Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0030587 sorocarp development	HMP PMID:17659086 High-throughput analysis of spatio-temporal dynamics in Dict...	ACCEPT	Summary: A high-throughput time-lapse phenotyping screen of insertional mutants placed tipA among a cluster of mutants defective at the slug and culmination stages of development, consistent with a requirement for tipA in sorocarp (fruiting body) development. This broad process term correctly captures the developmental role of the gene, even though the underlying molecular activity is unknown. Reason: tipA disruption produces a developmental phenotype affecting slug and culmination stages, so involvement in sorocarp development is well supported. The term is general but appropriate as the umbrella developmental process, and this HMP annotation is consistent with the independent IMP evidence from the tipA knockout. Supporting Evidence: PMID:17659086 Particularly noticeable are five mutants disrupted in tagB/C, mutations in tipA, tipB, tipC, and tipD PMID:17659086 Another major mutant cluster contains clones showing defective behavior at the slug and culmination stage, but wild-type behavior during aggregation
GO:0005737 cytoplasm	IDA PMID:9169048 Sorting of the initial cell types in Dictyostelium is depend...	UNDECIDED	Summary: Direct-assay (IDA) cytoplasmic localization annotated by dictyBase from the 1997 tipA characterization paper. The cached publication is abstract-only (full text not available), and the abstract does not describe subcellular localization, so the supporting evidence cannot be verified here. Cytoplasmic localization is plausible for this ~83 kDa PP2C-like protein, but the evidence is not verifiable from available material. Reason: The only cited reference is abstract-only in the cache and the abstract does not address subcellular localization. Per policy this experimental curator annotation is not overruled; it is marked UNDECIDED because the supporting evidence cannot be independently verified.
GO:0031154 culmination involved in sorocarp development	IMP PMID:9169048 Sorting of the initial cell types in Dictyostelium is depend...	ACCEPT	Summary: Loss of tipA by REMI mutagenesis blocks normal development - mutant cells fail to sort prestalk cells to the top of the aggregate, fail to form slugs, and produce very few spores - placing TipA upstream of the events leading to culmination and fruiting body formation. This IMP annotation from the tipA knockout is well supported by the mutant phenotype. Reason: The developmental arrest of tipA mutants (failure of prestalk sorting, tip formation and slug/fruiting-body formation) supports an acts_upstream_of_or_within relationship to culmination within sorocarp development. This is an experimental IMP annotation supported by the described phenotype and is retained as a core developmental role of the gene. Supporting Evidence: PMID:9169048 This mutant fails to form slugs and appears to have a defect in sorting of prestalk cells. PMID:9169048 The tipA gene appears to play an essential role in the sorting of the initial cell types.

Core Functions

TipA is required for the sorting of the initial prestalk (PstO) cell type and for formation of the organizing tip during the mound-to-slug transition of Dictyostelium multicellular development, acting cell-autonomously upstream of slug formation and culmination. Its molecular activity is not established; the protein carries a predicted but experimentally unverified PP2C-like (PPM-type) phosphatase domain, so no molecular function term is asserted.

Directly Involved In:

culmination involved in sorocarp development sorocarp development

Supporting Evidence:

PMID:9169048
The tipA gene appears to play an essential role in the sorting of the initial cell types.
PMID:9169048
This mutant fails to form slugs and appears to have a defect in sorting of prestalk cells.

References

PMID:17659086

High-throughput analysis of spatio-temporal dynamics in Dictyostelium.

tipA mutants cluster with mutants defective at the slug and culmination stages of development while behaving normally during aggregation.

"Another major mutant cluster contains clones showing defective behavior at the slug and culmination stage, but wild-type behavior during aggregation"

PMID:9169048

Sorting of the initial cell types in Dictyostelium is dependent on the tipA gene.

tipA encodes a novel ~83 kDa protein preferentially expressed in prestalk PstO cells after cell-type sorting.

"The disrupted gene, tipA, encodes a novel 83-kDa protein and is preferentially expressed in PST-O cells after the cell types have sorted out."
tipA mutants fail to form slugs and are defective in sorting of prestalk cells.

