VSX2_MOUSE
ID VSX2_MOUSE Reviewed; 361 AA.
AC Q61412;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Visual system homeobox 2;
DE AltName: Full=Ceh-10 homeodomain-containing homolog;
DE AltName: Full=Homeobox protein CHX10;
GN Name=Vsx2 {ECO:0000303|PubMed:17919464, ECO:0000312|MGI:MGI:88401};
GN Synonyms=Chx10 {ECO:0000303|PubMed:17919464};
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].
RC STRAIN=CD-1 X 129/Sv; TISSUE=Eye;
RX PubMed=7914735; DOI=10.1016/0896-6273(94)90354-9;
RA Liu I.S.C., Chen J.-D., Ploder L., Vidgen D., van der Kooy D.,
RA Kalnins V.I., McInnes R.R.;
RT "Developmental expression of a novel murine homeobox gene (Chx10): evidence
RT for roles in determination of the neuroretina and inner nuclear layer.";
RL Neuron 13:377-393(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN
RP OR(J).
RX PubMed=8630490; DOI=10.1038/ng0496-376;
RA Burmeister M., Novak J., Liang M.Y., Basu S., Ploder L., Hawes N.L.,
RA Vidgen D., Hoover F., Goldman D., Kalnins V.I., Roderick T.H., Taylor B.A.,
RA Hankin M.H., McInnes R.R.;
RT "Ocular retardation mouse caused by Chx10 homeobox null allele: impaired
RT retinal progenitor proliferation and bipolar cell differentiation.";
RL Nat. Genet. 12:376-384(1996).
RN [4]
RP FUNCTION.
RX PubMed=16236706; DOI=10.1074/jbc.m509470200;
RA Dorval K.M., Bobechko B.P., Fujieda H., Chen S., Zack D.J., Bremner R.;
RT "CHX10 targets a subset of photoreceptor genes.";
RL J. Biol. Chem. 281:744-751(2006).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16547132; DOI=10.1073/pnas.0600083103;
RA Livne-Bar I., Pacal M., Cheung M.C., Hankin M., Trogadis J., Chen D.,
RA Dorval K.M., Bremner R.;
RT "Chx10 is required to block photoreceptor differentiation but is
RT dispensable for progenitor proliferation in the postnatal retina.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:4988-4993(2006).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-200.
RX PubMed=17919464; DOI=10.1016/j.brainres.2007.06.007;
RA Clark A.M., Yun S., Veien E.S., Wu Y.Y., Chow R.L., Dorsky R.I.,
RA Levine E.M.;
RT "Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the
RT vertebrate retina.";
RL Brain Res. 1192:99-113(2008).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18417110; DOI=10.1016/j.ydbio.2008.02.055;
RA Sigulinsky C.L., Green E.S., Clark A.M., Levine E.M.;
RT "Vsx2/Chx10 ensures the correct timing and magnitude of Hedgehog signaling
RT in the mouse retina.";
RL Dev. Biol. 317:560-575(2008).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19843539; DOI=10.1093/hmg/ddp484;
RA Reichman S., Kalathur R.K., Lambard S., Ait-Ali N., Yang Y., Lardenois A.,
RA Ripp R., Poch O., Zack D.J., Sahel J.A., Leveillard T.;
RT "The homeobox gene CHX10/VSX2 regulates RdCVF promoter activity in the
RT inner retina.";
RL Hum. Mol. Genet. 19:250-261(2010).
RN [9]
RP FUNCTION, INTERACTION WITH MITF, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP ARG-200 AND ARG-227.
RX PubMed=23028343; DOI=10.1371/journal.pgen.1002924;
RA Zou C., Levine E.M.;
RT "Vsx2 controls eye organogenesis and retinal progenitor identity via
RT homeodomain and non-homeodomain residues required for high affinity DNA
RT binding.";
RL PLoS Genet. 8:E1002924-E1002924(2012).
RN [10]
RP FUNCTION.
RX PubMed=27477290; DOI=10.1016/j.celrep.2016.06.100;
RA Clovis Y.M., Seo S.Y., Kwon J.S., Rhee J.C., Yeo S., Lee J.W., Lee S.,
RA Lee S.K.;
RT "Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene
RT Repression Modes.";
RL Cell Rep. 16:1642-1652(2016).
CC -!- FUNCTION: Acts as a transcriptional regulator through binding to DNA at
CC the consensus sequence 5'-[TC]TAATT[AG][AG]-3' upstream of gene
CC promoters (PubMed:17919464). Plays a significant role in the
CC specification and morphogenesis of the sensory retina (PubMed:8630490).
CC Mediates differentiation of V2a interneurons by repression of motor
CC neuron gene transcription, via competitively binding to response
CC elements that are activated by the ISL1-LHX3 complex, such as VSX1
CC (PubMed:17919464, PubMed:27477290). Acts as a positive transcriptional
CC regulator of NXNL1; regulation is significantly increased in synergy
CC with VSX1 (PubMed:19843539). Acts as a negative transcriptional
CC regulator of MITF (PubMed:23028343). Represses SAG transcription by
CC competitive inhibition of ISL1-LHX3 response elements (By similarity).
CC Binds to the photoreceptor conserved element-1 (PCE-1) in the promoter
CC of rod photoreceptor arrestin SAG and acts as a transcriptional
CC repressor (PubMed:16236706). Involved in the development of retinal
CC ganglion cells (RGCs) which leads to release of SHH by RGCs, promoting
CC Hedgehog signaling and subsequent proliferation of retinal progenitor
CC cells (PubMed:18417110). Participates in the development of the cells
CC of the inner nuclear layer, by promoting postnatal differentiation of
CC bipolar cells with a comparable inhibition of rod cell differentiation
CC (PubMed:8630490, PubMed:16547132). May play a role in the maintenance
CC of neural retina identity during development by regulation of canonical
CC Wnt genes and CTNNB1 localization, suggesting a role in the regulation
CC of canonical Wnt signaling (By similarity).
CC {ECO:0000250|UniProtKB:P58304, ECO:0000269|PubMed:16236706,
CC ECO:0000269|PubMed:16547132, ECO:0000269|PubMed:17919464,
CC ECO:0000269|PubMed:18417110, ECO:0000269|PubMed:19843539,
CC ECO:0000269|PubMed:23028343, ECO:0000269|PubMed:27477290,
CC ECO:0000269|PubMed:8630490}.
CC -!- SUBUNIT: Interacts with MITF. {ECO:0000269|PubMed:23028343}.
CC -!- INTERACTION:
CC Q61412; P13405: Rb1; NbExp=2; IntAct=EBI-1208174, EBI-971782;
CC Q61412; Q08999: RBL2; Xeno; NbExp=4; IntAct=EBI-1208174, EBI-971439;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8630490}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level)
CC (PubMed:8630490, PubMed:16547132, PubMed:17919464, PubMed:18417110,
CC PubMed:19843539, PubMed:23028343). Expressed throughout the anterior
CC optic vesicle and all neuroblasts of the optic cup (at protein level)
CC (PubMed:8630490). In the mature and postnatal retina is restricted to
CC the inner nuclear layer, in which its expression decreases from the
CC outer to the inner margin (at protein level) (PubMed:8630490,
CC PubMed:17919464, PubMed:19843539). Also detected in regions of the
CC developing thalamus, hindbrain, and ventral spinal cord
CC (PubMed:8630490). {ECO:0000269|PubMed:16547132,
CC ECO:0000269|PubMed:17919464, ECO:0000269|PubMed:18417110,
CC ECO:0000269|PubMed:19843539, ECO:0000269|PubMed:23028343,
CC ECO:0000269|PubMed:8630490}.
CC -!- DEVELOPMENTAL STAGE: Detected by embryonic day 25, by which time the
CC optic cup has formed and the ganglion cell layer can be distinguished.
CC A rapid increase to levels 3- to 4-fold greater than those seen in
CC adult retina occurs in the period from birth (P0) to postnatal day 6
CC (P6). During this interval, the horizontal, bipolar, amacrine, and cone
CC cells arise from the neuroretinal layer, the inner nuclear layer, and
CC outer nuclear layer separate, and the outer plexiform layer begins to
CC form. Levels begin to decrease by P8, when the rod outer segments are
CC Still differentiating, and reaches its lowest levels in adult retina.
CC -!- DISEASE: Note=Defects in Vsx2 are the cause of ocular retardation
CC (OR(J)), a mouse disease characterized by microphthalmia, progressive
CC destruction of the retina, and absence of the optic nerve. The OR(J)
CC mutation is due to an OCHR (STOP) mutation.
