Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003925 G protein activity	IBA GO_REF:0000033	ACCEPT	Summary: Correct and core molecular function. GPA-12 is a heterotrimeric G protein alpha subunit (Galpha-12/13 subfamily) that cycles between GTP- and GDP-bound states to act as a signal-transducing molecular switch. GO:0003925 is the appropriate MF for such subunits, and its behavior is supported experimentally in worm by the constitutively active Q205L (catalytic-glutamine) mutant. Reason: Best and most specific molecular-function term for a Galpha subunit; consistent with family membership, intact G1-G5 motifs, and the behavior of activated GPA-12. Supporting Evidence: PMID:12646136 We characterized a C. elegans Galpha subunit gene, gpa-12, which is a homolog of mammalian G(12)/G(13)alpha, and found that animals defective in gpa-12 are viable
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) localization to cytoplasm, independently corroborated by the experimental IDA cytoplasm annotation from PMID:12646136. This is a reasonable functional cellular compartment for a peripheral, membrane-associated Galpha subunit that cycles at the cytoplasmic face of the plasma membrane. Reason: Consistent, independently corroborated cellular localization for a Galpha subunit; accepted as the cellular compartment in which GPA-12 acts.
GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	REMOVE	Summary: Over-propagation from the pan-Galpha PANTHER family node. Adenylate cyclase/cAMP modulation is the defining function of the Gs (stimulatory) and Gi (inhibitory) subfamilies, not of the Galpha-12/13 subfamily to which GPA-12 belongs. There is no evidence that GPA-12 modulates adenylate cyclase, and this pathway type is biologically inappropriate for a G12/13 protein. Reason: Biologically incorrect for the G12/13 subfamily; the term propagated electronically from Gs/Gi paralogs in the broad pan-Galpha tree and should not transfer to GPA-12. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000026392 · pan-Galpha family node SUPPORTS SOURCE BUT NOT TARGET
GO:0007266 Rho protein signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Canonical mammalian Galpha-12/13 signaling activates RhoGEFs to relay signals through Rho GTPases, so this term is biologically apt at the family level and propagates from the G12/13 node (mouse Gna12/Gna13). However, the Rho effector arm has not been demonstrated for C. elegans GPA-12; the experimentally defined worm effector arm runs through phospholipase (PLC-3) and PKCdelta (TPA-1). Retained as a homology-based, non-core inference. Reason: Homology-supported canonical G12/13 function, but not experimentally established in worm, where the demonstrated downstream arm is PLC/PKCdelta rather than Rho.
GO:0005834 heterotrimeric G-protein complex	IBA GO_REF:0000033	ACCEPT	Summary: Correct. As a Galpha subunit, GPA-12 assembles into a heterotrimeric G protein (Galpha-beta-gamma) complex; in the epidermal immune pathway it partners with the Gbeta RACK-1. Reason: Accurate and well-supported complex membership for a Galpha subunit. Supporting Evidence: PMID:22470487 Wounding and infection require G-protein signaling, involving the Gα protein GPA-12 and the Gß RACK-1, while infection specifically involves the Tribbles-like kinase NIPI-3
GO:0031526 brush border membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Over-specific location propagated from mammalian (rat) orthologs. Brush border membrane is the plasma membrane of intestinal microvilli; GPA-12's demonstrated site of action is the epidermis/hypodermis. There is no C. elegans evidence for brush border localization. Reason: Narrow mammalian-tissue location transferred by phylogenetic inference; not supported for the worm protein and inconsistent with its known site of action. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000026689 · Galpha-12/13 node SUPPORTS SOURCE BUT NOT TARGET
GO:0031752 D5 dopamine receptor binding	IBA GO_REF:0000033	REMOVE	Summary: Hyper-specific molecular function propagated from a single mammalian ortholog annotation. Binding to a D5 dopamine receptor is not a plausible or supported activity for C. elegans GPA-12 (worms lack a D5 dopamine receptor ortholog), and there is no worm evidence for it. Reason: Over-propagated, organism-specific receptor-binding annotation with no relevance or evidence for the worm protein. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000026689 · Galpha-12/13 node SUPPORTS SOURCE BUT NOT TARGET
GO:0001664 G protein-coupled receptor binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic InterPro-based inference. Galpha subunits are activated by, and physically couple to, GPCRs, so GPCR binding is a defensible general molecular function. However, the specific cognate receptor for GPA-12 is not established, so this remains a generic, non-core capability. Reason: True general Galpha property (more informative than 'protein binding') but generic; the actual GPA-12 receptor is unknown.
GO:0003924 GTPase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Galpha subunits have intrinsic GTPase activity that terminates signaling by returning the switch to the GDP-bound state. Correct for GPA-12, whose G-box motifs are intact and whose catalytic-glutamine (Q205L) mutant behaves as a GTP-hydrolysis-defective, constitutively active protein. The more specific GO:0003925 (G protein activity) better captures the defining signaling-switch role, so this generic GTPase term is retained as a supporting, non-core activity. Reason: Correct enzymatic capability for a Galpha subunit, but a supporting activity underlying the switch rather than the defining core function, which is better represented by GO:0003925 (G protein activity).
GO:0007165 signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: High-level, generic biological process. True (GPA-12 is a signal transducer) but far less informative than the specific GPCR-signaling and immune-signaling processes it participates in. Reason: Correct but uninformatively general; subsumed by more specific process terms.
