IRX3_XENLA
ID IRX3_XENLA Reviewed; 448 AA.
AC O42261; Q32NJ5;
DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Iroquois-class homeodomain protein irx-3;
DE AltName: Full=Iroquois homeobox protein 3 {ECO:0000250|UniProtKB:P78415};
DE Short=Xiro3 {ECO:0000312|EMBL:AAB84027.1};
GN Name=irx3; Synonyms=iro3 {ECO:0000303|PubMed:9427753};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB84027.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Neurula {ECO:0000269|PubMed:9427753};
RX PubMed=9427753; DOI=10.1093/emboj/17.1.191;
RA Bellefroid E.J., Kobbe A., Gruss P., Pieler T., Gurdon J.B., Papalopulu N.;
RT "Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and
RT functions in neural specification.";
RL EMBO J. 17:191-203(1998).
RN [2] {ECO:0000312|EMBL:AAI08596.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula {ECO:0000312|EMBL:AAI08596.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=12385755; DOI=10.1016/s0925-4773(02)00296-4;
RA de la Calle-Mustienes E., Glavic A., Modolell J., Gomez-Skarmeta J.L.;
RT "Xiro homeoproteins coordinate cell cycle exit and primary neuron formation
RT by upregulating neuronal-fate repressors and downregulating the cell-cycle
RT inhibitor XGadd45-gamma.";
RL Mech. Dev. 119:69-80(2002).
RN [4] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17875669; DOI=10.1101/gad.450707;
RA Reggiani L., Raciti D., Airik R., Kispert A., Braendli A.W.;
RT "The prepattern transcription factor Irx3 directs nephron segment
RT identity.";
RL Genes Dev. 21:2358-2370(2007).
RN [5] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18715948; DOI=10.1242/dev.023697;
RA Alarcon P., Rodriguez-Seguel E., Fernandez-Gonzalez A., Rubio R.,
RA Gomez-Skarmeta J.L.;
RT "A dual requirement for Iroquois genes during Xenopus kidney development.";
RL Development 135:3197-3207(2008).
RN [6] {ECO:0000305}
RP INDUCTION.
RX PubMed=19250931; DOI=10.1016/j.ydbio.2009.02.019;
RA Yan B., Neilson K.M., Moody S.A.;
RT "foxD5 plays a critical upstream role in regulating neural ectodermal fate
RT and the onset of neural differentiation.";
RL Dev. Biol. 329:80-95(2009).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19268445; DOI=10.1016/j.ydbio.2009.02.028;
RA Rodriguez-Seguel E., Alarcon P., Gomez-Skarmeta J.L.;
RT "The Xenopus Irx genes are essential for neural patterning and define the
RT border between prethalamus and thalamus through mutual antagonism with the
RT anterior repressors Fezf and Arx.";
RL Dev. Biol. 329:258-268(2009).
CC -!- FUNCTION: Acts partially redundantly with other irx members in neural
CC patterning. Required for formation of the posterior forebrain,
CC midbrain, hindbrain, and to a lesser extent, spinal cord. Both up-
CC regulates and down-regulates gene expression during neural development.
CC Acts early in neural plate development to induce proneural gene
CC expression and specify a neural precursor state. Also up-regulates
CC repressors that prevent neuronal differentiation. Required during at
CC least two stages of pronephros kidney development; during neurula
CC stages, maintains transcription of key renal genes to define the size
CC and identity of the pronephric anlage, probably in part through
CC regulation of bmp-signaling. Subsequently required for proper formation
CC of the intermediate tubule segment of the pronephros.
CC {ECO:0000269|PubMed:12385755, ECO:0000269|PubMed:17875669,
CC ECO:0000269|PubMed:18715948, ECO:0000269|PubMed:19268445,
CC ECO:0000269|PubMed:9427753}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in the developing central
CC nervous system (CNS). At gastrula stage, expressed in both the
CC superficial and deep layers of the presumptive neural plate with
CC expression spreading to the prospective hindbrain, spinal cord and
CC midbrain-hindbrain junction as neurulation proceeds. Not expressed in
CC the anterior neural plate and CNS expression in the tadpole excludes
CC the forebrain. Outside of the CNS, expressed around the closing
CC blastopore at early gastrula stages and as gastrulation proceeds,
CC expression switches to the anterior lateral plate mesoderm. In
CC tadpoles, expressed in the ectodermal layer of the branchial arches,
CC and in the otic vesicle. Also expressed in specific and overlapping
CC dynamic patterns with irx1 and irx2 during pronephric kidney
CC development. Renal expression begins before segment-specific terminal
CC differentiation in the pronephric anlage at mid-neurula stage, and is
CC later found in proximal tubule PT3 as well as intermediate tubule
CC segments IT1 and IT2, with expression in the kidney being maintained
CC through to the tadpole stage. {ECO:0000269|PubMed:17875669,
CC ECO:0000269|PubMed:18715948, ECO:0000269|PubMed:19268445,
CC ECO:0000269|PubMed:9427753}.
