Q8VCN5 · CGL_MOUSE
- ProteinCystathionine gamma-lyase
- GeneCth
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids398 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate. Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione. Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce hydrogen sulfide (H2S). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, and two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia. Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (By similarity).
Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:19903941, PubMed:22244329).
By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (By similarity) (PubMed:18948540).
Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (PubMed:33826201).
Can also accept homoserine as substrate (By similarity).
Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity).
Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:19903941, PubMed:22244329).
By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (By similarity) (PubMed:18948540).
Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (PubMed:33826201).
Can also accept homoserine as substrate (By similarity).
Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity).
Catalytic activity
- H2O + L,L-cystathionine = 2-oxobutanoate + L-cysteine + NH4+This reaction proceeds in the forward direction.
- H2O + L-selenocystathionine = 2-oxobutanoate + L-selenocysteine + NH4+This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Activated by calmodulin in the presence of calcium ions.
Pathway
Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine from L-homocysteine and L-serine: step 2/2.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 61 | substrate | ||||
Sequence: R | ||||||
Binding site | 113 | substrate | ||||
Sequence: Y | ||||||
Binding site | 118 | substrate | ||||
Sequence: R | ||||||
Binding site | 338 | substrate | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCystathionine gamma-lyase
- EC number
- Short namesCGL; CSE
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8VCN5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
No visible phenotype at birth. Mice exhibit strongly decreased levels of hydrogen sulfide (H2S) in heart and aorta. Mice also show absence of protein sulfhydration on target proteins. Hydrogen sulfide serum levels are also lower than normal. No effect on brain hydrogen sulfide levels. Age-dependent hypertension beginning at about seven weeks of age (PubMed:18948540, PubMed:19903941).
Deteriorated the loss of skeletal muscle mass in aging mice (PubMed:33826201).
Deteriorated the loss of skeletal muscle mass in aging mice (PubMed:33826201).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 28 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000114751 | 1-398 | Cystathionine gamma-lyase | |||
Sequence: MQKDASLSGFLPSFQHFATQAIHVGQEPEQWNSRAVVLPISLATTFKQDFPGQSSGFEYSRSGNPTRNCLEKAVAALDGAKHSLAFASGLAATITITHLLKAGDEIICMDEVYGGTNRYFRRVASEFGLKISFVDCSKTKLLEAAITPQTKLVWIETPTNPTLKLADIGACAQIVHKRGDIILVVDNTFMSAYFQRPLALGADICMCSATKYMNGHSDVVMGLVSVNSDDLNSRLRFLQNSLGAVPSPFDCYLCCRGLKTLQVRMEKHFKNGMAVARFLETNPRVEKVVYPGLPSHPQHELAKRQCSGCPGMVSFYIKGALQHAKAFLKNLKLFTLAESLGGYESLAELPAIMTHASVPEKDRATLGINDTLIRLSVGLEDEQDLLEDLDRALKAAHP | ||||||
Modified residue | 211 | N6-(pyridoxal phosphate)lysine | ||||
Sequence: K |
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in liver and kidney, and at lower levels in small intestine (at protein level) (PubMed:15038791).
Highly expressed in liver, kidney and lung, detected at lower levels in stomach, small intestine and adipose tissue, and hardly found in heart, bone, and thymus (PubMed:15038791, PubMed:20305127).
Highly expressed in liver, kidney and lung, detected at lower levels in stomach, small intestine and adipose tissue, and hardly found in heart, bone, and thymus (PubMed:15038791, PubMed:20305127).
Induction
Tumor necrosis factor alpha (TNF-alpha) promotes the binding of SP1 to the CSE promoter, inducing its transcription.
Developmental stage
First detected at low levels in embryonic liver after 12.5 days of embryonic development. Highly expressed in liver and kidney after 18.5 days of embryonic development. Expressed at high levels in liver and kidney after birth and in adults. Age-dependent expression in mouse skeletal muscles; protein expression in skeletal muscles increased 5 days after birth, and remained stable until 10 weeks, then slightly decreased at 26 weeks and was significantly lower at 51 weeks (PubMed:33826201).
Gene expression databases
Structure
Sequence
- Sequence statusComplete
- Length398
- Mass (Da)43,567
- Last updated2002-03-01 v1
- ChecksumB2F89625B9978599
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY083352 EMBL· GenBank· DDBJ | AAL99218.1 EMBL· GenBank· DDBJ | mRNA | ||
AY262829 EMBL· GenBank· DDBJ | AAP86975.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH466532 EMBL· GenBank· DDBJ | EDL11858.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC019483 EMBL· GenBank· DDBJ | AAH19483.1 EMBL· GenBank· DDBJ | mRNA |