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Homeobox protein SIX4 (Sine oculis homeobox homolog 4) (Skeletal muscle-specific ARE-binding protein AREC3)

 SIX4_MOUSE              Reviewed;         775 AA.
Q61321; B2RQH3; Q61322; Q61323;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
31-JAN-2018, entry version 153.
RecName: Full=Homeobox protein SIX4;
AltName: Full=Sine oculis homeobox homolog 4;
AltName: Full=Skeletal muscle-specific ARE-binding protein AREC3;
Name=Six4; Synonyms=Arec3;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE
[MRNA] (ISOFORMS 2 AND 3), AND SUBCELLULAR LOCATION.
STRAIN=BALB/cJ; TISSUE=Myoblast, and Skeletal muscle;
PubMed=8628654; DOI=10.1093/nar/24.2.303;
Kawakami K., Ohto H., Ikeda K., Roeder R.G.;
"Structure, function and expression of a murine homeobox protein
AREC3, a homologue of Drosophila sine oculis gene product, and
implication in development.";
Nucleic Acids Res. 24:303-310(1996).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
SUBCELLULAR LOCATION.
PubMed=9990334; DOI=10.1006/exer.1998.0562;
Niiya A., Ohto H., Kawakami K., Araki M.;
"Localization of Six4/AREC3 in the developing mouse retina;
implications in mammalian retinal development.";
Exp. Eye Res. 67:699-707(1998).
[4]
FUNCTION.
PubMed=10490620; DOI=10.1128/MCB.19.10.6815;
Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S.,
Kawakami K.;
"Cooperation of six and eya in activation of their target genes
through nuclear translocation of Eya.";
Mol. Cell. Biol. 19:6815-6824(1999).
[5]
DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
PubMed=11313460; DOI=10.1128/MCB.21.10.3343-3350.2001;
Ozaki H., Watanabe Y., Takahashi K., Kitamura K., Tanaka A., Urase K.,
Momoi T., Sudo K., Sakagami J., Asano M., Iwakura Y., Kawakami K.;
"Six4, a putative myogenin gene regulator, is not essential for mouse
embryonal development.";
Mol. Cell. Biol. 21:3343-3350(2001).
[6]
INTERACTION WITH EYA3.
PubMed=12215533; DOI=10.1128/MCB.22.19.6759-6766.2002;
Ikeda K., Watanabe Y., Ohto H., Kawakami K.;
"Molecular interaction and synergistic activation of a promoter by
Six, Eya, and Dach proteins mediated through CREB binding protein.";
Mol. Cell. Biol. 22:6759-6766(2002).
[7]
FUNCTION.
PubMed=14966291; DOI=10.1128/MCB.24.5.2132-2143.2004;
Himeda C.L., Ranish J.A., Angello J.C., Maire P., Aebersold R.,
Hauschka S.D.;
"Quantitative proteomic identification of six4 as the trex-binding
factor in the muscle creatine kinase enhancer.";
Mol. Cell. Biol. 24:2132-2143(2004).
[8]
FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
PubMed=15788460; DOI=10.1242/dev.01773;
Grifone R., Demignon J., Houbron C., Souil E., Niro C., Seller M.J.,
Hamard G., Maire P.;
"Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression
during myogenesis in the mouse embryo.";
Development 132:2235-2249(2005).
[9]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=15955062; DOI=10.1111/j.1742-4658.2005.04716.x;
Ando Z., Sato S., Ikeda K., Kawakami K.;
"Slc12a2 is a direct target of two closely related homeobox proteins,
Six1 and Six4.";
FEBS J. 272:3026-3041(2005).
[10]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=16938278; DOI=10.1016/j.brainres.2006.07.103;
Konishi Y., Ikeda K., Iwakura Y., Kawakami K.;
"Six1 and Six4 promote survival of sensory neurons during early
trigeminal gangliogenesis.";
Brain Res. 1116:93-102(2006).
[11]
FUNCTION.
