ABHD5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	IDA PMID:18606822 CGI-58, the causative gene for Chanarin-Dorfman syndrome, me...	REMOVE	Summary: The reported intrinsic human LPA acyltransferase activity is contradicted by contaminant-controlled assays. Reason: The original human study used His-tagged ABHD5 expressed in E. coli and nickel-affinity purification, followed by LPA-to-PA assays; yeast overexpression also increased extract activity. Full PMID:24879803 directly tests these premises: bacterial PlsC contamination explains affinity-purified activity, stricter purification retains ATGL coactivation while removing LPAAT, and human Protein-A-ABHD5 expressed in wild-type or ict1-deleted yeast does not increase LPAAT activity. These are biochemical counterexperiments, not an inference from an inaccessible abstract. Later PMID:25315780 reports LPAAT in human-ABHD5-overexpressing 293T homogenates and purified Sf9 LPGAT activity; that different substrate/preparation does not isolate intrinsic human LPAAT from endogenous enzymes. The direct LPAAT assignment is therefore not retained; indirect phospholipid effects and other catalytic activities are not excluded. Supporting Evidence: PMID:18606822 the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to specifically acylate lysophosphatidic acid in an acyl-CoA-dependent manner. PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	IEA GO_REF:0000120	REMOVE	Summary: The EC/Rhea mappings inherit a disputed direct LPA acylation assignment. Reason: The source Rhea reactions and EC:2.3.1.51 describe acyl-CoA-dependent formation of phosphatidic acid, matching GO:0003841. Their chemistry is coherent, but the frozen UniProt record grounds ABHD5 catalysis in PMID:18606822. Contaminant-controlled PMID:24879803 challenges that protein-to-reaction assignment, including a negative human yeast experiment. Remove the target mapping without changing the authentic reaction identifiers or treating them as separate experimental confirmations. The later homogenate/LPGAT results in PMID:25315780 do not directly resolve intrinsic human LPAAT. Propagation Review Root cause: SOURCE BAD Sources checked: RHEA:19709 SOURCE BAD RHEA:19709 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:33187 SOURCE BAD RHEA:33187 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37131 SOURCE BAD RHEA:37131 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37143 SOURCE BAD RHEA:37143 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37147 SOURCE BAD RHEA:37147 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37163 SOURCE BAD RHEA:37163 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37443 SOURCE BAD RHEA:37443 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37451 SOURCE BAD RHEA:37451 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. RHEA:37455 SOURCE BAD RHEA:37455 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. EC:2.3.1.51 SOURCE BAD EC:2.3.1.51 is an authentic input mapping in the seed. It encodes LPA acylation, but the human protein-to-reaction evidence in the frozen UniProt record traces to the challenged 2008 experiment; this is not a bad reaction identifier. Supporting Evidence: PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0004620 glycerophospholipase activity	IBA GO_REF:0000033	REMOVE	Summary: Ancestral phospholipid-hydrolase activity does not fit the experimentally tested human ABHD5 protein. Reason: GO:0004620 requires hydrolysis of a glycerophospholipid. Indexed full PMID:18606822 reports that recombinant human ABHD5 lacked phospholipase and lysophospholipase activities; the mammalian canonical lipase nucleophile is also replaced by asparagine. The PAINT node includes enzymatic family members such as mouse Abhd4 (MGI:1915938), but descent does not overcome these target-specific tests and functional divergence. PMID:26745266 further challenges the plant donor catalytic premise. This removes the inherited lipid-hydrolase assertion, not the demonstrated coactivator role or the chemically different HDAC4 protease report. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE PSEUDO OR SUBACTIVITY LOSS Sources checked: PANTHER:PTN008676419 UNRESOLVED PTN008676419 is the seeded ancestral source. Target human negative phospholipid-hydrolysis results and mammalian lipase-site divergence challenge inheritance at this target. The full PAINT alignment/node evidence was not independently retrieved; no donor-count or self-evidence argument is used. Supporting Evidence: PMID:24879803 it lacks a serine residue in a conserved sequence (GXSXG) that normally harbors the nucleophilic component of the catalytic triad PMID:26745266 recombinant plant CGI-58 does not catalyze TAG or phospholipid hydrolysis.