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: Appropriate mechanistic process term: Galpha subunits are the canonical transducers of GPCR signaling. This captures the pathway type through which GPA-12 relays signals in the epidermis, even though the specific receptor is not yet identified. Reason: Accurate, mechanism-defining process for a Galpha subunit.
GO:0007266 Rho protein signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based duplicate of the IBA Rho protein signal transduction annotation, reflecting the canonical G12/13 -> RhoGEF -> Rho effector arm. As with the IBA version, this is homology-based and not experimentally demonstrated for worm GPA-12. Reason: Redundant with the IBA annotation; homology-supported canonical function not demonstrated in worm.
GO:0019001 guanyl nucleotide binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct supporting molecular function: GPA-12 binds guanine nucleotides (GTP/GDP) via its intact G-box motifs. This underlies the G protein switch but is a component capability rather than the core function. Reason: Accurate binding activity underpinning the GTPase/G-protein switch; supporting rather than core.
GO:0031683 G-protein beta/gamma-subunit complex binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct: the Galpha subunit binds the Gbeta/gamma dimer to form the inactive heterotrimer, releasing it upon GTP loading. Consistent with the curated GO-CAM (gomodel:5b91dbd100002057), which models GPA-12's molecular function as Gbeta/gamma-subunit complex binding, partnered with the Gbeta RACK-1. Reason: Accurate Galpha-Gbetagamma interaction supporting heterotrimer assembly; supporting rather than the core signaling function.
GO:0010628 positive regulation of gene expression	IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia...	ACCEPT	Summary: Experimentally supported: epidermis-restricted active GPA-12* drives a marked constitutive increase in antimicrobial peptide gene expression (nlp-29, nlp-31, nlp-34 and cnc-1, cnc-4), an effect abolished in a nipi-4 mutant. This is the transcriptional-induction readout of GPA-12's epidermal immune signaling. Reason: Directly supported by loss/gain-of-function transcriptional data; captures GPA-12's role in up-regulating immune-effector gene expression. Supporting Evidence: PMID:22470487 In uninfected transgenic worms carrying the Pcol-19::GPA-12* construct, we observed a very marked increase in the expression of Pnlp-29::GFP in the epidermis from the late L4 stage onwards PMID:22470487 the transgenic strain exhibited an elevated constitutive expression of nlp-29, nlp-31 and nlp-34, and cnc-1, cnc-4
GO:0050832 defense response to fungus	IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia...	ACCEPT	Summary: Experimentally supported core biological process. GPA-12 signaling is required for the epidermal antifungal defense program (nlp/cnc antimicrobial peptide induction) against the natural fungal pathogen Drechmeria coniospora. Reason: Well-supported IMP annotation reflecting GPA-12's core physiological role in antifungal defense. Supporting Evidence: PMID:22470487 When we crossed the Pcol-19::GPA-12* transgene into nipi-4(fr106) mutant, the elevated expression of the Pnlp-29::GFP reporter provoked by the active form of GPA-12 was abrogated
GO:0061760 antifungal innate immune response	IMP PMID:19380113 Antifungal innate immunity in C. elegans: PKCdelta links G p...	ACCEPT	Summary: Experimentally supported and the most specific immune process term for GPA-12. Epidermal antifungal innate immunity (nlp-29 induction) requires G protein signaling acting through PKCdelta and the p38 MAPK cascade, with GPA-12 as the Galpha subunit; this is the same activity modeled in the curated GO-CAM (gomodel:5b91dbd100002057). Reason: Core, well-supported immune process; most specific and informative BP term for this gene. Supporting Evidence: PMID:19380113 This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta PMID:19380113 C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29
GO:0005634 nucleus	IDA PMID:12646136 Hyperactivation of the G12-mediated signaling pathway in Cae...	KEEP AS NON CORE	Summary: WormBase IDA nuclear localization from PMID:12646136. Nuclear localization is unusual for a Galpha subunit, and the primary imaging data are in the full text, which is not in the cache (abstract-only). Per curation guidance I do not overrule an experimental IDA I cannot fully verify; I retain it as a non-core localization and defer to the WormBase curator. Reason: Experimental IDA from the curator (full text unavailable to verify); unusual for a Galpha and not a core function, but not to be removed on incomplete evidence.
GO:0005737 cytoplasm	IDA PMID:12646136 Hyperactivation of the G12-mediated signaling pathway in Cae...	ACCEPT	Summary: WormBase IDA cytoplasmic localization from PMID:12646136, consistent with the expected peripheral/cytoplasmic disposition of a membrane-associated Galpha subunit and with the IBA cytoplasm annotation. Accepted as the cellular compartment in which GPA-12 acts. Reason: Experimentally curated localization for a Galpha, corroborated by phylogenetic inference; accepted as GPA-12's cellular compartment of action.
GO:0050832 defense response to fungus	IMP PMID:19380113 Antifungal innate immunity in C. elegans: PKCdelta links G p...	ACCEPT	Summary: Experimentally supported core process (duplicate term with a distinct primary reference). GPA-12 is required for the epidermal antifungal defense response, as shown by its position upstream of PKCdelta and the p38 cascade controlling nlp-29 induction after fungal infection. Reason: Well-supported IMP annotation from the Ziegler et al. study; reinforces the core antifungal-defense role. Supporting Evidence: PMID:19380113 This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta

Core Functions

GPA-12 acts as a Galpha-12/13-type heterotrimeric G protein alpha subunit: a GTP/GDP-regulated molecular switch that transduces cell-surface (GPCR-type) signals in the C. elegans epidermis. Functioning upstream of PKCdelta (TPA-1) and the conserved TIR-1 -> NSY-1 -> SEK-1 -> PMK-1 (p38) MAPK cascade and the STAT-like factor STA-2, GPA-12 signaling drives induction of NLP- and CNC-family antimicrobial peptide genes in the antifungal innate immune response and after wounding. It assembles into a heterotrimer with a Gbeta (RACK-1)/gamma dimer, and an activated form (Q205L) is sufficient to drive the antimicrobial peptide program.

Molecular Function:

G protein activity

Directly Involved In:

antifungal innate immune response G protein-coupled receptor signaling pathway

Cellular Locations:

cytoplasm

In Complex:

heterotrimeric G-protein complex

Supporting Evidence:

PMID:19380113
This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta
PMID:22470487
Wounding and infection require G-protein signaling, involving the Gα protein GPA-12 and the Gß RACK-1, while infection specifically involves the Tribbles-like kinase NIPI-3
PMID:12646136
We characterized a C. elegans Galpha subunit gene, gpa-12, which is a homolog of mammalian G(12)/G(13)alpha, and found that animals defective in gpa-12 are viable

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

PMID:12646136

Hyperactivation of the G12-mediated signaling pathway in Caenorhabditis elegans induces a developmental growth arrest via protein kinase C.

PMID:19380113

Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.

PMID:22470487

The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene expression.

Knowledge Gaps

What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: The cognate receptor and activating input for GPA-12 are not biochemically defined. It is unknown which cell-surface receptor couples to GPA-12 to initiate epidermal immune signaling, what ligand/damage cue activates it, and whether GPA-12 engages such a receptor directly.

OPEN BIOLOGY RESIDUAL_SUBGAP

What is known: Established: GPA-12 is a Galpha-12/13 subunit that acts upstream of PKCdelta (TPA-1) and the p38 MAPK cascade to drive antimicrobial peptide expression after fungal infection and wounding, and its activity is required for this response. Unknown: the identity of the activating receptor and whether coupling is direct.

Significance: Identifying the receptor that switches on GPA-12 would define the sensing step of epidermal surveillance immunity and connect damage/infection detection to the p38/PMK-1 defense program.

Provenance (the field's own admissions):

"Our current understanding of both epidermal and intestinal innate immunity is far from complete" — PMID:22470487

Gap: The immediate downstream effector of GPA-12 is undetermined. Genetic epistasis places GPA-12 upstream of phospholipase (PLC-3) and PKCdelta (TPA-1), but it is not known whether GPA-12 directly activates a phospholipase, a RhoGEF/Rho module (the canonical mammalian Galpha-12/13 effector arm), or another target.

OPEN BIOLOGY MF_DARK

What is known: Established: GPA-12/G-protein signaling acts genetically upstream of C-type phospholipases and PKCdelta, and activated GPA-12 drives the p38-dependent antimicrobial peptide program. Unknown: the direct biochemical effector; the canonical G12/13 -> RhoGEF -> Rho arm has not been demonstrated in worm.

Significance: Whether worm GPA-12 signals through a Rho arm (like mammalian G12/13) or through a phospholipase/PKCdelta arm (more Gq-like) determines how this subfamily was wired into nematode epidermal immunity and would resolve an apparent divergence from the mammalian paradigm.

Provenance (the field's own admissions):

"This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta" — PMID:19380113

Gap: The full endogenous tissue and physiological repertoire of GPA-12 is unresolved. Its immune requirement is epidermis/cell-type restricted, and hyperactive G12 separately perturbs pharyngeal pumping/feeding and growth, but why the immune requirement is tissue-restricted and what other endogenous processes GPA-12 normally controls are not defined.

OPEN BIOLOGY BP_DARK

What is known: Established: active GPA-12 drives antimicrobial peptide expression in the epidermis and, when broadly hyperactivated, causes a growth arrest via a pharyngeal-pumping defect (with TPA-1 downstream); loss-of-function animals are viable. Unknown: the complete set of tissues/behaviors in which endogenous GPA-12 acts, and the basis of its tissue-restricted immune role.

Significance: Mapping GPA-12's endogenous functions would distinguish its dedicated immune role from its developmental/feeding role and clarify how one Galpha subunit is deployed across contexts.

Provenance (the field's own admissions):

"Expression of activated GPA-12 (G(12)QL) results in a developmental growth arrest caused by a feeding behavior defect that is due to a dramatic reduction in pharyngeal pumping" — PMID:12646136

📚 Additional Documentation

Notes

(gpa-12-notes.md)

gpa-12 (C. elegans) — research notes

UniProt: Q19572 (GPA12_CAEEL) · WormBase: WBGene00001674 / F18G5.3 · 355 aa · Chromosome X

Summary / identity

GPA-12 is a heterotrimeric guanine-nucleotide-binding protein alpha subunit of the
Gα12/13 subfamily (InterPro IPR000469 Gprotein_alpha_12/13; PRINTS PR00440 GPROTEINA12;
PANTHER PTHR10218 "GTP-binding protein alpha subunit"). It is the C. elegans homolog of
mammalian Gα12/Gα13 PMID:12646136.
The protein has the canonical G-alpha domain with all five G-box GTP/Mg2+-binding motifs
(G1 31–44 … G5 325–330; UniProt) and N-terminal cysteines (…MVCCFGKK…) typical of
membrane-anchored Gα subunits.

KNOWN (well supported)

Molecular function

G protein (Gα) GTP/GDP molecular switch — GO:0003925 G protein activity. Family
membership and the intact G1–G5 nucleotide-binding motifs (UniProt) support intrinsic
guanine-nucleotide binding and GTPase-based cycling. The functional read-out of the switch
is demonstrated genetically: a Q205L substitution in the catalytic Gln (the residue whose
mutation blocks GTP hydrolysis in Gα subunits) yields a constitutively active GPA-12
that drives constitutive antimicrobial-peptide gene expression [UniProt MUTAGEN Q205L,
ECO:0000269|PMID:22470487]. Intrinsic GTPase activity of the worm protein has not been
measured biochemically (inferred from homology + the behavior of the GQ→L mutant).
Assembles into a heterotrimeric G protein complex (Gα·Gβγ). The curated GO-CAM
(gomodel:5b91dbd100002057) models GPA-12's molecular function as GO:0031683 G-protein
beta/gamma-subunit complex binding, partnered in the pathway with the Gβ RACK-1.

