| Tag | Content |
|---|---|
| Uniprot ID | Q61321; B2RQH3; Q61322; Q61323; |
| Entrez ID | 20474 |
| Genbank protein ID | BAA08916.1; BAA08915.1; AAI37935.1; AAI37932.1; BAA08917.1; |
| Genbank nucleotide ID | NM_011382.2 |
| Ensembl protein ID | ENSMUSP00000036150 |
| Ensembl nucleotide ID | ENSMUSG00000034460 |
| Gene name | Homeobox protein SIX4 |
| Gene symbol | Six4 |
| Organism | Mus musculus |
| NCBI taxa ID | 10090 |
| Cleft type | CPO |
| Developmental stage | |
| Data sources | Manually collected |
| Reference | 17499702 |
| 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 from a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer (PubMed:14966291). Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein (PubMed:10490620). 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 (PubMed:15788460). Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6 (PubMed:15788460, PubMed:17592144). Controls somitic differentiation in myocyte through MYOG transactivation (PubMed:15788460). 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 (PubMed:19962975, PubMed:21884692). 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 (PubMed:21884692). During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression (PubMed:20696153). During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression (PubMed:17300925). 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 (PubMed:23987514). 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 (PubMed:19027001). Promotes survival of sensory neurons during early trigeminal gangliogenesis (PubMed:16938278). In the developing dorsal root ganglia, up-regulates SLC12A2 transcription (PubMed:15955062). Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression (PubMed:16530750). Forms gustatory papillae during development of the tongue (PubMed:21978088). Also plays a role during embryonic cranial skeleton morphogenesis (PubMed:20515681). |
| Sequence | MSSSSPTGQI ASAADIKQEN GMESASEGQE AHREVAGGAA AGLSPPAPAP FPLEPGDAAA 60 ASRVSREEGA AAAGAADQVQ LHSELLGRHQ HAAAAQPPLA FSPDHVACVC EALQQGGNLD 120 RLARFLWSLP QSDLLRGNES LLKARALVAF HQGIYPELYS ILESHSFESA NHPLLQQLWY 180 KARYTEAERA RGRPLGAVDK YRLRRKFPLP RTIWDGEETV YCFKEKSRNA LKELYKQNRY 240 PSPAEKRHLA KITGLSLTQV SNWFKNRRQR DRNPSETQSK SESDGNPSTE DESSKGHEDL 300 SPHPLSGASD GVTNLSLSSH VEPVYMQQIG NAKISLSSSG VLLNGSLVPA STSPVFLNGN 360 SFIQGHNGVI LNGLNVGNTQ TVSLNPPKMS SNIVGNGIAM TDILGSTSQD VKEFKVLQSS 420 AVNSAATTSY SPSAPVSFPG LIPCTEVKRE GIQTVASQDG GSVVTFTTPV QINQYGIVQI 480 PNSGANGQFL NGSIGFSPLQ LPPVSVAASQ GNLSVTPSTS DGSTFTSEPA TVQHGKLFLS 540 PLTPSAVVYT VPNSGQTVGA VKQEGLERGL VFSQLMPVNH SAQVNASLSS ENLSGSGLHP 600 LTSSLVNVSA AHGFSLTPPT LLNPTELNPD LAESQPVSAP VASKCTVSSV SNTNYATLQN 660 CSLIPGQDLL SGPMTQAALG EIVPTAEEQV SHASTAVHQD FVREQRLVLQ SVPNIKENFL 720 QNSENKATNN LMMLDSKSKY VLDGMVEAGC EDLGTDKKEL AKLQTVQLDE DMQDL 775 |
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 | SIX4 | 490720 | F6XRS2 | Canis lupus familiaris | Prediction | More>> | ||
| 1:1 ortholog | SIX4 | 102173941 | A0A452EBD2 | Capra hircus | Prediction | More>> | ||
| 1:1 ortholog | SIX4 | 51804 | Q9UIU6 | Homo sapiens | Prediction | More>> | ||
| 1:1 ortholog | Six4 | 20474 | Q61321 | CPO | Mus musculus | Publication | More>> | |
| 1:1 ortholog | SIX4 | 452953 | K7A7J5 | Pan troglodytes | Prediction | More>> | ||
| 1:1 ortholog | SIX4 | F1SRW3 | Sus scrofa | Prediction | More>> | |||
| 1:1 ortholog | Six4 | 299138 | D3ZAJ7 | Rattus norvegicus | 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 | IDA |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | IBA |
| 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:0005515 | protein binding | IPI |
| GO:0043565 | sequence-specific DNA binding | IDA |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0007519 | skeletal muscle tissue development | IGI |
| GO:0007519 | skeletal muscle tissue development | IMP |
| GO:0008582 | regulation of synaptic growth at neuromuscular junction | IGI |
| GO:0008584 | male gonad development | IMP |
| GO:0010468 | regulation of gene expression | IGI |
| GO:0030238 | male sex determination | IMP |
| GO:0030910 | olfactory placode formation | IMP |
| GO:0032880 | regulation of protein localization | IGI |
| GO:0034504 | protein localization to nucleus | IDA |
| GO:0042472 | inner ear morphogenesis | IGI |
| GO:0043066 | negative regulation of apoptotic process | IMP |
| GO:0043524 | negative regulation of neuron apoptotic process | IMP |
| GO:0043586 | tongue development | IMP |
| GO:0045214 | sarcomere organization | IMP |
| GO:0045892 | negative regulation of transcription, DNA-templated | IDA |
| GO:0045892 | negative regulation of transcription, DNA-templated | IBA |
| GO:0045893 | positive regulation of transcription, DNA-templated | IDA |
| GO:0045893 | positive regulation of transcription, DNA-templated | IMP |
| GO:0045944 | positive regulation of transcription by RNA polymerase II | IDA |
| GO:0046661 | male sex differentiation | IMP |
| GO:0048538 | thymus development | IGI |
| GO:0048699 | generation of neurons | IMP |
| GO:0048701 | embryonic cranial skeleton morphogenesis | IGI |
| GO:0048704 | embryonic skeletal system morphogenesis | IGI |
| GO:0048856 | anatomical structure development | IGI |
| GO:0048856 | anatomical structure development | IBA |
| GO:0050678 | regulation of epithelial cell proliferation | IMP |
| GO:0051451 | myoblast migration | IGI |
| GO:0060037 | pharyngeal system development | IMP |
| GO:0061055 | myotome development | IMP |
| GO:0061197 | fungiform papilla morphogenesis | IMP |
| GO:0061551 | trigeminal ganglion development | IMP |
| GO:0072075 | metanephric mesenchyme development | IMP |
| GO:0072095 | regulation of branch elongation involved in ureteric bud branching | IMP |
| GO:0072107 | positive regulation of ureteric bud formation | IMP |
| GO:0090190 | positive regulation of branching involved in ureteric bud morphogenesis | IMP |
| GO:0098528 | skeletal muscle fiber differentiation | IMP |
| GO:1902725 | negative regulation of satellite cell differentiation | IMP |
| GO ID | GO Term | Evidence |
|---|---|---|
| GO:0005634 | nucleus | IC |
| GO:0005634 | nucleus | IBA |
| GO:0005634 | nucleus | IDA |
| GO:0005667 | transcription factor complex | IBA |
| GO:0005737 | cytoplasm | IDA |
| Reactome ID | Reactome Term | Evidence |
|---|