IRX1A_XENLA
ID IRX1A_XENLA Reviewed; 467 AA.
AC Q9YGK8;
DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Iroquois-class homeodomain protein irx-1-A;
DE AltName: Full=Iroquois homeobox protein 1-A;
DE Short=Xiro-1 {ECO:0000303|PubMed:11747072};
DE Short=Xiro1 {ECO:0000303|PubMed:9427752};
GN Name=irx1-a; Synonyms=iro1 {ECO:0000303|PubMed:9427752}, iro1-a, irx1;
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:CAB38329.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Gastrula {ECO:0000269|PubMed:9427752};
RX PubMed=9427752; DOI=10.1093/emboj/17.1.181;
RA Gomez-Skarmeta J.L., Glavic A., de la Calle-Mustienes E., Modolell J.,
RA Mayor R.;
RT "Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls
RT development at the neural plate.";
RL EMBO J. 17:181-190(1998).
RN [2] {ECO:0000312|EMBL:AAI69342.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula {ECO:0000312|EMBL:AAI69342.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11171338; DOI=10.1242/dev.128.4.551;
RA Gomez-Skarmeta J.L., de La Calle-Mustienes E., Modolell J.;
RT "The Wnt-activated Xiro1 gene encodes a repressor that is essential for
RT neural development and downregulates Bmp4.";
RL Development 128:551-560(2001).
RN [4] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11747072; DOI=10.1002/dvdy.1189;
RA Glavic A., Gomez-Skarmeta J.L., Mayor R.;
RT "Xiro-1 controls mesoderm patterning by repressing bmp-4 expression in the
RT Spemann organizer.";
RL Dev. Dyn. 222:368-376(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11923198; DOI=10.1242/dev.129.7.1609;
RA Glavic A., Gomez-Skarmeta J.L., Mayor R.;
RT "The homeoprotein Xiro1 is required for midbrain-hindbrain boundary
RT formation.";
RL Development 129:1609-1621(2002).
RN [6] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11744385; DOI=10.1016/s0925-4773(01)00565-2;
RA de la Calle-Mustienes E., Modolell J., Gomez-Skarmeta J.L.;
RT "The Xiro-repressed gene CoREST is expressed in Xenopus neural
RT territories.";
RL Mech. Dev. 110:209-211(2002).
RN [7] {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 [8] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14651938; DOI=10.1016/j.ydbio.2003.09.002;
RA de la Calle-Mustienes E., Lu Z., Cortes M., Andersen B., Modolell J.,
RA Gomez-Skarmeta J.L.;
RT "Xenopus Xlmo4 is a GATA cofactor during ventral mesoderm formation and
RT regulates Ldb1 availability at the dorsal mesoderm and the neural plate.";
RL Dev. Biol. 264:564-581(2003).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=14681193; DOI=10.1242/dev.00945;
RA Glavic A., Silva F., Aybar M.J., Bastidas F., Mayor R.;
RT "Interplay between Notch signaling and the homeoprotein Xiro1 is required
RT for neural crest induction in Xenopus embryos.";
RL Development 131:347-359(2004).
RN [10] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=15223346; DOI=10.1016/j.ydbio.2004.04.013;
RA Schlosser G., Ahrens K.;
RT "Molecular anatomy of placode development in Xenopus laevis.";
RL Dev. Biol. 271:439-466(2004).
RN [11] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15242793; DOI=10.1016/j.ydbio.2004.04.020;
RA Glavic A., Maris Honore S., Gloria Feijoo C., Bastidas F., Allende M.L.,
RA Mayor R.;
RT "Role of BMP signaling and the homeoprotein Iroquois in the specification
RT of the cranial placodal field.";
RL Dev. Biol. 272:89-103(2004).
RN [12] {ECO:0000305}
RP 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 [13] {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 [14] {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 [15] {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. Acts early in
CC neural plate development to induce expression of some but not all
CC proneural genes, and specify a neural precursor state. Also up-
CC regulates repressors that prevent neuronal differentiation. Patterns
CC the neuroectoderm in both the anterior/posterior and dorsal/ventral
CC axes. Acts primarily as a transcriptional repressor during neural
CC development, and binds to the bmp4 promoter to repress gene expression
CC and thus mediate down-regulation of bmp4 by wnt signaling. Controls
CC multiple processes through bmp4-repression including neural plate
CC development, neural crest specification and Spemann organizer
CC development. Involved in the specification of the preplacodal field at
CC the anterior border of the neural plate. Regulates the genetic cascade
CC of interactions that are necessary for positioning the isthmus
CC organizer and the formation of the midbrain-hindbrain boundary.
CC Required during at least two stages of pronephros kidney development;
CC during neurula stages, maintains transcription of key renal genes to
CC define the size and identity of the pronephric anlage, probably in part
CC through regulation of bmp-signaling. Subsequently required for proper
CC formation of the intermediate tubule segment of the pronephros. Acts
CC principally as a transcriptional activator during pronephros
CC development. {ECO:0000269|PubMed:11171338, ECO:0000269|PubMed:11747072,
CC ECO:0000269|PubMed:11923198, ECO:0000269|PubMed:12385755,
CC ECO:0000269|PubMed:14651938, ECO:0000269|PubMed:14681193,
CC ECO:0000269|PubMed:15242793, ECO:0000269|PubMed:18715948,
CC ECO:0000269|PubMed:19268445}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed early in neural differentiation in the
CC neural plate, and expression continues in the neural tube after neural
CC fold closure. Expressed in the presumptive midbrain territory. Also
CC expressed in the prospective neural crest and the preplacodal field,
CC anterior to the neural plate. Strongly expressed in the profundal
CC placode and weakly expressed in the trigeminal placode. Also expressed
CC in the mesoderm in the Spemann organizer from the start of
CC gastrulation, and subsequently in its derivatives; namely in the
CC notochord as well as in the somites of stage 25 embryos, and the
CC somites and notochord of tailbud embryos. Also expressed in specific
CC and overlapping dynamic patterns with irx2 and irx3 during pronephric
CC kidney development. Renal expression begins in the dorsal region of the
CC pronephric anlage at mid neurula stage and continues to at least
CC tailbud stages where expression is confined to the intermediate tubule
CC segment IT1. Renal expression is maintained at tadpole stages.
CC {ECO:0000269|PubMed:11171338, ECO:0000269|PubMed:11744385,
CC ECO:0000269|PubMed:11747072, ECO:0000269|PubMed:11923198,
CC ECO:0000269|PubMed:14651938, ECO:0000269|PubMed:15223346,
CC ECO:0000269|PubMed:15242793, ECO:0000269|PubMed:17875669,
CC ECO:0000269|PubMed:18715948, ECO:0000269|PubMed:19268445,
CC ECO:0000269|PubMed:9427752}.
CC -!- INDUCTION: By wnt signaling. Mutually antagonizes bmp4 signaling.
CC Inhibited in the neural plate by foxd5. The anterior limit of
CC expression at the future border between the prethalamus and thalamus is
CC defined by mutual repression with the anterior repressor fezf2, and
CC also by arx. Induced by retinoic acid (RA) during kidney development.
CC {ECO:0000269|PubMed:11171338, ECO:0000269|PubMed:18715948,
CC ECO:0000269|PubMed:19250931, ECO:0000269|PubMed:19268445}.
CC -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000255}.
CC -!- CAUTION: Although PubMed:17875669 show that irx1 is dispensable for
CC pronephric kidney development, PubMed:18715948 show that irx1 is
CC required for formation of the pronephros. {ECO:0000305}.
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DR EMBL; AJ001834; CAB38329.1; -; mRNA.
DR EMBL; BC169342; AAI69342.1; -; mRNA.
DR EMBL; BC169344; AAI69344.1; -; mRNA.
DR RefSeq; NP_001081649.1; NM_001088180.2.
DR AlphaFoldDB; Q9YGK8; -.
DR SMR; Q9YGK8; -.
DR GeneID; 397976; -.
DR KEGG; xla:397976; -.
DR CTD; 397976; -.
DR Xenbase; XB-GENE-865648; irx1.L.
DR OMA; VMSVHAG; -.
DR OrthoDB; 827009at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 397976; Expressed in lung and 13 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0001708; P:cell fate specification; IMP:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:UniProtKB.
DR GO; GO:0072005; P:maintenance of kidney identity; IMP:UniProtKB.
DR GO; GO:0007498; P:mesoderm development; IMP:UniProtKB.
DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IMP:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0014036; P:neural crest cell fate specification; IMP:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; 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:0009954; P:proximal/distal pattern formation; IMP:UniProtKB.
DR GO; GO:0072196; P:proximal/distal pattern formation involved in pronephric nephron development; IMP:UniProtKB.
DR GO; GO:0039005; P:specification of pronephric tubule identity; IMP:UniProtKB.
DR GO; GO:0060062; P:Spemann organizer formation at the dorsal lip of the blastopore; 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..467
FT /note="Iroquois-class homeodomain protein irx-1-A"
FT /id="PRO_0000388713"
FT DNA_BIND 126..188
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 197..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..241
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..262
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 280..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 319..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..433
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 435..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 467 AA; 50658 MW; 14C41715EE048376 CRC64;
MSFPQLGYPQ YLTAGQAAVY GGERPGVLAA AAAAAAAAAA AGSGRPTGAE LGSSSTAAVT
SVLGMYASPY SAPNYSAFLP YTTDLTLFSQ MGSQYELKDN PGVHPATFAA HTTPGYYPYG
QFQYGDPGRP KNATRESTGT LKAWLNEHRK NPYPTKGEKI MLAIITKMTL TQVSTWFANA
RRRLKKENKV TWGARSKEDD NIFGSDNEGD HEKNEDDEEI DLESIDIDKI DDNDGEQSNE
EEDEKLEHLR QGEKESLKKE SEVMIPSSDG LKPKDSMSLG KESSDTSNTR IVSPGGQGNI
QVPPHSKPKI WSLAETATSP DGALKSSPPP SQGNHTSPPI QHPAFLPSHG LYTCQIGKFH
NWTNGAFLTQ SSLINMRSLL GVNPHHAAHH NHHHLQAHQQ APFLATNLSS LSSDKTPERT
SPKHSDRENV PRTDSPPQLK PSFQAVRENT LSQQEGTSRI LTALPSA
