Acadvl (CG7461; dACADVL) is the Drosophila melanogaster ortholog of human very-long-chain specific acyl-CoA dehydrogenase (VLCAD). It is an FAD-dependent flavoenzyme of the acyl-CoA dehydrogenase (ACAD) family that catalyzes the first, committed step of each cycle of mitochondrial fatty acid beta-oxidation: the stereospecific alpha,beta-dehydrogenation of saturated and unsaturated acyl-CoA thioesters, producing the corresponding trans-2-enoyl-CoA and transferring the abstracted electrons to the electron-transfer flavoprotein (ETF). Like its mammalian counterpart it acts specifically on long-chain and very-long-chain fatty acyl-CoAs (primary chains of roughly 12 to 24 carbons, e.g. palmitoyl-CoA, C16), distinguishing it from the medium- and short-chain acyl-CoA dehydrogenases. The protein carries the characteristic ACAD N-terminal, middle and C-terminal domains together with the extra ACAD9/ACADVL-type C-terminal extension, is FAD-dependent, and is a homodimer that associates as a peripheral protein with the matrix face of the mitochondrial inner membrane. Through this activity Acadvl feeds long-chain dietary and stored fatty acids into beta-oxidation for the production of acetyl-CoA and cellular energy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0017099
very-long-chain fatty acyl-CoA dehydrogenase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetically inferred very-long-chain acyl-CoA dehydrogenase activity (PANTHER PTN000856877, whose leaves include the experimentally characterized human VLCAD P49748). This is the defining catalytic activity of the VLCAD family and, together with the CDD VLCAD hit (cd01161) and the PANTHER subfamily assignment (PTHR43884:SF11, very long-chain specific acyl-CoA dehydrogenase), is well supported at this specific level for the fly ortholog. This captures the core molecular function.
Reason: The IBA call is grounded in a tree whose experimental leaves (human ACADVL) directly demonstrate very-long-chain acyl-CoA dehydrogenase activity, and the fly protein carries the VLCAD-specific domain architecture and subfamily assignment. UniProt assigns EC 1.3.8.9 (very-long-chain) to this protein.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
very long-chain specific acyl-CoA dehydrogenase acts specifically on
|
|
GO:0000062
fatty-acyl-CoA binding
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Phylogenetically inferred binding of the acyl-CoA substrate. VLCAD-family enzymes must bind fatty-acyl-CoA thioesters in order to dehydrogenate them, so this annotation is correct but ancillary (a prerequisite of the catalytic activity rather than a separate core function).
Reason: Substrate binding is subsumed by the catalytic dehydrogenase activity, which better represents the core molecular function; retained as a supporting non-core annotation.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
acts specifically on fatty acyl-CoAs
|
|
GO:0003995
acyl-CoA dehydrogenase activity
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: InterPro-based electronic annotation (IPR006089) to the general acyl-CoA dehydrogenase activity term. The protein contains the ACAD active-site signature (PROSITE PS00072/PS00073) and is a bona fide family member, so the term is correct but broader than the specific VLCAD/LCAD activities that are also annotated.
Reason: Correct general parent term subsumed by the specific GO:0017099 (very-long-chain) and GO:0004466 (long-chain) activities used as core; retained as a supporting non-core annotation.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Belongs to the acyl-CoA dehydrogenase family.
|
|
GO:0004466
long-chain fatty acyl-CoA dehydrogenase activity
|
IEA
GO_REF:0000003 |
ACCEPT |
Summary: Electronic annotation from EC mapping (EC 1.3.8.8) derived from UniProt. In addition to its very-long-chain activity, VLCAD has well-documented long-chain acyl-CoA dehydrogenase activity (classically assayed with palmitoyl-CoA, C16), so this is a valid and biologically accurate term for the fly ortholog.
Reason: UniProt assigns EC 1.3.8.8 (long-chain acyl-CoA dehydrogenase, RHEA:17721) to this protein and it acts on fatty acyl-CoAs down to ~12 carbons. Consistent with the ISS annotation to the same term.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
a long-chain 2,3-saturated fatty acyl-CoA + oxidized
|
|
GO:0005743
mitochondrial inner membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Electronic annotation from UniProt subcellular-location mapping. VLCAD-family enzymes are peripheral proteins of the mitochondrial inner membrane, distinguishing them from the soluble matrix ACADs; UniProt records mitochondrion inner membrane, peripheral membrane protein. This is the core cellular localization.
