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                "uniprot_canonical_ac": "P29350-1",
                "protein_name": "Tyrosine-protein phosphatase non-receptor type 6",
                "gene_name": "PTPN6",
                "tax_name": "Human"
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                "uniprot_canonical_ac": "Q14653-1",
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                "tax_name": "Human"
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            {
                "uniprot_canonical_ac": "Q13568-1",
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                "tax_name": "Human"
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            {
                "uniprot_canonical_ac": "P02795-1",
                "protein_name": "Metallothionein-2",
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                "tax_name": "Human"
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                "uniprot_canonical_ac": "Q9BZY9-1",
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                "tax_name": "Human"
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            {
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                "tax_name": "Human"
            },
            {
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                "tax_name": "Human"
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            {
                "uniprot_canonical_ac": "Q9C035-1",
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                "tax_name": "Human"
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            {
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            {
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            {
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                "gene_name": "CASP1",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "P70343-1",
                "protein_name": "Caspase-4",
                "gene_name": "Casp4",
                "tax_name": "Mouse"
            },
            {
                "uniprot_canonical_ac": "P01584-1",
                "protein_name": "Interleukin-1 beta",
                "gene_name": "IL1B",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "P49662-1",
                "protein_name": "Caspase-4",
                "gene_name": "CASP4",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "P51878-1",
                "protein_name": "Caspase-5",
                "gene_name": "CASP5",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "P57764-1",
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                "gene_name": "GSDMD",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "Q13478-1",
                "protein_name": "Interleukin-18 receptor 1",
                "gene_name": "IL18R1",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "Q14116-1",
                "protein_name": "Interleukin-18",
                "gene_name": "IL18",
                "tax_name": "Human"
            },
            {
                "uniprot_canonical_ac": "P42574-1",
                "protein_name": "Caspase-3",
                "gene_name": "CASP3",
                "tax_name": "Human"
            }
        ],
        "species": [
            {
                "name": "Mus musculus",
                "taxid": 10090,
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P70380",
                        "url": "https://www.uniprot.org/uniprotkb/P70380"
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                ],
                "common_name": "Mouse",
                "glygen_name": "Mouse",
                "reference_species": "Mus musculus [10090]"
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        ],
        "mutagenesis": [
            {
                "start_pos": 318,
                "end_pos": 320,
                "sequence_org": "IKK",
                "sequence_mut": "AKA",
                "comment": "Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P29466",
                        "url": "https://www.uniprot.org/uniprotkb/P29466"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P29466-1"
            },
            {
                "start_pos": 289,
                "end_pos": 289,
                "sequence_org": "L",
                "sequence_mut": "K",
                "comment": "Does not promote ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P70343",
                        "url": "https://www.uniprot.org/uniprotkb/P70343"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P70343-1"
            },
            {
                "start_pos": 152,
                "end_pos": 152,
                "sequence_org": "R",
                "sequence_mut": "A",
                "comment": "Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 212,
                "end_pos": 212,
                "sequence_org": "I",
                "sequence_mut": "D",
                "comment": "Abolished ability to cleave IL18; when associated with D-261.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 258,
                "end_pos": 258,
                "sequence_org": "C",
                "sequence_mut": "A",
                "comment": "Loss of enzymatic activity. Loss of LPS-induced pyroptosis. No effect on the interaction with LPS. Decrease in cell death induced by TMEM214 overexpression. Does not support IL1B and IL18 secretion following UVB irradiation.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "22246630",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/22246630"
                    },
                    {
                        "database": "PubMed",
                        "id": "25119034",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/25119034"
                    },
                    {
                        "database": "PubMed",
                        "id": "28314590",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/28314590"
                    },
                    {
                        "database": "PubMed",
                        "id": "23661706",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/23661706"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993712",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993712"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 261,
                "end_pos": 261,
                "sequence_org": "A",
                "sequence_mut": "D",
                "comment": "Abolished ability to cleave IL18; when associated with D-212.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 267,
                "end_pos": 267,
                "sequence_org": "W",
                "sequence_mut": "L",
                "comment": "Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. Abolished binding to IL18 and ability to mediate its cleavage.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "32109412",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/32109412"
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                    {
                        "database": "PubMed",
                        "id": "37993712",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993712"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 267,
                "end_pos": 267,
                "sequence_org": "W",
                "sequence_mut": "N",
                "comment": "Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. Abolished binding to IL18 and ability to mediate its cleavage.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "32109412",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/32109412"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993712",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993712"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 289,
                "end_pos": 289,
                "sequence_org": "D",
                "sequence_mut": "A",
                "comment": "Abolished autoprocessing.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 291,