"This mutant fails to form slugs and appears to have a defect in sorting of prestalk cells."
Cells lacking TipA express the prestalk marker ecmA at reduced levels and form very few spores.

"Mutant strains that lack TipA express the prestalk-specific gene ecmA at reduced levels and form very few spores."
TipA acts cell-autonomously at an early stage of development and is essential for sorting of the initial cell types.

"The tipA gene appears to play an essential role in the sorting of the initial cell types."

file:DICDI/tipA/tipA-hypotheses/tipa-pp2c-phosphatase/openscientist.md

OpenScientist function-assignment analysis of the TipA PP2C phosphatase hypothesis

Deep Research

OpenScientist

(tipA-hypotheses/tipa-pp2c-phosphatase/openscientist.md)

Focused Curation Report — *Dictyostelium discoideum* **tipA** (UniProt Q94489) OpenScientist openscientist-autonomous 2 artifacts 2026-07-12T12:23:21.414456

OpenScientist final report (text/html)

OpenScientist final report (application/pdf)

Focused Curation Report — Dictyostelium discoideum tipA (UniProt Q94489)

Hypothesis evaluated: TipA is a functional PP2C-family (PPM), metal-dependent protein serine/threonine phosphatase.
Focus type: function_assignment · Slug: tipa-pp2c-phosphatase
Date: 2026-07-12 · Iterations: 1–3

Executive Judgment

Verdict: PARTIALLY SUPPORTED (family/fold supported; catalytic "functional phosphatase" claim UNRESOLVED — over-annotation risk if asserted with experimental confidence).

The domain/fold assignment is well supported. Q94489 is annotated by multiple orthogonal signature databases as a PPM/PP2C-type phosphatase domain (InterPro IPR001932/IPR053287, Gene3D 3.60.40.10, SUPFAM SSF81606, PANTHER PTHR21586 "TIPA"; UniProt domain 388–706). AlphaFold models this region as a confident PP2C fold (domain mean pLDDT ≈ 81).
The "functional / catalytically active phosphatase" part is not demonstrated. There is no biochemical evidence — no phosphatase assay, no metal-dependence test, and no substrate has ever been reported for TipA. The only functional study (Stege et al. 1999, PMID 10402673) is a developmental-genetic phenotype (tip formation, cell sorting), not an enzymatic characterization.
A conserved-motif red flag: the invariant PP2C metal-1/general-acid signature [VY]-D-G-H-x-G ("DGH") — present in human PPM1A and in the Dictyostelium functional PP2C Spalten/SpnA — is absent from TipA (the equivalent position reads ADGC, His→Cys).
Counter-nuance from structure: despite the linear-motif loss, the AlphaFold model assembles a spatial cluster of aspartate carboxylates (D413, D430, D576, D642, D646) plus His645 into a pocket resembling a PP2C bimetal active site. So a divergent but real metal-dependent active site remains plausible; this is not a clearly collapsed pseudophosphatase.
Family-wide catalytic-motif loss (over-annotation signal, added Iteration 2): across the entire TIPA-specific PP2C-like family (InterPro IPR053287, n=100; Dictyostelium, Drosophila CG9801, Caenorhabditis, Trichinella, cnidarians, molluscs, Entamoeba), the canonical DGHxG motif is present in 0% and a bare DGH in only 7%, versus 79% in the canonical PP2C family (IPR001932). The TIPA family is a divergent lineage that systematically lacks the invariant catalytic His, so family/domain membership cannot by itself justify a "functional phosphatase" call — this is a textbook paralog/frequency-bias over-annotation scenario. TipA's His645 is a Dictyostelium-specific substitution (family consensus has Ser here), i.e., a speculative species-specific candidate general acid, not a conserved catalytic signature.
Metal binding vs catalysis (Iteration 3): the metal-coordinating aspartate scaffold is conserved family-wide (N-terminal motif 80%, C-terminal 86%, both 69% of 100 members) while the catalytic general-acid His is not (7%). This cleanly separates a plausibly retained metal-binding capacity from an unsupported catalytic capacity — the molecular signature of a metal-binding but catalytically divergent/pseudo-PP2C.

