TCSL3_PAES9
ID TCSL3_PAES9 Reviewed; 2364 AA.
AC T0D3N5;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Cytotoxin-L {ECO:0000303|PubMed:23873908};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q46342};
DE AltName: Full=Lethal toxin {ECO:0000303|PubMed:11500421};
DE Short=LT {ECO:0000303|PubMed:11500421};
DE Contains:
DE RecName: Full=Glucosyltransferase TcsL {ECO:0000305};
DE EC=2.4.1.- {ECO:0000250|UniProtKB:Q46342};
GN Name=tcsL {ECO:0000303|PubMed:23873908};
GN ORFNames=H477_0263 {ECO:0000312|EMBL:EPZ61151.1};
OS Paeniclostridium sordellii (strain ATCC 9714 / DSM 2141 / JCM 3814 / LMG
OS 15708 / NCIMB 10717 / 211) (Clostridium sordellii).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Paeniclostridium.
OX NCBI_TaxID=1292036;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717 / 211;
RX PubMed=23873908; DOI=10.1128/jb.00711-13;
RA Sirigi Reddy A.R., Girinathan B.P., Zapotocny R., Govind R.;
RT "Identification and characterization of Clostridium sordellii toxin gene
RT regulator.";
RL J. Bacteriol. 195:4246-4254(2013).
RN [2]
RP FUNCTION (CYTOTOXIN-L).
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717 / 211;
RX PubMed=11500421; DOI=10.1128/iai.69.9.5487-5493.2001;
RA Qa'Dan M., Spyres L.M., Ballard J.D.;
RT "pH-enhanced cytopathic effects of Clostridium sordellii lethal toxin.";
RL Infect. Immun. 69:5487-5493(2001).
RN [3]
RP SUBUNIT (CYTOTOXIN-L).
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717 / 211;
RX PubMed=15155642; DOI=10.1128/iai.72.6.3366-3372.2004;
RA Voth D.E., Qa'Dan M., Hamm E.E., Pelfrey J.M., Ballard J.D.;
RT "Clostridium sordellii lethal toxin is maintained in a multimeric protein
RT complex.";
RL Infect. Immun. 72:3366-3372(2004).
RN [4]
RP FUNCTION (CYTOTOXIN-L).
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717 / 211;
RX PubMed=19527792; DOI=10.1016/j.anaerobe.2009.06.002;
RA Hao Y., Senn T., Opp J.S., Young V.B., Thiele T., Srinivas G., Huang S.K.,
RA Aronoff D.M.;
RT "Lethal toxin is a critical determinant of rapid mortality in rodent models
RT of Clostridium sordellii endometritis.";
RL Anaerobe 16:155-160(2010).
RN [5]
RP FUNCTION (CYTOTOXIN-L), AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717 / 211;
RX PubMed=21199912; DOI=10.1128/iai.00968-10;
RA Carter G.P., Awad M.M., Hao Y., Thelen T., Bergin I.L., Howarth P.M.,
RA Seemann T., Rood J.I., Aronoff D.M., Lyras D.;
RT "TcsL is an essential virulence factor in Clostridium sordellii ATCC
RT 9714.";
RL Infect. Immun. 79:1025-1032(2011).
CC -!- FUNCTION: [Cytotoxin-L]: Precursor of a cytotoxin that targets the
CC vascular endothelium, inducing an anti-inflammatory effect and
CC resulting in lethal toxic shock syndrome (PubMed:19527792,
CC PubMed:21199912). TcsL constitutes the main toxin that mediates the
CC pathology of P.sordellii infection, an anaerobic Gram-positive
CC bacterium found in soil and in the gastrointestinal and vaginal tracts
CC of animals and humans; although the majority of carriers are
CC asymptomatic, pathogenic P.sordellii infections arise rapidly and are
CC highly lethal (By similarity). This form constitutes the precursor of
CC the toxin: it enters into host cells and mediates autoprocessing to
CC release the active toxin (Glucosyltransferase TcsL) into the host
CC cytosol (By similarity). Targets vascular endothelium by binding to the
CC semaphorin proteins SEMA6A and SEMA6B, and enters host cells via
CC clathrin-mediated endocytosis (By similarity). Once entered into host
CC cells, acidification in the endosome promotes the membrane insertion of
CC the translocation region and formation of a pore, leading to
CC translocation of the GT44 and peptidase C80 domains across the
CC endosomal membrane (By similarity) (PubMed:11500421). This activates
CC the peptidase C80 domain and autocatalytic processing, releasing the N-
CC terminal part (Glucosyltransferase TcsL), which constitutes the active
CC part of the toxin, in the cytosol (By similarity).
CC {ECO:0000250|UniProtKB:P18177, ECO:0000250|UniProtKB:Q46342,
CC ECO:0000269|PubMed:11500421, ECO:0000269|PubMed:19527792,
CC ECO:0000269|PubMed:21199912}.
CC -!- FUNCTION: [Glucosyltransferase TcsL]: Active form of the toxin, which
CC is released into the host cytosol following autoprocessing and
CC inactivates small GTPases. Acts by mediating monoglucosylation of small
CC GTPases of the Ras (H-Ras/HRAS, K-Ras/KRAS and N-Ras/NRAS) family in
CC host cells at the conserved threonine residue located in the switch I
CC region ('Thr-37/35'), using UDP-alpha-D-glucose as the sugar donor.
CC Also able to catalyze monoglucosylation of some members of the Rho
CC family (Rac1 and Rap2A), but with less efficiency than with Ras
CC proteins. Monoglucosylation of host small GTPases completely prevents
CC the recognition of the downstream effector, blocking the GTPases in
CC their inactive form and leading to apoptosis. Induces an anti-
CC inflammatory effect, mainly by inactivating Ras proteins which results
CC in blockage of the cell cycle and killing of immune cells. The absence
CC or moderate local inflammatory response allows C.sordellii spreading in
CC deep tissues, production of toxin which is released in the general
CC circulation and causes a toxic shock syndrome.
CC {ECO:0000250|UniProtKB:Q46342}.
CC -!- CATALYTIC ACTIVITY: [Glucosyltransferase TcsL]:
CC Reaction=L-threonyl-[protein] + UDP-alpha-D-glucose = 3-O-(alpha-D-
CC glucosyl)-L-threonyl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:64684,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:16656, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885,
CC ChEBI:CHEBI:156085; Evidence={ECO:0000250|UniProtKB:Q46342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64685;
CC Evidence={ECO:0000250|UniProtKB:Q46342};
CC -!- COFACTOR: [Cytotoxin-L]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P18177};
CC Note=Binds 1 Zn(2+) ion per subunit. Zn(2+) is required for
CC autocatalytic cleavage. {ECO:0000250|UniProtKB:P18177};
CC -!- COFACTOR: [Glucosyltransferase TcsL]:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q46342};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q46342};
CC Note=Has higher activity with Mn(2+), but most likely uses Mg(2+) in
CC host cells. Mn(2+) or Mg(2+) are required for glucosyltransferase
CC activity. {ECO:0000250|UniProtKB:Q46342};
CC -!- ACTIVITY REGULATION: [Cytotoxin-L]: Protease activity is activated upon
CC binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces
CC conformational reorganization. {ECO:0000250|UniProtKB:Q46342}.
CC -!- SUBUNIT: [Cytotoxin-L]: Homomultimer; forms an inactive homomultimer at
CC pH 8, which dissociates at pH 4, leading to cytotoxicity
CC (PubMed:15155642). Interacts with host SEMA6A; interaction promotes
CC toxin entry into host cell (By similarity). Interacts with host SEMA6B;
CC interaction promotes toxin entry into host cell (By similarity).
CC {ECO:0000250|UniProtKB:Q46342, ECO:0000269|PubMed:15155642}.
CC -!- SUBCELLULAR LOCATION: [Cytotoxin-L]: Secreted
CC {ECO:0000250|UniProtKB:P18177}. Host endosome membrane
CC {ECO:0000250|UniProtKB:P18177}. Note=Secreted from P.sordellii cell
CC into the extracellular environment via help of holin-like protein
CC TcdE/UtxA. Binds to the cell surface receptors via the receptor-binding
CC region and enters the cells via clathrin-mediated endocytosis.
CC Acidification in the endosome triggers conformational changes that
CC promote the membrane insertion of the translocation region, allowing
CC formation of a pore, leading to translocation of the GT44 and peptidase
CC C80 domains across the endosomal membrane (By similarity). 1D-myo-
CC inositol hexakisphosphate-binding (InsP6) activates the peptidase C80
CC domain and autoprocessing, generating the Glucosyltransferase TcsL
CC form, which is released in the host cytosol (By similarity).
