Ces2c encodes rat acylcarnitine hydrolase (ACH M1), a type-B carboxylesterase of the CES2 family that is made with an N-terminal signal peptide. It is an alpha/beta-hydrolase-fold serine hydrolase with an intact Ser-Glu-His catalytic triad that hydrolyzes carboxylic esters, with high activity toward long-chain acylcarnitines such as palmitoylcarnitine (releasing carnitine and a fatty acid) and activity toward retinyl palmitate (releasing all-trans-retinol). The protein is recovered in liver microsomes and resides in the endoplasmic reticulum, and is expressed in liver, stomach and kidney, where it contributes to hepatic acylcarnitine turnover and to the mobilization of retinol from stored retinyl esters.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0050253 retinyl-palmitate esterase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the retinyl-palmitate esterase activity annotation is supported by the fetched UniProt/GOA evidence (IBA, GO_REF:0000033) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. Rat Ces2c also has its own IDA support for this term, and the serine-hydrolase catalytic machinery is fully intact (see residue claim), so the phylogenetic assertion is corroborated on the target itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000168789 ยท PANTHER:PTN000168789 SUPPORTS TRANSFER One of two GO:0050253 IBDs in the current PTHR11559 PAINT slice (the other at PTN000168858), both on rodent carboxylesterase branches seeded by experimentally characterised rat/mouse CES members with retinyl ester hydrolase evidence; rat Ces2c descends from these nodes and has its own IDA for the term. Supporting Evidence: UniProtKB:O70631 GO; GO:0050253; F:retinyl-palmitate esterase activity; IDA:UniProtKB. file:rat/Ces2c/Ces2c-deep-research-falcon.md CES enzymes collectively hydrolyze diverse lipid esters and xenobiotic esters (e.g., retinyl esters, phorbol diesters, platelet-activating factor, phthalate diesters, and multiple drugs), with major activity in liver and also in extrahepatic tissues depending on isoform. |
| GO:0106435 carboxylesterase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The carboxylesterase activity annotation is plausible for Ces2c but should be kept as non-core context rather than used to define the gene product function. Reason: The annotation is compatible with Ces2c biology but is broader or more contextual than the core molecular function. Supporting Evidence: UniProtKB:O70631 FUNCTION: Hydrolase with high activity towards palmitoylcarnitine. Is also active with p-nitrophenylacetate and alpha-naphthylacetate (By similarity). May also hydrolyze retinyl esters (PubMed:12230550). file:rat/Ces2c/Ces2c-deep-research-falcon.md Carboxylesterases (CES) are **serine hydrolases** (ฮฑ/ฮฒ-hydrolase fold) that catalyze hydrolysis of **ester, thioester, amide, and carbamate** bonds in endogenous lipids and xenobiotics, contributing to detoxification and prodrug activation. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The endoplasmic reticulum annotation is plausible for Ces2c but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Ces2c. Supporting Evidence: UniProtKB:O70631 SUBCELLULAR LOCATION: Microsome {ECO:0000269|PubMed:12230550}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q91WG0}. file:rat/Ces2c/Ces2c-deep-research-falcon.md CES2 (the family context relevant to rat Ces2c) is described as **monomeric in the ER** (endoplasmic reticulum), and CES enzymes are commonly studied in **microsomal** fractions (reflecting ER association), although some preparations show both microsomal and cytosolic activity. |
| GO:0042572 retinol metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the retinol metabolic process annotation is supported by the fetched UniProt/GOA evidence (IEA, GO_REF:0000120) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:O70631 FUNCTION: Hydrolase with high activity towards palmitoylcarnitine. Is also active with p-nitrophenylacetate and alpha-naphthylacetate (By similarity). May also hydrolyze retinyl esters (PubMed:12230550). file:rat/Ces2c/Ces2c-deep-research-falcon.md CES enzymes collectively hydrolyze diverse lipid esters and xenobiotic esters (e.g., retinyl esters, phorbol diesters, platelet-activating factor, phthalate diesters, and multiple drugs), with major activity in liver and also in extrahepatic tissues depending on isoform. |
