ESPL1_HUMAN
ID ESPL1_HUMAN Reviewed; 2120 AA.
AC Q14674;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 195.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ACTIVITY REGULATION, AUTOCATALYTIC
RP CLEAVAGE, AND MUTAGENESIS OF CYS-2029; 1483-GLU--ARG-1486;
RP 1503-GLU--ARG-1506 AND 1532-GLU--ARG-1535.
RX PubMed=12194817; DOI=10.1016/s0960-9822(02)01073-4;
RA Waizenegger I., Gimenez-Abian J.F., Wernic D., Peters J.-M.;
RT "Regulation of human separase by securin binding and autocleavage.";
RL Curr. Biol. 12:1368-1378(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH PTTG1.
RX PubMed=10411507; DOI=10.1126/science.285.5426.418;
RA Zou H., McGarry T.J., Bernal T., Kirschner M.W.;
RT "Identification of a vertebrate sister-chromatid separation inhibitor
RT involved in transformation and tumorigenesis.";
RL Science 285:418-422(1999).
RN [5]
RP PROTEIN SEQUENCE OF 1117-1130, ACTIVITY REGULATION, AND PHOSPHORYLATION AT
RP SER-1126.
RX PubMed=11747808; DOI=10.1016/s0092-8674(01)00603-1;
RA Stemmann O., Zou H., Gerber S.A., Gygi S.P., Kirschner M.W.;
RT "Dual inhibition of sister chromatid separation at metaphase.";
RL Cell 107:715-726(2001).
RN [6]
RP PROTEIN SEQUENCE OF 1507-1517, ACTIVITY REGULATION, AUTOCATALYTIC CLEAVAGE,
RP AND MUTAGENESIS OF ARG-1486; ARG-1506 AND ARG-1535.
RX PubMed=12297314; DOI=10.1016/s0014-5793(02)03238-6;
RA Zou H., Stemman O., Anderson J.S., Mann M., Kirschner M.W.;
RT "Anaphase specific auto-cleavage of separase.";
RL FEBS Lett. 528:246-250(2002).
RN [7]
RP FUNCTION, AND INTERACTION WITH RAD21.
RX PubMed=11509732; DOI=10.1126/science.1061376;
RA Hauf S., Waizenegger I.C., Peters J.-M.;
RT "Cohesin cleavage by separase required for anaphase and cytokinesis in
RT human cells.";
RL Science 293:1320-1323(2001).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1396; SER-1399 AND SER-1508,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1396 AND SER-1399, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1508, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1508, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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.
CC {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}.
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-1126 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.
CC {ECO:0000269|PubMed:11747808, ECO:0000269|PubMed:12194817,
CC ECO:0000269|PubMed:12297314}.
CC -!- SUBUNIT: Interacts with PTTG1. Interacts with RAD21.
CC {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14674-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14674-2; Sequence=VSP_009361;
CC -!- PTM: Autocleaves. This function, which is not essential for its
CC protease activity, is unknown.
CC -!- PTM: Phosphorylated by CDK1. There are 8 Ser/Thr phosphorylation sites.
CC Among them, Ser-1126 phosphorylation is the major site, which conducts
CC to the enzyme inactivation. {ECO:0000269|PubMed:11747808}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY455930; AAR18247.1; -; mRNA.
DR EMBL; D79987; BAA11482.2; -; mRNA.
DR EMBL; AC021072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS8852.1; -. [Q14674-1]
DR RefSeq; NP_036423.4; NM_012291.4. [Q14674-1]
DR RefSeq; XP_006719768.1; XM_006719705.3. [Q14674-1]
DR RefSeq; XP_011537326.1; XM_011539024.2. [Q14674-1]
DR RefSeq; XP_016875742.1; XM_017020253.1. [Q14674-2]
DR PDB; 7NJ0; EM; 3.60 A; A=1-2120.
DR PDB; 7NJ1; EM; 2.90 A; A=1-2120.
DR PDBsum; 7NJ0; -.
DR PDBsum; 7NJ1; -.
DR AlphaFoldDB; Q14674; -.
DR SMR; Q14674; -.
DR BioGRID; 115052; 77.
DR CORUM; Q14674; -.
DR DIP; DIP-46079N; -.
DR ELM; Q14674; -.
DR IntAct; Q14674; 36.
DR MINT; Q14674; -.
DR STRING; 9606.ENSP00000257934; -.
DR BindingDB; Q14674; -.
DR ChEMBL; CHEMBL4523294; -.
DR MEROPS; C50.002; -.
DR iPTMnet; Q14674; -.
DR MetOSite; Q14674; -.
DR PhosphoSitePlus; Q14674; -.
DR BioMuta; ESPL1; -.
DR DMDM; 308153600; -.
DR EPD; Q14674; -.
DR jPOST; Q14674; -.
DR MassIVE; Q14674; -.
