Hmdb loader
Identification
HMDB Protein ID HMDBP00538
Secondary Accession Numbers
  • 5789
Name Cystathionine gamma-lyase
Synonyms
  1. Gamma-cystathionase
  2. Cysteine-protein sulfhydrase
Gene Name CTH
Protein Type Enzyme
Biological Properties
General Function Involved in pyridoxal phosphate binding
Specific Function Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. 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.
Pathways
  • 3-Phosphoglycerate dehydrogenase deficiency
  • Beta-mercaptolactate-cysteine disulfiduria
  • Cystathionine Beta-Synthase Deficiency
  • Cysteine and methionine metabolism
  • Cysteine Metabolism
  • Cystinosis, ocular nonnephropathic
  • Dihydropyrimidine Dehydrogenase Deficiency (DHPD)
  • Dimethylglycine Dehydrogenase Deficiency
  • Dimethylglycine Dehydrogenase Deficiency
  • Gamma-cystathionase deficiency (CTH)
  • Glycine N-methyltransferase Deficiency
  • Glycine, serine and threonine metabolism
  • Glycine, serine and threonine metabolism
  • Homocysteine Degradation
  • Homocystinuria, cystathionine beta-synthase deficiency
  • Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type
  • Hyperglycinemia, non-ketotic
  • Hypermethioninemia
  • L-cysteine biosynthesis
  • Methionine Adenosyltransferase Deficiency
  • Methionine Metabolism
  • Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
  • Non Ketotic Hyperglycinemia
  • S-Adenosylhomocysteine (SAH) Hydrolase Deficiency
  • Sarcosinemia
  • Selenocompound metabolism
  • Selenocompound metabolism
Reactions
L-Cystathionine + Water → L-Cysteine + Ammonia + 2-Ketobutyric acid details
L-Cysteine + Water → Hydrogen sulfide + Pyruvic acid + Ammonia details
L-Cystine + Water → Pyruvic acid + Ammonia + Thiocysteine details
Selenomethionine + Water → Methaneselenol + Ammonia + 2-Ketobutyric acid details
Selenocystathionine + Water → Selenocysteine + Ammonia + 2-Ketobutyric acid details
GO Classification
Biological Process
transsulfuration
cellular nitrogen compound metabolic process
sulfur amino acid catabolic process
cysteine biosynthetic process
endoplasmic reticulum unfolded protein response
glutathione metabolic process
protein sulfhydration
protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine
positive regulation of I-kappaB kinase/NF-kappaB cascade
negative regulation of cell growth
protein homotetramerization
negative regulation of cell proliferation
positive regulation of NF-kappaB transcription factor activity
hydrogen sulfide biosynthetic process
Cellular Component
cytosol
nucleus
Function
binding
catalytic activity
cofactor binding
pyridoxal phosphate binding
Molecular Function
cystathionine beta-lyase activity
cystathionine gamma-lyase activity
homocysteine desulfhydrase activity
L-cysteine desulfhydrase activity
L-cystine L-cysteine-lyase (deaminating)
pyridoxal phosphate binding
Process
metabolic process
cellular metabolic process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 1
Locus 1p31.1
SNPs CTH
Gene Sequence
>1218 bp
ATGCAGGAAAAAGACGCCTCCTCACAAGGTTTCCTGCCACACTTCCAACATTTCGCCACG
CAGGCGATCCATGTGGGCCAGGATCCAGAGCAATGGACCTCCAGGGCTGTAGTGCCCCCC
ATCTCACTGTCCACCACGTTCAAGCAAGGGGCGCCTGGCCAGCACTCGGGTTTTGAATAT
AGCCGTTCTGGAAATCCCACTAGGAATTGCCTTGAAAAAGCAGTGGCAGCACTGGATGGG
GCTAAGTACTGTTTGGCCTTTGCTTCAGGTTTAGCAGCCACTGTAACTATTACCCATCTT
TTAAAAGCAGGAGACCAAATTATTTGTATGGATGATGTGTATGGAGGTACAAACAGGTAC
TTCAGGCAAGTGGCATCTGAATTTGGATTAAAGATTTCTTTTGTTGATTGTTCCAAAATC
AAATTACTAGAGGCAGCAATTACACCAGAAACCAAGCTTGTTTGGATCGAAACCCCCACA
AACCCCACCCAGAAGGTGATTGACATTGAAGGCTGTGCACATATTGTCCATAAGCATGGA
GACATTATTTTGGTCGTGGATAACACTTTTATGTCACCATATTTCCAGCGCCCTTTGGCT
CTGGGAGCTGATATTTCTATGTATTCTGCAACAAAATACATGAATGGCCACAGTGATGTT
GTAATGGGCCTGGTGTCTGTTAATTGTGAAAGCCTTCATAATAGACTTCGTTTCTTGCAA
AACTCTCTTGGAGCAGTTCCATCTCCTATTGATTGTTACCTCTGCAATCGAGGTCTGAAG
ACTCTACATGTCCGAATGGAAAAGCATTTCAAAAACGGAATGGCAGTTGCCCAGTTCCTG
GAATCTAATCCTTGGGTAGAAAAGGTTATTTATCCTGGGCTGCCCTCTCATCCACAGCAT
GAGTTGGTGAAGCGTCAGTGTACAGGTTGTACAGGGATGGTCACCTTTTATATTAAGGGC
ACTCTTCAGCATGCTGAGATTTTCCTCAAGAACCTAAAGCTATTTACTCTGGCCGAGAGC
TTGGGAGGATTCGAAAGCCTTGCTGAGCTTCCGGCAATCATGACTCATGCATCAGTTCTT
AAGAATGACAGAGATGTCCTTGGAATTAGTGACACACTGATTCGACTTTCTGTGGGCTTA
GAGGATGAGGAAGACCTACTGGAAGATCTAGATCAAGCTTTGAAGGCAGCACACCCTCCA
AGTGGAATTCACAGCTAG
Protein Properties
Number of Residues 405
Molecular Weight 41259.91
Theoretical pI 6.861
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Cystathionine gamma-lyase
MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEY
SRSGNPTRNCLEKAVAALDGAKYCLAFASGLAATVTITHLLKAGDQIICMDDVYGGTNRY
FRQVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHG
DIILVVDNTFMSPYFQRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQ
NSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQH
ELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVL
KNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSHS
GenBank ID Protein 62898313
UniProtKB/Swiss-Prot ID P32929
UniProtKB/Swiss-Prot Entry Name CGL_HUMAN
PDB IDs
GenBank Gene ID AK223376
GeneCard ID CTH
GenAtlas ID CTH
HGNC ID HGNC:2501
References
General References
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  4. Lu Y, O'Dowd BF, Orrego H, Israel Y: Cloning and nucleotide sequence of human liver cDNA encoding for cystathionine gamma-lyase. Biochem Biophys Res Commun. 1992 Dec 15;189(2):749-58. [PubMed:1339280 ]
  5. Steegborn C, Clausen T, Sondermann P, Jacob U, Worbs M, Marinkovic S, Huber R, Wahl MC: Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration. J Biol Chem. 1999 Apr 30;274(18):12675-84. [PubMed:10212249 ]
  6. Chiku T, Padovani D, Zhu W, Singh S, Vitvitsky V, Banerjee R: H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia. J Biol Chem. 2009 Apr 24;284(17):11601-12. doi: 10.1074/jbc.M808026200. Epub 2009 Mar 4. [PubMed:19261609 ]
  7. Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J: Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S. J Biol Chem. 2009 Jan 30;284(5):3076-85. doi: 10.1074/jbc.M805459200. Epub 2008 Nov 19. [PubMed:19019829 ]
  8. Wang J, Hegele RA: Genomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH). Hum Genet. 2003 Apr;112(4):404-8. Epub 2003 Feb 6. [PubMed:12574942 ]
  9. Zhu W, Lin A, Banerjee R: Kinetic properties of polymorphic variants and pathogenic mutants in human cystathionine gamma-lyase. Biochemistry. 2008 Jun 10;47(23):6226-32. doi: 10.1021/bi800351a. Epub 2008 May 14. [PubMed:18476726 ]