| IED ID | IndEnz0002006364 |
| Enzyme Type ID | protease006364 |
| Protein Name |
Protein DDI1 homolog 2 EC 3.4.23.- |
| Gene Name | DDI2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLLTVYCVRRDLSEVTFSLQVDADFELHNFRALCELESGIPAAESQIVYAERPLTDNHRSLASYGLKDGDVVILRQKENADPRPPVQFPNLPRIDFSSIAVPGTSSPRQRQPPGTQQSHSSPGEITSSPQGLDNPALLRDMLLANPHELSLLKERNPPLAEALLSGDLEKFSRVLVEQQQDRARREQERIRLFSADPFDLEAQAKIEEDIRQQNIEENMTIAMEEAPESFGQVVMLYINCKVNGHPVKAFVDSGAQMTIMSQACAERCNIMRLVDRRWAGIAKGVGTQKIIGRVHLAQVQIEGDFLPCSFSILEEQPMDMLLGLDMLKRHQCSIDLKKNVLVIGTTGSQTTFLPEGELPECARLAYGAGREDVRPEEIADQELAEALQKSAEDAERQKP |
| Enzyme Length | 399 |
| Uniprot Accession Number | Q5TDH0 |
| Absorption | |
| Active Site | ACT_SITE 252; /evidence=ECO:0000305|PubMed:27528193 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.23.- |
| Enzyme Function | FUNCTION: Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane (PubMed:27676298, PubMed:27528193). Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1 (PubMed:27528193). Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2 (Probable). 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 (PubMed:29290612). {ECO:0000269|PubMed:27528193, ECO:0000269|PubMed:27676298, ECO:0000269|PubMed:29290612, ECO:0000305|PubMed:29290612}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (2); Beta strand (13); Chain (1); Compositional bias (1); Domain (1); Helix (12); Modified residue (6); Motif (1); Mutagenesis (1); Region (1); Turn (3) |
| Keywords | 3D-structure;Alternative splicing;Aspartyl protease;Chromosome;Cytoplasm;Hydrolase;Phosphoprotein;Protease;Reference proteome |
| Interact With | P54253; P14136; Q13148 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:27528193}. Chromosome {ECO:0000269|PubMed:29290612}. |
| Modified Residue | MOD_RES 104; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 106; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 121; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 128; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 150; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 194; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (1) |
| Cross Reference PDB | 2N7D; 4RGH; 5K57; |
| Mapped Pubmed ID | 20379614; 32521225; |
| Motif | MOTIF 376..395; /note=Ubiquitin-binding; /evidence=ECO:0000305|PubMed:27461074 |
| Gene Encoded By | |
| Mass | 44,523 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |