PA1611 is an orphan hybrid sensor histidine kinase of the Pseudomonas aeruginosa inner membrane. It has two transmembrane helices flanking a periplasmic sCache-like sensor region, a cytoplasmic HAMP linker, a HisKA dimerisation/phosphoacceptor domain with the conserved His275, an HATPase_c catalytic domain and a C-terminal receiver (REC) domain with the phosphoacceptor Asp565; it has no histidine phosphotransfer (Hpt) domain. The cytoplasmic part autophosphorylates and transfers the phosphoryl group, through its REC domain, to the separate histidine phosphotransfer protein HptB (PA3345), which passes it on to the response regulator/phosphatase HsbR (PA3346). This HptB multistep phosphorelay, which is also fed by the hybrid kinases ErcS' and SagS, controls flagellar and chemotactic behaviour, swarming and twitching motility and biofilm formation. Crystal structures of the REC domain (residues 507-651) show a canonical (beta/alpha)5 receiver fold that binds Mg2+ or Ca2+ at the active site. The signal it senses is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000155 phosphorelay sensor kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PAINT node PTN001976860. PA1611 is itself one of the three seeds, which is expected and reflects its own experimental phosphotransfer data; the other seeds are M. tuberculosis SenX3 (IDA) and P. aeruginosa PA3271 (IDA). PA1611 has an intact HisKA domain with the conserved His and an HATPase_c domain. Reason: Core activity of PA1611, supported by its own in vitro autophosphorylation/phosphotransfer data and by domain architecture; the node is well seeded. Supporting Evidence: PMID:16182517 We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1 PMID:32939285 between the cytosolic part of PA1611 (a.a. 202–652) and HptB has been confirmed with file:PSEAE/PA1611/PA1611-uniprot.txt PF00512; HisKA file:PSEAE/PA1611/PA1611-uniprot.txt PF02518; HATPase_c |
| GO:0000155 phosphorelay sensor kinase activity | IDA PMID:16182517 Identification of an HptB-mediated multi-step phosphorelay i... | ACCEPT | Summary: PseudoCAP IDA and one of three seeds of the PTN001976860 IBD. Lin et al. 2006 showed PA1611-to-HptB-to-PA3346 phosphotransfer; the same laboratory later states that the transfer from the PA1611 cytoplasmic part (aa 202-652) to HptB was confirmed with [gamma-32P]ATP in that work, i.e. a direct biochemical assay of autophosphorylation and phosphotransfer. Reason: Seed is SOUND: a direct in vitro phosphorylation assay on the PA1611 kinase portion supports the sensor histidine kinase activity. The signal sensed is unknown, but GO:0000155 does not require it to be identified. Supporting Evidence: PMID:16182517 We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1 PMID:32939285 between the cytosolic part of PA1611 (a.a. 202–652) and HptB has been confirmed with |
| GO:0000155 phosphorelay sensor kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping from the HisKA dimerisation/phosphoacceptor domain; consistent with the experimental and IBA rows. Reason: Same claim as the IDA and IBA rows; domain architecture supports it. Supporting Evidence: file:PSEAE/PA1611/PA1611-uniprot.txt PF00512; HisKA PMID:16182517 We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1 |
| GO:0000160 phosphorelay signal transduction system | IBA GO_REF:0000033 | ACCEPT | Summary: IBA phosphorelay signal transduction system. PA1611 is the entry kinase of the HptB multistep phosphorelay. Reason: PA1611 directly performs the first steps (autophosphorylation, His-Asp transfer, transfer to HptB) of a phosphorelay. Supporting Evidence: PMID:16182517 We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1 PMID:32939285 between the cytosolic part of PA1611 (a.a. 202–652) and HptB has been confirmed with PMID:27792789 Several upstream sensors have been proposed for the HptB pathway, including PA1611 |
| GO:0000160 phosphorelay signal transduction system | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (UniProt keyword/ARBA combined) phosphorelay signal transduction; same claim as the IBA row. Reason: Consistent with the experimentally supported HptB phosphorelay. Supporting Evidence: PMID:16182517 We herein demonstrate that the hybrid sensor PA1611 carries out specific signal transduction, through HptB (PA3345), to the response regulator PA3346 in Pseudomonas aeruginosa PAO1 file:PSEAE/PA1611/PA1611-uniprot.txt PF00072; Response_reg |
