Gene: SIX4

Basic information

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.

Gene expression information

Gene expression in different tissues (GTEx V7)