BAAT (Q14032) review notes

Human bile acid-CoA:amino acid N-acyltransferase (BAAT / BACAT / BAT). HGNC:932. Chromosome 9. 418 aa.
EC 2.3.1.65 (N-acyltransferase), EC 3.1.2.27 (choloyl-CoA hydrolase / thioesterase), EC 3.1.2.2 (long-chain fatty-acyl-CoA hydrolase).

Core biology (well established)

• BAAT catalyzes the FINAL conjugation step of bile-acid synthesis: it transfers the bile
  acid from its CoA thioester (bile-acyl-CoA, generated by SLC27A5/BACS) onto the amino group
  of glycine or taurine, forming glyco- and tauro-conjugated bile acids that are the major
  secreted/biliary forms.
  PMID:8034703
  PMID:2037576
  PMID:12810727

• A single enzyme conjugates BOTH glycine and taurine. Km values: taurine 1.1-1.8 mM,
  glycine 5.6-5.8 mM (UniProt kinetics). Monomer (PMID:2037576, SUBUNIT: Monomer).

• Catalytic triad Cys-235 / Asp-328 / His-362 (alpha/beta hydrolase-like; Cys is nucleophile).
  PMID:12239217
  PMID:12810727

• Secondary activity: acyl-CoA thioesterase/hydrolase. Cys235Ser mutant lowers acyltransferase
  but INCREASES thioesterase (they share the nucleophile).
  PMID:12239217
  In vitro also hydrolyzes long- and very-long-chain acyl-CoAs (C16-C26) and conjugates fatty
  acids to glycine.
  PMID:12810727
  Note: the fatty-acyl-CoA hydrolase and glycine-conjugation-of-fatty-acids activities were
  demonstrated with RECOMBINANT enzyme in vitro; physiological role in VLCFA regulation is
  hypothesized, not established.

Localization

• Peroxisome and cytosol. Historically reported largely cytosolic (up to 95%), but endogenous
  human/rat BAAT localizes to peroxisomes; cytosolic pool depends on cell type / import competition.
  PMID:12810727
  PMID:17256745
  PMID:17256745
  UniProt: Cytoplasm, cytosol; Peroxisome (by similarity Q63276). HPA IDA = cytosol.
  Both peroxisome (GO:0005777) and cytosol (GO:0005829) are legitimate; keep both.

Disease

• Familial hypercholanemia 3 (FHCA3, MIM:619232); autosomal recessive; reduced biliary
  secretion of conjugated bile acids, fat malabsorption, fat-soluble-vitamin deficiency,
  rickets/growth failure, coagulopathy; increased UNCONJUGATED bile acids. (UniProt DISEASE;
  PMID:23415802, PMID:12704386 — not cached, cited from UniProt record.)

Annotation-review decisions summary

CORE MF: glycine N-choloyltransferase activity GO:0047963 (EXP/IDA, well supported). This is
the specific bile acid-CoA:amino acid N-acyltransferase term present in GOA.
CORE BP: bile acid biosynthetic process GO:0006699 (IDA/TAS); bile acid conjugation GO:0002152
(IDA); bile acid metabolic process GO:0008206 (parent).
SECONDARY MF: acyl-CoA hydrolase / choloyl-CoA hydrolase (GO:0033882, GO:0016289) — real but
secondary; the specific medium/long/VLC fatty-acyl-CoA hydrolase IEAs (RHEA-mapped) and IDAs
(PMID:12810727) are in-vitro activities -> KEEP_AS_NON_CORE / MARK_AS_OVER_ANNOTATED.
LOCATION: peroxisome GO:0005777 (IDA PMID:17256745, IBA, ISS, IEA) ACCEPT; cytosol GO:0005829
(IDA HPA, PMID:17256745, PMID:12810727, PMID:8034703) ACCEPT.

protein binding GO:0005515 IPI x2 (PMID:25416956 systematic interactome; PMID:32814053 ND
interactome Y2H) -> MARK_AS_OVER_ANNOTATED (bare protein binding, uninformative, no functional
follow-up for BAAT; not REMOVE per policy).

liver development GO:0001889 and animal organ regeneration GO:0031100 (IEA Ensembl from rat
ortholog) -> KEEP_AS_NON_CORE / MARK_AS_OVER_ANNOTATED (electronic ortholog transfer, not a
molecular role of the enzyme).

fatty acid metabolic process GO:0006631 (IBA), lipid metabolic process GO:0006629 (ARBA),
monocarboxylic acid metabolic process GO:0032787 (ARBA) -> broad IEA/IBA; ACCEPT as broad or
KEEP_AS_NON_CORE.

thiolester hydrolase activity GO:0016790 (InterPro IEA) -> broad parent of the thioesterase
activity; ACCEPT (broad but correct).