| IED ID | IndEnz0002001014 |
| Enzyme Type ID | protease001014 |
| Protein Name |
Separin homolog sep-1 EC 3.4.22.49 Separase |
| Gene Name | sep-1 Y47G6A.12 |
| Organism | Caenorhabditis elegans |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Protostomia Ecdysozoa Nematoda (roundworms) Chromadorea Rhabditida Rhabditina Rhabditomorpha Rhabditoidea Rhabditidae Peloderinae Caenorhabditis Caenorhabditis elegans |
| Enzyme Sequence | MKITNKSVDKQHIEKLDELRKNVSCTVIGFAEQTAELQQEISELFIAEFGVNGPIDMNSLSKLARITSYYASSEYFQGLAKYQRTACKMFITWQTLRKEAMECRSKDREIFASIPAKLCFFYFYNGELCRAVVCLLDYIDLSDDTLAKEAALRWLMFLGETELIEKKLKTWKMDKSSKDMFSATEFAMNYLKKSEYRVEMLEKLMKLRDKVKSDPTRSFSRYELASYVSWLCSTLSNVPVGSALRECEFPDRVSHIQEAALKSDSLVRNRIPGLASSQFDNSVNASIWPFLDGHQEDSNYYVHIGSTIAWHFEMRRECALVNVTTAQTRDSMSAMILNLRVALKSASFFRVLQTTNTLAYYSSIIEEAGSEKNAKLMRVSCVNLLSSNPIIVRCSTPKETGATSRAHTPMAGSSVSEKQNTMRPDLADLLGDLELLDEQSFHPITRSCVCNVCTIYPLHSSFAAEYMMSYAIHSDFSQLSIKHFNDEFARIRERGMSSQVLMHRDSSVRPRPNIIQNEIFGMCVIRWLTKKLDSKESADEDTMEIFNNALKIVRYLQQRTTDMILAVTQLGRQLEFPMECNYSWMRPTIRKPRVKATIDCAVDILRAVSPFGRRPKVEKLEKNLQPFDKERFEKVRLAMRNEMNHYGHILYREWRCRLFAYVGRTSRDPWEAAYAWAESTQIGARNAVQSRLEKCKRGLVTMSGHDRFKTCVQSMPDEMTLVQIAMADDKTIYLVKLHADRDPIIMPLAHYSQAVELMDKFTFLLDEDEMIAKYPGDITPEEFWKRRKIVDGRMMTFVDEVQKHFLGVAASLLMPSGQLGPKAAELAIKIHKLSKGGLLLGEAKEMVYQSKLMDAKSWEALILRFCEMRTTDEKFKSFLPLMHRNSVEVMNQDDSIVTEKKYTYLVICPHLSQFCWERLPIFDEYPYVGRQVSIHSTFSQLEAMKSQEKQIPLQIDVQNAYYILDPDNNLGETQKRMVEYINKFNWEGTVGSAPKSNEISAALSQRDAFFFIGHGSGSSVMPRSVLKQSTCNAISLLMGCGSVRTIPQALGFDGKTAILDYAMAKCPLIVGCLWTVTDGEIDRFLIRMIDDCFEDSKSLTGIDKLRQLSEAMHEARSKARLKYLTGAAVVMYGLPVVAKQTTPFVEKDQRNLPQTPKTSARTSMRMETVPKTPKQEFVTSKSVPMTPIFSNNENKSPSRARMPSRVLKTPRQVKTFQEEDDEAPKRSTTRQLKPLVAPPIPATPTTRTTRSSARTPSRSRNL |
| Enzyme Length | 1262 |
| Uniprot Accession Number | G5ED39 |
| Absorption | |
| Active Site | ACT_SITE 1040; /evidence=ECO:0000255|PROSITE-ProRule:PRU01037 |
| Activity Regulation | ACTIVITY REGULATION: Probably maintained in an inactive state via its interaction with securin ify-1 which acts as a pseudosubstrate thereby blocking access to the catalytic site. Upon ify-1 degradation at the onset of anaphase, sep-1 is likely to become active. In addition, interaction with ify-1 stabilizes sep-1. {ECO:0000305|PubMed:23578927, ECO:0000305|PubMed:27249343, ECO:0000305|PubMed:28263324}. |
| 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; Evidence={ECO:0000305|PubMed:25919583}; |
| DNA Binding | |
| EC Number | 3.4.22.49 |
| Enzyme Function | FUNCTION: Cysteine protease, which plays a central role in homologous chromosome separation during meiosis I and in sister chromatid separation during embryonic mitosis (PubMed:11728305, PubMed:12498686, PubMed:20116245, PubMed:21878498). Promotes chromosome/sister chromatid segregation by cleaving the scc-1 (mitosis) and rec-8 (meiosis) subunits of the cohesin complex at the onset of anaphase (Probable). May cleave histone H3-like protein cpar-1 during meiosis I metaphase-anaphase transition (PubMed:25919583). Promotes cortical granule exocytosis after oocyte fertilization during the first meiotic anaphase (PubMed:17913784, PubMed:21878498). Essential for embryonic cytokinesis by regulating rab-11-positive vesicle trafficking at the plasma membrane at the cleavage furrow and midbody (PubMed:20116245). Regulates centriole segregation during spermatocyte meiosis (PubMed:23401519). Required for embryonic anterior-posterior axis formation (PubMed:11832245). {ECO:0000269|PubMed:11728305, ECO:0000269|PubMed:11832245, ECO:0000269|PubMed:12498686, ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:21878498, ECO:0000269|PubMed:23401519, ECO:0000269|PubMed:25919583, ECO:0000305}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Compositional bias (3); Domain (1); Mutagenesis (4); Region (1) |
| Keywords | 3D-structure;Cell cycle;Cell division;Chromosome;Chromosome partition;Cytoplasm;Cytoskeleton;Hydrolase;Meiosis;Mitosis;Protease;Reference proteome;Thiol protease |
| Interact With | Q18235 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:23401519}. Chromosome {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:23401519}. Cytoplasmic granule {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:21878498}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:17913784}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:23401519}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:21878498}. Cleavage furrow {ECO:0000269|PubMed:20116245}. Midbody {ECO:0000269|PubMed:20116245}. Note=Before ovulation, accumulates on chromosomes and cortical filaments in oocytes (PubMed:17913784). By metaphase I, dissociates from filaments and transiently localizes to cortical granules until their exocytosis during anaphase I followed by an accumulation at the cortex near the polar body (PubMed:17913784). Localizes to meiotic spindle matrix (PubMed:21878498). During mitotic metaphase and anaphase, localizes to chromosomes, centrosomes and the spindle matrix (PubMed:17913784, PubMed:20116245, PubMed:21878498). During spermatogenesis, localizes to the spermatocyte cytoplasm throughout meiotic prophase I (PubMed:23401519). At the diplotene stage of prophase I accumulates at low levels in puncta around the nuclear envelope (PubMed:23401519). At diakinesis, transiently localizes to centrosomes until nuclear envelope breakdown (PubMed:23401519). At metaphase I and II becomes highly enriched around chromosomes (PubMed:23401519). At anaphase I and II, chromosomal localization is reduced and centrosome localization is highly increased (PubMed:23401519). Localizes to residual body during the budding division leading to spermatid formation (PubMed:23401519). {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:21878498, ECO:0000269|PubMed:23401519}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1) |
| Cross Reference PDB | 5MZ6; |
| Mapped Pubmed ID | 10778742; 12015116; 12097347; 12529635; 12620985; 14551910; 14704431; 15791247; 15990870; 18425118; 18692475; 19368796; 20439774; 20439776; 21085631; 21177967; 21367940; 21529718; 22267497; 22286215; 22560298; 22992455; 23800452; 24884423; 25487147; 28820333; 29246899; 6593563; |
| Motif | |
| Gene Encoded By | |
| Mass | 144,121 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.49; |