Search Results

Overview

Uniprot IDQ13825
Protein NameMethylglutaconyl-CoA hydratase, mitochondrial
Gene NameAUH
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
100 GINRAYGKNSLSKNL
144 FCAGADLKERAKMSS
148 ADLKERAKMSSSEVG
204 RVAASSAKMGLVETK

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) (PubMed:11738050, PubMed:12434311, PubMed:12655555, PubMed:16640564). Can catalyze the reverse reaction but at a much lower rate in vitro (PubMed:16640564). HMG-CoA is then quickly degraded by another enzyme (such as HMG-CoA lyase) to give acetyl-CoA and acetoacetate (PubMed:16640564). 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) (PubMed:16640564). Originally it was identified as an RNA-binding protein as it binds to AU-rich elements (AREs) in vitro (PubMed:7892223). AREs direct rapid RNA degradation and mRNA deadenylation (PubMed:7892223). Might have itaconyl-CoA hydratase activity, converting itaconyl-CoA into citramalyl-CoA in the C5-dicarboxylate catabolism pathway (PubMed:29056341). 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 (PubMed:29056341)

Protein Sequence

10 MAAAVAAAPG 20 ALGSLHAGGA 30 RLVAACSAWL 40 CPGLRLPGSL 50 AGRRAGPAIW 60 AQGWVPAAGG 70 PAPKRGYSSE 80 MKTEDELRVR 90 HLEEENRGIV 100 VLGINRAYGK 110 NSLSKNLIKM 120 LSKAVDALKS 130 DKKVRTIIIR 140 SEVPGIFCAG 150 ADLKERAKMS 160 SSEVGPFVSK 170 IRAVINDIAN 180 LPVPTIAAID 190 GLALGGGLEL 200 ALACDIRVAA 210 SSAKMGLVET 220 KLAIIPGGGG 230 TQRLPRAIGM 240 SLAKELIFSA 250 RVLDGKEAKA 260 VGLISHVLEQ 270 NQEGDAAYRK 280 ALDLAREFLP 290 QGPVAMRVAK 300 LAINQGMEVD 310 LVTGLAIEEA 320 CYAQTIPTKD 330 RLEGLLAFKE KRPPRYKGE

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0004300 enoyl-CoA hydratase activity
Molecular Function GO:0050011 itaconyl-CoA hydratase activity
Molecular Function GO:0004490 methylglutaconyl-CoA hydratase activity
Molecular Function GO:0003730 mRNA 3'-UTR binding
Biological Process GO:0006635 fatty acid beta-oxidation
Biological Process GO:0006552 L-leucine catabolic process
Biological Process GO:0110052 toxic metabolite repair

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.