true1993-10-012024-01-24214CGL_HUMANCloning and nucleotide sequence of human liver cDNA encoding for cystathionine gamma-lyase.Lu Y.O'Dowd B.F.Orrego H.Israel Y.doi:10.1016/0006-291x(92)92265-y1992Biochem. Biophys. Res. Commun.189749-758NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)VARIANT ILE-403LiverCloning of human full-length CDSs in BD Creator(TM) system donor vector.Kalnine N.Chen X.Rolfs A.Halleck A.Hines L.Eisenstein S.Koundinya M.Raphael J.Moreira D.Kelley T.LaBaer J.Lin Y.Phelan M.Farmer A.2003-05EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)Complete sequencing and characterization of 21,243 full-length human cDNAs.Ota T.Suzuki Y.Nishikawa T.Otsuki T.Sugiyama T.Irie R.Wakamatsu A.Hayashi K.Sato H.Nagai K.Kimura K.Makita H.Sekine M.Obayashi M.Nishi T.Shibahara T.Tanaka T.Ishii S.Yamamoto J.Saito K.Kawai Y.Isono Y.Nakamura Y.Nagahari K.Murakami K.Yasuda T.Iwayanagi T.Wagatsuma M.Shiratori A.Sudo H.Hosoiri T.Kaku Y.Kodaira H.Kondo H.Sugawara M.Takahashi M.Kanda K.Yokoi T.Furuya T.Kikkawa E.Omura Y.Abe K.Kamihara K.Katsuta N.Sato K.Tanikawa M.Yamazaki M.Ninomiya K.Ishibashi T.Yamashita H.Murakawa K.Fujimori K.Tanai H.Kimata M.Watanabe M.Hiraoka S.Chiba Y.Ishida S.Ono Y.Takiguchi S.Watanabe S.Yosida M.Hotuta T.Kusano J.Kanehori K.Takahashi-Fujii A.Hara H.Tanase T.-O.Nomura Y.Togiya S.Komai F.Hara R.Takeuchi K.Arita M.Imose N.Musashino K.Yuuki H.Oshima A.Sasaki N.Aotsuka S.Yoshikawa Y.Matsunawa H.Ichihara T.Shiohata N.Sano S.Moriya S.Momiyama H.Satoh N.Takami S.Terashima Y.Suzuki O.Nakagawa S.Senoh A.Mizoguchi H.Goto Y.Shimizu F.Wakebe H.Hishigaki H.Watanabe T.Sugiyama A.Takemoto M.Kawakami B.Yamazaki M.'Watanabe K.Kumagai A.Itakura S.Fukuzumi Y.Fujimori Y.Komiyama M.Tashiro H.Tanigami A.Fujiwara T.Ono T.Yamada K.Fujii Y.Ozaki K.Hirao M.Ohmori Y.Kawabata A.Hikiji T.Kobatake N.Inagaki H.Ikema Y.Okamoto S.Okitani R.Kawakami T.Noguchi S.Itoh T.Shigeta K.Senba T.Matsumura K.Nakajima Y.Mizuno T.Morinaga M.Sasaki M.Togashi T.Oyama M.Hata H.Watanabe M.'Komatsu T.Mizushima-Sugano J.Satoh T.Shirai Y.Takahashi Y.Nakagawa K.Okumura K.Nagase T.Nomura N.Kikuchi H.Masuho Y.Yamashita R.Nakai K.Yada T.Nakamura Y.'Ohara O.Isogai T.Sugano S.doi:10.1038/ng12852004Nat. Genet.3640-45NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)VARIANT ILE-403TracheaTotoki Y.Toyoda A.Takeda T.Sakaki Y.Tanaka A.Yokoyama S.2005-04EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)VARIANT ILE-403KidneyThe DNA sequence and biological annotation of human chromosome 1.Gregory S.G.Barlow K.F.McLay K.E.Kaul R.Swarbreck D.Dunham A.Scott C.E.Howe K.L.Woodfine K.Spencer C.C.A.Jones M.C.Gillson C.Searle S.Zhou Y.Kokocinski F.McDonald L.Evans R.Phillips K.Atkinson A.Cooper R.Jones C.Hall R.E.Andrews T.D.Lloyd C.Ainscough R.Almeida J.P.Ambrose K.D.Anderson F.Andrew R.W.Ashwell R.I.S.Aubin K.Babbage A.K.Bagguley C.L.Bailey J.Beasley H.Bethel G.Bird C.P.Bray-Allen S.Brown J.Y.Brown A.J.Buckley D.Burton J.Bye J.Carder C.Chapman J.C.Clark S.Y.Clarke G.Clee C.Cobley V.Collier R.E.Corby N.Coville G.J.Davies J.Deadman R.Dunn M.Earthrowl M.Ellington A.G.Errington H.Frankish A.Frankland J.French L.Garner