IRX3_MOUSE
ID IRX3_MOUSE Reviewed; 507 AA.
AC P81067; Q3UPZ3; Q5U3K8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Iroquois-class homeodomain protein IRX-3;
DE AltName: Full=Homeodomain protein IRXB1;
DE AltName: Full=Iroquois homeobox protein 3;
GN Name=Irx3; Synonyms=Irxb1;
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 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RX PubMed=9486539; DOI=10.1016/s0925-4773(97)00165-2;
RA Bosse A., Zulch A., Becker M.B., Torres M., Gomez-Skarmeta J.-L.,
RA Modolell J., Gruss P.;
RT "Identification of the vertebrate Iroquois homeobox gene family with
RT overlapping expression during early development of the nervous system.";
RL Mech. Dev. 69:169-181(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RC STRAIN=FVB/N; TISSUE=Embryonic heart;
RX PubMed=10926765; DOI=10.1006/dbio.2000.9801;
RA Christoffels V.M., Keijser A.G.M., Houweling A.C., Clout D.E.W.,
RA Moorman A.F.M.;
RT "Patterning the embryonic heart: identification of five mouse Iroquois
RT homeobox genes in the developing heart.";
RL Dev. Biol. 224:263-274(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; 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 [6]
RP DEVELOPMENTAL STAGE.
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 [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10830170; DOI=10.1016/s0092-8674(00)80853-3;
RA Briscoe J., Pierani A., Jessell T.M., Ericson J.;
RT "A homeodomain protein code specifies progenitor cell identity and neuronal
RT fate in the ventral neural tube.";
RL Cell 101:435-445(2000).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=10704856; DOI=10.1016/s0925-4773(99)00263-4;
RA Cohen D.R., Cheng C.W., Cheng S.H., Hui C.-C.;
RT "Expression of two novel mouse Iroquois-class homeobox genes during
RT neurogenesis.";
RL Mech. Dev. 91:317-321(2000).
RN [9]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR.
RX PubMed=15201216; DOI=10.1242/dev.01179;
RA Lee S.K., Jurata L.W., Funahashi J., Ruiz E.C., Pfaff S.L.;
RT "Analysis of embryonic motoneuron gene regulation: derepression of general
RT activators function in concert with enhancer factors.";
RL Development 131:3295-3306(2004).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326 AND SER-329, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
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 [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24646999; DOI=10.1038/nature13138;
RA Smemo S., Tena J.J., Kim K.H., Gamazon E.R., Sakabe N.J., Gomez-Marin C.,
RA Aneas I., Credidio F.L., Sobreira D.R., Wasserman N.F., Lee J.H.,
RA Puviindran V., Tam D., Shen M., Son J.E., Vakili N.A., Sung H.K.,
RA Naranjo S., Acemel R.D., Manzanares M., Nagy A., Cox N.J., Hui C.C.,
RA Gomez-Skarmeta J.L., Nobrega M.A.;
RT "Obesity-associated variants within FTO form long-range functional
RT connections with IRX3.";
RL Nature 507:371-375(2014).
CC -!- FUNCTION: Transcription factor involved in SHH-dependent neural
CC patterning (PubMed:10830170, PubMed:15201216). Together with NKX2-2 and
CC NKX6-1 acts to restrict the generation of motor neurons to the
CC appropriate region of the neural tube (PubMed:10830170,
CC PubMed:15201216). Belongs to the class I proteins of neuronal
CC progenitor factors, which are repressed by SHH signals
CC (PubMed:10830170, PubMed:15201216). Involved in the transcriptional
CC repression of MNX1 in non-motor neuron cells (PubMed:15201216). Acts as
CC a regulator of energy metabolism (PubMed:24646999).
CC {ECO:0000269|PubMed:10830170, ECO:0000269|PubMed:15201216,
CC ECO:0000269|PubMed:24646999}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P81067-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P81067-2; Sequence=VSP_038351;
CC -!- TISSUE SPECIFICITY: Expressed by neural progenitor cells in discrete
CC domains of the ventral neural tube. Also expressed in specific and
CC overlapping patterns with Irx1 and Irx2 in the developing and adult
CC metanephric kidney. In the adult metanephros, renal expression is
CC confined to the S3 segment of the proximal tubule, in the loop of
CC Henle. {ECO:0000269|PubMed:10830170, ECO:0000269|PubMed:17875669}.
CC -!- DEVELOPMENTAL STAGE: The earliest expressed of the Irx family, with
CC expression seen in trophectoderm-derived extraembryonic tissues from
CC 6.5 dpc, including expression in the chorionic ectoderm at 8.0 dpc.
CC Embryonic expression starts at the end of gastrulation (7.5 dpc) in the
CC ectodermal layer which gives rise to the nervous system. At 8.0 dpc,
CC expression is confined to the thickening neural ectoderm corresponding
CC to the future mesencephalon (midbrain) and rhombencephalon (hindbrain)
CC and from 8.5 dpc onwards, expression also includes the rostral part of
CC the closing neural tube. After neural tube closure at 9.5 dpc,
CC expression predominates in the CNS in the midbrain, hindbrain and
CC spinal cord. Also expressed in a number of tissues outside of the CNS
CC including ectodermal layer of the branchial arches. Expressed in the
CC prospective limb buds of the lateral plate mesoderm, and from 10.5 dpc
CC onwards a gradient exists along the dorsoventral and proximodistal axes
CC of developing limbs. Expressed in the notochord at stage 9.0 dpc. At
CC 9.5 dpc found in the cephalic mesoderm surrounding the optic vesicle.
