEPT (binds 60S).
  • GO:0008270 zinc ion binding -> ACCEPT (RING structural, non-core).
  • GO:0005515 protein binding (IPI innate-immunity partners) -> KEEP_AS_NON_CORE.
  • cytosol/cytosolic ribosome terms -> ACCEPT.
  • GO:0004842, GO:0016567, GO:0051865 -> ACCEPT/KEEP_AS_NON_CORE (ubiquitination process/parent).

Pn Notes

(LTN1-pn-notes.md)

LTN1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O94822
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

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

AIGR Review Snapshot

  • Description: LTN1 (Listerin, also RNF160/ZNF294) is a large (1766 aa) cytosolic RING-type E3 ubiquitin-protein ligase (EC 2.3.2.27) that is the catalytic core of the ribosome-associated quality control (RQC) complex. Its N-terminal HEAT/ARM-repeat solenoid wraps around the 60S large ribosomal subunit while its C-terminal RING-CH (RING-type zinc finger) domain catalyzes ubiquitin transfer. When an elongating 80S ribosome stalls and is split into subunits by the rescue factors PELO/HBS1L/ABCE1, the incomplete nascent polypeptide remains attached to a peptidyl-tRNA housed in the 60S subunit; LTN1 is recruited to these 60S-nascent chain complexes by NEMF, which senses the exposed P-site tRNA, and poly-ubiquitinates the trapped nascent chain. This commits aberrant translation products to extraction by the VCP/p97 AAA-ATPase and degradation by the proteasome, preventing accumulation of potentially toxic incomplete proteins. LTN1 thus functions in nascent-chain surveillance and rescue of stalled ribosomes; it is broadly expressed and acts in the cytosol in association with the 60S subunit.
  • Existing/core annotation action counts: ACCEPT: 27; KEEP_AS_NON_CORE: 4

PN Consistency Summary

  • Consistency: Fully consistent. Deep research, review, and PN all describe LTN1/Listerin as the RING E3 ligase of the RQC complex (LTN1+NEMF+TCF25 on 60S) that poly-ubiquitinates 60S-housed stalled nascent chains for VCP/p97 + proteasomal degradation. Review is comprehensive: GO:0061630 ligase activity (IDA), GO:1990116 RQC catabolic process, GO:1990112 RQC complex, GO:0072344 rescue, GO:0043023 60S binding, GO:0008270 zinc (RING). All PN mappings land on terms LTN1 already holds.
  • PN story / NEW pressure: No NEW pressure. Every PN-projected term is already in GOA / the review: GO:0016567 protein ubiquitination (already_in_goa_exact), GO:0061630 ligase activity (already_in_goa_exact, ×2 rows), GO:0006515 (broad parent of the specific GO:1990116 LTN1 already holds). Conclusion: already captured, and more specifically (LTN1 carries the RQC-specific GO:1990116 / GO:1990112 that the generic PN GO:0006515 / GO:0016567 only approximate).
  • Evidence alignment: PN row 2 lists "19489725 / rev" as a reference; the review does NOT cite PMID:19489725. The review's definitive structural anchor is PMID:25578875 (RQC complex structure/assembly; LTN1 ligase + NEMF dependence) plus PMID:35452614 (RQC review) and PMID:28757607 (Hel2/40S context, LOW relevance). Minor divergence: the PN row-2 citation (19489725, the original Listerin/neurodegeneration paper) is not in the review's reference set.
  • Verdict: Fully consistent; PN story already captured (review more specific) — no NEW pressure. Recommended edits: none required for terms; treat group-node GO:0006515 as context-only/entailed (LTN1 has the specific GO:1990116) [MAP]; optionally add PMID:19489725 (PN row-2 reference) to references if it supports the Listerin RQC/neurodegeneration role [REF].

Full Consistency Review

  • UniProt: O94822 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: THREE rows. Row 1 (TR) Translation|Cytosolic translation|Ribosome-associated QC|Ubiquitination (type=mapped→GO:0016567 protein ubiquitination [already_in_goa_exact]; group→GO:0006515 protein quality control [new_to_goa]). Rows 2 & 3 (UPS) E3 ubiquitin and UBL ligases|RING ... and Ubiquitin and UBL binding|E3 ligase|RING/with UBD|RWD (LTN1) (group→GO:0061630 ubiquitin protein ligase activity [already_in_goa_exact]; subtype/type=no_mapping; class=context_only).
  • Consistency: Fully consistent. Deep research, review, and PN all describe LTN1/Listerin as the RING E3 ligase of the RQC complex (LTN1+NEMF+TCF25 on 60S) that poly-ubiquitinates 60S-housed stalled nascent chains for VCP/p97 + proteasomal degradation. Review is comprehensive: GO:0061630 ligase activity (IDA), GO:1990116 RQC catabolic process, GO:1990112 RQC complex, GO:0072344 rescue, GO:0043023 60S binding, GO:0008270 zinc (RING). All PN mappings land on terms LTN1 already holds.
  • PN story / NEW pressure: No NEW pressure. Every PN-projected term is already in GOA / the review: GO:0016567 protein ubiquitination (already_in_goa_exact), GO:0061630 ligase activity (already_in_goa_exact, ×2 rows), GO:0006515 (broad parent of the specific GO:1990116 LTN1 already holds). Conclusion: already captured, and more specifically (LTN1 carries the RQC-specific GO:1990116 / GO:1990112 that the generic PN GO:0006515 / GO:0016567 only approximate).
  • Mapping strategy: Correctly distinguishes broad from specific per the RQC-branch guidance: group GO:0006515 is the broad parent, and LTN1's own GO:1990116 (ribosome-associated ubiquitin-dependent catabolism) is the specific RQC term — so GO:0006515 should be entailed/context-only, not separately propagated. LTN1 = the RQC E3 ligase, exactly as the branch note states. No node change warranted by this gene.
  • Evidence alignment: PN row 2 lists "19489725 / rev" as a reference; the review does NOT cite PMID:19489725. The review's definitive structural anchor is PMID:25578875 (RQC complex structure/assembly; LTN1 ligase + NEMF dependence) plus PMID:35452614 (RQC review) and PMID:28757607 (Hel2/40S context, LOW relevance). Minor divergence: the PN row-2 citation (19489725, the original Listerin/neurodegeneration paper) is not in the review's reference set.
  • Verdict: Fully consistent; PN story already captured (review more specific) — no NEW pressure. Recommended edits: none required for terms; treat group-node GO:0006515 as context-only/entailed (LTN1 has the specific GO:1990116) [MAP]; optionally add PMID:19489725 (PN row-2 reference) to references if it supports the Listerin RQC/neurodegeneration role [REF].

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/LTN1/LTN1-ai-review.yaml
  • PN workbook rows: 3

PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | Ubiquitination

  • UniProt: O94822
  • In branches: TR, UPS
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Ribosome-associated QC|Ubiquitination
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0016567 protein ubiquitination]
      rationale: This PN RQC type denotes ubiquitination events on stalled translation complexes. Protein ubiquitination is the shared process target.
    • [group] Translation|Cytosolic translation|Ribosome-associated QC
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
      rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | RING | ubiquitin binding domain | Armadillo-like

  • UniProt: O94822
  • In branches: TR, UPS
  • Signature domains: IPR001841
  • Auxiliary domains: IPR011989
  • PN references (titles):
    • 19489725 / rev
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|RING|ubiquitin binding domain|Armadillo-like
      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|ubiquitin binding domain
      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.

PN row 3: Ubiquitin Proteasome System | Ubiquitin and UBL binding | E3 ligase | RING / with UBD | RWD (LTN1)

  • UniProt: O94822
  • In branches: TR, UPS
  • Signature domains: IPR054478
  • Auxiliary domains: IPR001841
  • PN-node mapping records (path + ancestors):
    • [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase|RING / with UBD|RWD (LTN1)
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower enzyme-family, domain, or architecture subdivision already covered by a curated parent enzyme mapping. No additional direct GO mapping is needed at this node.
    • [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase|RING / with UBD
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower enzyme-family, domain, or architecture subdivision already covered by a curated parent enzyme mapping. No additional direct GO mapping is needed at this node.
    • [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0061630 ubiquitin protein ligase activity]
      rationale: This PN group captures ubiquitin/UBL-binding factors that are E3 ligases. The shared molecular-function target is ubiquitin protein ligase activity.
    • [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
      status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
      rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
    • [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 (4)

  • GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
  • GO:0016567 protein ubiquitination | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Ribosome-associated QC|Ubiquitination
  • 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
  • GO:0061630 ubiquitin protein ligase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Ubiquitin Proteasome System|Ubiquitin and UBL binding|E3 ligase

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: O94822
gene_symbol: LTN1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: LTN1 (Listerin, also RNF160/ZNF294) is a large (1766 aa) cytosolic RING-type E3 ubiquitin-protein ligase (EC 2.3.2.27) that is the catalytic core of the ribosome-associated quality control (RQC) complex. Its N-terminal HEAT/ARM-repeat solenoid wraps around the 60S large ribosomal subunit while its C-terminal RING-CH (RING-type zinc finger) domain catalyzes ubiquitin transfer. When an elongating 80S ribosome stalls and is split into subunits by the rescue factors PELO/HBS1L/ABCE1, the incomplete nascent polypeptide remains attached to a peptidyl-tRNA housed in the 60S subunit; LTN1 is recruited to these 60S-nascent chain complexes by NEMF, which senses the exposed P-site tRNA, and poly-ubiquitinates the trapped nascent chain. This commits aberrant translation products to extraction by the VCP/p97 AAA-ATPase and degradation by the proteasome, preventing accumulation of potentially toxic incomplete proteins. LTN1 thus functions in nascent-chain surveillance and rescue of stalled ribosomes; it is broadly expressed and acts in the cytosol in association with the 60S subunit.
alternative_products:
- name: '1'
  id: O94822-1
- name: '2'
  id: O94822-2
  sequence_note: VSP_040138
- name: '3'
  id: O94822-3
  sequence_note: VSP_044911
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: LTN1 acts in the cytosol in association with the 60S subunit and the RQC complex. The phylogenetic (IBA) cytosolic localization is consistent with direct experimental evidence and the documented cytoplasmic site of action.
    action: ACCEPT
    reason: Cytosol is the correct site of action; supported by experimental IDA (PMID:25578875, PMID:28757607) and the UniProt subcellular location.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: LTN1 ubiquitinates 60S-stalled nascent chains to commit them to proteasomal degradation; this is its defining biological process and is well supported across the LTN1/Rkr1 family.
    action: ACCEPT
    reason: Directly supported experimentally; the RQC pathway degrades incompletely synthesized nascent chains via LTN1-mediated ubiquitination.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: The core molecular function of Listerin is RING-type ubiquitin ligase activity, transferring ubiquitin to nascent-chain lysines. Conserved across the LTN1/Rkr1 family.
    action: ACCEPT
    reason: Core molecular function; corroborated by IDA (PMID:25578875), EC 2.3.2.27, and the C-terminal RING-CH domain.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase component of the ribosome quality control complex
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: By clearing the nascent chain from 60S-stalled complexes, LTN1 participates in resolving stalled ribosomes. Conserved RQC role.
    action: ACCEPT
    reason: Phylogenetically and experimentally supported; LTN1 is a defining factor of the stalled-ribosome rescue/RQC pathway.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
- term:
    id: GO:1990112
    label: RQC complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: LTN1 is a constitutive component of the RQC complex (LTN1 + NEMF + TCF25) on the 60S subunit.
    action: ACCEPT
    reason: Directly demonstrated; LTN1 is one of the three defining RQC complex subunits.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit
- term:
    id: GO:0043023
    label: ribosomal large subunit binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: LTN1's HEAT/ARM-repeat solenoid wraps the 60S large subunit, and its C-terminal RWD domain contacts the ribosome; binding the 60S subunit is integral to its function.
    action: ACCEPT
    reason: Structurally and biochemically demonstrated; LTN1 cofractionates with and binds 60S-nascent chain complexes.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: Listerin's C-terminal RWD domain directly contacts the ribosome to position the adjacent ligase domain near the nascent polypeptide exit tunnel
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the cytosol localization from the UniProt subcellular location, consistent with stronger experimental evidence.
    action: ACCEPT
    reason: Redundant with IDA cytosol annotations; correct compartment.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The C-terminal RING-type zinc finger coordinates zinc as a structural requirement for the ligase fold. This is a structural attribute supporting, but not equal to, the ligase activity.
