Protein:ASL |
Protein Summary |
 Gene summary |
| Gene name: ASL | ASpdb.0 ID: 435 | Gene | Gene symbol | ASL | Gene ID | 435 |
| Gene name | argininosuccinate lyase |
| Synonyms | ASAL |
| Cytomap | 7q11.21 |
| Type of gene | protein-coding |
| Description | argininosuccinate lyaseargininosuccinasearginosuccinase |
| Modification date | 20240407 |
| UniProtAcc | P04424 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ASL | GO:0004056 | argininosuccinate lyase activity | 9045711|11747432|11747433 |
| Gene | ASL | GO:0006525 | arginine metabolic process | 9045711 |
| Gene | ASL | GO:0006526 | arginine biosynthetic process | 11747432|11747433 |
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 |
| P04424-1 | P04424-1_1k62_B.pdb | 1K62 | X-ray | 2.65 | B | 6 | 464 |
| 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 |
| P04424 | ASL | P04424-1 | P04424-2 | 464 | 444 | 307 | 326 | Deletion | none | none | 306 | 306 |
| P04424 | ASL | P04424-1 | P04424-3 | 464 | 438 | 176 | 201 | Deletion | none | none | 175 | 175 |
| Multiple sequence alignment of our canonical and alternatively spliced ASL |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ASL |
| UniProt-id | ENSG | ENST | ENSP |
| P04424-1 | ENSG00000126522.17 | ENST00000304874.14 | ENSP00000307188.9 |
| P04424-1 | ENSG00000126522.17 | ENST00000395332.8 | ENSP00000378741.3 |
| P04424-2 | ENSG00000126522.17 | ENST00000395331.4 | ENSP00000378740.3 |
| P04424-3 | ENSG00000126522.17 | ENST00000380839.9 | ENSP00000370219.4 |
| P04424-3 | ENSG00000126522.17 | ENST00000673518.1 | ENSP00000499889.1 |
| UniProt-id | NM ID | NP ID |
| P04424-1 | NM_000048.3 | NP_000039.2 |
| P04424-1 | NM_001024943.1 | NP_001020114.1 |
| P04424-2 | NM_001024944.1 | NP_001020115.1 |
| Amino acid sequences of our canonical and alternatively spliced ASL |
| accession_id | Protein sequence |
| P04424-1 | MASESGKLWGGRFVGAVDPIMEKFNASIAYDRHLWEVDVQGSKAYSRGLEKAGLLTKAEMDQILHGLDKVAEEWAQGTFKLNSNDEDIHT ANERRLKELIGATAGKLHTGRSRNDQVVTDLRLWMRQTCSTLSGLLWELIRTMVDRAEAERDVLFPGYTHLQRAQPIRWSHWILSHAVAL TRDSERLLEVRKRINVLPLGSGAIAGNPLGVDRELLRAELNFGAITLNSMDATSERDFVAEFLFWASLCMTHLSRMAEDLILYCTKEFSF VQLSDAYSTGSSLMPQKKNPDSLELIRSKAGRVFGRCAGLLMTLKGLPSTYNKDLQEDKEAVFEVSDTMSAVLQVATGVISTLQIHQENM GQALSPDMLATDLAYYLVRKGMPFRQAHEASGKAVFMAETKGVALNQLSLQELQTISPLFSGDVICVWDYGHSVEQYGALGGTARSSVDW |
| P04424-2 | MASESGKLWGGRFVGAVDPIMEKFNASIAYDRHLWEVDVQGSKAYSRGLEKAGLLTKAEMDQILHGLDKVAEEWAQGTFKLNSNDEDIHT ANERRLKELIGATAGKLHTGRSRNDQVVTDLRLWMRQTCSTLSGLLWELIRTMVDRAEAERDVLFPGYTHLQRAQPIRWSHWILSHAVAL TRDSERLLEVRKRINVLPLGSGAIAGNPLGVDRELLRAELNFGAITLNSMDATSERDFVAEFLFWASLCMTHLSRMAEDLILYCTKEFSF VQLSDAYSTGSSLMPQKKNPDSLELIRSKAGRVFGREDKEAVFEVSDTMSAVLQVATGVISTLQIHQENMGQALSPDMLATDLAYYLVRK |
| P04424-3 | MASESGKLWGGRFVGAVDPIMEKFNASIAYDRHLWEVDVQGSKAYSRGLEKAGLLTKAEMDQILHGLDKVAEEWAQGTFKLNSNDEDIHT ANERRLKELIGATAGKLHTGRSRNDQVVTDLRLWMRQTCSTLSGLLWELIRTMVDRAEAERDVLFPGYTHLQRAQPIRWSHWILSGAIAG NPLGVDRELLRAELNFGAITLNSMDATSERDFVAEFLFWASLCMTHLSRMAEDLILYCTKEFSFVQLSDAYSTGSSLMPQKKNPDSLELI RSKAGRVFGRCAGLLMTLKGLPSTYNKDLQEDKEAVFEVSDTMSAVLQVATGVISTLQIHQENMGQALSPDMLATDLAYYLVRKGMPFRQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ASL (go to UniProt):P04424 |
| 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 ASL |
| Gene structures of our canonical and alternative spliced genes of ASL * 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 P04424-1 |
| 3D view using mol* of P04424-2 |
| 3D view using mol* of P04424-3 |
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 P04424-1 |
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| pLDDT distribution across the protein length of P04424-2 |
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| pLDDT distribution across the protein length of P04424-3 |
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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 P04424-1 |
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| Ramachandran plot of P04424-2 |
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| Ramachandran plot of P04424-3 |
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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 |
| P04424-1 | 0.923 | 68 | 0.833 | 196.539 | 0.558 | 0.775 | 0.968 | 0.399 | 1.248 | 0.32 | 0.977 | 7,8,9,25,27,31,86,87,89,90,112,113,114,117,236,321 ,323,325,326,328,329 |
| P04424-2 | 0.815 | 60 | 0.688 | 132.741 | 0.649 | 0.669 | 0.889 | 0.138 | 1.355 | 0.102 | 0.583 | 264,265,266,267,269,271,272,273,286,287,288,289,29 0,336 |
| P04424-3 | 1.017 | 308 | 1.04 | 806.05 | 0.559 | 0.715 | 0.952 | 0.485 | 1.011 | 0.479 | 0.965 | 4,5,6,7,8,9,10,11,12,13,15,16,17,22,23,25,26,82,83 ,84,85,86,87,90,93,94,97,102,104,105,106,107,108,1 10,111,112,113,342,344,345,348,357,358,359,360,362 ,363,365,366,369 |
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 P04424-1_P04424-1_1k62_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04424-1_1k62_B_P04424-2.pdb |
| 3D view using mol* of P04424-1_1k62_B_P04424-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P04424-1_P04424-2.pdb |
| 3D view using mol* of P04424-1_P04424-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P04424-1_vs_P04424-2.png |
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| ./stats/secondary_structure/figure/P04424-1_vs_P04424-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P04424-1_vs_P04424-2.png |
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| ./stats/relative_asa/P04424-1_vs_P04424-3.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 ASL |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P04424 | ASL | DB03814 | 2-(N-morpholino)ethanesulfonic acid | experimental | |
| P04424 | ASL | DB02267 | Argininosuccinate | experimental | |
| P04424 | ASL | DB00125 | Arginine | investigational, nutraceutical |
Related Diseases to ASL |
| Previous studies relating to the alternative splicing of ASL and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ASL | 2263616 | Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region. | Argininosuccinic acid lyase (ASAL) deficiency is a clinically heterogeneous autosomal recessive urea cycle disorder. We previously established by complementation analysis that 28 ASAL-deficient patients have heterogeneous mutations in a single gene. To prove that the ASAL structural gene is the affected locus, we sequenced polymerase chain reaction-amplified ASAL cDNA of a representative mutant from the single complementation group. Fibroblast strain 944 (approximately 1% of residual ASAL activity), from a late-onset patient who was the product of a consanguineous mating, had only a single base-pair change in the coding region, a C-283----T transition at a CpG dinucleotide in exon 3. This substitution converts Arg-95 to Cys (R95C), occurs in a stretch of 13 residues that is identical in yeast and human ASAL, and was present in both of the patient's alleles but not in 14 other mutant or 10 normal alleles. Expression in COS cells demonstrated that the R95C mutation produces normal amounts of ASAL mRNA but little protein and less than 1% ASAL activity. We observed that amplified cDNA from mutant 944 and normal cells (liver, keratinocytes, lymphoblasts, and fibroblasts) contained, in addition to the expected 5' 513-base-pair band, a prominent 318-base-pair ASAL band formed by the splicing of exon 2 from the transcript. The short transcript maintains the ASAL reading frame but removes Lys-51, a residue that may be essential for catalysis, since it binds the argininosuccinate substrate. We conclude (i) that the identification of the R95C mutation in strain 944 demonstrates that virtually all ASAL deficiency results from defects in the ASAL structural gene and (ii) that minor alternative splicing of the coding region occurs at the ASAL locus. | D056807 | Argininosuccinic Aciduria |
Clinically important variants in ASL |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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