                "end_pos": 291,
                "sequence_org": "V",
                "sequence_mut": "N",
                "comment": "Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. Strongly decreased ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "32109412",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/32109412"
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                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 293,
                "end_pos": 293,
                "sequence_org": "K",
                "sequence_mut": "A",
                "comment": "Strongly decreased ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 314,
                "end_pos": 314,
                "sequence_org": "R",
                "sequence_mut": "A",
                "comment": "Abolished ability to cleave Gasdermin-D (GSDMD). Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "34671164",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/34671164"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 321,
                "end_pos": 321,
                "sequence_org": "I",
                "sequence_mut": "D",
                "comment": "Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P49662",
                        "url": "https://www.uniprot.org/uniprotkb/P49662"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P49662-1"
            },
            {
                "start_pos": 324,
                "end_pos": 324,
                "sequence_org": "W",
                "sequence_mut": "L",
                "comment": "Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P51878",
                        "url": "https://www.uniprot.org/uniprotkb/P51878"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P51878-1"
            },
            {
                "start_pos": 348,
                "end_pos": 350,
                "sequence_org": "VCK",
                "sequence_mut": "NCA",
                "comment": "Abolished ability to cleave IL18.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "P51878",
                        "url": "https://www.uniprot.org/uniprotkb/P51878"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "P51878-1"
            },
            {
                "start_pos": 12,
                "end_pos": 12,
                "sequence_org": "N",
                "sequence_mut": "A",
                "comment": "Strongly decreased processing by CASP4 or CASP5; when associated with A-28.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 28,
                "end_pos": 28,
                "sequence_org": "E",
                "sequence_mut": "A",
                "comment": "Strongly decreased processing by CASP4 or CASP5; when associated with A-12.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    }
                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 33,
                "end_pos": 35,
                "sequence_org": "LES",
                "sequence_mut": "AAA",
                "comment": "Abolished processing by CASP1, CASP4 or CASP5 and maturation.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993712",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993712"
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                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 36,
                "end_pos": 36,
                "sequence_org": "D",
                "sequence_mut": "A",
                "comment": "Abolished processing by CASP1 or CASP4 or CASP5 and maturation.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
                    },
                    {
                        "database": "PubMed",
                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 37,
                "end_pos": 38,
                "sequence_org": "YF",
                "sequence_mut": "AA",
                "comment": "Does not strongly affect cleavage by CASP4.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
                    },
                    {
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                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 38,
                "end_pos": 38,
                "sequence_org": "F",
                "sequence_mut": "D",
                "comment": "Abolished ability to bind the IL18R1 receptor without affecting its processing by CASP4.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "Q14116",
                        "url": "https://www.uniprot.org/uniprotkb/Q14116"
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                    {
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                        "id": "37993714",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/37993714"
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                ],
                "uniprot_canonical_ac": "Q14116-1"
            },
            {
                "start_pos": 70,
                "end_pos": 77,
                "sequence_org": "TDSDCRDN",
                "sequence_mut": "",
                "comment": "Abolished ability to bind the IL18R1 receptor without affecting its processing by CASP4.",
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                        "database": "UniProtKB",
                        "id": "Q14116",
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                "start_pos": 71,
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                "sequence_org": "D",
                "sequence_mut": "A",
                "comment": "Impairs binding to IL18R1 and the ability to induce IFNG production. Abolished cleavage by CASP3.",
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        "title": "KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.",
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        "date": "2018",
        "authors": "Chen J, Ou Y, Yang Y, Li W, Xu Y, Xie Y, Liu Y",
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            {
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                "comment": "No effect on interaction with KLHL22.",
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                        "url": "https://www.uniprot.org/uniprotkb/O75140"
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                "comment": "No effect on interaction with KLHL22.",
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                        "id": "O75140",
                        "url": "https://www.uniprot.org/uniprotkb/O75140"
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                        "id": "29769719",
                        "url": "https://pubmed.ncbi.nlm.nih.gov/29769719"
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                "sequence_org": "S",
                "sequence_mut": "A",
                "comment": "No effect on interaction with KLHL22.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "O75140",
                        "url": "https://www.uniprot.org/uniprotkb/O75140"
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                "sequence_org": "T",
                "sequence_mut": "A",
                "comment": "No effect on interaction with KLHL22.",
                "evidence": [
                    {
                        "database": "UniProtKB",
                        "id": "O75140",
                        "url": "https://www.uniprot.org/uniprotkb/O75140"
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                "comment": "No effect on interaction with KLHL22.",
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    {
        "title": "Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development.",
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        "authors": "Kong Xiangxing, Shu Xin, Wang Jiachuan, Liu Dandan, Ni Yingchun, Zhao Weiqi, Wang Lebo, Gao Zhihua, Chen Jiadong, Yang Bing, Guo Xing, Wang Zhiping",
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]
