GO terms mapped to EC:1.3.8.5

[sjm41]

The following 2 GO terms both have an EC:1.3.8.5 xref:

id: GO:0003853 name: 2-methylacyl-CoA dehydrogenase activity def: "Catalysis of the reaction: 2-methylbutanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]." [PMID:10989435, PMID:6401712, RHEA:43780] xref: EC:1.3.8.5 xref: RHEA:43780 is_a: GO:0003995 ! acyl-CoA dehydrogenase activity => 3 EXP annotations (2x Human ACADSB, 1x potato 2MBCD)

id: GO:0102035 name: isobutyryl-CoA:FAD oxidoreductase activity def: "Catalysis of the reaction: H+ + isobutyryl-CoA + FAD = methacrylyl-CoA + FADH2." [GOC:pz, PMID:3988734] xref: EC:1.3.8.5 is_a: GO:0003995 ! acyl-CoA dehydrogenase activity => 0 EXP annotations

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https://enzyme.expasy.org/EC/1.3.8.5 says: Name: short-chain 2-methylacyl-CoA dehydrogenase Reaction: 2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer flavoprotein] <=> (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]

There seems to be a mismatch in specificity between the name (short-chain 2-methylacyl) and the reaction (2-methylbutanoyl-CoA) here?

RHEA does map EC:1.3.8.5 to both reactions:

RHEA:43780 | 2-methylbutanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA+ reduced [electron-transfer flavoprotein]

RHEA:44180 | 2-methylpropanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-2-methylpropenoyl-CoA+ reduced [electron-transfer flavoprotein]

(Note: 'isobutyryl-CoA' has synonym '2-methylpropanoyl-CoA', and 'methacrylyl-CoA' has synonym '2E)-2-methylpropenoyl-CoA' in CHEBI)

@kaxelsen Can you comment on this please?

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Possible tasks (pending Kristian's input):

• [ ] Remove EC:1.3.8.5 from GO:0102035 -> No, EC:1.3.8.5 describes an enzyme that can act on both substrates here (see Kristian's reply below)
• [x] add RHEA:44180 to GO:0102035
• [x] Update GO:0102035 name and def to match RHEA:44180
• [x] Update GO:0003853 name to '2-methylbutanoyl-CoA dehydrogenase activity' to match GO/EC/RHEA def
• [x] change parent of both GO terms to the more specific "short-chain-acyl-CoA dehydrogenase activity" (GO:0016937) since 2-methylbutanoyl-CoA and 2-methylpropanoyl-CoA both have a chain length of <C6.

[sjm41]

Hi @kaxelsen

Can you comment on this point please?

https://enzyme.expasy.org/EC/1.3.8.5 says: Name: short-chain 2-methylacyl-CoA dehydrogenase Reaction: 2-methylbutanoyl-CoA + H(+) + oxidized [electron-transfer flavoprotein] <=> (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]

There seems to be a mismatch in specificity between the name (short-chain 2-methylacyl) and the reaction (2-methylbutanoyl-CoA) here?

[kaxelsen]

There seems to be a mismatch in specificity between the name (short-chain 2-methylacyl) and the reaction (2-methylbutanoyl-CoA) here?

No, it is fine. The chains can be branched as long as they are still aliphatic. Regarding the name, the EC 1.3.8.5 has the highest activity with 2-methylbutanoyl-CoA but also has activity with other short-chain 2-methylacyl-CoA cf pmid:11013134

[sjm41]

Thanks @kaxelsen. Yes, I see in pmid:11013134 that the enzyme acts on both 2-methylbutyryl-CoA (aka 2-methylbutanoyl-CoA) and isobutyryl-CoA (aka 2-methylpropanoyl-CoA), so it should remain an xref on both GO terms mentioned above.

[sjm41]

@pgaudet Looking at this again, with the wider aim of not having duplicate ECs on different GO terms, I think we should merge the following two EC:1.3.8.5-based GO terms:

id: GO:0003853 name: 2-methylbutanoyl-CoA dehydrogenase activity def: "Catalysis of the reaction: 2-methylbutanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]." [PMID:10989435, PMID:6401712, RHEA:43780] xref: EC:1.3.8.5 xref: KEGG_REACTION:R03169 xref: MetaCyc:2-METHYLACYL-COA-DEHYDROGENASE-RXN xref: RHEA:43780 is_a: GO:0016937 ! short-chain fatty acyl-CoA dehydrogenase activity

3 EXP

id: GO:0102035 name: 2-methylpropanoyl-CoA dehydrogenase activity def: "Catalysis of the reaction: 2-methylpropanoyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = (2E)-2-methylpropenoyl-CoA + reduced [electron-transfer flavoprotein]." [PMID:3988734, RHEA:44180] xref: EC:1.3.8.5 xref: MetaCyc:MEPROPCOA-FAD-RXN xref: RHEA:44180 is_a: GO:0016937 ! short-chain fatty acyl-CoA dehydrogenase activity

No manual annotations.

Merged GO term would look like something like this:

id: GO:0102035 name: short-chain 2-methyl fatty acyl-CoA dehydrogenase activity def: "Catalysis of the reaction: a short-chain 2-methyl fatty acyl-CoA + H+ + oxidized [electron-transfer flavoprotein] = a short-chain (2E)-2-methyl-2-enoyl-CoA + reduced [electron-transfer flavoprotein]." [MetaCyc:RXN-21774] xref: EC:1.3.8.5 [exactMatch] xref: MetaCyc:RXN-21774 [exactMatch] is_a: GO:0016937 ! short-chain fatty acyl-CoA dehydrogenase activity

[pgaudet]

Also: merge GO:0004085 'butyryl-CoA dehydrogenase activity' into parent short-chain fatty acyl-CoA dehydrogenase activity GO:0016937 since that also represents a specific substrate. 4 EXP annotations: RGD, AgBase, UniProt >> will be automatically remapped.