Cystathionine gamma-lyase

Details

Name
Cystathionine gamma-lyase
Synonyms
  • 4.4.1.1
  • Cysteine-protein sulfhydrase
  • Gamma-cystathionase
Gene Name
CTH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001578|Cystathionine gamma-lyase
MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEY
SRSGNPTRNCLEKAVAALDGAKYCLAFASGLAATVTITHLLKAGDQIICMDDVYGGTNRY
FRQVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHG
DIILVVDNTFMSPYFQRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQ
NSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQH
ELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVL
KNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSHS
Number of residues
405
Molecular Weight
44507.64
Theoretical pI
6.69
GO Classification
Functions
carbon-sulfur lyase activity / cystathionine gamma-lyase activity / homocysteine desulfhydrase activity / L-cysteine desulfhydrase activity / L-cystine L-cysteine-lyase (deaminating) / pyridoxal phosphate binding
Processes
cellular nitrogen compound metabolic process / cysteine biosynthetic process / cysteine biosynthetic process via cystathionine / cysteine metabolic process / endoplasmic reticulum unfolded protein response / hydrogen sulfide biosynthetic process / negative regulation of apoptotic signaling pathway / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of NF-kappaB transcription factor activity / protein homotetramerization / protein sulfhydration / protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine / small molecule metabolic process / sulfur amino acid catabolic process / sulfur amino acid metabolic process / transsulfuration
Components
cytoplasm / cytosol / extracellular exosome / nucleus
General Function
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010559|Cystathionine gamma-lyase (CTH)
ATGCAGGAAAAAGACGCCTCCTCACAAGGTTTCCTGCCACACTTCCAACATTTCGCCACG
CAGGCGATCCATGTGGGCCAGGATCCAGAGCAATGGACCTCCAGGGCTGTAGTGCCCCCC
ATCTCACTGTCCACCACGTTCAAGCAAGGGGCGCCTGGCCAGCACTCGGGTTTTGAATAT
AGCCGTTCTGGAAATCCCACTAGGAATTGCCTTGAAAAAGCAGTGGCAGCACTGGATGGG
GCTAAGTACTGTACAAACAGGTACTTCAGGCAAGTGGCATCTGAATTTGGATTAAAGATT
TCTTTTGTTGATTGTTCCAAAATCAAATTACTAGAGGCAGCAATTACACCAGAAACCAAG
CTTGTTTGGATCGAAACCCCCACAAACCCCACCCAGAAGGTGATTGACATTGAAGGCTGT
GCACATATTGTCCATAAGCATGGAGACATTATTTTGGTCGTGGATAACACTTTTATGTCA
CCATATTTCCAGCGCCCTTTGGCTCTGGGAGCTGATATTTCTATGTATTCTGCAACAAAA
TACATGAATGGCCACAGTGATGTTGTAATGGGCCTGGTGTCTGTTAATTGTGAAAGCCTT
CATAATAGACTTCGTTTCTTGCAAAACTCTCTTGGAGCAGTTCCATCTCCTATTGATTGT
TACCTCTGCAATCGAGGTCTGAAGACTCTACATGTCCGAATGGAAAAGCATTTCAAAAAC
GGAATGGCAGTTGCCCAGTTCCTGGAATCTAATCCTTGGGTAGAAAAGGTTATTTATCCT
GGGCTGCCCTCTCATCCACAGCATGAGTTGGTGAAGCGTCAGTGTACAGGTTGTACAGGG
ATGGTCACCTTTTATATTAAGGGCACTCTTCAGCATGCTGAGATTTTCCTCAAGAACCTA
AAGCTATTTACTCTGGCCGAGAGCTTGGGAGGATTCGAAAGCCTTGCTGAGCTTCCGGCA
ATCATGACTCATGCATCAGTTCTTAAGAATGACAGAGATGTCCTTGGAATTAGTGACACA
CTGATTCGACTTTCTGTGGGCTTAGAGGATGAGGAAGACCTACTGGAAGATCTAGATCAA
GCTTTGAAGGCAGCACACCCTCCAAGTGGAAGTCACAGCTAG
Chromosome Location
1
Locus
1p31.1
External Identifiers
ResourceLink
UniProtKB IDP32929
UniProtKB Entry NameCGL_HUMAN
GenBank Protein ID262476
GenBank Gene IDS52784
GenAtlas IDCTH
HGNC IDHGNC:2501
General References
  1. 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. [Article]
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  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. [Article]
  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. [Article]
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  8. Krishnan N, Fu C, Pappin DJ, Tonks NK: H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. [Article]
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00114Pyridoxal phosphateapproved, investigational, nutraceuticalunknowncofactorDetails
DB00151Cysteineapproved, nutraceuticalunknownDetails
DB04217L-2-amino-3-butynoic acidexperimentalunknownDetails
DB023282-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-Phosphono-Pent-3-Enoic AcidexperimentalunknownDetails
DB03928Carboxymethylthio-3-(3-Chlorophenyl)-1,2,4-OxadiazolexperimentalunknownDetails