CGL_MACFA
ID CGL_MACFA Reviewed; 405 AA.
AC Q60HG7; Q5EIB5;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Cystathionine gamma-lyase;
DE Short=CGL;
DE Short=CSE;
DE EC=4.4.1.1 {ECO:0000250|UniProtKB:P32929};
DE AltName: Full=Cysteine desulfhydrase;
DE AltName: Full=Cysteine-protein sulfhydrase;
DE AltName: Full=Gamma-cystathionase;
DE AltName: Full=Homocysteine desulfhydrase;
DE EC=4.4.1.2 {ECO:0000250|UniProtKB:P32929};
GN Name=CTH; ORFNames=QccE-22305;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhu Y.Z., Wang Z.J., Ling L.H., Wei D., Zhu Y.C., Yang H., Huang S.H.,
RA Tan C.S., Tan B.J., Whiteman M., Moore P.K.;
RT "Dual effects of hydrogen sulphide on vascular system in anesthesized
RT monkeys in vivo and cloning, characterization of cystathionine-gamma-
RT lyase.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the last step in the trans-sulfuration pathway from
CC L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent
CC manner, which consists on cleaving the L,L-cystathionine molecule into
CC L-cysteine, ammonia and 2-oxobutanoate. Part of the L-cysteine derived
CC from the trans-sulfuration pathway is utilized for biosynthesis of the
CC ubiquitous antioxidant glutathione. Besides its role in the conversion
CC of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-
CC homocysteine as substrates (at much lower rates than L,L-cystathionine)
CC to produce hydrogen sulfide (H2S). In vitro, it converts two L-cysteine
CC molecules into lanthionine and H2S, and two L-homocysteine molecules to
CC homolanthionine and H2S, which can be particularly relevant under
CC conditions of severe hyperhomocysteinemia. Lanthionine and
CC homolanthionine are structural homologs of L,L-cystathionine that
CC differ by the absence or presence of an extra methylene group,
CC respectively. Acts as a cysteine-protein sulfhydrase by mediating
CC sulfhydration of target proteins: sulfhydration consists of converting
CC -SH groups into -SSH on specific cysteine residues of target proteins
CC such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating
CC their function. By generating the gasotransmitter H2S, it participates
CC in a number of physiological processes such as vasodilation, bone
CC protection, and inflammation (By similarity). Plays an essential role
CC in myogenesis by contributing to the biogenesis of H2S in skeletal
CC muscle tissue (By similarity). Can also accept homoserine as substrate
CC (By similarity). Catalyzes the elimination of selenocystathionine
CC (which can be derived from the diet) to yield selenocysteine, ammonia
CC and 2-oxobutanoate (By similarity). {ECO:0000250|UniProtKB:P18757,
CC ECO:0000250|UniProtKB:P32929, ECO:0000250|UniProtKB:Q8VCN5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L,L-cystathionine = 2-oxobutanoate + L-cysteine +
CC NH4(+); Xref=Rhea:RHEA:14005, ChEBI:CHEBI:15377, ChEBI:CHEBI:16763,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:35235, ChEBI:CHEBI:58161; EC=4.4.1.1;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14006;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-cysteine = H(+) + hydrogen sulfide + NH4(+) +
CC pyruvate; Xref=Rhea:RHEA:24931, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:29919,
CC ChEBI:CHEBI:35235; EC=4.4.1.1;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24932;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-homocysteine = 2-oxobutanoate + H(+) + hydrogen
CC sulfide + NH4(+); Xref=Rhea:RHEA:14501, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16763, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29919, ChEBI:CHEBI:58199; EC=4.4.1.2;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14502;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine = 2-oxobutanoate + NH4(+); Xref=Rhea:RHEA:24923,
CC ChEBI:CHEBI:16763, ChEBI:CHEBI:28938, ChEBI:CHEBI:57476; EC=4.4.1.1;
CC Evidence={ECO:0000250|UniProtKB:P18757};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24924;
CC Evidence={ECO:0000250|UniProtKB:P18757};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-selenocystathionine = 2-oxobutanoate + L-
CC selenocysteine + NH4(+); Xref=Rhea:RHEA:31151, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16763, ChEBI:CHEBI:28938, ChEBI:CHEBI:57843,
CC ChEBI:CHEBI:62226; Evidence={ECO:0000250|UniProtKB:P18757};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31152;
CC Evidence={ECO:0000250|UniProtKB:P18757};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 2/2.
CC {ECO:0000250|UniProtKB:P32929}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with CALM in a
CC calcium-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P32929, ECO:0000250|UniProtKB:Q8VCN5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; AB125160; BAD51948.1; -; mRNA.
DR EMBL; AY879312; AAW71993.1; -; mRNA.
DR RefSeq; NP_001306395.1; NM_001319466.1.
DR RefSeq; XP_005595733.2; XM_005595676.2.
DR AlphaFoldDB; Q60HG7; -.
DR SMR; Q60HG7; -.
DR STRING; 9541.XP_005543095.1; -.
DR GeneID; 102117863; -.
DR CTD; 1491; -.
DR eggNOG; KOG0053; Eukaryota.
DR OrthoDB; 572061at2759; -.
DR UniPathway; UPA00136; UER00202.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0004123; F:cystathionine gamma-lyase activity; ISS:UniProtKB.
DR GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:RHEA.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IEA:UniProtKB-EC.
DR GO; GO:0044540; F:L-cystine L-cysteine-lyase (deaminating); ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:0098606; F:selenocystathionine gamma-lyase activity; IEA:RHEA.
DR GO; GO:0019344; P:cysteine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0044524; P:protein sulfhydration; ISS:UniProtKB.
DR GO; GO:0018272; P:protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine; ISS:UniProtKB.
DR GO; GO:0019346; P:transsulfuration; IEA:InterPro.
DR CDD; cd00614; CGS_like; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR PANTHER; PTHR11808; PTHR11808; 1.
DR Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR PIRSF; PIRSF001434; CGS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00868; CYS_MET_METAB_PP; 1.
PE 2: Evidence at transcript level;
KW Amino-acid biosynthesis; Calmodulin-binding; Cysteine biosynthesis;
KW Cytoplasm; Lipid metabolism; Lyase; Pyridoxal phosphate;
KW Reference proteome.
FT CHAIN 1..405
FT /note="Cystathionine gamma-lyase"
FT /id="PRO_0000114750"
FT BINDING 62
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 212
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P32929"
FT CONFLICT 405
FT /note="D -> N (in Ref. 2; AAW71993)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 44521 MW; DA0B73FDE511A3D2 CRC64;
MQEKDASSQG FLPHFQHFAT QAIHVGQEPE QWTSRAVVPL ISLSTTFKQA APGQHSGFEY
SRSGNPTRNC LEKAVAALDG AKYCLAFASG LAATVTITHL LKAGDQIICM DDVYGGTNRY
FRQVASEFGL KISFVDCSKI KLLEAAITPE TKLVWIETPT NPVLKMIDIE ACAHIVHKRG
DIILVVDNTF MSPYFQRPLA LGADICMCSA TKYMNGHSDV VMGLVSVNCE RLHNRLRFLQ
NSLGAVPSPL DCYLCNRGLK TLHVRMEKHF KNGMAVAQFL ESNPGVEKVI YPGLPSHPQH
ELAKRQCTGC TGMITFYIKG TLQHAEIFLK NLKLFTLAES LGGFESLVEL PAIMTHASVP
KNDRDVLGIS DTLIRLSVGL EDEKDLLEDL DQALKAAHPP SGSHD
