CGL_HUMAN
ID CGL_HUMAN Reviewed; 405 AA.
AC P32929; B4E1R2; E9PDV0; Q53FB3; Q53Y79; Q9H4W7; Q9H4W8;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2003, sequence version 3.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Cystathionine gamma-lyase {ECO:0000303|PubMed:10212249, ECO:0000303|PubMed:10727430, ECO:0000303|PubMed:18476726, ECO:0000303|PubMed:19019829, ECO:0000303|PubMed:19261609, ECO:0000303|PubMed:19961860, ECO:0000303|PubMed:22169477};
DE Short=CGL {ECO:0000303|PubMed:10212249, ECO:0000303|PubMed:10727430, ECO:0000303|PubMed:18476726};
DE Short=CSE {ECO:0000303|PubMed:19019829, ECO:0000303|PubMed:19261609, ECO:0000303|PubMed:19961860, ECO:0000303|PubMed:22169477};
DE EC=4.4.1.1 {ECO:0000269|PubMed:10212249, ECO:0000269|PubMed:10727430, ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860};
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:0000269|PubMed:18476726, ECO:0000269|PubMed:19261609};
GN Name=CTH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ILE-403.
RC TISSUE=Liver;
RX PubMed=1339280; DOI=10.1016/0006-291x(92)92265-y;
RA Lu Y., O'Dowd B.F., Orrego H., Israel Y.;
RT "Cloning and nucleotide sequence of human liver cDNA encoding for
RT cystathionine gamma-lyase.";
RL Biochem. Biophys. Res. Commun. 189:749-758(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ILE-403.
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-403.
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [8]
RP CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, COFACTOR, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10212249; DOI=10.1074/jbc.274.18.12675;
RA Steegborn C., Clausen T., Sondermann P., Jacob U., Worbs M., Marinkovic S.,
RA Huber R., Wahl M.C.;
RT "Kinetics and inhibition of recombinant human cystathionine gamma-lyase.
RT Toward the rational control of transsulfuration.";
RL J. Biol. Chem. 274:12675-12684(1999).
RN [9]
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10727430; DOI=10.1042/bj3470291;
RA Levonen A.L., Lapatto R., Saksela M., Raivio K.O.;
RT "Human cystathionine gamma-lyase: developmental and in vitro expression of
RT two isoforms.";
RL Biochem. J. 347:291-295(2000).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19261609; DOI=10.1074/jbc.m808026200;
RA Chiku T., Padovani D., Zhu W., Singh S., Vitvitsky V., Banerjee R.;
RT "H2S biogenesis by human cystathionine gamma-lyase leads to the novel
RT sulfur metabolites lanthionine and homolanthionine and is responsive to the
RT grade of hyperhomocysteinemia.";
RL J. Biol. Chem. 284:11601-11612(2009).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=19961860; DOI=10.1016/j.jmb.2009.11.058;
RA Huang S., Chua J.H., Yew W.S., Sivaraman J., Moore P.K., Tan C.H.,
RA Deng L.W.;
RT "Site-directed mutagenesis on human cystathionine-gamma-lyase reveals
RT insights into the modulation of H2S production.";
RL J. Mol. Biol. 396:708-718(2010).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP FUNCTION AS CYSTEINE-PROTEIN SULFHYDRASE.
RX PubMed=22169477; DOI=10.1126/scisignal.2002329;
RA Krishnan N., Fu C., Pappin D.J., Tonks N.K.;
RT "H2s-induced sulfhydration of the phosphatase PTP1B and its role in the
RT endoplasmic reticulum stress response.";
RL Sci. Signal. 4:RA86-RA86(2011).
RN [15]
RP FUNCTION, AND INDUCTION BY ESTROGEN RECEPTOR ALPHA.
RX PubMed=29254196; DOI=10.18632/oncotarget.21514;
RA Lambertini E., Penolazzi L., Angelozzi M., Grassi F., Gambari L.,
RA Lisignoli G., De Bonis P., Cavallo M., Piva R.;
RT "The expression of cystathionine gamma-lyase is regulated by estrogen
RT receptor alpha in human osteoblasts.";
RL Oncotarget 8:101686-101696(2017).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-402 IN COMPLEXES WITH PYRODOXAL
RP PHOSPHATE; NITRATE AND PROPARGYLGLYCINE, FUNCTION, SUBUNIT, ACTIVITY
RP REGULATION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19019829; DOI=10.1074/jbc.m805459200;
RA Sun Q., Collins R., Huang S., Holmberg-Schiavone L., Anand G.S., Tan C.-H.,
RA van-den-Berg S., Deng L.-W., Moore P.K., Karlberg T., Sivaraman J.;
RT "Structural basis for the inhibition mechanism of human cystathionine
RT gamma-lyase, an enzyme responsible for the production of H(2)S.";
RL J. Biol. Chem. 284:3076-3085(2009).
