mcr-4 encodes a membrane-associated phosphoethanolamine transferase in Salmonella sp. UniProt/CARD identify this entry as an MCR-family polymyxin resistance determinant. The expected core activity is transfer of phosphoethanolamine from phosphatidylethanolamine to lipid A, which lowers polymyxin/colistin binding and confers antibiotic resistance. UniProt names the protein 'MCR-4' (accession A0A222YQC1).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The cellular location is compatible with the encoded AMR enzyme and is retained. Reason: The location is consistent with the protein type and existing UniProt/GOA evidence. |
| GO:0009244 lipopolysaccharide core region biosynthetic process | IEA GO_REF:0000118 | MARK AS OVER ANNOTATED | Summary: This over-propagates lipid A phosphoethanolamine transfer into LPS core-region biosynthesis. Reason: MCR proteins modify lipid A to confer polymyxin resistance; they are not core LPS oligosaccharide biosynthetic enzymes. Supporting Evidence: file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Correct but broad membrane location; the more informative location for this determinant is plasma membrane. Reason: Use plasma membrane rather than the generic membrane term where possible. Proposed replacements: plasma membrane Supporting Evidence: file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | MODIFY | Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity. Reason: Replace the broad or over-specific electronic term 'transferase activity, transferring phosphorus-containing groups' with phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping. Proposed replacements: phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity Supporting Evidence: file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
| GO:0016776 phosphotransferase activity, phosphate group as acceptor | IEA GO_REF:0000118 | MODIFY | Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity. Reason: Replace the broad or over-specific electronic term 'phosphotransferase activity, phosphate group as acceptor' with phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping. Proposed replacements: phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity Supporting Evidence: file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
| GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity | RCA file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml | NEW | Summary: NEW candidate annotation from the curated ARO->GO mapping: phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity. Reason: The UniProt record cross-references a CARD/ARO AMR determinant, and the curated ARO->GO mapping projects the family-specific molecular function phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity. This focused draft accepts the candidate as a curator lead for this AMR determinant. Supporting Evidence: file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv A0A222YQC1 ARO:3004325 ARO:3004112 narrower RO:0002327 GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
| GO:0046677 response to antibiotic | RCA file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml | NEW | Summary: NEW process annotation: mcr-4 is an AMR determinant involved in antibiotic response/resistance. Reason: CARD/ARO identity places this gene in an antimicrobial-resistance determinant family; response to antibiotic is the appropriate high-level GO biological process for the resistance role. Supporting Evidence: file:genes/SALSP/mcr-4/mcr-4-uniprot.txt DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration. |
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Download this section (compressed HTML)Q: Is the ARO-derived phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity annotation sufficiently specific for mcr-4, or is a narrower substrate/site-specific GO term warranted?
Experiment: Biochemically assay purified mcr-4 against representative antibiotic substrates for the inferred AMR family and measure loss of drug activity or target modification.
Type: in vitro enzyme assay
Focused AMR batch review. UniProt accession: A0A222YQC1. Source organism: Salmonella sp.
DR CARD; ARO:3004325; MCR-4.1; ARO:0001001; antibiotic target alteration.projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv and projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml.Loading supporting content…
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