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UniProtKB - P60330 (ESPL1_MOUSE)
Protein
Separin
Gene
Espl1
Organism
Mus musculus (Mouse)
Status
Functioni
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).
By similarityCatalytic activityi
- 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
Activity regulationi
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).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 2025 | By similarity | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: GO_Central
- cysteine-type peptidase activity Source: MGI
- peptidase activity Source: MGI
GO - Biological processi
- chromosome segregation Source: MGI
- homologous chromosome segregation Source: MGI
- meiosis I Source: MGI
- meiotic chromosome separation Source: GO_Central
- meiotic spindle organization Source: MGI
- mitotic cell cycle Source: MGI
- mitotic sister chromatid segregation Source: MGI
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Chromosome partition |
Enzyme and pathway databases
BRENDAi | 3.4.22.49, 3474 |
Reactomei | R-MMU-2467813, Separation of Sister Chromatids |
Protein family/group databases
MEROPSi | C50.002 |
Names & Taxonomyi
Protein namesi | Recommended name: Separin (EC:3.4.22.49)Alternative name(s): Caspase-like protein ESPL1 Extra spindle poles-like 1 protein Separase |
Gene namesi | Name:Espl1 Synonyms:Esp1, Kiaa0165 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2146156, Espl1 |
VEuPathDBi | HostDB:ENSMUSG00000058290 |
Subcellular locationi
Cytoskeleton
- centrosome Source: MGI
- mitotic spindle Source: GO_Central
Nucleus
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000205901 | 1 – 2118 | SeparinAdd BLAST | 2118 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1121 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1391 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1394 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1504 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Autocleaves. This function, which is not essential for its protease activity, is unknown (By similarity).By similarity
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).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 1502 – 1503 | Cleavage; by autolysisBy similarity | 2 | |
Sitei | 1531 – 1532 | Cleavage; by autolysisBy similarity | 2 |
Keywords - PTMi
Autocatalytic cleavage, PhosphoproteinProteomic databases
EPDi | P60330 |
jPOSTi | P60330 |
MaxQBi | P60330 |
PaxDbi | P60330 |
PRIDEi | P60330 |
ProteomicsDBi | 275543 |
PTM databases
iPTMneti | P60330 |
PhosphoSitePlusi | P60330 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000058290, Expressed in primary oocyte and 209 other tissues |
ExpressionAtlasi | P60330, baseline and differential |
Genevisiblei | P60330, MM |
Interactioni
Subunit structurei
Interacts with PTTG1.
Interacts with RAD21 (By similarity).
By similarityProtein-protein interaction databases
BioGRIDi | 222968, 28 interactors |
IntActi | P60330, 26 interactors |
STRINGi | 10090.ENSMUSP00000064465 |
Miscellaneous databases
RNActi | P60330, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1941 – 2036 | Peptidase C50Add BLAST | 96 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1309 – 1352 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 1408 – 1428 | DisorderedSequence analysisAdd BLAST | 21 |
Phylogenomic databases
eggNOGi | KOG1849, Eukaryota |
GeneTreei | ENSGT00390000004990 |
HOGENOMi | CLU_001558_0_0_1 |
InParanoidi | P60330 |
OMAi | AMGHQAQ |
OrthoDBi | 14013at2759 |
PhylomeDBi | P60330 |
TreeFami | TF101169 |
Family and domain databases
InterProi | View protein in InterPro IPR005314, Peptidase_C50 IPR030397, SEPARIN_core_dom |
PANTHERi | PTHR12792, PTHR12792, 1 hit |
PROSITEi | View protein in PROSITE PS51700, SEPARIN, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
P60330-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MRNFKGVNFA TLLCSKEETQ QLLPDLKEFL SRSRTDFPSS RTDAERRQIC
60 70 80 90 100
DTILRACTQQ LTAKLDCPGH LRSILDLAEL ACDGYLLSTP QRPPLYLERI
110 120 130 140 150
LFILLRNGST QGSPDTVLRL AQPLHACLVQ NSGEAAPQDY EAVTRGSFSL
160 170 180 190 200
FWKGAEALLE RRAAFSTRLN ALSFLVLLED GSVPCEVPHF ASPTACRLVA
210 220 230 240 250
AYQLYDATGQ GLDEADADFL YEVLSRHLIR VLVGEGGSSP GPLSPQRALC
260 270 280 290 300
LLEITLEHCR RLCWNHHHRQ AARAVERARN HLEKTSVAPS LQLCQMGVEL
310 320 330 340 350
LEAVEERPGA VAQLLRKAAA VLINSIEAPS PPLRALYDSC QFFLSGLERG
360 370 380 390 400
IRRHCGLDAI LSLFAFLGGY SSLVRHLREV SEASSKQQQC LLQMHFQGFH
410 420 430 440 450
LFTGIVYDFA QGCQATELAQ LVDGCRSAAV WMLEALEGLS GGELADYLSM
460 470 480 490 500
TASYTSNLAY SFFSQKLYEE ACVISEPVCQ HLGSATSGAC PEVPPEKLHR
510 520 530 540 550
CFRLHVESLK KLGKQAQGCK MVTLWLAALK PYSLEHMVEP VTFWVRVKMD
560 570 580 590 600
ASRAGDKELQ LQTLRDSLSC WDPETQSLLL REELRAYKSV RADTGQERFN
610 620 630 640 650
IICDLLELSP EETAAGAWAR ATYLVELAQV LCYHNFTQQT NCSALDAVQE
660 670 680 690 700
ALQLLESVSP EAQEQDRLLD DKAQALLWLY ICTLEAKMQE GIERDRRAQA
710 720 730 740 750
PSNLEEFEVN DLNYEDKLQE DRFLYSSIAF NLAADAAQSK CLDQALTLWK
760 770 780 790 800
EVLTKGRAPA VRCLQQTAAS LQILAAVYQL VAKPLQALET LLLLQIVSKR
810 820 830 840 850
LQDHAKAASS SCQLTQLLLN LGCPSYAQLY LEEAESSLRS LDQTSDACQL
860 870 880 890 900
LSLTCALLGS QLCWACQKVT AGVSLLLSVL RDPALQKSSK AWYLLRVQAL
910 920 930 940 950
QVLAFYLSLS SNLLSSALRE QLWDQGWQTP ETALIDAHKL LRSIIILLMG
960 970 980 990 1000
SDVLSIQKAA TESPFLDYGE NLVQKWQVLT EVLTCSERLV GRLGRLGNVS
1010 1020 1030 1040 1050
EAKAFCLEAL KLTTKLQIPR QCALFLVLKG ELELARGDID LCQSDLQQVL
1060 1070 1080 1090 1100
FLLESSTEFG VVTQHPDSVK KVHTQKGKHK AQGPCFPPLS EEEPFLKGPA
1110 1120 1130 1140 1150
LELVDTVLNE PGPIQSSVNS SPVLKTKPPP NPGFLSHLPS CDCLLCASPA
1160 1170 1180 1190 1200
LSAVCLRWVL VTAGVRLATG HKAQGLDLLQ AVLTRCPAAT KRFTQSLQAS
1210 1220 1230 1240 1250
LNHRTTPSCV PSLFDEIMAQ VYTHLALEFL NQTSEKSLGK VLASGLKFVA
1260 1270 1280 1290 1300
TRIQSLEIWR AHLLLVQALA KLAHFSCCTS ELFASSWGWH PPLVKSLPVL
1310 1320 1330 1340 1350
EPAKIRRQKC SGRGRRRIAS VPPPLHNSSQ KGLEEEGPPC TPKPPGRARQ
1360 1370 1380 1390 1400
AGPRVPFTIF EEVHPTKSKL QVPLAPRVHR RAQTRLKVIF SDDSDLEDLV
1410 1420 1430 1440 1450
SADTQLVEEP KRRGTASRTR GQTRKGRSLK TDAVVAIEST PGHSSVSGRT
1460 1470 1480 1490 1500
RRARKVASRN CEEESPKAPL CVWASQGPEI MRSIPEEEPV DNHLEKSFEI
1510 1520 1530 1540 1550
LRGSDGEDSA SGEKAAAADT GLPVGECEVL RRDSSKAERP VLYSDTEANS
1560 1570 1580 1590 1600
DPSPWLPPFS VPAPIDLSTL DSISDSLSIA FRGVSHCPPS GLYAHLCRFL
1610 1620 1630 1640 1650
ALCLGHRDPY ATAFLVAESI SITCRHQLLT HLHRQLSKAQ KQQESPELAE
1660 1670 1680 1690 1700
HLQRLDLKER PGGVPLARIQ RLFSFKALGS GCFPQAEKES FQERLALIPS
1710 1720 1730 1740 1750
GVTVCVLALA TLQPGTLSNT LLLTRLEKDN PPITVKIPTA QNKLPLSAVL
1760 1770 1780 1790 1800
KEFDAIQKDQ KENSSCTEKR VWWTGRLALD QRMEALITAL EEQVLGCWRG
1810 1820 1830 1840 1850
LLLPCSADPS LAQEASKLQE LLRECGWEYP DSTLLKVILS GARILTSQDV
1860 1870 1880 1890 1900
QALACGLCPA QPDRAQVLLS EAVGQVQSQE APRSQHLVLV LDKDLQKLPW
1910 1920 1930 1940 1950
ESTPILQAQP VTRLPSFRFL LSYTVTKEAG ASSVLSQGVD PQNTFYVLNP
1960 1970 1980 1990 2000
HSNLSSTEER FRASFSSETG WKGVIGEVPS LDQVQAALTE RDLYIYAGHG
2010 2020 2030 2040 2050
AGARFLDGQA VLRLSCRAVA LLFGCSSAAL AVHGNLEGAG IVLKYIMAGC
2060 2070 2080 2090 2100
PLFLGNLWDV TDRDIDRYTE ALLQGWLGAG PGAPFLYYAS QARQAPRLKY
2110
LIGAAPVAYG LPISLQTP
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8VI27 | A0A2R8VI27_MOUSE | Separase | Espl1 | 110 | Annotation score: | ||
A0A2R8VHG0 | A0A2R8VHG0_MOUSE | Separin | Espl1 | 165 | Annotation score: | ||
A0A2R8VHV9 | A0A2R8VHV9_MOUSE | Separin | Espl1 | 99 | Annotation score: |
Sequence cautioni
The sequence BAC97882 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK129072 mRNA Translation: BAC97882.1 Different initiation. BC145846 mRNA Translation: AAI45847.1 |
CCDSi | CCDS27878.1 |
RefSeqi | NP_001014976.1, NM_001014976.2 XP_006520320.1, XM_006520257.3 XP_006520321.1, XM_006520258.3 XP_006520322.1, XM_006520259.3 XP_011243698.1, XM_011245396.2 |
Genome annotation databases
Ensembli | ENSMUST00000064924; ENSMUSP00000064465; ENSMUSG00000058290 ENSMUST00000229050; ENSMUSP00000155304; ENSMUSG00000058290 |
GeneIDi | 105988 |
KEGGi | mmu:105988 |
UCSCi | uc007xvf.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK129072 mRNA Translation: BAC97882.1 Different initiation. BC145846 mRNA Translation: AAI45847.1 |
CCDSi | CCDS27878.1 |
RefSeqi | NP_001014976.1, NM_001014976.2 XP_006520320.1, XM_006520257.3 XP_006520321.1, XM_006520258.3 XP_006520322.1, XM_006520259.3 XP_011243698.1, XM_011245396.2 |
3D structure databases
SMRi | P60330 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 222968, 28 interactors |
IntActi | P60330, 26 interactors |
STRINGi | 10090.ENSMUSP00000064465 |
Protein family/group databases
MEROPSi | C50.002 |
PTM databases
iPTMneti | P60330 |
PhosphoSitePlusi | P60330 |
Proteomic databases
EPDi | P60330 |
jPOSTi | P60330 |
MaxQBi | P60330 |
PaxDbi | P60330 |
PRIDEi | P60330 |
ProteomicsDBi | 275543 |
Protocols and materials databases
Antibodypediai | 26971, 676 antibodies from 28 providers |
Genome annotation databases
Ensembli | ENSMUST00000064924; ENSMUSP00000064465; ENSMUSG00000058290 ENSMUST00000229050; ENSMUSP00000155304; ENSMUSG00000058290 |
GeneIDi | 105988 |
KEGGi | mmu:105988 |
UCSCi | uc007xvf.2, mouse |
Organism-specific databases
CTDi | 9700 |
MGIi | MGI:2146156, Espl1 |
VEuPathDBi | HostDB:ENSMUSG00000058290 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG1849, Eukaryota |
GeneTreei | ENSGT00390000004990 |
HOGENOMi | CLU_001558_0_0_1 |
InParanoidi | P60330 |
OMAi | AMGHQAQ |
OrthoDBi | 14013at2759 |
PhylomeDBi | P60330 |
TreeFami | TF101169 |
Enzyme and pathway databases
BRENDAi | 3.4.22.49, 3474 |
Reactomei | R-MMU-2467813, Separation of Sister Chromatids |
Miscellaneous databases
BioGRID-ORCSi | 105988, 23 hits in 66 CRISPR screens |
ChiTaRSi | Espl1, mouse |
PROi | PR:P60330 |
RNActi | P60330, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000058290, Expressed in primary oocyte and 209 other tissues |
ExpressionAtlasi | P60330, baseline and differential |
Genevisiblei | P60330, MM |
Family and domain databases
InterProi | View protein in InterPro IPR005314, Peptidase_C50 IPR030397, SEPARIN_core_dom |
PANTHERi | PTHR12792, PTHR12792, 1 hit |
PROSITEi | View protein in PROSITE PS51700, SEPARIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ESPL1_MOUSE | |
Accessioni | P60330Primary (citable) accession number: P60330 Secondary accession number(s): A6H6E3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 2, 2004 |
Last sequence update: | February 2, 2004 | |
Last modified: | February 23, 2022 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot