Q8N0X4 · CLYBL_HUMAN
- ProteinCitramalyl-CoA lyase, mitochondrial
- GeneCLYBL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids340 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341).
Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (PubMed:29056341).
The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341).
Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:24334609, PubMed:29056341).
Also displays malyl-CoA thioesterase activity (PubMed:29056341).
Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341).
Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341).
Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (PubMed:29056341).
The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341).
Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:24334609, PubMed:29056341).
Also displays malyl-CoA thioesterase activity (PubMed:29056341).
Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341).
Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341).
Catalytic activity
- acetyl-CoA + glyoxylate + H2O = (S)-malate + CoA + H+
- glyoxylate + H2O + propanoyl-CoA = 3-methylmalate + CoA + H+
Cofactor
Note: Binds 1 Mg2+ ion per subunit.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
3.6 mM | glyoxylate (with acetyl-CoA as cosubstrate) | |||||
1.2 mM | glyoxylate (with propionyl-CoA as cosubstrate) | |||||
28.7 μM | propionyl-CoA (for beta-methylmalate synthase) | |||||
57.3 μM | acetyl-CoA (for malate synthase) | |||||
25 μM | acetyl-CoA (for citramalate synthase) | |||||
23 μM | (3S)-citramalyl-CoA (for citramalyl-CoA lyase) | |||||
74 μM | acetyl-CoA | |||||
23 μM | propionyl-CoA |
kcat is 0.12 sec-1 for malate synthase reaction (PubMed:24334609).
kcat is 0.09 sec-1 for beta-methylmalate synthase reaction (PubMed:24334609).
kcat is 0.135 sec-1 for beta-methylmalate synthase reaction (PubMed:29056341).
kcat is 0.146 sec-1 for malate synthase reaction (PubMed:29056341).
kcat is 0.08 sec-1 for citramalate synthase reaction (PubMed:29056341).
kcat is 14.1 sec-1 for citramalyl-CoA lyase reaction (PubMed:29056341).
kcat is 0.09 sec-1 for beta-methylmalate synthase reaction (PubMed:24334609).
kcat is 0.135 sec-1 for beta-methylmalate synthase reaction (PubMed:29056341).
kcat is 0.146 sec-1 for malate synthase reaction (PubMed:29056341).
kcat is 0.08 sec-1 for citramalate synthase reaction (PubMed:29056341).
kcat is 14.1 sec-1 for citramalyl-CoA lyase reaction (PubMed:29056341).
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 50 | substrate | ||||
Sequence: Y | ||||||
Binding site | 57 | substrate | ||||
Sequence: K | ||||||
Binding site | 61 | substrate | ||||
Sequence: K | ||||||
Binding site | 107 | substrate | ||||
Sequence: R | ||||||
Binding site | 171 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 206 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 272-273 | substrate | ||||
Sequence: IH | ||||||
Active site | 320 | |||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrion | |
Molecular Function | (S)-citramalyl-CoA lyase activity | |
Molecular Function | hydrolase activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | malate synthase activity | |
Biological Process | positive regulation of cobalamin metabolic process | |
Biological Process | protein homotrimerization | |
Biological Process | regulation of cobalamin metabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCitramalyl-CoA lyase, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8N0X4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_032099 | 28 | in dbSNP:rs17577293 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_032100 | 128 | in dbSNP:rs35680839 | |||
Sequence: V → I | ||||||
Natural variant | VAR_032101 | 241 | in dbSNP:rs3783185 | |||
Sequence: I → V | ||||||
Natural variant | VAR_073420 | 259-340 | loss of the protein product; reduction of circulating vitamin B12; dbSNP:rs41281112 | |||
Sequence: Missing | ||||||
Mutagenesis | 320 | Abolishes citramalyl-CoA lyase activity. | ||||
Sequence: D → A or N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 462 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-22 | Mitochondrion | ||||
Sequence: MALRLLRRAARGAAAAALLRLK | ||||||
Chain | PRO_0000286389 | 23-340 | Citramalyl-CoA lyase, mitochondrial | |||
Sequence: ASLAADIPRLGYSSSSHHKYIPRRAVLYVPGNDEKKIKKIPSLNVDCAVLDCEDGVAANKKNEARLRIVKTLEDIDLGPTEKCVRVNSVSSGLAEEDLETLLQSRVLPSSLMLPKVESPEEIQWFADKFSFHLKGRKLEQPMNLIPFVETAMGLLNFKAVCEETLKVGPQVGLFLDAVVFGGEDFRASIGATSSKETLDILYARQKIVVIAKAFGLQAIDLVYIDFRDGAGLLRQSREGAAMGFTGKQVIHPNQIAVVQEQFSPSPEKIKWAEELIAAFKEHQQLGKGAFTFQGSMIDMPLLKQAQNTVTLATSIKEK | ||||||
Modified residue | 57 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 61 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 82 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 82 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 92 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 92 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 309 | N6-succinyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q8N0X4-1
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.
- Name1
- Length340
- Mass (Da)37,359
- Last updated2007-05-01 v2
- Checksum0C99A5A4F09E03E2
Q8N0X4-2
- Name2
- Differences from canonical
- 147-180: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_034643 | 147-180 | in isoform 2 | |||
Sequence: Missing |
Polymorphism
The protein is absent in 2.7% of the human population due to a loss-of-function polymorphism (rs41281112) that changes Arg-259 to a premature stop codon, leading to loss of the protein product (PubMed:23754956, PubMed:24334609).
This polymorphism is associated with reduction of circulating vitamin B12 (PubMed:23754956, PubMed:24334609).
The reduction of circulating vitamin B12 is caused by accumulation of citramalyl-CoA, an intermediate in the C5-dicarboxylate metabolic pathway that includes itaconate (PubMed:29056341).
Itaconate acting as a vitamin B12-poisoning metabolite that inactivates the mitochondrial methylglutaconyl-CoA hydratase (AUH) enzyme (PubMed:29056341).
This polymorphism is associated with reduction of circulating vitamin B12 (PubMed:23754956, PubMed:24334609).
The reduction of circulating vitamin B12 is caused by accumulation of citramalyl-CoA, an intermediate in the C5-dicarboxylate metabolic pathway that includes itaconate (PubMed:29056341).
Itaconate acting as a vitamin B12-poisoning metabolite that inactivates the mitochondrial methylglutaconyl-CoA hydratase (AUH) enzyme (PubMed:29056341).
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF428253 EMBL· GenBank· DDBJ | AAL84703.1 EMBL· GenBank· DDBJ | mRNA | ||
AK095506 EMBL· GenBank· DDBJ | BAC04561.1 EMBL· GenBank· DDBJ | mRNA | ||
AL137139 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL139035 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC034360 EMBL· GenBank· DDBJ | AAH34360.1 EMBL· GenBank· DDBJ | mRNA |