Overview
| Uniprot ID | P32929 |
|---|
| Protein Name | Cystathionine gamma-lyase |
|---|
| Gene Name | CTH |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 139 |
ISFVDCSKIKLLEAA |
| 141 |
FVDCSKIKLLEAAIT |
| 260 |
YLCNRGLKTLHVRME |
| 304 |
HPQHELVKRQCTGCT |
| 73 |
PTRNCLEKAVAALDG |
Function
Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate (PubMed:10212249, PubMed:18476726, PubMed:19261609, PubMed:19961860). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19019829, PubMed:19261609, PubMed:19961860). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). 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 (PubMed:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (By similarity). Can also accept homoserine as substrate (By similarity). Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity)
Protein Sequence
10
MQEKDASSQG
20
FLPHFQHFAT
30
QAIHVGQDPE
40
QWTSRAVVPP
50
ISLSTTFKQG
60
APGQHSGFEY
70
SRSGNPTRNC
80
LEKAVAALDG
90
AKYCLAFASG
100
LAATVTITHL
110
LKAGDQIICM
120
DDVYGGTNRY
130
FRQVASEFGL
140
KISFVDCSKI
150
KLLEAAITPE
160
TKLVWIETPT
170
NPTQKVIDIE
180
GCAHIVHKHG
190
DIILVVDNTF
200
MSPYFQRPLA
210
LGADISMYSA
220
TKYMNGHSDV
230
VMGLVSVNCE
240
SLHNRLRFLQ
250
NSLGAVPSPI
260
DCYLCNRGLK
270
TLHVRMEKHF
280
KNGMAVAQFL
290
ESNPWVEKVI
300
YPGLPSHPQH
310
ELVKRQCTGC
320
TGMVTFYIKG
330
TLQHAEIFLK
340
NLKLFTLAES
350
LGGFESLAEL
360
PAIMTHASVL
370
KNDRDVLGIS
380
DTLIRLSVGL
390
EDEEDLLEDL
400
DQALKAAHPP
SGSHS
Gene Ontology
| Classification |
GO ID |
Description |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Molecular Function |
GO:0005516 |
calmodulin binding |
| Molecular Function |
GO:0004123 |
cystathionine gamma-lyase activity |
| Molecular Function |
GO:0047982 |
homocysteine desulfhydrase activity |
| Molecular Function |
GO:0080146 |
L-cysteine desulfhydrase activity |
| Molecular Function |
GO:0044540 |
L-cystine L-cysteine-lyase (deaminating) activity |
| Molecular Function |
GO:0030170 |
pyridoxal phosphate binding |
| Molecular Function |
GO:0098606 |
selenocystathionine gamma-lyase activity |
| Biological Process |
GO:0006534 |
cysteine metabolic process |
| Biological Process |
GO:0030968 |
endoplasmic reticulum unfolded protein response |
| Biological Process |
GO:0070814 |
hydrogen sulfide biosynthetic process |
| Biological Process |
GO:0019344 |
L-cysteine biosynthetic process |
| Biological Process |
GO:0019343 |
L-cysteine biosynthetic process via L-cystathionine |
| Biological Process |
GO:0006629 |
lipid metabolic process |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:1904831 |
positive regulation of aortic smooth muscle cell differentiation |
| Biological Process |
GO:0043123 |
positive regulation of canonical NF-kappaB signal transduction |
| Biological Process |
GO:0051289 |
protein homotetramerization |
| Biological Process |
GO:0044524 |
protein sulfhydration |
| Biological Process |
GO:0018272 |
protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine |
| Biological Process |
GO:0019346 |
transsulfuration |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.