UniProtKB - Q8VCN5 (CGL_MOUSE)
Protein
Cystathionine gamma-lyase
Gene
Cth
Organism
Mus musculus (Mouse)
Status
Functioni
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.3 Publications
Catalytic activityi
- EC:4.4.1.1
Cofactori
pyridoxal 5'-phosphateBy similarity
Activity regulationi
Activated by calmodulin in the presence of calcium ions.1 Publication
: L-cysteine biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes L-cysteine from L-homocysteine and L-serine.Proteins known to be involved in the 2 steps of the subpathway in this organism are:
- Cystathionine beta-synthase (Cbs)
- Cystathionine gamma-lyase (Cth)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-cysteine from L-homocysteine and L-serine, the pathway L-cysteine biosynthesis and in Amino-acid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 61 | SubstrateBy similarity | 1 | |
Binding sitei | 113 | SubstrateBy similarity | 1 | |
Binding sitei | 118 | SubstrateBy similarity | 1 | |
Binding sitei | 338 | SubstrateBy similarity | 1 |
GO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
- carbon-sulfur lyase activity Source: GO_Central
- cystathionine beta-lyase activity Source: MGI
- cystathionine gamma-lyase activity Source: MGI
- identical protein binding Source: MGI
- L-cysteine desulfhydrase activity Source: UniProtKB-EC
- L-cystine L-cysteine-lyase (deaminating) Source: UniProtKB
- pyridoxal phosphate binding Source: UniProtKB
GO - Biological processi
- cellular response to leukemia inhibitory factor Source: MGI
- cysteine biosynthetic process Source: UniProtKB
- cysteine biosynthetic process via cystathionine Source: MGI
- glutathione metabolic process Source: MGI
- homocysteine metabolic process Source: MGI
- hydrogen sulfide biosynthetic process Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of apoptotic signaling pathway Source: MGI
- negative regulation of cell growth Source: MGI
- negative regulation of cell population proliferation Source: MGI
- positive regulation of aortic smooth muscle cell differentiation Source: MGI
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- protein homotetramerization Source: MGI
- protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine Source: UniProtKB
- protein sulfhydration Source: UniProtKB
- transsulfuration Source: MGI
Keywordsi
Molecular function | Calmodulin-binding, Lyase |
Biological process | Amino-acid biosynthesis, Cysteine biosynthesis |
Ligand | Pyridoxal phosphate |
Enzyme and pathway databases
BRENDAi | 4.4.1.1, 3474 |
Reactomei | R-MMU-1614558, Degradation of cysteine and homocysteine R-MMU-1614603, Cysteine formation from homocysteine |
SABIO-RKi | Q8VCN5 |
UniPathwayi | UPA00136;UER00202 |
Names & Taxonomyi
Protein namesi | Recommended name: Cystathionine gamma-lyase (EC:4.4.1.1)Alternative name(s): Cysteine-protein sulfhydrase Gamma-cystathionase |
Gene namesi | Name:Cth |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1339968, Cth |
Pathology & Biotechi
Disruption phenotypei
No visible phenotype at birth. Mice exhibit strongly decreased levels of hydrogen sulfide (H2S) in heart and aorta. Mice also show absence of protein sulfhydration on target proteins. Hydrogen sulfide serum levels are also lower than normal. No effect on brain hydrogen sulfide levels. Mice develop hypertension beginning at about seven weeks of age.2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000114751 | 1 – 398 | Cystathionine gamma-lyaseAdd BLAST | 398 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 211 | N6-(pyridoxal phosphate)lysineBy similarity | 1 |
Proteomic databases
EPDi | Q8VCN5 |
jPOSTi | Q8VCN5 |
MaxQBi | Q8VCN5 |
PaxDbi | Q8VCN5 |
PeptideAtlasi | Q8VCN5 |
PRIDEi | Q8VCN5 |
PTM databases
iPTMneti | Q8VCN5 |
PhosphoSitePlusi | Q8VCN5 |
SwissPalmi | Q8VCN5 |
Expressioni
Tissue specificityi
Detected in liver and kidney, and at lower levels in small intestine (at protein level). Highly expressed in liver and kidney. detected at lower levels in stomach, small intestine and adipose tissue.1 Publication
Developmental stagei
First detected at low levels in embryonic liver after 12.5 days of embryonic development. Highly expressed in liver and kidney after 18.5 days of embryonic development. Expressed at high levels in liver and kidney after birth and in adults.
Gene expression databases
Bgeei | ENSMUSG00000028179, Expressed in multi-cellular organism and 84 other tissues |
Genevisiblei | Q8VCN5, MM |
Interactioni
Subunit structurei
Homotetramer (By similarity).
Interacts with CALM in a calcium-dependent manner.
By similarity1 PublicationGO - Molecular functioni
- calmodulin binding Source: UniProtKB-KW
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 223644, 4 interactors |
DIPi | DIP-60018N |
IntActi | Q8VCN5, 5 interactors |
MINTi | Q8VCN5 |
STRINGi | 10090.ENSMUSP00000113672 |
Miscellaneous databases
RNActi | Q8VCN5, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the trans-sulfuration enzymes family.Curated
Phylogenomic databases
eggNOGi | KOG0053, Eukaryota |
GeneTreei | ENSGT00390000000312 |
HOGENOMi | CLU_018986_2_3_1 |
InParanoidi | Q8VCN5 |
OMAi | YKQDGVG |
OrthoDBi | 572061at2759 |
PhylomeDBi | Q8VCN5 |
TreeFami | TF300720 |
Family and domain databases
CDDi | cd00614, CGS_like, 1 hit |
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 1 hit |
InterProi | View protein in InterPro IPR000277, Cys/Met-Metab_PyrdxlP-dep_enz IPR015424, PyrdxlP-dep_Trfase IPR015422, PyrdxlP-dep_Trfase_dom1 IPR015421, PyrdxlP-dep_Trfase_major |
PANTHERi | PTHR11808, PTHR11808, 1 hit |
Pfami | View protein in Pfam PF01053, Cys_Met_Meta_PP, 1 hit |
PIRSFi | PIRSF001434, CGS, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
PROSITEi | View protein in PROSITE PS00868, CYS_MET_METAB_PP, 1 hit |
i Sequence
Sequence statusi: Complete.
Q8VCN5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQKDASLSGF LPSFQHFATQ AIHVGQEPEQ WNSRAVVLPI SLATTFKQDF
60 70 80 90 100
PGQSSGFEYS RSGNPTRNCL EKAVAALDGA KHSLAFASGL AATITITHLL
110 120 130 140 150
KAGDEIICMD EVYGGTNRYF RRVASEFGLK ISFVDCSKTK LLEAAITPQT
160 170 180 190 200
KLVWIETPTN PTLKLADIGA CAQIVHKRGD IILVVDNTFM SAYFQRPLAL
210 220 230 240 250
GADICMCSAT KYMNGHSDVV MGLVSVNSDD LNSRLRFLQN SLGAVPSPFD
260 270 280 290 300
CYLCCRGLKT LQVRMEKHFK NGMAVARFLE TNPRVEKVVY PGLPSHPQHE
310 320 330 340 350
LAKRQCSGCP GMVSFYIKGA LQHAKAFLKN LKLFTLAESL GGYESLAELP
360 370 380 390
AIMTHASVPE KDRATLGIND TLIRLSVGLE DEQDLLEDLD RALKAAHP
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY083352 mRNA Translation: AAL99218.1 AY262829 Genomic DNA Translation: AAP86975.1 CH466532 Genomic DNA Translation: EDL11858.1 BC019483 mRNA Translation: AAH19483.1 |
CCDSi | CCDS51101.1 |
RefSeqi | NP_666065.1, NM_145953.2 |
Genome annotation databases
Ensembli | ENSMUST00000118539; ENSMUSP00000113672; ENSMUSG00000028179 |
GeneIDi | 107869 |
KEGGi | mmu:107869 |
UCSCi | uc008rvj.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY083352 mRNA Translation: AAL99218.1 AY262829 Genomic DNA Translation: AAP86975.1 CH466532 Genomic DNA Translation: EDL11858.1 BC019483 mRNA Translation: AAH19483.1 |
CCDSi | CCDS51101.1 |
RefSeqi | NP_666065.1, NM_145953.2 |
3D structure databases
SMRi | Q8VCN5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 223644, 4 interactors |
DIPi | DIP-60018N |
IntActi | Q8VCN5, 5 interactors |
MINTi | Q8VCN5 |
STRINGi | 10090.ENSMUSP00000113672 |
PTM databases
iPTMneti | Q8VCN5 |
PhosphoSitePlusi | Q8VCN5 |
SwissPalmi | Q8VCN5 |
Proteomic databases
EPDi | Q8VCN5 |
jPOSTi | Q8VCN5 |
MaxQBi | Q8VCN5 |
PaxDbi | Q8VCN5 |
PeptideAtlasi | Q8VCN5 |
PRIDEi | Q8VCN5 |
Protocols and materials databases
Antibodypediai | 19668, 394 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000118539; ENSMUSP00000113672; ENSMUSG00000028179 |
GeneIDi | 107869 |
KEGGi | mmu:107869 |
UCSCi | uc008rvj.1, mouse |
Organism-specific databases
CTDi | 1491 |
MGIi | MGI:1339968, Cth |
Phylogenomic databases
eggNOGi | KOG0053, Eukaryota |
GeneTreei | ENSGT00390000000312 |
HOGENOMi | CLU_018986_2_3_1 |
InParanoidi | Q8VCN5 |
OMAi | YKQDGVG |
OrthoDBi | 572061at2759 |
PhylomeDBi | Q8VCN5 |
TreeFami | TF300720 |
Enzyme and pathway databases
UniPathwayi | UPA00136;UER00202 |
BRENDAi | 4.4.1.1, 3474 |
Reactomei | R-MMU-1614558, Degradation of cysteine and homocysteine R-MMU-1614603, Cysteine formation from homocysteine |
SABIO-RKi | Q8VCN5 |
Miscellaneous databases
BioGRID-ORCSi | 107869, 0 hits in 19 CRISPR screens |
ChiTaRSi | Cth, mouse |
PROi | PR:Q8VCN5 |
RNActi | Q8VCN5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028179, Expressed in multi-cellular organism and 84 other tissues |
Genevisiblei | Q8VCN5, MM |
Family and domain databases
CDDi | cd00614, CGS_like, 1 hit |
Gene3Di | 3.40.640.10, 1 hit 3.90.1150.10, 1 hit |
InterProi | View protein in InterPro IPR000277, Cys/Met-Metab_PyrdxlP-dep_enz IPR015424, PyrdxlP-dep_Trfase IPR015422, PyrdxlP-dep_Trfase_dom1 IPR015421, PyrdxlP-dep_Trfase_major |
PANTHERi | PTHR11808, PTHR11808, 1 hit |
Pfami | View protein in Pfam PF01053, Cys_Met_Meta_PP, 1 hit |
PIRSFi | PIRSF001434, CGS, 1 hit |
SUPFAMi | SSF53383, SSF53383, 1 hit |
PROSITEi | View protein in PROSITE PS00868, CYS_MET_METAB_PP, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CGL_MOUSE | |
Accessioni | Q8VCN5Primary (citable) accession number: Q8VCN5 Secondary accession number(s): Q6H324 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2003 |
Last sequence update: | March 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 141 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families