Pax6 is a paired-box/paired-type homeobox transcription factor that binds DNA through an N-terminal bipartite paired domain (PAI and RED subdomains) and a C-terminal homeodomain, and activates or represses RNA polymerase II target genes via a C-terminal proline/serine/threonine-rich transactivation domain. Alternative splicing produces the canonical protein, the Pax6(5a) isoform with an altered paired domain, and a paired-less p32 isoform. Pax6 is a dosage-sensitive master regulator of eye development: it is required in head surface ectoderm for lens placode formation and lens development, in the optic cup for retinal progenitor and retinal pigment epithelium specification, and for cornea, iris and lacrimal gland development; heterozygous Small eye (Sey) mice model human aniridia. In the central nervous system it patterns the dorsal telencephalon (pallium) and pallial/subpallial boundary, sets rostrolateral cortical area identity, drives cortical radial glia neurogenesis through a Pax6-Eomes/Tbr2-Tbr1 cascade while restraining progenitor proliferation, establishes ventral progenitor domains in spinal cord and hindbrain in response to graded Shh, and contributes to diencephalic, cerebellar and olfactory development. In the pancreas Pax6 is required for endocrine (especially glucagon-producing alpha and insulin-producing beta) cell differentiation and directly activates proglucagon, MafB, cMaf and NeuroD1. Its activity is modulated by HIPK2 phosphorylation and p300 binding, SUMOylation, TRIM11-mediated degradation, and interaction with Smad3, Sox and Groucho-family partners.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:23990468 The paired-box homeodomain transcription factor Pax6 binds t... | ACCEPT | Summary: Pax6 represses transcription of target genes (e.g. Trap/Acp5 with the corepressor Grg6; Cdk6 in cortical progenitors). Reason: Direct promoter binding plus reporter repression; context-dependent repression is a core facet of Pax6 activity. Supporting Evidence: PMID:23990468 Pax6 binds endogenously to the proximal region of the tartrate acid phosphatase (TRAP) gene promoter and suppresses nuclear factor of activated T cells c1 (NFATc1)-induced TRAP gene expression |
| GO:0000132 establishment of mitotic spindle orientation | IMP PMID:22031545 The role of Pax6 in regulating the orientation and mode of c... | KEEP AS NON CORE | Summary: Pax6 loss alters orientation of cortical progenitor cell division, mediated by its direct target Spag5. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:22031545 This phenotype appears to be mediated by the direct Pax6 target Spag5, a microtubule-associated protein, reduced levels of which result in the replication of the Pax6 phenotype of altered cell division orientation |
| GO:0000785 chromatin | IDA PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: Pax6 is located on chromatin at its target loci. Reason: Supported by ChIP data (e.g. Six6, alpha-cell genes); consistent with human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000785 chromatin | IEA GO_REF:0000120 | ACCEPT | Summary: Pax6 is located on chromatin at its target loci. Reason: combined automated (IEA) annotation. Supported by ChIP data (e.g. Six6, alpha-cell genes); consistent with human review. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0000785 chromatin | ISO GO_REF:0000096 | ACCEPT | Summary: Pax6 is located on chromatin at its target loci. Reason: ISO transfer from the rat ortholog (RGD:3258). Supported by ChIP data (e.g. Six6, alpha-cell genes); consistent with human review. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0000785 chromatin | ISO GO_REF:0000119 | ACCEPT | Summary: Pax6 is located on chromatin at its target loci. Reason: ISO transfer from the human ortholog PAX6 (P26367). Supported by ChIP data (e.g. Six6, alpha-cell genes); consistent with human review. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:19521500 The level of the transcription factor Pax6 is essential for ... | ACCEPT | Summary: Pax6 binds transcription cis-regulatory regions (promoter/enhancer elements) of target genes. Reason: Direct promoter binding is documented by EMSA/ChIP for the Trap promoter in osteoclast lineage cells and genome-wide ChIP in cortical progenitors; this is the core DNA-binding activity of the protein. Consistent with the human PAX6 review. Supporting Evidence: PMID:19521500 finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:23990468 The paired-box homeodomain transcription factor Pax6 binds t... | ACCEPT | Summary: Pax6 binds transcription cis-regulatory regions (promoter/enhancer elements) of target genes. Reason: Direct promoter binding is documented by EMSA/ChIP for the Trap promoter in osteoclast lineage cells and genome-wide ChIP in cortical progenitors; this is the core DNA-binding activity of the protein. Consistent with the human PAX6 review. Supporting Evidence: PMID:23990468 Pax6 binds endogenously to the proximal region of the tartrate acid phosphatase (TRAP) gene promoter and suppresses nuclear factor of activated T cells c1 (NFATc1)-induced TRAP gene expression |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: IBA (PAINT phylogenetic inference). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:12756174 Retinal pigmented epithelium determination requires the redu... | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: combined automated (IEA) annotation. Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: ISO transfer from the rat ortholog (RGD:3258). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory regions via the paired domain and homeodomain. Reason: ISO transfer from the human ortholog PAX6 (P26367). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Binding to the Mitf RPE promoter, to the Sox2 promoter and to alpha-cell gene promoters is directly demonstrated; IBA/IEA/ISO rows agree with the experimental data and the human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding | IDA PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | KEEP AS NON CORE | Summary: Binding to a core promoter element (proglucagon promoter) reported in the HIPK2 phosphorylation study. Reason: Pax6 binding sites are mainly in proximal promoter/enhancer regions; core-promoter-specific binding is a narrower claim than the evidence warrants. Kept as non-core, consistent with the human PAX6 review. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: IBA (PAINT phylogenetic inference). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: combined automated (IEA) annotation. Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000096 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: ISO transfer from the rat ortholog (RGD:3258). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000119 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific: the core molecular function of Pax6. Reason: ISO transfer from the human ortholog PAX6 (P26367). Pax6 is a paired-box/homeodomain sequence-specific RNA polymerase II transcription factor that binds cis-regulatory elements of target genes (e.g. Mitf, Sox2, Six6, proglucagon, MafB, Cdk6, Trap/Acp5) to activate or repress them. Experimental (IDA) evidence from proglucagon and alpha-cell gene promoter studies plus IBA/IEA/ISO rows all agree. Core function. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0001221 transcription coregulator binding | IPI PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | ACCEPT | Summary: Pax6 binds transcriptional coregulators; HIPK2 phosphorylation of the Pax6 PST domain enhances binding of the coactivator p300. Reason: Coactivator (p300) binding is mechanistically part of Pax6 transactivation; consistent with human review. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:23622063 Pax6 exerts regional control of cortical progenitor prolifer... | ACCEPT | Summary: Pax6 acts as a sequence-specific repressor of cell-cycle genes (e.g. Cdk6) in cortical progenitors. Reason: Direct repression of Cdk6 by Pax6 binding is supported by biochemical assays; Pax6 also represses Trap with Grg6. Context-dependent repressor activity is a genuine core facet of the TF. Supporting Evidence: PMID:23622063 Biochemical assays indicated that Pax6 directly represses Cdk6 expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:12756174 Retinal pigmented epithelium determination requires the redu... | ACCEPT | Summary: Pax6 is a sequence-specific transcriptional activator of RNA pol II genes (Mitf, Spag5, alpha-cell genes, Sox2). Reason: Activator function is well documented by reporter and binding assays; PST domain is a potent transactivation domain. Consistent with human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:22031545 The role of Pax6 in regulating the orientation and mode of c... | ACCEPT | Summary: Pax6 is a sequence-specific transcriptional activator of RNA pol II genes (Mitf, Spag5, alpha-cell genes, Sox2). Reason: Activator function is well documented by reporter and binding assays; PST domain is a potent transactivation domain. Consistent with human review. Supporting Evidence: PMID:22031545 This phenotype appears to be mediated by the direct Pax6 target Spag5, a microtubule-associated protein, reduced levels of which result in the replication of the Pax6 phenotype of altered cell division orientation |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Pax6 is a sequence-specific transcriptional activator of RNA pol II genes (Mitf, Spag5, alpha-cell genes, Sox2). Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Activator function is well documented by reporter and binding assays; PST domain is a potent transactivation domain. Consistent with human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000119 | ACCEPT | Summary: Pax6 is a sequence-specific transcriptional activator of RNA pol II genes (Mitf, Spag5, alpha-cell genes, Sox2). Reason: ISO transfer from the human ortholog PAX6 (P26367). Activator function is well documented by reporter and binding assays; PST domain is a potent transactivation domain. Consistent with human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0001568 blood vessel development | IEA GO_REF:0000107 | REMOVE | Summary: Blood vessel development (IEA/ISO transfer from human). Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). No convincing evidence that Pax6 functions in blood vessel development; vascular (hyaloid) phenotypes in eye mutants are secondary to lens/eye defects. Removed, consistent with the human PAX6 review which removed the source IMP annotation. |