PubMed=16530750; DOI=10.1016/j.ydbio.2005.12.015;
Zou D., Silvius D., Davenport J., Grifone R., Maire P., Xu P.X.;
"Patterning of the third pharyngeal pouch into thymus/parathyroid by
Six and Eya1.";
Dev. Biol. 293:499-512(2006).
[12]
DEVELOPMENTAL STAGE, AND FUNCTION.
PubMed=17300925; DOI=10.1016/j.mod.2007.01.002;
Kobayashi H., Kawakami K., Asashima M., Nishinakamura R.;
"Six1 and Six4 are essential for Gdnf expression in the metanephric
mesenchyme and ureteric bud formation, while Six1 deficiency alone
causes mesonephric-tubule defects.";
Mech. Dev. 124:290-303(2007).
[13]
FUNCTION.
PubMed=17592144; DOI=10.1073/pnas.0611299104;
Giordani J., Bajard L., Demignon J., Daubas P., Buckingham M.,
Maire P.;
"Six proteins regulate the activation of Myf5 expression in embryonic
mouse limbs.";
Proc. Natl. Acad. Sci. U.S.A. 104:11310-11315(2007).
[14]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=19027001; DOI=10.1016/j.ydbio.2008.10.039;
Chen B., Kim E.H., Xu P.X.;
"Initiation of olfactory placode development and neurogenesis is
blocked in mice lacking both Six1 and Six4.";
Dev. Biol. 326:75-85(2009).
[15]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=19962975; DOI=10.1016/j.ydbio.2009.11.031;
Niro C., Demignon J., Vincent S., Liu Y., Giordani J., Sgarioto N.,
Favier M., Guillet-Deniau I., Blais A., Maire P.;
"Six1 and Six4 gene expression is necessary to activate the fast-type
muscle gene program in the mouse primary myotome.";
Dev. Biol. 338:168-182(2010).
[16]
FUNCTION.
PubMed=20515681; DOI=10.1016/j.ydbio.2010.05.509;
He G., Tavella S., Hanley K.P., Self M., Oliver G., Grifone R.,
Hanley N., Ward C., Bobola N.;
"Inactivation of Six2 in mouse identifies a novel genetic mechanism
controlling development and growth of the cranial base.";
Dev. Biol. 344:720-730(2010).
[17]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=20696153; DOI=10.1016/j.yexcr.2010.08.001;
Yajima H., Motohashi N., Ono Y., Sato S., Ikeda K., Masuda S.,
Yada E., Kanesaki H., Miyagoe-Suzuki Y., Takeda S., Kawakami K.;
"Six family genes control the proliferation and differentiation of
muscle satellite cells.";
Exp. Cell Res. 316:2932-2944(2010).
[18]
FUNCTION.
PubMed=21884692; DOI=10.1016/j.ydbio.2011.08.010;
Richard A.F., Demignon J., Sakakibara I., Pujol J., Favier M.,
Strochlic L., Le Grand F., Sgarioto N., Guernec A., Schmitt A.,
Cagnard N., Huang R., Legay C., Guillet-Deniau I., Maire P.;
"Genesis of muscle fiber-type diversity during mouse embryogenesis
relies on Six1 and Six4 gene expression.";
Dev. Biol. 359:303-320(2011).
[19]
FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
PubMed=21978088; DOI=10.1111/j.1469-7580.2011.01435.x;
Suzuki Y., Ikeda K., Kawakami K.;
"Development of gustatory papillae in the absence of Six1 and Six4.";
J. Anat. 219:710-721(2011).
[20]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=23987514; DOI=10.1016/j.devcel.2013.06.018;
Fujimoto Y., Tanaka S.S., Yamaguchi Y.L., Kobayashi H., Kuroki S.,
Tachibana M., Shinomura M., Kanai Y., Morohashi K., Kawakami K.,
Nishinakamura R.;
"Homeoproteins Six1 and Six4 regulate male sex determination and mouse
gonadal development.";
Dev. Cell 26:416-430(2013).