CC {ECO:0000250|UniProtKB:P18177, ECO:0000250|UniProtKB:Q46342}.
CC -!- SUBCELLULAR LOCATION: [Glucosyltransferase TcsL]: Host cytoplasm, host
CC cytosol {ECO:0000250|UniProtKB:Q46342}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q46342}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q46342}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q46342}. Note=Binding to phospholipids, such as
CC phosphatidylserine and phosphatidic acid promotes localization to the
CC inner face of the cell membrane close to its membrane anchored
CC substrates (small GTPases). {ECO:0000250|UniProtKB:Q46342}.
CC -!- DOMAIN: [Glucosyltransferase TcsL]: Consists of 4 functional domains:
CC (1) the N-terminal GT44 domain (glucosyltransferase, also named GTD),
CC which mediates glucosylation of host small GTPases, (2) an
CC autoprocessing region that catalyzes autoprocessing to release the N-
CC terminal GT44 domain in the host cytosol, (3) the translocation region
CC that forms a pore to promote translocation of the GT44 and peptidase
CC C80 domains across the endosomal membrane and (4) the receptor-binding
CC (CROPS) region that mediates binding to host cells and contribute to
CC entry into cells. {ECO:0000250|UniProtKB:Q46342}.
CC -!- DOMAIN: [Cytotoxin-L]: The receptor-binding (CROPS) region is dynamic
CC and can have open and closed conformations depending of the pH: has an
CC open conformation at endosomal pH and a closed conformation at neutral
CC pH. {ECO:0000250|UniProtKB:P18177}.
CC -!- DOMAIN: [Cytotoxin-L]: The cell wall-binding repeats bind
CC carbohydrates, probably contributing to entry into cells.
CC {ECO:0000250|UniProtKB:P16154}.
CC -!- DOMAIN: [Glucosyltransferase TcsL]: The four-helical bundle region
CC mediates binding to phospholipids, such as phosphatidylserine and
CC phosphatidic acid. This promotes localization to the inner face of the
CC cell membrane close to small GTPases. {ECO:0000250|UniProtKB:Q46342}.
CC -!- PTM: [Cytotoxin-L]: Undergoes autocatalytic cleavage to release the N-
CC terminal part (Glucosyltransferase TcsL), which constitutes the active
CC part of the toxin, in the host cytosol. 1D-myo-inositol
CC hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and
CC promotes autoprocessing. {ECO:0000250|UniProtKB:Q46342}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking tcsL are not able to induce lethal
CC infections (PubMed:21199912). Infected mice also show strongly reduced
CC formation of edema during uterine infection (PubMed:21199912).
CC {ECO:0000269|PubMed:21199912}.
CC -!- SIMILARITY: Belongs to the clostridial glucosylating toxin (LCGT)
CC family. {ECO:0000305}.
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DR EMBL; APWR01000088; EPZ61151.1; -; Genomic_DNA.
DR RefSeq; WP_021122190.1; NZ_CDNU01000031.1.
DR AlphaFoldDB; T0D3N5; -.
DR SMR; T0D3N5; -.
DR EnsemblBacteria; EPZ61151; EPZ61151; H477_0263.
DR PATRIC; fig|1292036.3.peg.1017; -.
DR Proteomes; UP000015748; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.11050; -; 1.
DR InterPro; IPR018337; Cell_wall/Cho-bd_repeat.
DR InterPro; IPR020974; CPD_dom.
DR InterPro; IPR038383; CPD_dom_sf.
DR InterPro; IPR020972; Dermonecrotic/RTX_toxin_MLD.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR024770; TcdA/TcdB_cat.
DR InterPro; IPR024772; TcdA/TcdB_N.
DR InterPro; IPR024769; TcdA/TcdB_pore_forming.
DR Pfam; PF01473; Choline_bind_1; 5.
DR Pfam; PF11647; MLD; 1.
DR Pfam; PF11713; Peptidase_C80; 1.
DR Pfam; PF12919; TcdA_TcdB; 1.
DR Pfam; PF12920; TcdA_TcdB_pore; 1.
DR Pfam; PF12918; TcdB_N; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51771; CGT_MARTX_CPD; 1.
DR PROSITE; PS51170; CW; 20.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Glycosyltransferase; Host cell membrane;
KW Host cytoplasm; Host endosome; Host membrane; Hydrolase; Lipid-binding;
KW Magnesium; Manganese; Membrane; Metal-binding; Protease;
KW Reference proteome; Repeat; Secreted; Thiol protease; Toxin; Transferase;
KW Virulence; Zinc.
FT CHAIN 1..2364
FT /note="Cytotoxin-L"
FT /id="PRO_0000451201"
FT CHAIN 1..543
FT /note="Glucosyltransferase TcsL"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT /id="PRO_0000451202"
FT DOMAIN 96..468
FT /note="GT44"
FT /evidence="ECO:0000255"
FT DOMAIN 567..774
FT /note="Peptidase C80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT REPEAT 1813..1832
FT /note="Cell wall-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1833..1852
FT /note="Cell wall-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1854..1873
FT /note="Cell wall-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1876..1895
FT /note="Cell wall-binding 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1926..1945
FT /note="Cell wall-binding 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1946..1965
FT /note="Cell wall-binding 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1967..1986
FT /note="Cell wall-binding 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1987..2006
FT /note="Cell wall-binding 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2007..2026
FT /note="Cell wall-binding 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2057..2076
FT /note="Cell wall-binding 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2077..2097
FT /note="Cell wall-binding 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2099..2118
FT /note="Cell wall-binding 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2119..2138
FT /note="Cell wall-binding 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2139..2158
FT /note="Cell wall-binding 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2209..2224
FT /note="Cell wall-binding 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2227..2249
FT /note="Cell wall-binding 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2250..2269
FT /note="Cell wall-binding 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2270..2289
FT /note="Cell wall-binding 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2320..2339
FT /note="Cell wall-binding 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2340..2359
FT /note="Cell wall-binding 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REGION 1..91
FT /note="Four-helical bundle"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 96..468
FT /note="Glucosyltransferase region"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 544..799
FT /note="Autoprocessing region"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 800..1500
FT /note="Translocation region"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 1433..1438
FT /note="Interaction with host SEMA6A and SEMA6B"
FT /evidence="ECO:0000250|UniProtKB:P0DUB4"
FT REGION 1466..1471
FT /note="Interaction with host SEMA6A and SEMA6B"
FT /evidence="ECO:0000250|UniProtKB:P0DUB4"
FT REGION 1484..1495
FT /note="Interaction with host SEMA6A and SEMA6B"
FT /evidence="ECO:0000250|UniProtKB:P0DUB4"
FT REGION 1504..1511
FT /note="Interaction with host SEMA6A and SEMA6B"
FT /evidence="ECO:0000250|UniProtKB:P0DUB4"
FT REGION 1596..1601
FT /note="Interaction with host SEMA6A and SEMA6B"
FT /evidence="ECO:0000250|UniProtKB:P0DUB4"
FT REGION 1835..2364
FT /note="Receptor-binding (CROPS) region"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT ACT_SITE 653
FT /note="For protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT ACT_SITE 698
FT /note="Nucleophile; for protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT BINDING 101..103
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 139
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 265..270
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 286..288
