gap2 (sll1342, P80505) - Synechocystis sp. PCC 6803 - notes

Session 2026-10-19

Deep research status

just deep-research SYNY3 gap2 --provider falcon was run twice in the foreground and failed both
times with an authentication error from the Edison API ("Failed to authenticate", HTTP 403). No
deep-research file exists. This review is grounded in the UniProt record, the GOA file and primary
literature cached under publications/ (fetched with just fetch-pmid).

Identity and family

• Gap2 is a 337-residue type I (phosphorylating) GAPDH, product of sll1342
  [file:SYNY3/gap2/gap2-uniprot.txt "GN Name=gap2; OrderedLocusNames=sll1342;"].
• Family: glyceraldehyde-3-phosphate dehydrogenase family; NCBIfam TIGR01534 (GAPDH-I) and
  NF005641 (PRK07403); PANTHER PTHR43148
  [file:SYNY3/gap2/gap2-uniprot.txt "DR NCBIfam; TIGR01534; GAPDH-I; 1."].
• Active-site nucleophile Cys154 by similarity to P00362
  [file:SYNY3/gap2/gap2-uniprot.txt "FT ACT_SITE 154"].
• Cyanobacteria have two divergent GAPDH genes; gap1 is related to plant cytosolic GAPDH and gap2
  to the chloroplast GAPDH PMID:9484473.

Activity and cofactor specificity

• Gap2 was cloned by complementing an E. coli gap mutant; native and recombinant enzymes are
  homotetramers with dual NAD/NADP specificity PMID:9226260.
• UniProt curates both the NADP+ and NAD+ reactions (EC 1.2.1.59) from PMID:9226260
  [file:SYNY3/gap2/gap2-uniprot.txt "can use both NADP and NAD."].
• Koksharova et al. measured anabolic (1,3-BPG reduction) activity in wild type and mutants:
  PMID:9484473
• The catabolic (G3P oxidation) activity of Gap2 in extracts is low and seems repressed by a
  low-molecular-weight inhibitor PMID:9484473.

Biological process

• gap2 insertion mutants grow only on glucose under dim light, not on organic acids, and do not
  survive photoautotrophically; gap1 mutants show the reciprocal phenotype PMID:9484473.
• Conclusion of the authors PMID:9484473.
• Review: PMID:39036361. Gap1 uses NADH only and is the active isoenzyme in low light
  or darkness, when Gap2 is inhibited by CP12 PMID:39036361.
• Valverde et al. proposed a possible amphibolic role (anabolic and catabolic) PMID:9226260. The mutant
  data argue that Gap1, not Gap2, is required for glycolytic glucose breakdown, so the glycolysis
  IEA (UniPathway) is an over-annotation for this paralog, though not strictly wrong.

Regulation by CP12

• Gap2 forms a CP12-mediated ternary complex with phosphoribulokinase (PRK) under oxidizing / dark
  conditions; NADPH dissociates it PMID:9689144.
• In vivo: eYFP-tagged GapDH2 (Sll1342) forms CP12-dependent foci in the dark PMID:36330266.
• No GO annotation records the CP12 complex membership. This is regulatory context, not the core
  catalytic function; no NEW annotation proposed for it.

Location

• Cytoplasm by UniProt curator inference (ECO:0000305). Soluble Calvin-cycle enzyme; some CP12
  complexes may associate with carboxysomes [PMID:36330266, speculative].

Low-quality paper

• PMID:39826747 (Hameed et al. 2025) describes "SyGAPDH2" as 350 aa, 86.48 kDa, with NuoI and
  NADH-ubiquinone oxidoreductase chain 6 domains. That is inconsistent with sll1342 (337 aa,
  ~36 kDa, Gp_dh_N/Gp_dh_C domains), so the cloned sequence and its conclusions cannot be trusted
  for this gene. Recorded as LOW_QUALITY; not used to support any annotation.

Annotation decisions (summary)

• MF GO:0047100 (NADP+) and GO:0004365 (NAD+): accept all rows (EXP, IBA, IEA, ISS).
• GO:0043891 [NAD(P)+]: the exact GO counterpart of EC 1.2.1.59 and of the enzyme's dual
  specificity; accept.
• GO:0016620: correct but general; MODIFY to GO:0047100 / GO:0004365.
• NAD binding / NADP binding: true (cosubstrates) but peripheral; KEEP_AS_NON_CORE.
• GO:0006006 glucose metabolic process (IBA, IEA): true but general; MODIFY to GO:0006094
  gluconeogenesis.
• GO:0006096 glycolysis (IEA): MARK_AS_OVER_ANNOTATED (Gap1 is the glycolytic paralog).
• NEW GO:0019253 reductive pentose-phosphate cycle (IMP, PMID:9484473). Participation test: GAPDH
  catalyses the reduction of 1,3-bisphosphoglycerate, a step of the cycle. Comparator check:
  Arabidopsis chloroplast GAPA1/GAPB (P25856, P25857) carry GO:0019253 in QuickGO (NAS, IEA).

PGAP

• WP_010874115.1 is named by NF005641.0 (PRK07403, "type I glyceraldehyde-3-phosphate
  dehydrogenase"), which carries EC 1.2.1.- and no GO terms. PGAP propagates GO only from the naming
  model, so the protein gets no GO, even though TIGR01534 (same product name) also matches and maps
  GO:0006006, GO:0016620, GO:0050661, GO:0051287.
• PGAP EC 1.2.1.- is correct but less precise than the curated EC 1.2.1.59: LSP.