Protein: Methylglutaconyl-CoA hydratase, mitochondrial (3-MG-CoA hydratase) (EC 4.2.1.18) (AU-specific RNA-binding enoyl-CoA hydratase) (AU-binding protein/enoyl-CoA hydratase) (Itaconyl-CoA hydratase) (EC 4.2.1.56) (Q13825)
Organism: Homo sapiens (Human)
Function: Catalyzes the fifth step in the leucine degradation pathway, the reversible hydration of 3-methylglutaconyl-CoA (3-MG-CoA) to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Can catalyze the reverse reaction but at a much lower rate in vitro. HMG-CoA is then quickly degraded by another enzyme (such as HMG-CoA lyase) to give acetyl-CoA and acetoacetate. Uses other substrates such as (2E)-glutaconyl-CoA efficiently in vitro, and to a lesser extent 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA), crotonyl-CoA ((2E)-butenoyl-CoA) and 3-hydroxybutanoyl-CoA (the missing carboxylate reduces affinity to the active site). Originally it was identified as an RNA-binding protein as it binds to AU-rich elements (AREs) in vitro. AREs direct rapid RNA degradation and mRNA deadenylation. Might have itaconyl-CoA hydratase activity, converting itaconyl-CoA into citramalyl-CoA in the C5-dicarboxylate catabolism pathway. The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, an antimicrobial metabolite and immunomodulator produced by macrophages during certain infections, that can act as a vitamin B12-poisoning metabolite.
Subcellular location: Mitochondrion {ECO:0000250|UniProtKB:Q9JLZ3}.
Sequence: MAAAVAAAPGALGSLHAGGARLVAACSAWLCPGLRLPGSLAGRRAGPAIWAQGWVPAAGGPAPKRGYSSEMKTEDELRVRHLEEENRGIVVLGINRAYGKNSLSKNLIKMLSKAVDALKSDKKVRTIIIRSEVPGIFCAGADLKERAKMSSSEVGPFVSKIRAVINDIANLPVPTIAAIDGLALGGGLELALACDIRVAASSAKMGLVETKLAIIPGGGGTQRLPRAIGMSLAKELIFSARVLDGKEAKAVGLISHVLEQNQEGDAAYRKALDLAREFLPQGPVAMRVAKLAINQGMEVDLVTGLAIEEACYAQTIPTKDRLEGLLAFKEKRPPRYKGE
InterPro domains: - IPR029045: ClpP/crotonase-like domain superfamily (homologous_superfamily) [83-338]
- IPR014748: Enoyl-CoA hydratase, C-terminal (homologous_superfamily) [280-339]
- IPR018376: Enoyl-CoA hydratase/isomerase, conserved site (conserved_site) [176-196]
- IPR001753: Enoyl-CoA hydratase/isomerase (family) [84-338]
Interaction partners: - Hydroxymethylglutaryl-CoA lyase, mitochondrial
- 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic
- Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
- Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
- Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
- Hydroxymethylglutaryl-CoA synthase, cytoplasmic
- Hydroxymethylglutaryl-CoA synthase, mitochondrial
- Mitochondrial import inner membrane translocase subunit TIM14
- Tafazzin
- Hydroxysteroid dehydrogenase-like protein 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0016829 (lyase activity), GO:0003676 (nucleic acid binding), GO:0016835 (carbon-oxygen lyase activity), GO:0003723 (RNA binding), GO:0016836 (hydro-lyase activity), GO:0004300 (enoyl-CoA hydratase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044282 (small molecule catabolic process), GO:0006629 (lipid metabolic process), GO:0006082 (organic acid metabolic process), GO:0044248 (cellular catabolic process), GO:0044255 (cellular lipid metabolic process), GO:0006520 (amino acid metabolic process), GO:1901575 (organic substance catabolic process), GO:0006631 (fatty acid metabolic process), GO:0016054 (organic acid catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0043436 (oxoacid metabolic process), GO:0009063 (amino acid catabolic process), GO:0030258 (lipid modification), GO:0009081 (branched-chain amino acid metabolic process), GO:0044242 (cellular lipid catabolic process), GO:0016042 (lipid catabolic process), GO:0019752 (carboxylic acid metabolic process), GO:0019395 (fatty acid oxidation), GO:0046395 (carboxylic acid catabolic process), GO:0034440 (lipid oxidation), GO:0009083 (branched-chain amino acid catabolic process), GO:0009062 (fatty acid catabolic process), GO:0006635 (fatty acid beta-oxidation), GO:0032787 (monocarboxylic acid metabolic process), GO:0072329 (monocarboxylic acid catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)