UniProt: Q9VL70 (unreviewed TrEMBL). FlyBase: FBgn0040064. Gene symbol Acaa; synonyms
Yip2 / yip2 / YIP2 ("Yippee interacting protein 2"), Dmel\CG4600. Ortholog of human ACAA2
(mitochondrial 3-ketoacyl-CoA thiolase, P42765; DIOPT 14/14 per FlyBase).
Like human ACAA2, Acaa/Yip2 is predicted to catalyze the fourth and final (thiolytic) step of
each cycle of the mitochondrial fatty acid beta-oxidation spiral: 3-ketoacyl-CoA + CoA ->
acetyl-CoA + acyl-CoA(n-2), releasing acetyl-CoA and a fatty acyl-CoA shortened by two carbons.
The reaction (EC 2.3.1.16) corresponds to GO:0003988 (acetyl-CoA C-acyltransferase activity).
The domain architecture, active-site residues, and 14/14 DIOPT orthology to ACAA2 all support
this assignment. No direct Drosophila enzyme-assay of Yip2 was located; the fly annotations are
sequence/orthology-based (ISS/IBA/IEA), which is appropriate for a well-conserved metabolic
enzyme.
dHNF4 mutants fail to mobilize lipid stores and are starvation-sensitive
PMID:19254568. This places Yip2 in the fly mitochondrial beta-oxidation program
but does not itself demonstrate Yip2's molecular activity.
Note: the paper treats yip2 and "thiolase" (CG9149) as separate genes in the list, and
distinguishes yip2 from "scully" (the fly MFE/HADH-type gene) — Yip2 is the degradative
3-ketoacyl-CoA thiolase (ACAA2 ortholog).
Faust, Verma, Peng & McNew, "An inventory of peroxisomal proteins and pathways in
Drosophila melanogaster" (Traffic 2012; PMID:22758915; abstract-only cache). A proteome
inventory / prediction study. It is the source of the ISM (predicted-from-sequence-model)
GO:0005739 mitochondrion annotation on Yip2 in GOA. The abstract is about peroxisomes and
does not describe Yip2 specifically; the associated GO annotation is a bioinformatic
targeting-signal prediction (CG4600 carries a mitochondrial rather than peroxisomal signal).
full_text_available: false.
The "Yippee interacting protein 2" (Yip2) name derives from a two-hybrid interaction with
the Drosophila Yippee protein (historical naming). No characterized, functionally meaningful
Yippee–Yip2 complex activity is documented in GOA, and there is no protein-binding annotation
in the fly GOA for Q9VL70. I did not find a validated fly interaction dataset to cite for a
binding function, so no binding annotation is proposed.
MF:
- GO:0003985 acetyl-CoA C-acetyltransferase activity (EC 2.3.1.9) — IBA, IEA(EC), ISS. The
biosynthetic/acetoacetyl-CoA reaction. Secondary capability (thiolase reversibility), not core.
- GO:0003988 acetyl-CoA C-acyltransferase activity (EC 2.3.1.16) — IEA(ARBA), ISS. CORE MF.
- GO:0016746 / GO:0016747 acyltransferase activity (InterPro2GO) — over-general ancestors of 0003988.
BP:
- GO:0006635 fatty acid beta-oxidation — IBA, ISS. CORE process.
- GO:0006629 lipid metabolic process — IEA(ARBA). Over-general ancestor of 0006635.
- GO:1902109 negative regulation of mitochondrial membrane permeability involved in apoptotic
process — ISS from human ACAA2 (BNIP3 story, PMID:18371312 in human). Transferred by orthology;
the underlying human evidence is a single overexpression study. Non-core / contextual at best.
CC:
- GO:0005759 mitochondrial matrix — ISS (from ortholog). CORE location (soluble matrix thiolase).
- GO:0005739 mitochondrion — IBA, ISM(PMID:22758915). Correct but less specific than matrix.