GALE is a cytosolic, NAD-bound homodimer with two reversible epimerase activities. It recycles UDP-glucose from UDP-galactose in the Leloir pathway and supplies UDP-galactose in the reverse direction for glycoconjugate synthesis. Its second activity interconverts UDP-GlcNAc and UDP-GalNAc. The latter is shared with endogenous fly GALE; it is not uniquely human (PMID:22654673). NAD binding is part of catalysis, rather than a separate core function. NADH generated by the coupled reporter in PMID:16302980 is not net consumption of NAD by GALE.
The broad galactose-metabolism and catabolism annotations are refined to the existing Leloir-pathway annotation through verified is_a edges: GO:0033499 → GO:0019388 → GO:0006012. The electronic InterPro/UniPathway mapping and human UniProt pathway statement are generic; a specific original UPA00214 definition was not recovered. Independent human enzyme evidence establishes the refinement. Reverse UDP-galactose supply remains explicit in the first catalytic core; no new biosynthetic process annotation is added. QuickGO currently names GO:0033499 “D-galactose catabolic process, Leloir pathway”; older cache labels remain historical.
Five self-interaction annotations are refined to the already accepted GO:0042803 protein homodimerization activity, an is_a descendant of GO:0042802. Human crosslinking and author-defined structural dimers establish the specific assembly. The individual GALE pair/clone tables of the five interaction screens were not inspected; no screen-specific stoichiometry, natural product or orthogonal validation is inferred. Two structured findings under PMID:16302980 hold the shared exact catalytic and crosslinking anchors. Rows and the core link to that reference without duplicating its excerpts.
Official direct FASTAs identify Q14376-1 (348 residues) and Q14376-2 (274 residues). In the short product, canonical residues 1–79 are replaced by MSPLQ. The reviewed full-length and tagged constructs do not establish equivalent activity of that natural short product. Its missing canonical N-terminal contacts do not by themselves prove inactivity.
In the actual PTHR43725 tree, human Q14376 is AN338/PTN002536271 and its ungapped sequence exactly matches canonical GALE. Activity and cytosol originate at AN287/PTN000041817; Leloir participation originates at AN323/PTN000821420. All origins lie on the target lineage. The two retained activity losses, PTN002886021 and PTN001621994, are off that lineage. Target self-donor evidence is valid grounding, and donor count is not an evidence score. The mouse Q8R059 donor GOA supports the ortholog context; its individual primary papers were not read.
The compact source evidence links immutable Git versions of the full original review, journal, 21 old quote/claim associations and complete raw/native mapping. These records remain recoverable without embedding a second full review or repeated raw annotation arrays. The original journal remains the unchanged prefix of GALE notes. Title-only and dataset-wide snippets remain historical, rather than serving as target-specific evidence. The current review holds four exact excerpts; the source-evidence ledger records byte offsets and hashes without repeating their text. All 38 normal sources remain unchanged.