Biological process — epidermal antifungal innate immunity (the core physiological role)

Required for antifungal innate immune response / defense response to fungus in the
epidermis: GPA-12 signaling is needed for infection- and wounding-induced up-regulation of
antimicrobial peptides of the NLP (nlp-29 cluster) and CNC families
[PMID:19380113 IMP; PMID:22470487 IMP].
Genetic pathway position (epistasis): GPA-12/G-protein signaling acts upstream of
PKCδ (TPA-1) and a conserved p38 MAPK cassette (TIR-1 → NSY-1 → SEK-1 → PMK-1) →
STAT-like STA-2, driving nlp/cnc gene expression [PMID:19380113 "This involves G protein
signaling and specific C-type phospholipases acting upstream of PKCdelta"; "C. elegans PKC
acts through the p38 MAPK pathway to regulate nlp-29"]. In PMID:22470487:
"Wounding and infection require G-protein signaling, involving the Gα protein GPA-12 and the
Gß RACK-1, while infection specifically involves the Tribbles-like kinase NIPI-3".
Gain-of-function drives the effector program: epidermis-restricted expression of active
GPA-12 (Pcol-19::GPA-12) causes marked constitutive Pnlp-29::GFP expression
["In uninfected transgenic worms carrying the Pcol-19::GPA-12 construct, we observed a very
marked increase in the expression of Pnlp-29::GFP in the epidermis from the late L4 stage
onwards"] and constitutive nlp/cnc transcript induction ["the transgenic strain exhibited an
elevated constitutive expression of nlp-29, nlp-31 and nlp-34, and cnc-1, cnc-4"]; this
effect is abrogated in a nipi-4 (downstream pseudokinase) mutant ["When we crossed the
Pcol-19::GPA-12 transgene into nipi-4(fr106) mutant, the elevated expression of the
Pnlp-29::GFP reporter provoked by the active form of GPA-12 was abrogated"] (all
PMID:22470487). → supports positive regulation of gene expression (GO:0010628, IMP).
GO-CAM causal structure (gomodel:5b91dbd100002057, "Antifungal innate immune response in
the hypodermis via MAPK cascade"): GPA-12 activity is causally upstream, positive effect
(RO:0002304) of TPA-1 activity, within GO:0061760 antifungal innate immune response
(evidence PMID:19380113). Consistent with the literature.

A second, developmental context (Gα12 gain-of-function)

Activated GPA-12 (G12QL) causes a developmental growth arrest via a feeding defect
(reduced pharyngeal pumping); genetic suppressors map to tpa-1 (PKCθ/δ), placing TPA-1
downstream of G12 signaling here too [PMID:12646136 "Expression of activated GPA-12 (G(12)QL)
results in a developmental growth arrest caused by a feeding behavior defect that is due to a
dramatic reduction in pharyngeal pumping"; "TPA-1 is a downstream target of both G(12)
signaling and PMA in modulating feeding and growth in C. elegans"]. gpa-12 loss-of-function
animals are viable (i.e. not essential).

Localization

WormBase IDA: cytoplasm (GO:0005737) and nucleus (GO:0005634) [PMID:12646136, IDA].
Full text of PMID:12646136 is not in cache (abstract-only); the localization data are in the
full text I cannot read. Cytoplasmic/peripheral-membrane localization is expected for a Gα;
nuclear localization of a Gα is unusual — I defer to the WormBase curator but treat these as
non-core.

NOT known / genuine knowledge gaps

Cognate receptor / activating input. The receptor(s) and ligand(s) that activate GPA-12
to launch epidermal immune signaling, and whether GPA-12 couples directly to a damage-sensing
GPCR, are not established from the cached primary literature. PMID:22470487 states the
upstream elements are only partly defined ("Our current understanding of both epidermal and
intestinal innate immunity is far from complete"). (A candidate epidermal GPCR, DCAR-1,
has been reported elsewhere in the field, but that paper is not in the cache and the direct
GPA-12↔receptor biochemical coupling is not shown here.)
Direct downstream effector. Genetic epistasis places GPA-12 upstream of PLC-3 / TPA-1
(PKCδ) and the p38 cascade, but the immediate biochemical effector of GPA-12 is unproven.
Notably, the canonical mammalian Gα12/13 effector arm (RhoGEF → Rho; GO:0007266 Rho protein
signal transduction) has not been demonstrated for the worm protein; in worm the demonstrated
arm runs through phospholipase/PKCδ, which is more Gq-like. Whether GPA-12 directly engages a
RhoGEF, a phospholipase, or another effector is unresolved.
Tissue-restricted requirement / broader physiology. GPA-12 is required for AMP induction
in the hyp7 epidermal syncytium (UniProt DISRUPTION PHENOTYPE, from PMID:19380113 full text),
and activated G12 separately perturbs pharyngeal pumping/feeding (PMID:12646136). The full
endogenous tissue/behavioral repertoire of GPA-12, and why the immune requirement is
epidermis/cell-type restricted, are not resolved.

Annotation review plan (existing_annotations, 20 total)

ACCEPT (core): GO:0003925 G protein activity (IBA); GO:0061760 antifungal innate immune
response (IMP); GO:0050832 defense response to fungus (IMP, ×2); GO:0007186 GPCR signaling
pathway (IEA); GO:0007266 Rho protein signal transduction (IBA) [canonical G12/13 effector,
homology]; GO:0005834 heterotrimeric G-protein complex (IBA, part_of); GO:0010628 positive
regulation of gene expression (IMP).
ACCEPT / KEEP_AS_NON_CORE (true but generic or supporting): GO:0003924 GTPase activity (IEA);
GO:0019001 guanyl nucleotide binding (IEA); GO:0031683 G-protein beta/gamma-subunit complex
binding (IEA); GO:0001664 GPCR binding (IEA); GO:0007165 signal transduction (IEA, generic);
GO:0007266 Rho signal transduction (IEA, redundant with IBA); GO:0005737 cytoplasm (IBA & IDA).
KEEP_AS_NON_CORE / defer: GO:0005634 nucleus (IDA) — unusual for a Gα, full text unavailable.
REMOVE / MARK_AS_OVER_ANNOTATED (over-propagated to this G12/13 worm protein):
GO:0007188 adenylate cyclase-modulating GPCR signaling pathway (IBA) — REMOVE: cAMP/adenylate
cyclase modulation is a Gs/Gi function; G12/13 subfamily does not signal this way (pan-Gα
PANTHER node PTN000026392 over-propagation).
GO:0031752 D5 dopamine receptor binding (IBA) — REMOVE: hyper-specific mammalian receptor;
no worm ortholog/evidence.
GO:0031526 brush border membrane (IBA) — MARK_AS_OVER_ANNOTATED: mammalian intestinal
microvillar location; GPA-12 acts in epidermis; no worm evidence.

Key references (cached)

PMID:12646136 — van der Linden et al. 2003, Curr Biol. gpa-12 = Gα12/13 homolog; active G12QL
→ growth arrest via feeding/pharyngeal-pumping defect; TPA-1/PKC downstream. (abstract-only)
PMID:19380113 — Ziegler et al. 2009, Cell Host Microbe. PKCδ links G-protein signaling and the
p38 MAPK cascade in antifungal immunity; GPA-12 upstream of TPA-1/p38 → nlp-29. (abstract-only)
PMID:22470487 — Labed et al. 2012, PLoS One. NIPI-4 pseudokinase downstream of TPA-1;
epidermal GPA-12* drives constitutive nlp/cnc AMP expression, nipi-4-dependent. (full text)
GO-CAM gomodel:5b91dbd100002057 — antifungal innate immune response in the hypodermis via MAPK
cascade; GPA-12 (Gβγ-binding) causally upstream (+) of TPA-1.

