{ "uniprot_canonical_ac": "A2ADY9-1", "ptm_annotation": [], "sequence": { "header": "sp|A2ADY9-1|DDI2_MOUSE Isoform 1 of Protein DDI1 homolog 2 OS=Mus musculus OX=10090 GN=Ddi2 PE=1 SV=1 CANONICAL=A2ADY9-1", "length": 399, "sequence": "MLLTVYCVRRDLSEVTFSLQVDADFELHNFRALCELESGIPAAESQIVYAERPLTDNHRSLASYGLKDGDVVILRQKENADPRPAVQFSNLPRIDFSSIAVPGTSNPQQRQLPRTQAQHSSPGEMASSPQGLDNPALLRDMLLANPHELSLLKERNPPLAEALLSGDLEKFSRVLVEQQQDRARREQERIRLFSADPFDLEAQAKIEEDIRQQNIEENMTIAMEEAPESFGQVAMLYINCRVNGHPVKAFVDSGAQMTIMSQACAERCNIMRLVDRRWAGIAKGVGTQKIIGRVHLAQVQIEGDFLACSFSILEEQPMDMLLGLDMLKRHQCSIDLKKNVLVIGTTGSQTTFLPEGELPECARLAYGTGREDIRPEEIADQELAEAIQKSAEDAERQKP" }, "uniprot_id": "DDI2_MOUSE", "enzyme_annotation": [ { "ec": "3.4.23.-", "activity": "" } ], "glycation": [], "keywords": [], "species": [ { "common_name": "Mouse", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "taxid": 10090, "name": "Mus musculus" } ], "crossref_internal": { "gene": [ "Ddi2" ], "site": [ "A2ADY9-1.104.104", "A2ADY9-1.194.194", "A2ADY9-1.128.128", "A2ADY9-1.121.121", "A2ADY9-1.150.150", "A2ADY9-1.120.120" ], "species": [ 10090 ] }, "publication": [ { "reference": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/12520002", "type": [ "PubMed" ], "id": "12520002" } ], "title": "BayGenomics: a resource of insertional mutations in mouse embryonic stem cells.", "journal": "Nucleic acids research", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "id": "NP_001017966.1", "database": "RefSeq" } ], "authors": "Stryke D, Kawamoto M, Huang CC, Johns SJ, King LA, Harper CA, Meng EC, Lee RE, Yee A, L'Italien L, Chuang PT, Young SG, Skarnes WC, Babbitt PC, Ferrin TE", "date": "2003" }, { "reference": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/17242355", "type": [ "PubMed" ], "id": "17242355" } ], "title": "Large-scale phosphorylation analysis of mouse liver.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "authors": "Beausoleil S.A., Gerber S.A., Gygi S.P., Villen J.", "date": "2007" }, { "reference": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/27528193", "type": [ "PubMed" ], "id": "27528193" } ], "title": "The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction.", "journal": "eLife", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "id": "NP_001017966.1", "database": "RefSeq" } ], "authors": "Koizumi S, Irie T, Hirayama S, Sakurai Y, Yashiroda H, Naguro I, Ichijo H, Hamazaki J, Murata S", "date": "2016" }, { "reference": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/28322824", "type": [ "PubMed" ], "id": "28322824" } ], "title": "MicroRNA-133 mediates cardiac diseases: Mechanisms and clinical implications.", "journal": "Experimental cell research", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "id": "NP_001017966.1", "database": "RefSeq" } ], "authors": "Liu Y, Liang Y, Zhang JF, Fu WM", "date": "2017" }, { "reference": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/29788202", "type": [ "PubMed" ], "id": "29788202" } ], "title": "Quantitative proteomics reveals neuronal ubiquitination of Rngo/Ddi1 and several proteasomal subunits by Ube3a, accounting for the complexity of Angelman syndrome.", "journal": "Human molecular genetics", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "id": "NP_001017966.1", "database": "RefSeq" } ], "authors": "Ramirez J, Lectez B, Osinalde N, Siva M, Elu N, Aloria K, Prochazkova M, Perez C, Martinez-Hernandez J, Barrio R, Saskova KG, Arizmendi JM, Mayor U", "date": "2018" } ], "uniprot_ac": "A2ADY9", "gene_names": [ { "url": "https://www.ncbi.nlm.nih.gov/protein/A2ADY9", "type": "synonym", "resource": "RefSeq", "name": "1110056G13Rik; 1700027M01Rik; 9130022E05Rik; AI604911; AU040698" }, { "url": "https://www.ncbi.nlm.nih.gov/protein/A2ADY9", "type": "synonym", "resource": "RefSeq", "name": "Ddi2" }, { "url": "https://www.uniprot.org/uniprot/A2ADY9", "type": "recommended", "resource": "UniProtKB", "name": "Ddi2" } ], "isoforms": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9#A2ADY9-1", "isoform_ac": "A2ADY9-1", "locus": { "end_pos": 141689318, "strand": "+", "start_pos": 141723194, "chromosome": "4", "evidence": [ { "url": "https://www.ensembl.org/id/ENSMUST00000102484", "id": "ENSMUST00000102484", "database": "Ensembl Transcript" }, { "url": "https://www.ensembl.org/id/ENSMUSP00000099542", "id": "ENSMUSP00000099542", "database": "Ensembl Peptide" } ] }, "sequence": { "header": "sp|A2ADY9-1|DDI2_MOUSE Isoform 1 of Protein DDI1 homolog 2 OS=Mus musculus OX=10090 GN=Ddi2 PE=1 SV=1 CANONICAL=A2ADY9-1", "length": 399, "sequence": "MLLTVYCVRRDLSEVTFSLQVDADFELHNFRALCELESGIPAAESQIVYAERPLTDNHRSLASYGLKDGDVVILRQKENADPRPAVQFSNLPRIDFSSIAVPGTSNPQQRQLPRTQAQHSSPGEMASSPQGLDNPALLRDMLLANPHELSLLKERNPPLAEALLSGDLEKFSRVLVEQQQDRARREQERIRLFSADPFDLEAQAKIEEDIRQQNIEENMTIAMEEAPESFGQVAMLYINCRVNGHPVKAFVDSGAQMTIMSQACAERCNIMRLVDRRWAGIAKGVGTQKIIGRVHLAQVQIEGDFLACSFSILEEQPMDMLLGLDMLKRHQCSIDLKKNVLVIGTTGSQTTFLPEGELPECARLAYGTGREDIRPEEIADQELAEAIQKSAEDAERQKP" } } ], "pathway": [ { "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:68817", "resource": "KEGG Pathway", "id": "mmu:68817", "name": "" } ], "function": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9#function", "annotation": "Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2. Required, with DDI1, for cellular survival following replication stress. Together or redudantly with DDI1, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity.", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9#function", "id": "A2ADY9", "database": "UniProtKB" } ] } ], "orthologs": [ { "uniprot_canonical_ac": "A0A096MJP9-1", "protein_name": "DNA damage-inducible 1 homolog 2", "sequence": { "length": 986, "sequence": "MLLTVYCVRRDLSEVTFSLQVDADFELHNFRALCELESGIPAAESQIVYAERPLTDNHRSLASYGLKDGDVVILRQKENADPRPSVQFSNLPRIDFSSIAVPGTSNPQQRQLPRTQAQLLSPGERTSTPQGLDSPALLRDMLLANPHELSLLKERNPPLAEALLSGDLEKFSRVLVEQQQDRARREQERIRLFSADPFDLEAQAKIEEDIRQQNIEENMTIAMEEAPESFGQVAMLYINCRVNGHPVKAFVDSGAQMTIMSQACAERCNIMRLVDRRWAGIAKGVGTQKIIGRVHLAQVQIEGDFLACSFSILEEQPMDMLLGLDMLKRHQCSIDLKKNVLVIGTTGSQTTFLPEGELPECARLAYGTGREDIRPEEIADQELAEAIQKSAEDAEKSSKESTSLGTPSLLTSEGLNHPAPSGHSPEVGSPTSLARSVSASVCAIKPSDPNSIGSPAVEATKASAEFQTNSKKTDPPLQVLPDLASSAERSLAMPLHNSSDEAFVTGNLEKSAEKRTQGLRVYLHTRQDASLSLTTTGTHEPQIFVEEKSWHPENQNSSQVNGLQQHRETERVQREPGAQSVPGDRECLCHTEDLELQEEAVGWEAVMKGSGALLSTAHLLSAEEGLPAPGRCSCSCSEALMEVDTAEQSPVASCNSTGRPVITSPGVSHVTSEHPSMEVETSQCNLSCDRVEHSILTRDLQLPDNVEMSTMDNKDDRSSSPLSGHGQPSLESAEEFCSSVTVALKELHELLVISCKPASEDSPEDITCQSEIAAESQASISDLTGRSTQSEHLTPSDQHPQVSCPQATSESEKTEILGAAPHAAGEDDTSTGFGGLGDGLSPGQEGLPRSTESVRKSCSVAITSAKLSEQLPCTSGVESSLELAAGEEGAHSQPSEHVQNPGPDRPETSTVCPGAVLPFGGLDQPTTQSLSTPSTLPPFVFPAADVDRILGAGFTLQEALGALHRVGGNADLALLVLLAKNIVVPT" }, "evidence": [ { "url": "http://www.informatics.jax.org/homology/121661", "id": "121661", "database": "MGI" } ], "common_name": "Rat", "organism": "Rattus norvegicus", "tax_id": 10116 }, { "uniprot_canonical_ac": "Q5TDH0-1", "protein_name": "Protein DDI1 homolog 2", "sequence": { "length": 399, "sequence": "MLLTVYCVRRDLSEVTFSLQVDADFELHNFRALCELESGIPAAESQIVYAERPLTDNHRSLASYGLKDGDVVILRQKENADPRPPVQFPNLPRIDFSSIAVPGTSSPRQRQPPGTQQSHSSPGEITSSPQGLDNPALLRDMLLANPHELSLLKERNPPLAEALLSGDLEKFSRVLVEQQQDRARREQERIRLFSADPFDLEAQAKIEEDIRQQNIEENMTIAMEEAPESFGQVVMLYINCKVNGHPVKAFVDSGAQMTIMSQACAERCNIMRLVDRRWAGIAKGVGTQKIIGRVHLAQVQIEGDFLPCSFSILEEQPMDMLLGLDMLKRHQCSIDLKKNVLVIGTTGSQTTFLPEGELPECARLAYGAGREDVRPEEIADQELAEALQKSAEDAERQKP" }, "evidence": [ { "url": "http://www.informatics.jax.org/homology/121661", "id": "121661", "database": "MGI" }, { "url": "https://omabrowser.org/oma/group/A2ADY9/", "id": "A2ADY9", "database": "OMA" } ], "common_name": "Human", "organism": "Homo sapiens", "tax_id": 9606 } ], "interactions": [], "synthesized_glycans": [], "snv": [], "cluster_types": [ { "name": "homologset.mgi", "label": "MGI Homologs" }, { "name": "homologset.oma", "label": "OMA Homologs" } ], "refseq": { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "ac": "NP_001017966.1", "name": "protein DDI1 homolog 2", "summary": "" }, "go_annotation": { "categories": [ { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0004190", "pmid": "27528193", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0004190", "name": "aspartic-type endopeptidase activity" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0042802", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0042802", "name": "identical protein binding" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043130", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0043130", "name": "ubiquitin binding" } ], "total": 3, "name": "Molecular Function" }, { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005654", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0005654", "name": "nucleoplasm" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005829", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0005829", "name": "cytosol" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005694", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0005694", "name": "chromosome" } ], "total": 3, "name": "Cellular Component" }, { "go_terms": [ { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0016485", "pmid": "27676298", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0016485", "name": "protein processing" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0016485", "pmid": "27528193", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0016485", "name": "protein processing" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0031647", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0031647", "name": "regulation of protein stability" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010498", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0010498", "name": "proteasomal protein catabolic process" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0097752", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0097752", "name": "regulation of DNA stability" }, { "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0072711", "pmid": "", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "id": "GO:0072711", "name": "cellular response to hydroxyurea" } ], "total": 6, "name": "Biological Process" } ] }, "site_annotation": [ { "end_pos": 220, "annotation": "n_glycosylation_sequon", "start_pos": 218 } ], "pro_annotation": [], "crossref": [ { "url": "https://bgee.org/?page=gene&gene_id=ENSMUSG00000078515", "id": "ENSMUSG00000078515", "database": "Bgee" }, { "url": "https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd05479", "id": "cd05479", "database": "CDD" }, { "url": "https://www.ncbi.nlm.nih.gov/gene/68817", "id": "68817", "database": "GeneID" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR000626", "id": "IPR000626", "database": "InterPro" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR019103", "id": "IPR019103", "database": "InterPro" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR021109", "id": "IPR021109", "database": "InterPro" }, { "url": "https://www.ebi.ac.uk/interpro/entry/IPR029071", "id": "IPR029071", "database": "InterPro" }, { "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:68817", "id": "mmu:68817", "database": "KEGG