General Information of Target

Target ID LDTP05988
Target Name Methylglutaconyl-CoA hydratase, mitochondrial (AUH)
Gene Name AUH
Gene ID 549
Synonyms
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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAAVAAAPGALGSLHAGGARLVAACSAWLCPGLRLPGSLAGRRAGPAIWAQGWVPAAGG
PAPKRGYSSEMKTEDELRVRHLEEENRGIVVLGINRAYGKNSLSKNLIKMLSKAVDALKS
DKKVRTIIIRSEVPGIFCAGADLKERAKMSSSEVGPFVSKIRAVINDIANLPVPTIAAID
GLALGGGLELALACDIRVAASSAKMGLVETKLAIIPGGGGTQRLPRAIGMSLAKELIFSA
RVLDGKEAKAVGLISHVLEQNQEGDAAYRKALDLAREFLPQGPVAMRVAKLAINQGMEVD
LVTGLAIEEACYAQTIPTKDRLEGLLAFKEKRPPRYKGE
Target Bioclass
Enzyme
Family
Enoyl-CoA hydratase/isomerase family
Subcellular location
Mitochondrion
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.
Uniprot ID
Q13825
Ensemble ID
ENST00000303617.5
HGNC ID
HGNC:890

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HEC1B Insertion: p.M205NfsTer5 .
IGROV1 SNV: p.P56L .
JURKAT SNV: p.A313T .
NCIH1299 SNV: p.V208I .
SNU1 SNV: p.A213V .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info 
K100(6.51); K211(2.17)  LDD0277  [1]
IPM
 Probe Info 
N.A.  LDD0241  [2]
DBIA
 Probe Info 
C138(0.97)  LDD3313  [3]
ATP probe
 Probe Info 
N.A.  LDD0199  [4]
IA-alkyne
 Probe Info 
N.A.  LDD0165  [5]
JW-RF-010
 Probe Info 
N.A.  LDD0026  [6]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C138(1.01)  LDD1507  [7]
 LDCM0259  AC14 HEK-293T C138(1.05)  LDD1512  [7]
 LDCM0276  AC17 HEK-293T C138(1.02)  LDD1515  [7]
 LDCM0282  AC22 HEK-293T C138(1.00)  LDD1521  [7]
 LDCM0285  AC25 HEK-293T C138(1.15)  LDD1524  [7]
 LDCM0291  AC30 HEK-293T C138(0.96)  LDD1530  [7]
 LDCM0294  AC33 HEK-293T C138(1.04)  LDD1533  [7]
 LDCM0299  AC38 HEK-293T C138(1.02)  LDD1538  [7]
 LDCM0303  AC41 HEK-293T C138(1.00)  LDD1542  [7]
 LDCM0308  AC46 HEK-293T C138(1.11)  LDD1547  [7]
 LDCM0311  AC49 HEK-293T C138(1.03)  LDD1550  [7]
 LDCM0317  AC54 HEK-293T C138(1.12)  LDD1556  [7]
 LDCM0320  AC57 HEK-293T C138(1.03)  LDD1559  [7]
 LDCM0323  AC6 HEK-293T C138(0.97)  LDD1562  [7]
 LDCM0326  AC62 HEK-293T C138(1.01)  LDD1565  [7]
 LDCM0356  AKOS034007680 HEK-293T C138(1.07)  LDD1570  [7]
 LDCM0367  CL1 HEK-293T C138(1.14)  LDD1571  [7]
 LDCM0368  CL10 HEK-293T C138(0.91)  LDD1572  [7]
 LDCM0370  CL101 HEK-293T C138(1.08)  LDD1574  [7]
 LDCM0372  CL103 HEK-293T C138(1.06)  LDD1576  [7]
 LDCM0374  CL105 HEK-293T C138(1.12)  LDD1578  [7]
 LDCM0376  CL107 HEK-293T C138(0.96)  LDD1580  [7]
 LDCM0378  CL109 HEK-293T C138(0.98)  LDD1582  [7]
 LDCM0381  CL111 HEK-293T C138(0.86)  LDD1585  [7]
