IRX5_MOUSE
ID IRX5_MOUSE Reviewed; 484 AA.
AC Q9JKQ4; Q80WV4; Q9JLL5;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Iroquois-class homeodomain protein IRX-5;
DE AltName: Full=Homeodomain protein IRXB2;
DE AltName: Full=Iroquois homeobox protein 5;
GN Name=Irx5; Synonyms=Irxb2;
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].
RX PubMed=10822268;
RX DOI=10.1002/(sici)1097-0177(200005)218:1<160::aid-dvdy14>3.0.co;2-2;
RA Bosse A., Stoykova A., Nieselt-Struwe K., Chowdhury K., Copeland N.G.,
RA Jenkins N.A., Gruss P.;
RT "Identification of a novel mouse Iroquois homeobox gene, Irx5, and
RT chromosomal localisation of all members of the mouse Iroquois gene
RT family.";
RL Dev. Dyn. 218:160-174(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 1-442, 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 [6]
RP DISRUPTION PHENOTYPE, AND POSSIBLE FUNCTION.
RX PubMed=16239150; DOI=10.1016/j.cell.2005.08.004;
RA Costantini D.L., Arruda E.P., Agarwal P., Kim K.-H., Zhu Y., Zhu W.,
RA Lebel M., Cheng C.W., Park C.Y., Pierce S.A., Guerchicoff A.,
RA Pollevick G.D., Chan T.Y., Kabir M.G., Cheng S.H., Husain M.,
RA Antzelevitch C., Srivastava D., Gross G.J., Hui C.C., Backx P.H.,
RA Bruneau B.G.;
RT "The homeodomain transcription factor Irx5 establishes the mouse cardiac
RT ventricular repolarization gradient.";
RL Cell 123:347-358(2005).
RN [7]
RP POSSIBLE FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16182275; DOI=10.1016/j.ydbio.2005.08.029;
RA Cheng C.W., Chow R.L., Lebel M., Sakuma R., Cheung H.O.-L.,
RA Thanabalasingham V., Zhang X., Bruneau B.G., Birch D.G., Hui C.C.,
RA McInnes R.R., Cheng S.H.;
RT "The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar
RT cell development.";
RL Dev. Biol. 287:48-60(2005).
RN [8]
RP LACK OF RENAL EXPRESSION.
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 [9]
RP POSSIBLE FUNCTION.
RX PubMed=18322081; DOI=10.1523/jneurosci.4784-07.2008;
RA Kerschensteiner D., Liu H., Cheng C.W., Demas J., Cheng S.H., Hui C.C.,
RA Chow R.L., Wong R.O.L.;
RT "Genetic control of circuit function: Vsx1 and Irx5 transcription factors
RT regulate contrast adaptation in the mouse retina.";
RL J. Neurosci. 28:2342-2352(2008).
CC -!- FUNCTION: Establishes the cardiac repolarization gradient by its
CC repressive actions on the KCND2 potassium-channel gene. Required for
CC retinal cone bipolar cell differentiation. May regulate contrast
CC adaptation in the retina and control specific aspects of visual
CC function in circuits of the mammalian retina. Involved in craniofacial
CC and gonadal development (By similarity). Modulates the migration of
CC progenitor cell populations in branchial arches and gonads by
CC repressing CXCL12. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- TISSUE SPECIFICITY: Not expressed in the developing metanephric kidney
CC or adult kidney.
CC -!- DEVELOPMENTAL STAGE: In 9.5 dpc embryos, expressed in the
CC rhombencephalon, metencephalon, and in the cephalic mesoderm surround
CC the optic vesicle. By 12.5 dpc, expression continues in the mesenchyme
CC and also begins in subsets of cells in the neuroretina, becoming
CC expressed in the retinal inner neuroblast layers by 16.5 dpc. Expressed
CC in developing bipolar cells during retinal development starting at
CC postnatal day 5, and expressed in a subset of cone bipolar cells in the
CC mature retina. Also expressed along the spinal cord, in the ventricular
CC layer, in motor neurons and in the proximal limb buds during embryonic
CC development. Expressed in the developing heart in the endocardium that
CC lines the heart chambers. {ECO:0000269|PubMed:10704856,
CC ECO:0000269|PubMed:10926765, ECO:0000269|PubMed:16182275}.
