Dic4 ProtNLM2 function-description review

Original prediction

Mitochondrial transporter that mediates uptake of thiamine pyrophosphate (ThPP) into mitochondria

Original wording and all model/source metadata are retained in Dic4-protnlm-source.json.

Assessment

UNC — mitochondrial thiamine pyrophosphate transport is unresolved. Q9VVS1 is the native 302-residue Dic4-PA/PC product in FlyBase. The mitochondrial location is supported experimentally, but PMID:21130726 reports no detectable transport by reconstituted Dic4 in its dicarboxylate-carrier study. That finding establishes neither uptake nor exclusion of an untested substrate such as ThPP.

The prediction cites fungal Q59Q36 with a sequence-search score of 76.6 and a model score of 0.30. Mitochondrial carriers share architecture while differing markedly in transported substrates, as the Dic1/Dic3/Dic4 comparison itself demonstrates. No target-specific ThPP uptake assay or specificity-determining alignment establishes this transfer. The appropriate next experiment is reconstitution with labeled ThPP, validated protein incorporation and an active ThPP-carrier control.

Sources: primary Dic4 study, current UniProt record, and the locally preserved FlyBase and donor records.