RN [18]
RP VARIANTS CSTNU ILE-67 AND GLU-240, AND VARIANT ILE-403.
RX PubMed=12574942; DOI=10.1007/s00439-003-0906-8;
RA Wang J., Hegele R.A.;
RT "Genomic basis of cystathioninuria (MIM 219500) revealed by multiple
RT mutations in cystathionine gamma-lyase (CTH).";
RL Hum. Genet. 112:404-408(2003).
RN [19]
RP CHARACTERIZATION OF VARIANTS CSTNU ILE-67 AND GLU-240, FUNCTION, COFACTOR,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=18476726; DOI=10.1021/bi800351a;
RA Zhu W., Lin A., Banerjee R.;
RT "Kinetic properties of polymorphic variants and pathogenic mutants in human
RT cystathionine gamma-lyase.";
RL Biochemistry 47:6226-6232(2008).
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 (PubMed:10212249,
CC PubMed:19261609, PubMed:19961860, PubMed:18476726). Part of the L-
CC cysteine derived from the trans-sulfuration pathway is utilized for
CC biosynthesis of the ubiquitous antioxidant glutathione
CC (PubMed:18476726). Besides its role in the conversion of L-
CC 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 the endogenous gaseous signaling molecule hydrogen sulfide
CC (H2S) (PubMed:10212249, PubMed:19261609, PubMed:19961860,
CC PubMed:19019829). In vitro, it converts two L-cysteine molecules into
CC lanthionine and H2S, also two L-homocysteine molecules to
CC homolanthionine and H2S, which can be particularly relevant under
CC conditions of severe hyperhomocysteinemia (which is a risk factor for
CC cardiovascular disease, diabetes, and Alzheimer's disease)
CC (PubMed:19261609). 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 (PubMed:19261609). Acts as a
CC cysteine-protein sulfhydrase by mediating sulfhydration of target
CC proteins: sulfhydration consists of converting -SH groups into -SSH on
CC specific cysteine residues of target proteins such as GAPDH, PTPN1 and
CC NF-kappa-B subunit RELA, thereby regulating their function
CC (PubMed:22169477). By generating the gasotransmitter H2S, it
CC participates in a number of physiological processes such as
CC vasodilation, bone protection, and inflammation (Probable)
CC (PubMed:29254196). Plays an essential role in myogenesis by
CC contributing to the biogenesis of H2S in skeletal muscle tissue (By
CC similarity). Can also accept homoserine as substrate (By similarity).
CC Catalyzes the elimination of selenocystathionine (which can be derived
CC from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By
CC similarity). {ECO:0000250|UniProtKB:P18757,
CC ECO:0000250|UniProtKB:Q8VCN5, ECO:0000269|PubMed:10212249,
CC ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19019829,
CC ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860,
CC ECO:0000269|PubMed:22169477, ECO:0000269|PubMed:29254196,
CC ECO:0000303|PubMed:18476726, ECO:0000305|PubMed:18476726,
CC ECO:0000305|PubMed:19019829}.
