ECHP_PONAB
ID ECHP_PONAB Reviewed; 723 AA.
AC Q5R5M8;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
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; Synonyms=ECHD;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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-346. 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; CR860829; CAH92938.1; -; mRNA.
DR RefSeq; NP_001127606.1; NM_001134134.1.
DR AlphaFoldDB; Q5R5M8; -.
DR SMR; Q5R5M8; -.
DR STRING; 9601.ENSPPYP00000016064; -.
DR PRIDE; Q5R5M8; -.
DR GeneID; 100174685; -.
DR KEGG; pon:100174685; -.
DR CTD; 1962; -.
DR eggNOG; KOG1683; Eukaryota.
DR InParanoid; Q5R5M8; -.
DR OrthoDB; 219667at2759; -.
DR UniPathway; UPA00659; -.
DR Proteomes; UP000001595; Unplaced.
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; IPR006180; 3-OHacyl-CoA_DH_CS.
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; PS00067; 3HCDH; 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; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..723
FT /note="Peroxisomal bifunctional enzyme"
FT /id="PRO_0000353181"
FT REGION 1..282
FT /note="Enoyl-CoA hydratase / isomerase"
FT REGION 283..572
FT /note="3-hydroxyacyl-CoA dehydrogenase"
FT REGION 699..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 721..723
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 706..723
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 104
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 124
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 165
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 165
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 219
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 219
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 250
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 280
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 290
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 350
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 464
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 532
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 548
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 577
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 584
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 584
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 591
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 591
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 710
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 710
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 718
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08426"
FT MOD_RES 722
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
SQ SEQUENCE 723 AA; 79481 MW; 8CAE3A1578A147C6 CRC64;
MAEYTRLHNA LALIRLRNPP VNAISTALLR DIKEGLQKAV IDHTIKAIVI CGAEGKFSAG
ADIHGFSAPR TFGFTLGHVV DEIQRNEKPV VAAIQGMAFG GGLELALGCH YRIAHSEAQV
GLPEVTLGLL PGARGTQLLP RLIGVPAALD LITSGRHILA DEALKLGILD KVVNSDPVEE
AIRFAQRVSD QPLESRRLCN KPIQSLPNMD TIFSEALLKM RRQHPGCLAQ EACVRAVQAA
VQYPYEVGVK KEEELFLYLF QSGQARALQY AFLAERKANK WSTPSGASWK TASARPVSSV
GVVGLGTMGR GIVISFARAR IPVIAVDSDK NQLATANKMI TSVLEKEASK MQQSGHPWSG
PKPRLTSSMK ELGGVDLVIE AVFEEMSLKK QVFAELSAIC KPEAFLCTNT SALDVDEIAS
STDRPHLVIG THFFSPAHVM KLLEVIPSQY SSPTTIATVM NLSKKIKKIG VVVGNCFGFV
GNRMLNPYYN QAYFLLEEGS KPEEVDQVLE EFGFKMGPFR VSDLAGLDVG WKSRKGQGLT
GPTLPPGTPA RKRGNRRYCP IPDVLCELGR FGQKTGKGWY QYDKPLGRIH KADPWLSKFL
SQYRETHHIE PRTISQDEIL ERCLYSLINE AFRILGEGIA ASPEHIDVVY LHGYGWPRHK
GGPMFYASTV GLPTVLEKLQ KYYRQNPDIP QLEPSDYLKK LASQGNPPQK EWQSLAGSPS
SKL
