ID   ECHP_HUMAN              Reviewed;         723 AA.
AC   Q08426; Q58EZ5;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 3.
DT   07-JUL-2009, entry version 99.
DE   RecName: Full=Peroxisomal bifunctional enzyme;
DE            Short=PBE;
DE            Short=PBFE;
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLY-40; ARG-41; ILE-75;
RP   GLY-325; THR-598 AND PRO-606.
RC   TISSUE=Liver;
RX   MEDLINE=94245181; PubMed=8188243; DOI=10.1006/geno.1994.1013;
RA   Hoefler G., Forstner M., McGuinness M.C., Hulla W., Hiden M.,
RA   Krisper P., Kenner L., Ried T., Lengauer C., Zechner R., Moser H.W.,
RA   Chen G.L.;
RT   "cDNA cloning of the human peroxisomal enoyl-CoA hydratase: 3-
RT   hydroxyacyl-CoA dehydrogenase bifunctional enzyme and localization to
RT   chromosome 3q26.3-3q28: a free left Alu Arm is inserted in the 3'
RT   noncoding region.";
RL   Genomics 19:60-67(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Cherkaoui-Malki M., Surapureddi S., Yeldandi A.V., Rao S.M., Zhu Y.,
RA   Reddy J.K.;
RT   "Structural organization of gene for human peroxisomal enoyl-CoA
RT   hydratase/L-3-hydroxyacyl-CoA dehydrogenase: L-bifunctional enzyme (L-
RT   PBE).";
RL   Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Uterus;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 502-723, AND VARIANTS THR-598 AND
RP   PRO-606.
RC   TISSUE=Liver;
RX   MEDLINE=91337043; PubMed=1651711; DOI=10.1016/0006-291X(91)91003-U;
RA   Chen G.L., Balfe A., Erwa W., Hoefler G., Gaertner J., Aikawa J.,
RA   Chen W.W.;
RT   "Import of human bifunctional enzyme into peroxisomes of human
RT   hepatoma cells in vitro.";
RL   Biochem. Biophys. Res. Commun. 178:1084-1091(1991).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-359, AND MASS
RP   SPECTROMETRY.
RX   PubMed=17287340; DOI=10.1073/pnas.0611217104;
RA   Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
RT   "Global proteomic profiling of phosphopeptides using electron transfer
RT   dissociation tandem mass spectrometry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
RN   [8]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
CC   -!- CATALYTIC ACTIVITY: (3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-
CC       CoA + H(2)O.
CC   -!- CATALYTIC ACTIVITY: (3Z)-dodec-3-enoyl-CoA = (2E)-dodec-2-enoyl-
CC       CoA.
CC   -!- CATALYTIC ACTIVITY: (S)-3-hydroxyacyl-CoA + NAD(+) = 3-oxoacyl-CoA
CC       + NADH.
CC   -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC   -!- SUBUNIT: Monomer.
CC   -!- SUBCELLULAR LOCATION: Peroxisome.
CC   -!- TISSUE SPECIFICITY: Liver and kidney. Lower amounts seen in the
CC       brain.
CC   -!- DISEASE: Absent in patients suffering with peroxisomal disorders
CC       such as Zellweger syndrome, neonatal adrenoleukodystrophy and
CC       infantile Refsum disease.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the enoyl-CoA
CC       hydratase/isomerase family.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the 3-
CC       hydroxyacyl-CoA dehydrogenase family.
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DR   EMBL; L07077; AAA53289.1; -; mRNA.
DR   EMBL; AJ427345; CAD22483.1; -; Genomic_DNA.
DR   EMBL; AJ427346; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AJ427347; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AJ427348; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AJ427349; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AJ427350; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AJ427351; CAD22483.1; JOINED; Genomic_DNA.
DR   EMBL; AK223460; BAD97180.1; -; mRNA.
DR   EMBL; CH471052; EAW78229.1; -; Genomic_DNA.
DR   EMBL; BC038948; AAH38948.1; -; mRNA.
DR   EMBL; BC110460; AAI10461.1; -; mRNA.
DR   EMBL; S50245; AAB19482.1; -; mRNA.
DR   IPI; IPI00216164; -.
DR   PIR; A49613; A49613.
DR   RefSeq; NP_001957.2; -.
DR   UniGene; Hs.429879; -.
DR   HSSP; P14604; 1MJ3.
DR   SMR; Q08426; 262-717.
DR   PhosphoSite; Q08426; -.
DR   PRIDE; Q08426; -.
DR   Ensembl; ENSG00000113790; Homo sapiens.
DR   GeneID; 1962; -.
DR   GeneCards; GC03M186391; -.
DR   HGNC; HGNC:3247; EHHADH.
DR   MIM; 607037; gene.
DR   Orphanet; 50812; Zellweger-like syndrome, without peroxisomal anomalies.
DR   PharmGKB; PA27682; -.
DR   HOGENOM; Q08426; -.
DR   HOVERGEN; Q08426; -.
DR   OMA; Q08426; QRNEKPV.
DR   BRENDA; 1.1.1.35; 247.
DR   BRENDA; 4.2.1.17; 247.
DR   BRENDA; 5.3.3.8; 247.
DR   DrugBank; DB00157; NADH.
DR   ArrayExpress; Q08426; -.