📄 View Raw YAML

id: Q19572
gene_symbol: gpa-12
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  GPA-12 is a heterotrimeric guanine-nucleotide-binding protein (G protein) alpha
  subunit of the Galpha-12/13 subfamily, the C. elegans homolog of mammalian
  Galpha-12/Galpha-13. It has a canonical Galpha domain with intact G1-G5
  nucleotide-binding motifs and functions as a GTP/GDP-regulated molecular switch
  that, in its GTP-bound state, engages downstream effectors to relay signals from
  the cell surface. Its best-characterized physiological role is in the epidermis
  (hypodermis), where GPA-12 signaling acts upstream of protein kinase C delta
  (TPA-1) and a conserved p38 MAPK cassette (TIR-1, NSY-1, SEK-1, PMK-1) and the
  STAT-like factor STA-2 to drive induction of antimicrobial peptide genes of the
  NLP (nlp-29 cluster) and CNC families in response to fungal infection and
  wounding. A constitutively active form (GPA-12 Q205L / G12QL) is sufficient to
  drive constitutive antimicrobial peptide gene expression, and, when hyperactivated
  more broadly, causes a developmental growth arrest through a pharyngeal-pumping
  (feeding) defect that also depends on TPA-1. gpa-12 loss-of-function animals are
  viable.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
- id: PMID:12646136
  title: Hyperactivation of the G12-mediated signaling pathway in Caenorhabditis elegans
    induces a developmental growth arrest via protein kinase C.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Foundational characterization of gpa-12 as the C. elegans Galpha-12/13 homolog;
      active G12QL causes growth arrest via a pharyngeal-pumping/feeding defect and
      places TPA-1/PKC downstream of G12 signaling. Verified against the cached
      abstract; this is also the IDA source for the cytoplasm/nucleus localization
      annotations, whose primary data are in the full text (not in cache).
- id: PMID:19380113
  title: 'Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling
    and a conserved p38 MAPK cascade.'
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes that epidermal antifungal immunity (nlp-29 induction) requires G
      protein signaling acting through PKCdelta (TPA-1) and the p38 MAPK cascade;
      GPA-12 is the Galpha in this pathway. IMP source for the antifungal
      innate immune response / defense response to fungus annotations.
- id: PMID:22470487
  title: The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene
    expression.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text available; epidermis-restricted active GPA-12* (Pcol-19::GPA-12*)
      drives constitutive nlp/cnc antimicrobial peptide expression in a
      nipi-4-dependent manner, and states GPA-12 (with the Gbeta RACK-1) is required
      for wound/infection-induced signaling. IMP source for positive regulation of
      gene expression and defense response to fungus.
existing_annotations:
- term:
    id: GO:0003925
    label: G protein activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Correct and core molecular function. GPA-12 is a heterotrimeric G protein alpha
      subunit (Galpha-12/13 subfamily) that cycles between GTP- and GDP-bound states
      to act as a signal-transducing molecular switch. GO:0003925 is the appropriate
      MF for such subunits, and its behavior is supported experimentally in worm by
      the constitutively active Q205L (catalytic-glutamine) mutant.
    action: ACCEPT
    reason: >-
      Best and most specific molecular-function term for a Galpha subunit; consistent
      with family membership, intact G1-G5 motifs, and the behavior of activated
      GPA-12.
    supported_by:
    - reference_id: PMID:12646136
      supporting_text: >-
        We characterized a C. elegans Galpha subunit gene, gpa-12, which is a homolog
        of mammalian G(12)/G(13)alpha, and found that animals defective in gpa-12 are
        viable
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) localization to cytoplasm, independently corroborated by the
      experimental IDA cytoplasm annotation from PMID:12646136. This is a reasonable
      functional cellular compartment for a peripheral, membrane-associated Galpha
      subunit that cycles at the cytoplasmic face of the plasma membrane.
    action: ACCEPT
    reason: >-
      Consistent, independently corroborated cellular localization for a Galpha
      subunit; accepted as the cellular compartment in which GPA-12 acts.
- term:
    id: GO:0007188
    label: adenylate cyclase-modulating G protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Over-propagation from the pan-Galpha PANTHER family node. Adenylate
      cyclase/cAMP modulation is the defining function of the Gs (stimulatory) and Gi
      (inhibitory) subfamilies, not of the Galpha-12/13 subfamily to which GPA-12
      belongs. There is no evidence that GPA-12 modulates adenylate cyclase, and this
      pathway type is biologically inappropriate for a G12/13 protein.
    action: REMOVE
    reason: >-
      Biologically incorrect for the G12/13 subfamily; the term propagated
      electronically from Gs/Gi paralogs in the broad pan-Galpha tree and should not
      transfer to GPA-12.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: PANTHER:PTN000026392
        source_label: pan-Galpha family node
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
- term:
    id: GO:0007266
    label: Rho protein signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Canonical mammalian Galpha-12/13 signaling activates RhoGEFs to relay signals
      through Rho GTPases, so this term is biologically apt at the family level and
      propagates from the G12/13 node (mouse Gna12/Gna13). However, the Rho effector
      arm has not been demonstrated for C. elegans GPA-12; the experimentally defined
      worm effector arm runs through phospholipase (PLC-3) and PKCdelta (TPA-1).
      Retained as a homology-based, non-core inference.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homology-supported canonical G12/13 function, but not experimentally established
      in worm, where the demonstrated downstream arm is PLC/PKCdelta rather than Rho.
- term:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      Correct. As a Galpha subunit, GPA-12 assembles into a heterotrimeric G protein
      (Galpha-beta-gamma) complex; in the epidermal immune pathway it partners with
      the Gbeta RACK-1.
    action: ACCEPT
    reason: >-
      Accurate and well-supported complex membership for a Galpha subunit.
    supported_by:
    - reference_id: PMID:22470487
      supporting_text: >-
        Wounding and infection require G-protein signaling, involving the Gα protein
        GPA-12 and the Gß RACK-1, while infection specifically involves the
        Tribbles-like kinase NIPI-3
- term:
    id: GO:0031526
    label: brush border membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Over-specific location propagated from mammalian (rat) orthologs. Brush border
      membrane is the plasma membrane of intestinal microvilli; GPA-12's demonstrated
      site of action is the epidermis/hypodermis. There is no C. elegans evidence for
      brush border localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Narrow mammalian-tissue location transferred by phylogenetic inference; not
      supported for the worm protein and inconsistent with its known site of action.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - CONTEXT_OR_TISSUE_MISMATCH
      - COMPARTMENT_OR_COMPLEX_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000026689
        source_label: Galpha-12/13 node
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
- term:
    id: GO:0031752