Pathway" }, { "url": "http://www.informatics.jax.org/marker/MGI:1917244", "id": "1917244", "database": "MGI" }, { "url": "https://omabrowser.org/oma/group/FNGLPLM/", "id": "FNGLPLM", "database": "OMA" }, { "url": "http://pfam.xfam.org/family/PF00240", "id": "PF00240", "database": "Pfam" }, { "url": "http://pfam.xfam.org/family/PF09668", "id": "PF09668", "database": "Pfam" }, { "url": "http://research.bioinformatics.udel.edu/pro/entry/PR_A2ADY9", "id": "PR_A2ADY9", "database": "PRO" }, { "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001017966.1", "id": "NP_001017966.1", "database": "RefSeq" } ], "expression_disease": [], "glycosylation": [], "mutagenesis": [], "disease": [], "phosphorylation": [ { "residue": "Thr", "position": "104", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "" }, { "residue": "Ser", "position": "120", "evidence": [ { "url": "http://phospho.elm.eu.org/byAccession/A2ADY9.html", "id": "A2ADY9", "database": "phospho.ELM" }, { "url": "https://www.ncbi.nlm.nih.gov/pubmed/17242355", "id": "17242355", "database": "PubMed" } ], "kinase_uniprot_canonical_ac": "Q3UD01-1", "kinase_gene_name": "Atxn7l3b" }, { "residue": "Ser", "position": "121", "evidence": [ { "url": "http://phospho.elm.eu.org/byAccession/A2ADY9.html", "id": "A2ADY9", "database": "phospho.ELM" }, { "url": "https://www.ncbi.nlm.nih.gov/pubmed/17242355", "id": "17242355", "database": "PubMed" }, { "url": "https://www.ncbi.nlm.nih.gov/pubmed/21183079", "id": "21183079", "database": "PubMed" } ], "kinase_uniprot_canonical_ac": "Q3UD01-1", "kinase_gene_name": "Atxn7l3b" }, { "residue": "Ser", "position": "121", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "" }, { "residue": "Ser", "position": "128", "evidence": [ { "url": "http://phospho.elm.eu.org/byAccession/A2ADY9.html", "id": "A2ADY9", "database": "phospho.ELM" }, { "url": "https://www.ncbi.nlm.nih.gov/pubmed/17242355", "id": "17242355", "database": "PubMed" }, { "url": "https://www.ncbi.nlm.nih.gov/pubmed/21183079", "id": "21183079", "database": "PubMed" } ], "kinase_uniprot_canonical_ac": "Q3UD01-1", "kinase_gene_name": "Atxn7l3b" }, { "residue": "Ser", "position": "128", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "" }, { "residue": "Ser", "position": "150", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "" }, { "residue": "Ser", "position": "194", "evidence": [ { "url": "https://www.ncbi.nlm.nih.gov/pubmed/21183079", "id": "21183079", "database": "PubMed" } ], "kinase_uniprot_canonical_ac": "Q3UD01-1", "kinase_gene_name": "Atxn7l3b" }, { "residue": "Ser", "position": "194", "evidence": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "id": "A2ADY9", "database": "UniProtKB" } ], "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "" } ], "mass": { "monoisotopic_mass": 44591.0, "chemical_mass": 44591.0 }, "expression_tissue": [], "gene": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "name": "Ddi2", "locus": { "end_pos": 141677549, "strand": "-", "start_pos": 141723419, "chromosome": "4", "evidence": [ { "url": "https://www.ensembl.org/id/ENSMUSG00000078515", "id": "ENSMUSG00000078515", "database": "Ensembl Gene" } ] } } ], "protein_names": [ { "url": "https://www.uniprot.org/uniprot/A2ADY9", "type": "synonym", "resource": "UniProtKB", "name": "3.4.23.-" }, { "url": "https://www.uniprot.org/uniprot/A2ADY9", "type": "recommended", "resource": "UniProtKB", "name": "Protein DDI1 homolog 2" }, { "url": "https://www.ncbi.nlm.nih.gov/protein/A2ADY9", "type": "synonym", "resource": "RefSeq", "name": "protein DDI1 homolog 2" } ] }