Protein:CTH |
Protein Summary |
 Gene summary |
| Gene name: CTH | ASpdb.0 ID: 1491 | Gene | Gene symbol | CTH | Gene ID | 1491 |
| Gene name | cystathionine gamma-lyase |
| Synonyms | CGL|CSE |
| Cytomap | 1p31.1 |
| Type of gene | protein-coding |
| Description | cystathionine gamma-lyasecystathionase (cystathionine gamma-lyase)cysteine desulfhydrasecysteine-protein sulfhydrasegamma-cystathionasehomocysteine desulfhydrasehomoserine deaminasehomoserine dehydratase |
| Modification date | 20240305 |
| UniProtAcc | P32929 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CTH | GO:0004123 | cystathionine gamma-lyase activity | 10212249|19019829|19428278 |
| Gene | CTH | GO:0018272 | protein-pyridoxal-5-phosphate linkage via peptidyl-N6-pyridoxal phosphate-L-lysine | 19019829 |
| Gene | CTH | GO:0019343 | cysteine biosynthetic process via cystathionine | 19428278 |
| Gene | CTH | GO:0019344 | cysteine biosynthetic process | 10212249 |
| Gene | CTH | GO:0019346 | transsulfuration | 19428278 |
| Gene | CTH | GO:0030170 | pyridoxal phosphate binding | 10212249|19019829 |
| Gene | CTH | GO:0070814 | hydrogen sulfide biosynthetic process | 19019829 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P32929-1 | P32929-1_3cog_C.pdb | 3COG | X-ray | 2.0 | C | 10 | 401 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P32929 | CTH | P32929-1 | P32929-2 | 405 | 361 | 153 | 196 | Deletion | none | none | 152 | 152 |
| P32929 | CTH | P32929-1 | P32929-3 | 405 | 373 | 85 | 116 | Deletion | none | none | 84 | 84 |
| Multiple sequence alignment of our canonical and alternatively spliced CTH |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CTH |
| UniProt-id | ENSG | ENST | ENSP |
| P32929-1 | ENSG00000116761.12 | ENST00000370938.8 | ENSP00000359976.3 |
| P32929-2 | ENSG00000116761.12 | ENST00000346806.2 | ENSP00000311554.2 |
| P32929-3 | ENSG00000116761.12 | ENST00000411986.6 | ENSP00000413407.2 |
| UniProt-id | NM ID | NP ID |
| P32929-1 | NM_001902.5 | NP_001893.2 |
| P32929-2 | NM_153742.4 | NP_714964.2 |
| P32929-3 | NM_001190463.1 | NP_001177392.1 |
| Amino acid sequences of our canonical and alternatively spliced CTH |
| accession_id | Protein sequence |
| P32929-1 | MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCLAFASG LAATVTITHLLKAGDQIICMDDVYGGTNRYFRQVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHG DIILVVDNTFMSPYFQRPLALGADISMYSATKYMNGHSDVVMGLVSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHF KNGMAVAQFLESNPWVEKVIYPGLPSHPQHELVKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVL |
| P32929-2 | MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCLAFASG LAATVTITHLLKAGDQIICMDDVYGGTNRYFRQVASEFGLKISFVDCSKIKLLEAAITPETKRPLALGADISMYSATKYMNGHSDVVMGL VSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQHELVKRQCTGCTGMV TFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVLKNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQALKAAHPPSGSH |
| P32929-3 | MQEKDASSQGFLPHFQHFATQAIHVGQDPEQWTSRAVVPPISLSTTFKQGAPGQHSGFEYSRSGNPTRNCLEKAVAALDGAKYCTNRYFR QVASEFGLKISFVDCSKIKLLEAAITPETKLVWIETPTNPTQKVIDIEGCAHIVHKHGDIILVVDNTFMSPYFQRPLALGADISMYSATK YMNGHSDVVMGLVSVNCESLHNRLRFLQNSLGAVPSPIDCYLCNRGLKTLHVRMEKHFKNGMAVAQFLESNPWVEKVIYPGLPSHPQHEL VKRQCTGCTGMVTFYIKGTLQHAEIFLKNLKLFTLAESLGGFESLAELPAIMTHASVLKNDRDVLGISDTLIRLSVGLEDEEDLLEDLDQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CTH (go to UniProt):P32929 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for CTH |
| Gene structures of our canonical and alternative spliced genes of CTH * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P32929-1 |
| 3D view using mol* of P32929-2 |
| 3D view using mol* of P32929-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P32929-1 |
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| pLDDT distribution across the protein length of P32929-2 |
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| pLDDT distribution across the protein length of P32929-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P32929-1 |
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| Ramachandran plot of P32929-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P32929-1 | 1.019 | 95 | 0.876 | 195.167 | 0.486 | 0.754 | 1.002 | 0.251 | 1.509 | 0.166 | 0.401 | 89,90,91,114,115,116,117,119,157,159,161,187,188,1 89,190,207,209,211,212,221,339,340,341,349,354,355 ,357,358,375 |
| P32929-2 | 1.039 | 270 | 1.084 | 1193.983 | 0.688 | 0.699 | 0.861 | 0.751 | 0.844 | 0.89 | 0.569 | 14,15,16,17,18,19,20,21,75,77,78,79,80,81,89,90,91 ,94,97,98,100,101,106,107,108,113,114,117,121,143, 147,151,152,153,154,155,156,159,160,161,162,163,16 4,165,167,168,169,170,177,182,183,184,188,191,218, 219,222,223,226,248,259,263,264,265,266,267,295,29 6,297,311,331 |
| P32929-3 | 1.026 | 344 | 1.061 | 978.579 | 0.524 | 0.703 | 0.862 | 0.656 | 0.922 | 0.711 | 0.557 | 86,87,88,89,90,91,93,97,98,99,100,101,102,103,104, 105,106,110,111,114,115,116,118,119,120,121,122,12 3,124,125,126,127,128,129,130,131,133,135,155,156, 157,158,159,175,177,179,180,189,190,191,215,216,21 9,309,324,326,327,328,331,334,335,337 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P32929-1_P32929-1_3cog_C.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P32929-1_3cog_C_P32929-2.pdb |
| 3D view using mol* of P32929-1_3cog_C_P32929-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P32929-1_P32929-2.pdb |
| 3D view using mol* of P32929-1_P32929-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P32929-1_vs_P32929-2.png |
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| ./stats/secondary_structure/figure/P32929-1_vs_P32929-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P32929-1_vs_P32929-2.png |
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| ./stats/relative_asa/P32929-1_vs_P32929-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CTH |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P32929 | CTH | DB02328 | 2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-Phosphono-Pent-3-Enoic Acid | experimental | |
| P32929 | CTH | DB00151 | Cysteine | approved, nutraceutical | |
| P32929 | CTH | DB03928 | Carboxymethylthio-3-(3-Chlorophenyl)-1,2,4-Oxadiazol | experimental | |
| P32929 | CTH | DB00114 | Pyridoxal phosphate | approved, investigational, nutraceutical | cofactor |
| P32929 | CTH | DB04217 | L-2-amino-3-butynoic acid | experimental |
Related Diseases to CTH |
| Previous studies relating to the alternative splicing of CTH and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CTH | 24491890 | [Cystathionine γ-lyase]. | γ-Cystathionase (CTH, EC: 4.4.1.1), an enzyme widely distributed in the world of prokaryotic and eukaryotic organisms, catalyzes the formation and transformations of sulfane sulfur-containing compounds and plays a pivotal role in the L-cysteine desulfuration pathway. Human, tetrameric CTH is composed of two dimers and each monomer binds pyridoxal phosphate (PLP). The gene, located on the short arm of chromosome 1, consists of 13 exons and 12 introns. As a result of alternative splicing, three isoforms of human CTH arise. Analysis of genetic variations of the CTH encoding gene showed a large number of polymorphisms. A decrease of the expression of CTH entails a drop in the level of cysteine , glutathione (GSH), taurine and hydrogen sulfide (H2S) in the cells and, more importantly, leads to cystathioninuria. H2S, endogenously formed by CTH, affects the vasodilation and regulation of blood pressure. CTH knockout mice have decreased levels of H2S, hypertension, and reduced capacity for vascular endothelium relaxation. Overexpression of the gene encoding CTH in the cells leads to increased production of H2S. H2S plays a role in protection of neurons against oxidative stress, and stimulates an increase in γ-glutamylcysteine synthetase and thereby an increase in the level of GSH. Sulfurtransferases, including CTH, can locally prevent oxidative stress due to reversible oxidation of - SH groups in the presence of increased levels of reactive oxygen species, and reduction in the presence of GSH and/or reduced thioredoxin. | D020138 | Hyperhomocysteinemia |
| CTH | 24491890 | [Cystathionine γ-lyase]. | γ-Cystathionase (CTH, EC: 4.4.1.1), an enzyme widely distributed in the world of prokaryotic and eukaryotic organisms, catalyzes the formation and transformations of sulfane sulfur-containing compounds and plays a pivotal role in the L-cysteine desulfuration pathway. Human, tetrameric CTH is composed of two dimers and each monomer binds pyridoxal phosphate (PLP). The gene, located on the short arm of chromosome 1, consists of 13 exons and 12 introns. As a result of alternative splicing, three isoforms of human CTH arise. Analysis of genetic variations of the CTH encoding gene showed a large number of polymorphisms. A decrease of the expression of CTH entails a drop in the level of cysteine , glutathione (GSH), taurine and hydrogen sulfide (H2S) in the cells and, more importantly, leads to cystathioninuria. H2S, endogenously formed by CTH, affects the vasodilation and regulation of blood pressure. CTH knockout mice have decreased levels of H2S, hypertension, and reduced capacity for vascular endothelium relaxation. Overexpression of the gene encoding CTH in the cells leads to increased production of H2S. H2S plays a role in protection of neurons against oxidative stress, and stimulates an increase in γ-glutamylcysteine synthetase and thereby an increase in the level of GSH. Sulfurtransferases, including CTH, can locally prevent oxidative stress due to reversible oxidation of - SH groups in the presence of increased levels of reactive oxygen species, and reduction in the presence of GSH and/or reduced thioredoxin. | D006973 | Hypertension |
Clinically important variants in CTH |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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