Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P60330 (ESPL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Separin

EC=3.4.22.49
Alternative name(s):
Caspase-like protein ESPL1
Extra spindle poles-like 1 protein
Separase
Gene names
Name:Espl1
Synonyms:Esp1, Kiaa0165
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length2118 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity.

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 a 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-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.

Subunit structure

Interacts with PTTG1. Interacts with RAD21 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Post-translational modification

Autocleaves. This function, which is not essential for its protease activity, is unknown 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.

Sequence similarities

Contains 1 peptidase C50 domain.

Sequence caution

The sequence BAC97882.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 21182118Separin
PRO_0000205901

Regions

Domain1941 – 203696Peptidase C50

Sites

Active site20251 By similarity
Site1502 – 15032Cleavage; by autolysis By similarity
Site1531 – 15322Cleavage; by autolysis By similarity

Amino acid modifications

Modified residue11211Phosphoserine By similarity
Modified residue13911Phosphoserine By similarity
Modified residue13941Phosphoserine By similarity
Modified residue15041Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P60330 [UniParc].

Last modified February 2, 2004. Version 1.
Checksum: 484FCE178C0984B6

FASTA2,118233,035
        10         20         30         40         50         60 
MRNFKGVNFA TLLCSKEETQ QLLPDLKEFL SRSRTDFPSS RTDAERRQIC DTILRACTQQ 

        70         80         90        100        110        120 
LTAKLDCPGH LRSILDLAEL ACDGYLLSTP QRPPLYLERI LFILLRNGST QGSPDTVLRL 

       130        140        150        160        170        180 
AQPLHACLVQ NSGEAAPQDY EAVTRGSFSL FWKGAEALLE RRAAFSTRLN ALSFLVLLED 

       190        200        210        220        230        240 
GSVPCEVPHF ASPTACRLVA AYQLYDATGQ GLDEADADFL YEVLSRHLIR VLVGEGGSSP 

       250        260        270        280        290        300 
GPLSPQRALC LLEITLEHCR RLCWNHHHRQ AARAVERARN HLEKTSVAPS LQLCQMGVEL 

       310        320        330        340        350        360 
LEAVEERPGA VAQLLRKAAA VLINSIEAPS PPLRALYDSC QFFLSGLERG IRRHCGLDAI 

       370        380        390        400        410        420 
LSLFAFLGGY SSLVRHLREV SEASSKQQQC LLQMHFQGFH LFTGIVYDFA QGCQATELAQ 

       430        440        450        460        470        480 
LVDGCRSAAV WMLEALEGLS GGELADYLSM TASYTSNLAY SFFSQKLYEE ACVISEPVCQ 

       490        500        510        520        530        540 
HLGSATSGAC PEVPPEKLHR CFRLHVESLK KLGKQAQGCK MVTLWLAALK PYSLEHMVEP 

       550        560        570        580        590        600 
VTFWVRVKMD ASRAGDKELQ LQTLRDSLSC WDPETQSLLL REELRAYKSV RADTGQERFN 

       610        620        630        640        650        660 
IICDLLELSP EETAAGAWAR ATYLVELAQV LCYHNFTQQT NCSALDAVQE ALQLLESVSP 

       670        680        690        700        710        720 
EAQEQDRLLD DKAQALLWLY ICTLEAKMQE GIERDRRAQA PSNLEEFEVN DLNYEDKLQE 

       730        740        750        760        770        780 
DRFLYSSIAF NLAADAAQSK CLDQALTLWK EVLTKGRAPA VRCLQQTAAS LQILAAVYQL 

       790        800        810        820        830        840 
VAKPLQALET LLLLQIVSKR LQDHAKAASS SCQLTQLLLN LGCPSYAQLY LEEAESSLRS 

       850        860        870        880        890        900 
LDQTSDACQL LSLTCALLGS QLCWACQKVT AGVSLLLSVL RDPALQKSSK AWYLLRVQAL 

       910        920        930        940        950        960 
QVLAFYLSLS SNLLSSALRE QLWDQGWQTP ETALIDAHKL LRSIIILLMG SDVLSIQKAA 

       970        980        990       1000       1010       1020 
TESPFLDYGE NLVQKWQVLT EVLTCSERLV GRLGRLGNVS EAKAFCLEAL KLTTKLQIPR 

      1030       1040       1050       1060       1070       1080 
QCALFLVLKG ELELARGDID LCQSDLQQVL FLLESSTEFG VVTQHPDSVK KVHTQKGKHK 

      1090       1100       1110       1120       1130       1140 
AQGPCFPPLS EEEPFLKGPA LELVDTVLNE PGPIQSSVNS SPVLKTKPPP NPGFLSHLPS 

      1150       1160       1170       1180       1190       1200 
CDCLLCASPA LSAVCLRWVL VTAGVRLATG HKAQGLDLLQ AVLTRCPAAT KRFTQSLQAS 

      1210       1220       1230       1240       1250       1260 
LNHRTTPSCV PSLFDEIMAQ VYTHLALEFL NQTSEKSLGK VLASGLKFVA TRIQSLEIWR 

      1270       1280       1290       1300       1310       1320 
AHLLLVQALA KLAHFSCCTS ELFASSWGWH PPLVKSLPVL EPAKIRRQKC SGRGRRRIAS 

      1330       1340       1350       1360       1370       1380 
VPPPLHNSSQ KGLEEEGPPC TPKPPGRARQ AGPRVPFTIF EEVHPTKSKL QVPLAPRVHR 

      1390       1400       1410       1420       1430       1440 
RAQTRLKVIF SDDSDLEDLV SADTQLVEEP KRRGTASRTR GQTRKGRSLK TDAVVAIEST 

      1450       1460       1470       1480       1490       1500 
PGHSSVSGRT RRARKVASRN CEEESPKAPL CVWASQGPEI MRSIPEEEPV DNHLEKSFEI 

      1510       1520       1530       1540       1550       1560 
LRGSDGEDSA SGEKAAAADT GLPVGECEVL RRDSSKAERP VLYSDTEANS DPSPWLPPFS 

      1570       1580       1590       1600       1610       1620 
VPAPIDLSTL DSISDSLSIA FRGVSHCPPS GLYAHLCRFL ALCLGHRDPY ATAFLVAESI 

      1630       1640       1650       1660       1670       1680 
SITCRHQLLT HLHRQLSKAQ KQQESPELAE HLQRLDLKER PGGVPLARIQ RLFSFKALGS 

      1690       1700       1710       1720       1730       1740 
GCFPQAEKES FQERLALIPS GVTVCVLALA TLQPGTLSNT LLLTRLEKDN PPITVKIPTA 

      1750       1760       1770       1780       1790       1800 
QNKLPLSAVL KEFDAIQKDQ KENSSCTEKR VWWTGRLALD QRMEALITAL EEQVLGCWRG 

      1810       1820       1830       1840       1850       1860 
LLLPCSADPS LAQEASKLQE LLRECGWEYP DSTLLKVILS GARILTSQDV QALACGLCPA 

      1870       1880       1890       1900       1910       1920 
QPDRAQVLLS EAVGQVQSQE APRSQHLVLV LDKDLQKLPW ESTPILQAQP VTRLPSFRFL 

      1930       1940       1950       1960       1970       1980 
LSYTVTKEAG ASSVLSQGVD PQNTFYVLNP HSNLSSTEER FRASFSSETG WKGVIGEVPS 

      1990       2000       2010       2020       2030       2040 
LDQVQAALTE RDLYIYAGHG AGARFLDGQA VLRLSCRAVA LLFGCSSAAL AVHGNLEGAG 

      2050       2060       2070       2080       2090       2100 
IVLKYIMAGC PLFLGNLWDV TDRDIDRYTE ALLQGWLGAG PGAPFLYYAS QARQAPRLKY 

      2110 
LIGAAPVAYG LPISLQTP 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Embryonic tail.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1241-1260, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[4]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK129072 mRNA. Translation: BAC97882.1. Different initiation.
BC145846 mRNA. Translation: AAI45847.1.
CCDSCCDS27878.1.
RefSeqNP_001014976.1. NM_001014976.2.
XP_006520320.1. XM_006520257.1.
XP_006520321.1. XM_006520258.1.
XP_006520322.1. XM_006520259.1.
UniGeneMm.288324.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid222968. 5 interactions.
IntActP60330. 5 interactions.
STRING10090.ENSMUSP00000064465.

Protein family/group databases

MEROPSC50.002.

PTM databases

PhosphoSiteP60330.

Proteomic databases

PaxDbP60330.
PRIDEP60330.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000064924; ENSMUSP00000064465; ENSMUSG00000058290.
GeneID105988.
KEGGmmu:105988.
UCSCuc007xvf.2. mouse.

Organism-specific databases

CTD9700.
MGIMGI:2146156. Espl1.
RougeSearch...

Phylogenomic databases

eggNOGCOG5155.
GeneTreeENSGT00390000004990.
HOGENOMHOG000290657.
HOVERGENHBG051510.
InParanoidA6H6E3.
KOK02365.
OMAELAQVLC.
OrthoDBEOG7PCJGQ.
PhylomeDBP60330.
TreeFamTF101169.

Gene expression databases

BgeeP60330.
CleanExMM_ESPL1.
GenevestigatorP60330.

Family and domain databases

InterProIPR005314. Peptidase_C50.
[Graphical view]
PANTHERPTHR12792. PTHR12792. 1 hit.
PfamPF03568. Peptidase_C50. 1 hit.
[Graphical view]
PROSITEPS51700. SEPARIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio357998.
PROP60330.
SOURCESearch...

Entry information

Entry nameESPL1_MOUSE
AccessionPrimary (citable) accession number: P60330
Secondary accession number(s): A6H6E3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: February 2, 2004
Last modified: July 9, 2014
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot