ID ELAP_ECOLX Reviewed; 258 AA. AC P06717; P01554; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1988, sequence version 1. DT 28-JUN-2023, entry version 108. DE RecName: Full=Heat-labile enterotoxin A chain; DE AltName: Full=LT-A, porcine; DE AltName: Full=LTP-A; DE Flags: Precursor; GN Name=eltA; Synonyms=ltpA; OS Escherichia coli. OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=562; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate P307 / ETEC, and Isolate PCG86 / ETEC; RX PubMed=3546273; DOI=10.1128/jb.169.3.1352-1357.1987; RA Yamamoto T., Gojobori T., Yokota T.; RT "Evolutionary origin of pathogenic determinants in enterotoxigenic RT Escherichia coli and Vibrio cholerae O1."; RL J. Bacteriol. 169:1352-1357(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate P307 / ETEC; RA Dykes C.W., Halliday I.J., Hobden A.N., Read M.J., Harford S.; RT "A comparison of the nucleotide sequence of the A subunit of heat-labile RT enterotoxin and cholera toxin."; RL FEMS Microbiol. Lett. 26:171-174(1985). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate P307 / ETEC; RX PubMed=6279611; DOI=10.1016/s0021-9258(19)83837-1; RA Spicer E.K., Noble J.A.; RT "Escherichia coli heat-labile enterotoxin. Nucleotide sequence of the A RT subunit gene."; RL J. Biol. Chem. 257:5716-5721(1982). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-258. RC STRAIN=Isolate P307 / ETEC; RX PubMed=2266142; DOI=10.1016/s0021-9258(18)45736-5; RA Tsuji T., Inoue T., Miyama A., Okamoto K., Honda T., Miwatani T.; RT "A single amino acid substitution in the A subunit of Escherichia coli RT enterotoxin results in a loss of its toxic activity."; RL J. Biol. Chem. 265:22520-22525(1990). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40. RA Trachman J.D., Maas W.K.; RL Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases. RN [6] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). RX PubMed=2034287; DOI=10.1038/351371a0; RA Sixma T.K., Pronk S.E., Kalk K.H., Wartna E.S., van Zanten B.A.M., RA Witholt B., Hol W.G.J.; RT "Crystal structure of a cholera toxin-related heat-labile enterotoxin from RT E. coli."; RL Nature 351:371-377(1991). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS). RX PubMed=8478941; DOI=10.1006/jmbi.1993.1209; RA Sixma T.K., van Zanten B.A.M., Dauter Z., Hol W.G.J.; RT "Refined structure of Escherichia coli heat-labile enterotoxin, a close RT relative of cholera toxin."; RL J. Mol. Biol. 230:890-918(1993). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 19-258, AND MUTAGENESIS OF ARG-25; RP VAL-71; ARG-72; TYR-77; SER-81; ALA-90; VAL-115; TYR-122; HIS-125; GLU-128; RP GLU-130; SER-132 AND ARG-210. RX PubMed=7830560; DOI=10.1111/j.1365-2958.1994.tb01266.x; RA Pizza M., Domenighini M., Hol W.G.J., Giannelli V., Fontana M.R., RA Giuliani M.M., Magagnoli C., Peppoloni S., Manetti R., Rappuoli R.; RT "Probing the structure-activity relationship of Escherichia coli LT-A by RT site-directed mutagenesis."; RL Mol. Microbiol. 14:51-60(1994). RN [9] RP DISCUSSION OF SEQUENCE. RX PubMed=7623669; DOI=10.1111/j.1365-2958.1995.tb02289.x; RA Domenighini M., Pizza M., Jobling M.G., Holmes R.K., Rappuoli R.; RT "Identification of errors among database sequence entries and comparison of RT correct amino acid sequences for the heat-labile enterotoxins of RT Escherichia coli and Vibrio cholerae."; RL Mol. Microbiol. 15:1165-1167(1995). CC -!- FUNCTION: The biological activity of the toxin is produced by the A CC chain, which activates intracellular adenyl cyclase. CC -!- SUBUNIT: Heterohexamer of one A chain and of five B chains. CC -!- SIMILARITY: Belongs to the enterotoxin A family. {ECO:0000305}. 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; M15361; AAA24791.1; -; Genomic_DNA. DR EMBL; M15362; AAA24793.1; -; Genomic_DNA. DR EMBL; M35581; AAA98202.1; -; Genomic_DNA. DR EMBL; V00275; CAA23532.1; -; Genomic_DNA. DR EMBL; M57244; AAB59161.1; -; Genomic_DNA. DR EMBL; M61015; AAA24335.1; -; Genomic_DNA. DR PIR; I55231; QLECA. DR RefSeq; WP_042634421.1; NZ_WVUR01000120.1. DR PDB; 1HTL; X-ray; 2.50 A; A=19-209, C=210-258. DR PDB; 1LT3; X-ray; 2.00 A; A=19-258. DR PDB; 1LT4; X-ray; 2.00 A; A=19-251. DR PDB; 1LTA; X-ray; 2.20 A; A=19-206, C=210-258. DR PDB; 1LTB; X-ray; 2.60 A; A=22-206, C=210-254. DR PDB; 1LTG; X-ray; 2.40 A; A=19-209, C=210-258. DR PDB; 1LTI; X-ray; 2.13 A; A=19-210, C=211-258. DR PDB; 1LTS; X-ray; 1.95 A; A=22-206, C=214-254. DR PDB; 1LTT; X-ray; 2.30 A; A=22-206, C=214-254. DR PDBsum; 1HTL; -. DR PDBsum; 1LT3; -. DR PDBsum; 1LT4; -. DR PDBsum; 1LTA; -. DR PDBsum; 1LTB; -. DR PDBsum; 1LTG; -. DR PDBsum; 1LTI; -. DR PDBsum; 1LTS; -. DR PDBsum; 1LTT; -. DR AlphaFoldDB; P06717; -. DR SMR; P06717; -. DR IntAct; P06717; 1. DR EvolutionaryTrace; P06717; -. DR GO; GO:0005615; C:extracellular space; IEA:InterPro. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW. DR Gene3D; 1.20.5.240; -; 1. DR Gene3D; 3.90.210.10; Heat-Labile Enterotoxin, subunit A; 1. DR InterPro; IPR001144; Enterotoxin_A. DR Pfam; PF01375; Enterotoxin_a; 1. DR PRINTS; PR00771; ENTEROTOXINA. DR SUPFAM; SSF56399; ADP-ribosylation; 1. PE 1: Evidence at protein level; KW 3D-structure; Disulfide bond; Enterotoxin; Signal; Toxin; Virulence. FT SIGNAL 1..18 FT CHAIN 19..258 FT /note="Heat-labile enterotoxin A chain" FT /id="PRO_0000019351" FT ACT_SITE 130 FT BINDING 25..39 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT DISULFID 205..217 FT VARIANT 130 FT /note="E -> K (in inactive mutant)" FT MUTAGEN 25 FT /note="R->K: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 71 FT /note="V->D,E: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 72 FT /note="R->A,K: No effect." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 77 FT /note="Y->M: No effect." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 81 FT /note="S->K: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 90 FT /note="A->E,H,R: No effect." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 115 FT /note="V->K: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 122 FT /note="Y->D,K: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 125 FT /note="H->E: Strongly reduces toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 128 FT /note="E->S: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 130 FT /note="E->S: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 132 FT /note="S->E,K: Abolishes toxicity." FT /evidence="ECO:0000269|PubMed:7830560" FT MUTAGEN 210 FT /note="R->N: No effect." FT /evidence="ECO:0000269|PubMed:7830560" FT CONFLICT 37..39 FT /note="SGG -> FRS (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT CONFLICT 45 FT /note="Missing (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT CONFLICT 93 FT /note="S -> Y (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT CONFLICT 100..110 FT /note="TYYIYVIATAP -> LTIYIVIA (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT CONFLICT 119..120 FT /note="LG -> IS (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="R -> G (in Ref. 4; AAB59161)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="N -> D (in Ref. 3; CAA23532)" FT /evidence="ECO:0000305" FT STRAND 23..29 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 31..37 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:1LTI" FT STRAND 51..53 FT /evidence="ECO:0007829|PDB:1LTA" FT HELIX 59..64 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 77..83 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 84..94 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 95..97 FT /evidence="ECO:0007829|PDB:1LTI" FT STRAND 99..106 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 115..119 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 120..122 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 126..128 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 130..134 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 142..149 FT /evidence="ECO:0007829|PDB:1LTS" FT STRAND 152..159 FT /evidence="ECO:0007829|PDB:1LT3" FT HELIX 165..170 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 176..179 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 190..193 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 197..200 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 215..240 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 241..244 FT /evidence="ECO:0007829|PDB:1LTS" FT HELIX 250..253 FT /evidence="ECO:0007829|PDB:1LTS" SQ SEQUENCE 258 AA; 29902 MW; 2F0786442619F81F CRC64; MKNITFIFFI LLASPLYANG DRLYRADSRP PDEIKRSGGL MPRGHNEYFD RGTQMNINLY DHARGTQTGF VRYDDGYVST SLSLRSAHLA GQSILSGYST YYIYVIATAP NMFNVNDVLG VYSPHPYEQE VSALGGIPYS QIYGWYRVNF GVIDERLHRN REYRDRYYRN LNIAPAEDGY RLAGFPPDHQ AWREEPWIHH APQGCGNSSR TITGDTCNEE TQNLSTIYLR EYQSKVKRQI FSDYQSEVDI YNRIRDEL //