mcr2

UniProt ID: A0A1C3NEV1
Organism: Escherichia coli
Review Status: DRAFT
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Gene Description

mcr2 encodes a membrane-associated phosphoethanolamine transferase in Escherichia coli. 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 'Phosphatidylethanolamine transferase Mcr-2' (accession A0A1C3NEV1).

Existing Annotations Review

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/ECOLX/mcr2/mcr2-uniprot.txt
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers
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/ECOLX/mcr2/mcr2-uniprot.txt
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers
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.
Supporting Evidence:
file:genes/ECOLX/mcr2/mcr2-uniprot.txt
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers
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.
Supporting Evidence:
file:genes/ECOLX/mcr2/mcr2-uniprot.txt
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers
GO:0005886 plasma membrane
ISS
GO_REF:0000024 		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: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
A0A1C3NEV1 ARO:3004110 ARO:3004112 narrower RO:0002327 GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity
file:genes/ECOLX/mcr2/mcr2-uniprot.txt
CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers
GO:0046677 response to antibiotic
RCA
file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml 		NEW
Summary: NEW process annotation: mcr2 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/ECOLX/mcr2/mcr2-uniprot.txt
DR CARD; ARO:3004110; MCR-2.1; ARO:0001001; antibiotic target alteration.

Core Functions

mcr2 modifies lipid A with phosphoethanolamine in the bacterial membrane, a target-modification mechanism that reduces polymyxin/colistin susceptibility.

Molecular Function:
phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity
Directly Involved In:
response to antibiotic
Cellular Locations:
plasma membrane
Supporting Evidence:
  • file:genes/ECOLX/mcr2/mcr2-uniprot.txt
    CC -!- FUNCTION: Probably catalyzes the addition of a phosphoethanolamine CC moiety to lipid A (PubMed:30194678). Phosphoethanolamine modification CC of lipid A confers polymyxin resistance (By similarity). Confers

References

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Suggested Questions for Experts

Q: Is the ARO-derived phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity annotation sufficiently specific for mcr2, or is a narrower substrate/site-specific GO term warranted?

Suggested Experiments

Experiment: Biochemically assay purified mcr2 against representative antibiotic substrates for the inferred AMR family and measure loss of drug activity or target modification.

Type: in vitro enzyme assay

📚 Additional Documentation

Notes

(mcr2-notes.md)

Notes: mcr2

Focused AMR batch review. UniProt accession: A0A1C3NEV1. Source organism: Escherichia coli.

  • UniProt/CARD provenance: DR CARD; ARO:3004110; MCR-2.1; ARO:0001001; antibiotic target alteration.
  • ARO-to-GO candidate: GO:0043838 (phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity) from projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv and projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml.
  • This is a DRAFT focused review intended to cover the AMR annotation gap; it has not had a gene-specific deep-research pass.

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