GO:0004806 triacylglycerol lipase activity	ISS NOT GO_REF:0000024	ACCEPT	Summary: The NOT annotation correctly separates ABHD5 from the triglyceride hydrolase it activates. Reason: This is a negated annotation transferred from mouse Abhd5 Q9DBL9, not a positive lipase assignment. Full human PMID:18606822 explicitly reports no triolein lipase activity, while PMID:16679289 establishes stimulation of ATGL. The negative conclusion is scoped to intrinsic triglyceride hydrolysis and does not deny the separately reported peptide-bond cleavage of HDAC4. Exact donor annotation provenance was not recovered, but independent human evidence supports retaining the curator assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 Q9DBL9 is the ortholog source. The exact source NOT experiment was not independently recovered; direct human negative triolein assays and positive ATGL coactivation corroborate this target judgment. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:24879803 it lacks a serine residue in a conserved sequence (GXSXG) that normally harbors the nucleophilic component of the catalytic triad
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–PCNX2 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:A6NKB5-5; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; A6NKB5-5: PCNX2; NbExp=3; IntAct=EBI-2813554, EBI-17616589;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–GET1 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:O00258; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; O00258: GET1; NbExp=3; IntAct=EBI-2813554, EBI-18908258;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–TPD52L2 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:O43399; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; O43399: TPD52L2; NbExp=3; IntAct=EBI-2813554, EBI-782604;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–PLIN3 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:O60664; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Independent perilipin-dependent recruitment biology is relevant to ABHD5 localization, but does not establish an informative molecular-function replacement for this particular HuRI assay. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; O60664: PLIN3; NbExp=3; IntAct=EBI-2813554, EBI-725795;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–GRIA4 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:P48058-2; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; P48058-2: GRIA4; NbExp=3; IntAct=EBI-2813554, EBI-17517256;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–CLCN4 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:P51793; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; P51793: CLCN4; NbExp=3; IntAct=EBI-2813554, EBI-22754239;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–PLIN5 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q00G26; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Independent perilipin-dependent recruitment biology is relevant to ABHD5 localization, but does not establish an informative molecular-function replacement for this particular HuRI assay. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q00G26: PLIN5; NbExp=3; IntAct=EBI-2813554, EBI-21732470;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–GAD2 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q05329; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q05329: GAD2; NbExp=3; IntAct=EBI-2813554, EBI-9304251;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–CERCAM pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q5T4B2; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q5T4B2: CERCAM; NbExp=3; IntAct=EBI-2813554, EBI-12261896;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–ZCCHC12 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q6PEW1; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q6PEW1: ZCCHC12; NbExp=3; IntAct=EBI-2813554, EBI-748373;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–DGAT2L6 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q6ZPD8; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-2813554, EBI-12831978;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–RBFA pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q8N0V3; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q8N0V3: RBFA; NbExp=3; IntAct=EBI-2813554, EBI-3232108;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–SLC44A3 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q8N4M1-3; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q8N4M1-3: SLC44A3; NbExp=3; IntAct=EBI-2813554, EBI-12056955;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–COQ8A pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q8NI60; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-2813554, EBI-745535;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–PLIN2 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q99541; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Independent perilipin-dependent recruitment biology is relevant to ABHD5 localization, but does not establish an informative molecular-function replacement for this particular HuRI assay. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q99541: PLIN2; NbExp=3; IntAct=EBI-2813554, EBI-2115275;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–RUSC1 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q9BVN2; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-2813554, EBI-6257312;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–MIEF1 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q9NQG6; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q9NQG6: MIEF1; NbExp=5; IntAct=EBI-2813554, EBI-740987;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–TMEM14B pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q9NUH8; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-2813554, EBI-8638294;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–RNF24 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q9Y225-2; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q9Y225-2: RNF24; NbExp=3; IntAct=EBI-2813554, EBI-13044680;
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The reported ABHD5–SH3GLB1 pair does not make generic protein binding an informative function. Reason: This HuRI IPI assertion identifies UniProtKB:Q9Y371; the same pair is recorded with IntAct provenance in the immutable UniProt record. The study maps binary interactions, and this source does not establish a specific catalytic, adaptor or other functional activity for the pair. Remove GO:0005515 under the generic-binding policy without claiming that the interaction is false, that an isoform was untested, or that the partner is biologically irrelevant. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. file:human/ABHD5/ABHD5-uniprot.txt Q8WTS1; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-2813554, EBI-2623095;
GO:0005737 cytoplasm	EXP PMID:18832586 CGI-58 is an alpha/beta-hydrolase within lipid transporting ...	ACCEPT	Summary: ABHD5 is experimentally localized to human cytoplasm. Reason: Indexed full PMID:18832586 Results and Figure 2H,I report discrete cytoplasmic immunofluorescence in human hepatocytes and neurons; the same study separately localizes protein to keratinocyte lamellar granules by immunoelectron microscopy. The broad cytoplasm assertion is supported at its stated resolution and is compatible with the soluble and droplet-associated pools. The local publication cache is abstract-only; the granular localization detail was read on the indexed primary PMC2570125 page, not inferred from that abstract. The external primary Discussion states, "CGI-58 is expressed in the cytoplasm of hepatocytes" (https://pmc.ncbi.nlm.nih.gov/articles/PMC2570125/), consistent with the human tissue immunofluorescence in Figure 2. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: The curated cytoplasm mapping captures a supported broad compartment. Reason: The UniProt SL-0086 mapping is concordant with human tissue microscopy and the established cytosol/droplet distribution. Preserve the broad source assertion rather than substitute a finer compartment from a different assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER SL-0086 is the cytoplasm vocabulary source; the frozen record cites human tissue evidence and agrees with the target localization. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005811 lipid droplet	IBA GO_REF:0000033	ACCEPT	Summary: Lipid droplets are a central site of ABHD5-dependent lipid-enzyme regulation. Reason: The inherited location is consistent with human A431 lipid-droplet proteomics in PMID:21498505 and human constructs in the 2025 localization experiments. ABHD5 is a droplet-associated cofactor rather than a transmembrane droplet enzyme. The target in the descendant list is legitimate experimental grounding, not circularity; the exact PAINT ancestral reconstruction was not independently retrieved. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000106002 UNRESOLVED PTN000106002 is the seeded ancestral node. Target human lipid-droplet observations support acceptance, but full node/MSA provenance was not independently retrieved. Target self-evidence is legitimate. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005811 lipid droplet	IDA PMID:21498505 Human lysophosphatidylcholine acyltransferases 1 and 2 are l...	ACCEPT	Summary: The LPCAT study also detects CGI-58 in a human lipid-droplet protein fraction. Reason: The indexed full Results of PMID:21498505 describe isolation of A431 lipid-droplet proteins and mass spectrometry, comparing LPCAT abundance indices with CGI-58 in supplemental Figure 1. Thus the LPCAT-focused title does not imply wrong-gene attribution. I did not independently inspect the supplementary peptide list or assign the LPCAT microscopy panels to ABHD5. The curator IDA is retained with independent human droplet-localization evidence in PMID:40818613. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005811 lipid droplet	IEA GO_REF:0000120	ACCEPT	Summary: Combined mappings support the conserved droplet-associated ABHD5 pool. Reason: The row combines a rule, rodent orthologs and the UniProt lipid-droplet keyword. Human primary proteomic and construct-localization evidence independently supports this compartment. Rule internals and each donor experiment were not independently recovered, so their provenance limits are kept separate from the supported target location. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029131 UNRESOLVED Seeded ARBA rule; its current conditions were not retrieved. Target localization is independently supported, not inferred from a guessed rule. UniProtKB:Q6QA69 UNRESOLVED Rat Abhd5 ortholog identifier; NCBI Gene 316122 links Q6QA69 and ENSRNOP00000000239. Exact donor experimental chain was not recovered. ensembl:ENSRNOP00000000239 UNRESOLVED Rat Abhd5 ortholog identifier; NCBI Gene 316122 links Q6QA69 and ENSRNOP00000000239. Exact donor experimental chain was not recovered. UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 ortholog source; exact donor localization evidence was not recovered, while independent human observations support the target location. ensembl:ENSMUSP00000122274 UNRESOLVED Mouse Abhd5 ortholog source; exact donor localization evidence was not recovered, while independent human observations support the target location. UniProtKB-SubCell:SL-0154 UNRESOLVED The frozen UniProt lipid-droplet location is the keyword source; independent human primary evidence agrees. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005811 lipid droplet	ISS GO_REF:0000024	ACCEPT	Summary: Mouse-to-human transfer of lipid-droplet association is supported by human observations. Reason: Mouse Q9DBL9 is Abhd5; conserved coactivator biology and human A431 proteomic/2025 tagged-protein localization support the same compartment. Retain the ISS source without relabeling the rodent experiments as human. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 Q9DBL9 identity is verified. The exact donor location assertion was not recovered, but human primary localization independently supports this transfer. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: The curated immunofluorescence cytosol assignment is consistent with ABHD5 distribution. Reason: GO_REF:0000052 records curation of immunofluorescence data. The exact HPA cell-line image was not independently retrieved. There is no contradictory localization evidence: the frozen UniProt record explicitly identifies a cytosolic pool, and primary studies describe cytoplasmic/droplet redistribution. Retain the curator assertion at cytosol resolution without treating human tissue cytoplasmic staining as a separate cytosol-specific assay. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: A conserved cytosolic ABHD5 pool complements its lipid-droplet association. Reason: The mouse Abhd5 ortholog and frozen UniProt record support a soluble cytosolic pool. The transfer is biologically compatible with regulated droplet association, not an inference that all protein resides in cytosol. Exact donor imaging provenance was not independently recovered; the human immunofluorescence annotation is retained with curator deference. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 donor identity is established; exact cytosol source experiment remains unresolved. Human curated immunofluorescence and the frozen localization record independently agree. ensembl:ENSMUSP00000122274 UNRESOLVED Mouse Abhd5 donor identity is established; exact cytosol source experiment remains unresolved. Human curated immunofluorescence and the frozen localization record independently agree. UniProtKB-SubCell:SL-0091 UNRESOLVED The UniProt SL-0091 cytosol mapping is explicit in the immutable record. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0005829 cytosol	ISS GO_REF:0000024	ACCEPT	Summary: A conserved cytosolic ABHD5 pool complements its lipid-droplet association. Reason: The mouse Abhd5 ortholog and frozen UniProt record support a soluble cytosolic pool. The transfer is biologically compatible with regulated droplet association, not an inference that all protein resides in cytosol. Exact donor imaging provenance was not independently recovered; the human immunofluorescence annotation is retained with curator deference. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 donor identity is established; exact cytosol source experiment remains unresolved. Human curated immunofluorescence and the frozen localization record independently agree. Supporting Evidence: file:human/ABHD5/ABHD5-uniprot.txt Cytoplasm {ECO:0000269\|PubMed:18832586}. Lipid CC droplet {ECO:0000250\|UniProtKB:Q9DBL9}. Cytoplasm, cytosol CC {ECO:0000250\|UniProtKB:Q9DBL9}.
GO:0006654 phosphatidic acid biosynthetic process	IBA GO_REF:0000033	REMOVE	Summary: The direct phosphatidic-acid synthesis assignment depends on challenged LPAAT chemistry. Reason: The source interpretation places ABHD5 at the LPA-to-PA catalytic step. PMID:24879803 directly challenges the original recombinant and human-yeast LPAAT experiments. The 2008 increase in phospholipid labeling is a genuine measured phenotype, but does not distinguish ABHD5 catalysis from altered substrate supply or regulation of endogenous enzymes. The later 293T homogenate observation in PMID:25315780 likewise does not isolate this direct role. Remove this asserted synthesis mechanism while retaining established lipid homeostasis and lipase activation. Propagation Review Root cause: SOURCE BAD Sources checked: PANTHER:PTN008676419 UNRESOLVED PTN008676419 is the ancestral source. Human target evidence is an appropriate descendant seed, but its direct LPAAT/PA-synthesis interpretation is challenged by controlled follow-up experiments. The yeast Ict1 contribution is not declared false. Supporting Evidence: PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0006654 phosphatidic acid biosynthetic process	IDA PMID:18606822 CGI-58, the causative gene for Chanarin-Dorfman syndrome, me...	REMOVE	Summary: The direct phosphatidic-acid synthesis assignment depends on challenged LPAAT chemistry. Reason: The source interpretation places ABHD5 at the LPA-to-PA catalytic step. PMID:24879803 directly challenges the original recombinant and human-yeast LPAAT experiments. The 2008 increase in phospholipid labeling is a genuine measured phenotype, but does not distinguish ABHD5 catalysis from altered substrate supply or regulation of endogenous enzymes. The later 293T homogenate observation in PMID:25315780 likewise does not isolate this direct role. Remove this asserted synthesis mechanism while retaining established lipid homeostasis and lipase activation. Supporting Evidence: PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0010898 positive regulation of triglyceride catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: ABHD5 activates ATGL to increase triglyceride breakdown. Reason: The PAINT assertion is compatible with conserved mammalian coactivation; the human target in WITH/FROM is legitimate descendant evidence. PMID:16679289 reports direct interaction and stimulation of ATGL activity, failure of disease variants to activate ATGL, and rescue of lipolysis in CDS fibroblasts. These assays establish the regulatory work ABHD5 performs, beyond necessity or lipid-storage phenotype alone. The abstract also includes COS-7 and mouse 3T3-L1 experiments, which are not relabeled as human. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002872529 UNRESOLVED The seeded PTN002872529 ancestral node supports a conserved regulatory interpretation. Full source-chain reconstruction was not retrieved; independent target assays establish activation and phenotype rescue. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:16679289 expression of functional CGI-58 in CDS fibroblasts restores lipolysis and reverses the abnormal TG accumulation typical for CDS.
GO:0010898 positive regulation of triglyceride catabolic process	IDA PMID:16679289 Adipose triglyceride lipase-mediated lipolysis of cellular f...	ACCEPT	Summary: ABHD5 activates ATGL to increase triglyceride breakdown. Reason: PMID:16679289 reports direct interaction and stimulation of ATGL activity, failure of disease variants to activate ATGL, and rescue of lipolysis in CDS fibroblasts. These assays establish the regulatory work ABHD5 performs, beyond necessity or lipid-storage phenotype alone. The abstract also includes COS-7 and mouse 3T3-L1 experiments, which are not relabeled as human. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:16679289 expression of functional CGI-58 in CDS fibroblasts restores lipolysis and reverses the abnormal TG accumulation typical for CDS.
GO:0010898 positive regulation of triglyceride catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: ABHD5 activates ATGL to increase triglyceride breakdown. Reason: The mouse Compara transfer is supported independently by human disease-variant and fibroblast experiments. PMID:16679289 reports direct interaction and stimulation of ATGL activity, failure of disease variants to activate ATGL, and rescue of lipolysis in CDS fibroblasts. These assays establish the regulatory work ABHD5 performs, beyond necessity or lipid-storage phenotype alone. The abstract also includes COS-7 and mouse 3T3-L1 experiments, which are not relabeled as human. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED The seeded mouse Abhd5 source supports a conserved regulatory interpretation. Full source-chain reconstruction was not retrieved; independent target assays establish activation and phenotype rescue. ensembl:ENSMUSP00000122274 UNRESOLVED The seeded mouse Abhd5 source supports a conserved regulatory interpretation. Full source-chain reconstruction was not retrieved; independent target assays establish activation and phenotype rescue. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:16679289 expression of functional CGI-58 in CDS fibroblasts restores lipolysis and reverses the abnormal TG accumulation typical for CDS.
GO:0042171 lysophosphatidic acid acyltransferase activity	IBA GO_REF:0000033	REMOVE	Summary: The broad ancestral LPAAT assignment conflicts with contaminant-controlled target evidence. Reason: GO:0042171 still requires intrinsic acyl transfer from acyl-CoA to LPA, rather than enzyme activation. Human recombinant/yeast results supporting that role were challenged by PMID:24879803, while PMID:26745266 also reexamined plant and mouse LPAAT with negative results. This is a source-evidence and target-chemistry problem, not weak support because few descendants seeded the node or because human ABHD5 appears in its own source list. Later LPGAT/homogenate observations do not resolve purified human intrinsic LPAAT. Propagation Review Root cause: SOURCE BAD Sources checked: PANTHER:PTN008676419 UNRESOLVED PTN008676419 is the ancestral assertion. Human and plant LPAAT evidence has specific biochemical counterevidence; no claim is made that every descendant experiment or yeast activity is invalid. Full PAINT reconstruction was not retrieved. Supporting Evidence: PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0042171 lysophosphatidic acid acyltransferase activity	IDA PMID:18606822 CGI-58, the causative gene for Chanarin-Dorfman syndrome, me...	REMOVE	Summary: The reported intrinsic human LPA acyltransferase activity is contradicted by contaminant-controlled assays. Reason: The original human study used His-tagged ABHD5 expressed in E. coli and nickel-affinity purification, followed by LPA-to-PA assays; yeast overexpression also increased extract activity. Full PMID:24879803 directly tests these premises: bacterial PlsC contamination explains affinity-purified activity, stricter purification retains ATGL coactivation while removing LPAAT, and human Protein-A-ABHD5 expressed in wild-type or ict1-deleted yeast does not increase LPAAT activity. These are biochemical counterexperiments, not an inference from an inaccessible abstract. Later PMID:25315780 reports LPAAT in human-ABHD5-overexpressing 293T homogenates and purified Sf9 LPGAT activity; that different substrate/preparation does not isolate intrinsic human LPAAT from endogenous enzymes. The direct LPAAT assignment is therefore not retained; indirect phospholipid effects and other catalytic activities are not excluded. Supporting Evidence: PMID:18606822 the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to specifically acylate lysophosphatidic acid in an acyl-CoA-dependent manner. PMID:24879803 Cell-free extracts from both strains of yeast showed comparable LPAAT activity, whether or not hCGI-58 was expressed PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.