 LDCM0383  CL113 HEK-293T C138(1.01)  LDD1587  [7]
 LDCM0385  CL115 HEK-293T C138(0.95)  LDD1589  [7]
 LDCM0387  CL117 HEK-293T C138(1.12)  LDD1591  [7]
 LDCM0389  CL119 HEK-293T C138(1.02)  LDD1593  [7]
 LDCM0392  CL121 HEK-293T C138(1.13)  LDD1596  [7]
 LDCM0394  CL123 HEK-293T C138(1.05)  LDD1598  [7]
 LDCM0396  CL125 HEK-293T C138(1.04)  LDD1600  [7]
 LDCM0398  CL127 HEK-293T C138(1.08)  LDD1602  [7]
 LDCM0400  CL13 HEK-293T C138(1.05)  LDD1604  [7]
 LDCM0402  CL15 HEK-293T C138(0.94)  LDD1606  [7]
 LDCM0404  CL17 HEK-293T C138(1.04)  LDD1608  [7]
 LDCM0410  CL22 HEK-293T C138(1.19)  LDD1614  [7]
 LDCM0413  CL25 HEK-293T C138(1.05)  LDD1617  [7]
 LDCM0415  CL27 HEK-293T C138(1.02)  LDD1619  [7]
 LDCM0417  CL29 HEK-293T C138(1.09)  LDD1621  [7]
 LDCM0418  CL3 HEK-293T C138(1.00)  LDD1622  [7]
 LDCM0423  CL34 HEK-293T C138(1.12)  LDD1627  [7]
 LDCM0426  CL37 HEK-293T C138(1.01)  LDD1630  [7]
 LDCM0428  CL39 HEK-293T C138(1.03)  LDD1632  [7]
 LDCM0431  CL41 HEK-293T C138(0.98)  LDD1635  [7]
 LDCM0436  CL46 HEK-293T C138(1.08)  LDD1640  [7]
 LDCM0439  CL49 HEK-293T C138(1.11)  LDD1643  [7]
 LDCM0440  CL5 HEK-293T C138(1.04)  LDD1644  [7]
 LDCM0444  CL53 HEK-293T C138(1.13)  LDD1647  [7]
 LDCM0449  CL58 HEK-293T C138(1.12)  LDD1652  [7]
 LDCM0453  CL61 HEK-293T C138(1.14)  LDD1656  [7]
 LDCM0455  CL63 HEK-293T C138(1.01)  LDD1658  [7]
 LDCM0457  CL65 HEK-293T C138(1.11)  LDD1660  [7]
 LDCM0463  CL70 HEK-293T C138(1.00)  LDD1666  [7]
 LDCM0466  CL73 HEK-293T C138(1.06)  LDD1669  [7]
 LDCM0470  CL77 HEK-293T C138(0.98)  LDD1673  [7]
 LDCM0476  CL82 HEK-293T C138(1.12)  LDD1679  [7]
 LDCM0479  CL85 HEK-293T C138(1.09)  LDD1682  [7]
 LDCM0481  CL87 HEK-293T C138(1.08)  LDD1684  [7]
 LDCM0483  CL89 HEK-293T C138(1.12)  LDD1686  [7]
 LDCM0489  CL94 HEK-293T C138(1.15)  LDD1692  [7]
 LDCM0492  CL97 HEK-293T C138(1.00)  LDD1695  [7]
 LDCM0494  CL99 HEK-293T C138(0.97)  LDD1697  [7]
 LDCM0495  E2913 HEK-293T C138(1.23)  LDD1698  [7]
 LDCM0468  Fragment33 HEK-293T C138(1.01)  LDD1671  [7]
 LDCM0022  KB02 CCK-81 C138(1.87)  LDD2297  [3]
 LDCM0023  KB03 CCK-81 C138(1.94)  LDD2714  [3]
 LDCM0024  KB05 Hs 936.T C138(0.97)  LDD3313  [3]

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
3 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
4 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
5 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
6 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
7 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402