| GO:0001568 blood vessel development | ISO GO_REF:0000119 | REMOVE | Summary: Blood vessel development (IEA/ISO transfer from human). Reason: ISO transfer from the human ortholog PAX6 (P26367). No convincing evidence that Pax6 functions in blood vessel development; vascular (hyaloid) phenotypes in eye mutants are secondary to lens/eye defects. Removed, consistent with the human PAX6 review which removed the source IMP annotation. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P26367 Β· PAX6 SOURCE WEAK OR INFERRED Human PAX6 blood vessel development (IMP) was itself removed in the human PAX6 review: vascular findings are secondary to eye malformation rather than a PAX6 vascular function. |
| GO:0001709 cell fate determination | IMP PMID:12756174 Retinal pigmented epithelium determination requires the redu... | KEEP AS NON CORE | Summary: Cell fate determination: Pax2/Pax6 redundantly direct RPE determination by activating Mitf. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12756174 the redundant activities of Pax2 and Pax6 direct the determination of RPE |
| GO:0001755 neural crest cell migration | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neural crest cell migration; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0001764 neuron migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neuron migration; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0001764 neuron migration | IMP PMID:15758185 Selective requirement of Pax6, but not Emx2, in the specific... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neuron migration; IMP evidence from PMID:15758185. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15758185 there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex |
| GO:0001764 neuron migration | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neuron migration; IMP evidence from PMID:30186101. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:30186101 Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression |
| GO:0001764 neuron migration | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neuron migration; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0001933 negative regulation of protein phosphorylation | IMP PMID:16497297 Heat shock protein 27 rescues motor neurons following nerve ... | UNDECIDED | Summary: Negative regulation of protein phosphorylation (IMP). Reason: The cited paper (HSP27 overexpression rescues motor neurons after nerve injury) does not mention Pax6 in its abstract and full text is not cached; the basis for this Pax6 annotation cannot be verified. Pax6 does limit pRb phosphorylation indirectly via Cdk6 repression (PMID:23622063), but that is a transcriptional effect. |
| GO:0002052 positive regulation of neuroblast proliferation | IMP PMID:18287938 Pax6 directly modulate Sox2 expression in the neural progeni... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of neuroblast proliferation; IMP evidence from PMID:18287938. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:18287938 neural progenitors isolated from the Pax6(-/-) embryos showed a decreased neurosphere formation as well as proliferation |
| GO:0002064 epithelial cell development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) epithelial cell development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0002088 lens development in camera-type eye | IMP PMID:6877261 A comparison of the dominant cataract and recessive specific... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) lens development in camera-type eye; IMP evidence from PMID:6877261. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Evidence from PMID:6877261 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0003002 regionalization | IMP PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regionalization; IMP evidence from PMID:24528677. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:24528677 deleting paired-box and homeobox-containing gene Pax6 results in precocious and expanded expression of Shh in the prospective MDO in fish and mice |
| GO:0003002 regionalization | IMP PMID:9169845 Pax-6 functions in boundary formation and axon guidance in t... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regionalization; IMP evidence from PMID:9169845. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9169845 Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance |
| GO:0003002 regionalization | IMP PMID:9169845 Pax-6 functions in boundary formation and axon guidance in t... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regionalization; IMP evidence from PMID:9169845. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9169845 Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance |
| GO:0003309 type B pancreatic cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) type B pancreatic cell differentiation; IBA evidence from GO_REF:0000033. Reason: IBA (PAINT phylogenetic inference). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003309 type B pancreatic cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) type B pancreatic cell differentiation; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:22764048 Pancreas-enriched miRNA refines endocrine cell differentiati... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) type B pancreatic cell differentiation; IMP evidence from PMID:22764048. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:22764048 miR-7 overexpression in developing pancreas explants or in transgenic mice led to Pax6 downregulation and inhibition of Ξ±- and Ξ²-cell differentiation |
| GO:0003309 type B pancreatic cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) type B pancreatic cell differentiation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003310 pancreatic A cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pancreatic A cell differentiation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003322 pancreatic A cell development | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pancreatic A cell development; IEA evidence from GO_REF:0000120. Reason: combined automated (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003322 pancreatic A cell development | IMP PMID:20592023 Pax6 controls the expression of critical genes involved in p... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pancreatic A cell development; IMP evidence from PMID:20592023. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:20592023 homozygous mutant mice for Pax6 are characterized by markedly decreased Ξ² and Ξ΄ cells and absent Ξ± cells |
| GO:0003322 pancreatic A cell development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pancreatic A cell development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003322 pancreatic A cell development | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pancreatic A cell development; ISO evidence from GO_REF:0000119. Reason: ISO transfer from the human ortholog PAX6 (P26367). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0003677 DNA binding | IDA PMID:12756174 Retinal pigmented epithelium determination requires the redu... | KEEP AS NON CORE | Summary: Generic DNA binding; correct but less informative than sequence-specific Pol II cis-regulatory region binding. Reason: Pax6 certainly binds DNA, but more specific terms (GO:0000978, GO:0043565) capture the function. Kept as non-core, consistent with human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic DNA binding; correct but less informative than sequence-specific Pol II cis-regulatory region binding. Reason: InterPro2GO mapping (paired domain/homeobox). Pax6 certainly binds DNA, but more specific terms (GO:0000978, GO:0043565) capture the function. Kept as non-core, consistent with human review. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0003680 minor groove of adenine-thymine-rich DNA binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Minor-groove AT-rich DNA binding, transferred from rat. Reason: ISO transfer from the rat ortholog (RGD:3258). Paired-domain and homeodomain DNA recognition involves minor-groove contacts (the paired-domain N-terminal beta-turn and homeodomain N-terminal arm), but AT-rich minor-groove binding is not a defining activity; retained as non-core, subsumed by sequence-specific DNA binding. |
| GO:0003682 chromatin binding | IDA PMID:19146846 The LIM homeobox transcription factor Lhx2 is required to sp... | ACCEPT | Summary: Pax6 associates with chromatin at target loci (e.g. Six6 regulatory regions, Paupar-bound promoters). Reason: ChIP evidence shows Pax6 occupancy of chromatin at target loci; consistent with nuclear TF function and the human review. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0003682 chromatin binding | IDA PMID:23637604 Differential adaptation of Candida albicans in vivo modulate... | UNDECIDED | Summary: Chromatin binding (IDA) attributed to a paper on Dectin-1 and Candida albicans adaptation. Reason: The cached full text of PMID:23637604 (Candida albicans/Dectin-1 immunology) does not mention Pax6 at all, suggesting a reference identifier problem in the source annotation. Chromatin binding by Pax6 is itself well supported by other rows (PMID:19146846, PMID:24488179), so the function is not in doubt, but this specific row cannot be verified. |
| GO:0003682 chromatin binding | IDA PMID:24488179 The long non-coding RNA Paupar regulates the expression of b... | ACCEPT | Summary: Pax6 associates with chromatin at target loci (e.g. Six6 regulatory regions, Paupar-bound promoters). Reason: ChIP evidence shows Pax6 occupancy of chromatin at target loci; consistent with nuclear TF function and the human review. Supporting Evidence: PMID:24488179 in part through physical association with PAX6 protein |
| GO:0003690 double-stranded DNA binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Double-stranded DNA binding (ISO from rat). Reason: ISO transfer from the rat ortholog (RGD:3258). Correct but general; subsumed by sequence-specific double-stranded DNA binding (GO:1990837) and Pol II cis-regulatory region binding. Non-core. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:18287938 Pax6 directly modulate Sox2 expression in the neural progeni... | ACCEPT | Summary: DNA-binding transcription factor activity. Reason: Pax6 is a canonical sequence-specific transcription factor; the Sox2 promoter study and the Pax family review support this. Accept (the RNA pol II-specific child GO:0000981 is the preferred core term). Supporting Evidence: PMID:18287938 We confirmed that Pax6 could bind to the Sox2 promoter by chromatin immunoprecipitation assay and activate Sox2 expression by a luciferase reporter gene assay |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:10197584 Pax genes and their role in organogenesis. | ACCEPT | Summary: DNA-binding transcription factor activity. Reason: Pax6 is a canonical sequence-specific transcription factor; the Sox2 promoter study and the Pax family review support this. Accept (the RNA pol II-specific child GO:0000981 is the preferred core term). Supporting Evidence: PMID:10197584 They share a common domain, the paired domain, that is sufficient to mediate sequence-specific DNA binding |
