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Protein

Peroxisomal bifunctional enzyme

Gene

EHHADH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Miscellaneous

Absent in patients suffering with peroxisomal disorders such as Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease.

Catalytic activityi

(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O.
A (3Z)-alk-3-enoyl-CoA = a (2E)-alk-2-enoyl-CoA.
A (3E)-alk-3-enoyl-CoA = a (2E)-alk-2-enoyl-CoA.
(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.

Activity regulationi

Enzyme activity enhanced by acetylation.1 Publication

Pathwayi: fatty acid beta-oxidation

This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei101Substrate; via amide nitrogenBy similarity1
Sitei104Important for catalytic activityBy similarity1
Sitei124Important for catalytic activityBy similarity1

GO - Molecular functioni

  • 3-hydroxyacyl-CoA dehydrogenase activity Source: GO_Central
  • dodecenoyl-CoA delta-isomerase activity Source: UniProtKB-EC
  • enoyl-CoA hydratase activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • long-chain-enoyl-CoA hydratase activity Source: Reactome
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Lyase, Multifunctional enzyme, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS03720-MONOMER
ReactomeiR-HSA-390247 Beta-oxidation of very long chain fatty acids
R-HSA-9033241 Peroxisomal protein import
SABIO-RKiQ08426
UniPathwayi
UPA00659

Chemistry databases

SwissLipidsiSLP:000000543

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxisomal bifunctional enzyme
Short name:
PBE
Short name:
PBFE
Including the following 2 domains:
Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase (EC:4.2.1.17, EC:5.3.3.8)
3-hydroxyacyl-CoA dehydrogenase (EC:1.1.1.35)
Gene namesi
Name:EHHADH
Synonyms:ECHD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000113790.10
HGNCiHGNC:3247 EHHADH
MIMi607037 gene
neXtProtiNX_Q08426

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Peroxisome

Pathology & Biotechi

Involvement in diseasei

Fanconi renotubular syndrome 3 (FRTS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency.
See also OMIM:615605
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0709493E → K in FRTS3; the mutant is mistargeted to mitochondria; results in impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids across the epithelium of renal proximal tubular cells. 1 PublicationCorresponds to variant dbSNP:rs398124646EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi165K → Q: Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-171; Q-346 and Q-584. 1 Publication1
Mutagenesisi171K → Q: Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-346 and Q-584. 1 Publication1
Mutagenesisi346K → Q: Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-171 and Q-584. 1 Publication1
Mutagenesisi584K → Q: Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-171 and Q-346. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1962
51807
MalaCardsiEHHADH
MIMi615605 phenotype
OpenTargetsiENSG00000113790
Orphaneti300 Bifunctional enzyme deficiency
3337 Primary Fanconi syndrome
PharmGKBiPA27682

Chemistry databases

DrugBankiDB00157 NADH

Polymorphism and mutation databases

BioMutaiEHHADH
DMDMi223590229

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001092471 – 723Peroxisomal bifunctional enzymeAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38N6-succinyllysineBy similarity1
Modified residuei165N6-acetyllysine; alternate1 Publication1
Modified residuei165N6-succinyllysine; alternateBy similarity1
Modified residuei171N6-acetyllysine1 Publication1
Modified residuei219N6-acetyllysine; alternateBy similarity1
Modified residuei219N6-succinyllysine; alternateBy similarity1
Modified residuei250N6-acetyllysineBy similarity1
Modified residuei280N6-succinyllysineBy similarity1
Modified residuei290N6-succinyllysineBy similarity1
Modified residuei346N6-acetyllysine1 Publication1
Modified residuei350N6-acetyllysineBy similarity1
Modified residuei464N6-acetyllysineBy similarity1
Modified residuei532N6-succinyllysineBy similarity1
Modified residuei548PhosphothreonineCombined sources1
Modified residuei577N6-succinyllysineBy similarity1
Modified residuei584N6-acetyllysine; alternateCombined sources1 Publication1
Modified residuei584N6-succinyllysine; alternateBy similarity1
Modified residuei591N6-acetyllysine; alternateBy similarity1
Modified residuei591N6-succinyllysine; alternateBy similarity1
Modified residuei710N6-acetyllysine; alternateBy similarity1
Modified residuei710N6-succinyllysine; alternateBy similarity1
Modified residuei718PhosphoserineCombined sources1
Modified residuei722N6-succinyllysineBy similarity1

Post-translational modificationi

Acetylated, leading to enhanced enzyme activity. Acetylation is enhanced by up to 80% after treatment either with trichostin A (TSA) or with nicotinamide (NAM) with highest increase on Lys-346. Acetylation and enzyme activity increased by about 1.5% on addition of fatty acids.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ08426
MaxQBiQ08426
PaxDbiQ08426
PeptideAtlasiQ08426
PRIDEiQ08426
ProteomicsDBi58608
58609 [Q08426-2]

PTM databases

iPTMnetiQ08426
PhosphoSitePlusiQ08426

Expressioni

Tissue specificityi

Liver and kidney. Strongly expressed in the terminal segments of the proximal tubule. Lower amounts seen in the brain.2 Publications

Gene expression databases

BgeeiENSG00000113790 Expressed in 197 organ(s), highest expression level in liver
CleanExiHS_EHHADH
ExpressionAtlasiQ08426 baseline and differential
GenevisibleiQ08426 HS

Organism-specific databases

HPAiHPA036401
HPA042021

Interactioni

Subunit structurei

Monomer.

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108282, 31 interactors
IntActiQ08426, 97 interactors
STRINGi9606.ENSP00000231887

Structurei

3D structure databases

ProteinModelPortaliQ08426
SMRiQ08426
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 282Enoyl-CoA hydratase / isomeraseAdd BLAST282
Regioni283 – 5723-hydroxyacyl-CoA dehydrogenaseAdd BLAST290

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi721 – 723Microbody targeting signal3

Sequence similaritiesi

In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.Curated
In the C-terminal section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.Curated

Phylogenomic databases

eggNOGiKOG1683 Eukaryota
COG1024 LUCA
COG1250 LUCA
GeneTreeiENSGT00880000137923
HOGENOMiHOG000261347
HOVERGENiHBG104990
InParanoidiQ08426
KOiK07514
OMAiIDLCMIL
OrthoDBiEOG091G082G
PhylomeDBiQ08426
TreeFamiTF316708

Family and domain databases

InterProiView protein in InterPro
IPR006180 3-OHacyl-CoA_DH_CS
IPR006176 3-OHacyl-CoA_DH_NAD-bd
IPR006108 3HC_DH_C
IPR008927 6-PGluconate_DH-like_C_sf
IPR029045 ClpP/crotonase-like_dom_sf
IPR018376 Enoyl-CoA_hyd/isom_CS
IPR001753 Enoyl-CoA_hydra/iso
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF00725 3HCDH, 2 hits
PF02737 3HCDH_N, 1 hit
PF00378 ECH_1, 1 hit
SUPFAMiSSF48179 SSF48179, 2 hits
SSF51735 SSF51735, 1 hit
SSF52096 SSF52096, 1 hit
PROSITEiView protein in PROSITE
PS00067 3HCDH, 1 hit
PS00166 ENOYL_COA_HYDRATASE, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q08426-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAEYTRLHNA LALIRLRNPP VNAISTTLLR DIKEGLQKAV IDHTIKAIVI
60 70 80 90 100
CGAEGKFSAG ADIRGFSAPR TFGLTLGHVV DEIQRNEKPV VAAIQGMAFG
110 120 130 140 150
GGLELALGCH YRIAHAEAQV GLPEVTLGLL PGARGTQLLP RLTGVPAALD
160 170 180 190 200
LITSGRRILA DEALKLGILD KVVNSDPVEE AIRFAQRVSD QPLESRRLCN
210 220 230 240 250
KPIQSLPNMD SIFSEALLKM RRQHPGCLAQ EACVRAVQAA VQYPYEVGIK
260 270 280 290 300
KEEELFLYLL QSGQARALQY AFFAERKANK WSTPSGASWK TASARPVSSV
310 320 330 340 350
GVVGLGTMGR GIVISFARAR IPVIAVDSDK NQLATANKMI TSVLEKEASK
360 370 380 390 400
MQQSGHPWSG PKPRLTSSVK ELGGVDLVIE AVFEEMSLKK QVFAELSAVC
410 420 430 440 450
KPEAFLCTNT SALDVDEIAS STDRPHLVIG THFFSPAHVM KLLEVIPSQY
460 470 480 490 500
SSPTTIATVM NLSKKIKKIG VVVGNCFGFV GNRMLNPYYN QAYFLLEEGS
510 520 530 540 550
KPEEVDQVLE EFGFKMGPFR VSDLAGLDVG WKSRKGQGLT GPTLLPGTPA
560 570 580 590 600
RKRGNRRYCP IPDVLCELGR FGQKTGKGWY QYDKPLGRIH KPDPWLSKFL
610 620 630 640 650
SRYRKTHHIE PRTISQDEIL ERCLYSLINE AFRILGEGIA ASPEHIDVVY
660 670 680 690 700
LHGYGWPRHK GGPMFYASTV GLPTVLEKLQ KYYRQNPDIP QLEPSDYLKK
710 720
LASQGNPPLK EWQSLAGSPS SKL
Length:723
Mass (Da):79,495
Last modified:February 10, 2009 - v3
Checksum:iFC3B44B030A7BCBD
GO
Isoform 2 (identifier: Q08426-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.

Show »
Length:627
Mass (Da):69,154
Checksum:iF1F1A30F0E89ED98
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JJE0C9JJE0_HUMAN
Peroxisomal bifunctional enzyme
EHHADH
76Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti117E → D in AAA53289 (PubMed:8188243).Curated1
Sequence conflicti656 – 657WP → CA in AAA53289 (PubMed:8188243).Curated2
Sequence conflicti656 – 657WP → CA in AAB19482 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0709493E → K in FRTS3; the mutant is mistargeted to mitochondria; results in impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids across the epithelium of renal proximal tubular cells. 1 PublicationCorresponds to variant dbSNP:rs398124646EnsemblClinVar.1
Natural variantiVAR_05432940V → G1 PublicationCorresponds to variant dbSNP:rs1062551Ensembl.1
Natural variantiVAR_05433041I → R1 PublicationCorresponds to variant dbSNP:rs1062552Ensembl.1
Natural variantiVAR_04713275T → I1 PublicationCorresponds to variant dbSNP:rs1062553Ensembl.1
Natural variantiVAR_047133274A → T1 PublicationCorresponds to variant dbSNP:rs2302819Ensembl.1
Natural variantiVAR_054331325A → G1 PublicationCorresponds to variant dbSNP:rs1062555Ensembl.1
Natural variantiVAR_054332598K → T2 PublicationsCorresponds to variant dbSNP:rs1042437Ensembl.1
Natural variantiVAR_047134606T → P2 PublicationsCorresponds to variant dbSNP:rs1042438Ensembl.1
Natural variantiVAR_047135685Q → K. Corresponds to variant dbSNP:rs11919970Ensembl.1
Natural variantiVAR_047136715L → S. Corresponds to variant dbSNP:rs11927618Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0428111 – 96Missing in isoform 2. 1 PublicationAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07077 mRNA Translation: AAA53289.1
AJ427345
, AJ427346, AJ427347, AJ427348, AJ427349, AJ427350, AJ427351 Genomic DNA Translation: CAD22483.1
AK291798 mRNA Translation: BAF84487.1
AK223460 mRNA Translation: BAD97180.1
AK301521 mRNA Translation: BAG63025.1
AC007934 Genomic DNA No translation available.
AC128680 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78229.1
CH471052 Genomic DNA Translation: EAW78230.1
BC038948 mRNA Translation: AAH38948.1
BC110460 mRNA Translation: AAI10461.1
S50245 mRNA Translation: AAB19482.1
CCDSiCCDS33901.1 [Q08426-1]
CCDS54694.1 [Q08426-2]
PIRiA49613
RefSeqiNP_001159887.1, NM_001166415.1 [Q08426-2]
NP_001957.2, NM_001966.3 [Q08426-1]
XP_011510819.1, XM_011512517.1
UniGeneiHs.429879

Genome annotation databases

EnsembliENST00000231887; ENSP00000231887; ENSG00000113790 [Q08426-1]
ENST00000456310; ENSP00000387746; ENSG00000113790 [Q08426-2]
GeneIDi1962
KEGGihsa:1962
UCSCiuc003fpf.3 human [Q08426-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07077 mRNA Translation: AAA53289.1
AJ427345
, AJ427346, AJ427347, AJ427348, AJ427349, AJ427350, AJ427351 Genomic DNA Translation: CAD22483.1
AK291798 mRNA Translation: BAF84487.1
AK223460 mRNA Translation: BAD97180.1
AK301521 mRNA Translation: BAG63025.1
AC007934 Genomic DNA No translation available.
AC128680 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78229.1
CH471052 Genomic DNA Translation: EAW78230.1
BC038948 mRNA Translation: AAH38948.1
BC110460 mRNA Translation: AAI10461.1
S50245 mRNA Translation: AAB19482.1
CCDSiCCDS33901.1 [Q08426-1]
CCDS54694.1 [Q08426-2]
PIRiA49613
RefSeqiNP_001159887.1, NM_001166415.1 [Q08426-2]
NP_001957.2, NM_001966.3 [Q08426-1]
XP_011510819.1, XM_011512517.1
UniGeneiHs.429879

3D structure databases

ProteinModelPortaliQ08426
SMRiQ08426
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108282, 31 interactors
IntActiQ08426, 97 interactors
STRINGi9606.ENSP00000231887

Chemistry databases

DrugBankiDB00157 NADH
SwissLipidsiSLP:000000543

PTM databases

iPTMnetiQ08426
PhosphoSitePlusiQ08426

Polymorphism and mutation databases

BioMutaiEHHADH
DMDMi223590229

Proteomic databases

EPDiQ08426
MaxQBiQ08426
PaxDbiQ08426
PeptideAtlasiQ08426
PRIDEiQ08426
ProteomicsDBi58608
58609 [Q08426-2]

Protocols and materials databases

DNASUi1962
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000231887; ENSP00000231887; ENSG00000113790 [Q08426-1]
ENST00000456310; ENSP00000387746; ENSG00000113790 [Q08426-2]
GeneIDi1962
KEGGihsa:1962
UCSCiuc003fpf.3 human [Q08426-1]

Organism-specific databases

CTDi1962
DisGeNETi1962
51807
EuPathDBiHostDB:ENSG00000113790.10
GeneCardsiEHHADH
HGNCiHGNC:3247 EHHADH
HPAiHPA036401
HPA042021
MalaCardsiEHHADH
MIMi607037 gene
615605 phenotype
neXtProtiNX_Q08426
OpenTargetsiENSG00000113790
Orphaneti300 Bifunctional enzyme deficiency
3337 Primary Fanconi syndrome
PharmGKBiPA27682
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1683 Eukaryota
COG1024 LUCA
COG1250 LUCA
GeneTreeiENSGT00880000137923
HOGENOMiHOG000261347
HOVERGENiHBG104990
InParanoidiQ08426
KOiK07514
OMAiIDLCMIL
OrthoDBiEOG091G082G
PhylomeDBiQ08426
TreeFamiTF316708

Enzyme and pathway databases

UniPathwayi
UPA00659

BioCyciMetaCyc:HS03720-MONOMER
ReactomeiR-HSA-390247 Beta-oxidation of very long chain fatty acids
R-HSA-9033241 Peroxisomal protein import
SABIO-RKiQ08426

Miscellaneous databases

GenomeRNAii1962
PROiPR:Q08426
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113790 Expressed in 197 organ(s), highest expression level in liver
CleanExiHS_EHHADH
ExpressionAtlasiQ08426 baseline and differential
GenevisibleiQ08426 HS

Family and domain databases

InterProiView protein in InterPro
IPR006180 3-OHacyl-CoA_DH_CS
IPR006176 3-OHacyl-CoA_DH_NAD-bd
IPR006108 3HC_DH_C
IPR008927 6-PGluconate_DH-like_C_sf
IPR029045 ClpP/crotonase-like_dom_sf
IPR018376 Enoyl-CoA_hyd/isom_CS
IPR001753 Enoyl-CoA_hydra/iso
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF00725 3HCDH, 2 hits
PF02737 3HCDH_N, 1 hit
PF00378 ECH_1, 1 hit
SUPFAMiSSF48179 SSF48179, 2 hits
SSF51735 SSF51735, 1 hit
SSF52096 SSF52096, 1 hit
PROSITEiView protein in PROSITE
PS00067 3HCDH, 1 hit
PS00166 ENOYL_COA_HYDRATASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiECHP_HUMAN
AccessioniPrimary (citable) accession number: Q08426
Secondary accession number(s): A8K6Y3
, B4DWG3, D3DNU0, Q58EZ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: February 10, 2009
Last modified: October 10, 2018
This is version 189 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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