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peroxisomal multifunctional enzyme type 2; MFE-2; 17-beta-hydroxysteroid dehydrogenase 4; 17-beta-HSD 4; D-bifunctional protein; DBP; multifunctional protein 2; MPF-2; contains: (3R)-hydroxyacyl-CoA dehydrogenase; enoyl-CoA hydratase 2; 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase (HSD17B4, EDH17B4)
Function:
1) bifunctional enzyme acting on peroxisomal beta-oxidation pathway for fatty acids
2) catalyzes formation of 3-ketoacyl-CoA intermediates from both straight-chain & 2-methyl-branched-chain fatty acids
3) fatty acid beta-oxidation cycle, steps 2 & 3
Kinetic parameters:
- KM=10 uM for D-3-hydroxy-octanoyl-CoA
- KM=13 uM for NAD
- KM=2.7 uM for 3-ketooctanoyl-CoA
- KM=5.4 uM for NADH
- Vmax=8.8 umol/min/mg enzyme
Structure:
- homodimer
- belongs to the short-chain dehydrogenases/reductases (SDR) family
- contains 1 MaoC-like domain
- contains 1 SCP2 domain
Compartment: peroxisome
Expression: highest in liver, heart, prostate, testis
Pathology:
- defects in HSD17B4 are a cause of D-bifunctional protein deficiency
- defects in HSD17B4 are the cause of Perrault syndrome
Laboratory:
- HSD17B4 gene mutation
Note:
- HSD17B4 is found both as a full length peptide & in a cleaved peptide
General
3-OH acyl CoA dehydrogenase
acyl CoA dehydrogenase
hydro-lyase, hydratase or dehydratase
multifunctional enzyme
phosphoprotein
Properties
SIZE: entity length = 736 aa
MW = 80 kD
COMPARTMENT: peroxisome
MOTIF: (3R)-hydroxyacyl-CoA dehydrogenase {2-305}
MOTIF: Ser phosphorylation site {S3}
cofactor-binding site [21-21]
COFACTOR-BOUND: NAD
cofactor-binding site [40-40]
COFACTOR-BOUND: NAD
cofactor-binding site [75-76]
COFACTOR-BOUND: NAD
cofactor-binding site [99-99]
COFACTOR-BOUND: NAD
binding site
SITE: 151-151
FOR-BINDING-OF: Substrate
cofactor-binding site [164-168]
COFACTOR-BOUND: NAD
tyrosine residue {Y164}
cofactor-binding site [196-199]
COFACTOR-BOUND: NAD
Thr phosphorylation site {T265}
Thr phosphorylation site {T292}
Ser phosphorylation site {S294}
Ser phosphorylation site {S304}
Ser phosphorylation site {S309}
Thr phosphorylation site {T317}
Ser phosphorylation site {S318}
Enoyl-CoA hydratase 2 {322-622}
MOTIF: (3R)-3-hydroxydecanoyl-CoA binding {406-407}
binding site
SITE: 435-435
FOR-BINDING-OF: (3R)-3-hydroxydecanoyl-CoA
MaoC-like {484-600}
(3R)-3-hydroxydecanoyl-CoA binding {510-515}
binding site
SITE: 533-533
FOR-BINDING-OF: (3R)-3-hydroxydecanoyl-CoA
binding site
SITE: 563-563
FOR-BINDING-OF: (3R)-3-hydroxydecanoyl-CoA
Thr phosphorylation site {T608}
SCP2 {624-736}
MOTIF: binding site
SITE: 706-706
FOR-BINDING-OF: Substrate
binding site
SITE: 724-724
FOR-BINDING-OF: Substrate
microbody-targeting signal {734-736}
Database Correlations
OMIM correlations
MORBIDMAP 601860
UniProt P51659
PFAM correlations
Entrez Gene 3295
Kegg hsa:3295
ENZYME correlations
References
- UniProt :accession P51659
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/HSD17B4