SIX3
entrez
6496
canonical
uniprot
O95343
canonical
ensembl
ENSG00000138083
resolver
ensp
ENSP00000260653
resolver
enst
ENST00000260653
resolver
genesymbol
SIX3
resolver
hgnc
HGNC:10889
resolver
uniprot
D6W5A5
resolver
uniprot
Q53T42
resolver
uniprot_entry
SIX3_HUMAN
resolver
uniprot_sec
D6W5A5
resolver
uniprot_sec
Q53T42
resolver
amino_acid_sequence
MVFRSPLDLYSSHFLLPNFADSHHRSILLASSGGGNGAGGGGGAGGGSGGGNGAGGGGAGGAGGGGGGGSRAPPEELSMFQLPTLNFSPEQVASVCETLEETGDIERLGRFLWSLPVAPGACEAINKHESILRARAVVAFHTGNFRDLYHILENHKFTKESHGKLQAMWLEAHYQEAEKLRGRPLGPVDKYRVRKKFPLPRTIWDGEQKTHCFKERTRSLLREWYLQDPYPNPSKKRELAQATGLTPTQVGNWFKNRRQRDRAAAAKNRLQHQAIGPSGMRSLAEPGCPTHGSAESPSTAASPTTSVSSLTERADTGTSILSVTSSDSECDV
uniprot
proteins
disease_involvement
DISEASE: Holoprosencephaly 2 (HPE2) [MIM:157170]: A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE2 inheritance is autosomal dominant. {ECO:0000269|PubMed:10369266, ECO:0000269|PubMed:15221788, ECO:0000269|PubMed:15523651, ECO:0000269|PubMed:17001667, ECO:0000269|PubMed:18791198, ECO:0000269|PubMed:20531442}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Schizencephaly (SCHZC) [MIM:269160]: Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid. {ECO:0000269|PubMed:20157829}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. 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. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 and CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. 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. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 also functions in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway. {ECO:0000250|UniProtKB:Q62233, ECO:0000269|PubMed:18791198}.
uniprot
proteins
mass_dalton
35487
uniprot
proteins
mutagenesis
MUTAGEN 87; /note="F->E: Decreased interaction with TLE5 and loss of interaction with TLE1."; /evidence="ECO:0000269|PubMed:12441302"; MUTAGEN 95; /note="V->P: Loss of interaction with TLE1 and TLE5; when associated with P-99."; /evidence="ECO:0000269|PubMed:12441302"; MUTAGEN 99; /note="L->P: Loss of interaction with TLE1 and TLE5; when associated with P-95."; /evidence="ECO:0000269|PubMed:12441302
uniprot
proteins
protein_family
SIX/Sine oculis homeobox family
uniprot
proteins
pubmed
10369266
uniprot
proteins
pubmed
10415461
uniprot
proteins
pubmed
12441302
uniprot
proteins
pubmed
12543801
uniprot
proteins
pubmed
14973488
uniprot
proteins
pubmed
15221788
uniprot
proteins
pubmed
15523651
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
17001667
uniprot
proteins
pubmed
18775421
uniprot
proteins
pubmed
18791198
uniprot
proteins
pubmed
20157829
uniprot
proteins
pubmed
20531442
uniprot
proteins
pubmed
9889003
uniprot
proteins
sequence_length
332
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q62233, ECO:0000255|PROSITE-ProRule:PRU00108}.
uniprot
proteins