ECHP_DANRE
ID ECHP_DANRE Reviewed; 718 AA.
AC Q6NYL3;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
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; ORFNames=si:dkeyp-30d5.2, zgc:77526;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (FEB-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 straight 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 -!- 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 -!- 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; CR936497; CAP19438.1; -; Genomic_DNA.
DR EMBL; BC066545; AAH66545.1; -; mRNA.
DR RefSeq; NP_996951.1; NM_207068.1.
DR AlphaFoldDB; Q6NYL3; -.
DR SMR; Q6NYL3; -.
DR STRING; 7955.ENSDARP00000093211; -.
DR PaxDb; Q6NYL3; -.
DR PRIDE; Q6NYL3; -.
DR Ensembl; ENSDART00000102434; ENSDARP00000093211; ENSDARG00000070029.
DR GeneID; 100000859; -.
DR KEGG; dre:100000859; -.
DR CTD; 1962; -.
DR ZFIN; ZDB-GENE-040426-2581; ehhadh.
DR eggNOG; KOG1683; Eukaryota.
DR GeneTree; ENSGT00940000157516; -.
DR HOGENOM; CLU_009834_16_3_1; -.
DR InParanoid; Q6NYL3; -.
DR OMA; TGAGWPF; -.
DR OrthoDB; 219667at2759; -.
DR PhylomeDB; Q6NYL3; -.
DR TreeFam; TF316708; -.
DR Reactome; R-DRE-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-DRE-9033241; Peroxisomal protein import.
DR UniPathway; UPA00659; -.
DR PRO; PR:Q6NYL3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 9.
DR Bgee; ENSDARG00000070029; Expressed in liver and 27 other tissues.
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 Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..718
FT /note="Peroxisomal bifunctional enzyme"
FT /id="PRO_0000353182"
FT REGION 2..280
FT /note="Enoyl-CoA hydratase / isomerase"
FT REGION 281..567
FT /note="3-hydroxyacyl-CoA dehydrogenase"
FT MOTIF 716..718
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 123
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
SQ SEQUENCE 718 AA; 78508 MW; EA4DC2FDDCAE95B1 CRC64;
MARYELVKRS VALITLTNPP VNALSSAVRH AISKTMERAL SDPKVTAVVI CGENGRFCGG
ADIREFAGPL RGPPLVPLLD AIEAGEKPVV AAIEGVALGG GFELALVCHY RIAHYKARLG
LPEVTLGILP AAGGTQRLPR LIGIPAALEL ITTGRHVSAQ EALKLGMVDQ VTEQNTCEVA
LEFALKAVGK PLSSRRLSML TTPCPPGLDG IFEAATMQVQ KKARGVMAPL ACVQAVRAAT
LPYSEGIKRE GELMATLFSS GQAQALQYSF FAQRTAEKWT LPSGAQWNNS KPREIQSAAV
IGLGTMGRGI VVSLARVGIS VIAVESEKKL LETGRQMVIG MLERDAKRRG VSASLNLLKF
SLSLQDLKDV DLVIEAVFED MALKKQIFRE LSRVCRPATL LCSNTSGLDV DALADVTDRP
QLVAGMHFFS PAHVMKLLEV VCGPRSSKEA IATAMSLGKR MGKVSVAVGN CPGFVGNRML
MPYLEQATFL LEEGATPQQI DKALEDFGFA MGVFRMSDLA GLDVGWRVRK ESGLTGPDVD
PKDPPRRRQG RKYCPIPDMV CQQGRFGQKT GRGWYMYDKP GDTNAKPDPL IQNLLETYRS
RYGIQPRKIT DQEIIERCLF ALANEGFRIL KDKIAGQPED IDVIYLFGYG FPRHRGGPMF
YASMVGLERV LERLEYYHHA LPDVPHLEPS PLLKKLVARG SPPIQKWREH IKSMHSHL
