ID   IRX2_MOUSE              Reviewed;         474 AA.
AC   P81066; O55121; Q3UFG3; Q9ERN1; Q9JLL4;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2002, sequence version 2.
DT   24-JAN-2024, entry version 154.
DE   RecName: Full=Iroquois-class homeodomain protein IRX-2;
DE   AltName: Full=Homeodomain protein IRXA2;
DE   AltName: Full=Iroquois homeobox protein 2;
DE   AltName: Full=Iroquois-class homeobox protein Irx6;
GN   Name=Irx2; Synonyms=Irx6, Irxa2;
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], 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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC   TISSUE=Brain;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
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 MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   NUCLEOTIDE SEQUENCE [MRNA] OF 109-186, 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   [6]
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).
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in specific and overlapping patterns with
CC       Irx1 and Irx3 in the developing and adult metanephric kidney. In the
CC       adult metanephros, renal expression is found in the loop of Henle in
CC       the S3 proximal tubule segment and in the thick ascending limb (TAL) of
CC       the distal tubule. {ECO:0000269|PubMed:17875669}.
CC   -!- DEVELOPMENTAL STAGE: First expressed at 8.0 dpc. During neural tube
CC       closure (8.5 dpc), expression appears for the first time in the
CC       rhombencephalon in the presumptive region of future rhombomere 4.
CC       During neurogenesis (9.5 dpc to 10.5 dpc), predominantly expressed
CC       along the anteroposterior axis of the CNS in the mesencephalon,
CC       metencephalon and rhombencephalon. Expression is strong in the tectum
CC       of the mesencephalon and in the hindbrain, expression is restricted to
CC       rhombomeres. Expression in the spinal cord is weak and confined to the
CC       alar plate. Beginning at 9.5 dpc, expressed in the epithelial component
CC       of the branchial arches and foregut. At 10.5 dpc, expression extends
CC       rostrally into the dorsal diencephalon. Starting at the otic vesicle
CC       stage, shows regionalized expression in the developing inner ear with
CC       expression in the entire otic vesicle from 10.5 dpc onwards. From 10.5
CC       dpc onwards, weak expression begins in the limb bud. Also expressed in
CC       other tissues during organogenesis; at 9.5 dpc, expressed in the
CC       superficial ectoderm surrounding the body and in the region of the
CC       foregut, which will form the pharynx and the lung bud. at 10.5 dpc,
CC       found in the cephalic mesenchyme around the optic vesicle. By 12.5 dpc,
CC       still expressed in the mesenchyme, and expression begins in specific
CC       subsets of post-mitotic cells in the neuroretina. As development
CC       ensues, expression increases in the neuroretina and mesenchymal
CC       expression gradually decreases. At 16.5 dpc, expressed exclusively in
CC       the inner neuroblast layers of the neuroretina. Expressed in the
CC       developing heart in the ventricular septum from the onset of its
CC       formation (10.5 dpc) onward. In fetal stages, expression becomes
CC       confined to the myocardium of the atrioventricular bundle and bundle
CC       branches of the forming ventricular conduction system.
CC       {ECO:0000269|PubMed:10704856, ECO:0000269|PubMed:10926765,
CC       ECO:0000269|PubMed:9486539}.
CC   -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000305}.
CC   -!- CAUTION: Called Irx6 by PubMed:10704856. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF63956.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF295369; AAG10083.1; -; mRNA.
DR   EMBL; AF165986; AAF63956.1; ALT_FRAME; mRNA.
DR   EMBL; AK148520; BAE28598.1; -; mRNA.
DR   EMBL; BC029750; AAH29750.1; -; mRNA.
DR   EMBL; Y15000; CAA75232.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS26628.1; -.
DR   RefSeq; NP_034704.1; NM_010574.3.
DR   AlphaFoldDB; P81066; -.
DR   SMR; P81066; -.
DR   STRING; 10090.ENSMUSP00000073976; -.
DR   iPTMnet; P81066; -.
