| Tag | Content |
|---|---|
| Uniprot ID | Q62233; P70176; P70177; Q4QQQ3; |
| Entrez ID | 20473 |
| Genbank protein ID | BAA11822.1; CAA62379.1; BAA11823.1; AAH98096.1; |
| Genbank nucleotide ID | NM_011381.4 |
| Ensembl protein ID | ENSMUSP00000135312; ENSMUSP00000135677; |
| Ensembl nucleotide ID | ENSMUSG00000038805 |
| Gene name | Homeobox protein SIX3 |
| Gene symbol | Six3 |
| Organism | Mus musculus |
| NCBI taxa ID | 10090 |
| Cleft type | CPO |
| Developmental stage | |
| Data sources | Manually collected |
| Reference | 18694563 |
| Functional description | Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon (PubMed:18094027). Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression (PubMed:18775421). In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration (PubMed:22071110). Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2 (PubMed:17576749). During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm (PubMed:17066077). In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation (PubMed:12072567). Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory (PubMed:20890044). Its action during retina development and lens morphogenesis is TLE5 and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element (PubMed:11139622). Directly activates RHO transcription, or cooperates with CRX or NRL (PubMed:17666527). Six3 functions also in the formation of the proximodistal axis of the optic cup (PubMed:12163408), and promotes the formation of optic vesicles-like structures (PubMed:11458394). During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (PubMed:18694563). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway (By similarity). |
| Sequence | MVFRSPLDLY SSHFLLPNFA DSHHCSLLLA SSGGGSGASG GGGGAGGGGG GNRAGGGGAG 60 GAGGGSGGGG SRAPPEELSM FQLPTLNFSP EQVASVCETL EETGDIERLG RFLWSLPVAP 120 GACEAINKHE SILRARAVVA FHTGNFRDLY HILENHKFTK ESHGKLQAMW LEAHYQEAEK 180 LRGRPLGPVD KYRVRKKFPL PRTIWDGEQK THCFKERTRS LLREWYLQDP YPNPSKKREL 240 AQATGLTPTQ VGNWFKNRRQ RDRAAAAKNR LQHQAIGPSG MRSLAEPGCP THGSAESPST 300 AASPTTSVSS LTERADTGTS ILSVTSSDSE CDV 333 |
Abbreviation :
CLO : cleft lip only. CPO : cleft palate only.
CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.
| Relation | Gene symbol | Entrez ID | UniProt ID | Cleft type | Developmental stage | Species | Evidence | Details |
|---|---|---|---|---|---|---|---|---|
| 1:1 ortholog | SIX3 | 616756 | E1BMT1 | Bos taurus | Prediction | More>> | ||
| 1:1 ortholog | SIX3 | 102179678 | A0A452E3R7 | Capra hircus | Prediction | More>> | ||
| 1:1 ortholog | SIX3 | 6496 | O95343 | Homo sapiens | Prediction | More>> | ||
| 1:1 ortholog | Six3 | 20473 | Q62233 | CPO | Mus musculus | Publication | More>> | |
| 1:1 ortholog | SIX3 | 470367 | H2QHU7 | Pan troglodytes | Prediction | More>> | ||
| 1:1 ortholog | Six3 | A0A0G2K2C0 | Rattus norvegicus | Prediction | More>> | |||
| 1:1 ortholog | six3a | Q6PCA5 | Danio rerio | Prediction | More>> |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0000976 | transcription regulatory region sequence-specific DNA binding | IBA |
| GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO |
| GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | IDA |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | IBA |
| GO:0001222 | transcription corepressor binding | ISO |
| GO:0001222 | transcription corepressor binding | IPI |
| GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IDA |
| GO:0003677 | DNA binding | IDA |
| GO:0003700 | DNA-binding transcription factor activity | IDA |
| GO:0003713 | transcription coactivator activity | IDA |
| GO:0005102 | signaling receptor binding | ISO |
| GO:0005515 | protein binding | IPI |
| GO:0042826 | histone deacetylase binding | IPI |
| GO:0043565 | sequence-specific DNA binding | IDA |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0001654 | eye development | ISO |
| GO:0001654 | eye development | IDA |
| GO:0001654 | eye development | IBA |
| GO:0002070 | epithelial cell maturation | IMP |
| GO:0002088 | lens development in camera-type eye | IDA |
| GO:0003404 | optic vesicle morphogenesis | IDA |
| GO:0006606 | protein import into nucleus | IDA |
| GO:0007420 | brain development | IMP |
| GO:0007420 | brain development | IBA |
| GO:0009946 | proximal/distal axis specification | IDA |
| GO:0014016 | neuroblast differentiation | IMP |
| GO:0021536 | diencephalon development | IGI |
| GO:0021537 | telencephalon development | IMP |
| GO:0021797 | forebrain anterior/posterior pattern specification | IGI |
| GO:0021797 | forebrain anterior/posterior pattern specification | IMP |
| GO:0021798 | forebrain dorsal/ventral pattern formation | ISS |
| GO:0021798 | forebrain dorsal/ventral pattern formation | ISO |
| GO:0021846 | cell proliferation in forebrain | IMP |
| GO:0021978 | telencephalon regionalization | IMP |
| GO:0021983 | pituitary gland development | IMP |
| GO:0030178 | negative regulation of Wnt signaling pathway | IMP |
| GO:0042127 | regulation of cell population proliferation | IMP |
| GO:0043010 | camera-type eye development | IGI |
| GO:0045665 | negative regulation of neuron differentiation | IDA |
| GO:0045892 | negative regulation of transcription, DNA-templated | ISO |
| GO:0045892 | negative regulation of transcription, DNA-templated | IDA |
| GO:0045892 | negative regulation of transcription, DNA-templated | IBA |
| GO:0045944 | positive regulation of transcription by RNA polymerase II | IDA |
| GO:0048512 | circadian behavior | IMP |
| GO:0048856 | anatomical structure development | IBA |
| GO:0060235 | lens induction in camera-type eye | IMP |
| GO:0061074 | regulation of neural retina development | IMP |
| GO:0070306 | lens fiber cell differentiation | IDA |
| GO:0097402 | neuroblast migration | IMP |
| GO:1901987 | regulation of cell cycle phase transition | IDA |
| GO:1902692 | regulation of neuroblast proliferation | IMP |
| GO:1902742 | apoptotic process involved in development | IMP |
| GO:1990086 | lens fiber cell apoptotic process | IDA |
| GO:2000177 | regulation of neural precursor cell proliferation | IDA |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0005634 | nucleus | IDA |
| GO:0005634 | nucleus | IBA |
| GO:0005667 | transcription factor complex | IBA |
| Reactome ID | Reactome Term | Evidence |
|---|
| PROSITE ID | PROSITE Term |
|---|---|
| PS50071 | HOMEOBOX_2 |