Dic4

UniProt ID: Q9VVS1
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Dic4 is a Drosophila mitochondrial carrier-family protein. The 302-residue PA/PC product has the tripartite architecture of an inner-membrane carrier, but its physiological substrate remains unresolved. Reconstituted Dic4 did not exhibit transport in the published dicarboxylate-carrier assay panel, unlike Dic1 and Dic3.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005310 dicarboxylic acid transmembrane transporter activity
IDA NOT
PMID:21130726
A novel subfamily of mitochondrial dicarboxylate carriers fr...
ACCEPT
Summary: Retain the experimentally supported NOT annotation. Recombinant Dic4 lacked detectable transport in the reported assay, including the dicarboxylate-carrier comparison. This does not exclude an untested physiological substrate.
Reason: Retain the experimentally supported NOT annotation. Recombinant Dic4 lacked detectable transport in the reported assay, including the dicarboxylate-carrier comparison. This does not exclude an untested physiological substrate.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
GO:0005739 mitochondrion
IDA
PMID:21130726
A novel subfamily of mitochondrial dicarboxylate carriers fr...
ACCEPT
Summary: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Reason: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Supporting Evidence:
PMID:21130726
All expressed proteins are localized in mitochondria.
GO:0005743 mitochondrial inner membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Reason: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Supporting Evidence:
PMID:21130726
All expressed proteins are localized in mitochondria.
GO:0005743 mitochondrial inner membrane
TAS
PMID:21130726
A novel subfamily of mitochondrial dicarboxylate carriers fr...
ACCEPT
Summary: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Reason: Mitochondrial localization is experimentally supported, and the conserved mitochondrial carrier architecture supports residence in the inner membrane.
Supporting Evidence:
PMID:21130726
All expressed proteins are localized in mitochondria.
GO:0006835 dicarboxylic acid transport
IDA NOT
PMID:21130726
A novel subfamily of mitochondrial dicarboxylate carriers fr...
ACCEPT
Summary: Retain the experimentally supported NOT annotation. Recombinant Dic4 lacked detectable transport in the reported assay, including the dicarboxylate-carrier comparison. This does not exclude an untested physiological substrate.
Reason: Retain the experimentally supported NOT annotation. Recombinant Dic4 lacked detectable transport in the reported assay, including the dicarboxylate-carrier comparison. This does not exclude an untested physiological substrate.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
GO:0015116 sulfate transmembrane transporter activity
IBA
GO_REF:0000033
UNDECIDED
Summary: The substrate-specific ancestral transport inference remains unresolved against the negative Dic4 reconstitution result.
Reason: PTHR45618 places this substrate-related IBD at PTN000756618. PMID:21130726 reports no transport activity for DmDic4p; the accessible primary abstract and review PMID:32842667 support a real target-specific conflict. The existing OpenScientist report discusses the negative assays but does not settle substrate-by-substrate conditions, folding/insertion competence, or untested alternatives. Its absence-of-experiment and alternative-carrier arguments are not adopted as proof of loss. Retain UNDECIDED and request human inspection of the full primary assay panel, rather than commission a duplicate report.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN000756618 · PTN000756618 UNRESOLVED
Current IBD persists; target reconstitution is negative, but assay-specific interpretation remains unresolved after the existing report.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
**Conditions of the negative result.** *Gap:* whether Dic4 was correctly folded/inserted in the assay.
GO:0015117 thiosulfate transmembrane transporter activity
IBA
GO_REF:0000033
UNDECIDED
Summary: The substrate-specific ancestral transport inference remains unresolved against the negative Dic4 reconstitution result.
Reason: PTHR45618 places this substrate-related IBD at PTN000756618. PMID:21130726 reports no transport activity for DmDic4p; the accessible primary abstract and review PMID:32842667 support a real target-specific conflict. The existing OpenScientist report discusses the negative assays but does not settle substrate-by-substrate conditions, folding/insertion competence, or untested alternatives. Its absence-of-experiment and alternative-carrier arguments are not adopted as proof of loss. Retain UNDECIDED and request human inspection of the full primary assay panel, rather than commission a duplicate report.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN000756618 · PTN000756618 UNRESOLVED
Current IBD persists; target reconstitution is negative, but assay-specific interpretation remains unresolved after the existing report.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
**Conditions of the negative result.** *Gap:* whether Dic4 was correctly folded/inserted in the assay.
GO:0015709 thiosulfate transport
IBA
GO_REF:0000033
UNDECIDED
Summary: The substrate-specific ancestral transport inference remains unresolved against the negative Dic4 reconstitution result.
Reason: PTHR45618 places this substrate-related IBD at PTN000756618. PMID:21130726 reports no transport activity for DmDic4p; the accessible primary abstract and review PMID:32842667 support a real target-specific conflict. The existing OpenScientist report discusses the negative assays but does not settle substrate-by-substrate conditions, folding/insertion competence, or untested alternatives. Its absence-of-experiment and alternative-carrier arguments are not adopted as proof of loss. Retain UNDECIDED and request human inspection of the full primary assay panel, rather than commission a duplicate report.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN000756618 · PTN000756618 UNRESOLVED
Current IBD persists; target reconstitution is negative, but assay-specific interpretation remains unresolved after the existing report.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
**Conditions of the negative result.** *Gap:* whether Dic4 was correctly folded/inserted in the assay.
GO:0016020 membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Membrane is a correct broad location for mitochondrial Dic4.
Reason: The primary study localizes DmDic4p to mitochondria, and mitochondrial-carrier architecture plus the inherited inner-membrane annotation specify its membrane context. A valid broad membrane term need not be replaced merely because a narrower localization is also annotated.
Supporting Evidence:
PMID:21130726
All expressed proteins are localized in mitochondria.
GO:0035435 phosphate ion transmembrane transport
IBA
GO_REF:0000033
UNDECIDED
Summary: The substrate-specific ancestral transport inference remains unresolved against the negative Dic4 reconstitution result.
Reason: PTHR45618 places this substrate-related IBD at PTN000756618. PMID:21130726 reports no transport activity for DmDic4p; the accessible primary abstract and review PMID:32842667 support a real target-specific conflict. The existing OpenScientist report discusses the negative assays but does not settle substrate-by-substrate conditions, folding/insertion competence, or untested alternatives. Its absence-of-experiment and alternative-carrier arguments are not adopted as proof of loss. Retain UNDECIDED and request human inspection of the full primary assay panel, rather than commission a duplicate report.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN000756618 · PTN000756618 UNRESOLVED
Current IBD persists; target reconstitution is negative, but assay-specific interpretation remains unresolved after the existing report.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
**Conditions of the negative result.** *Gap:* whether Dic4 was correctly folded/inserted in the assay.
GO:0055085 transmembrane transport
IEA
GO_REF:0000002
ACCEPT
Summary: Retain general transmembrane transport as an inferred carrier function while leaving substrate identity unresolved.
Reason: PTHR45618 retains general transmembrane transporter activity at PTN002515516. Negative reconstitution results for a tested substrate panel do not demonstrate absence of transport for every substrate and condition. The existing OpenScientist report itself acknowledges untested substrates and unresolved folding/insertion conditions. The carrier architecture and curated ancestral transport function support this broad IEA without converting sulfate, thiosulfate, phosphate or ThPP into demonstrated Dic4 substrates.
Supporting Evidence:
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
"no activity" cannot formally exclude an untested substrate.
GO:1902358 sulfate transmembrane transport
IBA
GO_REF:0000033
UNDECIDED
Summary: The substrate-specific ancestral transport inference remains unresolved against the negative Dic4 reconstitution result.
Reason: PTHR45618 places this substrate-related IBD at PTN000756618. PMID:21130726 reports no transport activity for DmDic4p; the accessible primary abstract and review PMID:32842667 support a real target-specific conflict. The existing OpenScientist report discusses the negative assays but does not settle substrate-by-substrate conditions, folding/insertion competence, or untested alternatives. Its absence-of-experiment and alternative-carrier arguments are not adopted as proof of loss. Retain UNDECIDED and request human inspection of the full primary assay panel, rather than commission a duplicate report.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
PANTHER:PTN000756618 · PTN000756618 UNRESOLVED
Current IBD persists; target reconstitution is negative, but assay-specific interpretation remains unresolved after the existing report.
Supporting Evidence:
PMID:21130726
No transport activity was observed for DmDic4p.
file:DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md
**Conditions of the negative result.** *Gap:* whether Dic4 was correctly folded/inserted in the assay.

