ESPL1_MOUSE
ID ESPL1_MOUSE Reviewed; 2118 AA.
AC P60330; A6H6E3;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Separin;
DE EC=3.4.22.49;
DE AltName: Full=Caspase-like protein ESPL1;
DE AltName: Full=Extra spindle poles-like 1 protein;
DE AltName: Full=Separase;
GN Name=Espl1; Synonyms=Esp1, Kiaa0165;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 1241-1260, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1504, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Caspase-like protease, which plays a central role in the
CC chromosome segregation by cleaving the SCC1/RAD21 subunit of the
CC cohesin complex at the onset of anaphase. During most of the cell
CC cycle, it is inactivated by different mechanisms (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=All bonds known to be hydrolyzed by this endopeptidase have
CC arginine in P1 and an acidic residue in P4. P6 is often occupied by
CC an acidic residue or by a hydroxy-amino-acid residue, the
CC phosphorylation of which enhances cleavage.; EC=3.4.22.49;
CC -!- ACTIVITY REGULATION: Regulated by at least two independent mechanisms.
CC First, it is inactivated via its interaction with securin/PTTG1, which
CC probably covers its active site. The association with PTTG1 is not only
CC inhibitory, since PTTG1 is also required for activating it, the enzyme
CC being inactive in cells in which PTTG1 is absent. PTTG1 degradation at
CC anaphase, liberates it and triggers RAD21 cleavage. Second,
CC phosphorylation at Ser-1121 inactivates it. The complete
CC phosphorylation during mitosis, is removed when cells undergo anaphase.
CC Activation of the enzyme at the metaphase-anaphase transition probably
CC requires the removal of both securin and inhibitory phosphate (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PTTG1. Interacts with RAD21 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- PTM: Autocleaves. This function, which is not essential for its
CC protease activity, is unknown (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by CDK1. There is 8 Ser/Thr phosphorylation sites.
CC Among them, only Ser-1121 phosphorylation is the major site, which
CC conducts to the enzyme inactivation (By similarity). {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC97882.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK129072; BAC97882.1; ALT_INIT; mRNA.
DR EMBL; BC145846; AAI45847.1; -; mRNA.
DR CCDS; CCDS27878.1; -.
DR RefSeq; NP_001014976.1; NM_001014976.2.
DR RefSeq; XP_006520320.1; XM_006520257.3.
DR RefSeq; XP_006520321.1; XM_006520258.3.
DR RefSeq; XP_006520322.1; XM_006520259.3.
DR RefSeq; XP_011243698.1; XM_011245396.2.
DR AlphaFoldDB; P60330; -.
DR SMR; P60330; -.
DR BioGRID; 222968; 28.
DR IntAct; P60330; 26.
DR STRING; 10090.ENSMUSP00000064465; -.
DR MEROPS; C50.002; -.
DR iPTMnet; P60330; -.
DR PhosphoSitePlus; P60330; -.
DR EPD; P60330; -.
DR jPOST; P60330; -.
DR MaxQB; P60330; -.
DR PaxDb; P60330; -.
DR PRIDE; P60330; -.
DR ProteomicsDB; 275543; -.
DR Antibodypedia; 26971; 677 antibodies from 28 providers.
DR Ensembl; ENSMUST00000064924; ENSMUSP00000064465; ENSMUSG00000058290.
DR Ensembl; ENSMUST00000229050; ENSMUSP00000155304; ENSMUSG00000058290.
DR GeneID; 105988; -.
DR KEGG; mmu:105988; -.
DR UCSC; uc007xvf.2; mouse.
DR CTD; 9700; -.
DR MGI; MGI:2146156; Espl1.
DR VEuPathDB; HostDB:ENSMUSG00000058290; -.
DR eggNOG; KOG1849; Eukaryota.
DR GeneTree; ENSGT00390000004990; -.
DR HOGENOM; CLU_001558_0_0_1; -.
DR InParanoid; P60330; -.
DR OMA; AMGHQAQ; -.
DR OrthoDB; 14013at2759; -.
DR PhylomeDB; P60330; -.
DR TreeFam; TF101169; -.
DR BRENDA; 3.4.22.49; 3474.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR BioGRID-ORCS; 105988; 28 hits in 77 CRISPR screens.
DR ChiTaRS; Espl1; mouse.
DR PRO; PR:P60330; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P60330; protein.
DR Bgee; ENSMUSG00000058290; Expressed in dorsal pancreas and 173 other tissues.
DR ExpressionAtlas; P60330; baseline and differential.
DR Genevisible; P60330; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0007059; P:chromosome segregation; IGI:MGI.
DR GO; GO:0045143; P:homologous chromosome segregation; IMP:MGI.
DR GO; GO:0007127; P:meiosis I; IMP:MGI.
DR GO; GO:0051307; P:meiotic chromosome separation; IBA:GO_Central.
DR GO; GO:0000212; P:meiotic spindle organization; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IGI:MGI.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR005314; Peptidase_C50.
DR InterPro; IPR030397; SEPARIN_core_dom.
DR PANTHER; PTHR12792; PTHR12792; 1.
DR PROSITE; PS51700; SEPARIN; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Chromosome partition; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease.
FT CHAIN 1..2118
FT /note="Separin"
FT /id="PRO_0000205901"
FT DOMAIN 1941..2036
FT /note="Peptidase C50"
FT REGION 1309..1352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1408..1428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2025
FT /evidence="ECO:0000250"
FT SITE 1502..1503
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT SITE 1531..1532
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14674"
FT MOD_RES 1391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14674"
FT MOD_RES 1394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14674"
FT MOD_RES 1504
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 2118 AA; 233035 MW; 484FCE178C0984B6 CRC64;
MRNFKGVNFA TLLCSKEETQ QLLPDLKEFL SRSRTDFPSS RTDAERRQIC DTILRACTQQ
LTAKLDCPGH LRSILDLAEL ACDGYLLSTP QRPPLYLERI LFILLRNGST QGSPDTVLRL
AQPLHACLVQ NSGEAAPQDY EAVTRGSFSL FWKGAEALLE RRAAFSTRLN ALSFLVLLED
GSVPCEVPHF ASPTACRLVA AYQLYDATGQ GLDEADADFL YEVLSRHLIR VLVGEGGSSP
GPLSPQRALC LLEITLEHCR RLCWNHHHRQ AARAVERARN HLEKTSVAPS LQLCQMGVEL
LEAVEERPGA VAQLLRKAAA VLINSIEAPS PPLRALYDSC QFFLSGLERG IRRHCGLDAI
LSLFAFLGGY SSLVRHLREV SEASSKQQQC LLQMHFQGFH LFTGIVYDFA QGCQATELAQ
LVDGCRSAAV WMLEALEGLS GGELADYLSM TASYTSNLAY SFFSQKLYEE ACVISEPVCQ
HLGSATSGAC PEVPPEKLHR CFRLHVESLK KLGKQAQGCK MVTLWLAALK PYSLEHMVEP
VTFWVRVKMD ASRAGDKELQ LQTLRDSLSC WDPETQSLLL REELRAYKSV RADTGQERFN
IICDLLELSP EETAAGAWAR ATYLVELAQV LCYHNFTQQT NCSALDAVQE ALQLLESVSP
EAQEQDRLLD DKAQALLWLY ICTLEAKMQE GIERDRRAQA PSNLEEFEVN DLNYEDKLQE
DRFLYSSIAF NLAADAAQSK CLDQALTLWK EVLTKGRAPA VRCLQQTAAS LQILAAVYQL
VAKPLQALET LLLLQIVSKR LQDHAKAASS SCQLTQLLLN LGCPSYAQLY LEEAESSLRS
LDQTSDACQL LSLTCALLGS QLCWACQKVT AGVSLLLSVL RDPALQKSSK AWYLLRVQAL
QVLAFYLSLS SNLLSSALRE QLWDQGWQTP ETALIDAHKL LRSIIILLMG SDVLSIQKAA
TESPFLDYGE NLVQKWQVLT EVLTCSERLV GRLGRLGNVS EAKAFCLEAL KLTTKLQIPR
QCALFLVLKG ELELARGDID LCQSDLQQVL FLLESSTEFG VVTQHPDSVK KVHTQKGKHK
AQGPCFPPLS EEEPFLKGPA LELVDTVLNE PGPIQSSVNS SPVLKTKPPP NPGFLSHLPS
CDCLLCASPA LSAVCLRWVL VTAGVRLATG HKAQGLDLLQ AVLTRCPAAT KRFTQSLQAS
LNHRTTPSCV PSLFDEIMAQ VYTHLALEFL NQTSEKSLGK VLASGLKFVA TRIQSLEIWR
AHLLLVQALA KLAHFSCCTS ELFASSWGWH PPLVKSLPVL EPAKIRRQKC SGRGRRRIAS
VPPPLHNSSQ KGLEEEGPPC TPKPPGRARQ AGPRVPFTIF EEVHPTKSKL QVPLAPRVHR
RAQTRLKVIF SDDSDLEDLV SADTQLVEEP KRRGTASRTR GQTRKGRSLK TDAVVAIEST
PGHSSVSGRT RRARKVASRN CEEESPKAPL CVWASQGPEI MRSIPEEEPV DNHLEKSFEI
LRGSDGEDSA SGEKAAAADT GLPVGECEVL RRDSSKAERP VLYSDTEANS DPSPWLPPFS
VPAPIDLSTL DSISDSLSIA FRGVSHCPPS GLYAHLCRFL ALCLGHRDPY ATAFLVAESI
SITCRHQLLT HLHRQLSKAQ KQQESPELAE HLQRLDLKER PGGVPLARIQ RLFSFKALGS
GCFPQAEKES FQERLALIPS GVTVCVLALA TLQPGTLSNT LLLTRLEKDN PPITVKIPTA
QNKLPLSAVL KEFDAIQKDQ KENSSCTEKR VWWTGRLALD QRMEALITAL EEQVLGCWRG
LLLPCSADPS LAQEASKLQE LLRECGWEYP DSTLLKVILS GARILTSQDV QALACGLCPA
QPDRAQVLLS EAVGQVQSQE APRSQHLVLV LDKDLQKLPW ESTPILQAQP VTRLPSFRFL
LSYTVTKEAG ASSVLSQGVD PQNTFYVLNP HSNLSSTEER FRASFSSETG WKGVIGEVPS
LDQVQAALTE RDLYIYAGHG AGARFLDGQA VLRLSCRAVA LLFGCSSAAL AVHGNLEGAG
IVLKYIMAGC PLFLGNLWDV TDRDIDRYTE ALLQGWLGAG PGAPFLYYAS QARQAPRLKY
LIGAAPVAYG LPISLQTP
