| IED ID | IndEnz0002009828 |
| Enzyme Type ID | protease009828 |
| Protein Name |
Deubiquitinating protein VCPIP1 EC 3.4.19.12 Valosin-containing protein p97/p47 complex-interacting protein 1 Valosin-containing protein p97/p47 complex-interacting protein p135 VCP/p47 complex-interacting 135-kDa protein |
| Gene Name | VCPIP1 KIAA1850 VCIP135 |
| 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 | MSQPPPPPPPLPPPPPPPEAPQTPSSLASAAASGGLLKRRDRRILSGSCPDPKCQARLFFPASGSVSIECTECGQRHEQQQLLGVEEVTDPDVVLHNLLRNALLGVTGAPKKNTELVKVMGLSNYHCKLLSPILARYGMDKQTGRAKLLRDMNQGELFDCALLGDRAFLIEPEHVNTVGYGKDRSGSLLYLHDTLEDIKRANKSQECLIPVHVDGDGHCLVHAVSRALVGRELFWHALRENLKQHFQQHLARYQALFHDFIDAAEWEDIINECDPLFVPPEGVPLGLRNIHIFGLANVLHRPIILLDSLSGMRSSGDYSATFLPGLIPAEKCTGKDGHLNKPICIAWSSSGRNHYIPLVGIKGAALPKLPMNLLPKAWGVPQDLIKKYIKLEEDGGCVIGGDRSLQDKYLLRLVAAMEEVFMDKHGIHPSLVADVHQYFYRRTGVIGVQPEEVTAAAKKAVMDNRLHKCLLCGALSELHVPPEWLAPGGKLYNLAKSTHGQLRTDKNYSFPLNNLVCSYDSVKDVLVPDYGMSNLTACNWCHGTSVRKVRGDGSIVYLDGDRTNSRSTGGKCGCGFKHFWDGKEYDNLPEAFPITLEWGGRVVRETVYWFQYESDSSLNSNVYDVAMKLVTKHFPGEFGSEILVQKVVHTILHQTAKKNPDDYTPVNIDGAHAQRVGDVQGQESESQLPTKIILTGQKTKTLHKEELNMSKTERTIQQNITEQASVMQKRKTEKLKQEQKGQPRTVSPSTIRDGPSSAPATPTKAPYSPTTSKEKKIRITTNDGRQSMVTLKSSTTFFELQESIAREFNIPPYLQCIRYGFPPKELMPPQAGMEKEPVPLQHGDRITIEILKSKAEGGQSAAAHSAHTVKQEDIAVTGKLSSKELQEQAEKEMYSLCLLATLMGEDVWSYAKGLPHMFQQGGVFYSIMKKTMGMADGKHCTFPHLPGKTFVYNASEDRLELCVDAAGHFPIGPDVEDLVKEAVSQVRAEATTRSRESSPSHGLLKLGSGGVVKKKSEQLHNVTAFQGKGHSLGTASGNPHLDPRARETSVVRKHNTGTDFSNSSTKTEPSVFTASSSNSELIRIAPGVVTMRDGRQLDPDLVEAQRKKLQEMVSSIQASMDRHLRDQSTEQSPSDLPQRKTEVVSSSAKSGSLQTGLPESFPLTGGTENLNTETTDGCVADALGAAFATRSKAQRGNSVEELEEMDSQDAEMTNTTEPMDHS |
| Enzyme Length | 1222 |
| Uniprot Accession Number | Q96JH7 |
| Absorption | |
| Active Site | ACT_SITE 216; /evidence=ECO:0000250|UniProtKB:Q96FW1; ACT_SITE 219; /note=Nucleophile; /evidence=ECO:0000305|PubMed:32649882; ACT_SITE 354; /evidence=ECO:0000250|UniProtKB:Q96FW1 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:32649882}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681). {ECO:0000250|UniProtKB:Q8CF97, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:32649882}.; FUNCTION: (Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients. {ECO:0000269|PubMed:28584101}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Compositional bias (4); Domain (1); Erroneous initiation (1); Frameshift (1); Modified residue (10); Mutagenesis (2); Region (6); Sequence conflict (5) |
| Keywords | Acetylation;Cytoplasm;DNA damage;DNA repair;Endoplasmic reticulum;Golgi apparatus;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32649882}. Cytoplasm {ECO:0000269|PubMed:32649882}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q8CF97}. Golgi apparatus, Golgi stack {ECO:0000250|UniProtKB:Q8CF97}. Note=Associated with Golgi stacks and endoplasmic reticulum (By similarity). Displays cytoplasmic to nuclear translocation in response to DNA-protein cross-links (DPCs)-inducing agents (PubMed:32649882). {ECO:0000250|UniProtKB:Q8CF97, ECO:0000269|PubMed:32649882}. |
| Modified Residue | MOD_RES 408; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 747; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 757; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 763; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 768; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 994; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 998; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 1077; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 1198; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 1207; /note="Phosphoserine; by ATM"; /evidence="ECO:0000269|PubMed:32649882" |
| Post Translational Modification | PTM: Phosphorylated at Ser-1207 by ATM or ATR following induction of covalent DNA-protein cross-links (DPCs). {ECO:0000269|PubMed:32649882}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12509440; 15231748; 18654987; 18775313; 19615732; 20711500; 23500464; 24163436; 25904330; 26496610; 26638075; |
| Motif | |
| Gene Encoded By | |
| Mass | 134,321 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |