ACL4

Summary: The mitochondrial inference remains unresolved after correcting the overly strong exclusion rationale.

Reason: The IBD at PTN002340064 is a genuine TOM70-family ancestral assertion. Primary Acl4 studies establish a soluble Rpl4-specific chaperone pathway but do not test or exclude every mitochondrial client interaction or peripheral membrane contribution. The existing report neither reconstructs the PAINT topology nor demonstrates target-specific loss of these particular activities. Its use of absent transmembrane helices as universal refutation is insufficient for a peripheral factor or complex contribution.

Summary: The mitochondrial inference remains unresolved after correcting the overly strong exclusion rationale.

Reason: The IBD at PTN002340064 is a genuine TOM70-family ancestral assertion. Primary Acl4 studies establish a soluble Rpl4-specific chaperone pathway but do not test or exclude every mitochondrial client interaction or peripheral membrane contribution. The existing report neither reconstructs the PAINT topology nor demonstrates target-specific loss of these particular activities. Its use of absent transmembrane helices as universal refutation is insufficient for a peripheral factor or complex contribution. This row is explicitly contributes_to: it does not assert that Acl4 itself forms a membrane-spanning channel. Rpl4 nuclear-pore passage does not by itself establish mitochondrial transmembrane transport either.

Summary: The mitochondrial inference remains unresolved after correcting the overly strong exclusion rationale.

Reason: The IBD at PTN002340064 is a genuine TOM70-family ancestral assertion. Primary Acl4 studies establish a soluble Rpl4-specific chaperone pathway but do not test or exclude every mitochondrial client interaction or peripheral membrane contribution. The existing report neither reconstructs the PAINT topology nor demonstrates target-specific loss of these particular activities. Its use of absent transmembrane helices as universal refutation is insufficient for a peripheral factor or complex contribution.

Summary: The mitochondrial inference remains unresolved after correcting the overly strong exclusion rationale.

Reason: GO:0030943 (mitochondrion targeting sequence binding) is obsolete in the current GO release (consider GO:0140436 / GO:0008320). No replacement is proposed while the underlying PAINT inference remains unresolved. The IBD at PTN002340064 is a genuine TOM70-family ancestral assertion. Primary Acl4 studies establish a soluble Rpl4-specific chaperone pathway but do not test or exclude every mitochondrial client interaction or peripheral membrane contribution. The existing report neither reconstructs the PAINT topology nor demonstrates target-specific loss of these particular activities. Its use of absent transmembrane helices as universal refutation is insufficient for a peripheral factor or complex contribution. The targeting-sequence-binding assertion is present in the original GOA but absent from the newer PTHR46208 PAINT table; a version difference is not biological refutation.

Summary: The mitochondrial inference remains unresolved after correcting the overly strong exclusion rationale.

Reason: The IBD at PTN002340064 is a genuine TOM70-family ancestral assertion. Primary Acl4 studies establish a soluble Rpl4-specific chaperone pathway but do not test or exclude every mitochondrial client interaction or peripheral membrane contribution. The existing report neither reconstructs the PAINT topology nor demonstrates target-specific loss of these particular activities. Its use of absent transmembrane helices as universal refutation is insufficient for a peripheral factor or complex contribution.

Summary: UniProt subcellular-location mapping to nucleus is consistent with direct Acl4 localization studies and with Acl4 delivery of Rpl4 to nuclear pre-60S particles.

Reason: Acl4 is enriched in the nucleus and performs its client-delivery function at the nuclear pre-60S assembly site.

Summary: Automated cytoplasm assignment is consistent with direct studies showing Acl4 in the cytoplasm, where Rpl4 is synthesized and first captured.

Reason: Cytoplasmic localization is part of the supported escort path from nascent Rpl4 capture to nuclear assembly.

Summary: The keyword-derived ribosome biogenesis term is broad but accurate for Acl4, which is required for efficient production of 60S ribosomal subunits.

Reason: Experimental annotations to ribosomal large subunit biogenesis provide the more specific evidence; this parent process is correct as an automated summary of Acl4 function.

Summary: Direct experimental localization supports nuclear Acl4, consistent with the Rpl4 pre-60S assembly site.

Reason: The localization matches the mechanistic model in which Acl4 delivers Rpl4 to nuclear pre-60S assembly intermediates.

Summary: Direct microscopy in the dedicated Acl4-Rpl4 study supports nuclear localization.

Reason: Acl4 localizes to the nucleus as expected for a factor escorting Rpl4 to nuclear pre-60S assembly sites.

Summary: Direct microscopy supports cytoplasmic Acl4 localization.

Reason: Acl4 must encounter newly translated Rpl4 in the cytoplasm before nuclear delivery, so this localization is mechanistically coherent.

Summary: Mutant phenotype evidence shows that ACL4 is required for normal 60S subunit production through Rpl4 assembly.

Reason: Acl4 shields Rpl4 until it can be inserted into the pre-ribosome; ACL4 loss causes large-subunit biogenesis defects, making this a core process.

Summary: The dedicated chaperone study shows that Acl4 escorts Rpl4 to its nuclear pre-60S assembly site and that loss of Acl4 compromises 60S production.

Reason: This is the central biological process for Acl4 and is supported by genetic, localization, and biochemical evidence.

Summary: The obsolete unfolded-protein-binding term is best represented by the dedicated carrier-chaperone activity.

Reason: Live QuickGO marks GO:0051082 obsolete. Primary Acl4/Rpl4 studies demonstrate client shielding and escort to pre-60S assembly, supporting GO:0140597 protein carrier chaperone as the specific replacement.

Proposed replacements: protein carrier chaperone

Summary: The evidence supports Acl4 directly binding and escorting Rpl4 to the pre-60S assembly pathway, matching the current definition of protein transporter activity as binding and delivering a specific protein to a cellular location.

Reason: QuickGO places GO:0140318 under transporter activity and GO:0140597 under molecular carrier activity rather than as a parent-child pair. Retaining this SGD IDA annotation is therefore not a redundant parent annotation, and the PMID:26447800 evidence supports Acl4 escorting Rpl4 to the pre-60S assembly pathway.

Summary: Cotranslational Rpl4 capture is demonstrated, while the precise folding contribution in the HGI source remains unresolved.

Reason: GO:0051083 concerns correct noncovalent assembly of nascent chains while translation continues, and does not imply a general chaperone for all substrates. PMID:26447800 directly supports cotranslational Rpl4 recognition, but recognition/protection need not itself demonstrate the folding step. The cached PMID:19325107 remains abstract-only after full-text retrieval attempts; its ACL4 genetic-interaction evidence should not be overruled from the abstract or the preference for a more specific carrier role.

Summary: High-throughput localization to nucleus is consistent with direct Acl4 localization and its nuclear pre-60S assembly role.

Reason: Multiple independent sources support nuclear localization.

Summary: High-throughput localization to cytoplasm is consistent with direct Acl4 localization and nascent Rpl4 capture.

Reason: Acl4 is distributed through cytoplasm and nucleus, matching its escort function.