CC Around 10.5 dpc, expression in the head mesoderm extends into the nasal
CC pits. By 12.5 dpc, still expressed in the mesenchyme, and expressions
CC begins in specific subsets of post-mitotic cells in the neuroretina. As
CC development ensues, expression increases in the neuroretina and
CC mesenchymal expression gradually decreases. At 16.5 dpc, expressed
CC exclusively in the inner neuroblast layers of the neuroretina. In the
CC developing heart, first expressed in the trabecules of embryonic
CC ventricles at 9.5 dpc, and from then onwards localizes specifically to
CC the trabeculated myocardium of the ventricles.
CC {ECO:0000269|PubMed:10704856, ECO:0000269|PubMed:10926765,
CC ECO:0000269|PubMed:9427753, ECO:0000269|PubMed:9486539}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but display a
CC significant reduction of body weight, primarily through the loss of fat
CC mass and increase in basal metabolic rate with browning of white
CC adipose tissue. {ECO:0000269|PubMed:24646999}.
CC -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA75233.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Y15001; CAA75233.1; ALT_FRAME; mRNA.
DR EMBL; AK143023; BAE25251.1; -; mRNA.
DR EMBL; CH466525; EDL11081.1; -; Genomic_DNA.
DR EMBL; BC085500; AAH85500.1; -; mRNA.
DR CCDS; CCDS57630.1; -. [P81067-2]
DR CCDS; CCDS57631.1; -. [P81067-1]
DR RefSeq; NP_001240751.1; NM_001253822.1. [P81067-2]
DR RefSeq; NP_032419.2; NM_008393.3. [P81067-1]
DR AlphaFoldDB; P81067; -.
DR SMR; P81067; -.
DR STRING; 10090.ENSMUSP00000091002; -.
DR iPTMnet; P81067; -.
DR PhosphoSitePlus; P81067; -.
DR PaxDb; P81067; -.
DR PRIDE; P81067; -.
DR ProteomicsDB; 301671; -. [P81067-1]
DR ProteomicsDB; 301672; -. [P81067-2]
DR Antibodypedia; 14619; 362 antibodies from 29 providers.
DR DNASU; 16373; -.
DR Ensembl; ENSMUST00000093312; ENSMUSP00000091002; ENSMUSG00000031734. [P81067-2]
DR Ensembl; ENSMUST00000175795; ENSMUSP00000135488; ENSMUSG00000031734. [P81067-1]
DR GeneID; 16373; -.
DR KEGG; mmu:16373; -.
DR UCSC; uc009msu.2; mouse. [P81067-1]
DR UCSC; uc009msv.2; mouse. [P81067-2]
DR CTD; 79191; -.
DR MGI; MGI:1197522; Irx3.
DR VEuPathDB; HostDB:ENSMUSG00000031734; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00940000161299; -.
DR HOGENOM; CLU_042927_0_1_1; -.
DR InParanoid; P81067; -.
DR OMA; PNWTNRA; -.
DR OrthoDB; 814237at2759; -.
DR PhylomeDB; P81067; -.
DR TreeFam; TF319371; -.
DR BioGRID-ORCS; 16373; 2 hits in 75 CRISPR screens.
DR PRO; PR:P81067; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P81067; protein.
DR Bgee; ENSMUSG00000031734; Expressed in epithelium of cochlear duct and 236 other tissues.
DR Genevisible; P81067; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003167; P:atrioventricular bundle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0048468; P:cell development; IBA:GO_Central.
DR GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
DR GO; GO:0060932; P:His-Purkinje system cell differentiation; IMP:BHF-UCL.
DR GO; GO:0001822; P:kidney development; ISO:MGI.
DR GO; GO:0007498; P:mesoderm development; IGI:MGI.
DR GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:1903598; P:positive regulation of gap junction assembly; IMP:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0072047; P:proximal/distal pattern formation involved in nephron development; IEP:UniProtKB.
DR GO; GO:0003165; P:Purkinje myocyte development; IMP:BHF-UCL.
DR GO; GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0072086; P:specification of loop of Henle identity; IEP: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 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..507
FT /note="Iroquois-class homeodomain protein IRX-3"
FT /id="PRO_0000049156"
FT DNA_BIND 130..192
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 19..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..208
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..261
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..338
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 468..507
FT /note="DRCSALEVEKKLLKTAFQPVPRRPQNHLDAALVLSALSSS -> GDKKNIAV
FT VPWKWRKSYSRQLSSRCQGGHRTIWTLLWSYQLSPRLNFSTIFKSLY (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038351"
FT CONFLICT 494
FT /note="H -> R (in Ref. 1; CAA75233)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 52693 MW; 04FD67E8F5C29AB6 CRC64;
MSFPQLGYQY IRPLYPPERP GAAGGGGGGS SAGGRSGPGA GASELAASGS LSNVLSSVYG
APYAAAAAAA AAAQGYGAFL PYATELPIFP QLGAQYELKD SPGVQHPATA AAFPHPHPAF
YPYGQYQFGD PSRPKNATRE STSTLKAWLN EHRKNPYPTK GEKIMLAIIT KMTLTQVSTW
FANARRRLKK ENKMTWAPRS RTDEEGNAYG SEREEEDEEE DEEESKRELE MEEEELAGEE
EDTGGEGLAD DDEDEEIDLE NLDSAAAGSE LTLAGAAHRN GDFGLGPISD CKTSDSDDSS
EGLEDRPLSV LSLAPPPPPV ARAPASPPSP PSSLDPCAPA PAPSSALQKP KIWSLAETAT
SPDNPRRSPP GAGGSPPGAA VAPPTLQLSP AAAAAAAAAH RLVSAPLGKF PAWTNRPFPG
PPAGPRPHPL SMLGSAPQHL LGLPGAAGHP AAAAAAYARP AEPESGTDRC SALEVEKKLL
KTAFQPVPRR PQNHLDAALV LSALSSS
