AUHM_MOUSE
ID AUHM_MOUSE Reviewed; 314 AA.
AC Q9JLZ3; Q80YD7; Q8QZS0; Q9CY78; Q9D155;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 152.
DE RecName: Full=Methylglutaconyl-CoA hydratase, mitochondrial;
DE Short=3-MG-CoA hydratase;
DE EC=4.2.1.18 {ECO:0000250|UniProtKB:Q13825};
DE AltName: Full=AU-specific RNA-binding enoyl-CoA hydratase;
DE Short=AU-binding enoyl-CoA hydratase;
DE Short=muAUH;
DE AltName: Full=Itaconyl-CoA hydratase;
DE EC=4.2.1.56 {ECO:0000250|UniProtKB:Q13825};
DE Flags: Precursor;
GN Name=Auh;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=10072761; DOI=10.1016/s0378-1119(99)00003-7;
RA Brennan L.E., Nakagawa J., Egger D., Bienz K., Moroni C.;
RT "Characterisation and mitochondrial localisation of AUH, an AU-specific
RT RNA-binding enoyl-CoA hydratase.";
RL Gene 228:85-91(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-75; LYS-84; LYS-88; LYS-119;
RP LYS-123; LYS-135; LYS-179; LYS-186 AND LYS-304, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-75; LYS-88; LYS-119; LYS-179 AND
RP LYS-186, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Catalyzes the fifth step in the leucine degradation pathway,
CC the reversible hydration of 3-methylglutaconyl-CoA (3-MG-CoA) to 3-
CC hydroxy-3-methylglutaryl-CoA (HMG-CoA). Can catalyze the reverse
CC reaction but at a much lower rate in vitro. HMG-CoA is then quickly
CC degraded by another enzyme (such as HMG-CoA lyase) to give acetyl-CoA
CC and acetoacetate. Uses other substrates such as (2E)-glutaconyl-CoA
CC efficiently in vitro, and to a lesser extent 3-methylcrotonyl-CoA (3-
CC methyl-(2E)-butenoyl-CoA), crotonyl-CoA ((2E)-butenoyl-CoA) and 3-
CC hydroxybutanoyl-CoA (the missing carboxylate reduces affinity to the
CC active site) (By similarity). Originally it was identified as an RNA-
CC binding protein as it binds to AU-rich elements (AREs) in vitro. AREs
CC direct rapid RNA degradation and mRNA deadenylation (PubMed:10072761).
CC Might have itaconyl-CoA hydratase activity, converting itaconyl-CoA
CC into citramalyl-CoA in the C5-dicarboxylate catabolism pathway. The C5-
CC dicarboxylate catabolism pathway is required to detoxify itaconate, an
CC antimicrobial metabolite and immunomodulator produced by macrophages
CC during certain infections, that can act as a vitamin B12-poisoning
CC metabolite (By similarity). {ECO:0000250|UniProtKB:Q13825,
CC ECO:0000269|PubMed:10072761}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxy-3-methylglutaryl-CoA = 3-methyl-(2E)-glutaconyl-
CC CoA + H2O; Xref=Rhea:RHEA:21536, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43074, ChEBI:CHEBI:57346; EC=4.2.1.18;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21538;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-citramalyl-CoA = H2O + itaconyl-CoA;
CC Xref=Rhea:RHEA:13785, ChEBI:CHEBI:15377, ChEBI:CHEBI:57381,
CC ChEBI:CHEBI:58668; EC=4.2.1.56;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13787;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxyisovaleryl-CoA = 3-methyl-(2E)-butenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31079, ChEBI:CHEBI:15377, ChEBI:CHEBI:57344,
CC ChEBI:CHEBI:62555; Evidence={ECO:0000250|UniProtKB:Q13825};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31081;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-3-hydroxyglutaryl-CoA = (2E)-glutaconyl-CoA + H2O;
CC Xref=Rhea:RHEA:68456, ChEBI:CHEBI:15377, ChEBI:CHEBI:57353,
CC ChEBI:CHEBI:177916; Evidence={ECO:0000250|UniProtKB:Q13825};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68458;
CC Evidence={ECO:0000250|UniProtKB:Q13825};
CC -!- PATHWAY: Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-
CC 3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 3/3.
CC {ECO:0000250|UniProtKB:Q13825}.
CC -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:Q13825}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10072761}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9JLZ3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLZ3-2; Sequence=VSP_008337, VSP_008340;
CC Name=3;
CC IsoId=Q9JLZ3-3; Sequence=VSP_008338, VSP_008339;
CC -!- TISSUE SPECIFICITY: Detected in heart, brain, liver, spleen, skeletal
CC muscle and kidney. Expressed in brain, kidney, liver and spleen tissue
CC (at protein level). {ECO:0000269|PubMed:10072761}.