Reason: Inner-membrane association is a conserved feature of VLCAD; UniProt records the inner-membrane, peripheral-membrane localization for this protein.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Mitochondrion inner membrane
|
|
GO:0006631
fatty acid metabolic process
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: ARBA electronic annotation placing Acadvl in fatty acid metabolism. Correct, but this is a broad parent of the specific fatty acid beta-oxidation process that the enzyme actually performs.
Reason: Correct but general; subsumed by the more specific beta-oxidation process (GO:0033539) used as the core biological process. Retained as non-core.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Lipid metabolism; mitochondrial fatty acid beta-oxidation.
|
|
GO:0016627
oxidoreductase activity, acting on the CH-CH group of donors
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: InterPro-based annotation to the intermediate oxidoreductase term. The acyl-CoA dehydrogenase reaction introduces a double bond between the alpha and beta carbons (oxidation of a CH-CH group), so this term is accurate at an appropriate intermediate level.
Reason: Correct intermediate parent between general oxidoreductase activity and the specific acyl-CoA dehydrogenase activities, which are the core molecular functions.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Belongs to the acyl-CoA dehydrogenase family.
|
|
GO:0017099
very-long-chain fatty acyl-CoA dehydrogenase activity
|
IEA
GO_REF:0000003 |
ACCEPT |
Summary: Electronic annotation from EC mapping (EC 1.3.8.9). This is the defining catalytic activity of VLCAD and is redundant with the IBA and ISS annotations to the same term, so the electronic call is correct and represents the core molecular function.
Reason: Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the EC 1.3.8.9 assignment independently supports the very-long-chain acyl-CoA dehydrogenase activity.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized
|
|
GO:0050660
flavin adenine dinucleotide binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro-based annotation for FAD binding. Acadvl is an FAD-containing flavoprotein; FAD is the obligate redox cofactor of all acyl-CoA dehydrogenases (UniProt COFACTOR: FAD). The term is correct and corresponds to a core feature of the enzyme.
Reason: FAD is the essential prosthetic group of VLCAD-family enzymes; UniProt lists FAD (ChEBI:CHEBI:57692) as the cofactor and flags the protein as a flavoprotein.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Name=FAD; Xref=ChEBI:CHEBI:57692;
|
|
GO:0005739
mitochondrion
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: ISS annotation transferred by FlyBase from the human ortholog UniProtKB:P49748 (VLCAD). Mitochondrial localization is unquestionably correct for Acadvl but is less specific than the inner-membrane annotation.
Reason: Correct mitochondrial localization (the enzyme is imported into the mitochondrion) but subsumed by the more specific GO:0005743 inner-membrane annotation; retained as non-core.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
Homodimerizes after import into the mitochondrion.
|
|
GO:0004466
long-chain fatty acyl-CoA dehydrogenase activity
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748), whose long-chain acyl-CoA dehydrogenase activity (EC 1.3.8.8, palmitoyl-CoA/C16) is directly demonstrated. The term is correct for the fly ortholog and duplicates the EC-based IEA annotation.
Reason: Correct long-chain acyl-CoA dehydrogenase activity, consistent with the EC-derived IEA annotation to the same term and with the experimentally characterized human ortholog.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
a long-chain 2,3-saturated fatty acyl-CoA + oxidized
|
|
GO:0017099
very-long-chain fatty acyl-CoA dehydrogenase activity
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748). This is the defining catalytic activity, well supported for the human source and consistent with the fly protein VLCAD subfamily assignment; redundant with the IBA and EC-based annotations to the same term.
Reason: Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the homology transfer from the experimentally characterized human ortholog supports it.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized
|
|
GO:0033539
fatty acid beta-oxidation using acyl-CoA dehydrogenase
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: ISS annotation transferred by FlyBase from human VLCAD (P49748). This is precisely the process Acadvl performs: it catalyzes the acyl-CoA dehydrogenase step of mitochondrial fatty acid beta-oxidation. Core biological process.
Reason: VLCAD-family enzymes catalyze the first (dehydrogenation) step of mitochondrial fatty acid beta-oxidation; UniProt records the pathway lipid metabolism, mitochondrial fatty acid beta-oxidation for this protein.