P.Garnett J.Gay L.Ghori M.R.J.Gibson R.Gilby L.M.Gillett W.Glithero R.J.Grafham D.V.Griffiths C.Griffiths-Jones S.Grocock R.Hammond S.Harrison E.S.I.Hart E.Haugen E.Heath P.D.Holmes S.Holt K.Howden P.J.Hunt A.R.Hunt S.E.Hunter G.Isherwood J.James R.Johnson C.Johnson D.Joy A.Kay M.Kershaw J.K.Kibukawa M.Kimberley A.M.King A.Knights A.J.Lad H.Laird G.Lawlor S.Leongamornlert D.A.Lloyd D.M.Loveland J.Lovell J.Lush M.J.Lyne R.Martin S.Mashreghi-Mohammadi M.Matthews L.Matthews N.S.W.McLaren S.Milne S.Mistry S.Moore M.J.F.Nickerson T.O'Dell C.N.Oliver K.Palmeiri A.Palmer S.A.Parker A.Patel D.Pearce A.V.Peck A.I.Pelan S.Phelps K.Phillimore B.J.Plumb R.Rajan J.Raymond C.Rouse G.Saenphimmachak C.Sehra H.K.Sheridan E.Shownkeen R.Sims S.Skuce C.D.Smith M.Steward C.Subramanian S.Sycamore N.Tracey A.Tromans A.Van Helmond Z.Wall M.Wallis J.M.White S.Whitehead S.L.Wilkinson J.E.Willey D.L.Williams H.Wilming L.Wray P.W.Wu Z.Coulson A.Vaudin M.Sulston J.E.Durbin R.M.Hubbard T.Wooster R.Dunham I.Carter N.P.McVean G.Ross M.T.Harrow J.Olson M.V.Beck S.Rogers J.Bentley D.R.doi:10.1038/nature047272006Nature441315-321NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Mural R.J.Istrail S.Sutton G.G.Florea L.Halpern A.L.Mobarry C.M.Lippert R.Walenz B.Shatkay H.Dew I.Miller J.R.Flanigan M.J.Edwards N.J.Bolanos R.Fasulo D.Halldorsson B.V.Hannenhalli S.Turner R.Yooseph S.Lu F.Nusskern D.R.Shue B.C.Zheng X.H.Zhong F.Delcher A.L.Huson D.H.Kravitz S.A.Mouchard L.Reinert K.Remington K.A.Clark A.G.Waterman M.S.Eichler E.E.Adams M.D.Hunkapiller M.W.Myers E.W.Venter J.C.2005-09EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)SkinKinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration.Steegborn C.Clausen T.Sondermann P.Jacob U.Worbs M.Marinkovic S.Huber R.Wahl M.C.doi:10.1074/jbc.274.18.126751999J. Biol. Chem.27412675-12684CATALYTIC ACTIVITYFUNCTIONSUBUNITCOFACTORACTIVITY REGULATIONBIOPHYSICOCHEMICAL PROPERTIESHuman cystathionine gamma-lyase: developmental and in vitro expression of two isoforms.Levonen A.L.Lapatto R.Saksela M.Raivio K.O.doi:10.1042/bj34702912000Biochem. J.347291-295CATALYTIC ACTIVITYTISSUE SPECIFICITYDEVELOPMENTAL STAGEH2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia.Chiku T.Padovani D.Zhu W.Singh S.Vitvitsky V.Banerjee R.doi:10.1074/jbc.m8080262002009J. Biol. Chem.28411601-11612FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESSite-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production.Huang S.Chua J.H.Yew W.S.Sivaraman J.Moore P.K.Tan C.H.Deng L.W.doi:10.1016/j.jmb.2009.11.0582010J. Mol. Biol.396708-718FUNCTIONCATALYTIC ACTIVITYCOFACTORRegulation of homocysteine metabolism and methylation in human and mouse tissues.Chen N.C.Yang F.Capecci L.M.Gu Z.Schafer A.I.Durante W.Yang X.F.Wang H.doi:10.1096/fj.09-1436512010FASEB J.242804-2817TISSUE SPECIFICITYInitial characterization of the human central proteome.Burkard T.R.Planyavsky M.Kaupe I.Breitwieser F.P.Buerckstuemmer T.Bennett K.L.Superti-Furga G.Colinge J.