aadK encodes an aminoglycoside nucleotidyltransferase in Bacillus subtilis (strain 168). UniProt/CARD identify this entry as an aminoglycoside-modifying resistance enzyme that inactivates aminoglycoside antibiotics by adenylylation/nucleotidyl transfer. UniProt names the protein 'Aminoglycoside 6-adenylyltransferase' (accession P17585).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
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:0005737
cytoplasm
|
IDA
DOI:10.1111/j.1574-6968.1987.tb02029.x |
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:0042803
protein homodimerization activity
|
IDA
PMID:15984036 Molecular recognition of aminoglycoside antibiotics by bacte... |
KEEP AS NON CORE |
Summary: Homodimerization can be retained as a biochemical property but is not the AMR core function.
Reason: The core function is antibiotic modification; oligomerization is ancillary to the AMR annotation objective.
|
|
GO:0070566
adenylyltransferase activity
|
IDA
DOI:10.1111/j.1574-6968.1987.tb02029.x |
MODIFY |
Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
Reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
Proposed replacements:
aminoglycoside nucleotidyltransferase activity
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0070566
adenylyltransferase activity
|
IDA
PMID:15984036 Molecular recognition of aminoglycoside antibiotics by bacte... |
MODIFY |
Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
Reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
Proposed replacements:
aminoglycoside nucleotidyltransferase activity
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0070566
adenylyltransferase activity
|
IDA
PMID:17609790 Rescue of the streptomycin antibiotic activity by using stre... |
MODIFY |
Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
Reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
Proposed replacements:
aminoglycoside nucleotidyltransferase activity
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0070566
adenylyltransferase activity
|
IDA
PMID:3137862 Structure of adenylylated streptomycin synthesized enzymatic... |
MODIFY |
Summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
Reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
Proposed replacements:
aminoglycoside nucleotidyltransferase activity
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0071239
cellular response to streptomycin
|
IDA
PMID:17609790 Rescue of the streptomycin antibiotic activity by using stre... |
ACCEPT |
Summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
Reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0071239
cellular response to streptomycin
|
IDA
PMID:3137862 Structure of adenylylated streptomycin synthesized enzymatic... |
ACCEPT |
Summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
Reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0071239
cellular response to streptomycin
|
IMP
PMID:8293959 Genetic mapping in Bacillus subtilis 168 of the aadK gene wh... |
ACCEPT |
Summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
Reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
Supporting Evidence:
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0034068
aminoglycoside nucleotidyltransferase activity
|
RCA
file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml |
NEW |
Summary: NEW candidate annotation from the curated ARO->GO mapping: aminoglycoside nucleotidyltransferase activity.
Reason: The UniProt record cross-references a CARD/ARO AMR determinant, and the curated ARO->GO mapping projects the family-specific molecular function aminoglycoside nucleotidyltransferase 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
P17585 ARO:3002627 ARO:3000218 narrower RO:0002327 GO:0034068 aminoglycoside nucleotidyltransferase activity
file:genes/BACSU/aadK/aadK-uniprot.txt
CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates
|
|
GO:0046677
response to antibiotic
|
RCA
file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml |
NEW |
Summary: NEW process annotation: aadK 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/BACSU/aadK/aadK-uniprot.txt
DR CARD; ARO:3002627; aadK; ARO:0001004; antibiotic inactivation.
|
Q: Is the ARO-derived aminoglycoside nucleotidyltransferase activity annotation sufficiently specific for aadK, or is a narrower substrate/site-specific GO term warranted?
Experiment: Biochemically assay purified aadK 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: P17585. Source organism: Bacillus subtilis (strain 168).
DR CARD; ARO:3002627; aadK; ARO:0001004; antibiotic inactivation.projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv and projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml.id: P17585
gene_symbol: aadK
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:224308
label: Bacillus subtilis (strain 168)
description: aadK encodes an aminoglycoside nucleotidyltransferase in Bacillus subtilis (strain 168). UniProt/CARD identify this entry as an aminoglycoside-modifying resistance enzyme that inactivates aminoglycoside antibiotics by adenylylation/nucleotidyl transfer. UniProt names the protein 'Aminoglycoside 6-adenylyltransferase' (accession P17585).
existing_annotations:
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: The cellular location is compatible with the encoded AMR enzyme and is retained.
action: ACCEPT
reason: The location is consistent with the protein type and existing UniProt/GOA evidence.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: DOI:10.1111/j.1574-6968.1987.tb02029.x
qualifier: located_in
review:
summary: The cellular location is compatible with the encoded AMR enzyme and is retained.
action: ACCEPT
reason: The location is consistent with the protein type and existing UniProt/GOA evidence.
- term:
id: GO:0042803
label: protein homodimerization activity
evidence_type: IDA
original_reference_id: PMID:15984036
qualifier: enables
review:
summary: Homodimerization can be retained as a biochemical property but is not the AMR core function.
action: KEEP_AS_NON_CORE
reason: The core function is antibiotic modification; oligomerization is ancillary to the AMR annotation objective.
- term:
id: GO:0070566
label: adenylyltransferase activity
evidence_type: IDA
original_reference_id: DOI:10.1111/j.1574-6968.1987.tb02029.x
qualifier: enables
review:
summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
action: MODIFY
reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
proposed_replacement_terms:
- id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0070566
label: adenylyltransferase activity
evidence_type: IDA
original_reference_id: PMID:15984036
qualifier: enables
review:
summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
action: MODIFY
reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
proposed_replacement_terms:
- id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0070566
label: adenylyltransferase activity
evidence_type: IDA
original_reference_id: PMID:17609790
qualifier: enables
review:
summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
action: MODIFY
reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
proposed_replacement_terms:
- id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0070566
label: adenylyltransferase activity
evidence_type: IDA
original_reference_id: PMID:3137862
qualifier: enables
review:
summary: The existing MF term is directionally correct but less informative than the family-specific AMR activity aminoglycoside nucleotidyltransferase activity.
action: MODIFY
reason: Replace the less-specific existing term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity, direct assay support, and the curated ARO->GO mapping.
proposed_replacement_terms:
- id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0071239
label: cellular response to streptomycin
evidence_type: IDA
original_reference_id: PMID:17609790
qualifier: involved_in
review:
summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
action: ACCEPT
reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0071239
label: cellular response to streptomycin
evidence_type: IDA
original_reference_id: PMID:3137862
qualifier: involved_in
review:
summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
action: ACCEPT
reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0071239
label: cellular response to streptomycin
evidence_type: IMP
original_reference_id: PMID:8293959
qualifier: involved_in
review:
summary: The gene product is an antimicrobial-resistance determinant, so the antibiotic-response annotation is retained.
action: ACCEPT
reason: The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
evidence_type: RCA
original_reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
qualifier: enables
review:
summary: 'NEW candidate annotation from the curated ARO->GO mapping: aminoglycoside nucleotidyltransferase activity.'
action: NEW
reason: The UniProt record cross-references a CARD/ARO AMR determinant, and the curated ARO->GO mapping projects the family-specific molecular function aminoglycoside nucleotidyltransferase activity. This focused draft accepts the candidate as a curator lead for this AMR determinant.
additional_reference_ids:
- file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
- file:genes/BACSU/aadK/aadK-uniprot.txt
supported_by:
- reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
supporting_text: "P17585\tARO:3002627\tARO:3000218\tnarrower\tRO:0002327\tGO:0034068\taminoglycoside nucleotidyltransferase activity"
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- term:
id: GO:0046677
label: response to antibiotic
evidence_type: RCA
original_reference_id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
qualifier: involved_in
review:
summary: 'NEW process annotation: aadK is an AMR determinant involved in antibiotic response/resistance.'
action: NEW
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.
additional_reference_ids:
- file:genes/BACSU/aadK/aadK-uniprot.txt
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: DR CARD; ARO:3002627; aadK; ARO:0001004; antibiotic inactivation.
references:
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: DOI:10.1111/j.1574-6968.1987.tb02029.x
title: Purification and characterization of chromosomal streptomycin adenylyltransferase from derivatives of<i>Bacillus subtilis</i>Marburg 168
findings: []
- id: PMID:15984036
title: 'Molecular recognition of aminoglycoside antibiotics by bacterial defence proteins: NMR study of the structural and conformational features of streptomycin inactivation by Bacillus subtilis aminoglycoside-6-adenyl transferase.'
findings: []
- id: PMID:17609790
title: Rescue of the streptomycin antibiotic activity by using streptidine as a "decoy acceptor" for the aminoglycoside-inactivating enzyme adenyl transferase.
findings: []
- id: PMID:3137862
title: Structure of adenylylated streptomycin synthesized enzymatically by Bacillus subtilis.
findings: []
- id: PMID:8293959
title: Genetic mapping in Bacillus subtilis 168 of the aadK gene which encodes aminoglycoside 6-adenylyltransferase.
findings: []
- id: file:genes/BACSU/aadK/aadK-uniprot.txt
title: UniProt flat file for aadK (P17585)
findings:
- statement: UniProt/CARD identity and protein naming for aadK.
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
- id: file:projects/ANTIMICROBIAL_RESISTANCE/aro2go.sssom.yaml
title: Curated ARO to GO mapping set for AMR gene families
findings:
- statement: Manual ARO-to-GO mappings used to identify focused AMR annotation gains.
supporting_text: 'mapping_set_title: ARO to GO mapping (AMR gene families and resistance mechanisms)'
- id: file:projects/ANTIMICROBIAL_RESISTANCE/data/candidate_new_annotations.tsv
title: Annotation-gain candidates from ARO to GO mappings
findings:
- statement: Candidate GO annotations projected from the ARO-to-GO mapping set.
supporting_text: Candidate GO annotations that UniProtKB entries with a CARD cross-reference would gain from the
core_functions:
- description: aadK covalently modifies aminoglycoside antibiotics by nucleotidyl transfer, reducing drug activity and contributing to antibiotic resistance.
molecular_function:
id: GO:0034068
label: aminoglycoside nucleotidyltransferase activity
directly_involved_in:
- id: GO:0046677
label: response to antibiotic
supported_by:
- reference_id: file:genes/BACSU/aadK/aadK-uniprot.txt
supporting_text: 'CC -!- FUNCTION: Mediates bacterial resistance to streptomycin
CC (PubMed:17609790, PubMed:3137862). Adenylates streptomycin on the O-6
CC residue (PubMed:15984036, PubMed:17609790, PubMed:3137862). Adenylates'
locations:
- id: GO:0005737
label: cytoplasm
suggested_questions:
- question: Is the ARO-derived aminoglycoside nucleotidyltransferase activity annotation sufficiently specific for aadK, or is a narrower substrate/site-specific GO term warranted?
experts: []
suggested_experiments:
- description: Biochemically assay purified aadK against representative antibiotic substrates for the inferred AMR family and measure loss of drug activity or target modification.
experiment_type: in vitro enzyme assay