    label: D5 dopamine receptor binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Hyper-specific molecular function propagated from a single mammalian ortholog
      annotation. Binding to a D5 dopamine receptor is not a plausible or supported
      activity for C. elegans GPA-12 (worms lack a D5 dopamine receptor ortholog),
      and there is no worm evidence for it.
    action: REMOVE
    reason: >-
      Over-propagated, organism-specific receptor-binding annotation with no relevance
      or evidence for the worm protein.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - WRONG_ORTHOLOG_OR_PARALOG
      - CONTEXT_OR_TISSUE_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN000026689
        source_label: Galpha-12/13 node
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
- term:
    id: GO:0001664
    label: G protein-coupled receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic InterPro-based inference. Galpha subunits are activated by, and
      physically couple to, GPCRs, so GPCR binding is a defensible general molecular
      function. However, the specific cognate receptor for GPA-12 is not established,
      so this remains a generic, non-core capability.
    action: KEEP_AS_NON_CORE
    reason: >-
      True general Galpha property (more informative than 'protein binding') but
      generic; the actual GPA-12 receptor is unknown.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Galpha subunits have intrinsic GTPase activity that terminates signaling by
      returning the switch to the GDP-bound state. Correct for GPA-12, whose G-box
      motifs are intact and whose catalytic-glutamine (Q205L) mutant behaves as a
      GTP-hydrolysis-defective, constitutively active protein. The more specific
      GO:0003925 (G protein activity) better captures the defining signaling-switch
      role, so this generic GTPase term is retained as a supporting, non-core activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct enzymatic capability for a Galpha subunit, but a supporting activity
      underlying the switch rather than the defining core function, which is better
      represented by GO:0003925 (G protein activity).
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      High-level, generic biological process. True (GPA-12 is a signal transducer)
      but far less informative than the specific GPCR-signaling and immune-signaling
      processes it participates in.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but uninformatively general; subsumed by more specific process terms.
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Appropriate mechanistic process term: Galpha subunits are the canonical
      transducers of GPCR signaling. This captures the pathway type through which
      GPA-12 relays signals in the epidermis, even though the specific receptor is not
      yet identified.
    action: ACCEPT
    reason: >-
      Accurate, mechanism-defining process for a Galpha subunit.
- term:
    id: GO:0007266
    label: Rho protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro-based duplicate of the IBA Rho protein signal transduction annotation,
      reflecting the canonical G12/13 -> RhoGEF -> Rho effector arm. As with the IBA
      version, this is homology-based and not experimentally demonstrated for worm
      GPA-12.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the IBA annotation; homology-supported canonical function not
      demonstrated in worm.
- term:
    id: GO:0019001
    label: guanyl nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Correct supporting molecular function: GPA-12 binds guanine nucleotides
      (GTP/GDP) via its intact G-box motifs. This underlies the G protein switch but
      is a component capability rather than the core function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate binding activity underpinning the GTPase/G-protein switch; supporting
      rather than core.
- term:
    id: GO:0031683
    label: G-protein beta/gamma-subunit complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Correct: the Galpha subunit binds the Gbeta/gamma dimer to form the inactive
      heterotrimer, releasing it upon GTP loading. Consistent with the curated GO-CAM
      (gomodel:5b91dbd100002057), which models GPA-12's molecular function as
      Gbeta/gamma-subunit complex binding, partnered with the Gbeta RACK-1.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate Galpha-Gbetagamma interaction supporting heterotrimer assembly;
      supporting rather than the core signaling function.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:22470487
  qualifier: involved_in
  review:
    summary: >-
      Experimentally supported: epidermis-restricted active GPA-12* drives a marked
      constitutive increase in antimicrobial peptide gene expression (nlp-29, nlp-31,
      nlp-34 and cnc-1, cnc-4), an effect abolished in a nipi-4 mutant. This is the
      transcriptional-induction readout of GPA-12's epidermal immune signaling.
    action: ACCEPT
    reason: >-
      Directly supported by loss/gain-of-function transcriptional data; captures
      GPA-12's role in up-regulating immune-effector gene expression.
    supported_by:
    - reference_id: PMID:22470487
      supporting_text: >-
        In uninfected transgenic worms carrying the Pcol-19::GPA-12* construct, we
        observed a very marked increase in the expression of Pnlp-29::GFP in the
        epidermis from the late L4 stage onwards
    - reference_id: PMID:22470487
      supporting_text: >-
        the transgenic strain exhibited an elevated constitutive expression of nlp-29,
        nlp-31 and nlp-34, and cnc-1, cnc-4
- term:
    id: GO:0050832
    label: defense response to fungus
  evidence_type: IMP
  original_reference_id: PMID:22470487
  qualifier: involved_in
  review:
    summary: >-
      Experimentally supported core biological process. GPA-12 signaling is required
      for the epidermal antifungal defense program (nlp/cnc antimicrobial peptide
      induction) against the natural fungal pathogen Drechmeria coniospora.
    action: ACCEPT
    reason: >-
      Well-supported IMP annotation reflecting GPA-12's core physiological role in
      antifungal defense.
    supported_by:
    - reference_id: PMID:22470487
      supporting_text: >-
        When we crossed the Pcol-19::GPA-12* transgene into nipi-4(fr106) mutant, the
        elevated expression of the Pnlp-29::GFP reporter provoked by the active form of
        GPA-12 was abrogated
- term:
    id: GO:0061760
    label: antifungal innate immune response
  evidence_type: IMP
  original_reference_id: PMID:19380113
  qualifier: involved_in
  review:
    summary: >-
      Experimentally supported and the most specific immune process term for GPA-12.
      Epidermal antifungal innate immunity (nlp-29 induction) requires G protein
      signaling acting through PKCdelta and the p38 MAPK cascade, with GPA-12 as the
      Galpha subunit; this is the same activity modeled in the curated GO-CAM
      (gomodel:5b91dbd100002057).
    action: ACCEPT
    reason: >-
      Core, well-supported immune process; most specific and informative BP term for
      this gene.
    supported_by:
    - reference_id: PMID:19380113
      supporting_text: >-
        This involves G protein signaling and specific C-type phospholipases acting
        upstream of PKCdelta
    - reference_id: PMID:19380113
      supporting_text: >-
        C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12646136
  qualifier: located_in
  review:
    summary: >-
      WormBase IDA nuclear localization from PMID:12646136. Nuclear localization is
      unusual for a Galpha subunit, and the primary imaging data are in the full text,
