Mouse anti-Human/Rat sapiens (Human) CTH Monoclonal Antibody

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 (PubMed:10212249, PubMed:18476726, PubMed:19261609, PubMed:19961860). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). 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 the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19019829, PubMed:19261609, PubMed:19961860). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). 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:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (By similarity). 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)

Subcellular Location

Cytoplasm

Disease Association

Cystathioninuria (CSTNU) : Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Highly expressed in liver (PubMed:10727430, PubMed:20305127). Also in muscle and lower expression in most tissues except heart, pituitary gland, spleen, thymus, and vascular tissue, where it is hardly detected (PubMed:20305127)

Subunit

Homotetramer (PubMed:19019829). Interacts with CALM in a calcium-dependent manner (By similarity)

Pathway

Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine from L-homocysteine and L-serine: step 2/2

• Lu Y. et al. Cloning and nucleotide sequence of human liver cDNA encoding for cystathionine gamma-lyase. — Biochem. Biophys. Res. Commun. (1992)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (MAY-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Totoki Y. et al. PubMed: CI-58UKVFP8TE70J (APR-)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Steegborn C. et al. Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration. — J. Biol. Chem. (1999)