UniProt: P43304 (GPDM_HUMAN), gene symbol GPD2 (HGNC:4456). 727 aa precursor;
mitochondrial transit peptide 1–42; mature chain 43–727. Isoform 2 (P43304-2)
lacks residues 1–126 (VSP_017134).
GPD2 is the mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase
(mGPDH; also mtGPD, m-GDH, GPD-M). It is an inner-membrane flavoenzyme that
oxidises sn-glycerol-3-phosphate to dihydroxyacetone phosphate (DHAP), passing
electrons via its bound FAD to the ubiquinone (quinone) pool of the respiratory
chain.
Together with cytosolic NAD-linked GPD1, GPD2 constitutes the glycerol-phosphate
shuttle, delivering cytosolic reducing equivalents to the ubiquinone pool
(bypassing Complex I). Reactome R-HSA-188467 summary:
[Reactome:R-HSA-188467 "FAD-linked mitochondrial glycerol 3-phosphate dehydrogenase (GPD2, alias: mGPDH) and its NAD-linked cytosolic isoform (GPD1, alias:cGPDH) constitute glycerol phosphate shuttle."]
and [Reactome:R-HSA-188467 "GPD2 catalyzes the unidirectional conversion of glycerol-3-phosphate (G-3-P) to dihydroxyacetone phosphate (DHAP) with concomitant reduction of the enzyme-bound FAD."].
GO:0006127 (glycerol-3-phosphate shuttle) OLS def confirms the shuttle transfers
reducing equivalents from cytosolic NADH into mitochondria via G3P, with
mitochondrial GPDH using FAD to convert G3P back to DHAP and feeding FADH2
electrons into the electron transport chain.
GPD2 carries two C-terminal EF-hand domains (623–658, 659–694) and binds Ca2+
(FT BINDING residues 672,674,676,678,683). Calcium binding is regulatory:
[file:human/GPD2/GPD2-uniprot.txt "Calcium-binding enhance the activity of the"]
("enzyme."). This underlies its role as a beta-cell glucose sensor. The GOA
calcium-ion-binding annotation (GO:0005509, IEA from InterPro EF-hand
IPR002048) is consistent with the EF-hand domains but is a regulatory/accessory
feature, not the core catalytic function → KEEP_AS_NON_CORE.
UniProt FUNCTION: [file:human/GPD2/GPD2-uniprot.txt "Calcium-responsive mitochondrial glycerol-3-phosphate"]
("dehydrogenase which seems to be a key component of the pancreatic beta-")
("cell glucose-sensing device."). PMID:9070847 (Novials et al. 1997,
abstract-only, full_text_available: false) reports EC/CATALYTIC-ACTIVITY and
ACTIVITY-REGULATION evidence and a calcium-binding-domain mutation in diabetic
subjects. Abstract:
PMID:9070847
("dehydrogenase (m-GDH) represents an essential component of the pancreatic B-cell")
("glucose-sensing device."). This is the source of the IDA on GO:0004368
(enables) in GOA — accept as the experimental basis of the core catalytic MF.
Core (evolved) function:
- GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity — MF core.
ACCEPT the IDA (PMID:9070847) and the IBA; the two Reactome TAS and the
ARBA/InterPro IEA are redundant duplicates of the same activity → ACCEPT
(duplicates of an experimentally supported term).
- GO:0006127 glycerol-3-phosphate shuttle — BP core (IBA + Reactome TAS). ACCEPT.
- GO:0006072 glycerol-3-phosphate metabolic process — parent BP; correct but
general → KEEP_AS_NON_CORE (glycerophosphate shuttle / catabolism is the
specific process).
- GO:0005743 mitochondrial inner membrane — specific correct location (TAS
Reactome). ACCEPT.
Non-core / supporting:
- GO:0005739 mitochondrion (IBA is_active_in; IEA located_in; HPA IDA; HTP) —
correct but less specific than the inner membrane → KEEP_AS_NON_CORE.
- GO:0005509 calcium ion binding (IEA InterPro EF-hand) — real regulatory
feature, not core catalysis → KEEP_AS_NON_CORE.
- GO:0019563 glycerol catabolic process (IEA UniPathway) — GPD2 acts on
glycerol-3-phosphate, not glycerol directly; it is one step of the glycerol
degradation pathway (glycerol -> G3P by glycerol kinase -> DHAP by GPD2).
UniProt PATHWAY: [file:human/GPD2/GPD2-uniprot.txt "Polyol metabolism; glycerol degradation via glycerol kinase"]
("pathway; glycerone phosphate from sn-glycerol 3-phosphate (anaerobic")
("route): step 1/1."). Pathway-level term; over-general for the specific
activity but pathway-appropriate → KEEP_AS_NON_CORE.
No REMOVE actions: the only IEAs present (quinone MF, inner membrane, mitochondrion,
Ca-binding, glycerol catabolism) are all biologically correct, so none are
"clearly wrong". Experimental IDA (PMID:9070847) accepted.