ID AATC_HUMAN Reviewed; 413 AA. AC P17174; B2R6R7; B7Z7E9; Q5VW80; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 228. DE RecName: Full=Aspartate aminotransferase, cytoplasmic {ECO:0000305}; DE Short=cAspAT; DE EC=2.6.1.1 {ECO:0000269|PubMed:21900944}; DE EC=2.6.1.3 {ECO:0000250|UniProtKB:P13221}; DE AltName: Full=Cysteine aminotransferase, cytoplasmic; DE AltName: Full=Cysteine transaminase, cytoplasmic; DE Short=cCAT; DE AltName: Full=Glutamate oxaloacetate transaminase 1; DE AltName: Full=Transaminase A; GN Name=GOT1 {ECO:0000312|HGNC:HGNC:4432}; 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] (ISOFORM 1), AND SUBCELLULAR LOCATION. RC TISSUE=Liver; RX PubMed=1974457; DOI=10.1021/bi00474a011; RA Bousquet-Lemercier B., Pol S., Pave-Preux M., Hanoune J., Barouki R.; RT "Properties of human liver cytosolic aspartate aminotransferase mRNAs RT generated by alternative polyadenylation site selection."; RL Biochemistry 29:5293-5299(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang C.Y., Huang Y.Q., Shi J.D., Marron M.P., Ruan Q.G., Hawkins-Lee B., RA Ochoa B., She J.X.; RT "Genomic structure and mutation analysis of GOT1 in the urofacial (Ochoa) RT syndrome gene critical region on chromosome 10."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Yu W., Sarginson J., Gibbs R.A.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). 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=Lung; 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 PROTEIN SEQUENCE OF 2-413. RC TISSUE=Liver; RX PubMed=2241899; DOI=10.1042/bj2700651; RA Doyle J.M., Schinina M.E., Bossa F., Doonan S.; RT "The amino acid sequence of cytosolic aspartate aminotransferase from human RT liver."; RL Biochem. J. 270:651-657(1990). RN [9] RP FUNCTION. RX PubMed=16039064; DOI=10.1016/j.neulet.2005.06.030; RA D'Aniello A., Fisher G., Migliaccio N., Cammisa G., D'Aniello E., RA Spinelli P.; RT "Amino acids and transaminases activity in ventricular CSF and in brain of RT normal and Alzheimer patients."; RL Neurosci. Lett. 388:49-53(2005). RN [10] 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 [11] RP INVOLVEMENT IN ASTQTL1, VARIANT ASN-389 DEL, FUNCTION, CATALYTIC ACTIVITY, RP CHARACTERIZATION OF VARIANT ASN-389 DEL, AND POLYMORPHISM. RX PubMed=21900944; DOI=10.1038/jhg.2011.105; RA Shen H., Damcott C., Shuldiner S.R., Chai S., Yang R., Hu H., Gibson Q., RA Ryan K.A., Mitchell B.D., Gong D.W.; RT "Genome-wide association study identifies genetic variants in GOT1 RT determining serum aspartate aminotransferase levels."; RL J. Hum. Genet. 56:801-805(2011). RN [12] RP FETAL BLOOD LEVELS. RX PubMed=22633534; DOI=10.1016/j.earlhumdev.2012.05.001; RA Zlotnik A., Tsesis S., Gruenbaum B.F., Ohayon S., Gruenbaum S.E., Boyko M., RA Sheiner E., Brotfain E., Shapira Y., Teichberg V.I.; RT "Relationship between glutamate, GOT and GPT levels in maternal and fetal RT blood: a potential mechanism for fetal neuroprotection."; RL Early Hum. Dev. 88:773-778(2012). RN [13] RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] 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 [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=27827456; DOI=10.1038/srep36749; RA Irino Y., Toh R., Nagao M., Mori T., Honjo T., Shinohara M., Tsuda S., RA Nakajima H., Satomi-Kobayashi S., Shinke T., Tanaka H., Ishida T., RA Miyata O., Hirata K.I.; RT "2-Aminobutyric acid modulates glutathione homeostasis in the myocardium."; RL Sci. Rep. 6:36749-36749(2016). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-412 IN COMPLEX WITH PYRIDOXAL RP PHOSPHATE AND TARTARIC ACID, SUBUNIT, AND PYRIDOXAL PHOSPHATE AT LYS-259. RG Structural genomics consortium (SGC); RT "Crystal structure of human glutamate oxaloacetate transaminase 1 (GOT1)."; RL Submitted (AUG-2009) to the PDB data bank. CC -!- FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L-cysteine CC (PubMed:21900944). Important regulator of levels of glutamate, the CC major excitatory neurotransmitter of the vertebrate central nervous CC system. Acts as a scavenger of glutamate in brain neuroprotection. The CC aspartate aminotransferase activity is involved in hepatic glucose CC synthesis during development and in adipocyte glyceroneogenesis. Using CC L-cysteine as substrate, regulates levels of mercaptopyruvate, an CC important source of hydrogen sulfide. Mercaptopyruvate is converted CC into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase CC (3MST). Hydrogen sulfide is an important synaptic modulator and CC neuroprotectant in the brain. In addition, catalyzes (2S)-2- CC aminobutanoate, a by-product in the cysteine biosynthesis pathway CC (PubMed:27827456). {ECO:0000269|PubMed:16039064, CC ECO:0000269|PubMed:21900944, ECO:0000269|PubMed:27827456}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; CC Xref=Rhea:RHEA:21824, ChEBI:CHEBI:16452, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:29991; EC=2.6.1.1; CC Evidence={ECO:0000269|PubMed:21900944}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21825; CC Evidence={ECO:0000250|UniProtKB:P13221}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteine + 2-oxoglutarate = 2-oxo-3-sulfanylpropanoate + L- CC glutamate; Xref=Rhea:RHEA:17441, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:35235, ChEBI:CHEBI:57678; EC=2.6.1.3; CC Evidence={ECO:0000250|UniProtKB:P13221}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17442; CC Evidence={ECO:0000250|UniProtKB:P13221}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L- CC glutamate; Xref=Rhea:RHEA:70223, ChEBI:CHEBI:16763, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:74359; CC Evidence={ECO:0000269|PubMed:27827456}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70225; CC Evidence={ECO:0000269|PubMed:27827456}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-sulfino-L-alanine + 2-oxoglutarate = 3-sulfinopyruvate + L- CC glutamate; Xref=Rhea:RHEA:70295, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:61085, ChEBI:CHEBI:140699; CC Evidence={ECO:0000250|UniProtKB:P13221}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70297; CC Evidence={ECO:0000250|UniProtKB:P13221}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.17}. CC -!- INTERACTION: CC P17174; P15056: BRAF; NbExp=5; IntAct=EBI-727329, EBI-365980; CC P17174; P00533: EGFR; NbExp=3; IntAct=EBI-727329, EBI-297353; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1974457}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P17174-1; Sequence=Displayed; CC Name=2; CC IsoId=P17174-2; Sequence=VSP_055799; CC -!- POLYMORPHISM: Genetic variations in GOT1 are associated with low serum CC aspartate aminotransferase and define the aspartate aminotransferase CC serum level quantitative trait locus 1 (ASTQTL1) [MIM:614419]. CC {ECO:0000269|PubMed:21900944}. CC -!- MISCELLANEOUS: In eukaryotes there are cytoplasmic, mitochondrial and CC chloroplastic isozymes. CC -!- MISCELLANEOUS: Aspartate aminotransferase activity found to be CC increased in cerebral spinal fluid (CSF) of patients with Alzheimer CC disease (PubMed:16039064). Fetal serum levels of the enzyme in the CC umbilical artery and vein are found to be significantly higher than CC maternal serum levels (PubMed:22633534). {ECO:0000305|PubMed:16039064, CC ECO:0000305|PubMed:22633534}. CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent CC aminotransferase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M37400; AAA35563.1; -; mRNA. DR EMBL; AF080467; AAC32851.1; -; Genomic_DNA. DR EMBL; AF080459; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080460; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080461; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080462; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080463; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080464; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080465; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF080466; AAC32851.1; JOINED; Genomic_DNA. DR EMBL; AF052153; AAC28622.1; -; mRNA. DR EMBL; AK301916; BAH13585.1; -; mRNA. DR EMBL; AK312684; BAG35564.1; -; mRNA. DR EMBL; AL391684; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49869.1; -; Genomic_DNA. DR EMBL; BC000498; AAH00498.1; -; mRNA. DR CCDS; CCDS7479.1; -. [P17174-1] DR PIR; S13035; S13035. DR PIR; S29027; S29027. DR RefSeq; NP_002070.1; NM_002079.3. [P17174-1] DR PDB; 3II0; X-ray; 2.05 A; A/B/C/D=14-412. DR PDB; 3WZF; X-ray; 2.99 A; A=2-413. DR PDB; 6DNA; X-ray; 3.00 A; A/B/C/D/E/F=6-410. DR PDB; 6DNB; X-ray; 1.70 A; A=3-413. DR PDB; 6DND; X-ray; 2.10 A; A/B=3-413. DR PDB; 6LIG; X-ray; 2.62 A; A/B=3-413. DR PDB; 8Z0E; X-ray; 1.82 A; A/B=1-413. DR PDBsum; 3II0; -. DR PDBsum; 3WZF; -. DR PDBsum; 6DNA; -. DR PDBsum; 6DNB; -. DR PDBsum; 6DND; -. DR PDBsum; 6LIG; -. DR PDBsum; 8Z0E; -. DR AlphaFoldDB; P17174; -. DR SMR; P17174; -. DR BioGRID; 109067; 274. DR FunCoup; P17174; 2117. DR IntAct; P17174; 194. DR MINT; P17174; -. DR STRING; 9606.ENSP00000359539; -. DR BindingDB; P17174; -. DR ChEMBL; CHEMBL2189139; -. DR DrugBank; DB00210; Adapalene. DR DrugBank; DB00128; Aspartic acid. DR DrugBank; DB09130; Copper. DR DrugBank; DB00151; Cysteine. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB04299; Maleic acid. DR DrugBank; DB00114; Pyridoxal phosphate. DR DrugCentral; P17174; -. DR GlyGen; P17174; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P17174; -. DR PhosphoSitePlus; P17174; -. DR SwissPalm; P17174; -. DR BioMuta; GOT1; -. DR DMDM; 5902703; -. DR REPRODUCTION-2DPAGE; IPI00219029; -. DR jPOST; P17174; -. DR MassIVE; P17174; -. DR PaxDb; 9606-ENSP00000359539; -. DR PeptideAtlas; P17174; -. DR PRIDE; P17174; -. DR ProteomicsDB; 53459; -. [P17174-1] DR ProteomicsDB; 6862; -. DR Pumba; P17174; -. DR Antibodypedia; 31077; 571 antibodies from 38 providers. DR DNASU; 2805; -. DR Ensembl; ENST00000370508.7; ENSP00000359539.5; ENSG00000120053.13. [P17174-1] DR GeneID; 2805; -. DR KEGG; hsa:2805; -. DR MANE-Select; ENST00000370508.7; ENSP00000359539.5; NM_002079.3; NP_002070.1. DR UCSC; uc001kpr.4; human. [P17174-1] DR AGR; HGNC:4432; -. DR ClinPGx; PA28817; -. DR CTD; 2805; -. DR DisGeNET; 2805; -. DR GeneCards; GOT1; -. DR HGNC; HGNC:4432; GOT1. DR HPA; ENSG00000120053; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MalaCards; GOT1; -. DR MIM; 138180; gene. DR MIM; 614419; phenotype. DR OpenTargets; ENSG00000120053; -. DR VEuPathDB; HostDB:ENSG00000120053; -. DR eggNOG; KOG1412; Eukaryota. DR GeneTree; ENSGT00950000183082; -. DR HOGENOM; CLU_032440_1_2_1; -. DR InParanoid; P17174; -. DR OMA; GTWTHIT; -. DR OrthoDB; 6752799at2759; -. DR PAN-GO; P17174; 3 GO annotations based on evolutionary models. DR PhylomeDB; P17174; -. DR BioCyc; MetaCyc:HS04361-MONOMER; -. DR BRENDA; 2.6.1.1; 2681. DR BRENDA; 2.6.1.64; 2681. DR PathwayCommons; P17174; -. DR Reactome; R-HSA-1237112; Methionine salvage pathway. DR Reactome; R-HSA-8963693; Aspartate and asparagine metabolism. DR Reactome; R-HSA-9856872; Malate-aspartate shuttle. DR SABIO-RK; P17174; -. DR SignaLink; P17174; -. DR SIGNOR; P17174; -. DR Agora; ENSG00000120053; -. DR BioGRID-ORCS; 2805; 25 hits in 1159 CRISPR screens. DR ChiTaRS; GOT1; human. DR EvolutionaryTrace; P17174; -. DR GeneWiki; GOT1; -. DR GenomeRNAi; 2805; -. DR Pharos; P17174; Tbio. DR PRO; PR:P17174; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P17174; protein. DR Bgee; ENSG00000120053; Expressed in heart right ventricle and 205 other cell types or tissues. DR ExpressionAtlas; P17174; baseline and differential. DR GO; GO:0043679; C:axon terminus; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0120554; F:2-aminobutanoate transaminase activity; IDA:FlyBase. DR GO; GO:0031406; F:carboxylic acid binding; IEA:Ensembl. DR GO; GO:0004069; F:L-aspartate:2-oxoglutarate aminotransferase activity; IDA:UniProtKB. DR GO; GO:0047801; F:L-cysteine transaminase activity; ISS:UniProtKB. DR GO; GO:0004609; F:phosphatidylserine decarboxylase activity; IEA:Ensembl. DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro. DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB. DR GO; GO:0006532; P:aspartate biosynthetic process; IBA:GO_Central. DR GO; GO:0006531; P:aspartate metabolic process; ISS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl. DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl. DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB. DR GO; GO:0006114; P:glycerol biosynthetic process; ISS:UniProtKB. DR GO; GO:0006533; P:L-aspartate catabolic process; IDA:UniProtKB. DR GO; GO:0097054; P:L-glutamate biosynthetic process; IEA:Ensembl. DR GO; GO:0019550; P:L-glutamate catabolic process to aspartate; IEA:Ensembl. DR GO; GO:0043490; P:malate-aspartate shuttle; IMP:FlyBase. DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IEA:Ensembl. DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl. DR GO; GO:0009743; P:response to carbohydrate; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEP:UniProtKB. DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl. DR GO; GO:1990267; P:response to transition metal nanoparticle; IEA:Ensembl. DR GO; GO:0060290; P:transdifferentiation; IEA:Ensembl. DR CDD; cd00609; AAT_like; 1. DR FunFam; 3.40.640.10:FF:000044; Aspartate aminotransferase; 1. DR FunFam; 3.90.1150.10:FF:000001; Aspartate aminotransferase; 1. DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1. DR InterPro; IPR004839; Aminotransferase_I/II_large. DR InterPro; IPR000796; Asp_trans. DR InterPro; IPR004838; NHTrfase_class1_PyrdxlP-BS. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small. DR NCBIfam; NF006719; PRK09257.1; 1. DR PANTHER; PTHR11879; ASPARTATE AMINOTRANSFERASE; 1. DR PANTHER; PTHR11879:SF3; ASPARTATE AMINOTRANSFERASE, CYTOPLASMIC; 1. DR Pfam; PF00155; Aminotran_1_2; 1. DR PRINTS; PR00799; TRANSAMINASE. DR SUPFAM; SSF53383; PLP-dependent transferases; 1. DR PROSITE; PS00105; AA_TRANSFER_CLASS_1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amino-acid biosynthesis; KW Aminotransferase; Cytoplasm; Direct protein sequencing; Phosphoprotein; KW Proteomics identification; Pyridoxal phosphate; Reference proteome; KW Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:2241899, FT ECO:0007744|PubMed:22223895" FT CHAIN 2..413 FT /note="Aspartate aminotransferase, cytoplasmic" FT /id="PRO_0000123879" FT BINDING 39 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT BINDING 141 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT BINDING 195 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT BINDING 387 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13221" FT MOD_RES 259 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000250" FT VAR_SEQ 1..39 FT /note="MAPPSVFAEVPQAQPVLVFKLTADFREDPDPRKVNLGVG -> MQVWSPWKG FT AMCPRPHKP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055799" FT VARIANT 389 FT /note="Missing (results in markedly diminished enzymatic FT activity; dbSNP:rs749913156)" FT /evidence="ECO:0000269|PubMed:21900944" FT /id="VAR_067256" FT CONFLICT 215 FT /note="H -> R (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT TURN 6..9 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 17..27 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 29..31 FT /evidence="ECO:0007829|PDB:6DNA" FT HELIX 52..63 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 78..89 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 94..97 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 101..107 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 108..123 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 124..128 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 142..151 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 156..160 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 164..167 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 171..179 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 186..190 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 195..197 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 203..216 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 227..231 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 234..237 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 239..246 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 251..256 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 258..260 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 264..266 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 268..274 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 278..294 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 296..298 FT /evidence="ECO:0007829|PDB:6LIG" FT HELIX 302..311 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 314..344 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 353..356 FT /evidence="ECO:0007829|PDB:6DNB" FT STRAND 359..363 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 368..376 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 384..386 FT /evidence="ECO:0007829|PDB:3WZF" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 390..392 FT /evidence="ECO:0007829|PDB:6DNB" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:6DNB" FT HELIX 398..411 FT /evidence="ECO:0007829|PDB:6DNB" SQ SEQUENCE 413 AA; 46248 MW; 69FE68BF0C045219 CRC64; MAPPSVFAEV PQAQPVLVFK LTADFREDPD PRKVNLGVGA YRTDDCHPWV LPVVKKVEQK IANDNSLNHE YLPILGLAEF RSCASRLALG DDSPALKEKR VGGVQSLGGT GALRIGADFL ARWYNGTNNK NTPVYVSSPT WENHNAVFSA AGFKDIRSYR YWDAEKRGLD LQGFLNDLEN APEFSIVVLH ACAHNPTGID PTPEQWKQIA SVMKHRFLFP FFDSAYQGFA SGNLERDAWA IRYFVSEGFE FFCAQSFSKN FGLYNERVGN LTVVGKEPES ILQVLSQMEK IVRITWSNPP AQGARIVAST LSNPELFEEW TGNVKTMADR ILTMRSELRA RLEALKTPGT WNHITDQIGM FSFTGLNPKQ VEYLVNEKHI YLLPSGRINV SGLTTKNLDY VATSIHEAVT KIQ // 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 28-JAN-2026, entry version 222. 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:18476726, PubMed:19261609, PubMed:19961860). 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:19019829, PubMed:19261609, CC PubMed:19961860). 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=L,L-cystathionine + H2O = 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=L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+) + CC H(+); 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=L-homocysteine + H2O = 2-oxobutanoate + hydrogen sulfide + CC NH4(+) + H(+); 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=L-selenocystathionine + H2O = L-selenocysteine + 2- CC oxobutanoate + 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001190463.2. [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; 72. DR FunCoup; P32929; 1008. DR IntAct; P32929; 31. 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 DrugCentral; P32929; -. DR GuidetoPHARMACOLOGY; 1444; -. DR GlyGen; P32929; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P32929; -. DR PhosphoSitePlus; P32929; -. DR SwissPalm; P32929; -. DR BioMuta; CTH; -. DR DMDM; 27735163; -. DR jPOST; P32929; -. DR MassIVE; P32929; -. DR PaxDb; 9606-ENSP00000359976; -. DR PeptideAtlas; P32929; -. DR ProteomicsDB; 19753; -. DR ProteomicsDB; 54890; -. [P32929-1] DR ProteomicsDB; 54891; -. [P32929-2] DR Pumba; P32929; -. DR Antibodypedia; 19668; 429 antibodies from 35 providers. DR DNASU; 1491; -. DR Ensembl; ENST00000346806.2; ENSP00000311554.2; ENSG00000116761.13. [P32929-2] DR Ensembl; ENST00000370938.8; ENSP00000359976.3; ENSG00000116761.13. [P32929-1] DR Ensembl; ENST00000411986.6; ENSP00000413407.2; ENSG00000116761.13. [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 AGR; HGNC:2501; -. DR ClinPGx; PA27004; -. 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 OpenTargets; ENSG00000116761; -. DR Orphanet; 212; Cystathioninuria. 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; 3512640at2759; -. DR PAN-GO; P32929; 5 GO annotations based on evolutionary models. DR PhylomeDB; P32929; -. DR BioCyc; MetaCyc:HS04050-MONOMER; -. 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 SIGNOR; P32929; -. DR UniPathway; UPA00136; UER00202. DR Agora; ENSG00000116761; -. DR BioGRID-ORCS; 1491; 15 hits in 1170 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 165 other cell types or tissues. 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:0004123; F:cystathionine gamma-lyase activity; IDA:UniProtKB. DR GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:UniProtKB-EC. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0080146; F:L-cysteine desulfhydrase activity; IEA:RHEA. 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 canonical NF-kappaB signal transduction; 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 FunFam; 3.90.1150.10:FF:000008; Cystathionine gamma-synthase; 1. DR FunFam; 3.40.640.10:FF:000009; Cystathionine gamma-synthase homolog; 1. DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1. DR InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz. DR InterPro; IPR054542; Cys_met_metab_PP. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small. DR PANTHER; PTHR11808:SF15; CYSTATHIONINE GAMMA-LYASE; 1. DR PANTHER; PTHR11808; TRANS-SULFURATION ENZYME FAMILY MEMBER; 1. DR Pfam; PF01053; Cys_Met_Meta_PP; 1. DR PIRSF; PIRSF001434; CGS; 1. DR SUPFAM; SSF53383; PLP-dependent transferases; 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; Proteomics identification; Pyridoxal phosphate; KW 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 //