Supporting Evidence:
file:DROME/Acadvl/Acadvl-uniprot.txt
catalyze the first step of mitochondrial
|
Q: In Drosophila, is CG7461/Acadvl the sole ortholog covering both the VLCAD and ACAD9 functions of the mammalian clade (the protein carries the ACAD9/ACADVL-type C-terminal domain), and if so does it also participate in mitochondrial respiratory-chain complex I assembly as mammalian ACAD9 does?
Q: What is the physiological substrate-chain-length profile of Acadvl in fly tissues, and how is long-chain fatty acid oxidation partitioned between Acadvl and the other fly acyl-CoA dehydrogenases across the fed, starved, and flight-muscle-active states?
Experiment: Generate an Acadvl (CG7461) loss-of-function allele (or RNAi knockdown) and measure whole-animal and tissue acylcarnitine/acyl-CoA profiles by mass spectrometry under fed and starved conditions, testing for accumulation of long-chain species characteristic of a VLCAD block.
Hypothesis: Loss of Acadvl impairs long-chain fatty acid beta-oxidation in Drosophila, producing accumulation of long-chain acylcarnitines and reduced starvation resistance, mirroring mammalian VLCAD deficiency.
Experiment: Enzymatically characterize recombinant Drosophila Acadvl with a panel of acyl-CoA substrates of varying chain length (C8-C24) using an ETF- or ferricenium-based dehydrogenase assay, and test FAD dependence.
Hypothesis: Drosophila Acadvl has maximal acyl-CoA dehydrogenase activity toward long- and very-long-chain substrates (C14-C24) and requires bound FAD, confirming conservation of VLCAD substrate specificity.
UniProt: A1ZBJ2 (TrEMBL, unreviewed). FlyBase: FBgn0034432. Gene: Acadvl / CG7461.
NCBI TaxID 7227. Ortholog of human ACADVL (P49748, VLCAD).
Acadvl is the single Drosophila ortholog of the human very-long-chain acyl-CoA
dehydrogenase (VLCAD). It is a member of the acyl-CoA dehydrogenase (ACAD) family,
an FAD-dependent flavoenzyme that catalyzes the first, committed step of each cycle
of mitochondrial fatty acid beta-oxidation for long- and very-long-chain acyl-CoA
thioesters.
From the local UniProt record (A1ZBJ2):
- FUNCTION: "Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA
dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation
(FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy
from fats." ... "very long-chain specific acyl-CoA dehydrogenase acts specifically on
fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains."
[ECO:0000256|ARBA:ARBA00094192 — electronic/ARBA, transferred by rule]
- EC assignments: EC=1.3.8.8 (long-chain acyl-CoA dehydrogenase) and EC=1.3.8.9
(very-long-chain acyl-CoA dehydrogenase); catalytic-activity blocks give the RHEA
reactions with electron-transfer flavoprotein (ETF) as electron acceptor.
- COFACTOR: FAD [ChEBI:CHEBI:57692].
- PATHWAY: "Lipid metabolism; mitochondrial fatty acid beta-oxidation."
- SUBUNIT: "Homodimer. Homodimerizes after import into the mitochondrion."
- SUBCELLULAR LOCATION: "Mitochondrion inner membrane; Peripheral membrane protein."
- SIMILARITY: "Belongs to the acyl-CoA dehydrogenase family."
- Domain architecture (Pfam): Acyl-CoA_dh_N (PF02771), Acyl-CoA_dh_M (PF02770),
Acyl-CoA_dh_1 (PF00441), ACAD9-ACADV_C (PF21343). CDD cd01161 = VLCAD.
- PANTHER subfamily PTHR43884:SF11 "VERY LONG-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE,
MITOCHONDRIAL" — supports the VLCAD-specific (not generic ACAD) assignment.
- PE 1: Evidence at protein level (PeptideAtlas A1ZBJ2 peptides); Reactome R-DME-77305
"Beta oxidation of palmitoyl-CoA to myristoyl-CoA" (fly reaction).
Note on the C-terminal domain (PF21343 / IPR049448 "ACAD9/ACADV-like C"): both VLCAD
and ACAD9 carry this extra C-terminal extension. In human, ACADVL and ACAD9 are close
paralogs; in Drosophila, CG7461/Acadvl is reported as the single ortholog covering the
VLCAD/ACAD9 clade. The PANTHER subfamily call (SF11, VLCAD) and CDD VLCAD hit favor the
VLCAD assignment, and the fly gene is named Acadvl by FlyBase.
