Protein:ALOX5 |
Protein Summary |
 Gene summary |
| Gene name: ALOX5 | ASpdb.0 ID: 240 | Gene | Gene symbol | ALOX5 | Gene ID | 240 |
| Gene name | arachidonate 5-lipoxygenase |
| Synonyms | 5-LO|5-LOX|5LPG|LOG5 |
| Cytomap | 10q11.21 |
| Type of gene | protein-coding |
| Description | polyunsaturated fatty acid 5-lipoxygenaseLOX-5arachidonic acid 5-lipoxygenaseleukotriene A4 synthase |
| Modification date | 20240411 |
| UniProtAcc | P09917 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ALOX5 | GO:0004051 | arachidonate 5-lipoxygenase activity | 8615788|8631361|19022417|21233389|22516296|23246375|24282679|24893149 |
| Gene | ALOX5 | GO:0005506 | iron ion binding | 21233389 |
| Gene | ALOX5 | GO:0005635 | nuclear envelope | 19233132 |
| Gene | ALOX5 | GO:0005641 | nuclear envelope lumen | 8245774 |
| Gene | ALOX5 | GO:0005654 | nucleoplasm | - |
| Gene | ALOX5 | GO:0005829 | cytosol | 19233132 |
| Gene | ALOX5 | GO:0016363 | nuclear matrix | 19233132 |
| Gene | ALOX5 | GO:0019370 | leukotriene biosynthetic process | 21233389|24893149 |
| Gene | ALOX5 | GO:0031965 | nuclear membrane | 8245774 |
| Gene | ALOX5 | GO:0048471 | perinuclear region of cytoplasm | 19022417 |
| Gene | ALOX5 | GO:0050728 | negative regulation of inflammatory response | 21206090 |
| Gene | ALOX5 | GO:1901753 | leukotriene A4 biosynthetic process | 24282679 |
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 |
| P09917-1 | P09917-1_3o8y_B.pdb | 3O8Y | X-ray | 2.39 | B | 2 | 674 |
| 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 |
| P09917 | ALOX5 | P09917-1 | P09917-2 | 674 | 617 | 559 | 615 | Deletion | none | none | 558 | 558 |
| P09917 | ALOX5 | P09917-1 | P09917-3 | 674 | 642 | 424 | 455 | Deletion | none | none | 423 | 423 |
| P09917 | ALOX5 | P09917-1 | P09917-4 | 674 | 533 | 425 | 533 | Substitution | ANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSR | VHGRGGRHLLRGRPGGGGGPGAAGLRERCLRVRHAGPQVLRLPQVGQEPGAAVGVPDRGDLHRLRPARRGQLRPAVPGHVPRRAFYREACEGSHGPIPQEPRGHCQRDC | 425 | 533 |
| P09917 | ALOX5 | P09917-1 | P09917-4 | 674 | 533 | 534 | 674 | Deletion | none | none | 533 | 533 |
| P09917 | ALOX5 | P09917-1 | P09917-5 | 674 | 484 | 485 | 674 | Deletion | none | none | 484 | 484 |
| Multiple sequence alignment of our canonical and alternatively spliced ALOX5 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ALOX5 |
| UniProt-id | ENSG | ENST | ENSP |
| P09917-1 | ENSG00000012779.12 | ENST00000374391.7 | ENSP00000363512.2 |
| P09917-1 | ENSG00000275565.4 | ENST00000610656.4 | ENSP00000484468.1 |
| P09917-2 | ENSG00000012779.12 | ENST00000542434.5 | ENSP00000437634.1 |
| P09917-2 | ENSG00000275565.4 | ENST00000622021.4 | ENSP00000479958.1 |
| UniProt-id | NM ID | NP ID |
| P09917-1 | NM_000698.4 | NP_000689.1 |
| P09917-2 | NM_001256154.2 | NP_001243083.1 |
| P09917-3 | NM_001256153.2 | NP_001243082.1 |
| Amino acid sequences of our canonical and alternatively spliced ALOX5 |
| accession_id | Protein sequence |
| P09917-1 | MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKT PHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQ LSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLC FPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYL TVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKP |
| P09917-2 | MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKT PHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQ LSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLC FPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYL |
| P09917-3 | MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKT PHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQ LSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKARGMESKEDIPYYFYRDDGLLVWEAI RTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTM RAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYYY |
| P09917-4 | MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKT PHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQ LSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKVHGRGGRHLLRGRPGGGGGPGAAGLR |
| P09917-5 | MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKT PHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQ LSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLC |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ALOX5 (go to UniProt):P09917 |
| 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 |
| P09917 | Domain | 119 | 674 | Note=Lipoxygenase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00726 | Type=Deletion;Start=559;End=615 |
| P09917 | Domain | 119 | 674 | Note=Lipoxygenase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00726 | Type=Deletion;Start=424;End=455 |
| P09917 | Domain | 119 | 674 | Note=Lipoxygenase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00726 | Type=Substitution;Start=425;End=533 |
| P09917 | Domain | 119 | 674 | Note=Lipoxygenase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00726 | Type=Deletion;Start=534;End=674 |
| P09917 | Domain | 119 | 674 | Note=Lipoxygenase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00726 | Type=Deletion;Start=485;End=674 |
Gene Isoform Structures and Expression Levels for ALOX5 |
| Gene structures of our canonical and alternative spliced genes of ALOX5 * 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 P09917-1 |
| 3D view using mol* of P09917-2 |
| 3D view using mol* of P09917-3 |
| 3D view using mol* of P09917-4 |
| 3D view using mol* of P09917-5 |
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 P09917-1 |
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| pLDDT distribution across the protein length of P09917-2 |
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| pLDDT distribution across the protein length of P09917-3 |
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| pLDDT distribution across the protein length of P09917-4 |
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| pLDDT distribution across the protein length of P09917-5 |
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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 P09917-1 |
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| Ramachandran plot of P09917-2 |
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| Ramachandran plot of P09917-3 |
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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 |
| P09917-1 | 1.147 | 89 | 1.068 | 151.949 | 0.407 | 0.98 | 1.29 | 1.024 | 1.248 | 0.821 | 1.402 | 178,182,360,364,365,368,369,373,407,408,411,415,41 6,421,422,424,425,426,433,551,555,570,600,601,604, 605,608,674 |
| P09917-2 | 1.172 | 136 | 0.905 | 240.443 | 0.382 | 0.955 | 1.269 | 0.284 | 1.864 | 0.152 | 0.707 | 13,82,99,100,101,102,103,111,112,113,114,115,131,1 35,139,142,143,167,168,169,171,384,388,389,390,394 ,395,398,399,401,402,403,404,405,406,565,566,568 |
| P09917-3 | 1.061 | 305 | 0.99 | 619.458 | 0.462 | 0.789 | 1.052 | 0.574 | 1.298 | 0.442 | 0.626 | 13,27,67,69,71,72,82,99,100,101,102,103,104,105,10 6,107,108,109,110,111,112,113,114,115,126,127,130, 131,134,135,137,138,139,141,142,143,144,156,157,15 8,163,164,165,166,167,168,169,171,384,389,390,394, 395,398,399,401,402,403,404,405,406,584,590,591,59 3 |
| P09917-4 | 1.051 | 305 | 0.963 | 611.226 | 0.442 | 0.774 | 1.055 | 0.457 | 1.353 | 0.337 | 0.559 | 13,27,67,69,82,99,100,101,102,103,104,105,106,107, 108,109,110,111,112,113,114,115,126,127,130,131,13 2,134,135,138,139,142,143,164,165,166,167,168,169, 171,384,388,389,390,394,395,398,399,401,402,403,40 4,405,406 |
| P09917-5 | 1.068 | 177 | 0.941 | 333.739 | 0.44 | 0.8 | 1.106 | 0.555 | 1.468 | 0.378 | 0.528 | 13,82,99,100,101,102,103,110,111,112,113,114,131,1 32,135,138,139,142,143,166,167,168,169,171,384,388 ,389,390,394,395,398,399,401,402,403,404,405,406 |