References

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External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM External predictions

View prediction review YAML · Dic4-protnlm-predictions-review.yaml · Review status: COMPLETE

The ProtNLM2 API snapshot retrieved 2026-09-08 contains no GO-term predictions for Q9VVS1. Mitochondrion (GO:0005739) is a supported omission candidate because the primary Dic4 study reports mitochondrial localization of the expressed Dic proteins, and the current exact accession is the native 302-residue Dic4 product. A specific transport-activity omission is not established: reconstituted Dic4 showed no detectable transport in the published dicarboxylate-carrier assays, while the accessible abstract does not establish that thiamine pyrophosphate was tested. The separate FUNCTION prediction of mitochondrial thiamine pyrophosphate uptake therefore remains UNC. This completed record assesses the absence of GO output; predictions is empty because no GO or EC prediction was emitted. The narrative judgment remains in the linked function review and is not a score assigned to the omission.

Source documents: genes/DROME/Dic4/Dic4-protnlm-source.json · projects/PROTNLM_EVALUATION/fly-benchmark/manifest.json · genes/DROME/Dic4/Dic4-protnlm-function-review.md · genes/DROME/Dic4/Dic4-uniprot.txt · publications/PMID_21130726.md · genes/DROME/Dic4/Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md

No GO/EC predictions in the reviewed source.

Deep Research

Falcon

(Dic4-deep-research-falcon.md)

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OpenScientist

(Dic4-hypotheses/fly41-thiamine-pyrophosphate-transport/openscientist.md)

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📚 Additional Documentation

Notes

(Dic4-notes.md)

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Protnlm Function Review

(Dic4-protnlm-function-review.md)

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📄 View Raw YAML

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