HST3_ECOLX
ID HST3_ECOLX Reviewed; 72 AA.
AC P07965; P26588;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=Heat-stable enterotoxin A3/A4;
DE AltName: Full=ST-H;
DE AltName: Full=ST-IB;
DE AltName: Full=STA3/STA4;
DE AltName: INN=Linaclotide;
DE Flags: Precursor;
GN Name=sta3; Synonyms=sta4;
OS Escherichia coli.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=562;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3071819; DOI=10.1016/0147-619x(88)90006-6;
RA Stieglitz H., Cervantes L., Robledo R., Fonseca R., Covarrubias L.,
RA Bolivar F., Kupersztoch Y.M.;
RT "Cloning, sequencing, and expression in Ficoll-generated minicells of an
RT Escherichia coli heat-stable enterotoxin gene.";
RL Plasmid 20:42-53(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=153837-2;
RX PubMed=6341230; DOI=10.1128/iai.39.3.1167-1174.1983;
RA Moseley S.L., Hardy J.W., Huq M.I., Echeverria P., Falkow S.;
RT "Isolation and nucleotide sequence determination of a gene encoding a heat-
RT stable enterotoxin of Escherichia coli.";
RL Infect. Immun. 39:1167-1174(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2190361; DOI=10.1016/0041-0101(90)90085-l;
RA Zhou X., Shen L.P., Chi C.W.;
RT "Isolation and nucleotide sequence determination of a gene encoding a heat-
RT stable enterotoxin of Escherichia coli.";
RL Toxicon 28:453-456(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2643580; DOI=10.1128/iai.57.2.645-648.1989;
RA Guzman-Verduzio L.M., Kupersztoch Y.M.;
RT "Rectification of two Escherichia coli heat-stable enterotoxin allele
RT sequences and lack of biological effect of changing the carboxy-terminal
RT tyrosine to histidine.";
RL Infect. Immun. 57:645-648(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2680769; DOI=10.1016/0378-1119(89)90182-0;
RA Dwarakanath P., Visweswariah S.S., Subrahmanyam Y.V.B.K., Shanthi G.,
RA Jagannatha H.M., Balganesh T.S.;
RT "Cloning and hyperexpression of a gene encoding the heat-stable toxin of
RT Escherichia coli.";
RL Gene 81:219-226(1989).
RN [6]
RP PROTEIN SEQUENCE OF 54-72.
RX PubMed=6759126; DOI=10.1111/j.1432-1033.1982.tb07047.x;
RA Aimoto S., Takao T., Shimonishi Y., Hara S., Takeda T., Takeda Y.,
RA Miwatani T.;
RT "Amino-acid sequence of a heat-stable enterotoxin produced by human
RT enterotoxigenic Escherichia coli.";
RL Eur. J. Biochem. 129:257-263(1982).
RN [7]
RP DISULFIDE BONDS.
RX PubMed=3552731; DOI=10.1016/0014-5793(87)80134-5;
RA Shimonishi Y., Hidaka Y., Koizumi M., Hane M., Aimoto S., Takeda T.,
RA Miwatani T., Takeda Y.;
RT "Mode of disulfide bond formation of a heat-stable enterotoxin (STh)
RT produced by a human strain of enterotoxigenic Escherichia coli.";
RL FEBS Lett. 215:165-170(1987).
RN [8]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2187146; DOI=10.1111/j.1365-2958.1990.tb00593.x;
RA Rasheed J.K., Guzman-Verduzco L.M., Kupersztoch Y.M.;
RT "Two precursors of the heat-stable enterotoxin of Escherichia coli:
RT evidence of extracellular processing.";
RL Mol. Microbiol. 4:265-273(1990).
CC -!- FUNCTION: Toxin which activates the particulate form of guanylate
CC cyclase and increases cyclic GMP levels within the host intestinal
CC epithelial cells.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PHARMACEUTICAL: Linaclotide is under clinical trial by Microbia to be
CC used to improve bowel function in patients with chronic constipation.
CC Linaclotide corresponds to residues 59 to 72 with Tyr-62.
CC -!- SIMILARITY: Belongs to the heat-stable enterotoxin family.
CC {ECO:0000305}.
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DR EMBL; J03311; AAA24652.1; -; Genomic_DNA.
DR EMBL; M34916; AAA23990.1; -; Genomic_DNA.
DR EMBL; M18346; AAA23730.1; -; Genomic_DNA.
DR EMBL; M29255; AAA24686.1; -; Genomic_DNA.
DR PIR; JS0292; QHECIB.
DR PIR; JT0373; QHEC4.
DR RefSeq; WP_013188501.1; NZ_UGEK01000002.1.
DR RefSeq; YP_008531452.1; NC_022333.1.
DR PDB; 7CSS; NMR; -; A=59-71.
DR PDB; 7D37; NMR; -; A=59-71.
DR PDBsum; 7CSS; -.
DR PDBsum; 7D37; -.
DR AlphaFoldDB; P07965; -.
DR SMR; P07965; -.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR019806; Heat-stable_enterotox_CS.
DR InterPro; IPR001489; Heat-stable_enterotox_STa.
DR Pfam; PF02048; Enterotoxin_ST; 1.
DR PROSITE; PS00273; ENTEROTOXIN_H_STABLE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Enterotoxin;
KW Pharmaceutical; Secreted; Signal; Toxin; Virulence.
FT SIGNAL 1..19
FT PROPEP 20..53
FT /evidence="ECO:0000269|PubMed:6759126"
FT /id="PRO_0000035130"
FT PEPTIDE 54..72
FT /note="Heat-stable enterotoxin A3/A4"
FT /id="PRO_0000035131"
FT DISULFID 59..64
FT /evidence="ECO:0000269|PubMed:3552731"
FT DISULFID 60..68
FT /evidence="ECO:0000269|PubMed:3552731"
FT DISULFID 63..71
FT /evidence="ECO:0000269|PubMed:3552731"
FT CONFLICT 19
FT /note="A -> P (in Ref. 2; AAA23990)"
FT /evidence="ECO:0000305"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:7D37"
SQ SEQUENCE 72 AA; 7909 MW; 1C5C9292BFCBA6BA CRC64;
MKKSILFIFL SVLSFSPFAQ DAKPVESSKE KITLESKKCN IAKKSNKSGP ESMNSSNYCC
ELCCNPACTG CY
