CGL_PIG
ID CGL_PIG Reviewed; 405 AA.
AC Q19QT7;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Cystathionine gamma-lyase;
DE Short=CGL;
DE Short=CSE;
DE EC=4.4.1.1;
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16978188; DOI=10.1111/j.1365-2052.2006.01499.x;
RA Kim J.H., Lim H.T., Park E.W., Ovilo C., Lee J.H., Jeon J.T.;
RT "A gene-based radiation hybrid map of the pig chromosome 6q32 region
RT associated with a QTL for fat deposition traits.";
RL Anim. Genet. 37:522-523(2006).
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; DQ499449; ABF72039.1; -; mRNA.
DR RefSeq; NP_001038050.1; NM_001044585.1.
DR STRING; 9823.ENSSSCP00000004099; -.
DR PaxDb; Q19QT7; -.
DR PeptideAtlas; Q19QT7; -.
DR PRIDE; Q19QT7; -.
DR GeneID; 733654; -.
DR KEGG; ssc:733654; -.
DR CTD; 1491; -.
DR eggNOG; KOG0053; Eukaryota.
DR InParanoid; Q19QT7; -.
DR OrthoDB; 572061at2759; -.
DR UniPathway; UPA00136; UER00202.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0016846; F:carbon-sulfur lyase activity; IBA:GO_Central.
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:0019343; P:cysteine biosynthetic process via cystathionine; IBA:GO_Central.
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; IBA:GO_Central.
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_0000289803"
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"
SQ SEQUENCE 405 AA; 44490 MW; 70A0D86B575C1062 CRC64;
MQEKDVSSHG FLPRFQHFAT QAIHAGQEPE QWASKAVVPP ISLSTTFKQE APGQHSGFEY
SRSGNPTXNC LEKAVAVLDG AKYSLAFASG LAATVTITHL LKAGXQIISM DDVYGGTNRY
FRQVAAEFGL KISFVDCSKS KLLEAAITPE TKLVWIETPT NPILKMIDIE ACAQIVHKHG
DIILVVDNTF MSAYFQRPLA LGADICMYSA TKYMNGHSDV VMGLVSLNSE TLHSRLRFLQ
NSLGAVPSPI DCYLCNRGLK TLQVRMEKHF ENGMAVAQFL ESHPLVEKVI YPGLPSHPQH
ELAKRQCTGC PGMISFYIKG SLHHAETFLK SLKLFTLAES LGGYESLAEL PAIMTHSSVP
KSDREVLGIR DTLIRLSVGL EDKQDLMDDL DQALKAAHPT NASHN
