ral2 (SPBC21.05c) - Research Notes

Gene Identity

• UniProt: P15258
• Systematic name: SPBC21.05c
• 611 amino acids, 69.8 kDa
• Contains 3 Kelch repeats (aa 43-91, 96-149, 175-224) and a Kelch-type beta propeller domain
• Also contains SKP1/BTB/POZ superfamily domain
• Phosphorylated at Ser-604 PMID:18257517

Core Function

Ral2 is a Ras1-Scd pathway protein essential for mating/conjugation and cell morphology in S. pombe. It functions upstream of Ras1 in a signaling pathway that controls both mating pheromone response and elongated cell shape via the Ras1-Scd1-Cdc42 axis.

Key Evidence

• ral2 deletion mutants are spherical (not rod-shaped), have no mating activity, and do not respond to mating pheromone, phenocopying ras1- mutants PMID:2586528
• Activated ras1 (ras1Val-17) rescues ral2 mutants, placing ral2 upstream of ras1 PMID:2586528
• Genetic epistasis: ral1, ral2, ras1 function in a common pathway in that order PMID:3071741
• Multiple copies of ral2 or ral3 partially rescue ral1- strains PMID:3071741
• ral2 deletion increases cell width, along with other Cdc42-pathway deletions (scd1, scd2, rga4, ras1, efc25) PMID:21551073

Pathway Context

The Ras1 signaling pathway in S. pombe:
- Morphology branch: Ras1 -> Scd1 (GEF for Cdc42) -> Cdc42 -> Shk1 (PAK kinase) -> cell polarity
- Mating branch: Ras1 -> Byr2 -> MAPK cascade -> mating gene expression
- Ral2 acts upstream of Ras1, likely facilitating Ras1 activation
- Ral2's Kelch repeats suggest a protein-interaction role, but its direct partners
and biochemical mechanism in this pathway remain unresolved.

Protein Interactions (from BioGRID)

• Interacts with Gef1 (Cdc42 GEF) and Skp1 (SCF ubiquitin ligase component)
• The P. oryzae homolog PoRal2's kelch domain is sufficient for interaction with Scd1, Gef1, and Mst50 [PMID:34354729, Frontiers in Plant Science 2021]

Localization

• PomBase records endoplasmic-reticulum is_active_in from the proteome-wide YFP
  screen, but the accessible PMID:16823372 record contains only the study-level abstract,
  not the Ral2-specific image or classification. No independent Ral2 localization
  study was recovered, so this annotation is UNDECIDED and ER is not used as a core
  location. PMID:16823372

PANTHER family interpretation

PTHR43503 is a heterogeneous family whose broad ancestral node contains peroxiredoxins,
but Ral2 is correctly classified in subfamily PTHR43503:SF2, "NEGATIVE REGULATOR OF
SPORULATION MDS3-RELATED," together with fungal Mds3/Pmd1-like Kelch proteins. PAINT
records explicit IRD function-loss edges from the peroxiredoxin ancestor to the
Ral2/Mds3 node PTN005166285 for peroxidase activity, cytosol, and cell redox homeostasis.
Those obsolete redox-related GOA rows have now disappeared. The current IBA to regulation
of conjugation is placed directly on PTN005166285 and is grounded by Ral2's own
experimental phenotype; it is accepted rather than treated as a bad family transfer.

Molecular Function

The specific molecular function of ral2 is not well characterized at the biochemical level. It is NOT a GEF, GAP, or kinase. Based on its kelch repeat domain and genetic interactions, it likely functions as a signaling adaptor/scaffold that facilitates Ras1 activation, possibly by:
- Bringing together pathway components via kelch-mediated protein-protein interactions
- Facilitating the action of a Ras GEF on Ras1
- The ND (no biological data) annotation for MF is appropriate given the lack of biochemical characterization

Vegetative Growth

ral2 deletion does NOT affect vegetative growth - only mating and cell morphology are impaired PMID:2586528.

2026-09-01 re-review journal

• Refreshed Ral2 through just fetch-gene SCHPO ral2 --force. Current GOA contains
  five unique review tuples. Removed four stale redox/peroxiredoxin-derived annotations
  that are no longer present in GOA, consistent with the PAINT IRD loss edges at the
  Ral2/Mds3 node. The refresh also removed the experimental GO:0032005 IGI from
  PMID:2586528 (with PomBase:SPAC17H9.09c) while adding the GO:2000784 IMP on
  2026-01-18, consistent with a PomBase re-curation of the paper. GO:0032005 is
  retained in core_functions because activated ras1Val-17 rescue still supports
  the more specific positive conjugation signal-transduction synthesis.
• Accepted the new GO:0031137 IBA because the node is grounded by Ral2's direct mating
  phenotype; Ral2 appearing in its own source set is expected experimental grounding,
  not circularity. PMID:2586528
• Accepted GO:2000784 because activated ras1Val-17 restores rod-like morphology to
  ral2 mutants, directly placing Ral2 upstream of Ras1 in cell-polarity control.
  PMID:2586528
• Refreshed PMID:2586528 and PMID:2038319 through the publication wrapper. PMC exposes
  only abstract and document furniture for these scanned-era articles, so their
  records remain abstract-only and no unavailable full-text claims are made.
• Launched a focused OpenScientist job for the GO:0005783 ER HDA through
  just gene-hypothesis-research. The external provider produced no output or
  artifact after more than one hour and the polling process was stopped. With no
  gene-specific image available from PMID:16823372 and no independent localization
  study recovered, the annotation remains UNDECIDED rather than being accepted,
  rejected, or used as a core location.