ECHP_CAVPO
ID ECHP_CAVPO Reviewed; 726 AA.
AC P55100;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Peroxisomal bifunctional enzyme;
DE Short=PBE;
DE Short=PBFE;
DE AltName: Full=Multifunctional enzyme 1;
DE Short=MFE1;
DE Includes:
DE RecName: Full=Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase;
DE EC=4.2.1.17;
DE EC=5.3.3.8;
DE Includes:
DE RecName: Full=3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.35;
GN Name=EHHADH;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8549802; DOI=10.1016/0014-5793(95)01425-x;
RA Caira F., Cherkaoui-Malki M., Hoefler G., Latruffe N.;
RT "Cloning and tissue expression of two cDNAs encoding the peroxisomal 2-
RT enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in the guinea pig
RT liver.";
RL FEBS Lett. 378:57-60(1996).
CC -!- FUNCTION: Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA
CC hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-
CC CoA isomerase activities. Catalyzes two of the four reactions of the
CC long chain fatty acids peroxisomal beta-oxidation pathway (By
CC similarity). Can also use branched-chain fatty acids such as 2-methyl-
CC 2E-butenoyl-CoA as a substrate, which is hydrated into (2S,3S)-3-
CC hydroxy-2-methylbutanoyl-CoA (By similarity). Optimal isomerase for 2,5
CC double bonds into 3,5 form isomerization in a range of enoyl-CoA
CC species. Also able to isomerize both 3-cis and 3-trans double bonds
CC into the 2-trans form in a range of enoyl-CoA species (By similarity).
CC Regulates the amount of medium-chain dicarboxylic fatty acids which are
CC essential regulators of all fatty acid oxidation pathways (By
CC similarity). Also involved in the degradation of long-chain
CC dicarboxylic acids through peroxisomal beta-oxidation (By similarity).
CC {ECO:0000250|UniProtKB:P07896, ECO:0000250|UniProtKB:Q08426,
CC ECO:0000250|UniProtKB:Q9DBM2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:58856; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16106;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521,
CC ChEBI:CHEBI:137480; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20725;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3Z)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45900, ChEBI:CHEBI:85097, ChEBI:CHEBI:85489;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45901;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45229;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA = (2E)-2-methylbut-2-
CC enoyl-CoA + H2O; Xref=Rhea:RHEA:31119, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57312, ChEBI:CHEBI:57337;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31121;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31163, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenedioyl-CoA + H2O = (3S)-hydroxyhexadecanedioyl-
CC CoA; Xref=Rhea:RHEA:40259, ChEBI:CHEBI:15377, ChEBI:CHEBI:77075,
CC ChEBI:CHEBI:77080; Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40260;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanedioyl-CoA + NAD(+) = 3-
CC oxohexadecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40267,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:77080, ChEBI:CHEBI:77081;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40268;
CC Evidence={ECO:0000250|UniProtKB:Q08426};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-tetradecadienoyl-CoA = (2E,5Z)-tetradecadienoyl-CoA;
CC Xref=Rhea:RHEA:47464, ChEBI:CHEBI:71586, ChEBI:CHEBI:87701;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47466;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-octadienoyl-CoA = (2E,5Z)-octadienoyl-CoA;
CC Xref=Rhea:RHEA:49932, ChEBI:CHEBI:85108, ChEBI:CHEBI:131990;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:49934;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-decenoyl-CoA = (2E)-decenoyl-CoA; Xref=Rhea:RHEA:45752,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:84793;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45753;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3Z)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45748,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:85415;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45749;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45736,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:84790;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45737;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31191, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:62616; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31193;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:30547, ChEBI:CHEBI:15377, ChEBI:CHEBI:62075,
CC ChEBI:CHEBI:62077; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30549;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- ACTIVITY REGULATION: Enzyme activity enhanced by acetylation.
CC {ECO:0000250|UniProtKB:Q08426}.
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:Q08426}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P07896}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:Q08426}.
