TRF2 (G4N2B2, MGG_04853) relative placement, 2026-10-21

Script: compare_relatives.py (PEP 723; uv run --script compare_relatives.py > RESULTS.txt).
Raw output: RESULTS.txt. Sequences and cross-references are fetched live from UniProt REST.

Method

Global pairwise alignment (Biopython PairwiseAligner, BLOSUM62, gap open -10, extend -0.5) of the full
TRF2 sequence and of its UniProt homeodomain DNA_BIND window (residues 73-132) against PANTHER
PTHR24324 members that have experimental literature, plus the Aspergillus nidulans PF24818 protein.
Identity is identical aligned positions divided by the shorter sequence length (inflated for short
proteins such as yox1 and HHEX; the homeodomain value is the fairer comparison). HOGENOM/OrthoDB sharing
is read from the UniProt records. A UniProt REST query counts PF24818 proteins in P. oryzae 70-15.

Results

Accession	Gene	Species	Full-length id %	Homeodomain id %	Shares TRF2 HOGENOM cluster	Has PF24818	PANTHER subfamily
Q7S7W0	kal-1	Neurospora crassa	67.3	93.3	yes	yes	SF5
C8VLD7	ANIA_02009	Aspergillus nidulans	50.3	81.7	yes	yes	SF5
Q99160	HOY1	Yarrowia lipolytica	32.0	55.0	no	yes	SF5
Q10328	phx1	Schizosaccharomyces pombe	33.3	51.7	no	no	SF5
P07269	PHO2	Saccharomyces cerevisiae	24.9	43.3	no	no	SF5
P40923	yox1	Schizosaccharomyces pombe	32.8	36.7	no	no	SF5
Q03014	HHEX	Homo sapiens	27.8	33.3	no	no	SF5
Q04116	YHP1	Saccharomyces cerevisiae	23.5	40.0	no	no	SF9
P34161	YOX1	Saccharomyces cerevisiae	26.2	41.7	no	no	SF9

The TRF2 homeodomain (residues 73-132) carries the helix-3 recognition motif WFQNRR (residues 120-125),
with I47, Q50, N51 and R53 (canonical homeodomain numbering) at residues 119, 122, 123 and 125.
TRF2 is the only PF24818 protein returned for P. oryzae 70-15.

Interpretation

TRF2 has an intact, typical homeodomain whose DNA-contacting helix-3 residues (I47/Q50/N51/R53) are those
of canonical TAAT-core-binding homeodomains, so sequence-specific DNA binding is well supported by sequence.
N. crassa KAL-1 is the TRF2 ortholog (same PANTHER subfamily SF5, same HOGENOM cluster CLU_023524_1_0_1,
same homeodomain + PF24818 architecture, 67% full-length / 93% homeodomain identity, a single PF24818
protein in each proteome). The OrthoDB group 6159439at2759 is a eukaryote-level group that also contains
PHO2 and HHEX, so it is not by itself evidence of 1:1 orthology; the HOGENOM cluster and PF24818
architecture are the discriminating features.
HOY1 (Yarrowia) shares architecture and subfamily but is distant (55% homeodomain identity).
The yeast and animal SF5 members with experimental data (PHO2, phx1, yox1, HHEX) share only the
homeodomain (33-52% identity) and lack PF24818. Only the shared homeodomain activity
(sequence-specific DNA binding, RNA polymerase II-specific transcription factor activity) is a safe
transfer; their physiological roles (phosphate regulation, cell-cycle repression, vertebrate development)
are not.