    action: KEEP_AS_NON_CORE
    reason: Accurate structural feature of the RING domain (residues 1715-1762) but subsidiary to the informative ubiquitin ligase activity; not a standalone core function.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: RING-type
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment of the core RING E3 ligase activity, consistent with the experimental IDA evidence and EC 2.3.2.27.
    action: ACCEPT
    reason: Correct core molecular function; redundant with IDA/IBA evidence.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: EC=2.3.2.27
- term:
    id: GO:1990112
    label: RQC complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: InterPro-based electronic assignment to the RQC complex, consistent with the experimental IDA annotation.
    action: ACCEPT
    reason: Correct; LTN1 is a defining RQC complex subunit.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: Component of the ribosome quality control complex (RQC)
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic assignment of the RQC catabolic process, consistent with experimental evidence.
    action: ACCEPT
    reason: Correct defining biological process; redundant with IDA/IBA.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21903422
  qualifier: enables
  review:
    summary: High-throughput innate-immunity interactome capturing LTN1 interactions with IRF7, STING1 and TIRAP. The bare protein binding term is uninformative and the partners are unrelated to LTN1's RQC ligase function.
    action: KEEP_AS_NON_CORE
    reason: Records real IntAct interactions (IRF7/STING1/TIRAP) from an innate-immunity screen, but bare protein binding is uninformative and these partners do not reflect the core RQC ligase function; per guidelines not elevated to core.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'O94822; Q92985: IRF7'
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Ortholog-based electronic transfer of ubiquitin-protein transferase activity, a parent/sibling of the more precise ubiquitin protein ligase activity that LTN1 enables.
    action: ACCEPT
    reason: Correct general molecular function; the more specific GO:0061630 captures the core RING E3 ligase activity.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: RING-type E3 ubiquitin transferase listerin
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: LTN1 is autoubiquitinated, a common property of RING E3 ligases reflecting their catalytic activity on themselves. Peripheral to the substrate-directed function.
    action: KEEP_AS_NON_CORE
    reason: Supported by the UniProt PTM (autoubiquitinated) but a secondary property of the ligase, not its core nascent-chain-directed function.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: Autoubiquitinated
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948299
  qualifier: involved_in
  review:
    summary: Reactome curation of LTN1 in stalled-ribosome rescue, consistent with experimental evidence and the IBA/IDA annotations.
    action: ACCEPT
    reason: Correct; redundant with experimentally supported RQC role.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: General protein ubiquitination process annotation derived from the UniPathway ubiquitination pathway; a parent of the specific RQC catabolic process.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific GO:1990116 (RQC ubiquitin-dependent catabolism) better captures LTN1's biological role.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'PATHWAY: Protein modification; protein ubiquitination.'
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948362
  qualifier: enables
  review:
    summary: Reactome curation of the core RING E3 ligase activity of LTN1, consistent with experimental evidence.
    action: ACCEPT
    reason: Correct core molecular function.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: E3 ubiquitin-protein ligase component of the ribosome quality control complex
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with LTN1's site of action.
    action: ACCEPT
    reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: NAS
  original_reference_id: PMID:35452614
  qualifier: involved_in
  review:
    summary: Review-based (NAS, ComplexPortal) assertion of LTN1's role in stalled-ribosome rescue, drawn from the RQC review by Filbeck et al.
    action: ACCEPT
    reason: Consistent with the experimentally supported RQC role; the cited review summarizes RQC mechanisms from bacteria to humans.
    supported_by:
    - reference_id: PMID:35452614
      supporting_text: Ribosome-associated quality-control mechanisms from bacteria to humans
- term:
    id: GO:1990112
