arcA (PA5171, P13981) notes

Identity

UniProt P13981 (ARCA_PSEAE), 418 aa, Swiss-Prot reviewed. Arginine deiminase
(ADI, EC 3.5.3.6), arginine deiminase family (HAMAP MF_00242, NCBIfam TIGR01078,
Pfam PF02274, InterPro IPR003876, PANTHER PTHR47271:SF3). Active site Cys406.
Five PDB structures of the PAO1 enzyme (1RXX, 2A9G, 2AAF, 2ABR, 2ACI).
First enzyme-encoding gene of the anaerobically induced arcDABC operon (PA5170
arcD, PA5171 arcA, PA5172 arcB, PA5173 arcC).

Biology (literature)

Genetics: mutants unable to grow anaerobically on arginine fell into arcA, arcB,
arcC (each lacking one ADI-pathway enzyme) and arcD classes, closely linked at
17 min PMID:6438064.
The same paper notes that some arc mutations lowered all three enzymes, i.e.
regulatory rather than structural mutations
PMID:6438064.
Structural gene identification: arcA was sequenced, and the purified ADI
subunit size and N-terminal sequence matched the ORF
PMID:2537202;
the purified enzyme was characterised kinetically
PMID:2537202.
Structure and mechanism: P. aeruginosa ADI crystal structure, pentein fold
shared with DDAH and amidinotransferases
PMID:14701825;
Cys406 nucleophile, substrate complex and thiouronium intermediate structures
PMID:16091358.
Pathway: ADI pathway (ADI, catabolic OTC ArcB, carbamate kinase ArcC; ArcD
arginine:ornithine antiporter) generates ATP from arginine under anoxia
PMID:2158926.

PseudoCAP IBA-seed assessment

PTN node	node term	n_seeds	leaf IBAs	seed annotation (term, evidence, PMID)	verdict	rationale
PTN005338738	GO:0016990 arginine deiminase activity	1 (sole seed)	23 (18 taxa)	GO:0016990 arginine deiminase activity, IMP, PMID:6438064 (PseudoCAP)	SOUND	Classic enzyme-deficient mutant evidence: arcA mutants were defined by loss of ADI activity, separate from the regulatory class that lost all three enzymes, and the locus was later shown to be the ADI structural gene (PMID:2537202: purified ADI N-terminus matches the arcA ORF). A mutant phenotype can support an MF when the mutant is shown to lack that specific activity and the mutation is in the structural gene; both hold here. Stronger direct evidence (purified enzyme kinetics, crystal structures, Cys406 mechanism) exists for this very protein, so the IBD is very well anchored; IDA from PMID:2537202 would be a better seed.

Node breadth: PTN005338738 spans the whole PTHR47271 family (SF2 + SF3): bacterial,
archaeal and protist (Giardia, Trichomonas, Chlamydomonas) ADIs. Most leaves are
~400-420 aa canonical ADIs, which fits the term. A few leaves are much shorter and
are not annotated as ADIs: B. subtilis YkgA (O34497, 286 aa, UniProt "Belongs to the
DDAH family", "Uncharacterized protein"), Methanosarcina Q8TSK4 (335 aa), Sulfolobus
Q97TX4 (341 aa) and Korarchaeum B1L3J0 ("N-dimethylarginine dimethylaminohydrolase").
B. subtilis 168 degrades arginine via arginase, not the ADI pathway. These leaves may
be over-propagations within the pentein superfamily; this was flagged to GO_CENTRAL
as a CHECK (SUSPECTED) on the IBA row. Not verified by sequence analysis here.

Decisions summary

ACCEPT: arginine deiminase activity (IBA, IEA, IMP), L-arginine catabolic process
(IEA), cytoplasm (IEA).
PSEUDOCAP: no defect; IMP is acceptable (enzyme-deficient structural-gene mutant).
GO_CENTRAL: CHECK (SUSPECTED) for DDAH-like short leaves under PTN005338738.

PANTHER tree check (2026-11-05)

Topology of PTN005338738 fetched with projects/PSEUDOCAP/panther_tree.py node PTN005338738 --depth 5 / --leaves (PANTHER treeinfo for PTHR47271).

PTN005338738: SPECIATION, placed at LUCA, 23 leaves (PTHR47271:SF2 20, SF3 3).

child node	event / taxon	leaves	subfamilies	content	verdict for GO:0016990
PTN005338739	SPECIATION Archaea-Eukaryota	10	SF2	Bikonts PTN008230055 (Giardia ADI; Trichomonas triplet PTN009208904; Chlamydomonas ADI) + Archaea PTN005338744	mixed; see below
└ PTN005338744	SPECIATION Archaea	5	SF2	Korarchaeum pair PTN008230056 (B1L3J0 DDAH-named, B1L477 amidinotransferase); Sulfolobus Q97TX4 "arginine deiminase, hypothetical"; Euryarchaeota pair PTN005338745 = Methanosarcina Q8TSK4 + Halobacterium F2Z681, both named arginine deiminase	only PTN008230056 still doubtful
PTN008715727	DUPLICATION	13	SF2 10, SF3 3	the two bacterial clades	—
└ PTN008715728	SPECIATION Eubacteria	3	SF3	S. coelicolor Q9RJN1, Bradyrhizobium Q89DX7, PAO1 ArcA P13981 (PTN002291359)	the seed clade
└ PTN000978201	SPECIATION Eubacteria	10	SF2	Terrabacteria PTN008230058 (Actinomycetales pair; Firmicutes PTN001763871) + Gammaproteobacteria PTN001763884 (Vibrio, Salmonella ArcA)	all named ArcA
└ PTN002933241	SPECIATION Bacillus	2	SF2	B. subtilis YkgA (O34497) + B. cereus ArcA (Q81II1)	YkgA's sister is a genuine ArcA

Conclusions (three quarters of the original concern is withdrawn):

Q8TSK4 and Q97TX4 are not "unannotated". Methanosarcina Q8TSK4 pairs with
Halobacterium F2Z681 (PTN005338745) and both carry the UniProt name arginine
deiminase, as does Sulfolobus Q97TX4. Their shorter length alone is weak evidence
against the term, so they are dropped from the defect.
B. subtilis YkgA sits inside a Bacillales ADI clade. Its sister is B. cereus
ArcA (node PTN002933241), within PTN001763879 alongside the S. aureus and
L. monocytogenes ArcA enzymes. The topology argues YkgA is an orthologous ADI whose
Swiss-Prot name lags, not an over-propagation -- even though B. subtilis 168 itself
uses arginase rather than the ADI pathway.
What survives is the Korarchaeum cryptofilum duplication pair PTN008230056
(B1L3J0 N-dimethylarginine dimethylaminohydrolase, B1L477 amidinotransferase): the
only leaves of the node whose names point to a different pentein activity, and a
clean 2-leaf NOT target.
The Trichomonas triplet PTN009208904 is not flagged: its names are
uninformative ("amidinotransferase family protein") and trichomonads do run an
arginine dihydrolase pathway.
The general point stands and is now evidenced: the node is a LUCA-level
SPECIATION, so the IBD asserts a substrate-specific pentein activity as ancestral to
all life.

Defect raised SUSPECTED -> PROBABLE and retargeted from four scattered leaves to
PTN008230056; the suggested question and experiment were rewritten to match. No
annotation actions changed (the GO:0016990 IBA stays ACCEPT for ArcA itself).