DR   PhosphoSitePlus; P81066; -.
DR   PaxDb; 10090-ENSMUSP00000073976; -.
DR   ProteomicsDB; 269335; -.
DR   Antibodypedia; 9121; 212 antibodies from 27 providers.
DR   DNASU; 16372; -.
DR   Ensembl; ENSMUST00000074372.6; ENSMUSP00000073976.5; ENSMUSG00000001504.11.
DR   GeneID; 16372; -.
DR   KEGG; mmu:16372; -.
DR   UCSC; uc007rde.1; mouse.
DR   AGR; MGI:1197526; -.
DR   CTD; 153572; -.
DR   MGI; MGI:1197526; Irx2.
DR   VEuPathDB; HostDB:ENSMUSG00000001504; -.
DR   eggNOG; KOG0773; Eukaryota.
DR   GeneTree; ENSGT00940000161198; -.
DR   HOGENOM; CLU_048118_1_0_1; -.
DR   InParanoid; P81066; -.
DR   OMA; TLGQGCQ; -.
DR   OrthoDB; 2915644at2759; -.
DR   PhylomeDB; P81066; -.
DR   TreeFam; TF319371; -.
DR   BioGRID-ORCS; 16372; 6 hits in 77 CRISPR screens.
DR   ChiTaRS; Irx2; mouse.
DR   PRO; PR:P81066; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; P81066; Protein.
DR   Bgee; ENSMUSG00000001504; Expressed in pretectal region and 248 other cell types or tissues.
DR   ExpressionAtlas; P81066; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0072272; P:proximal/distal pattern formation involved in metanephric nephron development; IEP:UniProtKB.
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   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; IPR008422; Homeobox_KN_domain.
DR   InterPro; IPR003893; Iroquois_homeo.
DR   PANTHER; PTHR11211; IROQUOIS-CLASS HOMEODOMAIN PROTEIN IRX; 1.
DR   PANTHER; PTHR11211:SF15; IROQUOIS-CLASS HOMEODOMAIN PROTEIN IRX-2; 1.
DR   Pfam; PF05920; Homeobox_KN; 1.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00548; IRO; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; P81066; MM.
PE   2: Evidence at transcript level;
KW   DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..474
FT                   /note="Iroquois-class homeodomain protein IRX-2"
FT                   /id="PRO_0000049154"
FT   DNA_BIND        115..177
FT                   /note="Homeobox; TALE-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          177..220
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          262..373
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          420..461
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        198..220
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         187
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BZI1"
FT   CONFLICT        27..33
FT                   /note="ALAAPRS -> GGARA (in Ref. 2; AAF63956)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        185..186
FT                   /note="NK -> EQ (in Ref. 5)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   474 AA;  49484 MW;  04E39C42E717F98B CRC64;
     MSYPQGYLYQ APGSLALYSC PAYGASALAA PRSEELARSA SGSAFSPYPG SAAFTAQAAT
     GFGSPLQYSA DAAAAAAAGF PSYVGSPYDT HTTGMTGAIS YHPYGSAAYP YQLNDPAYRK
     NATRDATATL KAWLNEHRKN PYPTKGEKIM LAIITKMTLT QVSTWFANAR RRLKKENKMT
     WAPRNKSEDE DEDEGDASRS KEESSDKAQD GTETSAEDEG ISLHVDSLTD HSCSAESDGE
     KLPCRAGDAL CESGSECKDK FEDLEDEEDE EDECERDLAP PKPVTSSPLT GVEAPLLSPA
     PEAAPRGGSG GKTPLGSRTS PGAPPPASKP KLWSLAEIAT SDLKQPSLGP GCGPPGLPAA
     AAPASTGAPP GGSPYSASPL LGRHLYYTSP FYGNYTNYGN LNAALQGQGL LRYNTAASSP
     GETLHAMPKA ASDTGKAGSH SLESHYRPPG GGYEPKKDTS EGCAVVGAGV QTYL
//