| GO:0003723 RNA binding | IDA PMID:24488179 The long non-coding RNA Paupar regulates the expression of b... | KEEP AS NON CORE | Summary: RNA binding: Pax6 physically associates with the lncRNA Paupar. Reason: Paupar transcript associates with PAX6 protein and co-occupies regulatory elements; this is an experimentally supported but peripheral property, not a defined RNA-binding molecular function. The human review removed the IEA version (no direct evidence); here the IDA row is the primary evidence so it is kept as non-core. Supporting Evidence: PMID:24488179 in part through physical association with PAX6 protein |
| GO:0005515 protein binding | IPI PMID:16098226 A screen for proteins that interact with PAX6: C-terminal mu... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' from a yeast two-hybrid screen (partners HOMER3, DNCL1/Dynll1, TRIM11). The TRIM11 interaction is better captured by ubiquitin protein ligase binding (GO:0031625, PMID:18628401). Removal does not imply the interaction is false. Supporting Evidence: PMID:16098226 Three novel PAX6-interacting proteins were identified: the post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11 |
| GO:0005515 protein binding | IPI PMID:16098226 A screen for proteins that interact with PAX6: C-terminal mu... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' from a yeast two-hybrid screen (partners HOMER3, DNCL1/Dynll1, TRIM11). The TRIM11 interaction is better captured by ubiquitin protein ligase binding (GO:0031625, PMID:18628401). Removal does not imply the interaction is false. Supporting Evidence: PMID:16098226 Three novel PAX6-interacting proteins were identified: the post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11 |
| GO:0005515 protein binding | IPI PMID:16098226 A screen for proteins that interact with PAX6: C-terminal mu... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' from a yeast two-hybrid screen (partners HOMER3, DNCL1/Dynll1, TRIM11). The TRIM11 interaction is better captured by ubiquitin protein ligase binding (GO:0031625, PMID:18628401). Removal does not imply the interaction is false. Supporting Evidence: PMID:16098226 Three novel PAX6-interacting proteins were identified: the post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11 |
| GO:0005515 protein binding | IPI PMID:16675956 Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a ... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' (partner Smarca4/BRG1, a chromatin remodeller recruited to alphaA-crystallin locus). No specific MF term is clearly established from the cached text. Removal does not imply the interaction is false. Supporting Evidence: PMID:16675956 Chromatin immunoprecipitations showed binding of Pax6 to DCR1 and the Ξ±A-crystallin promoter in lens chromatin |
| GO:0005515 protein binding | IPI PMID:21084637 Sumoylation activates the transcriptional activity of Pax-6,... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' to SUMO1; reflects Pax6 (p32 isoform) being a sumoylation substrate. Removal does not imply the interaction is false. Supporting Evidence: PMID:21084637 Pax-6 and SUMO1 are colocalized in the embryonic optic and lens vesicles and can be coimmunoprecipitated |
| GO:0005515 protein binding | IPI PMID:23447615 Paired related homeobox protein 1 is a regulator of stemness... | REMOVE | Summary: Generic protein binding (IPI). Reason: Uninformative 'protein binding' to Sox2 (identified in a Sox2-partner screen in adult NSCs). Sox-Pax6 partnership is better represented by HMG box domain binding (GO:0071837). Removal does not imply the interaction is false. Supporting Evidence: PMID:23447615 our screen for Sox2 binding partners in adult NSCs also identified another paired-type homeobox transcription factor, Pax6 |
| GO:0005515 protein binding | IPI PMID:23990468 The paired-box homeodomain transcription factor Pax6 binds t... | MODIFY | Summary: Pax6 binds the Groucho-family corepressor Grg6/Tle6, which contributes to Pax6-mediated repression of Trap. Reason: UniProt records the Pax6-TLE6/GRG6 interaction from this paper, and Grg6 acts as a corepressor for Pax6 repression of Trap. The informative MF is transcription corepressor binding. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:23990468 the Groucho family member co-repressor Grg6 contributes to Pax6-mediated suppression of the TRAP gene expression induced by NFATc1 |
| GO:0005634 nucleus | EXP PMID:21084637 Sumoylation activates the transcriptional activity of Pax-6,... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:21084637 SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: IBA (PAINT phylogenetic inference). Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. |
| GO:0005634 nucleus | IDA PMID:11209945 Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the devel... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:11209945 Coordinated expression of Hoxa2, Hoxd1 and Pax6 proteins were found to coincide with the three developmental stages of the diencephalon |
| GO:0005634 nucleus | IDA PMID:12050133 Six3-mediated auto repression and eye development requires i... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Evidence from PMID:12050133 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0005634 nucleus | IDA PMID:14625556 Otx2 homeobox gene controls retinal photoreceptor cell fate ... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Evidence from PMID:14625556 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0005634 nucleus | IDA PMID:16464444 Analysis of Pax6 expression using a BAC transgene reveals th... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:16464444 we identify, for the first time in mammals, an isoform of the Pax6 protein lacking the paired domain |
| GO:0005634 nucleus | IDA PMID:19409883 The transcriptional repressor RP58 is crucial for cell-divis... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Evidence from PMID:19409883 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0005634 nucleus | IDA PMID:22764048 Pancreas-enriched miRNA refines endocrine cell differentiati... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:22764048 miR-7 overexpression in developing pancreas explants or in transgenic mice led to Pax6 downregulation and inhibition of Ξ±- and Ξ²-cell differentiation |
| GO:0005634 nucleus | IDA PMID:23434913 Scratch regulates neuronal migration onset via an epithelial... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Evidence from PMID:23434913 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0005634 nucleus | IDA PMID:23990468 The paired-box homeodomain transcription factor Pax6 binds t... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:23990468 Pax6 binds endogenously to the proximal region of the tartrate acid phosphatase (TRAP) gene promoter and suppresses nuclear factor of activated T cells c1 (NFATc1)-induced TRAP gene expression |
| GO:0005634 nucleus | IDA PMID:24466353 Mouse model reveals the role of RERE in cerebellar foliation... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:24466353 we looked for co-expression of RERE and PAX6βa marker GCPs |
| GO:0005634 nucleus | IDA PMID:25100583 Proliferative defects and formation of a double cortex in mi... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:25100583 We used Pax6 as a marker for RGCs |
| GO:0005634 nucleus | IDA PMID:9230312 Pax6 controls progenitor cell identity and neuronal fate in ... | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. Supporting Evidence: PMID:9230312 Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: combined automated (IEA) annotation. Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. |
| GO:0005634 nucleus | ISO GO_REF:0000096 | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: ISO transfer from the rat ortholog (RGD:3258). Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: ISO transfer from the human ortholog PAX6 (P26367). Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Pax6 is a nuclear transcription factor. Reason: ISS curator transfer from an ortholog. Nuclear localization is well established (immunostaining in many tissues; UniProt). Many IDA rows come from papers that used Pax6 nuclear immunostaining as a progenitor marker, which still directly shows nuclear localization. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleoplasm. Reason: combined automated (IEA) annotation. Consistent with nuclear TF function; accepted as in the human review. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: Nucleoplasm. Reason: ISO transfer from the human ortholog PAX6 (P26367). Consistent with nuclear TF function; accepted as in the human review. |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-5619441 | ACCEPT | Summary: Nucleoplasm. Reason: Reactome TAS (Pax6 bound at a target-gene regulatory region). Consistent with nuclear TF function; accepted as in the human review. |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9832816 | ACCEPT | Summary: Nucleoplasm. Reason: Reactome TAS (Pax6 bound at a target-gene regulatory region). Consistent with nuclear TF function; accepted as in the human review. |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Transcription regulator complex. Reason: ARBA machine-learning (IEA) annotation. Pax6 acts with partners (Sox2, Maf, Lhx2, Smad3, Grg6, REST-corepressor complexes), but no stable defined Pax6-containing complex is characterised; kept as non-core. Supporting Evidence: PMID:23643363 modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors |
| GO:0005667 transcription regulator complex | TAS PMID:10197584 Pax genes and their role in organogenesis. | KEEP AS NON CORE | Summary: Transcription regulator complex. Reason: Pax6 acts with partners (Sox2, Maf, Lhx2, Smad3, Grg6, REST-corepressor complexes), but no stable defined Pax6-containing complex is characterised; kept as non-core. Supporting Evidence: PMID:23643363 modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors |
| GO:0005737 cytoplasm | EXP PMID:21084637 Sumoylation activates the transcriptional activity of Pax-6,... | KEEP AS NON CORE | Summary: Cytoplasm: the p32 (paired-less) isoform, when SUMO-conjugated, is found in both nucleus and cytoplasm. Reason: Minor/isoform-specific localization; nuclear location is the functional one. Non-core, consistent with human review. Supporting Evidence: PMID:21084637 SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cytoplasm: the p32 (paired-less) isoform, when SUMO-conjugated, is found in both nucleus and cytoplasm. Reason: combined automated (IEA) annotation. Minor/isoform-specific localization; nuclear location is the functional one. Non-core, consistent with human review. Supporting Evidence: PMID:21084637 SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cytoplasm: the p32 (paired-less) isoform, when SUMO-conjugated, is found in both nucleus and cytoplasm. Reason: ISO transfer from the human ortholog PAX6 (P26367). Minor/isoform-specific localization; nuclear location is the functional one. Non-core, consistent with human review. Supporting Evidence: PMID:21084637 SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm |
| GO:0005829 cytosol | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Cytosol (ISO from human). Reason: ISO transfer from the human ortholog PAX6 (P26367). Minor localization, as for cytoplasm; non-core. |
| GO:0006338 chromatin remodeling | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | MARK AS OVER ANNOTATED | Summary: Chromatin remodeling (IMP). Reason: Pax6 regulates expression of epigenetic-factor genes (including chromatin remodellers) and recruits remodelling enzymes to lens loci, but Pax6 itself does not remodel chromatin. Over-annotation, consistent with human review. Supporting Evidence: PMID:30186101 many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1 |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Regulation of DNA-templated transcription. Reason: InterPro2GO mapping (paired domain/homeobox). Correct, general; Pax6 is a sequence-specific TF. Accept (Pol II-specific children preferred). Supporting Evidence: PMID:10197584 They share a common domain, the paired domain, that is sufficient to mediate sequence-specific DNA binding |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:10197584 Pax genes and their role in organogenesis. | ACCEPT | Summary: Regulation of DNA-templated transcription. Reason: Correct, general; Pax6 is a sequence-specific TF. Accept (Pol II-specific children preferred). Supporting Evidence: PMID:10197584 They share a common domain, the paired domain, that is sufficient to mediate sequence-specific DNA binding |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: IBA (PAINT phylogenetic inference). Core process for a Pol II sequence-specific TF; IBA and IMP rows agree. Supporting Evidence: PMID:19521500 finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis PMID:9230312 Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:19521500 The level of the transcription factor Pax6 is essential for ... | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: Core process for a Pol II sequence-specific TF; IBA and IMP rows agree. Supporting Evidence: PMID:19521500 finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:9230312 Pax6 controls progenitor cell identity and neuronal fate in ... | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: Core process for a Pol II sequence-specific TF; IBA and IMP rows agree. Supporting Evidence: PMID:9230312 Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons |
| GO:0007224 smoothened signaling pathway | IDA PMID:18590716 FKBP8 cell-autonomously controls neural tube patterning thro... | UNDECIDED | Summary: Smoothened signaling pathway (IDA, FKBP8 neural tube patterning paper). Reason: Pax6 is a classical transcriptional readout of graded Shh signalling in the neural tube (repressed by high Shh), but being a target of a pathway is not participation in it. The abstract does not mention Pax6 and full text is not cached, so the curator's basis cannot be assessed. |
| GO:0007399 nervous system development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) nervous system development; IEA evidence from GO_REF:0000107. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0007399 nervous system development | IMP PMID:24802670 MiR-135b is a direct PAX6 target and specifies human neuroec... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) nervous system development; IMP evidence from PMID:24802670. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Evidence from PMID:24802670 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0007399 nervous system development | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) nervous system development; ISO evidence from GO_REF:0000119. Reason: ISO transfer from the human ortholog PAX6 (P26367). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0007409 axonogenesis | IMP PMID:15514979 Pax6 guides a relay of pioneer longitudinal axons in the emb... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) axonogenesis; IMP evidence from PMID:15514979. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15514979 In Pax6 mutants, both longitudinal tracts failed to form due to errors by every population of early longitudinal axons |
| GO:0007411 axon guidance | IMP PMID:11967891 Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) axon guidance; IMP evidence from PMID:11967891. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11967891 In Pax6 mutants, neither corticothalamic nor thalamocortical axons reached their targets |
| GO:0007411 axon guidance | IMP PMID:14586016 R-cadherin is a Pax6-regulated, growth-promoting cue for pio... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) axon guidance; IMP evidence from PMID:14586016. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:14586016 these studies implicate Pax6 as an early brain patterning gene that establishes regional adhesive codes to guide pioneer axons |
| GO:0007420 brain development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) brain development; IBA evidence from GO_REF:0000033. Reason: IBA (PAINT phylogenetic inference). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0007420 brain development | IMP PMID:10409504 Role of Pax6 in development of the cerebellar system. | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) brain development; IMP evidence from PMID:10409504. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10409504 Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos |
| GO:0007420 brain development | IMP PMID:12196586 Distinct actions of Emx1, Emx2, and Pax6 in regulating the s... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) brain development; IMP evidence from PMID:12196586. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12196586 opposite effects occur in Pax6 mutants, consistent with their opposing gradients of expression |
| GO:0007423 sensory organ development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) sensory organ development; IBA evidence from GO_REF:0000033. Reason: IBA (PAINT phylogenetic inference). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0007435 salivary gland morphogenesis | IMP PMID:11731698 Embryonic submandibular gland morphogenesis: stage-specific ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) salivary gland morphogenesis; IMP evidence from PMID:11731698. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11731698 our observations of abnormal SMGs in BMP7(-/-) and Pax6(-/-) indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis |
| GO:0007601 visual perception | IMP PMID:38155679 A visually guided swim assay for mouse models of human retin... | MARK AS OVER ANNOTATED | Summary: Visual perception (IMP) from eyeless Pax6 Sey-Dey mice used as non-sighted controls in a swim assay. Reason: Loss of vision is a downstream consequence of anophthalmia; Pax6 does not act in the process of visual perception. Over-annotation (phenotype propagation). Supporting Evidence: PMID:38155679 we have included eyeless Pax6Sey-Dey mice, which completely lack vision due to anophthalmia |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) negative regulation of cell population proliferation; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 Retrovirally mediated overexpression of Pax6 containing exon 5a inhibited cell proliferation without affecting cell fate |
| GO:0009611 response to wounding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to wounding (IEA transfer from human PAX6 IEP corneal wound-healing data). Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Anatomical structure morphogenesis (ARBA IEA). Reason: ARBA machine-learning (IEA) annotation. Extremely general; more specific developmental terms exist. Over-annotation, consistent with human review. |
| GO:0009786 regulation of asymmetric cell division | IMP PMID:22031545 The role of Pax6 in regulating the orientation and mode of c... | KEEP AS NON CORE | Summary: Pax6-deficient cortical progenitors show altered mode (symmetric/asymmetric) of division via the target Spag5. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:22031545 This phenotype appears to be mediated by the direct Pax6 target Spag5, a microtubule-associated protein, reduced levels of which result in the replication of the Pax6 phenotype of altered cell division orientation |
| GO:0009950 dorsal/ventral axis specification | IMP PMID:10588713 Pax6 is essential for establishing ventral-dorsal cell bound... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral axis specification; IMP evidence from PMID:10588713. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10588713 We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals |
| GO:0009950 dorsal/ventral axis specification | IMP PMID:10588713 Pax6 is essential for establishing ventral-dorsal cell bound... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral axis specification; IMP evidence from PMID:10588713. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10588713 We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals |
| GO:0009952 anterior/posterior pattern specification | IGI PMID:15917450 Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) anterior/posterior pattern specification; IGI evidence from PMID:15917450. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15917450 In the embryonic day 9.5 Emx2-/-Pax6-/- double mutant, the caudal forebrain remained unspecified and subsequently transformed into tectum |
| GO:0009952 anterior/posterior pattern specification | IMP PMID:12196586 Distinct actions of Emx1, Emx2, and Pax6 in regulating the s... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) anterior/posterior pattern specification; IMP evidence from PMID:12196586. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12196586 opposite effects occur in Pax6 mutants, consistent with their opposing gradients of expression |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral pattern formation; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6 |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral pattern formation; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6 |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral pattern formation; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6 |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:15878992 Ventralized dorsal telencephalic progenitors in Pax6 mutant ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) dorsal/ventral pattern formation; IMP evidence from PMID:15878992. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15878992 Pax6 delimits the appropriate proliferative zone for GABA INs and regulates their numbers and distributions by repressing the ventral fates of dTel progenitors and progeny |
