| IED ID | IndEnz0002005444 |
| Enzyme Type ID | protease005444 |
| Protein Name |
Separin EC 3.4.22.49 Caspase-like protein ESPL1 Extra spindle poles-like 1 protein Separase |
| Gene Name | Espl1 Esp1 Kiaa0165 |
| Organism | Mus musculus (Mouse) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MRNFKGVNFATLLCSKEETQQLLPDLKEFLSRSRTDFPSSRTDAERRQICDTILRACTQQLTAKLDCPGHLRSILDLAELACDGYLLSTPQRPPLYLERILFILLRNGSTQGSPDTVLRLAQPLHACLVQNSGEAAPQDYEAVTRGSFSLFWKGAEALLERRAAFSTRLNALSFLVLLEDGSVPCEVPHFASPTACRLVAAYQLYDATGQGLDEADADFLYEVLSRHLIRVLVGEGGSSPGPLSPQRALCLLEITLEHCRRLCWNHHHRQAARAVERARNHLEKTSVAPSLQLCQMGVELLEAVEERPGAVAQLLRKAAAVLINSIEAPSPPLRALYDSCQFFLSGLERGIRRHCGLDAILSLFAFLGGYSSLVRHLREVSEASSKQQQCLLQMHFQGFHLFTGIVYDFAQGCQATELAQLVDGCRSAAVWMLEALEGLSGGELADYLSMTASYTSNLAYSFFSQKLYEEACVISEPVCQHLGSATSGACPEVPPEKLHRCFRLHVESLKKLGKQAQGCKMVTLWLAALKPYSLEHMVEPVTFWVRVKMDASRAGDKELQLQTLRDSLSCWDPETQSLLLREELRAYKSVRADTGQERFNIICDLLELSPEETAAGAWARATYLVELAQVLCYHNFTQQTNCSALDAVQEALQLLESVSPEAQEQDRLLDDKAQALLWLYICTLEAKMQEGIERDRRAQAPSNLEEFEVNDLNYEDKLQEDRFLYSSIAFNLAADAAQSKCLDQALTLWKEVLTKGRAPAVRCLQQTAASLQILAAVYQLVAKPLQALETLLLLQIVSKRLQDHAKAASSSCQLTQLLLNLGCPSYAQLYLEEAESSLRSLDQTSDACQLLSLTCALLGSQLCWACQKVTAGVSLLLSVLRDPALQKSSKAWYLLRVQALQVLAFYLSLSSNLLSSALREQLWDQGWQTPETALIDAHKLLRSIIILLMGSDVLSIQKAATESPFLDYGENLVQKWQVLTEVLTCSERLVGRLGRLGNVSEAKAFCLEALKLTTKLQIPRQCALFLVLKGELELARGDIDLCQSDLQQVLFLLESSTEFGVVTQHPDSVKKVHTQKGKHKAQGPCFPPLSEEEPFLKGPALELVDTVLNEPGPIQSSVNSSPVLKTKPPPNPGFLSHLPSCDCLLCASPALSAVCLRWVLVTAGVRLATGHKAQGLDLLQAVLTRCPAATKRFTQSLQASLNHRTTPSCVPSLFDEIMAQVYTHLALEFLNQTSEKSLGKVLASGLKFVATRIQSLEIWRAHLLLVQALAKLAHFSCCTSELFASSWGWHPPLVKSLPVLEPAKIRRQKCSGRGRRRIASVPPPLHNSSQKGLEEEGPPCTPKPPGRARQAGPRVPFTIFEEVHPTKSKLQVPLAPRVHRRAQTRLKVIFSDDSDLEDLVSADTQLVEEPKRRGTASRTRGQTRKGRSLKTDAVVAIESTPGHSSVSGRTRRARKVASRNCEEESPKAPLCVWASQGPEIMRSIPEEEPVDNHLEKSFEILRGSDGEDSASGEKAAAADTGLPVGECEVLRRDSSKAERPVLYSDTEANSDPSPWLPPFSVPAPIDLSTLDSISDSLSIAFRGVSHCPPSGLYAHLCRFLALCLGHRDPYATAFLVAESISITCRHQLLTHLHRQLSKAQKQQESPELAEHLQRLDLKERPGGVPLARIQRLFSFKALGSGCFPQAEKESFQERLALIPSGVTVCVLALATLQPGTLSNTLLLTRLEKDNPPITVKIPTAQNKLPLSAVLKEFDAIQKDQKENSSCTEKRVWWTGRLALDQRMEALITALEEQVLGCWRGLLLPCSADPSLAQEASKLQELLRECGWEYPDSTLLKVILSGARILTSQDVQALACGLCPAQPDRAQVLLSEAVGQVQSQEAPRSQHLVLVLDKDLQKLPWESTPILQAQPVTRLPSFRFLLSYTVTKEAGASSVLSQGVDPQNTFYVLNPHSNLSSTEERFRASFSSETGWKGVIGEVPSLDQVQAALTERDLYIYAGHGAGARFLDGQAVLRLSCRAVALLFGCSSAALAVHGNLEGAGIVLKYIMAGCPLFLGNLWDVTDRDIDRYTEALLQGWLGAGPGAPFLYYASQARQAPRLKYLIGAAPVAYGLPISLQTP |
| Enzyme Length | 2118 |
| Uniprot Accession Number | P60330 |
| Absorption | |
| Active Site | ACT_SITE 2025; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Regulated by at least two independent mechanisms. First, it is inactivated via its interaction with securin/PTTG1, which probably covers its active site. The association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent. PTTG1 degradation at anaphase, liberates it and triggers RAD21 cleavage. Second, phosphorylation at Ser-1121 inactivates it. The complete phosphorylation during mitosis, is removed when cells undergo anaphase. Activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin and inhibitory phosphate (By similarity). {ECO:0000250}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=All bonds known to be hydrolyzed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by a hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage.; EC=3.4.22.49; |
| DNA Binding | |
| EC Number | 3.4.22.49 |
| Enzyme Function | FUNCTION: Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms (By similarity). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Domain (1); Erroneous initiation (1); Modified residue (4); Region (2); Site (2) |
| Keywords | Autocatalytic cleavage;Chromosome partition;Cytoplasm;Direct protein sequencing;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. |
| Modified Residue | MOD_RES 1121; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q14674; MOD_RES 1391; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q14674; MOD_RES 1394; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q14674; MOD_RES 1504; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079 |
| Post Translational Modification | PTM: Autocleaves. This function, which is not essential for its protease activity, is unknown (By similarity). {ECO:0000250}.; PTM: Phosphorylated by CDK1. There is 8 Ser/Thr phosphorylation sites. Among them, only Ser-1121 phosphorylation is the major site, which conducts to the enzyme inactivation (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10725249; 11516952; 11581162; 11839785; 11839787; 12520002; 12904583; 14561405; 14681479; 16030258; 16533944; 16533945; 16839882; 18003702; 18232736; 18728194; 18799693; 18843049; 19124608; 19249208; 19625504; 20360068; 21267068; 21494564; 21677750; 21799785; 21865557; 22516201; 23975099; 24276237; 26496610; 26858254; 27694478; 30305303; 31704793; 32366979; 33777955; 33798452; |
| Motif | |
| Gene Encoded By | |
| Mass | 233,035 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.49; |