P30084 · ECHM_HUMAN
- ProteinEnoyl-CoA hydratase, mitochondrial
- GeneECHS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids290 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-CoA) to the corresponding (3S)-3hydroxyacyl-CoA species through addition of a water molecule to the double bond (PubMed:25125611, PubMed:26251176).
Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:26251176).
Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176).
Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (PubMed:26251176).
Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation (PubMed:25125611, PubMed:26251176).
At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).
Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:26251176).
Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176).
Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (PubMed:26251176).
Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation (PubMed:25125611, PubMed:26251176).
At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).
Catalytic activity
- a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3E)-hexenoyl-CoA = (2E)-hexenoyl-CoAThis reaction proceeds in the forward direction.
- (3S)-3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- 3-hydroxyisovaleryl-CoA = 3-methyl-(2E)-butenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- 3-hydroxypropanoyl-CoA = acryloyl-CoA + H2OThis reaction proceeds in the backward direction.
- 3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (2E)-2-methylpropenoyl-CoA + H2O = (S)-3-hydroxyisobutanoyl-CoAThis reaction proceeds in the forward direction.
- (3S)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2OThis reaction proceeds in the backward direction.
- (3S)-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2OThis reaction proceeds in the backward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
12.75 μM | crotonyl-CoA ((2E)-butenoyl-CoA) | |||||
34.04 μM | acryloyl-CoA | |||||
45.83 μM | 3-Methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) | |||||
57.87 μM | tiglyl-CoA (2-methylcrotonoyl-CoA) |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
54.64 μmol/min/mg | toward crotonyl-CoA | ||||
42.92 μmol/min/mg | toward acryloyl-CoA | ||||
49.02 μmol/min/mg | toward 3-Methylcrotonyl-CoA | ||||
6.66 μmol/min/mg | toward tiglyl-CoA |
Pathway
Lipid metabolism; fatty acid beta-oxidation.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 98-101 | substrate | ||||
Sequence: ADIK | ||||||
Binding site | 141 | substrate | ||||
Sequence: G | ||||||
Site | 164 | Important for catalytic activity | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | 3-hydroxypropionyl-CoA dehydratase activity | |
Molecular Function | crotonyl-CoA hydratase activity | |
Molecular Function | delta(3)-delta(2)-enoyl-CoA isomerase activity | |
Molecular Function | enoyl-CoA hydratase activity | |
Biological Process | branched-chain amino acid catabolic process | |
Biological Process | fatty acid beta-oxidation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameEnoyl-CoA hydratase, mitochondrial
- EC number
- Short namesmECH; mECH1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP30084
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D)
- Note
- DescriptionA severe, autosomal recessive inborn error affecting valine metabolism. Disease features include brain lesions in the basal ganglia, neurodegeneration, delayed psychomotor development, hypotonia, spasticity, and increased lactic acid in serum and cerebral serum fluid.
- See alsoMIM:616277
Natural variants in ECHS1D
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_073373 | 2 | A>V | in ECHS1D; dbSNP:rs587776498 | |
VAR_076185 | 33 | F>S | in ECHS1D | |
VAR_076186 | 54 | R>H | in ECHS1D; dbSNP:rs375266808 | |
VAR_076187 | 59 | N>S | in ECHS1D; decreases significantly enoyl-CoA hydratase activity; decreases significantly protein expression; dbSNP:rs201865375 | |
VAR_076188 | 66 | I>T | in ECHS1D; dbSNP:rs371063211 | |
VAR_076189 | 77 | E>Q | in ECHS1D; dbSNP:rs1426014295 | |
VAR_076190 | 90 | G>R | in ECHS1D; uncertain significance; dbSNP:rs1085307550 | |
VAR_076191 | 132 | A>T | in ECHS1D; dbSNP:rs770931871 | |
VAR_076479 | 138 | A>V | in ECHS1D; decreases enoyl-CoA hydratase activity of 70%; decreases significantly protein expression; dbSNP:rs864309656 | |
VAR_076192 | 150 | D>G | in ECHS1D | |
VAR_073374 | 158 | A>D | in ECHS1D; dbSNP:rs786204001 | |
VAR_076193 | 159 | Q>R | in ECHS1D; dbSNP:rs375032130 | |
VAR_076194 | 195 | G>S | in ECHS1D; dbSNP:rs761989177 | |
VAR_076195 | 225 | C>R | in ECHS1D; dbSNP:rs769429279 | |
VAR_076196 | 273 | K>E | in ECHS1D; dbSNP:rs565090080 | |
VAR_076480 | 281 | E>G | in ECHS1D; uncertain significance |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_073373 | 2 | in ECHS1D; dbSNP:rs587776498 | |||
Sequence: A → V | ||||||
Natural variant | VAR_022273 | 11 | in dbSNP:rs10466126 | |||
Sequence: V → A | ||||||
Natural variant | VAR_076185 | 33 | in ECHS1D | |||
Sequence: F → S | ||||||
Natural variant | VAR_076186 | 54 | in ECHS1D; dbSNP:rs375266808 | |||
Sequence: R → H | ||||||
Natural variant | VAR_076187 | 59 | in ECHS1D; decreases significantly enoyl-CoA hydratase activity; decreases significantly protein expression; dbSNP:rs201865375 | |||
Sequence: N → S | ||||||
Natural variant | VAR_076188 | 66 | in ECHS1D; dbSNP:rs371063211 | |||
Sequence: I → T | ||||||
Natural variant | VAR_022274 | 75 | in dbSNP:rs1049951 | |||
Sequence: T → I | ||||||
Natural variant | VAR_076189 | 77 | in ECHS1D; dbSNP:rs1426014295 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_076190 | 90 | in ECHS1D; uncertain significance; dbSNP:rs1085307550 | |||
Sequence: G → R | ||||||
Natural variant | VAR_076191 | 132 | in ECHS1D; dbSNP:rs770931871 | |||
Sequence: A → T | ||||||
Natural variant | VAR_076479 | 138 | in ECHS1D; decreases enoyl-CoA hydratase activity of 70%; decreases significantly protein expression; dbSNP:rs864309656 | |||
Sequence: A → V | ||||||
Natural variant | VAR_076192 | 150 | in ECHS1D | |||
Sequence: D → G | ||||||
Natural variant | VAR_073374 | 158 | in ECHS1D; dbSNP:rs786204001 | |||
Sequence: A → D | ||||||
Natural variant | VAR_076193 | 159 | in ECHS1D; dbSNP:rs375032130 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_076194 | 195 | in ECHS1D; dbSNP:rs761989177 | |||
Sequence: G → S | ||||||
Natural variant | VAR_076195 | 225 | in ECHS1D; dbSNP:rs769429279 | |||
Sequence: C → R | ||||||
Natural variant | VAR_076196 | 273 | in ECHS1D; dbSNP:rs565090080 | |||
Sequence: K → E | ||||||
Natural variant | VAR_076480 | 281 | in ECHS1D; uncertain significance | |||
Sequence: E → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 364 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-27 | UniProt | Mitochondrion | ||||
Sequence: MAALRVLLSCVRGPLRPPVRCPAWRPF | |||||||
Chain | PRO_0000007411 | 28-290 | UniProt | Enoyl-CoA hydratase, mitochondrial | |||
Sequence: ASGANFEYIIAEKRGKNNTVGLIQLNRPKALNALCDGLIDELNQALKTFEEDPAVGAIVLTGGDKAFAAGADIKEMQNLSFQDCYSSKFLKHWDHLTQVKKPVIAAVNGYAFGGGCELAMMCDIIYAGEKAQFAQPEILIGTIPGAGGTQRLTRAVGKSLAMEMVLTGDRISAQDAKQAGLVSKICPVETLVEEAIQCAEKIASNSKIVVAMAKESVNAAFEMTLTEGSKLEKKLFYSTFATDDRKEGMTAFVEKRKANFKDQ | |||||||
Modified residue | 46 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 101 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 101 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 114 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 115 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 115 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 118 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 186 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 204 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 211 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Interaction
Subunit
Homohexamer; dimer of trimers.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P30084 | LRRK2 Q5S007 | 4 | EBI-719602, EBI-5323863 | |
BINARY | P30084 | STAT3 P40763 | 3 | EBI-719602, EBI-518675 | |
XENO | P30084 | Stat3 P42227 | 3 | EBI-719602, EBI-602878 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length290
- Mass (Da)31,387
- Last updated2005-04-26 v4
- Checksum0CCD0C7F891B1704
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 84 | in Ref. 1; BAA03001 | ||||
Sequence: A → G | ||||||
Sequence conflict | 121 | in Ref. 1; BAA03001 | ||||
Sequence: D → G | ||||||
Sequence conflict | 138 | in Ref. 1; BAA03001 | ||||
Sequence: A → P | ||||||
Sequence conflict | 188-189 | in Ref. 1; BAA03001 | ||||
Sequence: AM → EL | ||||||
Sequence conflict | 197 | in Ref. 1; BAA03001 | ||||
Sequence: R → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D13900 EMBL· GenBank· DDBJ | BAA03001.1 EMBL· GenBank· DDBJ | mRNA | ||
X98126 EMBL· GenBank· DDBJ | CAA66808.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X98127 EMBL· GenBank· DDBJ | CAA66808.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X98128 EMBL· GenBank· DDBJ | CAA66808.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X98129 EMBL· GenBank· DDBJ | CAA66808.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT007123 EMBL· GenBank· DDBJ | AAP35787.1 EMBL· GenBank· DDBJ | mRNA | ||
AL360181 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC008906 EMBL· GenBank· DDBJ | AAH08906.1 EMBL· GenBank· DDBJ | mRNA |