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UniProtKB/Swiss-Prot Q14674 (ESPL1_HUMAN)
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June 16, 2009.
Version 87.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Separin EC=3.4.22.49 Alternative name(s): Separase Caspase-like protein ESPL1 Extra spindle poles-like 1 protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2120 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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. Ref.3 Ref.6 |
| Catalytic activity | 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 an hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage. |
| Enzyme 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-1126 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. Ref.1 Ref.4 Ref.5 |
| Subunit structure | |
| Subcellular location | |
| Post-translational modification | Autocleaves. This function, which is not essential for its protease activity, is unknown. Phosphorylated by CDC2. There are 8 Ser/Thr phosphorylation sites. Among them, Ser-1126 phosphorylation is the major site, which conducts to the enzyme inactivation. Ref.4 Ref.7 Ref.8 |
| Sequence similarities | Belongs to the peptidase C50 family. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q14674-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q14674-2) The sequence of this isoform differs from the canonical sequence as follows: 1-325: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2120 | 2120 | Separin | PRO_0000205900 | |||||
Sites | |||||||||
| Active site | 2029 | 1 | |||||||
| Site | 1506 – 1507 | 2 | Cleavage; by autolysis | ||||||
| Site | 1535 – 1536 | 2 | Cleavage; by autolysis | ||||||
Amino acid modifications | |||||||||
| Modified residue | 1126 | 1 | Phosphoserine Ref.4 | ||||||
| Modified residue | 1396 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 1399 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 1508 | 1 | Phosphoserine Ref.7 Ref.8 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 325 | 325 | Missing in isoform 2. | VSP_009361 | |||||
| Natural variant | 614 | 1 | S → R: dbSNP rs1318648. | VAR_057703 | |||||
| Natural variant | 699 | 1 | R → Q: dbSNP rs34424268. | VAR_057704 | |||||
| Natural variant | 1136 | 1 | I → V: dbSNP rs34130634. | VAR_057705 | |||||
| Natural variant | 1157 | 1 | T → A: dbSNP rs35428211. | VAR_057706 | |||||
| Natural variant | 1237 | 1 | Q → H: dbSNP rs34396464. | VAR_057707 | |||||
| Natural variant | 1435 | 1 | K → M: dbSNP rs1110719. | VAR_057708 | |||||
Experimental info | |||||||||
| Mutagenesis | 1126 | 1 | S → A: Abolishes phosphorylation at this site, as well as the negative regulation due to phosphorylation. | ||||||
| Mutagenesis | 1483 – 1486 | 4 | EIMR → RIME: Abolishes autocleavage; when associated with R-1178; E-1181; R-1207 and E-1210. Does not affect the protease function. Ref.1 Ref.5 | ||||||
| Mutagenesis | 1486 | 1 | R → A: Abolishes autocleavage; when associated with A-1181 and A-1210. Ref.5 | ||||||
| Mutagenesis | 1503 – 1506 | 4 | EILR → RILE: Does not affect autocleavage. Does not affect the protease function. Ref.1 Ref.5 | ||||||
| Mutagenesis | 1506 | 1 | R → A: Abolishes autocleavage; when associated with A-1161 and A-1210. Ref.5 | ||||||
| Mutagenesis | 1532 – 1535 | 4 | ELLR → RLLE: Strongly reduces autocleavage at this site, but enhances autocleavage at site 1. Does not affect the protease function. Ref.1 Ref.5 | ||||||
| Mutagenesis | 1535 | 1 | R → A: Abolishes autocleavage; when associated with A-1161 and A-1281. Ref.5 | ||||||
| Mutagenesis | 2029 | 1 | C → A: Abolishes protease activity. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Regulation of human separase by securin binding and autocleavage." Waizenegger I., Gimenez-Abian J.F., Wernic D., Peters J.-M. Curr. Biol. 12:1368-1378(2002) [PubMed: 12194817] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME REGULATION, AUTOPROTEOLYTIC CLEAVAGE, MUTAGENESIS OF CYS-2029; 1483-GLU--ARG-1486; 1503-GLU--ARG-1506 AND 1532-GLU--ARG-1535. |
| [2] | "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N. DNA Res. 3:17-24(1996) [PubMed: 8724849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Bone marrow. |
| [3] | "Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis." Zou H., McGarry T.J., Bernal T., Kirschner M.W. Science 285:418-422(1999) [PubMed: 10411507] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PTTG1. |
| [4] | "Dual inhibition of sister chromatid separation at metaphase." Stemmann O., Zou H., Gerber S.A., Gygi S.P., Kirschner M.W. Cell 107:715-726(2001) [PubMed: 11747808] [Abstract] Cited for: PROTEIN SEQUENCE OF 1117-1130, ENZYME REGULATION, PHOSPHORYLATION AT SER-1126. |
| [5] | "Anaphase specific auto-cleavage of separase." Zou H., Stemman O., Anderson J.S., Mann M., Kirschner M.W. FEBS Lett. 528:246-250(2002) [PubMed: 12297314] [Abstract] Cited for: PROTEIN SEQUENCE OF 1507-1517, ENZYME REGULATION, AUTOPROTEOLYTIC CLEAVAGE, MUTAGENESIS OF ARG-1486; ARG-1506 AND ARG-1535. |
| [6] | "Cohesin cleavage by separase required for anaphase and cytokinesis in human cells." Hauf S., Waizenegger I.C., Peters J.-M. Science 293:1320-1323(2001) [PubMed: 11509732] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAD21. |
| [7] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1508, MASS SPECTROMETRY. Tissue: Epithelium. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1396; SER-1399 AND SER-1508, MASS SPECTROMETRY. |
| [9] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AY455930 mRNA. Translation: AAR18247.1. D79987 mRNA. Translation: BAA11482.2. | |
| IPI | IPI00017538. IPI00397474. |
| RefSeq | NP_036423.4. |
| UniGene | Hs.153479 |
3D structure databases | |
| ModBase | Search... |
Protein family/group databases | |
| MEROPS | C50.002. |
PTM databases | |
| PhosphoSite | Q14674. |
Proteomic databases | |
| PRIDE | Q14674. |
Genome annotation databases | |
| Ensembl | ENSG00000135476. Homo sapiens. [Contig view] |
| GeneID | 9700. |
| KEGG | hsa:9700. |
Organism-specific databases | |
| GeneCards | GC12P051948. |
| H-InvDB | HIX0010680. |
| HGNC | HGNC:16856. ESPL1. |
| HPA | CAB012185. |
| MIM | 604143. gene. |
| PharmGKB | PA27884. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q14674. |
| HOVERGEN | Q14674. |
Enzyme and pathway databases | |
| BRENDA | 3.4.22.49. 247. |
Gene expression databases | |
| ArrayExpress | Q14674. |
| Bgee | Q14674. |
| CleanEx | HS_ESPL1. |
| GermOnline | ENSG00000135476. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005314. Peptidase_C50. [Graphical view] |
| PANTHER | PTHR12792. Peptidase_C50. 1 hit. |
| Pfam | PF03568. Peptidase_C50. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 36451. |
| SOURCE | Search... |
Entry information
| Entry name | ESPL1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q14674 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |
