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Database: UniProt
Entry: ARX_MOUSE
LinkDB: ARX_MOUSE
Original site: ARX_MOUSE 
ID   ARX_MOUSE               Reviewed;         564 AA.
AC   O35085; A2A4G9; Q9QYT4;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   27-JAN-2003, sequence version 3.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Homeobox protein ARX;
DE   AltName: Full=Aristaless-related homeobox;
GN   Name=Arx;
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   FUNCTION, AND NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9256348; DOI=10.1016/s0925-4773(97)00062-2;
RA   Miura H., Yanazawa M., Kato K., Kitamura K.;
RT   "Expression of a novel aristaless related homeobox gene 'Arx' in the
RT   vertebrate telencephalon, diencephalon and floor plate.";
RL   Mech. Dev. 65:99-109(1997).
RN   [2]
RP   SEQUENCE REVISION TO 391 AND 442.
RA   Kitamura K.;
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BALB/cJ;
RA   Ohsaki K.;
RT   "Homeobox genes and nervous development.";
RL   Thesis (1999), Nara Institute of Science and Technology, Japan.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; 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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=12379852; DOI=10.1038/ng1009;
RA   Kitamura K., Yanazawa M., Sugiyama N., Miura H., Iizuka-Kogo A., Kusaka M.,
RA   Omichi K., Suzuki R., Kato-Fukui Y., Kamiirisa K., Matsuo M., Kamijo S.,
RA   Kasahara M., Yoshioka H., Ogata T., Fukuda T., Kondo I., Kato M.,
RA   Dobyns W.B., Yokoyama M., Morohashi K.;
RT   "Mutation of ARX causes abnormal development of forebrain and testes in
RT   mice and X-linked lissencephaly with abnormal genitalia in humans.";
RL   Nat. Genet. 32:359-369(2002).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=31691806; DOI=10.1093/hmg/ddz254;
RA   Poeta L., Padula A., Attianese B., Valentino M., Verrillo L., Filosa S.,
RA   Shoubridge C., Barra A., Schwartz C.E., Christensen J., van Bokhoven H.,
RA   Helin K., Lioi M.B., Collombat P., Gecz J., Altucci L., Di Schiavi E.,
RA   Miano M.G.;
RT   "Histone demethylase KDM5C is a SAHA-sensitive central hub at the
RT   crossroads of transcriptional axes involved in multiple neurodevelopmental
RT   disorders.";
RL   Hum. Mol. Genet. 28:4089-4102(2019).
CC   -!- FUNCTION: Transcription factor (By similarity). Binds to specific
CC       sequence motif 5'-TAATTA-3' in regulatory elements of target genes,
CC       such as histone demethylase KDM5C (By similarity). Positively modulates
CC       transcription of KDM5C (PubMed:31691806). Activates expression of KDM5C
CC       synergistically with histone lysine demethylase PHF8 and perhaps in
CC       competition with transcription regulator ZNF711; synergy may be related
CC       to enrichment of histone H3K4me3 in regulatory elements (By
CC       similarity). Required for normal brain development (PubMed:12379852).
CC       Plays a role in neuronal proliferation, interneuronal migration and
CC       differentiation in the embryonic forebrain (PubMed:12379852,
CC       PubMed:31691806). May also be involved in axonal guidance in the floor
CC       plate (PubMed:9256348). {ECO:0000250|UniProtKB:Q96QS3,
CC       ECO:0000269|PubMed:12379852, ECO:0000269|PubMed:31691806,
CC       ECO:0000269|PubMed:9256348}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC       ECO:0000255|PROSITE-ProRule:PRU00138}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the developing forebrain and also in
CC       the floor plate (PubMed:9256348). Expressed in the interstitium of the
CC       male gonad at 14.5 dpc, but only weakly in a region of the female gonad
CC       proximal to the mesonephros (PubMed:12379852).
CC       {ECO:0000269|PubMed:12379852, ECO:0000269|PubMed:9256348}.
CC   -!- DISRUPTION PHENOTYPE: Hemizygous knockout males were born at 19.5 dpc
CC       and died within a half day (PubMed:12379852). Neonatal males have small
CC       brains, small olfactory bulbs, small testes, hypoplasia of the seminal
CC       vesicle and abnormally enlarged seminiferous tubules (PubMed:12379852).
CC       Abnormal morphology in each of the developing brain regions in which
CC       ARX is normally expressed (PubMed:12379852). Suppressed proliferation
CC       and nearly normal migration of neuroepithelial cells in the neocortex
CC       (PubMed:12379852). Aberrant formation of many nerve fiber tracts at
CC       19.5 dpc (PubMed:12379852). Abnormal primary migration of GABAergic
CC       interneurons from the ganglionic eminence (PubMed:12379852). Abolished
CC       expression of wingless-related WNT8B and LIM homeobox protein LHX9 in
CC       the thalamic eminence at 12.5 dpc, and decreased expression of DLX1 in
CC       the ventral thalamus at 12.5 dpc (PubMed:12379852). Testes have a
CC       dysplastic interstitium, probably owing to a considerable decrease in
CC       cells containing an abundant cytoplasm as the interstitium is occupied
CC       predominantly by fibroblast-like cells (PubMed:12379852). Expression of
CC       Leydig cell marker HSD3B1 is severely diminished in the interstitial
CC       region of testes, suggesting that Leydig cell differentiation is
CC       blocked (PubMed:12379852). Expression of KDM5C is reduced at both mRNA
CC       and protein levels (PubMed:31691806). Increased expression of SYN1,
CC       SCN2A and some isoforms of BDNF (PubMed:31691806).
CC       {ECO:0000269|PubMed:12379852, ECO:0000269|PubMed:31691806}.
CC   -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AB006103; BAA28284.2; -; mRNA.
DR   EMBL; AB026674; BAA85852.1; -; Genomic_DNA.
DR   EMBL; AL590876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC052033; AAH52033.1; -; mRNA.
DR   CCDS; CCDS30271.1; -.
DR   RefSeq; NP_001292869.1; NM_001305940.1.
DR   RefSeq; NP_031518.2; NM_007492.4.
DR   AlphaFoldDB; O35085; -.
DR   SMR; O35085; -.
DR   STRING; 10090.ENSMUSP00000049039; -.
DR   iPTMnet; O35085; -.
DR   PhosphoSitePlus; O35085; -.
DR   PaxDb; 10090-ENSMUSP00000049039; -.
DR   ProteomicsDB; 277241; -.
DR   ABCD; O35085; 1 sequenced antibody.
DR   Antibodypedia; 24612; 423 antibodies from 32 providers.
DR   DNASU; 11878; -.
DR   Ensembl; ENSMUST00000046565.13; ENSMUSP00000049039.8; ENSMUSG00000035277.16.
DR   Ensembl; ENSMUST00000113947.6; ENSMUSP00000109580.3; ENSMUSG00000035277.16.
DR   GeneID; 11878; -.
DR   KEGG; mmu:11878; -.
DR   UCSC; uc009tsq.1; mouse.
DR   AGR; MGI:1097716; -.
DR   CTD; 170302; -.
DR   MGI; MGI:1097716; Arx.
DR   VEuPathDB; HostDB:ENSMUSG00000035277; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000160633; -.
DR   HOGENOM; CLU_047013_7_0_1; -.
DR   InParanoid; O35085; -.
DR   OMA; EESCPER; -.
DR   OrthoDB; 3151856at2759; -.
DR   PhylomeDB; O35085; -.
DR   TreeFam; TF350743; -.
DR   BioGRID-ORCS; 11878; 1 hit in 61 CRISPR screens.
DR   PRO; PR:O35085; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; O35085; Protein.
DR   Bgee; ENSMUSG00000035277; Expressed in rostral migratory stream and 97 other cell types or tissues.
DR   Genevisible; O35085; MM.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0007411; P:axon guidance; IMP:MGI.
DR   GO; GO:0021846; P:cell proliferation in forebrain; IMP:MGI.
DR   GO; GO:0021853; P:cerebral cortex GABAergic interneuron migration; IMP:MGI.
DR   GO; GO:0021800; P:cerebral cortex tangential migration; IMP:MGI.
DR   GO; GO:0021831; P:embryonic olfactory bulb interneuron precursor migration; IMP:MGI.
DR   GO; GO:0072148; P:epithelial cell fate commitment; IMP:MGI.
DR   GO; GO:0030900; P:forebrain development; IMP:MGI.
DR   GO; GO:0021759; P:globus pallidus development; IMP:MGI.
DR   GO; GO:1904936; P:interneuron migration; IMP:MGI.
DR   GO; GO:0044241; P:lipid digestion; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0001764; P:neuron migration; IMP:MGI.
DR   GO; GO:0021772; P:olfactory bulb development; IMP:MGI.
DR   GO; GO:0035265; P:organ growth; IMP:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR   GO; GO:0046622; P:positive regulation of organ growth; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR003654; OAR_dom.
DR   PANTHER; PTHR24329; HOMEOBOX PROTEIN ARISTALESS; 1.
DR   PANTHER; PTHR24329:SF337; HOMEOBOX PROTEIN ARX; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF03826; OAR; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 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   Developmental protein; Differentiation; DNA-binding; Homeobox;
KW   Neurogenesis; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..564
FT                   /note="Homeobox protein ARX"
FT                   /id="PRO_0000048820"
FT   DNA_BIND        330..389
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          54..79
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          111..264
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           532..545
FT                   /note="OAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT   COMPBIAS        160..174
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        221..252
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        59
FT                   /note="D -> E (in Ref. 3; BAA85852)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        127
FT                   /note="P -> H (in Ref. 3; BAA85852)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        316
FT                   /note="S -> A (in Ref. 3; BAA85852)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        360
FT                   /note="Missing (in Ref. 3; BAA85852)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        485
FT                   /note="Missing (in Ref. 3; BAA85852)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   564 AA;  58490 MW;  74FEBBD3BA92B39C CRC64;
     MSNQYQEEGC SERPECKSKS PTLLSSYCID SILGRRSPCK MRLLGAAQSL PAPLASRADQ
     EKAMQGSPKS SSAPFEAELH LPPKLRRLYG PGGGRLLQGA AAAAAAAAAA AAAATATGTA
     GPRGEVPPPP PPAARPGERQ DSAGAVAAAA AAAAWDTLKI SQAPQVSISR SKSYRENGAP
     FVPPPPALDE LSGPGGVAHP EERLSAASGP GSAPAAGGGT GAEDDEEELL EDEEDEEEEE
     ELLEDDDEEL LEDDARALLK EPRRCSVATT GTVAAAAAAA AAAVATEGGE LSPKEELLLH
     PEDAEGKDGE DSVCLSAGSD SEEGLLKRKQ RRYRTTFTSY QLEELERAFQ KTHYPDVFTR
     EELAMRLDLT EARVQVWFQN RRAKWRKREK AGAQTHPPGL PFPGPLSATH PLSPYLDASP
     FPPHHPALDS AWTAAAAAAA AAFPSLPPPP GSASLPPSGA PLGLSTFLGA AVFRHPAFIS
     PAFGRLFSTM APLTSASTAA ALLRQPTPAV EGAVASGALA DPATAAADRR ASSIAALRLK
     AKEHAAQLTQ LNILPGTSTG KEVC
//
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