DR   Bgee; Q08426; -.
DR   CleanEx; HS_EHHADH; -.
DR   GermOnline; ENSG00000113790; Homo sapiens.
DR   GO; GO:0005777; C:peroxisome; TAS:ProtInc.
DR   GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; TAS:ProtInc.
DR   GO; GO:0050662; F:coenzyme binding; IEA:InterPro.
DR   GO; GO:0004165; F:dodecenoyl-CoA delta-isomerase activity; IEA:EC.
DR   GO; GO:0004300; F:enoyl-CoA hydratase activity; TAS:ProtInc.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
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; IPR001753; Crotonase_core.
DR   InterPro; IPR013328; DH_multihelical.
DR   InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR   InterPro; IPR016040; NAD(P)-bd_dom.
DR   Gene3D; G3DSA:3.40.50.720; NAD(P)-bd; 1.
DR   Gene3D; G3DSA:1.10.1040.10; Opine_DH; 2.
DR   Pfam; PF00725; 3HCDH; 2.
DR   Pfam; PF02737; 3HCDH_N; 1.
DR   Pfam; PF00378; ECH; 1.
DR   PROSITE; PS00067; 3HCDH; 1.
DR   PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Fatty acid metabolism; Isomerase; Lipid metabolism;
KW   Lyase; Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome;
KW   Phosphoprotein; Polymorphism.
FT   INIT_MET      1      1       Removed (By similarity).
FT   CHAIN         2    723       Peroxisomal bifunctional enzyme.
FT                                /FTId=PRO_0000109247.
FT   REGION        2    282       Enoyl-CoA hydratase / isomerase.
FT   REGION      283    572       3-hydroxyacyl-CoA dehydrogenase.
FT   MOTIF       721    723       Microbody targeting signal.
FT   BINDING     101    101       Substrate; via amide nitrogen (By
FT                                similarity).
FT   SITE        124    124       Important for catalytic activity (By
FT                                similarity).
FT   MOD_RES     359    359       Phosphoserine.
FT   VARIANT      40     40       V -> G (in dbSNP:rs1062551).
FT                                /FTId=VAR_054329.
FT   VARIANT      41     41       I -> R (in dbSNP:rs1062552).
FT                                /FTId=VAR_054330.
FT   VARIANT      75     75       T -> I (in dbSNP:rs1062553).
FT                                /FTId=VAR_047132.
FT   VARIANT     274    274       A -> T (in dbSNP:rs2302819).
FT                                /FTId=VAR_047133.
FT   VARIANT     325    325       A -> G (in dbSNP:rs1062555).
FT                                /FTId=VAR_054331.
FT   VARIANT     598    598       K -> T (in dbSNP:rs1042437).
FT                                /FTId=VAR_054332.
FT   VARIANT     606    606       T -> P (in dbSNP:rs1042438).
FT                                /FTId=VAR_047134.
FT   VARIANT     685    685       Q -> K (in dbSNP:rs11919970).
FT                                /FTId=VAR_047135.
FT   VARIANT     715    715       L -> S (in dbSNP:rs11927618).
FT                                /FTId=VAR_047136.
FT   CONFLICT    117    117       E -> D (in Ref. 1; AAA53289).
FT   CONFLICT    656    657       WP -> CA (in Ref. 1; AAA53289 and 6;
FT                                AAB19482).
SQ   SEQUENCE   723 AA;  79495 MW;  FC3B44B030A7BCBD CRC64;
     MAEYTRLHNA LALIRLRNPP VNAISTTLLR DIKEGLQKAV IDHTIKAIVI CGAEGKFSAG
     ADIRGFSAPR TFGLTLGHVV DEIQRNEKPV VAAIQGMAFG GGLELALGCH YRIAHAEAQV
     GLPEVTLGLL PGARGTQLLP RLTGVPAALD LITSGRRILA DEALKLGILD KVVNSDPVEE
     AIRFAQRVSD QPLESRRLCN KPIQSLPNMD SIFSEALLKM RRQHPGCLAQ EACVRAVQAA
     VQYPYEVGIK KEEELFLYLL QSGQARALQY AFFAERKANK WSTPSGASWK TASARPVSSV
     GVVGLGTMGR GIVISFARAR IPVIAVDSDK NQLATANKMI TSVLEKEASK MQQSGHPWSG
     PKPRLTSSVK ELGGVDLVIE AVFEEMSLKK QVFAELSAVC KPEAFLCTNT SALDVDEIAS
     STDRPHLVIG THFFSPAHVM KLLEVIPSQY SSPTTIATVM NLSKKIKKIG VVVGNCFGFV
     GNRMLNPYYN QAYFLLEEGS KPEEVDQVLE EFGFKMGPFR VSDLAGLDVG WKSRKGQGLT
     GPTLLPGTPA RKRGNRRYCP IPDVLCELGR FGQKTGKGWY QYDKPLGRIH KPDPWLSKFL
     SRYRKTHHIE PRTISQDEIL ERCLYSLINE AFRILGEGIA ASPEHIDVVY LHGYGWPRHK
     GGPMFYASTV GLPTVLEKLQ KYYRQNPDIP QLEPSDYLKK LASQGNPPLK EWQSLAGSPS
     SKL
//