Bottom line for the curator: the PP2C domain membership can be annotated (computational/ISS-level), and metal ion binding (GO:0046872) is the best-supported computed inference. A protein Ser/Thr phosphatase activity term should NOT be asserted with experimental evidence; catalytic activity is unproven and the canonical catalytic His motif is degenerate across the whole TIPA lineage. Treat "functional metal-dependent Ser/Thr phosphatase" as a hypothesis to be tested, not an established fact.

Evidence Matrix

#	Citation	Evidence type	Supports/Refutes/Qualifies	Claim tested	Key finding	Context	Confidence & limitations
1	UniProt Q94489; InterPro IPR001932/IPR053287; SUPFAM SSF81606; Gene3D 3.60.40.10; PANTHER PTHR21586	Structural/evolutionary (database)	Supports (domain)	TipA contains a PP2C/PPM domain	PPM-type phosphatase domain at 388–706; PANTHER "TIPA" family	Sequence/profile	High for fold membership; profile match ≠ catalytic competence
2	This work — direct motif scan	Computational	Refutes/Qualifies (catalysis)	Canonical PP2C catalytic motif conserved?	Invariant DGH (metal-1 Asp + general-acid His) present in PPM1A ("VYDGHAGS") and Spalten O15743 ("VYDGHGGT") but absent in TipA ("VADGCNWG", His→Cys)	Q94489 vs P35813 vs O15743	High (direct motif, reproducible). Single-motif view; ignores 3D relocation
3	This work — AlphaFold AF-Q94489-F1 (v6) geometry	Computational (structural)	Qualifies/Supports (catalysis plausible)	Does an active-site pocket assemble in 3D?	Domain pLDDT ≈ 81; Asp413/430/576/642/646 + His645 cluster within ~4–6 Å into a PP2C-like pocket	Predicted structure	Moderate. AF omits metals; rotamer distances uncertain; not proof of activity
4	Stege, Laub, Loomis 1999 (PMID 10402673)	Mutant phenotype	Supports BP/CC; silent on MF	What does TipA do biologically?	tipA-null: defective cell sorting, tip formation on mounds, reduced prespore/prestalk gene expression; cell-autonomous; acts in parallel with tipB/C/D	D. discoideum development	High for phenotype; no enzyme assay; does not establish catalytic mechanism
5	Aubry & Firtel 1998 (PMID 9585512)	Direct assay (paralog control)	Competing/Qualifies	Is there a bona fide Dictyostelium developmental PP2C?	Spalten (SpnA) encodes a functional PP2C (demonstrated), essential for cell-type differentiation; PP2C domain is the effector	D. discoideum development	High; shows a different gene is the validated developmental PP2C — TipA activity not assayed
5b	This work — InterPro family motif census	Computational (evolutionary)	Qualifies/Refutes (family-based inference)	Does TIPA-family membership imply catalytic residues?	Canonical DGHxG in 0/100 TIPA-family (IPR053287) vs 79/100 (DGH) in canonical PP2C (IPR001932); family shares divergent motifs "ADG[VC]NWG" and "(T/I)SDG[IV]xDN" but lacks the general-acid His	100 cross-species family members	High (reproducible census). Motif-based; does not exclude activity via non-canonical mechanism
5c	This work — metal-Asp scaffold census (Iteration 3)	Computational (evolutionary)	Qualifies (metal binding yes, catalysis no)	Are the metal-coordinating aspartates conserved family-wide?	Metal-Asp scaffolds retained: N-term [AG]DG[VCA]N[WF] 80/100, C-term SDG-Asp 86/100, both 69/100; but catalytic His only 7/100. TipA has both scaffolds + rare His645	100 TIPA-family members	High. Signature of metal-binding but catalytically divergent/pseudo-PP2C
6	Das, Helps, Cohen, Barford 1996 (PMID 9003755)	Structural (reference)	Orientation	What residues make PP2C catalytic?	PP2C is Mn²⁺/Mg²⁺-dependent; a binuclear metal centre with metal-bound water provides nucleophile/general acid; requires conserved Asp ligands	Human PP2Cα	High; establishes why metal-Asp/His conservation matters

GO Curation Implications (leads — require curator verification)

Molecular Function. Do not assign an experimentally-supported protein Ser/Thr phosphatase MF term. Options, in order of conservatism:
Acceptable as computational/ISS or IBA (from PANTHER PTHR21586 "TIPA"): GO:0004722 protein serine/threonine phosphatase activity or the more generic GO:0016791 phosphatase activity — with an ISS/IEA evidence code and a caveat note that the canonical catalytic His motif is degenerate and activity is unassayed.
GO:0046872 metal ion binding is the best-supported computed inference (the metal-coordinating aspartate scaffold is conserved family-wide: N-term 80%, C-term 86%, both 69%), but is still only sequence-level (ISS/IEA) — no metal-binding assay exists.
If the review’s prior action asserted an experimental MF phosphatase term, that is too strong → recommend downgrading to computational or removing pending assay.
Biological Process (retain). GO:0031154 culmination involved in sorocarp development (IMP) and GO:0030587 sorocarp development (HMP) are supported by Stege et al. 1999 (PMID 10402673). Keep.
Cellular Component (retain). GO:0005737 cytoplasm (IDA, dictyBase). Keep.
Net: the seed hypothesis, if used to add an experimentally-weighted MF phosphatase annotation, is too strong; a computational MF annotation with an explicit "atypical/unverified active site" caveat is defensible.

Mechanistic Scope

Immediate molecular function under test: metal-dependent hydrolysis of phosphoserine/phosphothreonine on protein substrates by a PPM/PP2C catalytic domain. This requires a binuclear Mn²⁺/Mg²⁺ centre coordinated by conserved aspartates plus a general acid (PMID 9003755).
What the evidence actually shows: TipA has the PP2C fold and can geometrically assemble a candidate metal-binding pocket, but no dephosphorylation, metal dependence, or substrate has been measured.
Downstream/indirect layers (not the MF): the tipA-null phenotype (cell sorting, tip formation, delayed prespore/prestalk differentiation, aggregate morphogenesis) is a developmental outcome, not direct evidence of catalytic activity. Attributing the phenotype to phosphatase catalysis is inference, not demonstration.

Conflicts and Alternatives

Paralog confusion (important). The validated Dictyostelium developmental PP2C is Spalten/SpnA (PMID 9585512), not TipA. Spalten retains the intact DGH catalytic motif; TipA does not. A curator should ensure phosphatase evidence is not being transferred from Spalten (or the broader PP2C family) onto TipA by homology/family inference.
Pseudophosphatase possibility. Loss of the invariant general-acid His (DGH→DGC) is a classic hallmark of degenerate/pseudo-phosphatases. TipA could function as a non-catalytic scaffold/adaptor whose PP2C-like fold binds phospho-proteins without turning them over.
Divergent-but-active possibility. The AlphaFold carboxylate+His cluster leaves open that TipA is a sequence-atypical active phosphatase (His role relocated to His645). This cannot be resolved without an assay.
Prediction-quality caveats. Family-level annotation (PANTHER "TIPA") is prone to frequency/paralog bias; AlphaFold does not model catalysis; the linear-motif call ignores 3D. Each tool, alone, is weak — hence the "unresolved" MF verdict.
Family-wide degeneracy quantified (Iteration 2). The catalytic His loss is not idiosyncratic to TipA but is shared by the whole TIPA/IPR053287 lineage (0/100 with DGHxG vs 79/100 in canonical PP2C). This means any "functional phosphatase" annotation propagated from family/domain membership is unsupported by conserved catalytic residues; if the review's assignment derives from InterPro2GO/PANTHER family inference, that is the specific over-annotation to flag.

