SIX4_MOUSE
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 03-AUG-2022, entry version 178.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE [MRNA]
RP (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 AREC3, a
RT homologue of Drosophila sine oculis gene product, and implication in
RT 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 project:
RT 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; implications in
RT 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., Kawakami K.;
RT "Cooperation of six and eya in activation of their target genes through
RT 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 Six,
RT 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 factor
RT 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, Six1
RT 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 trigeminal
RT 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 Six
RT 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 causes
RT 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., Maire P.;
RT "Six proteins regulate the activation of Myf5 expression in embryonic mouse
RT 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 blocked in
RT 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., Hanley N.,
RA 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., Yada E.,
RA Kanesaki H., Miyagoe-Suzuki Y., Takeda S., Kawakami K.;
RT "Six family genes control the proliferation and differentiation of muscle
RT 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., Cagnard N.,
RA Huang R., Legay C., Guillet-Deniau I., Maire P.;
RT "Genesis of muscle fiber-type diversity during mouse embryogenesis relies
RT 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 on
CC these target genes and is involved in processes like cell
CC differentiation, cell migration and cell survival. Transactivates gene
CC expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present
CC in the Trex site and from a 5'-TCA[AG][AG]TTNC-3' motif present in the
CC MEF3 site of the muscle-specific genes enhancer (PubMed:14966291). Acts
CC cooperatively with EYA proteins to transactivate their target genes
CC through interaction and nuclear translocation of EYA protein
CC (PubMed:10490620). Acts synergistically with SIX1 to regulate target
CC genes involved in formation of various organs, including muscle,
CC kidney, gonad, ganglia, olfactory epithelium and cranial skeleton.
CC Plays a role in several important steps of muscle development. Controls
CC the genesis of hypaxial myogenic progenitors in the dermomyotome by
CC transactivating PAX3 and the delamination and migration of the hypaxial
CC precursors from the ventral lip to the limb buds through the
CC transactivation of PAX3, MET and LBX1 (PubMed:15788460). Controls
CC myoblast determination by transactivating MYF5, MYOD1 and MYF6
CC (PubMed:15788460, PubMed:17592144). Controls somitic differentiation in
CC myocyte through MYOG transactivation (PubMed:15788460). Plays a role in
CC synaptogenesis and sarcomere organization by participating in myofiber
CC specialization during embryogenesis by activating fast muscle program
CC in the primary myotome resulting in an up-regulation of fast muscle
CC genes, including ATP2A1, MYL1 and TNNT3 (PubMed:19962975,
CC PubMed:21884692). Simultaneously, is also able to activate inhibitors
CC of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby
CC restricting the activation of the slow muscle genes (PubMed:21884692).
CC During muscle regeneration, negatively regulates differentiation of
CC muscle satellite cells through down-regulation of MYOG expression
CC (PubMed:20696153). During kidney development regulates the early stages
CC of metanephros development and ureteric bud formation through
CC regulation of GDNF, SALL1, PAX8 and PAX2 expression (PubMed:17300925).
CC Plays a role in gonad development by regulating both testis
CC determination and size determination. In gonadal sex determination,
CC transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in
CC SRY up-regulation. In gonadal size determination, transactivates NR5A1
CC by 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 pathways
CC and also regulates epithelial cell proliferation during placode
CC formation (PubMed:19027001). Promotes survival of sensory neurons
CC during early trigeminal gangliogenesis (PubMed:16938278). In the
CC developing dorsal root ganglia, up-regulates SLC12A2 transcription
CC (PubMed:15955062). Regulates early thymus/parathyroid organogenesis
CC through regulation of GCM2 and FOXN1 expression (PubMed:16530750).
CC Forms gustatory papillae during development of the tongue
CC (PubMed:21978088). Also plays a role during embryonic cranial skeleton
CC morphogenesis (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 Q61321; O70546: Kdm6a; NbExp=2; IntAct=EBI-986524, EBI-1573712;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8628654,
CC ECO:0000269|PubMed:9990334}. Cytoplasm {ECO:0000269|PubMed:8628654,
CC 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 Name=3; Synonyms=M8;
CC IsoId=Q61321-3; Sequence=VSP_002293, VSP_002295, VSP_002296;
CC -!- TISSUE SPECIFICITY: Mainly expressed in the skeletal muscle (isoform 1
CC and isoform 2 but not isoform 3), and weakly in the heart. Also found
CC in the retina and the distal tube of kidney. Expressed in skeletal
CC muscle, nasal epithelium, cochlea, parathyroid and salivary gland
CC (PubMed:11313460). Expressed in muscle satellite cells of normal and
CC regenerating muscles (PubMed:20696153). {ECO:0000269|PubMed:11313460,
CC ECO:0000269|PubMed:20696153}.
CC -!- DEVELOPMENTAL STAGE: At 8.5 dpc expressed at the surface ectoderm
CC outside the neural folds, somites, presomitic mesoderm. At 9.5 dpc
CC expressed at the nasal and otic placodes, cranial ganglia, branchial
CC arches, somites (dermamyotomes and sclerotomes). At 10.5-11.5 dpc
CC expressed at the nasal pits, otic vesicles, cranial ganglia, dorsal
CC root ganglia, branchial arches, somites, myotomes, limb mesenchyme,
CC notochord, mesonephros. At 12.5-13.5 dpc expressed in skeletal muscles,
CC mesenchyme in limbs and digits, nasal epithelium, inner ear
CC (PubMed:11313460). Weakly expressed in the nephrogenic cord on 9.5 dpc
CC and in the metanephric mesenchyme on 10.5 dpc (PubMed:17300925). At
CC 11.5 dpc expressed in the epithelium of the lateral lingual swellings,
CC and in the tongue epithelium, mesenchyme, and muscles at 12.5 dpc. In
CC the fungiform papillae, expressed in the epithelium at 14-16.5 dpc. In
CC the circumvallate and foliate papillae, expression is observed in the
CC trench wall of these papillae at 15.5 dpc-P0 (PubMed:21978088). At 11.5
CC dpc mainly found in limbs, and somites, where is expressed in the
CC dorsal root ganglion, myotomes, and ventral and dorsal dermomyotomal
CC lips (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 12.5
CC dpc-14.5 dpc, expression become progressively restricted to the apical
CC and basal progenitors.Also expressed strongly in the preplacodal region
CC at 8.0 dpc and in the presumptive olfactory ectoderm at 9.0 dpc
CC (PubMed:19027001). At 10.5 dpc expressed in the progenitors of the
CC dermomyotome and in the myocytes (PubMed:19962975).
CC {ECO:0000269|PubMed:11313460, ECO:0000269|PubMed:15788460,
CC ECO:0000269|PubMed:17300925, ECO:0000269|PubMed:19027001,
CC ECO:0000269|PubMed:19962975, 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 show
CC developmental defects in various organs (PubMed:15955062). Double
CC homozygous SIX1 and SIX4 knockout mice causes severe defects in the
CC trigeminal ganglia (PubMed:16938278). Double homozygous SIX1 and SIX4
CC knockout mice exhibit more severe kidney phenotypes than the SIX1
CC knockout mice. Double homozygous SIX1 and SIX4 knockout embryos show
CC distinct morphological changes: fusion of the lateral lingual swellings
CC is delayed, and the tongue is poorly developed. The primordia of
CC fungiform papillae appears earlier, and the papillae rapidly increases
CC in size; thus fusion of each papilla is evident. The circumvallate
CC papillae show severe defects: invagination of the trenches starts
CC asymmetrically, which results in longer and shorter trenches
CC (PubMed:21978088). Double homozygous SIX1 and SIX4 knockout neonatal
CC mice have a male-to-female sex-reversal phenotype in XY mutant gonads
CC (PubMed:23987514). Double homozygous SIX1 and SIX4 knockout neonatal
CC mice are characterized by severe craniofacial and rib defects, and
CC 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 -!- MISCELLANEOUS: [Isoform 2]: Incomplete sequence. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
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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 AlphaFoldDB; Q61321; -.
DR SMR; Q61321; -.
DR BioGRID; 203262; 1.
DR IntAct; Q61321; 2.
DR MINT; Q61321; -.
DR STRING; 10090.ENSMUSP00000036150; -.
DR PhosphoSitePlus; Q61321; -.
DR MaxQB; Q61321; -.
DR PaxDb; Q61321; -.
DR PRIDE; Q61321; -.
DR ProteomicsDB; 257184; -. [Q61321-1]
DR ProteomicsDB; 257185; -. [Q61321-2]
DR ProteomicsDB; 257186; -. [Q61321-3]
DR Antibodypedia; 24389; 181 antibodies from 27 providers.
DR DNASU; 20474; -.
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 VEuPathDB; HostDB:ENSMUSG00000034460; -.
DR eggNOG; KOG0775; Eukaryota.
DR GeneTree; ENSGT00940000160820; -.
DR HOGENOM; CLU_020633_2_0_1; -.
DR InParanoid; Q61321; -.
DR OMA; MCGEMEA; -.
DR OrthoDB; 1061244at2759; -.
DR PhylomeDB; Q61321; -.
DR TreeFam; TF315545; -.
DR BioGRID-ORCS; 20474; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q61321; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q61321; protein.
DR Bgee; ENSMUSG00000034460; Expressed in lumbar dorsal root ganglion and 210 other tissues.
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:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
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 by RNA polymerase II; 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 assembly at neuromuscular junction; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; Homeodomain; 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; Cytoplasm; Developmental protein;
KW DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UIU6"
FT CHAIN 2..775
FT /note="Homeobox protein SIX4"
FT /id="PRO_0000049304"
FT DNA_BIND 216..275
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 582..775
FT /note="Transactivation domain"
FT COMPBIAS 285..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UIU6"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UIU6"
FT VAR_SEQ 1..9
FT /note="MSSSSPTGQ -> QKAAIRLHYFALAAILM (in isoform 2 and
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002293"
FT VAR_SEQ 37..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002294"
FT VAR_SEQ 188..319
FT /note="ERARGRPLGAVDKYRLRRKFPLPRTIWDGEETVYCFKEKSRNALKELYKQNR
FT YPSPAEKRHLAKITGLSLTQVSNWFKNRRQRDRNPSETQSKSESDGNPSTEDESSKGHE
FT DLSPHPLSGASDGVTNLSLSS -> AGNSPCPAPSGTARRRCIVSRRSRATRSRSSTSR
FT IATPRRLRSGTWPRSPASPSPRSATGSRTGGSVTETPPRPSPKANRMATPVPRMNPARD
FT MRICLLIHFQAHLMASPTSASLATWSQYICNKLEMLRYH (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002295"
FT VAR_SEQ 320..775
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="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