-!- FUNCTION: 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). {ECO:0000269|PubMed:10490620,
ECO:0000269|PubMed:14966291, ECO:0000269|PubMed:15788460,
ECO:0000269|PubMed:15955062, ECO:0000269|PubMed:16530750,
ECO:0000269|PubMed:16938278, ECO:0000269|PubMed:17300925,
ECO:0000269|PubMed:17592144, ECO:0000269|PubMed:19027001,
ECO:0000269|PubMed:19962975, ECO:0000269|PubMed:20515681,
ECO:0000269|PubMed:20696153, ECO:0000269|PubMed:21884692,
ECO:0000269|PubMed:21978088, ECO:0000269|PubMed:23987514,
ECO:0000303|PubMed:10490620}.
-!- SUBUNIT: Interacts with EYA3; acts cooperatively with EYA3 to
transactivate target genes through interaction and nuclear
translocation of EYA3 protein (PubMed:12215533, PubMed:10490620).
{ECO:0000269|PubMed:10490620, ECO:0000269|PubMed:12215533,
ECO:0000303|PubMed:10490620}.
-!- INTERACTION:
O70546:Kdm6a; NbExp=2; IntAct=EBI-986524, EBI-1573712;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8628654,
ECO:0000269|PubMed:9990334}. Cytoplasm
{ECO:0000269|PubMed:8628654, ECO:0000269|PubMed:9990334}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Comment=Additional isoforms seem to exist.;
Name=1; Synonyms=SM;
IsoId=Q61321-1; Sequence=Displayed;
Name=2; Synonyms=M18;
IsoId=Q61321-2; Sequence=VSP_002293, VSP_002294;
Note=Incomplete sequence.;
Name=3; Synonyms=M8;
IsoId=Q61321-3; Sequence=VSP_002293, VSP_002295, VSP_002296;
Note=Incomplete sequence.;
-!- TISSUE SPECIFICITY: Mainly expressed in the skeletal muscle
(isoform 1 and isoform 2 but not isoform 3), and weakly in the
heart. Also found in the retina and the distal tube of kidney.
Expressed in skeletal muscle, nasal epithelium, cochlea,
parathyroid and salivary gland (PubMed:11313460). Expressed in
muscle satellite cells of normal and regenerating muscles
(PubMed:20696153). {ECO:0000269|PubMed:11313460,
ECO:0000269|PubMed:20696153}.
-!- DEVELOPMENTAL STAGE: At E8.5 expressed at the surface ectoderm
outside the neural folds, somites, presomitic mesoderm. At E9.5
expressed at the nasal and otic placodes, cranial ganglia,
branchial arches, somites (dermamyotomes and sclerotomes). At
E10.5-E11.5 expressed at the nasal pits, otic vesicles, cranial
ganglia, dorsal root ganglia, branchial arches, somites, myotomes,
limb mesenchyme, notochord, mesonephros. At E12.5-E13.5 expressed
in skeletal muscles, mesenchyme in limbs and digits, nasal
epithelium, inner ear (PubMed:11313460). Weakly expressed in the
nephrogenic cord on E9.5 and in the metanephric mesenchyme on
E10.5 (PubMed:17300925). At E11.5 expressed in the epithelium of
the lateral lingual swellings, and in the tongue epithelium,
mesenchyme, and muscles at E12.5. In the fungiform papillae,
expressed in the epithelium at E14-E16.5. In the circumvallate and
foliate papillae, expression is observed in the trench wall of
these papillae at E15.5-P0 (PubMed:21978088). At E11.5 mainly
found in limbs, and somites, where is expressed in the dorsal root
ganglion, myotomes, and ventral and dorsal dermomyotomal lips
(PubMed:15788460). Expressed in a wide domain of the ectoderm in
the presumptive olfactory region and in the thickened olfactory
placode. Expressed in the peripheral precursors of the pit. At
E12.5-E14.5, expression become progressively restricted to the
apical and basal progenitors.Also expressed strongly in the
preplacodal region at E8.0 and in the presumptive olfactory
ectoderm at E9.0 (PubMed:19027001). At E10.5 expressed in the
progenitors of the dermomyotome and in the myocytes
(PubMed:19962975). {ECO:0000269|PubMed:11313460,
ECO:0000269|PubMed:15788460, ECO:0000269|PubMed:17300925,
ECO:0000269|PubMed:19027001, ECO:0000269|PubMed:19962975,
ECO:0000269|PubMed:21978088}.
-!- DISRUPTION PHENOTYPE: Mice are viable and fertile; no gross
morphological or histological abnormalities, or defects in hearing
ability are detected in homozygous mice (PubMed:11313460). Double
homozygous SIX1 and SIX4 knockout mice die soon after birth and
show developmental defects in various organs (PubMed:15955062).
Double homozygous SIX1 and SIX4 knockout mice causes severe
defects in the trigeminal ganglia (PubMed:16938278). Double
homozygous SIX1 and SIX4 knockout mice exhibit more severe kidney
phenotypes than the SIX1 knockout mice. Double homozygous SIX1 and
SIX4 knockout embryos show distinct morphological changes: fusion
of the lateral lingual swellings is delayed, and the tongue is
poorly developed. The primordia of fungiform papillae appears
earlier, and the papillae rapidly increases in size; thus fusion
of each papilla is evident. The circumvallate papillae show severe
defects: invagination of the trenches starts asymmetrically, which
results in longer and shorter trenches (PubMed:21978088). Double
homozygous SIX1 and SIX4 knockout neonatal mice have a male-to-
female sex-reversal phenotype in XY mutant gonads
(PubMed:23987514). Double homozygous SIX1 and SIX4 knockout
neonatal mice are characterized by severe craniofacial and rib
defects, and general muscle hypoplasia (PubMed:15788460).
{ECO:0000269|PubMed:11313460, ECO:0000269|PubMed:15788460,
ECO:0000269|PubMed:15955062, ECO:0000269|PubMed:16938278,
ECO:0000269|PubMed:21978088, ECO:0000269|PubMed:23987514}.
-!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
{ECO:0000305}.
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EMBL; D50416; BAA08915.1; -; mRNA.
EMBL; D50417; BAA08916.1; -; mRNA.
EMBL; D50418; BAA08917.1; -; mRNA.
EMBL; BC137931; AAI37932.1; -; mRNA.
EMBL; BC137934; AAI37935.1; -; mRNA.
CCDS; CCDS25974.1; -. [Q61321-1]
PIR; S63626; S63626.
PIR; S63628; S63628.
PIR; S63629; S63629.
RefSeq; NP_035512.1; NM_011382.2. [Q61321-1]
UniGene; Mm.249575; -.
ProteinModelPortal; Q61321; -.
SMR; Q61321; -.
IntAct; Q61321; 2.
MINT; MINT-7949316; -.
STRING; 10090.ENSMUSP00000036150; -.
PhosphoSitePlus; Q61321; -.
PaxDb; Q61321; -.
PRIDE; Q61321; -.
Ensembl; ENSMUST00000043208; ENSMUSP00000036150; ENSMUSG00000034460. [Q61321-1]
GeneID; 20474; -.
KEGG; mmu:20474; -.
UCSC; uc007nwb.1; mouse. [Q61321-1]
CTD; 51804; -.
MGI; MGI:106034; Six4.
eggNOG; KOG0775; Eukaryota.
eggNOG; ENOG410XRPB; LUCA.
GeneTree; ENSGT00540000070251; -.
HOGENOM; HOG000261651; -.
HOVERGEN; HBG017802; -.
InParanoid; Q61321; -.
KO; K15615; -.
OMA; PVYMQQI; -.
OrthoDB; EOG091G083I; -.
PhylomeDB; Q61321; -.
TreeFam; TF315545; -.
PRO; PR:Q61321; -.
Proteomes; UP000000589; Chromosome 12.
Bgee; ENSMUSG00000034460; -.
ExpressionAtlas; Q61321; baseline and differential.
Genevisible; Q61321; MM.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0003700; F:DNA binding transcription factor activity; IDA:MGI.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0048856; P:anatomical structure development; IGI:MGI.
GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IGI:MGI.
GO; GO:0048704; P:embryonic skeletal system morphogenesis; IGI:MGI.
GO; GO:0061197; P:fungiform papilla morphogenesis; IMP:UniProtKB.
GO; GO:0048699; P:generation of neurons; IMP:UniProtKB.
GO; GO:0042472; P:inner ear morphogenesis; IGI:MGI.
GO; GO:0008584; P:male gonad development; IMP:UniProtKB.
GO; GO:0030238; P:male sex determination; IMP:UniProtKB.
GO; GO:0046661; P:male sex differentiation; IMP:UniProtKB.
GO; GO:0072075; P:metanephric mesenchyme development; IMP:UniProtKB.
GO; GO:0051451; P:myoblast migration; IGI:MGI.
GO; GO:0061055; P:myotome development; IMP:UniProtKB.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
GO; GO:1902725; P:negative regulation of satellite cell differentiation; IMP:UniProtKB.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0030910; P:olfactory placode formation; IMP:UniProtKB.
GO; GO:0060037; P:pharyngeal system development; IMP:UniProtKB.
GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0072107; P:positive regulation of ureteric bud formation; IMP:UniProtKB.
GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
GO; GO:0072095; P:regulation of branch elongation involved in ureteric bud branching; IMP:UniProtKB.
GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:UniProtKB.
GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
GO; GO:0032880; P:regulation of protein localization; IGI:MGI.
GO; GO:0008582; P:regulation of synaptic growth at neuromuscular junction; IGI:MGI.
GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB.
GO; GO:0098528; P:skeletal muscle fiber differentiation; IMP:UniProtKB.
GO; GO:0007519; P:skeletal muscle tissue development; IMP:UniProtKB.
GO; GO:0048538; P:thymus development; IGI:MGI.
GO; GO:0043586; P:tongue development; IMP:UniProtKB.
GO; GO:0061551; P:trigeminal ganglion development; IMP:UniProtKB.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR031701; SIX1_SD.
Pfam; PF00046; Homeobox; 1.
Pfam; PF16878; SIX1_SD; 1.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
Developmental protein; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
Reference proteome; Transcription; Transcription regulation.
INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q9UIU6}.
CHAIN 2 775 Homeobox protein SIX4.
/FTId=PRO_0000049304.
DNA_BIND 216 275 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
REGION 582 775 Transactivation domain.
COMPBIAS 2 5 Poly-Ser.
COMPBIAS 58 61 Poly-Ala.
COMPBIAS 70 76 Poly-Ala.
COMPBIAS 92 95 Poly-Ala.
MOD_RES 2 2 N-acetylserine.
{ECO:0000250|UniProtKB:Q9UIU6}.
MOD_RES 634 634 Phosphoserine.
{ECO:0000250|UniProtKB:Q9UIU6}.
VAR_SEQ 1 9 MSSSSPTGQ -> QKAAIRLHYFALAAILM (in
isoform 2 and isoform 3). {ECO:0000305}.
/FTId=VSP_002293.
VAR_SEQ 37 100 Missing (in isoform 2). {ECO:0000305}.
/FTId=VSP_002294.
VAR_SEQ 188 319 ERARGRPLGAVDKYRLRRKFPLPRTIWDGEETVYCFKEKSR
NALKELYKQNRYPSPAEKRHLAKITGLSLTQVSNWFKNRRQ
RDRNPSETQSKSESDGNPSTEDESSKGHEDLSPHPLSGASD
GVTNLSLSS -> AGNSPCPAPSGTARRRCIVSRRSRATRS
RSSTSRIATPRRLRSGTWPRSPASPSPRSATGSRTGGSVTE
TPPRPSPKANRMATPVPRMNPARDMRICLLIHFQAHLMASP
TSASLATWSQYICNKLEMLRYH (in isoform 3).
{ECO:0000305}.
/FTId=VSP_002295.
VAR_SEQ 320 775 Missing (in isoform 3). {ECO:0000305}.
/FTId=VSP_002296.
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


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