| Identification |
|---|
| HMDB Protein ID
| HMDBP12163 |
| Secondary Accession Numbers
| None |
| Name
| Subtilase cytotoxin subunit B |
| Synonyms
|
Not Available
|
| Gene Name
| SUBB |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Receptor-binding subunit of subtilase cytotoxin SubAB5. Required for receptor-binding and thus correct trafficking in the host cell (PubMed:18042253, PubMed:17024087). Has specificity for host glycans terminating in the sialic acid N-glycolyl-alpha-neuraminic acid (Neu5Gc); each subunit in the SubB pentamer binds one Neu5Gc (PubMed:18971931). The protease subunit (SubA) cleaves host BiP/HSPA5, inducing the host endoplasmic reticulum 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 with purified SubAB5 have microvascular thrombi in the brain and other organs, including the renal tubules and glomeruli. Mice fed E.coli cells expressing cloned SubAB5 experience drastic weight loss and appear ill and lethargic (PubMed:15226357). SubB alone at 2.5 ug/ml causes vacuolation of Vero cells, which requires the V-type ATPase proton pump; treated cells die (PubMed:17101670). 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 |
| sialic acid binding |
|
| 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
| 15408.53 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
Not Available |
| Signals
|
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q6EZC3 |
| UniProtKB/Swiss-Prot Entry Name
| SUBB_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 ]
- Paton AW, Beddoe T, Thorpe CM, Whisstock JC, Wilce MC, Rossjohn J, Talbot UM, Paton JC: AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature. 2006 Oct 5;443(7111):548-52. doi: 10.1038/nature05124. [PubMed:17024087 ]
- Morinaga N, Yahiro K, Matsuura G, Moss J, Noda M: Subtilase cytotoxin, produced by Shiga-toxigenic Escherichia coli, transiently inhibits protein synthesis of Vero cells via degradation of BiP and induces cell cycle arrest at G1 by downregulation of cyclin D1. Cell Microbiol. 2008 Apr;10(4):921-9. doi: 10.1111/j.1462-5822.2007.01094.x. Epub 2007 Nov 14. [PubMed:18005237 ]
- Wolfson JJ, May KL, Thorpe CM, Jandhyala DM, Paton JC, Paton AW: Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways. Cell Microbiol. 2008 Sep;10(9):1775-86. doi: 10.1111/j.1462-5822.2008.01164.x. Epub 2008 Apr 21. [PubMed:18433465 ]
- Matsuura G, Morinaga N, Yahiro K, Komine R, Moss J, Yoshida H, Noda M: Novel subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli induces apoptosis in vero cells via mitochondrial membrane damage. Infect Immun. 2009 Jul;77(7):2919-24. doi: 10.1128/IAI.01510-08. Epub 2009 Apr 20. [PubMed:19380466 ]
- Byres E, Paton AW, Paton JC, Lofling JC, Smith DF, Wilce MC, Talbot UM, Chong DC, Yu H, Huang S, Chen X, Varki NM, Varki A, Rossjohn J, Beddoe T: Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature. 2008 Dec 4;456(7222):648-52. doi: 10.1038/nature07428. Epub 2008 Oct 29. [PubMed:18971931 ]
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