| GO:0010467 gene expression | IMP PMID:15110720 Involvement of Pax6 and Otx2 in the forebrain-specific regul... | MODIFY | Summary: Gene expression (IMP) - Pax6 mutants show altered expression of target genes. Reason: 'Gene expression' itself is not something Pax6 executes; the mutant data reflect Pax6's role as a regulator of transcription. Replace with regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:15110720 in Pax6(-/-) mice the expression domain of the murine ANF orthologue Hesx1 was expanded and sustained |
| GO:0010467 gene expression | IMP PMID:24488179 The long non-coding RNA Paupar regulates the expression of b... | MODIFY | Summary: Gene expression (IMP) - Pax6 mutants show altered expression of target genes. Reason: 'Gene expression' itself is not something Pax6 executes; the mutant data reflect Pax6's role as a regulator of transcription. Replace with regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:24488179 in part through physical association with PAX6 protein |
| GO:0010467 gene expression | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | MODIFY | Summary: Gene expression (IMP) - Pax6 mutants show altered expression of target genes. Reason: 'Gene expression' itself is not something Pax6 executes; the mutant data reflect Pax6's role as a regulator of transcription. Replace with regulation of transcription by RNA polymerase II. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:30186101 many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1 |
| GO:0010468 regulation of gene expression | IMP PMID:12764040 Emx1, emx2 and pax6 in specification, regionalization and ar... | KEEP AS NON CORE | Summary: Regulation of gene expression inferred from altered target expression in Pax6 mutant cortex/telencephalon. Reason: Correct but very general; reflects TF function. Kept as non-core. Supporting Evidence: PMID:12764040 both genes are necessary and sufficient for a more basic developmental choice, i.e. the specification of neuroblasts in the dorsal telencephalon as cortical versus ganglionic neuroblasts |
| GO:0010468 regulation of gene expression | IMP PMID:16919471 Potential target genes of EMX2 include Odz/Ten-M and other g... | KEEP AS NON CORE | Summary: Regulation of gene expression inferred from altered target expression in Pax6 mutant cortex/telencephalon. Reason: Correct but very general; reflects TF function. Kept as non-core. Supporting Evidence: PMID:16919471 each of the genes analyzed shows different expression patterns in wild type cortex, Emx2, and Pax6 mutant cortex |
| GO:0010468 regulation of gene expression | IMP PMID:18799682 Molecular specification and patterning of progenitor cells i... | KEEP AS NON CORE | Summary: Regulation of gene expression inferred from altered target expression in Pax6 mutant cortex/telencephalon. Reason: Correct but very general; reflects TF function. Kept as non-core. Evidence from PMID:18799682 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of gene expression. Reason: combined automated (IEA) annotation. Pax6 activates target gene expression (e.g. alpha-cell genes); consistent with human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0010628 positive regulation of gene expression | IMP PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: Positive regulation of gene expression. Reason: Pax6 activates target gene expression (e.g. alpha-cell genes); consistent with human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000096 | ACCEPT | Summary: Positive regulation of gene expression. Reason: ISO transfer from the rat ortholog (RGD:3258). Pax6 activates target gene expression (e.g. alpha-cell genes); consistent with human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of gene expression. Reason: ISO transfer from the human ortholog PAX6 (P26367). Pax6 activates target gene expression (e.g. alpha-cell genes); consistent with human review. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0010975 regulation of neuron projection development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neuron projection development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0019901 protein kinase binding | IPI PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | KEEP AS NON CORE | Summary: Pax6 binds the kinase HIPK2, which phosphorylates its transactivation domain. Reason: HIPK2 is an upstream regulator of Pax6 rather than Pax6 having a kinase-binding function; kept as non-core, consistent with human review. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0021510 spinal cord development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) spinal cord development; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0021517 ventral spinal cord development | IMP PMID:20844123 Sox1 is required for the specification of a novel p2-derived... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) ventral spinal cord development; IMP evidence from PMID:20844123. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:20844123 subsets of these cells express the transcription factor Pax6 |
| GO:0021537 telencephalon development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) telencephalon development; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0021543 pallium development | IMP PMID:11124115 Gsh2 and Pax6 play complementary roles in dorsoventral patte... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pallium development; IMP evidence from PMID:11124115. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11124115 in the Pax6 mutants the VP is respecified into a dLGE-like structure |
| GO:0021593 rhombomere morphogenesis | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) rhombomere morphogenesis; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0021772 olfactory bulb development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) olfactory bulb development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0021778 oligodendrocyte cell fate specification | IMP PMID:9828088 Pax6 influences the time and site of origin of glial precurs... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) oligodendrocyte cell fate specification; IMP evidence from PMID:9828088. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9828088 In Small eye (Pax6-deficient) mice, the origin of OLPs is shifted dorsally and both OLPs and Isl2/Lim3 MNs are delayed |
| GO:0021796 cerebral cortex regionalization | IMP PMID:12764040 Emx1, emx2 and pax6 in specification, regionalization and ar... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cerebral cortex regionalization; IMP evidence from PMID:12764040. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12764040 both genes are necessary and sufficient for a more basic developmental choice, i.e. the specification of neuroblasts in the dorsal telencephalon as cortical versus ganglionic neuroblasts |
| GO:0021796 cerebral cortex regionalization | IMP PMID:23431145 The protomap is propagated to cortical plate neurons through... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cerebral cortex regionalization; IMP evidence from PMID:23431145. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:23431145 propagated by the Pax6 β Eomes β Tbr1 TF cascade |
| GO:0021796 cerebral cortex regionalization | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cerebral cortex regionalization; IMP evidence from PMID:30186101. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:30186101 Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression |
| GO:0021798 forebrain dorsal/ventral pattern formation | IMP PMID:11050125 Pax6 modulates the dorsoventral patterning of the mammalian ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain dorsal/ventral pattern formation; IMP evidence from PMID:11050125. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11050125 Pax6 has an essential role for the modulation of the dorsoventral patterning of the embryonic telencephalon |
| GO:0021798 forebrain dorsal/ventral pattern formation | IMP PMID:11124115 Gsh2 and Pax6 play complementary roles in dorsoventral patte... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain dorsal/ventral pattern formation; IMP evidence from PMID:11124115. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11124115 in the Pax6 mutants the VP is respecified into a dLGE-like structure |
| GO:0021798 forebrain dorsal/ventral pattern formation | IMP PMID:18701439 Differential regulation of telencephalic pallial-subpallial ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain dorsal/ventral pattern formation; IMP evidence from PMID:18701439. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:18701439 both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification |
| GO:0021798 forebrain dorsal/ventral pattern formation | IMP PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain dorsal/ventral pattern formation; IMP evidence from PMID:24528677. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:24528677 the thalamic domain is shifted dorsally and the epithalamus is missing in the alar plate of p2 in the Pax6 mutant mouse |
| GO:0021902 commitment of neuronal cell to specific neuron type in forebrain | IMP PMID:11124115 Gsh2 and Pax6 play complementary roles in dorsoventral patte... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) commitment of neuronal cell to specific neuron type in forebrain; IMP evidence from PMID:11124115. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11124115 in the Pax6 mutants the VP is respecified into a dLGE-like structure |
| GO:0021905 forebrain-midbrain boundary formation | IMP PMID:9169845 Pax-6 functions in boundary formation and axon guidance in t... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain-midbrain boundary formation; IMP evidence from PMID:9169845. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9169845 Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance |
| GO:0021905 forebrain-midbrain boundary formation | IMP PMID:9169845 Pax-6 functions in boundary formation and axon guidance in t... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain-midbrain boundary formation; IMP evidence from PMID:9169845. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9169845 Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance |
| GO:0021978 telencephalon regionalization | IMP PMID:18701439 Differential regulation of telencephalic pallial-subpallial ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) telencephalon regionalization; IMP evidence from PMID:18701439. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:18701439 both Pax6 and Gsh2 are directly required for major aspects of PSB progenitor specification |
