UniProt Accession

 CGL_MOUSE; Q8VCN5; Q6H324 

Genbank Protein ID

 AY083352; AY262829; CH466532; BC019483 

Genbank Nucleotide ID

 AAL99218.1; AAP86975.1; EDL11858.1; AAH19483.1 

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

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
47	ISLATTFKQDFPGQS	ubiquitination	[1]
72	PTRNCLEKAVAALDG	acetylation	[2, 3]
72	PTRNCLEKAVAALDG	ubiquitination	[1]
138	ISFVDCSKTKLLEAA	acetylation	[4]
138	ISFVDCSKTKLLEAA	succinylation	[4]
140	FVDCSKTKLLEAAIT	acetylation	[2, 5, 6]
140	FVDCSKTKLLEAAIT	ubiquitination	[1]
151	AAITPQTKLVWIETP	ubiquitination	[1]
259	YLCCRGLKTLQVRME	ubiquitination	[1]
270	VRMEKHFKNGMAVAR	ubiquitination	[1]
303	HPQHELAKRQCSGCP	ubiquitination	[1]
325	KGALQHAKAFLKNLK	acetylation	[4, 5]
325	KGALQHAKAFLKNLK	succinylation	[4]
325	KGALQHAKAFLKNLK	ubiquitination	[1]
329	QHAKAFLKNLKLFTL	acetylation	[5]
329	QHAKAFLKNLKLFTL	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [3] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [4] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [5] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [6] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654] 

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 61 61 Substrate (By similarity).
 BINDING 113 113 Substrate (By similarity).
 BINDING 118 118 Substrate (By similarity).
 BINDING 338 338 Substrate (By similarity).
 MOD_RES 211 211 N6-(pyridoxal phosphate)lysine (By
 MOD_RES 376 376 Phosphoserine.  

Keyword

 Amino-acid biosynthesis; Calmodulin-binding; Complete proteome; Cysteine biosynthesis; Cytoplasm; Lyase; Phosphoprotein; Pyridoxal phosphate; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 398 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0004123; F:cystathionine gamma-lyase activity; ISS:UniProtKB.
 GO:0080146; F:L-cysteine desulfhydrase activity; IEA:EC.
 GO:0044540; F:L-cystine L-cysteine-lyase (deaminating); IDA:UniProtKB.
 GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
 GO:0019344; P:cysteine biosynthetic process; ISS:UniProtKB.
 GO:0070814; P:hydrogen sulfide biosynthetic process; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:0051289; P:protein homotetramerization; IEA:Compara.
 GO:0044524; P:protein sulfhydration; IDA:UniProtKB.
 GO:0018272; P:protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine; ISS:UniProtKB. 

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