DR MaxQB; Q14674; -.
DR PaxDb; Q14674; -.
DR PeptideAtlas; Q14674; -.
DR PRIDE; Q14674; -.
DR ProteomicsDB; 60103; -. [Q14674-1]
DR ProteomicsDB; 60104; -. [Q14674-2]
DR Antibodypedia; 26971; 677 antibodies from 28 providers.
DR DNASU; 9700; -.
DR Ensembl; ENST00000257934.9; ENSP00000257934.4; ENSG00000135476.12. [Q14674-1]
DR GeneID; 9700; -.
DR KEGG; hsa:9700; -.
DR MANE-Select; ENST00000257934.9; ENSP00000257934.4; NM_012291.5; NP_036423.4.
DR UCSC; uc001sck.2; human. [Q14674-1]
DR CTD; 9700; -.
DR DisGeNET; 9700; -.
DR GeneCards; ESPL1; -.
DR HGNC; HGNC:16856; ESPL1.
DR HPA; ENSG00000135476; Tissue enhanced (bone marrow, esophagus, lymphoid tissue).
DR MIM; 604143; gene.
DR neXtProt; NX_Q14674; -.
DR OpenTargets; ENSG00000135476; -.
DR PharmGKB; PA27884; -.
DR VEuPathDB; HostDB:ENSG00000135476; -.
DR eggNOG; KOG1849; Eukaryota.
DR GeneTree; ENSGT00390000004990; -.
DR HOGENOM; CLU_001558_0_0_1; -.
DR InParanoid; Q14674; -.
DR OMA; AMGHQAQ; -.
DR OrthoDB; 14013at2759; -.
DR PhylomeDB; Q14674; -.
DR TreeFam; TF101169; -.
DR BioCyc; MetaCyc:ENSG00000135476-MON; -.
DR BRENDA; 3.4.22.49; 2681.
DR PathwayCommons; Q14674; -.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR SignaLink; Q14674; -.
DR SIGNOR; Q14674; -.
DR BioGRID-ORCS; 9700; 786 hits in 1059 CRISPR screens.
DR ChiTaRS; ESPL1; human.
DR GeneWiki; Separase; -.
DR GenomeRNAi; 9700; -.
DR Pharos; Q14674; Tbio.
DR PRO; PR:Q14674; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q14674; protein.
DR Bgee; ENSG00000135476; Expressed in secondary oocyte and 137 other tissues.
DR ExpressionAtlas; Q14674; baseline and differential.
DR Genevisible; Q14674; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0072686; C:mitotic spindle; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003824; F:catalytic activity; NAS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:Reactome.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0040001; P:establishment of mitotic spindle localization; NAS:UniProtKB.
DR GO; GO:0045143; P:homologous chromosome segregation; IEA:Ensembl.
DR GO; GO:0051307; P:meiotic chromosome separation; IBA:GO_Central.
DR GO; GO:0000212; P:meiotic spindle organization; IEA:Ensembl.
DR GO; GO:0000281; P:mitotic cytokinesis; NAS:UniProtKB.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:UniProtKB.
DR GO; GO:0045875; P:negative regulation of sister chromatid cohesion; NAS:UniProtKB.
DR GO; GO:0045842; P:positive regulation of mitotic metaphase/anaphase transition; NAS:UniProtKB.
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 3D-structure; Alternative splicing; Autocatalytic cleavage;
KW Chromosome partition; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease.
FT CHAIN 1..2120
FT /note="Separin"
FT /id="PRO_0000205900"
FT DOMAIN 1945..2040
FT /note="Peptidase C50"
FT REGION 1299..1355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1412..1485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1507..1561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1304..1318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1461..1476
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1534..1558
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2029
FT SITE 1506..1507
FT /note="Cleavage; by autolysis"
FT SITE 1535..1536
FT /note="Cleavage; by autolysis"
FT MOD_RES 1126
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11747808"
FT MOD_RES 1396
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1399
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..325
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8724849"
FT /id="VSP_009361"
FT VARIANT 614
FT /note="S -> R (in dbSNP:rs1318648)"
FT /id="VAR_057703"
FT VARIANT 699
FT /note="R -> Q (in dbSNP:rs34424268)"
FT /id="VAR_057704"
FT VARIANT 1136
FT /note="I -> V (in dbSNP:rs34130634)"
FT /id="VAR_057705"
FT VARIANT 1157
FT /note="T -> A (in dbSNP:rs35428211)"
FT /id="VAR_057706"
FT VARIANT 1237
FT /note="Q -> H (in dbSNP:rs34396464)"
FT /id="VAR_057707"
FT VARIANT 1435
FT /note="K -> M (in dbSNP:rs1110719)"
FT /id="VAR_057708"
FT MUTAGEN 1126
FT /note="S->A: Abolishes phosphorylation at this site, as
FT well as the negative regulation due to phosphorylation."
