hes6 (Q6P0J1): evidence and exact-input prediction review

The three emitted GO predictions are biologically supported but broad. Direct zebrafish biochemistry establishes DNA binding by the Her7:Hes6 heterodimer, so a blanket claim that Hes6 cannot contribute to DNA binding would be wrong.

Input identity and functional boundary

Q6P0J1 is zebrafish hes6/her13.2, a 226-residue product with bHLH and Orange domains. It is not her6 or her8a. The 2012 paper directly studies Hes6 alongside Her1 and Her7. The three generic protein-binding GOA rows have donors Her1/Q90463, Myod1/Q90477 and Her7/Q9I9K1 respectively; the separate identical-protein-binding row records Hes6 self-association. The primary paper includes MyoD as a promiscuous bHLH interaction comparison.

Biological evidence

• PMID:15905406 — Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites.: The primary reporter and interaction experiments establish transcriptional repression and Her1 association for Her13.2/Hes6.

Her13.2 augments autorepression of her1 in association with Her1 protein.

her13.2 is required for periodic repression of the
Notch-regulated genes her1 and her7, and for proper somite segmentation.

• PMID:16545363 — her1 and her13.2 are jointly required for somitic border specification along the entire axis of the fish embryo.: The primary abstract explicitly reports combined Her1/Her13.2 loss-of-function effects on somitic borders.

joint inactivation of her1 and her13.2 leads to a complete loss of all somitic
borders

• PMID:20637625 — Segment number and axial identity in a segmentation clock period mutant.: The period-mutant study supports clock-dependent segment number; target identity is independently corroborated by the full 2018 report.

precise control of segmentation
clock period in relation to axial growth ensures a species-specific segment
number

arguing
against an instructive role of the segmentation clock in determining axial
identities.

• PMID:22911291 — Topology and dynamics of the zebrafish segmentation clock core circuit.: Direct zebrafish biochemistry establishes partner-dependent DNA binding by Hes6 in the Her7:Hes6 heterodimer.

only Her1 homodimers and Her7:Hes6 heterodimers have strong DNA binding activity and target similar DNA sites.

all of the possible dimers between Her1, Her7 and Hes6 form

even the bHLH containing factor MyoD, but not the negative control non-bHLH protein PPARγ, was co-purified by Her1, Her7, and Hes6 to a similar extent

• PMID:29624170 — Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock.: The full primary report directly generates and analyzes a hes6 mutant; its focus on notochord-derived centra does not make the Hes6 annotation a wrong-gene citation.

The novel hes6 mutation was created by injection of a TALEN targeted against hes6 in wild type.

her1;hes6 mutants (n=15)

Exact non-GO claims

The complete emitted record is preserved in hes6-protnlm-source.json. Assessments below address the selected protein product; evidence on longer products is identified explicitly.

Protein name

Uncharacterized protein

UNSCORED: “Uncharacterized protein” has no ProtNLM evidence tag in the returned name field. It is an API default rather than a scored biological hypothesis.

Emitted GO claims

All 3 emitted GO claims are individually assessed in hes6-protnlm-predictions-review.yaml.

Family integration

Hairy/HES-family domains support dimer formation, but individual homo- and heterodimers differ strongly in DNA binding and regulatory effect. In zebrafish, Her7:Hes6 is directly DNA-binding while Hes6 homodimers are not in the tested assays. Neither a universal DNA-binding grant to every dimer nor a blanket non-DNA-binding label for Hes6 is appropriate. Somitogenesis and neurogenesis also require lineage- and tissue-specific evidence.

Evidence limits

Full text was read for the 2005, 2012 and 2018 target studies, including the interaction controls and hes6-mutant figure captions. The 2006 and 2010 cache entries are abstract-only, with target relevance corroborated by the full later reports. The genuine Falcon research synthesis identifies useful clock studies; the conclusions here are anchored to the experiments themselves. Neural function remains unresolved rather than rejected because mesoderm is the best-studied context.