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 P09917-1_P09917-1_3o8y_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 P09917-1_3o8y_B_P09917-2.pdb |
| 3D view using mol* of P09917-1_3o8y_B_P09917-3.pdb |
| 3D view using mol* of P09917-1_3o8y_B_P09917-4.pdb |
| 3D view using mol* of P09917-1_3o8y_B_P09917-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P09917-1_P09917-2.pdb |
| 3D view using mol* of P09917-1_P09917-3.pdb |
| 3D view using mol* of P09917-1_P09917-4.pdb |
| 3D view using mol* of P09917-1_P09917-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P09917-1_vs_P09917-2.png |
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| ./stats/secondary_structure/figure/P09917-1_vs_P09917-3.png |
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| ./stats/secondary_structure/figure/P09917-1_vs_P09917-4.png |
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| ./stats/secondary_structure/figure/P09917-1_vs_P09917-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P09917-1_vs_P09917-2.png |
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| ./stats/relative_asa/P09917-1_vs_P09917-3.png |
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| ./stats/relative_asa/P09917-1_vs_P09917-4.png |
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| ./stats/relative_asa/P09917-1_vs_P09917-5.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 ALOX5 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P09917 | ALOX5 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P09917 | ALOX5 | DB00163 | Vitamin E | approved, nutraceutical, vet_approved | |
| P09917 | ALOX5 | DB11994 | Diacerein | approved, investigational | inhibitor |
| P09917 | ALOX5 | DB01892 | Hyperforin | nutraceutical | inhibitor |
| P09917 | ALOX5 | DB02709 | Resveratrol | investigational | |
| P09917 | ALOX5 | DB00179 | Masoprocol | approved, investigational | inhibitor |
| P09917 | ALOX5 | DB00744 | Zileuton | approved, investigational, withdrawn | inhibitor |
| P09917 | ALOX5 | DB00159 | Icosapent | approved, nutraceutical | substrate |
| P09917 | ALOX5 | DB00711 | Diethylcarbamazine | approved, investigational, vet_approved | inhibitor |
| P09917 | ALOX5 | DB09285 | Morniflumate | experimental | antagonist |
| P09917 | ALOX5 | DB00471 | Montelukast | approved | other/unknown |
| P09917 | ALOX5 | DB00244 | Mesalazine | approved | inhibitor |
| P09917 | ALOX5 | DB01014 | Balsalazide | approved, investigational | inhibitor |
| P09917 | ALOX5 | DB00795 | Sulfasalazine | approved | inhibitor |
| P09917 | ALOX5 | DB14002 | D-alpha-Tocopherol acetate | approved, nutraceutical, vet_approved | |
| P09917 | ALOX5 | DB13174 | Rhein | experimental | inhibitor |
| P09917 | ALOX5 | DB00233 | Aminosalicylic acid | approved | inhibitor |
| P09917 | ALOX5 | DB05431 | MLN-977 | investigational | |
| P09917 | ALOX5 | DB00939 | Meclofenamic acid | approved, vet_approved | inhibitor |
| P09917 | ALOX5 | DB04725 | Licofelone | investigational | |
| P09917 | ALOX5 | DB01017 | Minocycline | approved, investigational | inhibitor |
| P09917 | ALOX5 | DB14001 | alpha-Tocopherol succinate | approved, nutraceutical, vet_approved |
Related Diseases to ALOX5 |
| Previous studies relating to the alternative splicing of ALOX5 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ALOX5 | 21098726 | Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. | 5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of leukotrienes, important mediators of inflammation. This study investigated whether variants of 5-LO exist in human leukocytes. 