    label: RQC complex
  evidence_type: NAS
  original_reference_id: PMID:35452614
  qualifier: part_of
  review:
    summary: Review-based (NAS, ComplexPortal) assertion of LTN1 as an RQC complex component.
    action: ACCEPT
    reason: Consistent with experimentally demonstrated RQC complex membership.
    supported_by:
    - reference_id: PMID:35452614
      supporting_text: Ribosome-associated quality-control mechanisms from bacteria to humans
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:35452614
  qualifier: involved_in
  review:
    summary: Review-based (NAS, ComplexPortal) assertion of LTN1's RQC ubiquitin-dependent catabolic role.
    action: ACCEPT
    reason: Consistent with the experimentally supported defining process.
    supported_by:
    - reference_id: PMID:35452614
      supporting_text: Ribosome-associated quality-control mechanisms from bacteria to humans
- term:
    id: GO:0022626
    label: cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: is_active_in
  review:
    summary: LTN1 acts on the cytosolic (60S) ribosome; the cryo-EM RQC complex study places Listerin directly on the 60S subunit.
    action: ACCEPT
    reason: Directly demonstrated; LTN1 functions while bound to the cytosolic ribosome.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: involved_in
  review:
    summary: Direct experimental evidence that Listerin acts on stalled 60S-nascent chain complexes within the RQC pathway.
    action: ACCEPT
    reason: Core, experimentally supported RQC/rescue function.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: its mammalian homolog Listerin was both necessary and sufficient for ubiquitination of stalled translation products
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: enables
  review:
    summary: Direct experimental demonstration that Listerin is the E3 ubiquitin ligase that poly-ubiquitinates 60S-housed nascent chains. This is LTN1's core molecular function.
    action: ACCEPT
    reason: Core molecular function with direct experimental (IDA) support and structural basis (C-terminal RING-CH domain).
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: located_in
  review:
    summary: Direct evidence for cytosolic localization of Listerin.
    action: ACCEPT
    reason: Correct compartment; LTN1 acts in the cytosol on ribosomes.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:1990112
    label: RQC complex
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: part_of
  review:
    summary: The cryo-EM structure resolves Listerin as part of the RQC complex bound to the 60S-nascent chain, with NEMF bridging.
    action: ACCEPT
    reason: Directly demonstrated structurally; LTN1 is a defining RQC complex subunit.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: ribosome-bound NEMF recruits and stabilizes Listerin's N-terminal domain
- term:
    id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:25578875
  qualifier: involved_in
  review:
    summary: Direct evidence that Listerin ubiquitinates 60S-stalled nascent chains, committing them to proteasomal degradation.
    action: ACCEPT
    reason: Core, experimentally supported defining biological process.
    supported_by:
    - reference_id: PMID:25578875
      supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:28757607
  qualifier: located_in
  review:
    summary: Cytosolic localization annotation derived from an RQC study (Matsuo et al. focused on Hel2/uS10 ubiquitination); consistent with LTN1's cytosolic site of action.
    action: ACCEPT
    reason: Correct compartment, consistent with stronger LTN1-specific evidence; the source paper primarily concerns the 40S/Hel2 branch but the localization is accurate.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948318
  qualifier: located_in
  review:
    summary: Reactome curation of LTN1 cytosolic localization.
    action: ACCEPT
    reason: Correct compartment; redundant with experimental cytosol annotations.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948362
  qualifier: located_in
  review:
    summary: Reactome curation of LTN1 cytosolic localization.
    action: ACCEPT
    reason: Correct compartment; redundant with experimental cytosol annotations.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948427
  qualifier: located_in
  review:
    summary: Reactome curation of LTN1 cytosolic localization.
    action: ACCEPT
    reason: Correct compartment; redundant with experimental cytosol annotations.
    supported_by:
    - reference_id: file:human/LTN1/LTN1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  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 Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic Assertion of Orthology
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:21903422