CC {ECO:0000269|PubMed:8630490}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the retina of newborn
CC mice results in an increase in the number of photoreceptor cells as a
CC result of a decrease in the number of bipolar cells and a comparable
CC increase in rod cells at postnatal day 21.
CC {ECO:0000269|PubMed:16547132}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR EMBL; L34808; AAA60431.1; -; mRNA.
DR EMBL; BC031869; AAH31869.1; -; mRNA.
DR CCDS; CCDS36493.1; -.
DR PIR; I49594; I49594.
DR RefSeq; NP_031727.1; NM_007701.3.
DR AlphaFoldDB; Q61412; -.
DR SMR; Q61412; -.
DR BioGRID; 198710; 2.
DR IntAct; Q61412; 3.
DR STRING; 10090.ENSMUSP00000131009; -.
DR iPTMnet; Q61412; -.
DR PhosphoSitePlus; Q61412; -.
DR PaxDb; Q61412; -.
DR PRIDE; Q61412; -.
DR ProteomicsDB; 297932; -.
DR Antibodypedia; 190; 189 antibodies from 32 providers.
DR DNASU; 12677; -.
DR Ensembl; ENSMUST00000021665; ENSMUSP00000021665; ENSMUSG00000021239.
DR GeneID; 12677; -.
DR KEGG; mmu:12677; -.
DR UCSC; uc007ofm.2; mouse.
DR CTD; 338917; -.
DR MGI; MGI:88401; Vsx2.
DR VEuPathDB; HostDB:ENSMUSG00000021239; -.
DR eggNOG; KOG0494; Eukaryota.
DR GeneTree; ENSGT00940000157776; -.
DR InParanoid; Q61412; -.
DR OMA; QDVHLQP; -.
DR PhylomeDB; Q61412; -.
DR BioGRID-ORCS; 12677; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Vsx2; mouse.
DR PRO; PR:Q61412; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q61412; protein.
DR Bgee; ENSMUSG00000021239; Expressed in retinal neural layer and 69 other tissues.
DR ExpressionAtlas; Q61412; baseline and differential.
DR Genevisible; Q61412; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0043010; P:camera-type eye development; IGI:MGI.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IMP:MGI.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR023339; CVC.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR003654; OAR_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS51496; CVC; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Repressor; Sensory transduction; Transcription;
KW Transcription regulation; Vision.
FT CHAIN 1..361
FT /note="Visual system homeobox 2"
FT /id="PRO_0000049363"
FT DOMAIN 208..261
FT /note="CVC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00829"
FT DNA_BIND 148..207
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 304..317
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT COMPBIAS 112..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 200
FT /note="R->Q: Loss of DNA binding activity; mice are
FT microphthalmic but viable with defects in retinal
FT morphology and pigmentation as a result of delayed retinal
FT neurogenesis. Reduction in transcription repression
FT activity."
FT /evidence="ECO:0000269|PubMed:17919464,
FT ECO:0000269|PubMed:23028343"
FT MUTAGEN 227
FT /note="R->W: Reduction in DNA binding activity; mice are
FT microphthalmic but viable with severe defects in retinal
FT morphology and extensive pigmentation as a result of a lack
FT of retinal neurogenesis."
FT /evidence="ECO:0000269|PubMed:23028343"
SQ SEQUENCE 361 AA; 39436 MW; 2DB7FF7F8C7BE0AA CRC64;
MTGKAGEALS KPKSETVAKS TSGGAPARCT GFGIQEILGL NKEPPSSHPR AALDGLAPGH
LLAARSVLSP AGVGSMGLLG PGGLPGFYTQ PTFLEVLSDP QSVHLQPLGR ASGPLDTSQT
ASSDSEDVSS SDRKMSKSAL NQTKKRKKRR HRTIFTSYQL EELEKAFNEA HYPDVYAREM
LAMKTELPED RIQVWFQNRR AKWRKREKCW GRSSVMAEYG LYGAMVRHSI PLPESILKSA
KDGIMDSCAP WLLGMHKKSL EAAAESGRKP EVERQALPKL DKMEQEERAP EAQAAISQEE
LRENSIAALR AKAQEHSTKV LGTVSGPDSL ARNAEKPEEE DATEEDRPAE KLSPPQLEDM
A
