Gene Ontology annotation through association of InterPro records with GO terms.

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

file:human/GDPD2/GDPD2-deep-research.md

Deep Research Report on GDPD2

GDPD2 colocalizes with actin filaments and may influence cytoskeletal remodeling

"GDPD2 has been observed in the cytoplasm associated with the cytoskeleton, co-localizing with actin filaments. This suggests that GDPD2 may concentrate at sites of actin-rich membrane structures (e.g. ruffles or protrusions), potentially linking its enzymatic activity to cytoskeletal remodeling"

file:human/GDPD2/GDPD2-deep-research-falcon.md

Falcon deep research on GDPD2 function (FutureHouse Falcon / Edison Scientific Literature)

Falcon corroborates the substrate-specific glycerophosphoinositol inositolphosphodiesterase activity of GDPD2 (EC 3.1.4.43), with explicit lack of activity on related glycerophosphodiesters (GroPIns-4-P, GPC, GPE, GPS). This independently supports the more specific MF annotation GO:0047394 over generic GO:0008889/GO:0008081/GO:0016787.

"GDPD2 functions primarily as a glycerophosphoinositol inositolphosphodiesterase. Its catalytic activity is highly substrate-specific, as it hydrolyzes glycerophosphoinositol while exhibiting no measurable activity towards substrates such as glycerophosphoinositol 4-phosphate, glycerophosphocholine, glycerophosphoethanolamine, or glycerophosphoserine. "
Falcon confirms plasma membrane localization as a multi-pass transmembrane protein, with the catalytic domain oriented for substrate engagement, supporting GO:0005886 as a core CC annotation.

"Experimental data indicate that GDPD2 is primarily localized to the plasma membrane, where it is embedded as a multi-pass transmembrane protein "
Falcon supports a secondary association of GDPD2 with the cytoplasm and cytoskeleton, consistent with the actin-filament association reported elsewhere. This is treated as non-core (peripheral) localization rather than a primary site.

"In addition to its presence in the plasma membrane, GDPD2 has been associated with the cytoplasm and the cytoskeleton, suggesting a dynamic distribution that may allow it to participate in the reorganization of cellular architecture "
Falcon independently supports GDPD2's role in promoting osteoblast differentiation and bone formation, consistent with GO:0045669 (positive regulation of osteoblast differentiation) as a core BP annotation.

"In this context, GDPD2 has been shown to stimulate osteoblast differentiation and growth, a function that likely depends on its capacity to modulate the lipid microenvironment at the plasma membrane "
Falcon supports a role for GDPD2 in actin cytoskeleton remodeling as a downstream consequence of its enzymatic activity, justifying keeping GO:0007015 (actin filament organization) as a non-core BP annotation rather than removing it.

"GDPD2 has also been implicated in the regulation of the actin cytoskeleton, an association that suggests a multifaceted role in cellular morphology and motility. The remodeling of the actin cytoskeleton, which is essential for various aspects of cell behavior including migration and adhesion, appears to be influenced by GDPD2 activity "
Falcon notes that GDPD2 contains a conserved phosphodiesterase domain (GP-PDE family), consistent with its classification as a glycerophosphoinositol inositolphosphodiesterase. Falcon does NOT independently provide GDPD2-specific PMIDs (its references are bioinformatic/general — Pinto-Pinho 2024 sex chromosome proteomes, Rolfe 2014 mechanosensitive genes, Lopez-Bigas 2008 functional protein divergence, Aleksander 2023 GO knowledgebase, plus a ClinicalTrials.gov aggregate count). Falcon also does NOT confirm the Ca2+ cofactor requirement, the extracellular orientation of the catalytic domain, or the Arg-231 active-site residue — those claims rely on the OpenAI deep research and primary literature cited there (PMID:19656770 / PMC2757188).

"GDPD2's structure is defined by the presence of a conserved phosphodiesterase domain that endows it with the enzymatic capacity to specifically hydrolyze glycerophosphoinositol. This domain is central to its function in modulating phospholipid metabolism, and sequence analyses indicate that it shares homology with other members of the phosphodiesterase family "