AUHM_RAT
ID AUHM_RAT Reviewed; 315 AA.
AC F1LU71;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 76.
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 AltName: Full=Itaconyl-CoA hydratase;
DE EC=4.2.1.56 {ECO:0000303|PubMed:13783048};
DE Flags: Precursor;
GN Name=Auh {ECO:0000312|RGD:1306087};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=13783048;
RA Wang S.F., Adler J., Lardy H.A.;
RT "The pathway of itaconate metabolism by liver mitochondria.";
RL J. Biol. Chem. 236:26-30(1961).
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). Originally it was identified as an RNA-binding protein as
CC it binds to AU-rich elements (AREs) in vitro. AREs direct rapid RNA
CC degradation and mRNA deadenylation (By similarity). Might have
CC itaconyl-CoA hydratase activity, converting itaconyl-CoA into
CC 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 (PubMed:13783048). {ECO:0000250|UniProtKB:Q13825,
CC ECO:0000303|PubMed:13783048}.
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:0000303|PubMed:13783048};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13787;
CC Evidence={ECO:0000303|PubMed:13783048};
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:0000250|UniProtKB:Q9JLZ3}.
CC -!- SIMILARITY: Belongs to the enoyl-CoA hydratase/isomerase family.
CC {ECO:0000305}.
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DR EMBL; AABR07027053; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07027054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07027055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473977; EDL98065.1; -; Genomic_DNA.
DR RefSeq; XP_006253736.1; XM_006253674.3.
DR AlphaFoldDB; F1LU71; -.
DR SMR; F1LU71; -.
DR IntAct; F1LU71; 6.
DR STRING; 10116.ENSRNOP00000015786; -.
DR jPOST; F1LU71; -.
DR PaxDb; F1LU71; -.
DR PRIDE; F1LU71; -.
DR Ensembl; ENSRNOT00000015786; ENSRNOP00000015786; ENSRNOG00000011684.
DR GeneID; 361215; -.
DR CTD; 549; -.
DR RGD; 1306087; Auh.
DR eggNOG; KOG1679; Eukaryota.
DR GeneTree; ENSGT00940000157484; -.
DR HOGENOM; CLU_009834_7_6_1; -.
DR InParanoid; F1LU71; -.
DR OMA; AMEMIMT; -.
DR OrthoDB; 1123666at2759; -.
DR TreeFam; TF314276; -.
DR Reactome; R-RNO-70895; Branched-chain amino acid catabolism.
DR UniPathway; UPA00363; UER00862.
DR PRO; PR:F1LU71; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Proteomes; UP000234681; Chromosome 17.
DR Bgee; ENSRNOG00000011684; Expressed in cerebellum and 19 other tissues.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0003723; F:RNA binding; ISO:RGD.
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; Branched-chain amino acid catabolism; Lyase; Mitochondrion;
KW Reference proteome; RNA-binding; Transit peptide.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q13825"
FT CHAIN 44..315
FT /note="Methylglutaconyl-CoA hydratase, mitochondrial"
FT /id="PRO_0000442770"
FT REGION 81..95
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13825"
FT MOD_RES 76
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 76
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 85
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 89
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 89
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 120
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 120
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 124
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 136
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 180
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 180
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 187
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 187
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
FT MOD_RES 305
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLZ3"
SQ SEQUENCE 315 AA; 33341 MW; 92935E12DE7A7A64 CRC64;
MAAAAAPGAL GALSAGRVRL VAACCARLGS AAWARGTAPR RGYSSEVKTE DELRVRHLEE
ENRGIVVLGI NRAYGKNSLS KNLLKMLSKA VDALKSDKKV RTIIIRSEVP GIFCAGADLK
ERAKMHSSEV GPFVSKIRAV INDIANLPVP TIAAIDGLAL GGGLELALAC DIRVAASSAK
MGLVETKLAI IPGGGGTQRL PRAIGMALAK ELIFSARVLD GQEAKAVGLI SHVLEQNQEG
DAAYRKALDL AREFLPQGPV AMRVAKLAIN QGMEVDLVTG LAIEEACYAQ TISTKDRLEG
LLAFKEKRPP RYKGE