Knowledge Gaps

Gap	What was checked	Why it matters	What would resolve it
No enzyme activity data	PubMed searches returned no biochemical assay for TipA	"Functional phosphatase" is the crux of the hypothesis	In vitro phosphatase assay (pNPP + protein/phosphopeptide substrate) ± Mn²⁺/Mg²⁺
Catalytic-residue identity	Motif scan (reliable) + AF geometry (suggestive); pairwise alignment was unreliable (failed even on the functional Spalten control)	Determines active vs pseudo-phosphatase	Structure-guided HMM/MSA of PPM family with metal modeling; site-directed mutagenesis of candidate Asp/His
Substrate & physiological target	None known	Needed to link catalysis to the tip/sorting phenotype	Phosphoproteomics of tipA-null vs WT; substrate trapping
Metal dependence	Not tested	Defines "metal-dependent" claim	Activity assay ± EDTA / with Mn²⁺, Mg²⁺ titration
Is His645 the general acid?	Inferred from AF cluster only	Distinguishes divergent-active from dead	H645A / D642A / D646A catalytic mutants + activity

Discriminating Tests (most efficient first)

In vitro phosphatase assay of recombinant TipA (or its 388–706 domain) on a generic substrate (pNPP or phosphopeptide) with and without Mn²⁺/Mg²⁺ — directly settles "functional metal-dependent phosphatase."
Structure-guided catalytic mutagenesis (candidate metal ligands D413/D430/D576/D642/D646 and His645) → test loss of activity and whether mutants fail to rescue the tipA-null developmental phenotype (links catalysis to biology).
Rigorous PPM-family MSA/HMM with metal-site mapping (e.g., against solved PP2C structures) to formally score active-site integrity rather than relying on a single linear motif.
Phosphoproteomics of tipA⁻ vs WT during aggregation/tip formation to identify candidate substrates (hyperphosphorylated targets).
Comparative check of the PANTHER "TIPA" subfamily (PTHR21586, incl. Drosophila CG9801) for conservation/loss of catalytic residues to see if the whole subfamily is degenerate.

Curation Leads (require curator verification)

Candidate references to cite/verify:
PMID 10402673 (Stege 1999) — snippet: "null mutations in tipA showed a primary defect in cell sorting and the formation of tips on the developing mound" → supports BP/CC only, not MF.
PMID 9585512 (Aubry & Firtel 1998) — snippet: "a carboxy-terminal domain that encodes a functional PP2C" → the validated developmental PP2C is Spalten, useful as paralog control (do not transfer to TipA).
PMID 9003755 (Das 1996) — snippet: "Mn²⁺- or Mg²⁺-dependent protein Ser/Thr phosphatase … binds two manganese ions … provide a nucleophile and general acid" → defines the catalytic requirements TipA has not been shown to meet.
Candidate GO actions:
Keep BP GO:0031154, GO:0030587; keep CC GO:0005737.
If an MF phosphatase term exists with experimental evidence → downgrade to ISS/IEA or remove (too strong).
If adding MF, use ISS/IBA GO:0004722 (or GO:0016791) with a caveat that the catalytic His motif is atypical and activity is unverified. Avoid a bare "protein binding" fallback.
Suggested curator questions:
Is any experimental phosphatase evidence for TipA in the source, or is the assignment homology-only?
Is the MF being transferred from Spalten/family membership (paralog carry-over)?
Suggested experiments: see Discriminating Tests 1–2.

Provenance / Reproducibility

UniProt Q94489 (759 aa; domain 388–706), P35813 (PPM1A), O15743 (Spalten/SpnA) fetched via UniProt REST.
Active-site motif scan (DG[HN].G, [ILVMFC]DG[ILVMFAWI]): DGH present in PPM1A@60 and Spalten@749; absent in TipA (ADGC@430).
AlphaFold AF-Q94489-F1 v6: domain mean pLDDT 80.8; carboxylate cluster D413/D430/D576/D642/D646 + His645 within ~4–6 Å.
InterPro family motif census (Iteration 2): IPR053287 (TIPA) n=100 → DGHxG 0%, DGH 7%; IPR001932 (canonical PP2C, reviewed) n=100 → DGH 79%. Conserved TIPA-family motifs: "ADG[VC]NWG" and "(T/I)SDG[IV]xDN"; His645 is a Dictyostelium-specific substitution of the family-consensus Ser.
Pairwise BLOSUM62 global alignment was explicitly judged unreliable (failed on the functional Spalten control) and was therefore not used for residue-level conclusions.