The GOA (Acadvl-goa.tsv) contains NO experimental (IDA/IMP/IPI/IGI/IEP) annotations —
this is a TrEMBL entry. All 13 annotations are electronic or homology-based:
- IBA (GO_REF:0000033, PANTHER PTN000856877 including human P49748, rat RGD:2014):
GO:0017099 VLCAD activity; GO:0000062 fatty-acyl-CoA binding.
- IEA/InterPro (GO_REF:0000002): GO:0003995 ACAD activity; GO:0016627 oxidoreductase
CH-CH; GO:0050660 FAD binding.
- IEA/EC (GO_REF:0000003): GO:0004466 (from EC 1.3.8.8); GO:0017099 (from EC 1.3.8.9).
- IEA/SubCell (GO_REF:0000044): GO:0005743 mitochondrial inner membrane.
- IEA/ARBA (GO_REF:0000117): GO:0006631 fatty acid metabolic process.
- ISS/FlyBase from human UniProtKB:P49748 (GO_REF:0000024): GO:0005739 mitochondrion;
GO:0004466 LCAD activity; GO:0017099 VLCAD activity; GO:0033539 FAO using ACAD.
Because the ISS annotations are transferred by curator judgment from the well-characterized
human VLCAD (P49748), and the IBA/IEA/EC/InterPro calls all converge on the same ACAD-family
FAD-dependent beta-oxidation function, the electronic annotations are collectively well
grounded for this gene. There is no cross-paralog mistransfer problem here (the human source
P49748 IS ACADVL, unlike the human-review case where mouse P50544=LCAD was mistransferred).
Web literature (not cached, so NOT used as verbatim supporting_text; recorded here as
provenance for the biological framing):
These corroborate the electronic annotations but cannot be used as supporting_text (not in
the cached publications/ folder). Verbatim supporting_text in the review is drawn from the
local UniProt record (file:DROME/Acadvl/Acadvl-uniprot.txt), which is an allowed local source.
No REMOVE actions: unlike the human entry, there are no cross-paralog mistransfers here; every
electronic call is consistent with the conserved ACAD/VLCAD function and with the human ortholog
P49748 source.
id: A1ZBJ2
gene_symbol: Acadvl
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:7227
label: Drosophila melanogaster
description: >-
Acadvl (CG7461; dACADVL) is the Drosophila melanogaster ortholog of human very-long-chain
specific acyl-CoA dehydrogenase (VLCAD). It is an FAD-dependent flavoenzyme of the acyl-CoA
dehydrogenase (ACAD) family that catalyzes the first, committed step of each cycle of
mitochondrial fatty acid beta-oxidation: the stereospecific alpha,beta-dehydrogenation of
saturated and unsaturated acyl-CoA thioesters, producing the corresponding trans-2-enoyl-CoA
and transferring the abstracted electrons to the electron-transfer flavoprotein (ETF). Like
its mammalian counterpart it acts specifically on long-chain and very-long-chain fatty
acyl-CoAs (primary chains of roughly 12 to 24 carbons, e.g. palmitoyl-CoA, C16), distinguishing
it from the medium- and short-chain acyl-CoA dehydrogenases. The protein carries the
characteristic ACAD N-terminal, middle and C-terminal domains together with the extra
ACAD9/ACADVL-type C-terminal extension, is FAD-dependent, and is a homodimer that associates
as a peripheral protein with the matrix face of the mitochondrial inner membrane. Through this
activity Acadvl feeds long-chain dietary and stored fatty acids into beta-oxidation for the
production of acetyl-CoA and cellular energy.
existing_annotations:
# --- Annotation 1: VLCAD activity (IBA) ---
- term:
id: GO:0017099
label: very-long-chain fatty acyl-CoA dehydrogenase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: >-
Phylogenetically inferred very-long-chain acyl-CoA dehydrogenase activity (PANTHER
PTN000856877, whose leaves include the experimentally characterized human VLCAD P49748).