| GO:0004673 protein histidine kinase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: Protein histidine kinase activity from the EC 2.7.13.3 mapping. True, but GO:0000155 phosphorelay sensor kinase activity, accepted here, is_a this term. Reason: Entailed by the accepted GO:0000155. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA plasma membrane (is_active_in). PA1611 has two predicted transmembrane helices flanking a periplasmic sensor region, the standard topology of an inner-membrane sensor kinase. Reason: Topology (Phobius TM helices 12-34 and 167-186) and the periplasmic sCache-like domain place it in the inner (plasma) membrane; no direct localisation study, but the claim is sound. Supporting Evidence: file:PSEAE/PA1611/PA1611-uniprot.txt TRANSMEM 167..186 file:PSEAE/PA1611/PA1611-uniprot.txt PF09984; sCache_4 |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (cell inner membrane) to plasma membrane; same claim as the IBA row. Reason: Consistent with the two TM helices. Supporting Evidence: file:PSEAE/PA1611/PA1611-uniprot.txt TRANSMEM 167..186 |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO signal transduction. True, but GO:0000160 phosphorelay signal transduction system, accepted here, is_a descendant. Reason: Entailed by the accepted GO:0000160. |
| GO:0009927 histidine phosphotransfer kinase activity | IBA GO_REF:0000033 | REMOVE | Summary: IBA histidine phosphotransfer kinase activity from PTN001976860, seeded by E. coli RcsD (an Hpt-domain phosphotransferase) and yeast SLN1. GO:0009927 is defined as serving as the phospho-His intermediate between a hybrid kinase and a response regulator, the role of an Hpt domain or protein. PA1611 has no Hpt domain (HAMP, HisKA, HATPase_c and REC only) and passes its phosphoryl group to the separate Hpt protein HptB, which is the protein that performs this activity in the pathway. Reason: Over-propagated IBA argued on domain-architecture grounds: PA1611 is the hybrid kinase, not the Hpt intermediate. The Hpt role in this relay belongs to HptB (PA3345). Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN001976860 · PTN001976860 SUPPORTS SOURCE BUT NOT TARGET The node mixes Hpt-domain proteins (RcsD) with hybrid kinases lacking an Hpt domain (PA1611, PA3271, SLN1). GO:0009927 suits only members with an Hpt domain. UniProtKB:P39838 · RcsD (E. coli) SUPPORTS SOURCE BUT NOT TARGET RcsD carries a C-terminal HPt domain; the activity is real for it but depends on that domain. SGD:S000001409 · SLN1 (yeast) UNRESOLVED SLN1 has HisKA and REC but no Hpt domain (its Hpt partner is YPD1); its own IDA/IMP for GO:0009927 (PMID:12455952) was not read here. Supporting Evidence: file:PSEAE/PA1611/PA1611-uniprot.txt PF00512; HisKA file:PSEAE/PA1611/PA1611-uniprot.txt PF00072; Response_reg file:PSEAE/PA1611/PA1611-notes.md PA1611 has no Hpt domain |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO membrane from the HAMP domain. True, but plasma membrane, accepted here, is the specific location. Reason: Entailed by the accepted GO:0005886 plasma membrane. |
| GO:0016301 kinase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: UniRule kinase activity. True but uninformative; GO:0000155 entails it. Reason: Entailed by the accepted GO:0000155. |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: UniRule transferase activity. True but uninformative; GO:0000155 entails it. Reason: Entailed by the accepted GO:0000155. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO transferase activity, transferring phosphorus-containing groups. True but uninformative; GO:0000155 entails it. Reason: Entailed by the accepted GO:0000155. |
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Download this section (compressed HTML)Q: What signal does the periplasmic sCache-like domain of PA1611 detect, and does it modulate PA1611 autokinase activity or its reported interaction with RetS?
Q: Should the GO:0009927 IBD at PTN001976860 be restricted to the RcsD-like members that have an HPt domain, given that PA1611, PA3271 and SLN1 lack one?
Experiment: Screen ligands against the purified periplasmic sensor domain (thermal shift or ITC) and test hit compounds for effects on PA1611 autophosphorylation and HptB phosphorylation in vitro.
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