| GO:0021983 pituitary gland development | IMP PMID:10588713 Pax6 is essential for establishing ventral-dorsal cell bound... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pituitary gland development; IMP evidence from PMID:10588713. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10588713 We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals |
| GO:0021983 pituitary gland development | IMP PMID:10588713 Pax6 is essential for establishing ventral-dorsal cell bound... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) pituitary gland development; IMP evidence from PMID:10588713. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10588713 We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals |
| GO:0021986 habenula development | IMP PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) habenula development; IMP evidence from PMID:24528677. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:24528677 the thalamic domain is shifted dorsally and the epithalamus is missing in the alar plate of p2 in the Pax6 mutant mouse |
| GO:0021987 cerebral cortex development | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cerebral cortex development; IMP evidence from PMID:30186101. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:30186101 Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression |
| GO:0022027 interkinetic nuclear migration | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) interkinetic nuclear migration; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0023019 signal transduction involved in regulation of gene expression | IDA PMID:18462699 ER71 acts downstream of BMP, Notch, and Wnt signaling in blo... | UNDECIDED | Summary: Signal transduction involved in regulation of gene expression (IDA, ER71 paper). Reason: The cited abstract (ER71 downstream of BMP/Notch/Wnt in blood/vessel progenitors) does not mention Pax6 and the full text is not cached; cannot verify what was assayed for Pax6. Pax6 is not a known signal transducer. |
| GO:0030154 cell differentiation | IMP PMID:15031110 The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic g... | MODIFY | Summary: Cell differentiation (IMP): Pax6 Sey/Sey mice have few pancreatic endocrine cells. Reason: The general term should be replaced by the specific endocrine differentiation term supported by the paper (glucagon-cell identity). Proposed replacements: pancreatic A cell differentiation Supporting Evidence: PMID:15031110 Pax6 mutant mice (pax6(Sey/Sey)), with a natural inactivating mutation in pax6, have few endocrine cells |
| GO:0030154 cell differentiation | IMP PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | MODIFY | Summary: Cell differentiation (IMP): loss of Pax6 abolishes epithalamus/habenular neuron specification in prosomere 2. Reason: The general term should be replaced by the specific process supported by the paper. Proposed replacements: habenula development Supporting Evidence: PMID:24528677 the thalamic domain is shifted dorsally and the epithalamus is missing in the alar plate of p2 in the Pax6 mutant mouse |
| GO:0030182 neuron differentiation | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neuron differentiation; IMP evidence from PMID:30186101. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:30186101 many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1 |
| GO:0030216 keratinocyte differentiation | IMP PMID:16080917 Developmental and cellular factors underlying corneal epithe... | MODIFY | Summary: Keratinocyte differentiation (IMP) from delayed K12 expression in Pax6+/- corneal epithelium. Reason: The phenotype concerns corneal epithelial cell differentiation, not epidermal keratinocytes. Replace with the specific term corneal epithelial cell differentiation. Proposed replacements: corneal epithelial cell differentiation Supporting Evidence: PMID:16080917 K12 expression was delayed and down-regulated in the Pax6+/- corneal epithelium, implying that differentiation of the Pax6+/- corneal epithelium was delayed and abnormal |
| GO:0030334 regulation of cell migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of cell migration; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0030334 regulation of cell migration | IMP PMID:10409504 Role of Pax6 in development of the cerebellar system. | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of cell migration; IMP evidence from PMID:10409504. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10409504 Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos |
| GO:0030334 regulation of cell migration | IMP PMID:18701439 Differential regulation of telencephalic pallial-subpallial ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of cell migration; IMP evidence from PMID:18701439. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:18701439 the establishment of the epidermal growth factor receptor positive lateral cortical stream migratory route to the basal telencephalon is Pax6 dependent |
| GO:0030858 positive regulation of epithelial cell differentiation | IMP PMID:16080917 Developmental and cellular factors underlying corneal epithe... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of epithelial cell differentiation; IMP evidence from PMID:16080917. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:16080917 K12 expression was delayed and down-regulated in the Pax6+/- corneal epithelium, implying that differentiation of the Pax6+/- corneal epithelium was delayed and abnormal |
| GO:0030900 forebrain development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain development; IBA evidence from GO_REF:0000033. Reason: IBA (PAINT phylogenetic inference). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0030900 forebrain development | IMP PMID:15514979 Pax6 guides a relay of pioneer longitudinal axons in the emb... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain development; IMP evidence from PMID:15514979. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15514979 In Pax6 mutants, both longitudinal tracts failed to form due to errors by every population of early longitudinal axons |
| GO:0030900 forebrain development | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain development; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6 |
| GO:0030900 forebrain development | IMP PMID:15758185 Selective requirement of Pax6, but not Emx2, in the specific... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) forebrain development; IMP evidence from PMID:15758185. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15758185 there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex |
| GO:0030902 hindbrain development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) hindbrain development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0031490 chromatin DNA binding | IDA PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | ACCEPT | Summary: Pax6 binds chromatin DNA at target loci (ChIP-seq in embryonic neocortex). Reason: Pax6 directly binds epigenetic-factor and TF genes in cortical chromatin; consistent with human review. Supporting Evidence: PMID:30186101 many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1 |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:18628401 Trim11 modulates the function of neurogenic transcription fa... | KEEP AS NON CORE | Summary: Pax6 binds the E3 ubiquitin ligase Trim11, which ubiquitinates Pax6 and targets it for proteasomal degradation. Reason: The interaction is real, but Pax6 is the substrate rather than having a ligase-binding function of its own; kept as non-core (the human review accepted the IEA version; we consider it a regulatory input rather than a core activity). Supporting Evidence: PMID:18628401 Trim11, a member of the TRIM/RBCC protein family of E3 ubiquitin ligases, interacts with Pax6 and mediates Pax6 degradation via the ubiquitin-proteasome system |
| GO:0032808 lacrimal gland development | IMP PMID:10821755 FGF10 is an inducer and Pax6 a competence factor for lacrima... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) lacrimal gland development; IMP evidence from PMID:10821755. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:10821755 the transcription factor Pax6 is required for normal development of the gland and is probably an important competence factor |
| GO:0035035 histone acetyltransferase binding | IDA PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | ACCEPT | Summary: Pax6 binds the histone acetyltransferase p300; binding is enhanced by HIPK2 phosphorylation. Reason: Coactivator (HAT) binding underlies Pax6 transactivation; consistent with human review. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0042462 eye photoreceptor cell development | IMP PMID:12648492 The roles of Pax6 in the cornea, retina, and olfactory epith... | UNDECIDED | Summary: Eye photoreceptor cell development (IMP, chimera study). Reason: The cited abstract describes Pax6 requirement in corneal epithelium/stroma, neural retina and olfactory epithelium but says nothing about photoreceptors; full text not cached. Pax6 is required for retinal progenitor multipotency rather than photoreceptor development specifically. Cannot verify. Supporting Evidence: PMID:12648492 Pax6(-/-) cells contributed only poorly to the neural retina, forming small clumps of cells that were normally restricted to the ganglion cell layer at E16.5 |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) glucose homeostasis; IEA evidence from GO_REF:0000107. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0042593 glucose homeostasis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) glucose homeostasis; ISO evidence from GO_REF:0000119. Reason: ISO transfer from the human ortholog PAX6 (P26367). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0042660 positive regulation of cell fate specification | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of cell fate specification; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0043010 camera-type eye development | IGI PMID:12072567 Mutually regulated expression of Pax6 and Six3 and its impli... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IGI evidence from PMID:12072567. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12072567 either transcription factor binds regulatory sequences from the counterpart gene and that both genes mutually activate their expression |
| GO:0043010 camera-type eye development | IGI PMID:12183364 Meis homeoproteins directly regulate Pax6 during vertebrate ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IGI evidence from PMID:12183364. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12183364 Pax6 and Meis2 exhibit a strong genetic interaction in lens development |
| GO:0043010 camera-type eye development | IMP PMID:11062307 Further genetic analysis of two autosomal dominant mouse eye... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IMP evidence from PMID:11062307. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11062307 The Pax6coop mutant differs in phenotype from known null alleles of Pax6, implying that it is a hypomorph |
| GO:0043010 camera-type eye development | IMP PMID:11069887 Pax6 activity in the lens primordium is required for lens fo... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IMP evidence from PMID:11069887. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:11069887 Pax6 activity was found to be essential in the specified ectoderm for lens placode formation |
| GO:0043010 camera-type eye development | IMP PMID:12648492 The roles of Pax6 in the cornea, retina, and olfactory epith... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IMP evidence from PMID:12648492. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12648492 Pax6(-/-) cells contributed only poorly to the neural retina, forming small clumps of cells that were normally restricted to the ganglion cell layer at E16.5 |
| GO:0043010 camera-type eye development | IMP PMID:12756174 Retinal pigmented epithelium determination requires the redu... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IMP evidence from PMID:12756174. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:12756174 the redundant activities of Pax2 and Pax6 direct the determination of RPE |
| GO:0043010 camera-type eye development | IMP PMID:16080917 Developmental and cellular factors underlying corneal epithe... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) camera-type eye development; IMP evidence from PMID:16080917. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:16080917 K12 expression was delayed and down-regulated in the Pax6+/- corneal epithelium, implying that differentiation of the Pax6+/- corneal epithelium was delayed and abnormal |
| GO:0043565 sequence-specific DNA binding | IDA PMID:23622063 Pax6 exerts regional control of cortical progenitor prolifer... | ACCEPT | Summary: Sequence-specific DNA binding via the bipartite paired domain and homeodomain. Reason: Direct binding to defined sites (e.g. Cdk6 regulatory region) is documented; core activity. Supporting Evidence: PMID:23622063 Biochemical assays indicated that Pax6 directly represses Cdk6 expression |
| GO:0043565 sequence-specific DNA binding | ISO GO_REF:0000096 | ACCEPT | Summary: Sequence-specific DNA binding via the bipartite paired domain and homeodomain. Reason: ISO transfer from the rat ortholog (RGD:3258). Direct binding to defined sites (e.g. Cdk6 regulatory region) is documented; core activity. Supporting Evidence: PMID:23622063 Biochemical assays indicated that Pax6 directly represses Cdk6 expression |
| GO:0045165 cell fate commitment | IGI PMID:15229646 Sequential phases of cortical specification involve Neurogen... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cell fate commitment; IGI evidence from PMID:15229646. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15229646 later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx |
| GO:0045165 cell fate commitment | IMP PMID:15878992 Ventralized dorsal telencephalic progenitors in Pax6 mutant ... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cell fate commitment; IMP evidence from PMID:15878992. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15878992 Pax6 delimits the appropriate proliferative zone for GABA INs and regulates their numbers and distributions by repressing the ventral fates of dTel progenitors and progeny |
| GO:0045597 positive regulation of cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of cell differentiation; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0045664 regulation of neuron differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neuron differentiation; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0045664 regulation of neuron differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neuron differentiation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0045665 negative regulation of neuron differentiation | IGI PMID:16950124 Wnt signaling inhibitors regulate the transcriptional respon... | UNDECIDED | Summary: Negative regulation of neuron differentiation (IGI, Wnt/Tcf-Nkx2.2 neural tube paper). Reason: The abstract does not mention Pax6 and full text is not cached; Pax6 is generally pro-neurogenic in cortex but can delay differentiation in some contexts. Cannot verify. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: Pax6 activates target genes (e.g. MafB, cMaf, NeuroD1 in alpha cells). Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Pax6 activates target genes (e.g. MafB, cMaf, NeuroD1 in alpha cells). Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: ISO transfer from the human ortholog PAX6 (P26367). Pax6 activates target genes (e.g. MafB, cMaf, NeuroD1 in alpha cells). Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12756174 Retinal pigmented epithelium determination requires the redu... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:15905411 Vax genes ventralize the embryonic eye. | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:15905411 ventralization is mediated, at least in part, via Vax repression of the Pax6 gene, a potent inducer of retinal development |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16407227 Phosphorylation and transactivation of Pax6 by homeodomain-i... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:16407227 HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:18287938 Pax6 directly modulate Sox2 expression in the neural progeni... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:18287938 We confirmed that Pax6 could bind to the Sox2 promoter by chromatin immunoprecipitation assay and activate Sox2 expression by a luciferase reporter gene assay |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19749747 AP2gamma regulates basal progenitor fate in a region- and la... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Evidence from PMID:19749747 (cached abstract does not explicitly state the specific finding; deferring to the MGI curator, who read the full text). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: combined automated (IEA) annotation. Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:19146846 The LIM homeobox transcription factor Lhx2 is required to sp... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:23643363 Chromatin regulation by BAF170 controls cerebral cortical si... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:23643363 modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:20592023 Pax6 controls the expression of critical genes involved in p... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:30186101 many EF genes are directly bound and transcriptionally regulated by Pax6, Tbr2, or Tbr1 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000096 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: ISO transfer from the rat ortholog (RGD:3258). Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: ISO transfer from the human ortholog PAX6 (P26367). Pax6 directly activates many targets (Mitf, Sox2, Six6, alpha-cell genes, Eomes/Tbr2). Core process. Supporting Evidence: PMID:20592023 Pax6 directly binds and activates the promoter region of the three genes through specific binding sites PMID:12756174 both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro |
| GO:0048505 regulation of timing of cell differentiation | IMP PMID:9828088 Pax6 influences the time and site of origin of glial precurs... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of timing of cell differentiation; IMP evidence from PMID:9828088. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:9828088 In Small eye (Pax6-deficient) mice, the origin of OLPs is shifted dorsally and both OLPs and Isl2/Lim3 MNs are delayed |
| GO:0048596 embryonic camera-type eye morphogenesis | IGI PMID:18653562 Cited2 is required for the proper formation of the hyaloid v... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) embryonic camera-type eye morphogenesis; IGI evidence from PMID:18653562. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:18653562 dual functions for Cited2: one upstream of, or together with, Pax6 in lens morphogenesis |
| GO:0048708 astrocyte differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) astrocyte differentiation; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0048708 astrocyte differentiation | IMP PMID:19258013 Spatially distinct functions of PAX6 and NKX2.2 during gliog... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) astrocyte differentiation; IMP evidence from PMID:19258013. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:19258013 deregulation of Slit1 expression in gliogenic neural progenitors leads to changes in Astrocyte subtype identity |
| GO:0048708 astrocyte differentiation | IMP PMID:30186101 The Epigenetic Factor Landscape of Developing Neocortex Is R... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) astrocyte differentiation; IMP evidence from PMID:30186101. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:30186101 Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade, with direct feedback repression |
| GO:0048708 astrocyte differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) astrocyte differentiation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0050680 negative regulation of epithelial cell proliferation | IMP PMID:16080917 Developmental and cellular factors underlying corneal epithe... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) negative regulation of epithelial cell proliferation; IMP evidence from PMID:16080917. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:16080917 BrdU incorporation showed enhanced proliferation of Pax6+/- corneal epithelium compared to wild-type controls |
| GO:0050767 regulation of neurogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neurogenesis; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0050767 regulation of neurogenesis | IMP PMID:15548580 Molecular dissection of Pax6 function: the specific roles of... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neurogenesis; IMP evidence from PMID:15548580. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:15548580 the PD is necessary for the regulation of neurogenesis, cell proliferation and patterning effects of Pax6 |
| GO:0050767 regulation of neurogenesis | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) regulation of neurogenesis; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0050877 nervous system process | IEA GO_REF:0000117 | REMOVE | Summary: Nervous system process (ARBA IEA). Reason: ARBA machine-learning (IEA) annotation. Vague physiological term with no specific support; Pax6 is a developmental TF. Removed, consistent with human review. |
| GO:0051656 establishment of organelle localization | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Establishment of organelle localization (ARBA IEA). Reason: ARBA machine-learning (IEA) annotation. Likely an echo of interkinetic nuclear migration phenotypes; far too general and indirect for a transcription factor. Over-annotation. |
| GO:0060041 retina development in camera-type eye | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) retina development in camera-type eye; IBA evidence from GO_REF:0000033. Reason: IBA (PAINT phylogenetic inference). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0060041 retina development in camera-type eye | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) retina development in camera-type eye; IEA evidence from GO_REF:0000117. Reason: ARBA machine-learning (IEA) annotation. Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0060041 retina development in camera-type eye | IGI PMID:19146846 The LIM homeobox transcription factor Lhx2 is required to sp... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) retina development in camera-type eye; IGI evidence from PMID:19146846. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:19146846 Lhx2 and Pax6 associate with the chromatin at several regions of Six6 in vivo and cooperate for trans-activation of Six6 regulatory elements in vitro |
| GO:0061034 olfactory bulb mitral cell layer development | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) olfactory bulb mitral cell layer development; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0061072 iris morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) iris morphogenesis; IEA evidence from GO_REF:0000107. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0061072 iris morphogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) iris morphogenesis; ISO evidence from GO_REF:0000119. Reason: ISO transfer from the human ortholog PAX6 (P26367). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0061303 cornea development in camera-type eye | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cornea development in camera-type eye; IEA evidence from GO_REF:0000107. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0061303 cornea development in camera-type eye | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) cornea development in camera-type eye; ISO evidence from GO_REF:0000119. Reason: ISO transfer from the human ortholog PAX6 (P26367). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0061351 neural precursor cell proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) neural precursor cell proliferation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:0070410 co-SMAD binding | IDA PMID:17251190 The MH1 domain of Smad3 interacts with Pax6 and represses au... | REMOVE | Summary: co-SMAD (Smad4) binding reported from GST pull-down. Reason: The cited paper itself states that the Smad4 interaction seen in GST pull-down could not be validated by co-immunoprecipitation and was invalidated, whereas Smad3 (R-SMAD) binding was validated. The co-SMAD binding claim is contradicted by the source paper; the R-SMAD binding annotation (GO:0070412) captures the validated interaction. The human PAX6 review removes its electronic co-SMAD row for the same reason, so the two reviews agree. Supporting Evidence: PMID:17251190 These data serve to validate the interaction of Smad3, and non-interaction of Smad2 with Pax6, while invalidating the Smad4 interaction that was observed only in vitro |
| GO:0070412 R-SMAD binding | IDA PMID:17251190 The MH1 domain of Smad3 interacts with Pax6 and represses au... | ACCEPT | Summary: Pax6 paired domain (RED subdomain) binds the MH1 domain of Smad3, linking TGF-beta signalling to repression of Pax6 autoregulation. Reason: Validated by co-IP and GST pull-down; consistent with human review. Supporting Evidence: PMID:17251190 the MH1 domain of Smad3 was observed binding the RED sub-domain of the Pax6 paired domain |
| GO:0070412 R-SMAD binding | IEA GO_REF:0000107 | ACCEPT | Summary: Pax6 paired domain (RED subdomain) binds the MH1 domain of Smad3, linking TGF-beta signalling to repression of Pax6 autoregulation. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Validated by co-IP and GST pull-down; consistent with human review. Supporting Evidence: PMID:17251190 the MH1 domain of Smad3 was observed binding the RED sub-domain of the Pax6 paired domain |
| GO:0070412 R-SMAD binding | ISO GO_REF:0000119 | ACCEPT | Summary: Pax6 paired domain (RED subdomain) binds the MH1 domain of Smad3, linking TGF-beta signalling to repression of Pax6 autoregulation. Reason: ISO transfer from the human ortholog PAX6 (P26367). Validated by co-IP and GST pull-down; consistent with human review. Supporting Evidence: PMID:17251190 the MH1 domain of Smad3 was observed binding the RED sub-domain of the Pax6 paired domain |
| GO:0071837 HMG box domain binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | ACCEPT | Summary: Pax6 binds the HMG-box domain of Sox proteins (Sox8/Sox10 yeast two-hybrid screen). Reason: Sox-Pax6 partnerships (e.g. Sox2-Pax6 on lens crystallin enhancers) are a well-known mode of Pax6 action; consistent with human review. Supporting Evidence: PMID:16582099 we identified several transcription factors including the homeodomain proteins Meox1 and Pax6 and the zinc-finger protein Hivep1 |
| GO:0098598 learned vocalization behavior or vocal learning | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Learned vocalization behavior (ISO from rat rSey2 heterozygotes). Reason: ISO transfer from the rat ortholog (RGD:3258). Behavioural phenotype downstream of brain developmental defects; Pax6 does not act directly in vocal learning. Over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:3258 Β· Pax6 SUPPORTS SOURCE BUT NOT TARGET Rat Pax6 rSey2 heterozygote vocalization phenotype is a behavioural consequence of brain developmental defects; transfer is faithful but the source term over-reaches for a developmental transcription factor. |
| GO:0120008 positive regulation of glutamatergic neuron differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of glutamatergic neuron differentiation; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:1901142 insulin metabolic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) insulin metabolic process; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:1902895 positive regulation of miRNA transcription | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of miRNA transcription (ortholog transfer from human PAX6, which directly activates MIR135B). Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Human PAX6 directly binds and activates the miR-135b locus; transfer to mouse is reasonable. Accepted, consistent with human review. |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000119 | ACCEPT | Summary: Positive regulation of miRNA transcription (ortholog transfer from human PAX6, which directly activates MIR135B). Reason: ISO transfer from the human ortholog PAX6 (P26367). Human PAX6 directly binds and activates the miR-135b locus; transfer to mouse is reasonable. Accepted, consistent with human review. |
| GO:1904937 sensory neuron migration | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) sensory neuron migration; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
| GO:1990830 cellular response to leukemia inhibitory factor | IEP PMID:20439489 miRNA 34a, 100, and 137 modulate differentiation of mouse em... | MARK AS OVER ANNOTATED | Summary: Cellular response to leukemia inhibitory factor (IEP). Reason: IEP reflects Pax6 expression changes during ES-cell differentiation upon LIF withdrawal (Pax6 is a neural differentiation marker); this is not a functional role in the LIF response. Over-annotation. |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sequence-specific double-stranded DNA binding. Reason: Ensembl Compara orthology transfer from experimentally annotated orthologs (human/rat). Correct core DNA-binding activity; consistent with human review. |
| GO:1990837 sequence-specific double-stranded DNA binding | ISO GO_REF:0000119 | ACCEPT | Summary: Sequence-specific double-stranded DNA binding. Reason: ISO transfer from the human ortholog PAX6 (P26367). Correct core DNA-binding activity; consistent with human review. |
| GO:2000178 negative regulation of neural precursor cell proliferation | IMP PMID:23622063 Pax6 exerts regional control of cortical progenitor prolifer... | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) negative regulation of neural precursor cell proliferation; IMP evidence from PMID:23622063. Reason: Pax6 loss-of-function (Small eye) phenotype; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. Supporting Evidence: PMID:23622063 We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels |
| GO:2001224 positive regulation of neuron migration | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Pax6 is required for (acts upstream of or within) positive regulation of neuron migration; ISO evidence from GO_REF:0000096. Reason: ISO transfer from the rat ortholog (RGD:3258). Transferred from ortholog/model data on Pax6 loss of function; Pax6 acts in this process as an upstream transcriptional regulator. Legitimate developmental role but downstream of the core TF activity; kept as non-core for this highly pleiotropic gene. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Do the canonical Pax6 and Pax6(5a) isoforms bind distinct target repertoires in vivo (paired domain PAI vs RED usage), and does this explain the proliferation-versus-fate split seen in retroviral overexpression?
Q: Several MGI experimental annotations (chromatin binding PMID:23637604; negative regulation of protein phosphorylation PMID:16497297; signal transduction PMID:18462699) cite papers whose available text does not mention Pax6. Can MGI confirm the intended references?
Q: Should the GO-level role of Pax6 in Shh-patterned neural tube be represented as a Shh-responsive transcriptional target (has-input/causal relation in GO-CAM) rather than as participation in smoothened signaling?
Experiment: Allelic series (Sey/+, wild type, PAX77 overexpression) combined with CUT&RUN for Pax6 and chromatin accessibility in lens placode and E12.5 cortical radial glia to relate binding-site affinity to dosage-dependent target expression.
Hypothesis: Pax6 dosage sensitivity in lens and cortex reflects concentration-dependent occupancy of low-affinity enhancers.
Experiment: Isoform-specific knock-in mice lacking p32 initiation or the K91 SUMO site, followed by RNA-seq and homeodomain-site ChIP in retina and olfactory bulb.
Hypothesis: The paired-less p32 isoform has distinct, SUMO-dependent homeodomain-only targets in eye and olfactory bulb.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)