CC -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC {ECO:0000305}.
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DR EMBL; AF118386; AAF28835.1; -; mRNA.
DR EMBL; AK003929; BAB23078.1; -; mRNA.
DR EMBL; AK019978; BAB31947.1; -; mRNA.
DR EMBL; BC026525; AAH26525.1; -; mRNA.
DR EMBL; BC049597; AAH49597.1; -; mRNA.
DR CCDS; CCDS26518.1; -. [Q9JLZ3-1]
DR RefSeq; NP_057918.2; NM_016709.2.
DR AlphaFoldDB; Q9JLZ3; -.
DR SMR; Q9JLZ3; -.
DR BioGRID; 198280; 4.
DR IntAct; Q9JLZ3; 3.
DR MINT; Q9JLZ3; -.
DR STRING; 10090.ENSMUSP00000021913; -.
DR iPTMnet; Q9JLZ3; -.
DR PhosphoSitePlus; Q9JLZ3; -.
DR SwissPalm; Q9JLZ3; -.
DR EPD; Q9JLZ3; -.
DR jPOST; Q9JLZ3; -.
DR MaxQB; Q9JLZ3; -.
DR PaxDb; Q9JLZ3; -.
DR PeptideAtlas; Q9JLZ3; -.
DR PRIDE; Q9JLZ3; -.
DR ProteomicsDB; 273631; -. [Q9JLZ3-1]
DR ProteomicsDB; 273632; -. [Q9JLZ3-2]
DR ProteomicsDB; 273633; -. [Q9JLZ3-3]
DR GeneID; 11992; -.
DR KEGG; mmu:11992; -.
DR UCSC; uc007qnd.1; mouse. [Q9JLZ3-1]
DR CTD; 549; -.
DR MGI; MGI:1338011; Auh.
DR eggNOG; KOG1679; Eukaryota.
DR InParanoid; Q9JLZ3; -.
DR OrthoDB; 1123666at2759; -.
DR PhylomeDB; Q9JLZ3; -.
DR TreeFam; TF314276; -.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR UniPathway; UPA00363; UER00862.
DR BioGRID-ORCS; 11992; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Auh; mouse.
DR PRO; PR:Q9JLZ3; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JLZ3; protein.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:MGI.
DR GO; GO:0050011; F:itaconyl-CoA hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0004490; F:methylglutaconyl-CoA hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR GO; GO:0006552; P:leucine catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.12.10; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR014748; Enoyl-CoA_hydra_C.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Branched-chain amino acid catabolism;
KW Lyase; Mitochondrion; Reference proteome; RNA-binding; Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q13825"
FT CHAIN 43..314
FT /note="Methylglutaconyl-CoA hydratase, mitochondrial"
FT /id="PRO_0000007416"
FT REGION 80..94
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13825"
FT MOD_RES 75
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 75
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 84
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 88
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 88
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 119
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 119
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 123
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 135
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 179
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 179
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 186
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 186
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 304
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 115..157
FT /note="GADLKERAKMHSSEVGPFVSKIRSVINDIANLPVPTIAAIDGL -> VSFQL
FT KADIQLCFQFAPFWWPLQSHSSQKPEVTPDSRCSPQIW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008337"
FT VAR_SEQ 144
FT /note="A -> V (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008338"
FT VAR_SEQ 145..314
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008339"
FT VAR_SEQ 159..314
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008340"
FT CONFLICT 15..16
FT /note="GR -> VG (in Ref. 2; BAB23078/BAB31947 and 3;
FT AAH49597)"
FT /evidence="ECO:0000305"
FT CONFLICT 22
FT /note="A -> P (in Ref. 2; BAB23078)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 33395 MW; 974694EAC28FA157 CRC64;
MAAAAPGALG ALRTGRVRLV AACCARLGPA AWARGTAPRR GYSSEVKTED ELRVRHLEEE
NRGIVVLGIN RAYGKNALSK NLLKMLSKAV DALKSDKKVR TIIIRSEVPG IFCAGADLKE
RAKMHSSEVG PFVSKIRSVI NDIANLPVPT IAAIDGLALG GGLELALACD IRVAASSAKM
GLVETKLAII PGGGGTQRLP RAIGMSLAKE LIFSARVLDG QEAKAVGLIS HVLEQNQEGD
AAYRKALDLA REFLPQGPVA MRVAKLAINQ GMEVDLVTGL AIEEACYAQT ISTKDRLEGL
LAFKEKRPPR YKGE
