Is a molecular function assignable to AAMDC from its family?

Generated by analyze_mth938.py. Every number below is fetched at run time from
the InterPro, UniProt and QuickGO REST APIs; re-run to refresh.

Question

The AAMDC review concludes that no molecular function is currently justifiable for
this protein. That is a negative claim. This analysis tests it the only way a
negative claim can be tested: enumerate the whole protein family and ask whether
any member has an experimentally supported molecular function that could transfer.

Family definition

Fetched from the InterPro API at run time:

Members enumerated below are the reviewed (Swiss-Prot) entries carrying Pfam
PF04430 — a small, manually curated subset of all proteins with the signature,
chosen because only reviewed entries carry curated function statements and GO
annotations worth counting.

Result

Reviewed family members 13
GO annotations successfully retrieved for 13 of 13
With any experimental MF term (excluding bare protein binding) 0
With an explicit GO:0003674 ND (curator: no function known) 4
With a UniProt CATALYTIC ACTIVITY block 0

No member of this family carries any experimentally supported molecular
function term.
The absence of an MF annotation on AAMDC is therefore not an
oversight specific to this gene: it is a property of the entire family.

What the one characterised relative does

The family is not entirely uncharacterised. 7 of its 13
reviewed members carry a UniProt FUNCTION statement about mitochondrial
complex I assembly, and all of them are NDUFAF3 entries. That branch is an
assembly factor for mitochondrial complex I, consistently across every
organism in which it has been studied; the Drosophila entry cites experimental
evidence (PubMed:34386730).

This is informative in a specific way. NDUFAF3 is an assembly factor, not an
enzyme
: it has no catalytic activity, it binds subunits and helps build a complex,
and it is not part of the finished complex. Consistent with that, no member of this
family - including NDUFAF3 itself - carries a CATALYTIC ACTIVITY block or an
experimental molecular function term.

So the family signal does not point toward a hidden enzymatic activity waiting to
be found for AAMDC. It points toward a protein-assembly / chaperone-like role, which
is a class of function GO struggles to express as a molecular function in any case
(there is no assembly-chaperone MF term; see the AAGAB review in this campaign).
That makes the AAMDC review's refusal to assign an MF the right call, and it also
suggests where to look experimentally: what complex, if any, does AAMDC help
assemble?

Members

Accession Entry Organism Len Catalytic block GO retrieved Experimental MF
Q32PA8 AAMDC_BOVIN Bos taurus 122 no yes —
Q2HJI2 NDUF3_BOVIN Bos taurus 184 no yes —
Q502H1 AAMDC_DANRE Danio rerio 122 no yes — (MF=ND)
A1L1F1 NDUF3_DANRE Danio rerio 174 no yes — (MF=ND)
Q9W1H9 NDUF3_DROME Drosophila melanogaster 196 no yes —
P18152 MP13_FRATH Francisella tularensis subsp. holarctica (strain LVS) 123 no yes —
Q9BU61 NDUF3_HUMAN Homo sapiens 184 no yes —
Q9H7C9 AAMDC_HUMAN Homo sapiens 122 no yes —
Q8R0P4 AAMDC_MOUSE Mus musculus 122 no yes — (MF=ND)
Q9JKL4 NDUF3_MOUSE Mus musculus 185 no yes — (MF=ND)
O08776 NDUF3_RAT Rattus norvegicus 185 no yes —
P29962 Y1784_RHOCB Rhodobacter capsulatus (strain ATCC BAA-309 / NBRC 16581 / SB1003) 124 no yes —
Q6DFN1 NDUF3_XENTR Xenopus tropicalis 183 no yes —

UniProt FUNCTION statements across the family