Protein:CBS |
Protein Summary |
 Gene summary |
| Gene name: CBS | ASpdb.0 ID: 875 | Gene | Gene symbol | CBS | Gene ID | 875 |
| Gene name | cystathionine beta-synthase |
| Synonyms | CBSL|HIP4 |
| Cytomap | 21q22.3 |
| Type of gene | protein-coding |
| Description | cystathionine beta-synthaseCystathionine beta-synthase-like proteinbeta-thionasemethylcysteine synthaseserine sulfhydrase |
| Modification date | 20240416 |
| UniProtAcc | P35520 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CBS | GO:0004122 | cystathionine beta-synthase activity | 7929220|18776696|19010420|22985361|23981774|24416422 |
| Gene | CBS | GO:0005634 | nucleus | 17087506 |
| Gene | CBS | GO:0005737 | cytoplasm | 23981774 |
| Gene | CBS | GO:0006563 | L-serine metabolic process | 19010420 |
| Gene | CBS | GO:0006565 | L-serine catabolic process | 18776696 |
| Gene | CBS | GO:0019344 | cysteine biosynthetic process | 24416422 |
| Gene | CBS | GO:0019448 | L-cysteine catabolic process | 15520012 |
| Gene | CBS | GO:0019825 | oxygen binding | 24515102 |
| Gene | CBS | GO:0020037 | heme binding | 7929220|24515102 |
| Gene | CBS | GO:0030170 | pyridoxal phosphate binding | 7929220|18776696 |
| Gene | CBS | GO:0042803 | protein homodimerization activity | 11483494 |
| Gene | CBS | GO:0043418 | homocysteine catabolic process | 18776696|24416422 |
| Gene | CBS | GO:0050421 | nitrite reductase (NO-forming) activity | 24416422 |
| Gene | CBS | GO:0050667 | homocysteine metabolic process | 19010420|20031578|23981774 |
| Gene | CBS | GO:0070025 | carbon monoxide binding | 24515102 |
| Gene | CBS | GO:0070026 | nitric oxide binding | 24416422|24515102 |
| Gene | CBS | GO:0070814 | hydrogen sulfide biosynthetic process | 15520012|24416422 |
| Gene | CBS | GO:0072341 | modified amino acid binding | 20031578 |
| Gene | CBS | GO:1904047 | S-adenosyl-L-methionine binding | 22985361 |
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 |
| P35520-1 | P35520-1_4l0d_A.pdb | 4L0D | X-ray | 2.97 | A | 41 | 550 |
| 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 |
| P35520 | CBS | P35520-1 | P35520-2 | 551 | 565 | 518 | 518 | Substitution | Y | SQDQAWAGVVGGPAD | 518 | 532 |
| Multiple sequence alignment of our canonical and alternatively spliced CBS |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CBS |
| UniProt-id | ENSG | ENST | ENSP |
| P35520-1 | ENSG00000160200.18 | ENST00000352178.9 | ENSP00000344460.5 |
| P35520-1 | ENSG00000160200.18 | ENST00000359624.7 | ENSP00000352643.3 |
| P35520-1 | ENSG00000160200.18 | ENST00000398158.5 | ENSP00000381225.1 |
| P35520-1 | ENSG00000160200.18 | ENST00000398165.8 | ENSP00000381231.4 |
| UniProt-id | NM ID | NP ID |
| P35520-1 | NM_000071.2 | NP_000062.1 |
| P35520-1 | NM_001178008.2 | NP_001171479.1 |
| P35520-1 | NM_001178009.2 | NP_001171480.1 |
| P35520-1 | NM_001320298.1 | NP_001307227.1 |
| P35520-1 | NM_001321073.1 | NP_001308002.1 |
| P35520-1 | XM_017028491.1 | XP_016883980.1 |
| P35520-2 | XM_011529777.1 | XP_011528079.1 |
| Amino acid sequences of our canonical and alternatively spliced CBS |
| accession_id | Protein sequence |
| P35520-1 | MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPASESPHHHTAPAKSPKILPDILKKIGDTPMV RINKIGKKFGLKCELLAKCEFFNAGGSVKDRISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEILQQCDGKLDMLVASVGTGGTITGIARKLKE KCPGCRIIGVDPEGSILAEPEELNQTEQTTYEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLSAPLTVLPTITCGHTIEILREKGFDQAPVVD EAGVILGMVTLGNMLSSLLAGKVQPSDQVGKVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQYHSTGKSSQRQMVFGVVTAIDLL |
| P35520-2 | MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPASESPHHHTAPAKSPKILPDILKKIGDTPMV RINKIGKKFGLKCELLAKCEFFNAGGSVKDRISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEILQQCDGKLDMLVASVGTGGTITGIARKLKE KCPGCRIIGVDPEGSILAEPEELNQTEQTTYEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLSAPLTVLPTITCGHTIEILREKGFDQAPVVD EAGVILGMVTLGNMLSSLLAGKVQPSDQVGKVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQSQDQAWAGVVGGPADHSTGKSSQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CBS (go to UniProt):P35520 |
| 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 CBS |
| Gene structures of our canonical and alternative spliced genes of CBS * 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 P35520-1 |
| 3D view using mol* of P35520-2 |
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 P35520-1 |
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| pLDDT distribution across the protein length of P35520-2 |
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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 P35520-1 |
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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 |
| P35520-1 | 1.066 | 136 | 0.981 | 306.642 | 0.449 | 0.796 | 1.039 | 0.274 | 1.34 | 0.204 | 1.17 | 146,147,170,172,173,191,192,193,194,195,196,197,20 2,203,223,256,257,284,285,299,300,301,302,303,304, 305,306,307,308,309 |
| P35520-2 | 1.112 | 115 | 0.978 | 277.83 | 0.407 | 0.865 | 1.125 | 0.29 | 1.474 | 0.197 | 1.415 | 146,147,170,172,173,191,192,193,194,195,196,197,20 2,203,223,256,284,285,299,300,301,304,305,306,307, 308,309 |
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 P35520-1_P35520-1_4l0d_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P35520-1_4l0d_A_P35520-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P35520-1_P35520-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P35520-1_vs_P35520-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P35520-1_vs_P35520-2.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 CBS |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P35520 | CBS | DB00118 | Ademetionine | approved, investigational, nutraceutical | activator |
| P35520 | CBS | DB00114 | Pyridoxal phosphate | approved, investigational, nutraceutical | cofactor |
| P35520 | CBS | DB00151 | Cysteine | approved, nutraceutical | |
| P35520 | CBS | DB00133 | Serine | investigational, nutraceutical |
Related Diseases to CBS |
| Previous studies relating to the alternative splicing of CBS and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CBS | 7903580 | Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. | Cystathionine beta-synthase (CBS) deficiency is the major cause of homocystinuria in humans. The most frequent symptoms of homocystinuria include: dislocated optic lenses, vascular disorders, skeletal abnormalities and mental retardation. Patients with this deficiency have elevated levels of homocyst(e)ine, methionine and low cysteine in their body fluids. These abnormal levels often partially or fully normalize upon treatment with pharmacological doses of vitamin B6. To investigate the molecular and biochemical basis for these conditions, it was necessary to determine the nucleotide and polypeptide sequence of CBS. We report here the human CBS cDNA sequence of 2,554 nucleotides encoding the CBS subunit of 551 amino acids. An intron of 214 bp appears to be retained in the 3'-untranslated region of most of the fibroblast and liver mRNA. We also report a frequent Mspl polymorphism in the 3'-untranslated sequence and two synonymous mutations in the coding region: 699C/T (Y233Y) and 1080C/T (A360A). The amino acid sequence similarity of human and rat CBS is greater than 90%; the enzyme also exhibits 52% similarity to O-acetylserine(thiol)-lyase from bacteria and plants. Lastly, we demonstrate that expression of the human enzyme in CHO cells yields enzymatically active protein of the expected size with a half-life of approximately 14 hrs. | D006712 | Homocystinuria |
| CBS | 11528503 | A 31 bp VNTR in the cystathionine beta-synthase (CBS) gene is associated with reduced CBS activity and elevated post-load homocysteine levels. | Molecular defects in genes encoding enzymes involved in homocysteine metabolism may account for mild hyperhomocysteinaemia, an independent and graded risk factor for cardiovascular disease (CVD). Although heterozygosity for cystathionine beta-synthase (CBS) deficiency has been excluded as a major genetic cause of mild hyperhomocysteinaemia in vascular disease, mutations in (non-)coding DNA sequences may lead to a mildly decreased CBS expression and, consequently, to elevated plasma homocysteine levels. We assessed the association between a 31 bp VNTR, that spans the exon 13-intron 13 boundary of the CBS gene, and fasting, post-methionine load and increase upon methionine load plasma homocysteine levels in 190 patients with arterial occlusive disease, and in 381 controls. The 31 bp VNTR consists of 16, 17, 18, 19 or 21 repeat units and shows a significant increase in plasma homocysteine concentrations with an increasing number of repeat elements, in particular after methionine loading. In 26 vascular disease patients the relationship between this 31 bp VNTR and CBS enzyme activity in cultured fibroblasts was studied. The CBS enzyme activity decreased with increasing number of repeat units of the 31 bp VNTR. RT-PCR experiments showed evidence of alternative splicing at the exon 13-intron 13 splice junction site. The 31 bp VNTR in the CBS gene is associated with post-methionine load hyperhomocysteinaemia that may predispose individuals to an increased risk of cardiovascular diseases. | D001157 | Arterial Occlusive Diseases |
Clinically important variants in CBS |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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