CAMTA1

Summary: The CG-1 domain belongs to a DNA-binding transcriptional regulator; the generic DNA-binding mapping can be refined.

Reason: InterPro-derived DNA binding is consistent with the conserved CG-1 domain in human Q9Y6Y1. Human CAMTA1 activates a LexA-tethered yeast reporter (PMID:11925432), while mammalian CAMTA motif and mutagenesis experiments support DNA-dependent regulation (PMID:25049392). The full primary study PMID:34499028 adds native in vivo family evidence: CRISPR-tagged C. elegans CAMT-1a occupies three cmd-1 promoter regions by ChIP-seq, and deleting all three regions produces behavioral defects rescued by neuronal CMD-1 expression. This joins promoter occupancy to cis-regulatory function, complementing the conserved CG-1 domain and mammalian DNA-recognition evidence. ChIP occupancy alone does not resolve direct nucleotide contacts, and the worm experiments are not human promoter-specificity assays. Together these findings support refinement to DNA-binding transcription factor activity for human CAMTA1. This gene-level refinement is not a proposal to remap every IPR005559-containing protein solely from domain occurrence.

Proposed replacements: DNA-binding transcription factor activity

Summary: Double-stranded DNA recognition is consistent with the inherited CAMTA transcription-factor activity.

Reason: Retain the PAINT inference at PTN000596526. The conserved CG-1 domain and mammalian functional evidence agree with DNA recognition; no target-specific loss or divergence was found. The extant plant and fly entries are descendant evidence for a curated ancestral assertion, not a pairwise transfer whose quality can be judged from donor count. This broader binding assertion remains valid alongside the more informative activity proposed for the InterPro row.

Summary: The inherited transcription-coregulator assertion remains plausible, but its distinct partner-mediated mechanism is unresolved.

Reason: GO:0003712 denotes transcriptional regulation through a DNA-binding transcription-factor partner at a genomic locus; it is distinct from intrinsic DNA-binding transcription-factor activity. The full primary worm CAMT-1 study was inspected: native cmd-1 promoter occupancy and promoter-region deletions support CAMTA-dependent transcription (PMID:34499028), but do not establish a separate partner-mediated mechanism in human CAMTA1. This is relevant experimental family evidence, not a reconstruction of this row's PAINT IBD. The frozen coregulator row lists PTN000596526, PomBase:SPAC26H5.05 and UniProtKB:O94983; the worm identifier occurs in other CAMTA1 IBA rows, not this row. A CAMTA can possess both intrinsic DNA-binding activity and an additional partner-mediated function, so promoter occupancy does not contradict coregulation. The exact ancestral placement and applicability of a distinct partner mechanism to human CAMTA1 remain unresolved; retain UNDECIDED without inferring target loss or a propagation error.

Summary: Nuclear activity is consistent with the inherited CAMTA transcriptional-regulatory function.

Reason: The PAINT nuclear inference agrees with the established transcriptional activity and the human UniProt nuclear assignment. The diverse descendant list does not weaken an ancestral assertion, and no evidence of target-specific exclusion from the nucleus was found. The 2002 Arabidopsis fractionation is family evidence, not a direct human localization experiment; this source distinction does not contradict the conserved nuclear function.

Summary: The UniProt-derived nuclear location is consistent with CAMTA1 transcriptional regulation.

Reason: Q9Y6Y1 carries a curated nuclear assignment and a predicted nuclear-localization signal, coherent with its transcription-factor activity. This IEA vocabulary mapping is retained as a biologically supported location. Its original source is not relabeled as a direct human fractionation experiment; the experimentally specified fractionation in the accessible 2002 abstract concerns Arabidopsis.

Summary: The curated cytoplasmic assignment cannot be independently resolved from the accessible human study.

Reason: UniProt Q9Y6Y1 assigns cytoplasm by curator inference with PMID:15138581. The accessible human neuroblastoma abstract describes cell-cycle-dependent CAMTA1 abundance and microscopy but does not specify the cytoplasmic distribution needed to assess this location. Full text was not retrieved. Nuclear transcriptional activity does not preclude a cytoplasmic pool, so the annotation is not removed; it remains unresolved pending the localization experiment.

Summary: CAMTA1 directly regulates transcription through its transcriptional-regulator activity.

Reason: The PAINT process assertion is coherent with the conserved CAMTA DNA-binding and activation architecture, human reporter activation, and mammalian CAMTA-dependent reporter transcription. It is retained as the broader transcriptional process, without treating altered expression of every downstream gene as evidence of direct CAMTA1 promoter occupancy. No lineage-specific loss of the inherited function was identified.

Summary: Sequence-specific DNA recognition is consistent with the conserved CAMTA1 CG-1 function.

Reason: Retain the existing Ensembl ortholog transfer from the exact source identifiers A2A891 and ENSMUSP00000054804. The human CG-1 domain and the mammalian CAMTA1 mutagenesis evidence support the biological assertion. The 2014 study reports disrupted CAMTA1 DNA-binding activity for K141E, not only a reporter effect. Detailed motif selection principally used mouse CAMTA2, so that assay is not presented as purified human CAMTA1 evidence.

Summary: CAMTA1 has conserved transcriptional activation capacity.

Reason: Retain the Ensembl transfer of positive RNA polymerase II transcriptional regulation. Direct human activation capacity is established in the LexA yeast system, and mammalian CAMTA motif-dependent reporter activation supplies complementary evidence. These observations support the direction of regulation without proving the native human target repertoire or that all CAMTA1-responsive genes are directly activated.

Summary: CAMTA1 positively affects NFAT signaling in the tested human cell system.

Reason: The original full-text study directly tests CAMTA1: its knockdown decreases stimulated NFAT reporter output in 293A cells and c-Myc-tagged NFATc2 dephosphorylation in 293T cells. This supports the existing perturbation-based positive-regulation assertion, although the molecular link to calcineurin-NFAT remains undefined. The paper separately examines miR-124 and its multiple targets in human pulmonary artery smooth-muscle cells; those miRNA phenotypes are not assigned wholesale to CAMTA1. Retain this contextual signaling role outside the central DNA-dependent transcriptional activity.