CC -!- PTM: Acetylated, leading to enhanced enzyme activity. Acetylation is
CC enhanced by up to 80% after treatment either with trichostin A (TSA) or
CC with nicotinamide (NAM) with highest increase on Lys-348. Acetylation
CC and enzyme activity increased by about 1.5% on addition of fatty acids.
CC {ECO:0000250|UniProtKB:Q08426}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the enoyl-CoA
CC hydratase/isomerase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the 3-hydroxyacyl-CoA
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; X92742; CAA63403.1; -; mRNA.
DR EMBL; X85112; CAA59431.1; -; mRNA.
DR PIR; S68697; S57651.
DR RefSeq; NP_001166417.1; NM_001172946.1.
DR AlphaFoldDB; P55100; -.
DR SMR; P55100; -.
DR STRING; 10141.ENSCPOP00000019312; -.
DR GeneID; 100135519; -.
DR KEGG; cpoc:100135519; -.
DR eggNOG; KOG1683; Eukaryota.
DR InParanoid; P55100; -.
DR OrthoDB; 219667at2759; -.
DR UniPathway; UPA00659; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0004165; F:delta(3)-delta(2)-enoyl-CoA isomerase activity; ISS:UniProtKB.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; ISS:UniProtKB.
DR GO; GO:0016863; F:intramolecular oxidoreductase activity, transposing C=C bonds; ISS:UniProtKB.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISS:UniProtKB.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
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; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 2.
DR Pfam; PF02737; 3HCDH_N; 1.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF48179; SSF48179; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome;
KW Reference proteome.
FT CHAIN 1..726
FT /note="Peroxisomal bifunctional enzyme"
FT /id="PRO_0000109246"
FT REGION 1..284
FT /note="Enoyl-CoA hydratase / isomerase"
FT REGION 285..575
FT /note="3-hydroxyacyl-CoA dehydrogenase"
FT REGION 352..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 724..726
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 352..367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 103
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 106
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 126
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 38
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 167
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 167
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 185
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 221
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 221
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 282
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 292
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 333
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 348
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 352
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 467
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 535
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 587
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 587
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 594
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 594
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 713
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 713
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 725
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
SQ SEQUENCE 726 AA; 79375 MW; F1702122D62C5FF3 CRC64;
MAEYLRLPHS LALIRLRNPP VNAISPAVIH GIKEGLQKAM SDYTIKGIVI SGANNIFCAG
ADIHGFSAPL SFGTGSGLGP IVDEMQRYEK PVVAAIQGMA LGGGLELSLG CHYRIAHAEA
RIGFPEVTLG ILPGARGTQL LPRLIGVPAA LDLITSGRHI TAGEALKLGI LDKVVNSAPV
EEAIKFAQKI LNQPLEPRRI LNRPVSSLPN MDAIFGEAVE KMRRQHPGQL APETCVRSVQ
ASVQYPYEGG IMKERELFLN LQHSGQAKAL QYAFFAERSA PKWSTPSGAS WKTAAARPVS
SVGVLGLGTM GRGIAISFAR VGIPVIAVES DPKQLETAQK LITSILEKEA SKSRQQCGQQ
RSGPKPRFSS SMKDLASVDL VVEAVFEDMN LKKRVFAELS AVCKPEAFLC TNTSALDVDE
IATSTNRPQQ VIGTHFFSPA HVMKLLEVIP SRHSSPTTIA TVMDLAKKIK KVAVVVGNCY
GFVGNRMLRS YYEQTNFLLE DGSKPEDIDQ ALEEFGFRMG PFRVSDLAGL DVGWKIRKGQ
GLTGPSLQGT APARKRGNAR YSPIADMLCE LGRFGQKTGQ GWYKYDKPLG RIHKPDPWLS
KFLSEYRETH HIKPRVIGRD EILERCLYAL INEAFRILGE GIAASPEHID VIYLHGYGWP
RHKGGPMFYA ASVGLPTVLE KLQKYYQQNP DIPHLEPCNY LKKLASQGNP PLKEWQSLAG
LPSSKL