FT MUTAGEN 1483..1486
FT /note="EIMR->RIME: Abolishes autocleavage; when associated
FT with R-1178; E-1181; R-1207 and E-1210. Does not affect the
FT protease function."
FT /evidence="ECO:0000269|PubMed:12194817"
FT MUTAGEN 1486
FT /note="R->A: Abolishes autocleavage; when associated with
FT A-1181 and A-1210."
FT /evidence="ECO:0000269|PubMed:12297314"
FT MUTAGEN 1503..1506
FT /note="EILR->RILE: Does not affect autocleavage. Does not
FT affect the protease function."
FT /evidence="ECO:0000269|PubMed:12194817"
FT MUTAGEN 1506
FT /note="R->A: Abolishes autocleavage; when associated with
FT A-1161 and A-1210."
FT /evidence="ECO:0000269|PubMed:12297314"
FT MUTAGEN 1532..1535
FT /note="ELLR->RLLE: Strongly reduces autocleavage at this
FT site, but enhances autocleavage at site 1. Does not affect
FT the protease function."
FT /evidence="ECO:0000269|PubMed:12194817"
FT MUTAGEN 1535
FT /note="R->A: Abolishes autocleavage; when associated with
FT A-1161 and A-1281."
FT /evidence="ECO:0000269|PubMed:12297314"
FT MUTAGEN 2029
FT /note="C->A: Abolishes protease activity."
FT /evidence="ECO:0000269|PubMed:12194817"
FT CONFLICT 25
FT /note="A -> D (in Ref. 1; AAR18247)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="A -> V (in Ref. 1; AAR18247)"
FT /evidence="ECO:0000305"
FT CONFLICT 693
FT /note="M -> I (in Ref. 1; AAR18247 and 2; BAA11482)"
FT /evidence="ECO:0000305"
FT CONFLICT 1329
FT /note="R -> S (in Ref. 1; AAR18247 and 2; BAA11482)"
FT /evidence="ECO:0000305"
FT CONFLICT 1561
FT /note="R -> Q (in Ref. 1; AAR18247 and 2; BAA11482)"
FT /evidence="ECO:0000305"
FT CONFLICT 2037
FT /note="R -> H (in Ref. 1; AAR18247 and 2; BAA11482)"
FT /evidence="ECO:0000305"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 265..270
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 278..290
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 302..312
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 313..319
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 330..345
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 352..366
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 377..389
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 401..417
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 428..441
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 446..468
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 474..489
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 500..516
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 520..533
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 534..536
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 539..542
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 543..559
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 563..566
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 569..572
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 578..594
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 600..613
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 619..636
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 649..662
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 667..669
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 670..701
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 729..736
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 740..758
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 769..785
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 789..805
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 809..825
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 830..844
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 848..850
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 851..870
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 874..885
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 888..891
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 895..912
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 921..928
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 935..953
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 971..974
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 976..1000
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1004..1021
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1024..1040
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1044..1061
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1148..1152
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1154..1173
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1178..1206
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1218..1231
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1233..1236
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 1242..1246
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1247..1256
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 1258..1260
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1263..1277
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1574..1588
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1589..1591
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1595..1607
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1610..1612
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1613..1622
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1626..1646