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]H2s-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response.Krishnan N.Fu C.Pappin D.J.Tonks N.K.doi:10.1126/scisignal.20023292011Sci. Signal.4RA86FUNCTION AS CYSTEINE-PROTEIN SULFHYDRASEThe expression of cystathionine gamma-lyase is regulated by estrogen receptor alpha in human osteoblasts.Lambertini E.Penolazzi L.Angelozzi M.Grassi F.Gambari L.Lisignoli G.De Bonis P.Cavallo M.Piva R.doi:10.18632/oncotarget.215142017Oncotarget8101686-101696FUNCTIONINDUCTION BY ESTROGEN RECEPTOR ALPHAAn enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.Bian Y.Song C.Cheng K.Dong M.Wang F.Huang J.Sun D.Wang L.Ye M.Zou H.doi:10.1016/j.jprot.2013.11.0142014J. Proteomics96253-262IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S.Sun Q.Collins R.Huang S.Holmberg-Schiavone L.Anand G.S.Tan C.-H.van-den-Berg S.Deng L.-W.Moore P.K.Karlberg T.Sivaraman J.doi:10.1074/jbc.m8054592002009J. Biol. Chem.2843076-3085X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-402 IN COMPLEXES WITH PYRODOXAL PHOSPHATE; NITRATE AND PROPARGYLGLYCINEFUNCTIONSUBUNITACTIVITY REGULATIONCATALYTIC ACTIVITYCOFACTORBIOPHYSICOCHEMICAL PROPERTIESGenomic basis of cystathioninuria (MIM 219500) revealed by multiple mutations in cystathionine gamma-lyase (CTH).Wang J.Hegele R.A.doi:10.1007/s00439-003-0906-82003Hum. Genet.112404-408VARIANTS CSTNU ILE-67 AND GLU-240VARIANT ILE-403Kinetic properties of polymorphic variants and pathogenic mutants in human cystathionine gamma-lyase.Zhu W.Lin A.Banerjee R.doi:10.1021/bi800351a2008Biochemistry476226-6232CHARACTERIZATION OF VARIANTS CSTNU ILE-67 AND GLU-240FUNCTIONCOFACTORCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESSUBUNIT2.60A/B/C/D=1-4022.00A/B/C/D=1-4022.40A/B/C/D=1-4052.70A/B/C/D/E/F/G/H=1-4052.20A/B/C/D/E/F/G/H=2-4052.95C/D=2-4052.50A/B/C/D=1-4022.72A/B/C/D/E/F/G/H=2-40567252-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-Phosphono-Pent-3-Enoic AcidCarboxymethylthio-3-(3-Chlorophenyl)-1,2,4-OxadiazolCysteineL-2-amino-3-butynoic acidPyridoxal phosphate1 site, 1 O-linked glycan (1 site)478 antibodies from 34 providershumanCTHGroup enriched (liver, ovary)phenotypegeneCystathioninuriaEukaryota2681Degradation of cysteine and homocysteineCysteine formation from homocysteineMetabolism of ingested SeMet, Sec, MeSec into H2Se15 hits in 1170 CRISPR screenshumanTchemProteinExpressed in right lobe of liver and 165 other cell types or tissuesCGS_likeAspartate Aminotransferase, domain 1Type I PLP-dependent aspartate aminotransferase-like (Major domain)Cys/Met-Metab_PyrdxlP-dep_enzPyrdxlP-dep_TrfasePyrdxlP-dep_Trfase_majorPyrdxlP-dep_Trfase_smallCYSTATHIONINE GAMMA-LYASETRANS-SULFURATION ENZYME FAMILY MEMBERCys_Met_Meta_PPCGSPLP-dependent transferasesCYS_MET_METAB_PPHSCystathionine gamma-lyaseCGLCSE4.4.1.1Cysteine desulfhydraseCysteine-protein sulfhydraseGamma-cystathionaseHomocysteine desulfhydrase4.4.1.2CTHCatalyzes 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 (PubMed:10212249, PubMed:19261609, PubMed:19961860, PubMed:18476726). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). 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 the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19261609, PubMed:19961860, PubMed:19019829). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). 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 (PubMed:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). 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).Inhibited by propargylglycine, trifluoroalanine and aminoethoxyvinylglycine.0.5 mM for L,L-cystathionine0.3 mM for L,L-cystathionine2.7 mM for L-homocysteine3.7 mM for L-cysteine2.75 mM for L-cysteine0.4 mM for L,L-cystathionine5.4 mM for L-homocysteine3.5 mM for L-cysteine2.5 umol/min/mg enzyme with L,L-cystathionine as substrate3.1 umol/min/mg enzyme with L,L-cystathionine as substrate2.3 umol/min/mg enzyme with L,L-cystathionine as substrate4.7 umol/min/mg enzyme with L-homocysteine as substrate0.9 umol/min/mg enzyme with L-cysteine as substrate0.14 umol/min/mg enzyme with L-cysteine as substrateOptimum pH is 8.2 with L,L-cystathionine.Homotetramer (PubMed:19019829). Interacts with CALM in a calcium-dependent manner (By similarity).Highly expressed in liver (PubMed:10727430, PubMed:20305127). Also in muscle and lower expression in most tissues except heart, pituitary gland, spleen, thymus, and vascular tissue, where it is hardly detected (PubMed:20305127).mRNA is detected from the 19th gestational week onwards at levels comparable with those of adult liver.Estrogen receptor alpha (ESR1) regulates CSE promoter activity and induces protein expression in human osteoblasts.The disease is caused by variants affecting the gene represented in this entry.Belongs to the trans-sulfuration enzymes family.Cystathionine gamma-lyase44508140562114119339N6-(pyridoxal phosphate)lysine212In isoform 3.85116In isoform 2.153196In CSTNU; reduces catalytic activity and affinity for pyridoxal phosphate.I67In CSTNU; strongly reduces catalytic activity and affinity for pyridoxal phosphate.E240I40318242931363845476163667982889098106112115123125128131135140146151159161163169176178180183187189191193195198202204209210215223227230243249259262281286290300306312320322331333337342345347349351358361367373377383397substratefalse7false3false3false3false6CTHGUCD1GUCD1NTAQ1RECK2003-01-103445084e62daa13af98c14570a252758b287011MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCLAFASGLAATVTITHLLKAGDQIICMDDVYGGTNRYFRQVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHGDIILVVDNTFMSPYFQRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQHELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVLKNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSHS2MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCLAFASGLAATVTITHLLKAGDQIICMDDVYGGTNRYFRQVASEFGLKISFVDCSKIKLLEAAITPETKRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQHELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVLKNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSHS3MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCTNRYFRQVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHGDIILVVDNTFMSPYFQRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQHELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVLKNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSHStruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue