| Tag | Content |
|---|---|
| Uniprot ID | Q9UIU6; Q4QQH5; Q4V764; |
| Entrez ID | 51804 |
| Genbank protein ID | AAH98282.1; AAI01935.1; EAW80786.1; AAH99722.1; AAH98135.1; BAA86223.1; |
| Genbank nucleotide ID | NM_017420.4 |
| Ensembl protein ID | ENSP00000216513 |
| Ensembl nucleotide ID | ENSG00000100625 |
| Gene name | Homeobox protein SIX4 |
| Gene symbol | SIX4 |
| Organism | Homo sapiens |
| NCBI taxa ID | 9606 |
| Cleft type | |
| Developmental stage | |
| Data sources | Homology search |
| Reference | |
| Functional description | Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3. Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation. During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up-regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis. |
| Sequence | MSSSSPTGQI ASAADIKQEN GMESASEGQE AHREVAGGAA VGLSPPAPAP FPLEPGDAAT 60 AAARVSGEEG AVAAAAAGAA ADQVQLHSEL LGRHHHAAAA AAQTPLAFSP DHVACVCEAL 120 QQGGNLDRLA RFLWSLPQSD LLRGNESLLK ARALVAFHQG IYPELYSILE SHSFESANHP 180 LLQQLWYKAR YTEAERARGR PLGAVDKYRL RRKFPLPRTI WDGEETVYCF KEKSRNALKE 240 LYKQNRYPSP AEKRHLAKIT GLSLTQVSNW FKNRRQRDRN PSETQSKSES DGNPSTEDES 300 SKGHEDLSPH PLSSSSDGIT NLSLSSHMEP VYMQQIGNAK ISLSSSGVLL NGSLVPASTS 360 PVFLNGNSFI QGPSGVILNG LNVGNTQAVA LNPPKMSSNI VSNGISMTDI LGSTSQDVKE 420 FKVLQSSANS ATTTSYSPSV PVSFPGLIPS TEVKREGIQT VASQDGGSVV TFTTPVQINQ 480 YGIVQIPNSG ANSQFLNGSI GFSPLQLPPV SVAASQGNIS VSSSTSDGST FTSESTTVQQ 540 GKVFLSSLAP SAVVYTVPNT GQTIGSVKQE GLERSLVFSQ LMPVNQNAQV NANLSSENIS 600 GSGLHPLASS LVNVSPTHNF SLSPSTLLNP TELNRDIADS QPMSAPVASK STVTSVSNTN 660 YATLQNCSLI TGQDLLSVPM TQAALGEIVP TAEDQVGHPS PAVHQDFVQE HRLVLQSVAN 720 MKENFLSNSE SKATSSLMML DSKSKYVLDG MVDTVCEDLE TDKKELAKLQ TVQLDEDMQD 780 L 781 |
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.