| Identification |
|---|
| HMDB Protein ID
| HMDBP12162 |
| Secondary Accession Numbers
| None |
| Name
| Subtilase cytotoxin subunit A |
| Synonyms
|
Not Available
|
| Gene Name
| SUBA |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Protease subunit of subtilase cytotoxin SubAB5 (PubMed:17024087). An endoprotease specific for host endoplasmic reticulum (ER) chaperone BiP/HSPA5, has no activity on human HSP70 or HSPA8 (PubMed:17024087). Cleaves between 'Leu-416' and 'Leu-417' of BiP/HSPA5 in the hinge between BiP's ATPase and protein-binding domains (PubMed:17024087). This induces host ER stress response and eventual cell death (PubMed:18005237, PubMed:18433465). Culture supernatant of E.coli expressing both subA and subB are toxic for Vero cells (African green monkey kidney cell line), Chinese hamster ovary cells and Hct-8 cells (human colonic epithelial cell line); the subunits are not toxic individually (PubMed:15226357). Purified SubAB5 is highly toxic, <0.1 pg is able to kill at least 50% of 30'000 Vero cells in a microtiter plate assay after 3 days; no cytotoxicity is seen at 24 hours (PubMed:15226357). Preabsorption with cells expressing a ganglioside GM2 mimic reduced cytotoxicity of SubAB5 by 93% in the Vero cytotoxicity assay (PubMed:15226357). Intraperitoneal injection of 200 ng of purified SubAB5 kills mice; the higher the dose the faster the mice die. Animals injected intraperitoneally with purified SubAB5 have microvascular thrombi in the brain and other organs, including the renal tubules and glomeruli (PubMed:15226357). Injection induces an unfolded response in mice (PubMed:17024087). Mice fed E.coli cells expressing cloned SubAB5 experience drastic weight loss and appear ill and lethargic (PubMed:15226357). Protein synthesis in Vero cells is transiently inhibited by SubAB5; both subunits are required for this effect (PubMed:17101670, PubMed:18005237, PubMed:18433465). Inhibition of protein synthesis is prevented by brefeldin A; cells are arrested in the G1 phase (PubMed:18005237). SubAB5 at 100 ng/ml induced caspase-dependent apoptosis in Vero cells through mitochondrial membrane damage (PubMed:19380466). |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| pathogenesis |
| Cellular Component |
| extracellular region |
| host cell cytosol |
| host cell endoplasmic reticulum lumen |
| Molecular Function |
| toxin activity |
| serine-type endopeptidase activity |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| Not Available |
| Molecular Weight
| 37493.62 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q6EZC2 |
| UniProtKB/Swiss-Prot Entry Name
| SUBA_ECOLX |
| PDB IDs
|
|
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Paton AW, Srimanote P, Woodrow MC, Paton JC: Characterization of Saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains that are virulent for humans. Infect Immun. 2001 Nov;69(11):6999-7009. doi: 10.1128/IAI.69.11.6999-7009.2001. [PubMed:11598075 ]
- Morinaga N, Yahiro K, Matsuura G, Watanabe M, Nomura F, Moss J, Noda M: Two distinct cytotoxic activities of subtilase cytotoxin produced by shiga-toxigenic Escherichia coli. Infect Immun. 2007 Jan;75(1):488-96. doi: 10.1128/IAI.01336-06. Epub 2006 Nov 13. [PubMed:17101670 ]
- Paton AW, Srimanote P, Talbot UM, Wang H, Paton JC: A new family of potent AB(5) cytotoxins produced by Shiga toxigenic Escherichia coli. J Exp Med. 2004 Jul 5;200(1):35-46. doi: 10.1084/jem.20040392. Epub 2004 Jun 28. [PubMed:15226357 ]
- Chong DC, Paton JC, Thorpe CM, Paton AW: Clathrin-dependent trafficking of subtilase cytotoxin, a novel AB5 toxin that targets the endoplasmic reticulum chaperone BiP. Cell Microbiol. 2008 Mar;10(3):795-806. doi: 10.1111/j.1462-5822.2007.01085.x. Epub 2007 Nov 27. [PubMed:18042253 ]
|
