lnuA, historically named linA in Staphylococcus haemolyticus, encodes a lincosamide resistance enzyme. The enzyme family inactivates lincomycin and clindamycin by O-nucleotidylation/adenylation, producing lincosamide 5'-adenylate derivatives. The fetched GOA file is empty for this accession, and GO lacks a lincosamide O-nucleotidyltransferase molecular-function term.
Definition: Catalysis of the transfer of a nucleotidyl group from a nucleoside 5'-triphosphate donor to a lincosamide antibiotic such as lincomycin or clindamycin, producing an O-nucleotidylated lincosamide with reduced antibiotic activity.
Justification: The Lnu/LinA mechanism is a direct antibiotic-inactivation activity, but GO currently lacks a lincosamide O-nucleotidyltransferase term. The AMR mapping records this as an explicit NoTermFound gap.
Parent term: transferase activity
Mappings:
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0046677
response to antibiotic
|
RCA
file:genes/STAHA/lnuA/lnuA-uniprot.txt |
NEW |
Summary: NEW high-level process annotation for a lincosamide-resistance determinant.
Reason: The GOA TSV is empty, but the UniProt flat file carries response to antibiotic and CARD identifies the entry as lnuA, an antibiotic inactivation determinant.
Supporting Evidence:
file:genes/STAHA/lnuA/lnuA-uniprot.txt
DR CARD; ARO:3002835; lnuA; ARO:0001004; antibiotic inactivation.
PMID:3091456
confers resistance to lincomycin by inactivating it in Staphylococcus haemolyticus.
|
|
GO:0016740
transferase activity
|
RCA
PMID:2846528 Inactivation of lincosaminide antibiotics in Staphylococcus.... |
NEW |
Summary: NEW broad molecular-function annotation for lincosamide O-nucleotidyltransferase activity.
Reason: GO lacks a lincosamide O-nucleotidyltransferase term. The broad transferase parent is a defensible interim MF, but the proposed new term below is the biologically useful target.
Supporting Evidence:
PMID:2846528
Identification of lincosaminide O-nucleotidyltransferases
PMID:2846528
linA encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase
|
Q: Should GO name this term lincosamide O-nucleotidyltransferase activity or lincosamide adenylyltransferase activity?
Experiment: Reconstitute purified LnuA/LinA with lincomycin and clindamycin plus ATP, GTP, CTP, or UTP donors and quantify nucleotidylated products by NMR or LC-MS.
Type: in vitro enzyme assay
Selected because this is a high-value zero-GOA case where UniProt/CARD and old biochemical literature point to a missing GO molecular function. The UniProt entry is historically named linA, while CARD labels the ARO determinant lnuA; the review uses lnuA as the project symbol and records linA as an alias [file:genes/STAHA/lnuA/lnuA-uniprot.txt]. The original linA sequence paper supports the phenotype: linA confers resistance to lincomycin by inactivating it in S. haemolyticus PMID:3091456. The follow-up biochemical paper identifies lincosaminide O-nucleotidyltransferases and reports lincomycin 3-(5'-adenylate) and clindamycin 4-(5'-adenylate) products PMID:2846528.
The AMR mapping file records ARO:3000221 as a GO gap because GO lacks a lincosamide O-nucleotidyltransferase molecular-function term [file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml]. The review proposes that term and uses only broad GO:0016740 transferase activity as an interim MF.
id: P06107
gene_symbol: lnuA
product_type: PROTEIN
aliases:
- linA
status: DRAFT
taxon:
id: NCBITaxon:1283
label: Staphylococcus haemolyticus
description: >-
lnuA, historically named linA in Staphylococcus haemolyticus, encodes a
lincosamide resistance enzyme. The enzyme family inactivates lincomycin and
clindamycin by O-nucleotidylation/adenylation, producing lincosamide
5'-adenylate derivatives. The fetched GOA file is empty for this accession,
and GO lacks a lincosamide O-nucleotidyltransferase molecular-function term.
existing_annotations:
- term:
id: GO:0046677
label: response to antibiotic
evidence_type: RCA
original_reference_id: file:genes/STAHA/lnuA/lnuA-uniprot.txt
qualifier: involved_in
review:
summary: NEW high-level process annotation for a lincosamide-resistance determinant.
action: NEW
reason: >-
The GOA TSV is empty, but the UniProt flat file carries response to
antibiotic and CARD identifies the entry as lnuA, an antibiotic
inactivation determinant.
additional_reference_ids:
- PMID:3091456
- PMID:2846528
supported_by:
- reference_id: file:genes/STAHA/lnuA/lnuA-uniprot.txt
supporting_text: "DR CARD; ARO:3002835; lnuA; ARO:0001004; antibiotic inactivation."
- reference_id: PMID:3091456
supporting_text: "confers resistance to lincomycin by inactivating it in Staphylococcus haemolyticus."
- term:
id: GO:0016740
label: transferase activity
evidence_type: RCA
original_reference_id: PMID:2846528
qualifier: enables
review:
summary: NEW broad molecular-function annotation for lincosamide O-nucleotidyltransferase activity.
action: NEW
reason: >-
GO lacks a lincosamide O-nucleotidyltransferase term. The broad transferase
parent is a defensible interim MF, but the proposed new term below is the
biologically useful target.
additional_reference_ids:
- file:genes/STAHA/lnuA/lnuA-uniprot.txt
- file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
supported_by:
- reference_id: PMID:2846528
supporting_text: "Identification of lincosaminide O-nucleotidyltransferases"
- reference_id: PMID:2846528
supporting_text: "linA encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase"
references:
- id: file:genes/STAHA/lnuA/lnuA-uniprot.txt
title: UniProt flat file for lnuA/linA (P06107)
findings:
- statement: UniProt/CARD identifies this entry as lnuA/linA, a lincosamide antibiotic-inactivation determinant.
supporting_text: "DR CARD; ARO:3002835; lnuA; ARO:0001004; antibiotic inactivation."
- id: PMID:3091456
title: Nucleotide sequence of gene linA encoding resistance to lincosamides in Staphylococcus haemolyticus.
findings:
- statement: The original linA sequence paper supports the lincosamide resistance and inactivation phenotype.
supporting_text: "which confers resistance to lincomycin by inactivating it in Staphylococcus haemolyticus."
- id: PMID:2846528
title: Inactivation of lincosaminide antibiotics in Staphylococcus. Identification of lincosaminide O-nucleotidyltransferases and comparison of the corresponding resistance genes.
findings:
- statement: The biochemical follow-up identifies LinA-family lincosamide O-nucleotidyltransferase products.
supporting_text: "inactivation of lincomycin gave rise to lincomycin 3-(5'-adenylate)"
- id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
title: Curated ARO to GO mapping set for AMR gene families
findings:
- statement: The AMR mapping records Lnu/lincosamide nucleotidyltransferase as a GO molecular-function gap.
supporting_text: "GO has no lincosamide (O-)nucleotidyltransferase MF term"
core_functions:
- description: >-
Lincosamide O-nucleotidyltransferase activity that inactivates lincomycin
and clindamycin by producing adenylated lincosamide derivatives.
molecular_function:
id: GO:0016740
label: transferase activity
directly_involved_in:
- id: GO:0046677
label: response to antibiotic
supported_by:
- reference_id: PMID:2846528
supporting_text: "clindamycin was inactivated through its conversion to clindamycin 4-(5'-adenylate)."
- reference_id: file:genes/STAHA/lnuA/lnuA-uniprot.txt
supporting_text: "DE RecName: Full=Lincosamide resistance protein;"
proposed_new_terms:
- proposed_name: lincosamide O-nucleotidyltransferase activity
proposed_definition: >-
Catalysis of the transfer of a nucleotidyl group from a nucleoside
5'-triphosphate donor to a lincosamide antibiotic such as lincomycin or
clindamycin, producing an O-nucleotidylated lincosamide with reduced
antibiotic activity.
justification: >-
The Lnu/LinA mechanism is a direct antibiotic-inactivation activity, but GO
currently lacks a lincosamide O-nucleotidyltransferase term. The AMR mapping
records this as an explicit NoTermFound gap.
proposed_parent:
id: GO:0016740
label: transferase activity
proposed_mappings:
- predicate: skos:exactMatch
target_term:
id: ARO:3000221
label: lincosamide nucleotidyltransferase (LNU)
supported_by:
- reference_id: PMID:2846528
supporting_text: "Identification of lincosaminide O-nucleotidyltransferases"
- reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
supporting_text: "GO has no lincosamide (O-)nucleotidyltransferase MF term"
suggested_questions:
- question: Should GO name this term lincosamide O-nucleotidyltransferase activity or lincosamide adenylyltransferase activity?
experts: []
suggested_experiments:
- description: >-
Reconstitute purified LnuA/LinA with lincomycin and clindamycin plus ATP,
GTP, CTP, or UTP donors and quantify nucleotidylated products by NMR or LC-MS.
experiment_type: in vitro enzyme assay