GO:0050996 positive regulation of lipid catabolic process	IEA GO_REF:0000107	MODIFY	Summary: The demonstrated lipid-catabolic regulation is more precisely triglyceride-catabolic activation. Reason: The mouse Compara annotation is directionally correct. Human evidence directly identifies ATGL-dependent triglyceride hydrolysis as the regulated process, so GO:0010898 is the evidence-backed specific term. This does not assign ABHD5 the hydrolytic step catalyzed by ATGL. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 is the donor; specific human ATGL activation supports the narrower process. Exact donor source experiment was not recovered. ensembl:ENSMUSP00000122274 UNRESOLVED Mouse Abhd5 is the donor; specific human ATGL activation supports the narrower process. Exact donor source experiment was not recovered. Proposed replacements: positive regulation of triglyceride catabolic process Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold.
GO:0052689 carboxylic ester hydrolase activity	IBA GO_REF:0000033	REMOVE	Summary: The inherited carboxylic-ester hydrolase role is not supported for the tested mammalian ABHD5 protein. Reason: GO:0052689 specifically requires ester-bond hydrolysis. Human biochemical work separates ABHD5 coactivation from intrinsic triolein and phospholipid hydrolysis, and its canonical lipase-site nucleophile differs from catalytic family members. The deep ancestral node includes mouse Abhd4, a separate phospholipid enzyme, as well as plant and yeast proteins; this family relationship does not establish conserved catalytic activity in ABHD5. The 2019 HDAC4 result concerns peptide-bond cleavage and cannot rescue an ester-hydrolase annotation. This judgment rejects the propagated lipid-esterase role, not all possible chemistry on every untested substrate. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE PSEUDO OR SUBACTIVITY LOSS Sources checked: PANTHER:PTN008676419 UNRESOLVED PTN008676419 is the ancestral source. Target-specific lipid-hydrolysis tests and canonical lipase-site divergence oppose this inheritance. The complete PAINT alignment was not retrieved; source node status remains unresolved rather than inventing a demonstrated loss placement. Supporting Evidence: PMID:24879803 it lacks a serine residue in a conserved sequence (GXSXG) that normally harbors the nucleophilic component of the catalytic triad PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold.
GO:0055088 lipid homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: ABHD5 directly regulates enzymes that maintain neutral and epidermal lipid balance. Reason: The plant-seeded ancestral homeostasis claim is broad enough to encompass conserved regulation without requiring identical plant and mammalian catalytic mechanisms. Human ATGL coactivation and CDS-fibroblast rescue establish a direct regulatory role in neutral-lipid balance, while human PNPLA1 experiments extend this to epidermal acylceramide production. The single plant descendant is not weak evidence merely because it is the sole listed seed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008676419 UNRESOLVED PTN008676419 is the inherited homeostasis node. Full PAINT placement was not retrieved; independent human enzyme-regulatory work supports the broad target process despite catalytic divergence among family members. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:16679289 expression of functional CGI-58 in CDS fibroblasts restores lipolysis and reverses the abnormal TG accumulation typical for CDS.
GO:0060229 lipase activator activity	IEA GO_REF:0000107	ACCEPT	Summary: ABHD5 binds and stimulates ATGL, meeting lipase-activator activity. Reason: The live GO definition requires binding to and increasing the activity of a lipase. PMID:16679289 reports both for ABHD5 and ATGL. The mouse Compara source is therefore corroborated by direct human-relevant functional evidence; ABHD5 is not assigned ATGL substrate hydrolysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9DBL9 UNRESOLVED Mouse Abhd5 donor identity is verified. Exact donor annotation provenance was not recovered; the human disease-variant/coactivation paper independently supports the target MF. ensembl:ENSMUSP00000122274 UNRESOLVED Mouse Abhd5 donor identity is verified. Exact donor annotation provenance was not recovered; the human disease-variant/coactivation paper independently supports the target MF. Supporting Evidence: PMID:16679289 CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. PMID:24879803 Alteration of purification methods to reduce plsC contamination eliminates LPAAT activity, without affecting the capacity of recombinant CGI-58 to coactivate TAG hydrolysis catalyzed by ATGL.

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