CC -!- INDUCTION: By a combination of a neural inducing signal (nog/noggin)
CC and a posteriorizing signal (bFGF). Inhibited in the neural plate by
CC foxd5. The anterior limit of expression at the future border between
CC the prethalamus and thalamus is defined by mutual repression with the
CC anterior repressor fezf2, and also by arx. Induced by retinoic acid
CC (RA) during kidney development. {ECO:0000269|PubMed:18715948,
CC ECO:0000269|PubMed:19250931, ECO:0000269|PubMed:19268445,
CC ECO:0000269|PubMed:9427753}.
CC -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000255}.
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DR EMBL; AF027175; AAB84027.1; -; mRNA.
DR EMBL; BC108595; AAI08596.1; -; mRNA.
DR RefSeq; NP_001084204.1; NM_001090735.1.
DR AlphaFoldDB; O42261; -.
DR SMR; O42261; -.
DR DNASU; 399365; -.
DR GeneID; 399365; -.
DR KEGG; xla:399365; -.
DR CTD; 399365; -.
DR Xenbase; XB-GENE-480490; irx3.L.
DR OMA; PNENNAP; -.
DR OrthoDB; 814237at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 399365; Expressed in internal ear and 13 other tissues.
DR GO; GO:0030424; C:axon; ISA:AgBase.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:UniProtKB.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0072005; P:maintenance of kidney identity; IMP:UniProtKB.
DR GO; GO:0007498; P:mesoderm development; ISA:AgBase.
DR GO; GO:0001656; P:metanephros development; ISA:AgBase.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0001840; P:neural plate development; IMP:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; IMP:UniProtKB.
DR GO; GO:0072047; P:proximal/distal pattern formation involved in nephron development; ISA:AgBase.
DR GO; GO:0072196; P:proximal/distal pattern formation involved in pronephric nephron development; IMP:UniProtKB.
DR GO; GO:0072086; P:specification of loop of Henle identity; ISA:AgBase.
DR GO; GO:0039005; P:specification of pronephric tubule identity; IMP:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR InterPro; IPR003893; Iroquois_homeo.
DR Pfam; PF05920; Homeobox_KN; 1.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00548; IRO; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 2: Evidence at transcript level;
KW Activator; Developmental protein; Differentiation; DNA-binding; Homeobox;
KW Neurogenesis; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..448
FT /note="Iroquois-class homeodomain protein irx-3"
FT /id="PRO_0000386621"
FT DNA_BIND 108..170
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 171..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 171..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 194..218
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..247
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 434
FT /note="N -> D (in Ref. 1; AAB84027)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 49312 MW; 63866B7E466ADDF4 CRC64;
MSFPQLGYQY IRPLYPSDRQ SVGVTRSGTE LSPAGTLSNV LSSVYGAPYA AAAAAQAYGA
FLPYSAELPI FPQLGSQYDM KDSPGVQHAA FSHPHPAFYP YGQYQFGDPS RPKNATREST
STLKAWLNEH RKNPYPTKGE KIMLAIITKM TLTQVSTWFA NARRRLKKEN KMTWAPRSRT
DEEGNAYGSD HEEDKHEDEE EIDLENIDTE DIESKEDLDD PDTDIHSDSK TDTRSDSEVS
DGFEDLNVPE DRLLKSVVGQ RQLLNEEPQD KCALSSDAKV PQPACEQIKL NRLPPSPPQE
NNMPVAHKPK IWSLAETATT PDNPRNSPNT GGSVNTQNLI AQHRLIASPG SRFQGWTGRA
FSAQQLSLLN SAHFLQGLGV SHTAPCSGNA SFPKAAESKC STNSLTDRPS TVDIEKTIPV
LNTAFQPVQR RSQNHLDAAM ILSALSSS
