ID SIX4_MOUSE Reviewed; 775 AA. AC Q61321; B2RQH3; Q61322; Q61323; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 28-FEB-2018, entry version 154. DE RecName: Full=Homeobox protein SIX4; DE AltName: Full=Sine oculis homeobox homolog 4; DE AltName: Full=Skeletal muscle-specific ARE-binding protein AREC3; GN Name=Six4; Synonyms=Arec3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE RP [MRNA] (ISOFORMS 2 AND 3), AND SUBCELLULAR LOCATION. RC STRAIN=BALB/cJ; TISSUE=Myoblast, and Skeletal muscle; RX PubMed=8628654; DOI=10.1093/nar/24.2.303; RA Kawakami K., Ohto H., Ikeda K., Roeder R.G.; RT "Structure, function and expression of a murine homeobox protein RT AREC3, a homologue of Drosophila sine oculis gene product, and RT implication in development."; RL Nucleic Acids Res. 24:303-310(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP SUBCELLULAR LOCATION. RX PubMed=9990334; DOI=10.1006/exer.1998.0562; RA Niiya A., Ohto H., Kawakami K., Araki M.; RT "Localization of Six4/AREC3 in the developing mouse retina; RT implications in mammalian retinal development."; RL Exp. Eye Res. 67:699-707(1998). RN [4] RP FUNCTION. RX PubMed=10490620; DOI=10.1128/MCB.19.10.6815; RA Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S., RA Kawakami K.; RT "Cooperation of six and eya in activation of their target genes RT through nuclear translocation of Eya."; RL Mol. Cell. Biol. 19:6815-6824(1999). RN [5] RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=11313460; DOI=10.1128/MCB.21.10.3343-3350.2001; RA Ozaki H., Watanabe Y., Takahashi K., Kitamura K., Tanaka A., Urase K., RA Momoi T., Sudo K., Sakagami J., Asano M., Iwakura Y., Kawakami K.; RT "Six4, a putative myogenin gene regulator, is not essential for mouse RT embryonal development."; RL Mol. Cell. Biol. 21:3343-3350(2001). RN [6] RP INTERACTION WITH EYA3. RX PubMed=12215533; DOI=10.1128/MCB.22.19.6759-6766.2002; RA Ikeda K., Watanabe Y., Ohto H., Kawakami K.; RT "Molecular interaction and synergistic activation of a promoter by RT Six, Eya, and Dach proteins mediated through CREB binding protein."; RL Mol. Cell. Biol. 22:6759-6766(2002). RN [7] RP FUNCTION. RX PubMed=14966291; DOI=10.1128/MCB.24.5.2132-2143.2004; RA Himeda C.L., Ranish J.A., Angello J.C., Maire P., Aebersold R., RA Hauschka S.D.; RT "Quantitative proteomic identification of six4 as the trex-binding RT factor in the muscle creatine kinase enhancer."; RL Mol. Cell. Biol. 24:2132-2143(2004). RN [8] RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE. RX PubMed=15788460; DOI=10.1242/dev.01773; RA Grifone R., Demignon J., Houbron C., Souil E., Niro C., Seller M.J., RA Hamard G., Maire P.; RT "Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression RT during myogenesis in the mouse embryo."; RL Development 132:2235-2249(2005). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=15955062; DOI=10.1111/j.1742-4658.2005.04716.x; RA Ando Z., Sato S., Ikeda K., Kawakami K.; RT "Slc12a2 is a direct target of two closely related homeobox proteins, RT Six1 and Six4."; RL FEBS J. 272:3026-3041(2005). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=16938278; DOI=10.1016/j.brainres.2006.07.103; RA Konishi Y., Ikeda K., Iwakura Y., Kawakami K.; RT "Six1 and Six4 promote survival of sensory neurons during early RT trigeminal gangliogenesis."; RL Brain Res. 1116:93-102(2006). RN [11] RP FUNCTION. RX PubMed=16530750; DOI=10.1016/j.ydbio.2005.12.015; RA Zou D., Silvius D., Davenport J., Grifone R., Maire P., Xu P.X.; RT "Patterning of the third pharyngeal pouch into thymus/parathyroid by RT Six and Eya1."; RL Dev. Biol. 293:499-512(2006). RN [12] RP DEVELOPMENTAL STAGE, AND FUNCTION. RX PubMed=17300925; DOI=10.1016/j.mod.2007.01.002; RA Kobayashi H., Kawakami K., Asashima M., Nishinakamura R.; RT "Six1 and Six4 are essential for Gdnf expression in the metanephric RT mesenchyme and ureteric bud formation, while Six1 deficiency alone RT causes mesonephric-tubule defects."; RL Mech. Dev. 124:290-303(2007). RN [13] RP FUNCTION. RX PubMed=17592144; DOI=10.1073/pnas.0611299104; RA Giordani J., Bajard L., Demignon J., Daubas P., Buckingham M., RA Maire P.; RT "Six proteins regulate the activation of Myf5 expression in embryonic RT mouse limbs."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11310-11315(2007). RN [14] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=19027001; DOI=10.1016/j.ydbio.2008.10.039; RA Chen B., Kim E.H., Xu P.X.; RT "Initiation of olfactory placode development and neurogenesis is RT blocked in mice lacking both Six1 and Six4."; RL Dev. Biol. 326:75-85(2009). RN [15] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=19962975; DOI=10.1016/j.ydbio.2009.11.031; RA Niro C., Demignon J., Vincent S., Liu Y., Giordani J., Sgarioto N., RA Favier M., Guillet-Deniau I., Blais A., Maire P.; RT "Six1 and Six4 gene expression is necessary to activate the fast-type RT muscle gene program in the mouse primary myotome."; RL Dev. Biol. 338:168-182(2010). RN [16] RP FUNCTION. RX PubMed=20515681; DOI=10.1016/j.ydbio.2010.05.509; RA He G., Tavella S., Hanley K.P., Self M., Oliver G., Grifone R., RA Hanley N., Ward C., Bobola N.; RT "Inactivation of Six2 in mouse identifies a novel genetic mechanism RT controlling development and growth of the cranial base."; RL Dev. Biol. 344:720-730(2010). RN [17] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=20696153; DOI=10.1016/j.yexcr.2010.08.001; RA Yajima H., Motohashi N., Ono Y., Sato S., Ikeda K., Masuda S., RA Yada E., Kanesaki H., Miyagoe-Suzuki Y., Takeda S., Kawakami K.; RT "Six family genes control the proliferation and differentiation of RT muscle satellite cells."; RL Exp. Cell Res. 316:2932-2944(2010). RN [18] RP FUNCTION. RX PubMed=21884692; DOI=10.1016/j.ydbio.2011.08.010; RA Richard A.F., Demignon J., Sakakibara I., Pujol J., Favier M., RA Strochlic L., Le Grand F., Sgarioto N., Guernec A., Schmitt A., RA Cagnard N., Huang R., Legay C., Guillet-Deniau I., Maire P.; RT "Genesis of muscle fiber-type diversity during mouse embryogenesis RT relies on Six1 and Six4 gene expression."; RL Dev. Biol. 359:303-320(2011). RN [19] RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE. RX PubMed=21978088; DOI=10.1111/j.1469-7580.2011.01435.x; RA Suzuki Y., Ikeda K., Kawakami K.; RT "Development of gustatory papillae in the absence of Six1 and Six4."; RL J. Anat. 219:710-721(2011). RN [20] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23987514; DOI=10.1016/j.devcel.2013.06.018; RA Fujimoto Y., Tanaka S.S., Yamaguchi Y.L., Kobayashi H., Kuroki S., RA Tachibana M., Shinomura M., Kanai Y., Morohashi K., Kawakami K., RA Nishinakamura R.; RT "Homeoproteins Six1 and Six4 regulate male sex determination and mouse RT gonadal development."; RL Dev. Cell 26:416-430(2013). CC -!- FUNCTION: Transcriptional regulator which can act as both a CC transcriptional repressor and activator by binding a DNA sequence CC on these target genes and is involved in processes like cell CC differentiation, cell migration and cell survival. Transactivates CC gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' CC motif present in the Trex site and from a 5'-TCA[AG][AG]TTNC-3' CC motif present in the MEF3 site of the muscle-specific genes CC enhancer (PubMed:14966291). Acts cooperatively with EYA proteins CC to transactivate their target genes through interaction and CC nuclear translocation of EYA protein (PubMed:10490620). Acts CC synergistically with SIX1 to regulate target genes involved in CC formation of various organs, including muscle, kidney, gonad, CC ganglia, olfactory epithelium and cranial skeleton. Plays a role CC in several important steps of muscle development. Controls the CC genesis of hypaxial myogenic progenitors in the dermomyotome by CC transactivating PAX3 and the delamination and migration of the CC hypaxial precursors from the ventral lip to the limb buds through CC the transactivation of PAX3, MET and LBX1 (PubMed:15788460). CC Controls myoblast determination by transactivating MYF5, MYOD1 and CC MYF6 (PubMed:15788460, PubMed:17592144). Controls somitic CC differentiation in myocyte through MYOG transactivation CC (PubMed:15788460). Plays a role in synaptogenesis and sarcomere CC organization by participating in myofiber specialization during CC embryogenesis by activating fast muscle program in the primary CC myotome resulting in an up-regulation of fast muscle genes, CC including ATP2A1, MYL1 and TNNT3 (PubMed:19962975, CC PubMed:21884692). Simultaneously, is also able to activate CC inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, CC thereby restricting the activation of the slow muscle genes CC (PubMed:21884692). During muscle regeneration, negatively CC regulates differentiation of muscle satellite cells through down- CC regulation of MYOG expression (PubMed:20696153). During kidney CC development regulates the early stages of metanephros development CC and ureteric bud formation through regulation of GDNF, SALL1, PAX8 CC and PAX2 expression (PubMed:17300925). Plays a role in gonad CC development by regulating both testis determination and size CC determination. In gonadal sex determination, transactivates ZFPM2 CC by binding a MEF3 consensus sequence, resulting in SRY up- CC regulation. In gonadal size determination, transactivates NR5A1 by CC binding a MEF3 consensus sequence resulting in gonadal precursor CC cell formation regulation (PubMed:23987514). During olfactory CC development mediates the specification and patterning of olfactory CC placode through fibroblast growth factor and BMP4 signaling CC pathways and also regulates epithelial cell proliferation during CC placode formation (PubMed:19027001). Promotes survival of sensory CC neurons during early trigeminal gangliogenesis (PubMed:16938278). CC In the developing dorsal root ganglia, up-regulates SLC12A2 CC transcription (PubMed:15955062). Regulates early CC thymus/parathyroid organogenesis through regulation of GCM2 and CC FOXN1 expression (PubMed:16530750). Forms gustatory papillae CC during development of the tongue (PubMed:21978088). Also plays a CC role during embryonic cranial skeleton morphogenesis CC (PubMed:20515681). {ECO:0000269|PubMed:10490620, CC ECO:0000269|PubMed:14966291, ECO:0000269|PubMed:15788460, CC ECO:0000269|PubMed:15955062, ECO:0000269|PubMed:16530750, CC ECO:0000269|PubMed:16938278, ECO:0000269|PubMed:17300925, CC ECO:0000269|PubMed:17592144, ECO:0000269|PubMed:19027001, CC ECO:0000269|PubMed:19962975, ECO:0000269|PubMed:20515681, CC ECO:0000269|PubMed:20696153, ECO:0000269|PubMed:21884692, CC ECO:0000269|PubMed:21978088, ECO:0000269|PubMed:23987514, CC ECO:0000303|PubMed:10490620}. CC -!- SUBUNIT: Interacts with EYA3; acts cooperatively with EYA3 to CC transactivate target genes through interaction and nuclear CC translocation of EYA3 protein (PubMed:12215533, PubMed:10490620). CC {ECO:0000269|PubMed:10490620, ECO:0000269|PubMed:12215533, CC ECO:0000303|PubMed:10490620}. CC -!- INTERACTION: CC O70546:Kdm6a; NbExp=2; IntAct=EBI-986524, EBI-1573712; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8628654, CC ECO:0000269|PubMed:9990334}. Cytoplasm CC {ECO:0000269|PubMed:8628654, ECO:0000269|PubMed:9990334}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=SM; CC IsoId=Q61321-1; Sequence=Displayed; CC Name=2; Synonyms=M18; CC IsoId=Q61321-2; Sequence=VSP_002293, VSP_002294; CC Note=Incomplete sequence.; CC Name=3; Synonyms=M8; CC IsoId=Q61321-3; Sequence=VSP_002293, VSP_002295, VSP_002296; CC Note=Incomplete sequence.; CC -!- TISSUE SPECIFICITY: Mainly expressed in the skeletal muscle CC (isoform 1 and isoform 2 but not isoform 3), and weakly in the CC heart. Also found in the retina and the distal tube of kidney. CC Expressed in skeletal muscle, nasal epithelium, cochlea, CC parathyroid and salivary gland (PubMed:11313460). Expressed in CC muscle satellite cells of normal and regenerating muscles CC (PubMed:20696153). {ECO:0000269|PubMed:11313460, CC ECO:0000269|PubMed:20696153}. CC -!- DEVELOPMENTAL STAGE: At E8.5 expressed at the surface ectoderm CC outside the neural folds, somites, presomitic mesoderm. At E9.5 CC expressed at the nasal and otic placodes, cranial ganglia, CC branchial arches, somites (dermamyotomes and sclerotomes). At CC E10.5-E11.5 expressed at the nasal pits, otic vesicles, cranial CC ganglia, dorsal root ganglia, branchial arches, somites, myotomes, CC limb mesenchyme, notochord, mesonephros. At E12.5-E13.5 expressed CC in skeletal muscles, mesenchyme in limbs and digits, nasal CC epithelium, inner ear (PubMed:11313460). Weakly expressed in the CC nephrogenic cord on E9.5 and in the metanephric mesenchyme on CC E10.5 (PubMed:17300925). At E11.5 expressed in the epithelium of CC the lateral lingual swellings, and in the tongue epithelium, CC mesenchyme, and muscles at E12.5. In the fungiform papillae, CC expressed in the epithelium at E14-E16.5. In the circumvallate and CC foliate papillae, expression is observed in the trench wall of CC these papillae at E15.5-P0 (PubMed:21978088). At E11.5 mainly CC found in limbs, and somites, where is expressed in the dorsal root CC ganglion, myotomes, and ventral and dorsal dermomyotomal lips CC (PubMed:15788460). Expressed in a wide domain of the ectoderm in CC the presumptive olfactory region and in the thickened olfactory CC placode. Expressed in the peripheral precursors of the pit. At CC E12.5-E14.5, expression become progressively restricted to the CC apical and basal progenitors.Also expressed strongly in the CC preplacodal region at E8.0 and in the presumptive olfactory CC ectoderm at E9.0 (PubMed:19027001). At E10.5 expressed in the CC progenitors of the dermomyotome and in the myocytes CC (PubMed:19962975). {ECO:0000269|PubMed:11313460, CC ECO:0000269|PubMed:15788460, ECO:0000269|PubMed:17300925, CC ECO:0000269|PubMed:19027001, ECO:0000269|PubMed:19962975, CC ECO:0000269|PubMed:21978088}. CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile; no gross CC morphological or histological abnormalities, or defects in hearing CC ability are detected in homozygous mice (PubMed:11313460). Double CC homozygous SIX1 and SIX4 knockout mice die soon after birth and CC show developmental defects in various organs (PubMed:15955062). CC Double homozygous SIX1 and SIX4 knockout mice causes severe CC defects in the trigeminal ganglia (PubMed:16938278). Double CC homozygous SIX1 and SIX4 knockout mice exhibit more severe kidney CC phenotypes than the SIX1 knockout mice. Double homozygous SIX1 and CC SIX4 knockout embryos show distinct morphological changes: fusion CC of the lateral lingual swellings is delayed, and the tongue is CC poorly developed. The primordia of fungiform papillae appears CC earlier, and the papillae rapidly increases in size; thus fusion CC of each papilla is evident. The circumvallate papillae show severe CC defects: invagination of the trenches starts asymmetrically, which CC results in longer and shorter trenches (PubMed:21978088). Double CC homozygous SIX1 and SIX4 knockout neonatal mice have a male-to- CC female sex-reversal phenotype in XY mutant gonads CC (PubMed:23987514). Double homozygous SIX1 and SIX4 knockout CC neonatal mice are characterized by severe craniofacial and rib CC defects, and general muscle hypoplasia (PubMed:15788460). CC {ECO:0000269|PubMed:11313460, ECO:0000269|PubMed:15788460, CC ECO:0000269|PubMed:15955062, ECO:0000269|PubMed:16938278, CC ECO:0000269|PubMed:21978088, ECO:0000269|PubMed:23987514}. CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D50416; BAA08915.1; -; mRNA. DR EMBL; D50417; BAA08916.1; -; mRNA. DR EMBL; D50418; BAA08917.1; -; mRNA. DR EMBL; BC137931; AAI37932.1; -; mRNA. DR EMBL; BC137934; AAI37935.1; -; mRNA. DR CCDS; CCDS25974.1; -. [Q61321-1] DR PIR; S63626; S63626. DR PIR; S63628; S63628. DR PIR; S63629; S63629. DR RefSeq; NP_035512.1; NM_011382.2. [Q61321-1] DR UniGene; Mm.249575; -. DR ProteinModelPortal; Q61321; -. DR SMR; Q61321; -. DR IntAct; Q61321; 2. DR MINT; Q61321; -. DR STRING; 10090.ENSMUSP00000036150; -. DR PhosphoSitePlus; Q61321; -. DR PaxDb; Q61321; -. DR PRIDE; Q61321; -. DR Ensembl; ENSMUST00000043208; ENSMUSP00000036150; ENSMUSG00000034460. [Q61321-1] DR GeneID; 20474; -. DR KEGG; mmu:20474; -. DR UCSC; uc007nwb.1; mouse. [Q61321-1] DR CTD; 51804; -. DR MGI; MGI:106034; Six4. DR eggNOG; KOG0775; Eukaryota. DR eggNOG; ENOG410XRPB; LUCA. DR GeneTree; ENSGT00540000070251; -. DR HOGENOM; HOG000261651; -. DR HOVERGEN; HBG017802; -. DR InParanoid; Q61321; -. DR KO; K15615; -. DR OMA; PVYMQQI; -. DR OrthoDB; EOG091G083I; -. DR PhylomeDB; Q61321; -. DR TreeFam; TF315545; -. DR PRO; PR:Q61321; -. DR Proteomes; UP000000589; Chromosome 12. DR Bgee; ENSMUSG00000034460; -. DR ExpressionAtlas; Q61321; baseline and differential. DR Genevisible; Q61321; MM. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0003700; F:DNA binding transcription factor activity; IDA:MGI. DR GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0048856; P:anatomical structure development; IGI:MGI. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IGI:MGI. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IGI:MGI. DR GO; GO:0061197; P:fungiform papilla morphogenesis; IMP:UniProtKB. DR GO; GO:0048699; P:generation of neurons; IMP:UniProtKB. DR GO; GO:0042472; P:inner ear morphogenesis; IGI:MGI. DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB. DR GO; GO:0030238; P:male sex determination; IMP:UniProtKB. DR GO; GO:0046661; P:male sex differentiation; IMP:UniProtKB. DR GO; GO:0072075; P:metanephric mesenchyme development; IMP:UniProtKB. DR GO; GO:0051451; P:myoblast migration; IGI:MGI. DR GO; GO:0061055; P:myotome development; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB. DR GO; GO:1902725; P:negative regulation of satellite cell differentiation; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0030910; P:olfactory placode formation; IMP:UniProtKB. DR GO; GO:0060037; P:pharyngeal system development; IMP:UniProtKB. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0072107; P:positive regulation of ureteric bud formation; IMP:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB. DR GO; GO:0072095; P:regulation of branch elongation involved in ureteric bud branching; IMP:UniProtKB. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI. DR GO; GO:0032880; P:regulation of protein localization; IGI:MGI. DR GO; GO:0008582; P:regulation of synaptic growth at neuromuscular junction; IGI:MGI. DR GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB. DR GO; GO:0098528; P:skeletal muscle fiber differentiation; IMP:UniProtKB. DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:UniProtKB. DR GO; GO:0048538; P:thymus development; IGI:MGI. DR GO; GO:0043586; P:tongue development; IMP:UniProtKB. DR GO; GO:0061551; P:trigeminal ganglion development; IMP:UniProtKB. DR CDD; cd00086; homeodomain; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR031701; SIX1_SD. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF16878; SIX1_SD; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm; KW Developmental protein; DNA-binding; Homeobox; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q9UIU6}. FT CHAIN 2 775 Homeobox protein SIX4. FT /FTId=PRO_0000049304. FT DNA_BIND 216 275 Homeobox. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT REGION 582 775 Transactivation domain. FT COMPBIAS 2 5 Poly-Ser. FT COMPBIAS 58 61 Poly-Ala. FT COMPBIAS 70 76 Poly-Ala. FT COMPBIAS 92 95 Poly-Ala. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000250|UniProtKB:Q9UIU6}. FT MOD_RES 634 634 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9UIU6}. FT VAR_SEQ 1 9 MSSSSPTGQ -> QKAAIRLHYFALAAILM (in FT isoform 2 and isoform 3). {ECO:0000305}. FT /FTId=VSP_002293. FT VAR_SEQ 37 100 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_002294. FT VAR_SEQ 188 319 ERARGRPLGAVDKYRLRRKFPLPRTIWDGEETVYCFKEKSR FT NALKELYKQNRYPSPAEKRHLAKITGLSLTQVSNWFKNRRQ FT RDRNPSETQSKSESDGNPSTEDESSKGHEDLSPHPLSGASD FT GVTNLSLSS -> AGNSPCPAPSGTARRRCIVSRRSRATRS FT RSSTSRIATPRRLRSGTWPRSPASPSPRSATGSRTGGSVTE FT TPPRPSPKANRMATPVPRMNPARDMRICLLIHFQAHLMASP FT TSASLATWSQYICNKLEMLRYH (in isoform 3). FT {ECO:0000305}. FT /FTId=VSP_002295. FT VAR_SEQ 320 775 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_002296. SQ SEQUENCE 775 AA; 82263 MW; B06EBB64E04E5061 CRC64; MSSSSPTGQI ASAADIKQEN GMESASEGQE AHREVAGGAA AGLSPPAPAP FPLEPGDAAA ASRVSREEGA AAAGAADQVQ LHSELLGRHQ HAAAAQPPLA FSPDHVACVC EALQQGGNLD RLARFLWSLP QSDLLRGNES LLKARALVAF HQGIYPELYS ILESHSFESA NHPLLQQLWY KARYTEAERA RGRPLGAVDK YRLRRKFPLP RTIWDGEETV YCFKEKSRNA LKELYKQNRY PSPAEKRHLA KITGLSLTQV SNWFKNRRQR DRNPSETQSK SESDGNPSTE DESSKGHEDL SPHPLSGASD GVTNLSLSSH VEPVYMQQIG NAKISLSSSG VLLNGSLVPA STSPVFLNGN SFIQGHNGVI LNGLNVGNTQ TVSLNPPKMS SNIVGNGIAM TDILGSTSQD VKEFKVLQSS AVNSAATTSY SPSAPVSFPG LIPCTEVKRE GIQTVASQDG GSVVTFTTPV QINQYGIVQI PNSGANGQFL NGSIGFSPLQ LPPVSVAASQ GNLSVTPSTS DGSTFTSEPA TVQHGKLFLS PLTPSAVVYT VPNSGQTVGA VKQEGLERGL VFSQLMPVNH SAQVNASLSS ENLSGSGLHP LTSSLVNVSA AHGFSLTPPT LLNPTELNPD LAESQPVSAP VASKCTVSSV SNTNYATLQN CSLIPGQDLL SGPMTQAALG EIVPTAEEQV SHASTAVHQD FVREQRLVLQ SVPNIKENFL QNSENKATNN LMMLDSKSKY VLDGMVEAGC EDLGTDKKEL AKLQTVQLDE DMQDL //