CGL_RAT
ID CGL_RAT Reviewed; 398 AA.
AC P18757;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cystathionine gamma-lyase;
DE Short=CGL;
DE Short=CSE;
DE EC=4.4.1.1 {ECO:0000305|PubMed:13525371, ECO:0000305|PubMed:6456763};
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};
DE AltName: Full=Probasin-related antigen;
DE Short=PRB-RA;
GN Name=Cth;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8288556; DOI=10.1016/s0021-9258(17)42213-7;
RA Nishi N., Tanabe H., Oya H., Urushihara M., Miyanaka H., Wada F.;
RT "Identification of probasin-related antigen as cystathionine gamma-lyase by
RT molecular cloning.";
RL J. Biol. Chem. 269:1015-1019(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-398, AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2201285; DOI=10.1042/bj2690335;
RA Erickson P.F., Maxwell I.H., Su L.J., Baumann M., Glode L.M.;
RT "Sequence of cDNA for rat cystathionine gamma-lyase and comparison of
RT deduced amino acid sequence with related Escherichia coli enzymes.";
RL Biochem. J. 269:335-340(1990).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=13525371; DOI=10.1016/s0021-9258(18)70476-6;
RA Matsuo Y., Greenberg D.M.;
RT "A crystalline enzyme that cleaves homoserine and cystathionine. I.
RT Isolation procedure and some physicochemical properties.";
RL J. Biol. Chem. 230:545-560(1958).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=6456763; DOI=10.1021/bi00518a039;
RA Esaki N., Nakamura T., Tanaka H., Suzuki T., Morino Y., Soda K.;
RT "Enzymatic synthesis of selenocysteine in rat liver.";
RL Biochemistry 20:4492-4496(1981).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (Probable) (PubMed:13525371).
CC Part of the L-cysteine derived from the trans-sulfuration pathway is
CC utilized for biosynthesis of the ubiquitous antioxidant glutathione.
CC Besides its role in the conversion of L-cystathionine into L-cysteine,
CC it utilizes L-cysteine and L-homocysteine as substrates (at much lower
CC rates than L,L-cystathionine) to produce hydrogen sulfide (H2S). In
CC vitro, it converts two L-cysteine molecules into lanthionine and H2S,
CC and two L-homocysteine molecules to homolanthionine and H2S, which can
CC be particularly relevant under conditions of severe
CC hyperhomocysteinemia. Lanthionine and homolanthionine are structural
CC homologs of L,L-cystathionine that differ by the absence or presence of
CC an extra methylene group, respectively. Acts as a cysteine-protein
CC sulfhydrase by mediating sulfhydration of target proteins:
CC sulfhydration consists of converting -SH groups into -SSH on specific
CC cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-
CC B subunit RELA, thereby regulating their function. By generating the
CC gasotransmitter H2S, it participates in a number of physiological
CC processes such as vasodilation, bone protection, and inflammation (By
CC similarity). Plays an essential role in myogenesis by contributing to
CC the biogenesis of H2S in skeletal muscle tissue (By similarity). Can
CC also accept homoserine as substrate (PubMed:13525371). Catalyzes the
CC elimination of selenocystathionine (which can be derived from the diet)
CC to yield selenocysteine, ammonia and 2-oxobutanoate (Probable).
CC {ECO:0000250|UniProtKB:P32929, ECO:0000250|UniProtKB:Q8VCN5,
CC ECO:0000269|PubMed:13525371, ECO:0000305|PubMed:6456763}.
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:0000269|PubMed:13525371, ECO:0000305|PubMed:6456763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14006;
CC Evidence={ECO:0000269|PubMed:13525371, ECO:0000305|PubMed:6456763};
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:0000269|PubMed:13525371};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24924;
CC Evidence={ECO:0000269|PubMed:13525371};
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:0000305|PubMed:6456763};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31152;
CC Evidence={ECO:0000305|PubMed:6456763};
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 -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P32929};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0 with L-cystathionine.
CC {ECO:0000305|PubMed:13525371};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 2/2.
CC {ECO:0000305|PubMed:13525371}.
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.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; D17370; BAA04189.1; -; mRNA.
DR EMBL; X53460; CAA37547.1; -; mRNA.
DR PIR; A49864; A49864.
DR RefSeq; NP_058770.1; NM_017074.1.
DR AlphaFoldDB; P18757; -.
DR SMR; P18757; -.
DR STRING; 10116.ENSRNOP00000058914; -.
DR iPTMnet; P18757; -.
DR PhosphoSitePlus; P18757; -.
DR PaxDb; P18757; -.
DR GeneID; 24962; -.
DR KEGG; rno:24962; -.
DR CTD; 1491; -.
DR RGD; 2443; Cth.
DR eggNOG; KOG0053; Eukaryota.
DR InParanoid; P18757; -.
DR OrthoDB; 572061at2759; -.
DR PhylomeDB; P18757; -.
DR BioCyc; MetaCyc:MON-8584; -.
DR Reactome; R-RNO-1614558; Degradation of cysteine and homocysteine.
DR Reactome; R-RNO-1614603; Cysteine formation from homocysteine.
DR UniPathway; UPA00136; UER00202.
DR PRO; PR:P18757; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0004121; F:cystathionine beta-lyase activity; IDA:RGD.
DR GO; GO:0004123; F:cystathionine gamma-lyase activity; ISS:UniProtKB.
DR GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0019344; P:cysteine biosynthetic process; IDA:RGD.
DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; ISO:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; IMP:RGD.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:RGD.
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:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR GO; GO:1904831; P:positive regulation of aortic smooth muscle cell differentiation; ISO:RGD.
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:0051289; P:protein homotetramerization; ISO:RGD.
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; ISO:RGD.
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 1: Evidence at protein level;
KW Amino-acid biosynthesis; Calmodulin-binding; Cysteine biosynthesis;
KW Cytoplasm; Direct protein sequencing; Lipid metabolism; Lyase;
KW Phosphoprotein; Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..398
FT /note="Cystathionine gamma-lyase"
FT /id="PRO_0000114752"
FT BINDING 61
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 211
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P32929"
FT CONFLICT 35..41
FT /note="AVVLPIS -> CCGAAH (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="T -> N (in Ref. 2; CAA37547)"
FT /evidence="ECO:0000305"
FT CONFLICT 260..271
FT /note="TLQIRMEKHFRN -> HCRSGWRNTFQD (in Ref. 2; CAA37547)"
FT /evidence="ECO:0000305"
FT CONFLICT 305..308
FT /note="QCTG -> SARA (in Ref. 2; CAA37547)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 398 AA; 43605 MW; C6043988B03D725F CRC64;
MQKDASSSGF LPSFQHFATQ AIHVGPEPEQ WSSRAVVLPI SLATTFKQDS PGQSSGFVYS
RSGNPTRNCL EKAVAALDGA KHCLTFARGL AATTTITHLL KAGDEVICMD EVYGGTNRYF
RRVASEFGLK ISFVDCSKTK LLEAAITPQT KLVWIETPTN PTLKLADIKA CAQIVHKHKD
IILVVDNTFM SAYFQRPLAL GADICMCSAT KYMNGHSDVV MGLVSVTSDD LNERLRFLQN
SLGAVPSPFD CYLCCRGLKT LQIRMEKHFR NGMAVARFLE SNPRVEKVIY PGLPSHPQHE
LAKRQCTGCP GMVSFYIKGT LQHAQVFLKN IKLFALAESL GGYESLAELP AIMTHASVPE
KDRATLGISD TLIRLSVGLE DEKDLLEDLG QALKAAHP