This is the defining catalytic activity of the VLCAD family and, together with the CDD
VLCAD hit (cd01161) and the PANTHER subfamily assignment (PTHR43884:SF11, very long-chain
specific acyl-CoA dehydrogenase), is well supported at this specific level for the fly
ortholog. This captures the core molecular function.
action: ACCEPT
reason: >-
The IBA call is grounded in a tree whose experimental leaves (human ACADVL) directly
demonstrate very-long-chain acyl-CoA dehydrogenase activity, and the fly protein carries the
VLCAD-specific domain architecture and subfamily assignment. UniProt assigns EC 1.3.8.9
(very-long-chain) to this protein.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "very long-chain specific acyl-CoA dehydrogenase acts specifically on"
# --- Annotation 2: fatty-acyl-CoA binding (IBA) ---
- term:
id: GO:0000062
label: fatty-acyl-CoA binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: >-
Phylogenetically inferred binding of the acyl-CoA substrate. VLCAD-family enzymes must bind
fatty-acyl-CoA thioesters in order to dehydrogenate them, so this annotation is correct but
ancillary (a prerequisite of the catalytic activity rather than a separate core function).
action: KEEP_AS_NON_CORE
reason: >-
Substrate binding is subsumed by the catalytic dehydrogenase activity, which better
represents the core molecular function; retained as a supporting non-core annotation.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "acts specifically on fatty acyl-CoAs"
# --- Annotation 3: acyl-CoA dehydrogenase activity (IEA, InterPro) ---
- term:
id: GO:0003995
label: acyl-CoA dehydrogenase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
InterPro-based electronic annotation (IPR006089) to the general acyl-CoA dehydrogenase
activity term. The protein contains the ACAD active-site signature (PROSITE PS00072/PS00073)
and is a bona fide family member, so the term is correct but broader than the specific
VLCAD/LCAD activities that are also annotated.
action: KEEP_AS_NON_CORE
reason: >-
Correct general parent term subsumed by the specific GO:0017099 (very-long-chain) and
GO:0004466 (long-chain) activities used as core; retained as a supporting non-core annotation.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Belongs to the acyl-CoA dehydrogenase family."
# --- Annotation 4: long-chain acyl-CoA dehydrogenase activity (IEA, EC) ---
- term:
id: GO:0004466
label: long-chain fatty acyl-CoA dehydrogenase activity
evidence_type: IEA
original_reference_id: GO_REF:0000003
qualifier: enables
review:
summary: >-
Electronic annotation from EC mapping (EC 1.3.8.8) derived from UniProt. In addition to its
very-long-chain activity, VLCAD has well-documented long-chain acyl-CoA dehydrogenase
activity (classically assayed with palmitoyl-CoA, C16), so this is a valid and biologically
accurate term for the fly ortholog.
action: ACCEPT
reason: >-
UniProt assigns EC 1.3.8.8 (long-chain acyl-CoA dehydrogenase, RHEA:17721) to this protein
and it acts on fatty acyl-CoAs down to ~12 carbons. Consistent with the ISS annotation to the
same term.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "a long-chain 2,3-saturated fatty acyl-CoA + oxidized"
# --- Annotation 5: mitochondrial inner membrane (IEA, SubCell) ---
- term:
id: GO:0005743
label: mitochondrial inner membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: >-
Electronic annotation from UniProt subcellular-location mapping. VLCAD-family enzymes are
peripheral proteins of the mitochondrial inner membrane, distinguishing them from the soluble
matrix ACADs; UniProt records mitochondrion inner membrane, peripheral membrane protein. This
is the core cellular localization.
action: ACCEPT
reason: >-
Inner-membrane association is a conserved feature of VLCAD; UniProt records the inner-membrane,
peripheral-membrane localization for this protein.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Mitochondrion inner membrane"
# --- Annotation 6: fatty acid metabolic process (IEA, ARBA) ---
- term:
id: GO:0006631
label: fatty acid metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: >-
ARBA electronic annotation placing Acadvl in fatty acid metabolism. Correct, but this is a
broad parent of the specific fatty acid beta-oxidation process that the enzyme actually
performs.
action: KEEP_AS_NON_CORE
reason: >-
Correct but general; subsumed by the more specific beta-oxidation process (GO:0033539) used as
the core biological process. Retained as non-core.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Lipid metabolism; mitochondrial fatty acid beta-oxidation."
# --- Annotation 7: oxidoreductase activity, CH-CH group (IEA, InterPro) ---
- term:
id: GO:0016627
label: oxidoreductase activity, acting on the CH-CH group of donors
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
InterPro-based annotation to the intermediate oxidoreductase term. The acyl-CoA dehydrogenase
reaction introduces a double bond between the alpha and beta carbons (oxidation of a CH-CH
group), so this term is accurate at an appropriate intermediate level.
action: KEEP_AS_NON_CORE
reason: >-
Correct intermediate parent between general oxidoreductase activity and the specific acyl-CoA
dehydrogenase activities, which are the core molecular functions.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Belongs to the acyl-CoA dehydrogenase family."
