UniProt Accession

 CGL_HUMAN; P32929; B4E1R2; E9PDV0; Q53FB3; Q53Y79; Q9H4W7; Q9H4W8 

Genbank Protein ID

 S52784; S52028; BT006882; AK303946; AK223376; AL354872; AL354872; CH471059; BC015807 

Genbank Nucleotide ID

 AAB24700.1; AAB24699.1; AAP35528.1; BAG64874.1; BAD97096.1; CAC12901.1; CAC12902.1; EAX06450.1; AAH15807.1 

Protein Name

 Cystathionine gamma-lyase 

Protein Synonyms/Alias

 Cysteine-protein sulfhydrase; Gamma-cystathionase 

Gene Name

 CTH 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
48	ISLSTTFKQGAPGQH	ubiquitination	[1]
73	PTRNCLEKAVAALDG	ubiquitination	[1, 2, 3, 4]
139	ISFVDCSKIKLLEAA	ubiquitination	[1]
152	AAITPETKLVWIETP	ubiquitination	[3, 5]
271	VRMEKHFKNGMAVAQ	ubiquitination	[3]
304	HPQHELVKRQCTGCT	ubiquitination	[1]
333	EIFLKNLKLFTLAES	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 

Functional Description

 Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. 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. 

Sequence Annotation

 BINDING 62 62 Substrate.
 BINDING 114 114 Substrate.
 BINDING 119 119 Substrate.
 BINDING 339 339 Substrate.
 MOD_RES 212 212 N6-(pyridoxal phosphate)lysine (By
 MOD_RES 377 377 Phosphoserine (By similarity).  

Keyword

 3D-structure; Alternative splicing; Amino-acid biosynthesis; Calmodulin-binding; Complete proteome; Cysteine biosynthesis; Cytoplasm; Disease mutation; Lyase; Phosphoprotein; Polymorphism; Pyridoxal phosphate; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 405 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0004123; F:cystathionine gamma-lyase activity; IDA:UniProtKB.
 GO:0047982; F:homocysteine desulfhydrase activity; TAS:Reactome.
 GO:0080146; F:L-cysteine desulfhydrase activity; TAS:Reactome.
 GO:0044540; F:L-cystine L-cysteine-lyase (deaminating); IMP:UniProtKB.
 GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
 GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome.
 GO:0019344; P:cysteine biosynthetic process; IDA:UniProtKB.
 GO:0030968; P:endoplasmic reticulum unfolded protein response; TAS:UniProtKB.
 GO:0070814; P:hydrogen sulfide biosynthetic process; IDA:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Compara.
 GO:0051289; P:protein homotetramerization; IPI:UniProtKB.
 GO:0044524; P:protein sulfhydration; IMP:UniProtKB.
 GO:0018272; P:protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine; IDA:UniProtKB.
 GO:0000098; P:sulfur amino acid catabolic process; TAS:Reactome.
 GO:0019346; P:transsulfuration; TAS:Reactome. 

Interpro

 IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
 IPR015424; PyrdxlP-dep_Trfase.
 IPR015421; PyrdxlP-dep_Trfase_major_sub1.
 IPR015422; PyrdxlP-dep_Trfase_major_sub2. 

Pfam

 PF01053; Cys_Met_Meta_PP 

SMART

  

PROSITE

 PS00868; CYS_MET_METAB_PP 

PRINTS