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 288
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 515
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 518..520
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 518
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT BINDING 545
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 546
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 577
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 600
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 647
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 653
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 757
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 764
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 775
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 792
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT SITE 543..544
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P18177"
SQ SEQUENCE 2364 AA; 270466 MW; 3676CF127297D348 CRC64;
MNLVNKAQLQ KMAYVKFRIQ EDEYVAILNA LEEYHNMSES SVVEKYLKLK DINNLTDNYL
NTYKKSGRNK ALKKFKEYLT MEVLELKNNS LTPVEKNLHF IWIGGQINDT AINYINQWKD
VNSDYTVKVF YDSNAFLINT LKKTIVESAT NNTLESFREN LNDPEFDYNK FYRKRMEIIY
DKQKHFIDYY KSQIEENPEF IIDNIIKTYL SNEYSKDLEA LNKYIEESLN KITANNGNDI
RNLEKFADED LVRLYNQELV ERWNLAAASD ILRISMLKED GGVYLDVDML PGIQPDLFKS
INKPDSITNT SWEMIKLEAI MKYKEYIPGY TSKNFDMLDE EVQRSFESAL SSKSDKSEIF
LPLDDIKVSP LEVKIAFANN SVINQALISL KDSYCSDLVI NQIKNRYKIL NDNLNPSINE
GTDFNTTMKI FSDKLASISN EDNMMFMIKI TNYLKVGFAP DVRSTINLSG PGVYTGAYQD
LLMFKDNSTN IHLLEPELRN FEFPKTKISQ LTEQEITSLW SFNQARAKSQ FEEYKKGYFE
GALGEDDNLD FAQNTVLDKD YVSKKILSSM KTRNKEYIHY IVQLQGDKIS YEASCNLFSK
DPYSSILYQK NIEGSETAYY YSVADAEIKE IDKYRIPYQI SNKRKIKLTF IGHGKSEFNT
DTFANLDVDS LSSEIETILN LAKADISPKY IEINLLGCNM FSYSISAEET YPGKLLLKIK
DRVSELMPSI SQDSITVSAN QYEVRINEEG KREILDHSGK WINKEESIIK DISSKEYISF
NPKENKIIVK SKYLHELSTL LQEIRNNANS SDIDLEKKVM LTECEINVAS NIDRQIVEGR
IEEAKNLTSD SINYIKNEFK LIESISDSLY DLKHQNGLDD SHFISFEDIS KTENGFRIRF
INKETGNSIF IETEKEIFSE YATHISKEIS NIKDTIFDNV NGKLVKKVNL DAAHEVNTLN
SAFFIQSLIE YNTTKESLSN LSVAMKVQVY AQLFSTGLNT ITDASKVVEL VSTALDETID
LLPTLSEGLP IIATIIDGVS LGAAIKELSE TNDPLLRQEI EAKIGIMAVN LTAASTAIVT
SALGIASGFS ILLVPLAGIS AGIPSLVNNE LILQDKATKV IDYFKHISLA ETEGAFTLLD
DKIIMPQDDL VLSEIDFNNN SITLGKCEIW RAEGGSGHTL TDDIDHFFSS PSITYRKPWL
SIYDVLNIKK EKIDFSKDLM VLPNAPNRVF GYEMGWTPGF RSLDNDGTKL LDRIRDHYEG
QFYWRYFAFI ADALITKLKP RYEDTNVRIN LDGNTRSFIV PVITTEQIRK NLSYSFYGSG
GSYSLSLSPY NMNIDLNLVE NDTWVIDVDN VVKNITIESD EIQKGELIEN ILSKLNIEDN
KIILNNHTIN FYGDINESNR FISLTFSILE DINIIIEIDL VSKSYKILLS GNCMKLIENS
SDIQQKIDHI GFNGEHQKYI PYSYIDNETK YNGFIDYSKK EGLFTAEFSN ESIIRNIYMP
DSNNLFIYSS KDLKDIRIIN KGDVKLLIGN YFKDDMKVSL SFTIEDTNTI KLNGVYLDEN
GVAQILKFMN NAKSALNTSN SLMNFLESIN IKNIFYNNLD PNIEFILDTN FIISGSNSIG
QFELICDKDK NIQPYFIKFK IKETSYTLYV GNRQNLIVEP SYHLDDSGNI SSTVINFSQK
YLYGIDRYVN KVIIAPNLYT DEINITPVYK PNYICPEVII LDANYINEKI NVNINDLSIR
YVWDNDGSDL ILIANSEEDN QPQVKIRFVN VFKSDTAADK LSFNFSDKQD VSVSKIISTF
SLAAYSDGFF DYEFGLVSLD NDYFYINSFG NMVSGLIYIN DSLYYFKPPK NNLITGFTTI
DGNKYYFDPT KSGAASIGEI TIDGKDYYFN KQGILQVGVI NTSDGLKYFA PAGTLDENLE
GESVNFIGKL NIDGKIYYFE DNYRAAVEWK LLDDETYYFN PKTGEALKGL HQIGDNKYYF
DDNGIMQTGF ITINDKVFYF NNDGVMQVGY IEVNGKYFYF GKNGERQLGV FNTPDGFKFF
GPKDDDLGTE EGELTLYNGI LNFNGKIYFF DISNTAVVGW GTLDDGSTYY FDDNTAEACI
GLTVINDCKY YFDDNGIRQL GFITINDNIF YFSESGKIEL GYQNINGNYF YIDESGLVLI
GVFDTPDGYK YFAPLNTVND NIYGQAVKYS GLVRVNEDVY YFGETYKIET GWIENETDKY
YFDPETKKAY KGINVVDDIK YYFDENGIMR TGLISFENNN YYFNEDGKMQ FGYLNIKDKM
FYFGKDGKMQ IGVFNTPDGF KYFAHQNTLD ENFEGESINY TGWLDLDGKR YYFTDEYIAA
TGSLTIDGYN YYFDPDTAEL VVSE
