FoxB (Sp-FoxB / Spfkh1, Q9XZM6) — curation notes

Identity

UniProt Q9XZM6 (TrEMBL, 360 aa), "Winged helix transcription factor Forkhead-1", gene name
fkh1 (EMBL AAD34014.1), GeneID 373496. The RX citation is the original cloning paper
PMID:10433970, which places the gene in forkhead Class II
PMID:10433970;
Class II of the old Kaufmann/Knochel scheme corresponds to the FoxB subclass.
Mapping to the GRN gene: NCBI Gene 373496 (the GeneID cross-referenced from this UniProt entry,
checked with eutils esummary on 2026-10-03) carries the alias "FoxB". Minokawa et al. 2004
re-examined the expression of "SpFoxb" as one of four regulatory genes PMID:15183312, i.e. the gene was already known in 2004, consistent with it being one
of the three fox genes known before the genome survey PMID:17081512. Garfield et al. 2012 analysed the
"FoxB" upstream cis-regulatory region PMID:23017024, matching the cis-regulatory region sequenced by
David et al. 1999. Confidence that fkh1/Q9XZM6 is the foxb node of the Davidson skeletogenic GRN:
HIGH (GeneID alias + the single Class II / FoxB forkhead gene in the genome + continuity of the
Spfkh1 -> SpFoxb -> Sp-foxb naming in the Caltech papers).
Domains (UniProt DR): Fork_head IPR001766 (Pfam PF00250, PROSITE PS50039, residues 13-107);
PANTHER PTHR11829 (family), subfamily SF377. No GO-CAM contains this gene
(gocams/index.tsv has no STRPU rows).

Single ORF encoding DNA-binding domain, NLS and transactivation domain PMID:10433970; 40.7 kDa, pI 9.96.
Promoter region contains many predicted TF binding sites, including sites for Wnt/beta-catenin
and hedgehog pathway effectors PMID:10433970. This 1999 inference of an
endodermal role was made before the GRN work placed the gene in the skeletogenic lineage.

foxb is a late-tier regulatory gene of the skeletogenic micromere lineage, downstream of the
double-negative-gate outputs tbr and alx1 PMID:18413610. Nam & Davidson
2012 describe the same wiring PMID:22238426.
Oliveri et al. 2008 originally proposed a feed-forward (Ets1 > Alx1 > target) regulation of
Sp-foxb together with the biomineralization genes msp130 and msp103L; Shashikant et al. 2018
recall this PMID:29558892.
Output: FoxB is listed among the regulatory-state components whose products are required as
drivers of the skeletogenic differentiation gene batteries (perturbation data in Oliveri 2008
Table S1, not in the cached text) PMID:18413610. These differentiation genes are the biomineral genes
PMID:18413610.
Expression: the GRN papers describe foxb as transcribed in the micromere/skeletogenic lineage
(Oliveri 2008 Figs. 2, 3, 6). Minokawa 2004 reports additional expression domains
PMID:15183312, but the cached record is abstract-only, so
the later (oral ectoderm/stomodaeal, endodermal) domains mentioned in the orchestrator's brief
cannot be quoted from the cache and are not asserted in the review.

Saunders & McClay 2014 knocked down 13 skeletogenic TFs in L. variegatus PMID:24598159 and
found foxb required for PMC EMT PMID:24598159, specifically in the apical
constriction sub-circuit PMID:24598159.
This is the Lv orthologue, so it is recorded here and in suggested_questions rather than as an
S. purpuratus NEW annotation.

IBA rows (0000981, 0000978, 0005634, 0006357) accepted: family-level winged-helix DNA binding
and nuclear TF function are consistent with the cloning paper and GRN role.
IEA generic rows (0003677, 0003700, 0006355) MODIFY to the specific RNA pol II terms already on
the gene / proposed; 0043565 and 0005634 (IEA) accepted.
IBA 0030154 cell differentiation MODIFY -> GO:0070169; IBA 0009653 kept as non-core.
NEW: GO:0045944 (IMP, Oliveri 2008) and GO:0070169 (IMP, Oliveri 2008), both minimal and
resting on the perturbation data summarised in Oliveri 2008.
Not proposed: EMT terms (Lv data only), endoderm terms (1999 in silico promoter inference only),
activator MF GO:0001228 (no reporter/site-mutation evidence for FoxB itself).