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
//