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. 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. By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (By similarity). 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). H2O + L,L-cystathionine = 2-oxobutanoate + L-cysteine + NH4(+) H2O + L-cysteine = H(+) + hydrogen sulfide + NH4(+) + pyruvate H2O + L-homocysteine = 2-oxobutanoate + H(+) + hydrogen sulfide + NH4(+) L-homoserine = 2-oxobutanoate + NH4(+) H2O + L-selenocystathionine = 2-oxobutanoate + L-selenocysteine + NH4(+) Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine from L-homocysteine and L-serine: step 2/2. Homotetramer (By similarity). Interacts with CALM in a calcium-dependent manner (By similarity). Belongs to the trans-sulfuration enzymes family.