  title: Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput innate-immunity interactome; source of the IntAct protein binding partners (IRF7, STING1, TIRAP). Not relevant to LTN1's RQC ligase function.
- id: PMID:25578875
  title: Structure and assembly pathway of the ribosome quality control complex.
  findings:
  - statement: Listerin is the E3 ligase that poly-ubiquitinates 60S-housed nascent polypeptides during RQC, and its specificity for nascent chain-60S complexes depends on NEMF.
    reference_section_type: ABSTRACT
  - statement: NEMF recruits and stabilizes Listerin's N-terminal domain on the 60S while Listerin's C-terminal RWD domain contacts the ribosome to position the RING ligase domain near the nascent polypeptide exit tunnel.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive structural/mechanistic study of the human RQC complex; establishes LTN1 as the RQC ligase and the NEMF dependence.
- id: PMID:28757607
  title: Ubiquitination of stalled ribosome triggers ribosome-associated quality control.
  findings:
  - statement: Establishes the upstream RQC trigger in which Hel2/RQT1 ubiquitinates the 40S protein uS10; provides the cytosolic RQC context in which LTN1 acts on the 60S branch.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Primarily about the 40S/Hel2(ZNF598-ortholog) branch; cited in LTN1 GOA only for cytosol localization.
- id: PMID:35452614
  title: Ribosome-associated quality-control mechanisms from bacteria to humans.
  findings:
  - statement: Review summarizing RQC, including LTN1/Listerin as the RQC complex E3 ligase that ubiquitinates stalled nascent chains for degradation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Authoritative RQC review used by ComplexPortal for NAS annotations.
- id: Reactome:R-HSA-9948299
  title: 'Reactome: rescue of stalled ribosome (LTN1)'
  findings: []
- id: Reactome:R-HSA-9948318
  title: 'Reactome: LTN1 cytosol localization'
  findings: []
- id: Reactome:R-HSA-9948362
  title: 'Reactome: LTN1 ubiquitin ligase activity'
  findings: []
- id: Reactome:R-HSA-9948427
  title: 'Reactome: LTN1 cytosol localization'
  findings: []
- id: file:human/LTN1/LTN1-uniprot.txt
  title: UniProt entry O94822 (LTN1_HUMAN), E3 ubiquitin-protein ligase listerin
  findings:
  - statement: E3 ubiquitin-protein ligase component of the RQC complex (LTN1, TCF25, NEMF) on the 60S subunit; recruited to stalled 60S by NEMF and ubiquitinates stalled nascent chains for proteasomal extraction/degradation via VCP/p97; RING-type ligase, EC 2.3.2.27; cytosolic.
    reference_section_type: OTHER
core_functions:
- description: RING-type E3 ubiquitin ligase that poly-ubiquitinates incompletely synthesized nascent polypeptides housed in the stalled 60S ribosomal subunit, marking them for VCP/p97 extraction and proteasomal degradation.
  molecular_function:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  locations:
  - id: GO:0022626
    label: cytosolic ribosome
  supported_by:
  - reference_id: PMID:25578875
    supporting_text: the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin
  - reference_id: file:human/LTN1/LTN1-uniprot.txt
    supporting_text: E3 ubiquitin-protein ligase component of the ribosome quality control complex
- description: Catalytic component of the ribosome quality control (RQC) complex that, recruited to 60S-nascent chain complexes by NEMF, mediates ribosome-associated ubiquitin-dependent degradation of stalled translation products and contributes to rescue of stalled ribosomes.
  molecular_function:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  in_complex:
    id: GO:1990112
    label: RQC complex
  supported_by:
  - reference_id: file:human/LTN1/LTN1-uniprot.txt
    supporting_text: Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit
  - reference_id: PMID:25578875
    supporting_text: ribosome-bound NEMF recruits and stabilizes Listerin's N-terminal domain
  directly_involved_in:
  - id: GO:1990116
    label: ribosome-associated ubiquitin-dependent protein catabolic process
proposed_new_terms: []
suggested_questions:
- question: How is LTN1 RING ligase activity spatially coordinated with NEMF-mediated CAT-tailing on the same 60S-nascent chain complex, and what determines the order of these events?
- question: Do the innate-immunity interactions (IRF7/STING1/TIRAP) reflect a genuine moonlighting role for LTN1 or are they incidental high-throughput captures?
suggested_experiments:
- description: Reconstitute ubiquitination of defined 60S-nascent chain complexes with purified LTN1, NEMF and an E2 to map the lysine sites and ubiquitin chain topology Listerin builds on stalled nascent chains.
- description: CRISPR knockout of LTN1 in human cells followed by proteomics of stabilized, CAT-tailed aggregation-prone nascent chains to define the endogenous substrate repertoire.