      which is not in the cache (abstract-only). Per curation guidance I do not
      overrule an experimental IDA I cannot fully verify; I retain it as a non-core
      localization and defer to the WormBase curator.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimental IDA from the curator (full text unavailable to verify); unusual for
      a Galpha and not a core function, but not to be removed on incomplete evidence.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12646136
  qualifier: located_in
  review:
    summary: >-
      WormBase IDA cytoplasmic localization from PMID:12646136, consistent with the
      expected peripheral/cytoplasmic disposition of a membrane-associated Galpha
      subunit and with the IBA cytoplasm annotation. Accepted as the cellular
      compartment in which GPA-12 acts.
    action: ACCEPT
    reason: >-
      Experimentally curated localization for a Galpha, corroborated by phylogenetic
      inference; accepted as GPA-12's cellular compartment of action.
- term:
    id: GO:0050832
    label: defense response to fungus
  evidence_type: IMP
  original_reference_id: PMID:19380113
  qualifier: involved_in
  review:
    summary: >-
      Experimentally supported core process (duplicate term with a distinct primary
      reference). GPA-12 is required for the epidermal antifungal defense response, as
      shown by its position upstream of PKCdelta and the p38 cascade controlling
      nlp-29 induction after fungal infection.
    action: ACCEPT
    reason: >-
      Well-supported IMP annotation from the Ziegler et al. study; reinforces the core
      antifungal-defense role.
    supported_by:
    - reference_id: PMID:19380113
      supporting_text: >-
        This involves G protein signaling and specific C-type phospholipases acting
        upstream of PKCdelta
core_functions:
- description: >-
    GPA-12 acts as a Galpha-12/13-type heterotrimeric G protein alpha subunit: a
    GTP/GDP-regulated molecular switch that transduces cell-surface (GPCR-type)
    signals in the C. elegans epidermis. Functioning upstream of PKCdelta (TPA-1) and
    the conserved TIR-1 -> NSY-1 -> SEK-1 -> PMK-1 (p38) MAPK cascade and the
    STAT-like factor STA-2, GPA-12 signaling drives induction of NLP- and CNC-family
    antimicrobial peptide genes in the antifungal innate immune response and after
    wounding. It assembles into a heterotrimer with a Gbeta (RACK-1)/gamma dimer, and
    an activated form (Q205L) is sufficient to drive the antimicrobial peptide program.
  molecular_function:
    id: GO:0003925
    label: G protein activity
  directly_involved_in:
  - id: GO:0061760
    label: antifungal innate immune response
  - id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  in_complex:
    id: GO:0005834
    label: heterotrimeric G-protein complex
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:19380113
    supporting_text: >-
      This involves G protein signaling and specific C-type phospholipases acting
      upstream of PKCdelta
  - reference_id: PMID:22470487
    supporting_text: >-
      Wounding and infection require G-protein signaling, involving the Gα protein
      GPA-12 and the Gß RACK-1, while infection specifically involves the
      Tribbles-like kinase NIPI-3
  - reference_id: PMID:12646136
    supporting_text: >-
      We characterized a C. elegans Galpha subunit gene, gpa-12, which is a homolog of
      mammalian G(12)/G(13)alpha, and found that animals defective in gpa-12 are viable
knowledge_gaps:
- gap_statement: >-
    The cognate receptor and activating input for GPA-12 are not biochemically
    defined. It is unknown which cell-surface receptor couples to GPA-12 to initiate
    epidermal immune signaling, what ligand/damage cue activates it, and whether
    GPA-12 engages such a receptor directly.
  boundary: >-
    Established: GPA-12 is a Galpha-12/13 subunit that acts upstream of PKCdelta
    (TPA-1) and the p38 MAPK cascade to drive antimicrobial peptide expression after
    fungal infection and wounding, and its activity is required for this response.
    Unknown: the identity of the activating receptor and whether coupling is direct.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  significance: >-
    Identifying the receptor that switches on GPA-12 would define the sensing step of
    epidermal surveillance immunity and connect damage/infection detection to the
    p38/PMK-1 defense program.
  provenance:
  - reference_id: PMID:22470487
    supporting_text: >-
      Our current understanding of both epidermal and intestinal innate immunity is
      far from complete
- gap_statement: >-
    The immediate downstream effector of GPA-12 is undetermined. Genetic epistasis
    places GPA-12 upstream of phospholipase (PLC-3) and PKCdelta (TPA-1), but it is
    not known whether GPA-12 directly activates a phospholipase, a RhoGEF/Rho module
    (the canonical mammalian Galpha-12/13 effector arm), or another target.
  boundary: >-
    Established: GPA-12/G-protein signaling acts genetically upstream of C-type
    phospholipases and PKCdelta, and activated GPA-12 drives the p38-dependent
    antimicrobial peptide program. Unknown: the direct biochemical effector; the
    canonical G12/13 -> RhoGEF -> Rho arm has not been demonstrated in worm.
  gap_kind:
  - BIOLOGY
  dark_aspect: MF_DARK
  status: OPEN
  significance: >-
    Whether worm GPA-12 signals through a Rho arm (like mammalian G12/13) or through a
    phospholipase/PKCdelta arm (more Gq-like) determines how this subfamily was wired
    into nematode epidermal immunity and would resolve an apparent divergence from the
    mammalian paradigm.
  provenance:
  - reference_id: PMID:19380113
    supporting_text: >-
      This involves G protein signaling and specific C-type phospholipases acting
      upstream of PKCdelta
- gap_statement: >-
    The full endogenous tissue and physiological repertoire of GPA-12 is unresolved.
    Its immune requirement is epidermis/cell-type restricted, and hyperactive G12
    separately perturbs pharyngeal pumping/feeding and growth, but why the immune
    requirement is tissue-restricted and what other endogenous processes GPA-12
    normally controls are not defined.
  boundary: >-
    Established: active GPA-12 drives antimicrobial peptide expression in the
    epidermis and, when broadly hyperactivated, causes a growth arrest via a
    pharyngeal-pumping defect (with TPA-1 downstream); loss-of-function animals are
    viable. Unknown: the complete set of tissues/behaviors in which endogenous GPA-12
    acts, and the basis of its tissue-restricted immune role.
  gap_kind:
  - BIOLOGY
  dark_aspect: BP_DARK
  status: OPEN
  significance: >-
    Mapping GPA-12's endogenous functions would distinguish its dedicated immune role
    from its developmental/feeding role and clarify how one Galpha subunit is deployed
    across contexts.
  provenance:
  - reference_id: PMID:12646136
    supporting_text: >-
      Expression of activated GPA-12 (G(12)QL) results in a developmental growth arrest
      caused by a feeding behavior defect that is due to a dramatic reduction in
      pharyngeal pumping

gpa-12

Gene Description

Existing Annotations Review

Core Functions

References

Knowledge Gaps

📚 Additional Documentation

Notes

gpa-12 (C. elegans) — research notes

Summary / identity

KNOWN (well supported)

Molecular function

Biological process — epidermal antifungal innate immunity (the core physiological role)

A second, developmental context (Gα12 gain-of-function)

Localization

NOT known / genuine knowledge gaps

Annotation review plan (existing_annotations, 20 total)

Key references (cached)

📄 View Raw YAML