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1668..1677
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1686..1688
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1689..1700
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1706..1714
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1723..1730
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1732..1734
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1737..1742
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1744..1748
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1751..1767
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1773..1797
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 1798..1803
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1804..1806
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1812..1814
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1815..1829
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1837..1842
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1846..1848
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1851..1861
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1863..1865
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1867..1879
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1890..1894
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 1897..1899
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1900..1902
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1904..1906
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1911..1913
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1915..1917
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1921..1933
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1937..1940
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1948..1952
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1959..1971
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1978..1981
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 1985..1994
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 1996..2006
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 2012..2016
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 2022..2028
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 2029..2032
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 2045..2050
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 2051..2053
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 2055..2059
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 2067..2083
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 2089..2095
FT /evidence="ECO:0007829|PDB:7NJ1"
FT HELIX 2096..2098
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 2099..2102
FT /evidence="ECO:0007829|PDB:7NJ1"
FT TURN 2103..2105
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 2106..2108
FT /evidence="ECO:0007829|PDB:7NJ1"
FT STRAND 2111..2115
FT /evidence="ECO:0007829|PDB:7NJ1"
SQ SEQUENCE 2120 AA; 233175 MW; 0257A69093B4954C CRC64;
MRSFKRVNFG TLLSSQKEAE ELLPALKEFL SNPPAGFPSS RSDAERRQAC DAILRACNQQ
LTAKLACPRH LGSLLELAEL ACDGYLVSTP QRPPLYLERI LFVLLRNAAA QGSPEATLRL
AQPLHACLVQ CSREAAPQDY EAVARGSFSL LWKGAEALLE RRAAFAARLK ALSFLVLLED
ESTPCEVPHF ASPTACRAVA AHQLFDASGH GLNEADADFL DDLLSRHVIR ALVGERGSSS
GLLSPQRALC LLELTLEHCR RFCWSRHHDK AISAVEKAHS YLRNTNLAPS LQLCQLGVKL
LQVGEEGPQA VAKLLIKASA VLSKSMEAPS PPLRALYESC QFFLSGLERG TKRRYRLDAI
LSLFAFLGGY CSLLQQLRDD GVYGGSSKQQ QSFLQMYFQG LHLYTVVVYD FAQGCQIVDL
ADLTQLVDSC KSTVVWMLEA LEGLSGQELT DHMGMTASYT SNLAYSFYSH KLYAEACAIS
EPLCQHLGLV KPGTYPEVPP EKLHRCFRLQ VESLKKLGKQ AQGCKMVILW LAALQPCSPE
HMAEPVTFWV RVKMDAARAG DKELQLKTLR DSLSGWDPET LALLLREELQ AYKAVRADTG
QERFNIICDL LELSPEETPA GAWARATHLV ELAQVLCYHD FTQQTNCSAL DAIREALQLL
DSVRPEAQAR DQLLDDKAQA LLWLYICTLE AKMQEGIERD RRAQAPGNLE EFEVNDLNYE
DKLQEDRFLY SNIAFNLAAD AAQSKCLDQA LALWKELLTK GQAPAVRCLQ QTAASLQILA
ALYQLVAKPM QALEVLLLLR IVSERLKDHS KAAGSSCHIT QLLLTLGCPS YAQLHLEEAA
SSLKHLDQTT DTYLLLSLTC DLLRSQLYWT HQKVTKGVSL LLSVLRDPAL QKSSKAWYLL
RVQVLQLVAA YLSLPSNNLS HSLWEQLCAQ GWQTPEIALI DSHKLLRSII LLLMGSDILS
TQKAAVETSF LDYGENLVQK WQVLSEVLSC SEKLVCHLGR LGSVSEAKAF CLEALKLTTK
LQIPRQCALF LVLKGELELA RNDIDLCQSD LQQVLFLLES CTEFGGVTQH LDSVKKVHLQ
KGKQQAQVPC PPQLPEEELF LRGPALELVA TVAKEPGPIA PSTNSSPVLK TKPQPIPNFL
SHSPTCDCSL CASPVLTAVC LRWVLVTAGV RLAMGHQAQG LDLLQVVLKG CPEAAERLTQ
ALQASLNHKT PPSLVPSLLD EILAQAYTLL ALEGLNQPSN ESLQKVLQSG LKFVAARIPH
LEPWRASLLL IWALTKLGGL SCCTTQLFAS SWGWQPPLIK SVPGSEPSKT QGQKRSGRGR
QKLASAPLRL NNTSQKGLEG RGLPCTPKPP DRIRQAGPHV PFTVFEEVCP TESKPEVPQA
PRVQQRVQTR LKVNFSDDSD LEDPVSAEAW LAEEPKRRGT ASRGRGRARK GLSLKTDAVV
APGSAPGNPG LNGRSRRAKK VASRHCEERR PQRASDQARP GPEIMRTIPE EELTDNWRKM
SFEILRGSDG EDSASGGKTP APGPEAASGE WELLRLDSSK KKLPSPCPDK ESDKDLGPRL
RLPSAPVATG LSTLDSICDS LSVAFRGISH CPPSGLYAHL CRFLALCLGH RDPYATAFLV
TESVSITCRH QLLTHLHRQL SKAQKHRGSL EIADQLQGLS LQEMPGDVPL ARIQRLFSFR
ALESGHFPQP EKESFQERLA LIPSGVTVCV LALATLQPGT VGNTLLLTRL EKDSPPVSVQ
IPTGQNKLHL RSVLNEFDAI QKAQKENSSC TDKREWWTGR LALDHRMEVL IASLEKSVLG
CWKGLLLPSS EEPGPAQEAS RLQELLQDCG WKYPDRTLLK IMLSGAGALT PQDIQALAYG
LCPTQPERAQ ELLNEAVGRL QGLTVPSNSH LVLVLDKDLQ KLPWESMPSL QALPVTRLPS
FRFLLSYSII KEYGASPVLS QGVDPRSTFY VLNPHNNLSS TEEQFRANFS SEAGWRGVVG
EVPRPEQVQE ALTKHDLYIY AGHGAGARFL DGQAVLRLSC RAVALLFGCS SAALAVRGNL
EGAGIVLKYI MAGCPLFLGN LWDVTDRDID RYTEALLQGW LGAGPGAPLL YYVNQARQAP
RLKYLIGAAP IAYGLPVSLR
