CGL_MOUSE
ID CGL_MOUSE Reviewed; 398 AA.
AC Q8VCN5; Q6H324;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Cystathionine gamma-lyase {ECO:0000303|PubMed:18948540, ECO:0000303|PubMed:19903941, ECO:0000303|PubMed:22244329, ECO:0000303|PubMed:33826201};
DE Short=CGL;
DE Short=CSE {ECO:0000303|PubMed:18948540, ECO:0000303|PubMed:19903941, ECO:0000303|PubMed:22244329, ECO:0000303|PubMed:33826201};
DE EC=4.4.1.1 {ECO:0000305|PubMed:19903941};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/SvJ, and C57BL/6J; TISSUE=Kidney, and Spleen;
RX PubMed=15038791; DOI=10.1042/bj20040243;
RA Ishii I., Akahoshi N., Yu X.-N., Kobayashi Y., Namekata K., Komaki G.,
RA Kimura H.;
RT "Murine cystathionine gamma-lyase: complete cDNA and genomic sequences,
RT promoter activity, tissue distribution and developmental expression.";
RL Biochem. J. 381:113-123(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH CALM, AND ACTIVITY
RP REGULATION.
RX PubMed=18948540; DOI=10.1126/science.1162667;
RA Yang G., Wu L., Jiang B., Yang W., Qi J., Cao K., Meng Q., Mustafa A.K.,
RA Mu W., Zhang S., Snyder S.H., Wang R.;
RT "H2S as a physiologic vasorelaxant: hypertension in mice with deletion of
RT cystathionine gamma-lyase.";
RL Science 322:587-590(2008).
RN [5]
RP FUNCTION AS CYSTEINE-PROTEIN SULFHYDRASE, CATALYTIC ACTIVITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=19903941; DOI=10.1126/scisignal.2000464;
RA Mustafa A.K., Gadalla M.M., Sen N., Kim S., Mu W., Gazi S.K., Barrow R.K.,
RA Yang G., Wang R., Snyder S.H.;
RT "H2S signals through protein S-sulfhydration.";
RL Sci. Signal. 2:RA72-RA72(2009).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=20305127; DOI=10.1096/fj.09-143651;
RA Chen N.C., Yang F., Capecci L.M., Gu Z., Schafer A.I., Durante W.,
RA Yang X.F., Wang H.;
RT "Regulation of homocysteine metabolism and methylation in human and mouse
RT tissues.";
RL FASEB J. 24:2804-2817(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION AS CYSTEINE-PROTEIN SULFHYDRASE, AND INDUCTION BY SP1
RP TRANSCRIPTION FACTOR.
RX PubMed=22244329; DOI=10.1016/j.molcel.2011.10.021;
RA Sen N., Paul B.D., Gadalla M.M., Mustafa A.K., Sen T., Xu R., Kim S.,
RA Snyder S.H.;
RT "Hydrogen sulfide-linked sulfhydration of NF-kappaB mediates its
RT antiapoptotic actions.";
RL Mol. Cell 45:13-24(2012).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=33826201; DOI=10.1096/fj.202002675r;
RA Zhang Y., Masters L., Wang Y., Wu L., Pei Y., Guo B., Parissenti A.,
RA Lees S.J., Wang R., Yang G.;
RT "Cystathionine gamma-lyase/H2 S signaling facilitates myogenesis under
RT aging and injury condition.";
RL FASEB J. 35:e21511-e21511(2021).
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 (By similarity). Acts as a cysteine-protein sulfhydrase by
CC mediating sulfhydration of target proteins: sulfhydration consists of
CC converting -SH groups into -SSH on specific cysteine residues of target
CC proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby
CC regulating their function (PubMed:19903941, PubMed:22244329). By
CC generating the gasotransmitter H2S, it participates in a number of
CC physiological processes such as vasodilation, bone protection, and
CC inflammation (PubMed:18948540) (By similarity). Plays an essential role
CC in myogenesis by contributing to the biogenesis of H2S in skeletal
CC muscle tissue (PubMed:33826201). Can also accept homoserine as
CC substrate (By similarity). Catalyzes the elimination of
CC selenocystathionine (which can be derived from the diet) to yield
CC selenocysteine, ammonia and 2-oxobutanoate (By similarity).
CC {ECO:0000250|UniProtKB:P18757, ECO:0000250|UniProtKB:P32929,
CC ECO:0000269|PubMed:18948540, ECO:0000269|PubMed:19903941,
CC ECO:0000269|PubMed:22244329, ECO:0000269|PubMed:33826201}.
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:0000305|PubMed:19903941};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24932;
CC Evidence={ECO:0000305|PubMed:19903941};
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 -!- ACTIVITY REGULATION: Activated by calmodulin in the presence of calcium
CC ions. {ECO:0000269|PubMed:18948540}.
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 (PubMed:18948540).
CC {ECO:0000250|UniProtKB:P32929, ECO:0000269|PubMed:18948540}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in liver and kidney, and at lower levels
CC in small intestine (at protein level) (PubMed:15038791). Highly
CC expressed in liver, kidney and lung, detected at lower levels in
CC stomach, small intestine and adipose tissue, and hardly found in heart,
CC bone, and thymus (PubMed:15038791, PubMed:20305127).
CC {ECO:0000269|PubMed:15038791, ECO:0000269|PubMed:20305127}.
CC -!- DEVELOPMENTAL STAGE: First detected at low levels in embryonic liver
CC after 12.5 days of embryonic development. Highly expressed in liver and
CC kidney after 18.5 days of embryonic development. Expressed at high
CC levels in liver and kidney after birth and in adults. Age-dependent
CC expression in mouse skeletal muscles; protein expression in skeletal
CC muscles increased 5 days after birth, and remained stable until 10
CC weeks, then slightly decreased at 26 weeks and was significantly lower
CC at 51 weeks (PubMed:33826201). {ECO:0000269|PubMed:33826201}.
CC -!- INDUCTION: Tumor necrosis factor alpha (TNF-alpha) promotes the binding
CC of SP1 to the CSE promoter, inducing its transcription.
CC {ECO:0000269|PubMed:22244329}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth. Mice exhibit
CC strongly decreased levels of hydrogen sulfide (H2S) in heart and aorta.
CC Mice also show absence of protein sulfhydration on target proteins.
CC Hydrogen sulfide serum levels are also lower than normal. No effect on
CC brain hydrogen sulfide levels. Age-dependent hypertension beginning at
CC about seven weeks of age (PubMed:18948540, PubMed:19903941).
CC Deteriorated the loss of skeletal muscle mass in aging mice
CC (PubMed:33826201). {ECO:0000269|PubMed:18948540,
CC ECO:0000269|PubMed:19903941, ECO:0000269|PubMed:33826201}.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; AY083352; AAL99218.1; -; mRNA.
DR EMBL; AY262829; AAP86975.1; -; Genomic_DNA.
DR EMBL; CH466532; EDL11858.1; -; Genomic_DNA.
DR EMBL; BC019483; AAH19483.1; -; mRNA.
DR CCDS; CCDS51101.1; -.
DR RefSeq; NP_666065.1; NM_145953.2.
DR AlphaFoldDB; Q8VCN5; -.
DR SMR; Q8VCN5; -.
DR BioGRID; 223644; 4.
DR DIP; DIP-60018N; -.
DR IntAct; Q8VCN5; 1.
DR STRING; 10090.ENSMUSP00000113672; -.
DR BindingDB; Q8VCN5; -.
DR ChEMBL; CHEMBL4680037; -.
DR iPTMnet; Q8VCN5; -.
DR PhosphoSitePlus; Q8VCN5; -.
DR SwissPalm; Q8VCN5; -.
DR EPD; Q8VCN5; -.
DR jPOST; Q8VCN5; -.
DR MaxQB; Q8VCN5; -.
DR PaxDb; Q8VCN5; -.
DR PeptideAtlas; Q8VCN5; -.
DR PRIDE; Q8VCN5; -.
DR ProteomicsDB; 281657; -.
DR Antibodypedia; 19668; 424 antibodies from 34 providers.
DR DNASU; 107869; -.
DR Ensembl; ENSMUST00000118539; ENSMUSP00000113672; ENSMUSG00000028179.
DR GeneID; 107869; -.
DR KEGG; mmu:107869; -.
DR UCSC; uc008rvj.1; mouse.
DR CTD; 1491; -.
DR MGI; MGI:1339968; Cth.
DR VEuPathDB; HostDB:ENSMUSG00000028179; -.
DR eggNOG; KOG0053; Eukaryota.
DR GeneTree; ENSGT00390000000312; -.
DR HOGENOM; CLU_018986_2_3_1; -.
DR InParanoid; Q8VCN5; -.
DR OMA; YKQDGVG; -.
DR OrthoDB; 572061at2759; -.
DR PhylomeDB; Q8VCN5; -.
DR TreeFam; TF300720; -.
DR BRENDA; 4.4.1.1; 3474.
DR Reactome; R-MMU-1614558; Degradation of cysteine and homocysteine.
DR Reactome; R-MMU-1614603; Cysteine formation from homocysteine.
DR SABIO-RK; Q8VCN5; -.
DR UniPathway; UPA00136; UER00202.
DR BioGRID-ORCS; 107869; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Cth; mouse.
DR PRO; PR:Q8VCN5; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8VCN5; protein.
DR Bgee; ENSMUSG00000028179; Expressed in proximal tubule and 82 other tissues.
DR Genevisible; Q8VCN5; MM.
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; ISO:MGI.
DR GO; GO:0004123; F:cystathionine gamma-lyase activity; IDA:MGI.
DR GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IEA:UniProtKB-EC.
DR GO; GO:0044540; F:L-cystine L-cysteine-lyase (deaminating); IDA: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; IEP:MGI.
DR GO; GO:0019344; P:cysteine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; ISO:MGI.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:MGI.
DR GO; GO:0050667; P:homocysteine metabolic process; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1904831; P:positive regulation of aortic smooth muscle cell differentiation; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISO:MGI.
DR GO; GO:0044524; P:protein sulfhydration; IDA: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:MGI.
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; Lipid metabolism; Lyase; Pyridoxal phosphate;
KW Reference proteome.
FT CHAIN 1..398
FT /note="Cystathionine gamma-lyase"
FT /id="PRO_0000114751"
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 211
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P32929"
SQ SEQUENCE 398 AA; 43567 MW; B2F89625B9978599 CRC64;
MQKDASLSGF LPSFQHFATQ AIHVGQEPEQ WNSRAVVLPI SLATTFKQDF PGQSSGFEYS
RSGNPTRNCL EKAVAALDGA KHSLAFASGL AATITITHLL KAGDEIICMD EVYGGTNRYF
RRVASEFGLK ISFVDCSKTK LLEAAITPQT KLVWIETPTN PTLKLADIGA CAQIVHKRGD
IILVVDNTFM SAYFQRPLAL GADICMCSAT KYMNGHSDVV MGLVSVNSDD LNSRLRFLQN
SLGAVPSPFD CYLCCRGLKT LQVRMEKHFK NGMAVARFLE TNPRVEKVVY PGLPSHPQHE
LAKRQCSGCP GMVSFYIKGA LQHAKAFLKN LKLFTLAESL GGYESLAELP AIMTHASVPE
KDRATLGIND TLIRLSVGLE DEQDLLEDLD RALKAAHP