| GO:0047376 all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity | IEA GO_REF:0000116 | ACCEPT | Summary: The all-trans-retinyl-palmitate hydrolase term is a specific reaction-level annotation consistent with Ces2c retinyl ester hydrolase evidence. Reason: This is not a generic parent term; it captures the specific retinyl-palmitate hydrolysis reaction separately from the broader acylcarnitine hydrolase activity. Supporting Evidence: UniProtKB:O70631 FUNCTION: Hydrolase with high activity towards palmitoylcarnitine. Is also active with p-nitrophenylacetate and alpha-naphthylacetate (By similarity). May also hydrolyze retinyl esters (PubMed:12230550). file:rat/Ces2c/Ces2c-deep-research-falcon.md CES enzymes collectively hydrolyze diverse lipid esters and xenobiotic esters (e.g., retinyl esters, phorbol diesters, platelet-activating factor, phthalate diesters, and multiple drugs), with major activity in liver and also in extrahepatic tissues depending on isoform. |
| GO:0047619 acylcarnitine hydrolase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the acylcarnitine hydrolase activity annotation is supported by the fetched UniProt/GOA evidence (IEA, GO_REF:0000120) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:O70631 CATALYTIC ACTIVITY: Reaction=an O-acyl-(R)-carnitine + H2O = (R)-carnitine + a fatty acid + H(+) file:rat/Ces2c/Ces2c-deep-research-falcon.md Historical rat esterase literature recognizes **acylcarnitine hydrolase activity (EC 3.1.1.28)** as part of the broader hepatic carboxylesterase/ester hydrolase system (with multiple isoenzymes). This is consistent with UniProt O70631 being annotated as โacylcarnitine hydrolase.โ |
| GO:0052689 carboxylic ester hydrolase activity | IEA GO_REF:0000117 | MODIFY | Summary: The carboxylic ester hydrolase activity annotation is related to Ces2c function, but it is too generic compared with the supported specific term(s): acylcarnitine hydrolase activity, retinyl-palmitate esterase activity. Reason: The annotation is directionally related to Ces2c but is too broad; the specific catalytic activity is more informative. Proposed replacements: acylcarnitine hydrolase activity retinyl-palmitate esterase activity Supporting Evidence: UniProtKB:O70631 FUNCTION: Hydrolase with high activity towards palmitoylcarnitine. Is also active with p-nitrophenylacetate and alpha-naphthylacetate (By similarity). file:rat/Ces2c/Ces2c-deep-research-falcon.md Historical rat esterase literature recognizes **acylcarnitine hydrolase activity (EC 3.1.1.28)** as part of the broader hepatic carboxylesterase/ester hydrolase system (with multiple isoenzymes). This is consistent with UniProt O70631 being annotated as โacylcarnitine hydrolase.โ |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The endoplasmic reticulum annotation is plausible for Ces2c but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Ces2c. Supporting Evidence: UniProtKB:O70631 SUBCELLULAR LOCATION: Microsome {ECO:0000269|PubMed:12230550}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q91WG0}. file:rat/Ces2c/Ces2c-deep-research-falcon.md CES enzymes are synthesized into the **ER lumen** and are often recovered in **microsomal** preparations, consistent with ER association. |
| GO:0047619 acylcarnitine hydrolase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the acylcarnitine hydrolase activity annotation is supported by the fetched UniProt/GOA evidence (ISS, GO_REF:0000024) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:O70631 CATALYTIC ACTIVITY: Reaction=an O-acyl-(R)-carnitine + H2O = (R)-carnitine + a fatty acid + H(+) file:rat/Ces2c/Ces2c-deep-research-falcon.md Historical rat esterase literature recognizes **acylcarnitine hydrolase activity (EC 3.1.1.28)** as part of the broader hepatic carboxylesterase/ester hydrolase system (with multiple isoenzymes). This is consistent with UniProt O70631 being annotated as โacylcarnitine hydrolase.โ |
| GO:0050253 retinyl-palmitate esterase activity | IDA PMID:12230550 Identification of microsomal rat liver carboxylesterases and... | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the retinyl-palmitate esterase activity annotation is supported by the fetched UniProt/GOA evidence (IDA, PMID:12230550) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. PMID:12230550 purified six carboxylesterases from rat liver microsomes, including the AB010635 gene product (the Ces2c EMBL entry in UniProt O70631), and assayed retinyl palmitate hydrolysis. The cached abstract names AB010635 among the purified isoenzymes but does not itself list its retinyl palmitate rate; the full text (not cached) is what the curators and UniProt (RHEA:13933 catalytic activity, PubMed:12230550) relied on, so the IDA is accepted on their reading. Supporting Evidence: UniProtKB:O70631 GO; GO:0050253; F:retinyl-palmitate esterase activity; IDA:UniProtKB. PMID:12230550 In addition to previously characterized rat liver carboxylesterases ES10, ES4, ES3, the protein products for two cloned genes, AB010635 and D50580 (GenBank accession numbers), were also identified. UniProtKB:O70631 Reaction=all-trans-retinyl hexadecanoate + H2O = all-trans-retinol + hexadecanoate + H(+) |
| GO:0001523 retinoid metabolic process | TAS PMID:12230550 Identification of microsomal rat liver carboxylesterases and... | KEEP AS NON CORE | Summary: The retinoid metabolic process annotation is plausible for Ces2c but should be kept as non-core context rather than used to define the gene product function. Reason: The annotation is compatible with Ces2c biology but is broader or more contextual than the core molecular function. Supporting Evidence: UniProtKB:O70631 GO; GO:0001523; P:retinoid metabolic process; TAS:UniProtKB. file:rat/Ces2c/Ces2c-deep-research-falcon.md CES enzymes collectively hydrolyze diverse lipid esters and xenobiotic esters (e.g., retinyl esters, phorbol diesters, platelet-activating factor, phthalate diesters, and multiple drugs), with major activity in liver and also in extrahepatic tissues depending on isoform. |
| GO:0043231 intracellular membrane-bounded organelle | IDA PMID:12230550 Identification of microsomal rat liver carboxylesterases and... | MODIFY | Summary: This is a high-level generic organelle term that is subsumed by the more specific and already-annotated endoplasmic reticulum localization (GO:0005783). The underlying microsomal localization experiment (PMID:12230550) and falcon CES-family cell biology both point specifically to the ER, so this generic parent adds no information beyond the ER term and should be refined to it. Reason: GO:0043231 is a generic parent of the endoplasmic reticulum term that is already annotated for Ces2c from the same microsomal localization data; the specific ER term should be used instead of this uninformative parent. The experimental observation (purification from liver microsomal extracts) is sound, so the row is refined rather than flagged; microsomes are ER-derived vesicles and GO has no current microsome CC term, so GO:0005783 endoplasmic reticulum is the closest specific location. (Earlier action MARK_AS_OVER_ANNOTATED replaced, because the problem is generality, not a claim exceeding the evidence.) Proposed replacements: endoplasmic reticulum Supporting Evidence: UniProtKB:O70631 GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB. PMID:12230550 Six different carboxylesterases were identified and purified from rat liver microsomal extracts. UniProtKB:O70631 SUBCELLULAR LOCATION: Microsome {ECO:0000269|PubMed:12230550}. |
| GO:0047619 acylcarnitine hydrolase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Ces2c is a acylcarnitine/retinyl ester hydrolase; the acylcarnitine hydrolase activity annotation is supported by the fetched UniProt/GOA evidence (ISO, GO_REF:0000121) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ces2c core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:O70631 CATALYTIC ACTIVITY: Reaction=an O-acyl-(R)-carnitine + H2O = (R)-carnitine + a fatty acid + H(+) file:rat/Ces2c/Ces2c-deep-research-falcon.md Historical rat esterase literature recognizes **acylcarnitine hydrolase activity (EC 3.1.1.28)** as part of the broader hepatic carboxylesterase/ester hydrolase system (with multiple isoenzymes). This is consistent with UniProt O70631 being annotated as โacylcarnitine hydrolase.โ |
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