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:10212249, ECO:0000269|PubMed:10727430,
CC ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19261609};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14006;
CC Evidence={ECO:0000305|PubMed:10212249, ECO:0000305|PubMed:10727430,
CC ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19261609};
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; Evidence={ECO:0000269|PubMed:10212249,
CC ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19019829,
CC ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24932;
CC Evidence={ECO:0000269|PubMed:19961860, ECO:0000305|PubMed:10212249,
CC ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19019829,
CC ECO:0000305|PubMed:19261609};
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:0000269|PubMed:18476726, ECO:0000269|PubMed:19261609};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14502;
CC Evidence={ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19261609};
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:0000269|PubMed:10212249, ECO:0000269|PubMed:18476726,
CC ECO:0000269|PubMed:19019829, ECO:0000269|PubMed:19961860};
CC -!- ACTIVITY REGULATION: Inhibited by propargylglycine, trifluoroalanine
CC and aminoethoxyvinylglycine. {ECO:0000269|PubMed:10212249,
CC ECO:0000269|PubMed:19019829}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.5 mM for L,L-cystathionine {ECO:0000269|PubMed:10212249};
CC KM=0.3 mM for L,L-cystathionine {ECO:0000269|PubMed:19261609};
CC KM=2.7 mM for L-homocysteine {ECO:0000269|PubMed:19261609};
CC KM=3.7 mM for L-cysteine {ECO:0000269|PubMed:19261609};
CC KM=2.75 mM for L-cysteine {ECO:0000269|PubMed:19019829};
CC KM=0.4 mM for L,L-cystathionine {ECO:0000269|PubMed:18476726};
CC KM=5.4 mM for L-homocysteine {ECO:0000269|PubMed:18476726};
CC KM=3.5 mM for L-cysteine {ECO:0000269|PubMed:18476726};
CC Vmax=2.5 umol/min/mg enzyme with L,L-cystathionine as substrate
CC {ECO:0000269|PubMed:10212249};
CC Vmax=3.1 umol/min/mg enzyme with L,L-cystathionine as substrate
CC {ECO:0000269|PubMed:19261609};
CC Vmax=2.3 umol/min/mg enzyme with L,L-cystathionine as substrate
CC {ECO:0000269|PubMed:18476726};
CC Vmax=4.7 umol/min/mg enzyme with L-homocysteine as substrate
CC {ECO:0000269|PubMed:18476726};
CC Vmax=0.9 umol/min/mg enzyme with L-cysteine as substrate
CC {ECO:0000269|PubMed:18476726};
CC Vmax=0.14 umol/min/mg enzyme with L-cysteine as substrate
CC {ECO:0000269|PubMed:19019829};
CC pH dependence:
CC Optimum pH is 8.2 with L,L-cystathionine.
CC {ECO:0000269|PubMed:10212249, ECO:0000269|PubMed:18476726};
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 2/2.
CC {ECO:0000305|PubMed:10212249, ECO:0000305|PubMed:18476726,
CC ECO:0000305|PubMed:19261609}.
CC -!- SUBUNIT: Homotetramer (PubMed:19019829). Interacts with CALM in a
CC calcium-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:Q8VCN5, ECO:0000269|PubMed:19019829}.
CC -!- INTERACTION:
CC P32929; P32929: CTH; NbExp=7; IntAct=EBI-749763, EBI-749763;
CC P32929; Q96NT3: GUCD1; NbExp=3; IntAct=EBI-749763, EBI-8293751;
CC P32929; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-749763, EBI-11978177;
CC P32929; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-749763, EBI-741158;
CC P32929; Q6P9E2: RECK; NbExp=6; IntAct=EBI-749763, EBI-10253121;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P32929-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32929-2; Sequence=VSP_006306;
CC Name=3;
CC IsoId=P32929-3; Sequence=VSP_047274;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver (PubMed:10727430,
CC PubMed:20305127). Also in muscle and lower expression in most tissues
CC except heart, pituitary gland, spleen, thymus, and vascular tissue,
CC where it is hardly detected (PubMed:20305127).
CC {ECO:0000269|PubMed:10727430, ECO:0000269|PubMed:20305127}.
CC -!- DEVELOPMENTAL STAGE: mRNA is detected from the 19th gestational week
CC onwards at levels comparable with those of adult liver.
CC {ECO:0000269|PubMed:10727430}.
CC -!- INDUCTION: Estrogen receptor alpha (ESR1) regulates CSE promoter
CC activity and induces protein expression in human osteoblasts.
CC {ECO:0000269|PubMed:29254196}.
CC -!- DISEASE: Cystathioninuria (CSTNU) [MIM:219500]: Autosomal recessive
CC phenotype characterized by abnormal accumulation of plasma
CC cystathionine, leading to increased urinary excretion.
CC {ECO:0000269|PubMed:12574942, ECO:0000269|PubMed:18476726}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family.
CC {ECO:0000305}.
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DR EMBL; S52784; AAB24700.1; -; mRNA.
DR EMBL; S52028; AAB24699.1; -; mRNA.
DR EMBL; BT006882; AAP35528.1; -; mRNA.
DR EMBL; AK303946; BAG64874.1; -; mRNA.
DR EMBL; AK223376; BAD97096.1; -; mRNA.
DR EMBL; AL354872; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06450.1; -; Genomic_DNA.
DR EMBL; BC015807; AAH15807.1; -; mRNA.
DR CCDS; CCDS53333.1; -. [P32929-3]
DR CCDS; CCDS650.1; -. [P32929-1]
DR CCDS; CCDS651.1; -. [P32929-2]
DR PIR; JC1362; JC1362.
DR RefSeq; NP_001177392.1; NM_001190463.1. [P32929-3]
DR RefSeq; NP_001893.2; NM_001902.5. [P32929-1]
DR RefSeq; NP_714964.2; NM_153742.4. [P32929-2]
DR PDB; 2NMP; X-ray; 2.60 A; A/B/C/D=1-402.
DR PDB; 3COG; X-ray; 2.00 A; A/B/C/D=1-402.
DR PDB; 3ELP; X-ray; 2.40 A; A/B/C/D=1-405.
DR PDB; 5EIG; X-ray; 2.70 A; A/B/C/D/E/F/G/H=1-405.
DR PDB; 5TSU; X-ray; 2.20 A; A/B/C/D/E/F/G/H=2-405.
DR PDB; 5TT2; X-ray; 2.95 A; C/D=2-405.
DR PDB; 6NBA; X-ray; 2.50 A; A/B/C/D=1-402.
DR PDB; 6OVG; X-ray; 2.72 A; A/B/C/D/E/F/G/H=2-405.
DR PDBsum; 2NMP; -.
DR PDBsum; 3COG; -.
DR PDBsum; 3ELP; -.
DR PDBsum; 5EIG; -.
DR PDBsum; 5TSU; -.
DR PDBsum; 5TT2; -.
DR PDBsum; 6NBA; -.
DR PDBsum; 6OVG; -.
DR AlphaFoldDB; P32929; -.
DR SMR; P32929; -.
DR BioGRID; 107873; 61.
DR IntAct; P32929; 25.
DR MINT; P32929; -.
DR STRING; 9606.ENSP00000359976; -.
DR BindingDB; P32929; -.
DR ChEMBL; CHEMBL4295745; -.
DR DrugBank; DB02328; 2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-Phosphono-Pent-3-Enoic Acid.
DR DrugBank; DB03928; Carboxymethylthio-3-(3-Chlorophenyl)-1,2,4-Oxadiazol.
DR DrugBank; DB00151; Cysteine.
DR DrugBank; DB04217; L-2-amino-3-butynoic acid.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR GuidetoPHARMACOLOGY; 1444; -.
DR GlyGen; P32929; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P32929; -.
DR PhosphoSitePlus; P32929; -.
DR BioMuta; CTH; -.
DR DMDM; 27735163; -.
DR EPD; P32929; -.
DR jPOST; P32929; -.
DR MassIVE; P32929; -.
DR MaxQB; P32929; -.
DR PaxDb; P32929; -.
DR PeptideAtlas; P32929; -.
DR PRIDE; P32929; -.
DR ProteomicsDB; 19753; -.
DR ProteomicsDB; 54890; -. [P32929-1]
DR ProteomicsDB; 54891; -. [P32929-2]
DR Antibodypedia; 19668; 424 antibodies from 34 providers.
DR DNASU; 1491; -.
DR Ensembl; ENST00000346806.2; ENSP00000311554.2; ENSG00000116761.12. [P32929-2]
DR Ensembl; ENST00000370938.8; ENSP00000359976.3; ENSG00000116761.12. [P32929-1]
DR Ensembl; ENST00000411986.6; ENSP00000413407.2; ENSG00000116761.12. [P32929-3]
DR GeneID; 1491; -.
DR KEGG; hsa:1491; -.
DR MANE-Select; ENST00000370938.8; ENSP00000359976.3; NM_001902.6; NP_001893.2.
DR UCSC; uc001dfd.4; human. [P32929-1]
DR CTD; 1491; -.
DR DisGeNET; 1491; -.
DR GeneCards; CTH; -.
DR HGNC; HGNC:2501; CTH.
DR HPA; ENSG00000116761; Group enriched (liver, ovary).
DR MalaCards; CTH; -.
DR MIM; 219500; phenotype.
DR MIM; 607657; gene.
DR neXtProt; NX_P32929; -.
DR OpenTargets; ENSG00000116761; -.
DR Orphanet; 212; Cystathioninuria.
DR PharmGKB; PA27004; -.
DR VEuPathDB; HostDB:ENSG00000116761; -.
DR eggNOG; KOG0053; Eukaryota.
DR GeneTree; ENSGT00390000000312; -.
DR HOGENOM; CLU_018986_2_3_1; -.
DR InParanoid; P32929; -.
DR OMA; YKQDGVG; -.
DR OrthoDB; 572061at2759; -.
DR PhylomeDB; P32929; -.
DR TreeFam; TF300720; -.
DR BioCyc; MetaCyc:HS04050-MON; -.
DR BRENDA; 4.4.1.1; 2681.
DR PathwayCommons; P32929; -.
DR Reactome; R-HSA-1614558; Degradation of cysteine and homocysteine.
DR Reactome; R-HSA-1614603; Cysteine formation from homocysteine.
DR Reactome; R-HSA-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR SABIO-RK; P32929; -.
DR SignaLink; P32929; -.
DR UniPathway; UPA00136; UER00202.
DR BioGRID-ORCS; 1491; 13 hits in 1086 CRISPR screens.
DR ChiTaRS; CTH; human.
DR EvolutionaryTrace; P32929; -.
DR GenomeRNAi; 1491; -.
DR Pharos; P32929; Tchem.
DR PRO; PR:P32929; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P32929; protein.
DR Bgee; ENSG00000116761; Expressed in right lobe of liver and 163 other tissues.
DR Genevisible; P32929; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IEA:UniProtKB-EC.
DR GO; GO:0044540; F:L-cystine L-cysteine-lyase (deaminating); IMP:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0098606; F:selenocystathionine gamma-lyase activity; IEA:RHEA.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0019344; P:cysteine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; IDA:BHF-UCL.
DR GO; GO:0006534; P:cysteine metabolic process; TAS:ProtInc.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; TAS:UniProtKB.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1904831; P:positive regulation of aortic smooth muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB.
DR GO; GO:0044524; P:protein sulfhydration; IMP:UniProtKB.
DR GO; GO:0018272; P:protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine; IDA:UniProtKB.
DR GO; GO:0019346; P:transsulfuration; IDA:BHF-UCL.
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 3D-structure; Alternative splicing; Amino-acid biosynthesis;
KW Calmodulin-binding; Cysteine biosynthesis; Cytoplasm; Disease variant;
KW Lipid metabolism; Lyase; Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..405
FT /note="Cystathionine gamma-lyase"
FT /id="PRO_0000114749"
FT BINDING 62
FT /ligand="substrate"
FT BINDING 114
FT /ligand="substrate"
FT BINDING 119
FT /ligand="substrate"
FT BINDING 339
FT /ligand="substrate"
FT MOD_RES 212
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:19019829"
FT VAR_SEQ 85..116
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047274"
FT VAR_SEQ 153..196
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1339280"
FT /id="VSP_006306"
FT VARIANT 67
FT /note="T -> I (in CSTNU; reduces catalytic activity and
FT affinity for pyridoxal phosphate; dbSNP:rs28941785)"
FT /evidence="ECO:0000269|PubMed:12574942,
FT ECO:0000269|PubMed:18476726"
FT /id="VAR_015450"
FT VARIANT 240
FT /note="Q -> E (in CSTNU; strongly reduces catalytic
FT activity and affinity for pyridoxal phosphate;
FT dbSNP:rs28941786)"
FT /evidence="ECO:0000269|PubMed:12574942,
FT ECO:0000269|PubMed:18476726"
FT /id="VAR_015451"
FT VARIANT 403
FT /note="S -> I (in dbSNP:rs1021737)"
FT /evidence="ECO:0000269|PubMed:12574942,
FT ECO:0000269|PubMed:1339280, ECO:0000269|PubMed:14702039,
FT ECO:0000269|Ref.4"
FT /id="VAR_015452"
FT HELIX 18..24
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:5TSU"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 66..79
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 90..98
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 115..123
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 140..146
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 151..159
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 198..202
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 210..215
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 230..243
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 249..259
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 262..281
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 300..306
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 312..320
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 322..331
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:3COG"
FT TURN 351..358
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 361..367
FT /evidence="ECO:0007829|PDB:3COG"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:3COG"
FT HELIX 383..397
FT /evidence="ECO:0007829|PDB:3COG"
SQ SEQUENCE 405 AA; 44508 MW; 003246D7C1D16723 CRC64;
MQEKDASSQG FLPHFQHFAT QAIHVGQDPE QWTSRAVVPP ISLSTTFKQG APGQHSGFEY
SRSGNPTRNC LEKAVAALDG AKYCLAFASG LAATVTITHL LKAGDQIICM DDVYGGTNRY
FRQVASEFGL KISFVDCSKI KLLEAAITPE TKLVWIETPT NPTQKVIDIE GCAHIVHKHG
DIILVVDNTF MSPYFQRPLA LGADISMYSA TKYMNGHSDV VMGLVSVNCE SLHNRLRFLQ
NSLGAVPSPI DCYLCNRGLK TLHVRMEKHF KNGMAVAQFL ESNPWVEKVI YPGLPSHPQH
ELVKRQCTGC TGMVTFYIKG TLQHAEIFLK NLKLFTLAES LGGFESLAEL PAIMTHASVL
KNDRDVLGIS DTLIRLSVGL EDEEDLLEDL DQALKAAHPP SGSHS
