RX_HUMAN
ID RX_HUMAN Reviewed; 346 AA.
AC Q9Y2V3; Q86V11;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Retinal homeobox protein Rx;
DE AltName: Full=Retina and anterior neural fold homeobox protein;
GN Name=RAX; Synonyms=RX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=10625658; DOI=10.1074/jbc.275.2.1152;
RA Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., Shinohara T.;
RT "Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-
RT specific gene expression.";
RL J. Biol. Chem. 275:1152-1160(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Retinoblastoma;
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S.,
RA Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC 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 [5]
RP VARIANT MCOP3 GLN-192, VARIANT GLU-44, CHARACTERIZATION OF VARIANT GLU-44,
RP AND CHARACTERIZATION OF VARIANT MCOP3 GLN-192.
RX PubMed=14662654; DOI=10.1093/hmg/ddh025;
RA Voronina V.A., Kozhemyakina E.A., O'Kernick C.M., Kahn N.D., Wenger S.L.,
RA Linberg J.V., Schneider A.S., Mathers P.H.;
RT "Mutations in the human RAX homeobox gene in a patient with anophthalmia
RT and sclerocornea.";
RL Hum. Mol. Genet. 13:315-322(2004).
RN [6]
RP VARIANTS MCOP3 HIS-160; GLN-187 AND GLN-188.
RX PubMed=24033328; DOI=10.1111/cge.12275;
RA Chassaing N., Causse A., Vigouroux A., Delahaye A., Alessandri J.L.,
RA Boespflug-Tanguy O., Boute-Benejean O., Dollfus H., Duban-Bedu B.,
RA Gilbert-Dussardier B., Giuliano F., Gonzales M., Holder-Espinasse M.,
RA Isidor B., Jacquemont M.L., Lacombe D., Martin-Coignard D.,
RA Mathieu-Dramard M., Odent S., Picone O., Pinson L., Quelin C., Sigaudy S.,
RA Toutain A., Thauvin-Robinet C., Kaplan J., Calvas P.;
RT "Molecular findings and clinical data in a cohort of 150 patients with
RT anophthalmia/microphthalmia.";
RL Clin. Genet. 86:326-334(2014).
CC -!- FUNCTION: Plays a critical role in eye formation by regulating the
CC initial specification of retinal cells and/or their subsequent
CC proliferation. Binds to the photoreceptor conserved element-I (PCE-
CC 1/Ret 1) in the photoreceptor cell-specific arrestin promoter.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2V3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2V3-2; Sequence=VSP_053558, VSP_053559;
CC -!- TISSUE SPECIFICITY: Expressed in the developing eye and weakly
CC expressed in the adult retina.
CC -!- DISEASE: Microphthalmia, isolated, 3 (MCOP3) [MIM:611038]: A disorder
CC of eye formation, ranging from small size of a single eye to complete
CC bilateral absence of ocular tissues. Ocular abnormalities like
CC opacities of the cornea and lens, scaring of the retina and choroid,
CC and other abnormalities may also be present.
CC {ECO:0000269|PubMed:14662654, ECO:0000269|PubMed:24033328}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AF115392; AAD23438.1; -; mRNA.
DR EMBL; AB593018; BAJ83973.1; -; mRNA.
DR EMBL; AC067859; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051901; AAH51901.1; -; mRNA.
DR CCDS; CCDS11972.1; -. [Q9Y2V3-1]
DR RefSeq; NP_038463.2; NM_013435.2. [Q9Y2V3-1]
DR AlphaFoldDB; Q9Y2V3; -.
DR SMR; Q9Y2V3; -.
DR BioGRID; 119034; 9.
DR STRING; 9606.ENSP00000334813; -.
DR iPTMnet; Q9Y2V3; -.
DR PhosphoSitePlus; Q9Y2V3; -.
DR BioMuta; RAX; -.
DR DMDM; 296452886; -.
DR MassIVE; Q9Y2V3; -.
DR PaxDb; Q9Y2V3; -.
DR PeptideAtlas; Q9Y2V3; -.
DR PRIDE; Q9Y2V3; -.
DR ProteomicsDB; 69944; -.
DR ProteomicsDB; 85910; -. [Q9Y2V3-1]
DR Antibodypedia; 9851; 285 antibodies from 23 providers.
DR DNASU; 30062; -.
DR Ensembl; ENST00000256852.7; ENSP00000256852.7; ENSG00000134438.10. [Q9Y2V3-2]
DR Ensembl; ENST00000334889.4; ENSP00000334813.3; ENSG00000134438.10. [Q9Y2V3-1]
DR GeneID; 30062; -.
DR KEGG; hsa:30062; -.
DR MANE-Select; ENST00000334889.4; ENSP00000334813.3; NM_013435.3; NP_038463.2.
DR UCSC; uc002lhx.3; human. [Q9Y2V3-1]
DR CTD; 30062; -.
DR DisGeNET; 30062; -.
DR GeneCards; RAX; -.
DR HGNC; HGNC:18662; RAX.
DR HPA; ENSG00000134438; Group enriched (brain, pituitary gland, retina).
DR MalaCards; RAX; -.
DR MIM; 601881; gene.
DR MIM; 611038; phenotype.
DR neXtProt; NX_Q9Y2V3; -.
DR OpenTargets; ENSG00000134438; -.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 35612; Nanophthalmos.
DR PharmGKB; PA38626; -.
DR VEuPathDB; HostDB:ENSG00000134438; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000162144; -.
DR HOGENOM; CLU_047013_2_0_1; -.
DR InParanoid; Q9Y2V3; -.
DR OMA; PSYPCGP; -.
DR OrthoDB; 1085093at2759; -.
DR PhylomeDB; Q9Y2V3; -.
DR TreeFam; TF315976; -.
DR PathwayCommons; Q9Y2V3; -.
DR SignaLink; Q9Y2V3; -.
DR BioGRID-ORCS; 30062; 11 hits in 1095 CRISPR screens.
DR ChiTaRS; RAX; human.
DR GenomeRNAi; 30062; -.
DR Pharos; Q9Y2V3; Tbio.
DR PRO; PR:Q9Y2V3; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q9Y2V3; protein.
DR Bgee; ENSG00000134438; Expressed in neuron projection bundle connecting eye with brain and 20 other tissues.
DR ExpressionAtlas; Q9Y2V3; baseline and differential.
DR Genevisible; Q9Y2V3; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR003654; OAR_dom.
DR InterPro; IPR043562; RAX/RAX2.
DR PANTHER; PTHR46271; PTHR46271; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 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 Alternative splicing; Developmental protein; Disease variant; DNA-binding;
KW Homeobox; Microphthalmia; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..346
FT /note="Retinal homeobox protein Rx"
FT /id="PRO_0000049276"
FT DNA_BIND 136..195
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 46..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 33..40
FT /note="Octapeptide motif"
FT MOTIF 323..336
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT MOTIF 329..333
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 56..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..113
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..307
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 97..104
FT /note="APRPYCPK -> GVVPEPTG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:21697133"
FT /id="VSP_053558"
FT VAR_SEQ 105..346
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:21697133"
FT /id="VSP_053559"
FT VARIANT 44
FT /note="D -> E (in dbSNP:rs2271733)"
FT /evidence="ECO:0000269|PubMed:14662654"
FT /id="VAR_020150"
FT VARIANT 160
FT /note="Y -> H (in MCOP3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075630"
FT VARIANT 187
FT /note="R -> Q (in MCOP3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075631"
FT VARIANT 188
FT /note="R -> Q (in MCOP3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075632"
FT VARIANT 192
FT /note="R -> Q (in MCOP3; does not affect nuclear
FT localization; reduces DNA binding activity;
FT dbSNP:rs121909127)"
FT /evidence="ECO:0000269|PubMed:14662654"
FT /id="VAR_034905"
FT CONFLICT 107
FT /note="G -> W (in Ref. 1; AAD23438)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 36676 MW; FEDA196F6A326F31 CRC64;
MHLPGCAPAM ADGSFSLAGH LLRSPGGSTS RLHSIEAILG FTKDDGILGT FPAERGARGA
KERDRRLGAR PACPKAPEEG SEPSPPPAPA PAPEYEAPRP YCPKEPGEAR PSPGLPVGPA
TGEAKLSEEE QPKKKHRRNR TTFTTYQLHE LERAFEKSHY PDVYSREELA GKVNLPEVRV
QVWFQNRRAK WRRQEKLEVS SMKLQDSPLL SFSRSPPSAT LSPLGAGPGS GGGPAGGALP
LESWLGPPLP GGGATALQSL PGFGPPAQSL PASYTPPPPP PPFLNSPPLG PGLQPLAPPP
PSYPCGPGFG DKFPLDEADP RNSSIAALRL KAKEHIQAIG KPWQAL