# --- Annotation 8: VLCAD activity (IEA, EC) ---
- term:
id: GO:0017099
label: very-long-chain fatty acyl-CoA dehydrogenase activity
evidence_type: IEA
original_reference_id: GO_REF:0000003
qualifier: enables
review:
summary: >-
Electronic annotation from EC mapping (EC 1.3.8.9). This is the defining catalytic activity of
VLCAD and is redundant with the IBA and ISS annotations to the same term, so the electronic
call is correct and represents the core molecular function.
action: ACCEPT
reason: >-
Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the EC
1.3.8.9 assignment independently supports the very-long-chain acyl-CoA dehydrogenase activity.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized"
# --- Annotation 9: FAD binding (IEA, InterPro) ---
- term:
id: GO:0050660
label: flavin adenine dinucleotide binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
InterPro-based annotation for FAD binding. Acadvl is an FAD-containing flavoprotein; FAD is the
obligate redox cofactor of all acyl-CoA dehydrogenases (UniProt COFACTOR: FAD). The term is
correct and corresponds to a core feature of the enzyme.
action: ACCEPT
reason: >-
FAD is the essential prosthetic group of VLCAD-family enzymes; UniProt lists FAD
(ChEBI:CHEBI:57692) as the cofactor and flags the protein as a flavoprotein.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Name=FAD; Xref=ChEBI:CHEBI:57692;"
# --- Annotation 10: mitochondrion (ISS, from human P49748) ---
- term:
id: GO:0005739
label: mitochondrion
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: >-
ISS annotation transferred by FlyBase from the human ortholog UniProtKB:P49748 (VLCAD).
Mitochondrial localization is unquestionably correct for Acadvl but is less specific than the
inner-membrane annotation.
action: KEEP_AS_NON_CORE
reason: >-
Correct mitochondrial localization (the enzyme is imported into the mitochondrion) but subsumed
by the more specific GO:0005743 inner-membrane annotation; retained as non-core.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Homodimerizes after import into the mitochondrion."
# --- Annotation 11: long-chain acyl-CoA dehydrogenase activity (ISS, from human P49748) ---
- term:
id: GO:0004466
label: long-chain fatty acyl-CoA dehydrogenase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: >-
ISS annotation transferred by FlyBase from human VLCAD (P49748), whose long-chain acyl-CoA
dehydrogenase activity (EC 1.3.8.8, palmitoyl-CoA/C16) is directly demonstrated. The term is
correct for the fly ortholog and duplicates the EC-based IEA annotation.
action: ACCEPT
reason: >-
Correct long-chain acyl-CoA dehydrogenase activity, consistent with the EC-derived IEA
annotation to the same term and with the experimentally characterized human ortholog.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "a long-chain 2,3-saturated fatty acyl-CoA + oxidized"
# --- Annotation 12: VLCAD activity (ISS, from human P49748) ---
- term:
id: GO:0017099
label: very-long-chain fatty acyl-CoA dehydrogenase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: >-
ISS annotation transferred by FlyBase from human VLCAD (P49748). This is the defining catalytic
activity, well supported for the human source and consistent with the fly protein VLCAD
subfamily assignment; redundant with the IBA and EC-based annotations to the same term.
action: ACCEPT
reason: >-
Correct and identical to the core VLCAD-activity term captured by the IBA annotation; the
homology transfer from the experimentally characterized human ortholog supports it.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized"
# --- Annotation 13: FAO using acyl-CoA dehydrogenase (ISS, from human P49748) ---
- term:
id: GO:0033539
label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: >-
ISS annotation transferred by FlyBase from human VLCAD (P49748). This is precisely the process
Acadvl performs: it catalyzes the acyl-CoA dehydrogenase step of mitochondrial fatty acid
beta-oxidation. Core biological process.
action: ACCEPT
reason: >-
VLCAD-family enzymes catalyze the first (dehydrogenation) step of mitochondrial fatty acid
beta-oxidation; UniProt records the pathway lipid metabolism, mitochondrial fatty acid
beta-oxidation for this protein.
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "catalyze the first step of mitochondrial"
core_functions:
- description: >-
Very-long-chain/long-chain acyl-CoA dehydrogenase activity: Acadvl catalyzes the FAD-dependent,
stereospecific alpha,beta-dehydrogenation of long-chain and very-long-chain acyl-CoA thioesters
(roughly C12-C24, e.g. palmitoyl-CoA), the first and committed step of each cycle of mitochondrial
fatty acid beta-oxidation, transferring electrons to the electron-transfer flavoprotein (ETF).
molecular_function:
id: GO:0017099
label: very-long-chain fatty acyl-CoA dehydrogenase activity
directly_involved_in:
- id: GO:0033539
label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
locations:
- id: GO:0005743
label: mitochondrial inner membrane
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "catalyze the first step of mitochondrial"
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "very long-chain specific acyl-CoA dehydrogenase acts specifically on"
- description: >-
FAD cofactor binding: Acadvl binds FAD as its obligate redox prosthetic group; the bound flavin is
reduced during substrate dehydrogenation and re-oxidized by transfer of electrons to the
electron-transfer flavoprotein, and is required for catalysis and structural stability.
molecular_function:
id: GO:0050660
label: flavin adenine dinucleotide binding
directly_involved_in:
- id: GO:0033539
label: fatty acid beta-oxidation using acyl-CoA dehydrogenase
locations:
- id: GO:0005743
label: mitochondrial inner membrane
supported_by:
- reference_id: file:DROME/Acadvl/Acadvl-uniprot.txt
supporting_text: "Name=FAD; Xref=ChEBI:CHEBI:57692;"
proposed_new_terms: []
suggested_questions:
- question: >-
In Drosophila, is CG7461/Acadvl the sole ortholog covering both the VLCAD and ACAD9 functions of
the mammalian clade (the protein carries the ACAD9/ACADVL-type C-terminal domain), and if so does
it also participate in mitochondrial respiratory-chain complex I assembly as mammalian ACAD9 does?
- question: >-
What is the physiological substrate-chain-length profile of Acadvl in fly tissues, and how is
long-chain fatty acid oxidation partitioned between Acadvl and the other fly acyl-CoA
dehydrogenases across the fed, starved, and flight-muscle-active states?
suggested_experiments:
- description: >-
Generate an Acadvl (CG7461) loss-of-function allele (or RNAi knockdown) and measure whole-animal
and tissue acylcarnitine/acyl-CoA profiles by mass spectrometry under fed and starved conditions,
testing for accumulation of long-chain species characteristic of a VLCAD block.
hypothesis: >-
Loss of Acadvl impairs long-chain fatty acid beta-oxidation in Drosophila, producing accumulation
of long-chain acylcarnitines and reduced starvation resistance, mirroring mammalian VLCAD deficiency.
- description: >-
Enzymatically characterize recombinant Drosophila Acadvl with a panel of acyl-CoA substrates of
varying chain length (C8-C24) using an ETF- or ferricenium-based dehydrogenase assay, and test FAD
dependence.
hypothesis: >-
Drosophila Acadvl has maximal acyl-CoA dehydrogenase activity toward long- and very-long-chain
substrates (C14-C24) and requires bound FAD, confirming conservation of VLCAD substrate specificity.
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:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- 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: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: file:DROME/Acadvl/Acadvl-uniprot.txt
title: UniProtKB A1ZBJ2 (Acadvl / CG7461, Drosophila melanogaster) TrEMBL record
findings:
- statement: >-
UniProt TrEMBL record for the Drosophila VLCAD ortholog. Assigns the protein to the acyl-CoA
dehydrogenase family with EC 1.3.8.8 (long-chain) and EC 1.3.8.9 (very-long-chain) activities,
FAD as cofactor, the mitochondrial fatty acid beta-oxidation pathway, homodimeric quaternary
structure, and a peripheral inner-mitochondrial-membrane localization. PANTHER subfamily
PTHR43884:SF11 and CDD cd01161 assign it specifically to VLCAD.
supporting_text: >-
very long-chain specific acyl-CoA dehydrogenase acts specifically on
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
Local UniProt record for A1ZBJ2; the entry is unreviewed (TrEMBL) and its functional block is
ARBA/rule-derived, but the family assignment, EC numbers, cofactor and localization are
internally consistent and concordant with the well-characterized human ortholog P49748 and with
the fly VLCAD subfamily/CDD assignments.