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Protein

Cystathionine gamma-lyase

Gene

Cth

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

L-cystathionine + H2O = L-cysteine + NH3 + 2-oxobutanoate.

Cofactori

Enzyme regulationi

Activated by calmodulin in the presence of calcium ions.1 Publication

Pathwayi: L-cysteine biosynthesis

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:
  1. Cystathionine beta-synthase (Cbs)
  2. Cystathionine gamma-lyase (Cth)
This subpathway is part of the pathway L-cysteine biosynthesis, which is itself part of Amino-acid biosynthesis.
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei61SubstrateBy similarity1
Binding sitei113SubstrateBy similarity1
Binding sitei118SubstrateBy similarity1
Binding sitei338SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Amino-acid biosynthesis, Cysteine biosynthesis

Keywords - Ligandi

Calmodulin-binding, Pyridoxal phosphate

Enzyme and pathway databases

BRENDAi4.4.1.1. 3474.
ReactomeiR-MMU-1614558. Degradation of cysteine and homocysteine.
R-MMU-1614603. Cysteine formation from homocysteine.
R-MMU-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
SABIO-RKQ8VCN5.
UniPathwayiUPA00136; 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1339968. Cth.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

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 keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001147511 – 398Cystathionine gamma-lyaseAdd BLAST398

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211N6-(pyridoxal phosphate)lysineBy similarity1

Proteomic databases

MaxQBiQ8VCN5.
PaxDbiQ8VCN5.
PeptideAtlasiQ8VCN5.
PRIDEiQ8VCN5.

PTM databases

iPTMnetiQ8VCN5.
PhosphoSitePlusiQ8VCN5.
SwissPalmiQ8VCN5.

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

BgeeiENSMUSG00000028179.
CleanExiMM_CTH.
GenevisibleiQ8VCN5. MM.

Interactioni

Subunit structurei

Homotetramer (By similarity). Interacts with CALM in a calcium-dependent manner.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-60018N.
IntActiQ8VCN5. 4 interactors.
MINTiMINT-1855831.
STRINGi10090.ENSMUSP00000113672.

Structurei

3D structure databases

ProteinModelPortaliQ8VCN5.
SMRiQ8VCN5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the trans-sulfuration enzymes family.Curated

Phylogenomic databases

eggNOGiKOG0053. Eukaryota.
COG0626. LUCA.
GeneTreeiENSGT00390000000312.
HOGENOMiHOG000246415.
HOVERGENiHBG005322.
InParanoidiQ8VCN5.
KOiK01758.
OMAiPATASHC.
OrthoDBiEOG091G0C7Z.
PhylomeDBiQ8VCN5.
TreeFamiTF300720.

Family and domain databases

CDDicd00614. CGS_like. 1 hit.
Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR000277. Cys/Met-Metab_PyrdxlP-dep_enz.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]
PANTHERiPTHR11808. PTHR11808. 1 hit.
PfamiPF01053. Cys_Met_Meta_PP. 1 hit.
[Graphical view]
PIRSFiPIRSF001434. CGS. 1 hit.
SUPFAMiSSF53383. SSF53383. 1 hit.
PROSITEiPS00868. CYS_MET_METAB_PP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VCN5-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:398
Mass (Da):43,567
Last modified:March 1, 2002 - v1
Checksum:iB2F89625B9978599
GO

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.
CCDSiCCDS51101.1.
RefSeqiNP_666065.1. NM_145953.2.
UniGeneiMm.28301.

Genome annotation databases

EnsembliENSMUST00000118539; ENSMUSP00000113672; ENSMUSG00000028179.
GeneIDi107869.
KEGGimmu:107869.
UCSCiuc008rvj.1. mouse.

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.
CCDSiCCDS51101.1.
RefSeqiNP_666065.1. NM_145953.2.
UniGeneiMm.28301.

3D structure databases

ProteinModelPortaliQ8VCN5.
SMRiQ8VCN5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60018N.
IntActiQ8VCN5. 4 interactors.
MINTiMINT-1855831.
STRINGi10090.ENSMUSP00000113672.

PTM databases

iPTMnetiQ8VCN5.
PhosphoSitePlusiQ8VCN5.
SwissPalmiQ8VCN5.

Proteomic databases

MaxQBiQ8VCN5.
PaxDbiQ8VCN5.
PeptideAtlasiQ8VCN5.
PRIDEiQ8VCN5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000118539; ENSMUSP00000113672; ENSMUSG00000028179.
GeneIDi107869.
KEGGimmu:107869.
UCSCiuc008rvj.1. mouse.

Organism-specific databases

CTDi1491.
MGIiMGI:1339968. Cth.

Phylogenomic databases

eggNOGiKOG0053. Eukaryota.
COG0626. LUCA.
GeneTreeiENSGT00390000000312.
HOGENOMiHOG000246415.
HOVERGENiHBG005322.
InParanoidiQ8VCN5.
KOiK01758.
OMAiPATASHC.
OrthoDBiEOG091G0C7Z.
PhylomeDBiQ8VCN5.
TreeFamiTF300720.

Enzyme and pathway databases

UniPathwayiUPA00136; UER00202.
BRENDAi4.4.1.1. 3474.
ReactomeiR-MMU-1614558. Degradation of cysteine and homocysteine.
R-MMU-1614603. Cysteine formation from homocysteine.
R-MMU-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
SABIO-RKQ8VCN5.

Miscellaneous databases

PROiQ8VCN5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028179.
CleanExiMM_CTH.
GenevisibleiQ8VCN5. MM.

Family and domain databases

CDDicd00614. CGS_like. 1 hit.
Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR000277. Cys/Met-Metab_PyrdxlP-dep_enz.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
[Graphical view]
PANTHERiPTHR11808. PTHR11808. 1 hit.
PfamiPF01053. Cys_Met_Meta_PP. 1 hit.
[Graphical view]
PIRSFiPIRSF001434. CGS. 1 hit.
SUPFAMiSSF53383. SSF53383. 1 hit.
PROSITEiPS00868. CYS_MET_METAB_PP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCGL_MOUSE
AccessioniPrimary (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: November 2, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.