5-LO mRNA isoforms that are consistent with alternative splicing were identified by RT-PCR in a cell line or cell type-specific pattern. All evaluated cells expressed mRNA containing all 14 exons of 5-LO with the expected splicing sites. Individual isoforms that retained intron 10 (α-10), lacked exon 13 (Δ-13), and lacked exons 10 and 13 (Δ-10,13) or that lacked the first 96 base pairs of exon 10 (Δ-p10) were identified. Immunoreactive bands coeluting with the cloned α-10 and Δ-13 isoforms were measured in primary neutrophils and in Raji cells. When expressed in HEK293 cells, alternative proteins were without catalytic activity. However, when coexpressed with the active full-length 5-LO, alternative isoforms significantly decreased the biosynthesis of 5-LO products by up to 44%, as assessed by reverse-phase HPLC analysis. Additionally, in stimulated neutrophils the full-length active 5-LO was detected by immunoblot in both nuclear and non-nuclear compartments, while the Δ-13 isoform was only detected in the nuclear fraction. These alternative 5-LO isoforms may represent a new mechanism for the regulation of the 5-LO pathway and lipid mediator biosynthesis. | D002051 | Burkitt Lymphoma |
| ALOX5 | 21098726 | Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. | 5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of leukotrienes, important mediators of inflammation. This study investigated whether variants of 5-LO exist in human leukocytes. 5-LO mRNA isoforms that are consistent with alternative splicing were identified by RT-PCR in a cell line or cell type-specific pattern. All evaluated cells expressed mRNA containing all 14 exons of 5-LO with the expected splicing sites. Individual isoforms that retained intron 10 (α-10), lacked exon 13 (Δ-13), and lacked exons 10 and 13 (Δ-10,13) or that lacked the first 96 base pairs of exon 10 (Δ-p10) were identified. Immunoreactive bands coeluting with the cloned α-10 and Δ-13 isoforms were measured in primary neutrophils and in Raji cells. When expressed in HEK293 cells, alternative proteins were without catalytic activity. However, when coexpressed with the active full-length 5-LO, alternative isoforms significantly decreased the biosynthesis of 5-LO products by up to 44%, as assessed by reverse-phase HPLC analysis. Additionally, in stimulated neutrophils the full-length active 5-LO was detected by immunoblot in both nuclear and non-nuclear compartments, while the Δ-13 isoform was only detected in the nuclear fraction. These alternative 5-LO isoforms may represent a new mechanism for the regulation of the 5-LO pathway and lipid mediator biosynthesis. | D007249 | Inflammation |
| ALOX5 | 21098726 | Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. | 5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of leukotrienes, important mediators of inflammation. This study investigated whether variants of 5-LO exist in human leukocytes. 5-LO mRNA isoforms that are consistent with alternative splicing were identified by RT-PCR in a cell line or cell type-specific pattern. All evaluated cells expressed mRNA containing all 14 exons of 5-LO with the expected splicing sites. Individual isoforms that retained intron 10 (α-10), lacked exon 13 (Δ-13), and lacked exons 10 and 13 (Δ-10,13) or that lacked the first 96 base pairs of exon 10 (Δ-p10) were identified. Immunoreactive bands coeluting with the cloned α-10 and Δ-13 isoforms were measured in primary neutrophils and in Raji cells. When expressed in HEK293 cells, alternative proteins were without catalytic activity. However, when coexpressed with the active full-length 5-LO, alternative isoforms significantly decreased the biosynthesis of 5-LO products by up to 44%, as assessed by reverse-phase HPLC analysis. Additionally, in stimulated neutrophils the full-length active 5-LO was detected by immunoblot in both nuclear and non-nuclear compartments, while the Δ-13 isoform was only detected in the nuclear fraction. These alternative 5-LO isoforms may represent a new mechanism for the regulation of the 5-LO pathway and lipid mediator biosynthesis. | D007948 | Leukemia, Monocytic, Acute |
Clinically important variants in ALOX5 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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