Limitations: all sequence/structure analyses are computational; no wet-lab activity data exist. Conclusions distinguish direct results (motif presence/absence, fold confidence) from inference (catalytic competence).

Artifacts

📄 View Raw YAML

id: Q94489
gene_symbol: tipA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: TipA is a Dictyostelium discoideum protein required for the sorting of
  the initial prestalk and prespore cell types and for formation of the organizing
  tip during multicellular development. It is preferentially expressed in prestalk
  PstO cells after cell-type sorting and acts cell-autonomously at an early
  developmental stage. Cells lacking TipA fail to sort prestalk cells to the top of
  the aggregate, do not form a proper tip or migrating slug, express the
  prestalk-specific gene ecmA at reduced levels, and produce very few spores. The
  protein is a novel ~83 kDa polypeptide containing a predicted PP2C-like (PPM-type)
  protein phosphatase domain and a coiled-coil region, but its molecular activity
  has not been experimentally established. Through its role in tip formation and
  prestalk cell sorting, TipA is essential for the transition from mound to slug and
  for subsequent culmination into a fruiting body (sorocarp).
existing_annotations:
- term:
    id: GO:0030587
    label: sorocarp development
  evidence_type: HMP
  original_reference_id: PMID:17659086
  qualifier: acts_upstream_of_or_within
  review:
    summary: A high-throughput time-lapse phenotyping screen of insertional mutants
      placed tipA among a cluster of mutants defective at the slug and culmination
      stages of development, consistent with a requirement for tipA in sorocarp
      (fruiting body) development. This broad process term correctly captures the
      developmental role of the gene, even though the underlying molecular activity
      is unknown.
    action: ACCEPT
    reason: tipA disruption produces a developmental phenotype affecting slug and
      culmination stages, so involvement in sorocarp development is well supported.
      The term is general but appropriate as the umbrella developmental process,
      and this HMP annotation is consistent with the independent IMP evidence from
      the tipA knockout.
    supported_by:
    - reference_id: PMID:17659086
      supporting_text: Particularly noticeable are five mutants disrupted in tagB/C,
        mutations in tipA, tipB, tipC, and tipD
    - reference_id: PMID:17659086
      supporting_text: Another major mutant cluster contains clones showing
        defective behavior at the slug and culmination stage, but wild-type behavior
        during aggregation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:9169048
  qualifier: located_in
  review:
    summary: Direct-assay (IDA) cytoplasmic localization annotated by dictyBase from
      the 1997 tipA characterization paper. The cached publication is abstract-only
      (full text not available), and the abstract does not describe subcellular
      localization, so the supporting evidence cannot be verified here. Cytoplasmic
      localization is plausible for this ~83 kDa PP2C-like protein, but the evidence
      is not verifiable from available material.
    action: UNDECIDED
    reason: The only cited reference is abstract-only in the cache and the abstract
      does not address subcellular localization. Per policy this experimental
      curator annotation is not overruled; it is marked UNDECIDED because the
      supporting evidence cannot be independently verified.
- term:
    id: GO:0031154
    label: culmination involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:9169048
  qualifier: acts_upstream_of_or_within
  review:
    summary: Loss of tipA by REMI mutagenesis blocks normal development - mutant
      cells fail to sort prestalk cells to the top of the aggregate, fail to form
      slugs, and produce very few spores - placing TipA upstream of the events
      leading to culmination and fruiting body formation. This IMP annotation from
      the tipA knockout is well supported by the mutant phenotype.
    action: ACCEPT
    reason: The developmental arrest of tipA mutants (failure of prestalk sorting,
      tip formation and slug/fruiting-body formation) supports an
      acts_upstream_of_or_within relationship to culmination within sorocarp
      development. This is an experimental IMP annotation supported by the described
      phenotype and is retained as a core developmental role of the gene.
    supported_by:
    - reference_id: PMID:9169048
      supporting_text: This mutant fails to form slugs and appears to have a defect
        in sorting of prestalk cells.
    - reference_id: PMID:9169048
      supporting_text: The tipA gene appears to play an essential role in the sorting
        of the initial cell types.
references:
- id: PMID:17659086
  title: High-throughput analysis of spatio-temporal dynamics in Dictyostelium.
  findings:
  - statement: tipA mutants cluster with mutants defective at the slug and
      culmination stages of development while behaving normally during aggregation.
    supporting_text: Another major mutant cluster contains clones showing defective
      behavior at the slug and culmination stage, but wild-type behavior during
      aggregation
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full-text screen; independently corroborates a tipA developmental
      defect at slug/culmination stages, supporting the HMP sorocarp development
      annotation. It does not address molecular function.
- id: PMID:9169048
  title: Sorting of the initial cell types in Dictyostelium is dependent on the tipA
    gene.
  findings:
  - statement: tipA encodes a novel ~83 kDa protein preferentially expressed in
      prestalk PstO cells after cell-type sorting.
    supporting_text: The disrupted gene, tipA, encodes a novel 83-kDa protein and is
      preferentially expressed in PST-O cells after the cell types have sorted out.
  - statement: tipA mutants fail to form slugs and are defective in sorting of
      prestalk cells.
    supporting_text: This mutant fails to form slugs and appears to have a defect in
      sorting of prestalk cells.
  - statement: Cells lacking TipA express the prestalk marker ecmA at reduced levels
      and form very few spores.
    supporting_text: Mutant strains that lack TipA express the prestalk-specific gene
      ecmA at reduced levels and form very few spores.
  - statement: TipA acts cell-autonomously at an early stage of development and is
      essential for sorting of the initial cell types.
    supporting_text: The tipA gene appears to play an essential role in the sorting
      of the initial cell types.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary characterization of tipA. Cached copy is abstract-only
      (full_text_available false); the abstract establishes the developmental and
      cell-sorting role but does not describe subcellular localization, hence the
      cytoplasm IDA cannot be verified from available text.
- id: file:DICDI/tipA/tipA-hypotheses/tipa-pp2c-phosphatase/openscientist.md
  title: OpenScientist function-assignment analysis of the TipA PP2C phosphatase hypothesis
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Independent OpenScientist function-assignment run (3 iterations). Verdict
      PARTIALLY SUPPORTED. The PP2C/PPM domain membership is well supported
      (InterPro IPR001932 / IPR053287, PANTHER PTHR21586, confident AlphaFold
      PP2C fold), but the canonical catalytic-His motif (DGHxG) is absent across
      the entire TIPA-specific phosphatase family (0/100 members) while the
      metal-coordinating aspartate scaffold is conserved (~69-86 percent). Best
      supported computed molecular function is metal ion binding; protein
      Ser/Thr phosphatase activity should NOT be asserted with experimental
      confidence. Concordant with this review leaving molecular_function
      unasserted. Lead - TipA is likely a metal-binding but catalytically
      divergent (pseudo)PP2C; requires an enzyme assay to resolve.
core_functions:
- description: TipA is required for the sorting of the initial prestalk (PstO) cell
    type and for formation of the organizing tip during the mound-to-slug transition
    of Dictyostelium multicellular development, acting cell-autonomously upstream of
    slug formation and culmination. Its molecular activity is not established; the
    protein carries a predicted but experimentally unverified PP2C-like (PPM-type)
    phosphatase domain, so no molecular function term is asserted.
  directly_involved_in:
  - id: GO:0031154
    label: culmination involved in sorocarp development
  - id: GO:0030587
    label: sorocarp development
  supported_by:
  - reference_id: PMID:9169048
    supporting_text: The tipA gene appears to play an essential role in the sorting
      of the initial cell types.
  - reference_id: PMID:9169048
    supporting_text: This mutant fails to form slugs and appears to have a defect in
      sorting of prestalk cells.

tipA

Gene Description