CC -!- DISRUPTION PHENOTYPE: Disruption causes increased KCND2 potassium-
CC channel expression in endocardial myocardium leading to abolition of
CC the cardiac repolarization gradient, a selective increase of the major
CC cardiac repolarization current, I(to,f), and increased susceptibility
CC to arrhythmias. {ECO:0000269|PubMed:16239150}.
CC -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF63955.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF230074; AAF42871.1; -; mRNA.
DR EMBL; AK004747; BAB23528.1; -; mRNA.
DR EMBL; BC051959; AAH51959.2; -; mRNA.
DR EMBL; BC056994; AAH56994.1; -; mRNA.
DR EMBL; AF165985; AAF63955.1; ALT_FRAME; mRNA.
DR CCDS; CCDS22522.1; -.
DR RefSeq; NP_061296.1; NM_018826.2.
DR AlphaFoldDB; Q9JKQ4; -.
DR SMR; Q9JKQ4; -.
DR STRING; 10090.ENSMUSP00000034184; -.
DR iPTMnet; Q9JKQ4; -.
DR PhosphoSitePlus; Q9JKQ4; -.
DR PaxDb; Q9JKQ4; -.
DR PRIDE; Q9JKQ4; -.
DR ProteomicsDB; 267008; -.
DR Antibodypedia; 14623; 222 antibodies from 22 providers.
DR DNASU; 54352; -.
DR Ensembl; ENSMUST00000034184; ENSMUSP00000034184; ENSMUSG00000031737.
DR GeneID; 54352; -.
DR KEGG; mmu:54352; -.
DR UCSC; uc009mub.1; mouse.
DR CTD; 10265; -.
DR MGI; MGI:1859086; Irx5.
DR VEuPathDB; HostDB:ENSMUSG00000031737; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00940000159483; -.
DR HOGENOM; CLU_048118_0_0_1; -.
DR InParanoid; Q9JKQ4; -.
DR OMA; PSEGRHD; -.
DR OrthoDB; 768315at2759; -.
DR PhylomeDB; Q9JKQ4; -.
DR TreeFam; TF319371; -.
DR BioGRID-ORCS; 54352; 6 hits in 74 CRISPR screens.
DR PRO; PR:Q9JKQ4; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9JKQ4; protein.
DR Bgee; ENSMUSG00000031737; Expressed in epithelium of cochlear duct and 196 other tissues.
DR ExpressionAtlas; Q9JKQ4; baseline and differential.
DR Genevisible; Q9JKQ4; MM.
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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0048468; P:cell development; IMP:MGI.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISO:MGI.
DR GO; GO:0008406; P:gonad development; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0042551; P:neuron maturation; IGI:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0002027; P:regulation of heart rate; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IGI:MGI.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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 DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome;
KW Sensory transduction; Transcription; Vision.
FT CHAIN 1..484
FT /note="Iroquois-class homeodomain protein IRX-5"
FT /id="PRO_0000049161"
FT DNA_BIND 112..174
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 176..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..216
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..267
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..331
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78411"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78411"
SQ SEQUENCE 484 AA; 50755 MW; 4C9AB3ED9992EDC9 CRC64;
MSYPQGYLYQ PSASLALYSC PAYSTSVISG PRTDELGRSS SGSAFSPYAG STAFTAPSPG
YNSHLQYGAD PAAAAAAAFS YVGSPYDHTP GMAGSLGYHP YAAPLGSYPY GDPAYRKNAT
RDATATLKAW LNEHRKNPYP TKGEKIMLAI ITKMTLTQVS TWFANARRRL KKENKMTWTP
RNRSEDEEEE ENIDLEKNDE DEPQKPEDKG DLEGPESGGA EQKATAGCER LQGPLSPAGK
ETEGSLSDSD FKESSSEGRH DELPRPPRAG ESSPAGPATA RLAEDAGPHY PASVPAPGPH
PSAGELPPGS GGSSVIHSPP PPPPPPPAVL AKPKLWSLAE IATSSDKVKD GGGGSEGSPC
PPCPGPMGGQ TLGGSRASPA PAPARSPSAQ CPFPGGTVLS RPLYYTAPFY PGYTNYGSFG
HLHGHPGPGP SPTAGPGSHF NGLNQTVLNR ADVLAKDPKM LRSQSQLDLC KDSPYELKKG
MSDI
