Secreted microfilarial endochitinase (EC 3.2.1.14) of the lymphatic filarial nematode Brugia malayi, also known historically as the MF1 antigen. The protein is a glycosyl hydrolase family 18 (GH18) chitinase comprising a catalytic GH18 domain and a C-terminal type-2 chitin-binding (CBM14) module, and it catalyses the random endo-hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins. Expression is restricted to the microfilarial (first-stage larval) stage and coincides developmentally with the onset of infectivity to the mosquito vector. The enzyme is stored in the inner body of the microfilaria and is secreted; it is one of the most abundant proteins in microfilarial excretory-secretory products. Functionally it is implicated in degrading chitin-containing structures during parasite development and transmission, including a role in exsheathment of the microfilaria within the mosquito. As a stage-specific, secretion-associated antigen it is a recognized transmission-blocking vaccine candidate in brugian filariasis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0004553
hydrolase activity, hydrolyzing O-glycosyl compounds
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: Correct but more general than the specific function. This protein is a GH18 endochitinase; the broad parent O-glycosyl-hydrolase term should be replaced by the specific chitinase activity supported by the catalytic activity (EC 3.2.1.14) and experimental chitinolytic data.
Reason: The GH18 catalytic domain and demonstrated chitin-degrading activity indicate chitinase activity (GO:0004568, a child of GO:0004553) is the informative molecular-function term.
Proposed replacements:
chitinase activity
|
|
GO:0004568
chitinase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Accurate core molecular function. The protein is a GH18-family chitinase with the EC 3.2.1.14 catalytic activity; recombinant Brugia malayi microfilarial chitinase has demonstrated chitin-degrading activity, and chitinolytic bands comigrate with the MF1 antigen.
|
|
GO:0005576
extracellular region
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Consistent with the biology. The enzyme carries an N-terminal signal peptide, is secreted from the inner body of the microfilaria, and is among the most abundant proteins in microfilarial excretory-secretory products, so localization to the extracellular region is appropriate. Localization is not the core function, so retained as non-core.
|
|
GO:0005975
carbohydrate metabolic process
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: Correct but over-general. As a chitinase the protein participates in carbohydrate metabolism, but the specific and informative process is chitin catabolism (GO:0006032), which is independently annotated. The broad parent term adds little.
Reason: Chitin catabolic process (GO:0006032) is the specific child term capturing the actual biological role; the generic carbohydrate metabolic process is uninformative for this enzyme.
Proposed replacements:
chitin catabolic process
|
|
GO:0006032
chitin catabolic process
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Accurate core biological process. Endochitinase activity on chitin (degradation of chitin-containing structures during microfilarial development, transmission, and exsheathment in the mosquito vector) is well supported and represents the gene's principal biological role.
|
|
GO:0008061
chitin binding
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Supported by domain architecture. The protein contains a C-terminal type-2 chitin-binding (CBM14) domain in addition to the GH18 catalytic domain, and multiple residues are annotated as chitin-binding. Chitin binding is a real molecular activity but is ancillary to the catalytic chitinase function, so it is retained as non-core.
|
|
GO:0008843
endochitinase activity
|
IEA
GO_REF:0000003 |
ACCEPT |
Summary: Accurate and the most specific molecular-function term for this protein. The UniProt catalytic activity (random endo-hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and chitodextrins; EC 3.2.1.14) is precisely endochitinase activity. Accepted as the core molecular function.
|
id: P29030
gene_symbol: mf1
product_type: PROTEIN
status: INITIALIZED
taxon:
id: NCBITaxon:6279
label: Brugia malayi
description: >-
Secreted microfilarial endochitinase (EC 3.2.1.14) of the lymphatic filarial
nematode Brugia malayi, also known historically as the MF1 antigen. The protein
is a glycosyl hydrolase family 18 (GH18) chitinase comprising a catalytic GH18
domain and a C-terminal type-2 chitin-binding (CBM14) module, and it catalyses
the random endo-hydrolysis of N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages
in chitin and chitodextrins. Expression is restricted to the microfilarial
(first-stage larval) stage and coincides developmentally with the onset of
infectivity to the mosquito vector. The enzyme is stored in the inner body of
the microfilaria and is secreted; it is one of the most abundant proteins in
microfilarial excretory-secretory products. Functionally it is implicated in
degrading chitin-containing structures during parasite development and
transmission, including a role in exsheathment of the microfilaria within the
mosquito. As a stage-specific, secretion-associated antigen it is a recognized
transmission-blocking vaccine candidate in brugian filariasis.
existing_annotations:
- term:
id: GO:0004553
label: hydrolase activity, hydrolyzing O-glycosyl compounds
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
Correct but more general than the specific function. This protein is a
GH18 endochitinase; the broad parent O-glycosyl-hydrolase term should be
replaced by the specific chitinase activity supported by the catalytic
activity (EC 3.2.1.14) and experimental chitinolytic data.
action: MODIFY
proposed_replacement_terms:
- id: GO:0004568
label: chitinase activity
reason: >-
The GH18 catalytic domain and demonstrated chitin-degrading activity
indicate chitinase activity (GO:0004568, a child of GO:0004553) is the
informative molecular-function term.
- term:
id: GO:0004568
label: chitinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: >-
Accurate core molecular function. The protein is a GH18-family chitinase
with the EC 3.2.1.14 catalytic activity; recombinant Brugia malayi
microfilarial chitinase has demonstrated chitin-degrading activity, and
chitinolytic bands comigrate with the MF1 antigen.
action: ACCEPT
- term:
id: GO:0005576
label: extracellular region
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: >-
Consistent with the biology. The enzyme carries an N-terminal signal
peptide, is secreted from the inner body of the microfilaria, and is among
the most abundant proteins in microfilarial excretory-secretory products,
so localization to the extracellular region is appropriate. Localization is
not the core function, so retained as non-core.
action: KEEP_AS_NON_CORE
- term:
id: GO:0005975
label: carbohydrate metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: >-
Correct but over-general. As a chitinase the protein participates in
carbohydrate metabolism, but the specific and informative process is chitin
catabolism (GO:0006032), which is independently annotated. The broad parent
term adds little.
action: MODIFY
proposed_replacement_terms:
- id: GO:0006032
label: chitin catabolic process
reason: >-
Chitin catabolic process (GO:0006032) is the specific child term capturing
the actual biological role; the generic carbohydrate metabolic process is
uninformative for this enzyme.
- term:
id: GO:0006032
label: chitin catabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: >-
Accurate core biological process. Endochitinase activity on chitin
(degradation of chitin-containing structures during microfilarial
development, transmission, and exsheathment in the mosquito vector) is well
supported and represents the gene's principal biological role.
action: ACCEPT
- term:
id: GO:0008061
label: chitin binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: >-
Supported by domain architecture. The protein contains a C-terminal type-2
chitin-binding (CBM14) domain in addition to the GH18 catalytic domain, and
multiple residues are annotated as chitin-binding. Chitin binding is a real
molecular activity but is ancillary to the catalytic chitinase function, so
it is retained as non-core.
action: KEEP_AS_NON_CORE
- term:
id: GO:0008843
label: endochitinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000003
qualifier: enables
review:
summary: >-
Accurate and the most specific molecular-function term for this protein.
The UniProt catalytic activity (random endo-hydrolysis of
N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and
chitodextrins; EC 3.2.1.14) is precisely endochitinase activity. Accepted
as the core molecular function.
action: ACCEPT
core_functions:
- description: >-
Endochitinase that catalyses the random endo-hydrolysis of
N-acetyl-beta-D-glucosaminide (1->4)-beta-linkages in chitin and
chitodextrins (EC 3.2.1.14), degrading chitin-containing structures during
microfilarial development and transmission.
molecular_function:
id: GO:0008843
label: endochitinase activity
supported_by:
- reference_id: PMID:1542646
directly_involved_in:
- id: GO:0006032
label: chitin catabolic process
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000003
title: Gene Ontology annotation based on Enzyme Commission mapping
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:1542646
title: Transmission-blocking antibodies recognize microfilarial chitinase in brugian
lymphatic filariasis.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified primary report (Fuhrman et al., PNAS 1992) that cloned the
MF1 antigen, showed it is a microfilarial chitinase with chitin-degrading
activity comigrating with the antigen, and proposed its role in degrading
chitin-containing structures during development/transmission. Directly
establishes the chitinase function of P29030. Cached publication text is
abstract-only; no verbatim supporting_text quoted.