Protein:SIAH1 |
Protein Summary |
 Gene summary |
| Gene name: SIAH1 | ASpdb.0 ID: 6477 | Gene | Gene symbol | SIAH1 | Gene ID | 6477 |
| Gene name | siah E3 ubiquitin protein ligase 1 |
| Synonyms | BURHAS|SIAH1A |
| Cytomap | 16q12.1 |
| Type of gene | protein-coding |
| Description | E3 ubiquitin-protein ligase SIAH1RING-type E3 ubiquitin transferase SIAH1seven in absentia homolog 1siah-1a |
| Modification date | 20240403 |
| UniProtAcc | Q8IUQ4 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | SIAH1 | GO:0006511 | ubiquitin-dependent protein catabolic process | 23001567 |
| Gene | SIAH1 | GO:0008270 | zinc ion binding | 11863358|16085652 |
| Gene | SIAH1 | GO:0030163 | protein catabolic process | 11389840 |
| Gene | SIAH1 | GO:0030877 | beta-catenin destruction complex | 16085652 |
| Gene | SIAH1 | GO:0043065 | positive regulation of apoptotic process | 21185211 |
| Gene | SIAH1 | GO:0043161 | proteasome-mediated ubiquitin-dependent protein catabolic process | 33591310 |
| Gene | SIAH1 | GO:0061630 | ubiquitin protein ligase activity | 23001567 |
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 |
| Q8IUQ4-1 | Q8IUQ4-1_4ca1_A.pdb | 4CA1 | X-ray | 1.58 | A | 91 | 282 |
| 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 |
| Q8IUQ4 | SIAH1 | Q8IUQ4-1 | Q8IUQ4-2 | 282 | 313 | 1 | 1 | Substitution | M | MTGKATPPSLYSWRGVLFTCLPAARTRKRKEM | 1 | 32 |
| Q8IUQ4 | SIAH1 | Q8IUQ4-1 | Q8IUQ4-3 | 282 | 195 | 193 | 195 | Substitution | LEK | DLS | 193 | 195 |
| Q8IUQ4 | SIAH1 | Q8IUQ4-1 | Q8IUQ4-3 | 282 | 195 | 196 | 282 | Deletion | none | none | 195 | 195 |
| Multiple sequence alignment of our canonical and alternatively spliced SIAH1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of SIAH1 |
| UniProt-id | ENSG | ENST | ENSP |
| Q8IUQ4-1 | ENSG00000196470.12 | ENST00000380006.2 | ENSP00000369343.2 |
| Q8IUQ4-1 | ENSG00000196470.12 | ENST00000394725.3 | ENSP00000378214.2 |
| Q8IUQ4-1 | ENSG00000196470.12 | ENST00000568007.5 | ENSP00000456421.1 |
| Q8IUQ4-2 | ENSG00000196470.12 | ENST00000356721.3 | ENSP00000349156.3 |
| UniProt-id | NM ID | NP ID |
| Q8IUQ4-1 | NM_003031.3 | NP_003022.3 |
| Q8IUQ4-1 | XM_006721246.1 | XP_006721309.1 |
| Q8IUQ4-2 | NM_001006610.1 | NP_001006611.1 |
| Amino acid sequences of our canonical and alternatively spliced SIAH1 |
| accession_id | Protein sequence |
| Q8IUQ4-1 | MSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKV ANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVM MQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEATPRSIHEGIATAIMNSDCLVFDTSIAQLFAEN |
| Q8IUQ4-2 | MTGKATPPSLYSWRGVLFTCLPAARTRKRKEMSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGH LVCSNCRPKLTCCPTCRGPLGSIRNLAMEKVANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLM HQHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEAT |
| Q8IUQ4-3 | MSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKV ANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVM |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| SIAH1 (go to UniProt):Q8IUQ4 |
| 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 |
| Q8IUQ4 | Region | 1 | 22 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=1;End=1 |
| Q8IUQ4 | Region | 90 | 282 | Note=SBD;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P61092 | Type=Substitution;Start=193;End=195 |
| Q8IUQ4 | Region | 90 | 282 | Note=SBD;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:P61092 | Type=Deletion;Start=196;End=282 |
Gene Isoform Structures and Expression Levels for SIAH1 |
| Gene structures of our canonical and alternative spliced genes of SIAH1 * 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 Q8IUQ4-1 |
| 3D view using mol* of Q8IUQ4-2 |
| 3D view using mol* of Q8IUQ4-3 |
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 Q8IUQ4-1 |
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| pLDDT distribution across the protein length of Q8IUQ4-2 |
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| pLDDT distribution across the protein length of Q8IUQ4-3 |
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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 Q8IUQ4-1 |
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| Ramachandran plot of Q8IUQ4-2 |
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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 |
| Q8IUQ4-1 | 0.969 | 112 | 0.896 | 278.859 | 0.642 | 0.651 | 0.827 | 0.165 | 1.333 | 0.124 | 0.65 | 119,120,122,124,125,126,127,128,129,131,132,138,19 4,210,214,215,216,242,243,244,245,246,247,248,249, 250,251 |
| Q8IUQ4-2 | 1.039 | 213 | 1.062 | 472.997 | 0.45 | 0.74 | 1.011 | 0.577 | 0.988 | 0.583 | 1.144 | 8,9,10,11,12,13,14,15,16,18,162,163,164,165,185,18 6,187,195,196,197,198,199,200,203,206,207,208,209, 210,211,225,227 |
| Q8IUQ4-3 | 0.726 | 39 | 0.504 | 136.171 | 0.625 | 0.701 | 0.953 | 0.019 | 1.545 | 0.012 | 0.662 | 46,47,48,49,51,52,62,63,64,99,114,115,118
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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 Q8IUQ4-1_Q8IUQ4-1_4ca1_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 Q8IUQ4-1_4ca1_A_Q8IUQ4-2.pdb |
| 3D view using mol* of Q8IUQ4-1_4ca1_A_Q8IUQ4-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q8IUQ4-1_Q8IUQ4-2.pdb |
| 3D view using mol* of Q8IUQ4-1_Q8IUQ4-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q8IUQ4-1_vs_Q8IUQ4-2.png |
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| ./stats/secondary_structure/figure/Q8IUQ4-1_vs_Q8IUQ4-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q8IUQ4-1_vs_Q8IUQ4-2.png |
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| ./stats/relative_asa/Q8IUQ4-1_vs_Q8IUQ4-3.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 SIAH1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to SIAH1 |
| Previous studies relating to the alternative splicing of SIAH1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| SIAH1 | 23503458 | Downregulation of serine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells. | Serine/arginine-rich splicing factor 3 (SRSF3) likely has wide-ranging roles in gene expression and facilitation of tumor cell growth. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116) in association with altered expression of 833 genes. Pathway analysis revealed 'G1/S Checkpoint Regulation' as the most highly enriched category in the affected genes. SRSF3 knockdown did not induce p53 or stimulate phosphorylation of p53 or histone H2A.X in wild-type HCT116 cells. Furthermore, the knockdown induced G1 arrest in p53-null HCT116 cells, suggesting that p53-dependent DNA damage responses did not mediate the G1 arrest. Real-time reverse transcription-polymerase chain reaction and western blotting confirmed that SRSF3 knockdown reduced mRNA and protein levels of cyclins (D1, D3 and E1), E2F1 and E2F7. The decreased expression of cyclin D and E2F1 likely impaired the G1-to-S-phase progression. Consequently, retinoblastoma protein remained hypophosphorylated in SRSF3 knockdown cells. The knockdown also induced apoptosis in association with reduction of BCL2 protein levels. We also found that SRSF3 knockdown facilitated skipping of 81 5'-nucleotides (27 amino acids) from exon 8 of homeodomain-interacting protein kinase-2 (HIPK2) and produced a HIPK2 Δe8 isoform. Full-length HIPK2 (HIPK2 FL) is constantly degraded through association with an E3 ubiquitin ligase (Siah-1), whereas HIPK2 Δe8, lacking the 27 amino acids, lost Siah-1-binding ability and became resistant to proteasome digestion. Interestingly, selective knockdown of HIPK2 FL induced apoptosis in various colon cancer cells expressing wild-type or mutated p53. Thus, these findings disclose an important role of SRSF3 in the regulation of the G1-to-S-phase progression and alternative splicing of HIPK2 in tumor growth. | D003110 | Colonic Neoplasms |
Clinically important variants in SIAH1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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