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Protein

Iroquois-class homeodomain protein IRX-3

Gene

Irx3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor. Involved in SHH-dependent neural patterning. Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals. Involved in the transcriptional repression of MNX1 in non-motor neuron cells.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi130 – 19263Homeobox; TALE-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. sequence-specific DNA binding Source: InterPro

GO - Biological processi

  1. kidney development Source: MGI
  2. mesoderm development Source: MGI
  3. metanephros development Source: UniProtKB
  4. negative regulation of neuron differentiation Source: MGI
  5. positive regulation of neuron differentiation Source: MGI
  6. proximal/distal pattern formation involved in nephron development Source: UniProtKB
  7. regulation of transcription, DNA-templated Source: UniProtKB-KW
  8. specification of loop of Henle identity Source: UniProtKB
  9. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Iroquois-class homeodomain protein IRX-3
Alternative name(s):
Homeodomain protein IRXB1
Iroquois homeobox protein 3
Gene namesi
Name:Irx3
Synonyms:Irxb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:1197522. Irx3.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. axon Source: MGI
  2. cytoplasm Source: MGI
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 507507Iroquois-class homeodomain protein IRX-3PRO_0000049156Add
BLAST

Proteomic databases

PRIDEiP81067.

PTM databases

PhosphoSiteiP81067.

Expressioni

Tissue specificityi

Expressed by neural progenitor cells in discrete domains of the ventral neural tube. Also expressed in specific and overlapping patterns with Irx1 and Irx2 in the developing and adult metanephric kidney. In the adult metanephros, renal expression is confined to the S3 segment of the proximal tubule, in the loop of Henle.2 Publications

Developmental stagei

The earliest expressed of the Irx family, with expression seen in trophectoderm-derived extraembryonic tissues from E6.5, including expression in the chorionic ectoderm at E8.0. Embryonic expression starts at the end of gastrulation (E7.5) in the ectodermal layer which gives rise to the nervous system. At E8.0, expression is confined to the thickening neural ectoderm corresponding to the future mesencephalon (midbrain) and rhombencephalon (hindbrain) and from E8.5 onwards, expression also includes the rostral part of the closing neural tube. After neural tube closure at E9.5, expression predominates in the CNS in the midbrain, hindbrain and spinal cord. Also expressed in a number of tissues outside of the CNS including ectodermal layer of the branchial arches. Expressed in the prospective limb buds of the lateral plate mesoderm, and from E10.5 onwards a gradient exists along the dorsoventral and proximodistal axes of developing limbs. Expressed in the notochord at stage E9.0. At E9.5 found in the cephalic mesoderm surrounding the optic vesicle. Around E10.5, expression in the head mesoderm extends into the nasal pits. By E12.5, still expressed in the mesenchyme, and expressions begins in specific subsets of post-mitotic cells in the neuroretina. As development ensues, expression increases in the neuroretina and mesenchymal expression gradually decreases. At E16.5, expressed exclusively in the inner neuroblast layers of the neuroretina. In the developing heart, first expressed in the trabecules of embryonic ventricles at E9.5, and from then onwards localizes specifically to the trabeculated myocardium of the ventricles.4 Publications

Gene expression databases

BgeeiP81067.
CleanExiMM_IRX3.
GenevestigatoriP81067.

Structurei

3D structure databases

ProteinModelPortaliP81067.
SMRiP81067. Positions 139-188.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi24 – 296Poly-Gly
Compositional biasi64 – 7310Poly-Ala
Compositional biasi204 – 26057Glu-richAdd
BLAST
Compositional biasi315 – 429115Pro-richAdd
BLAST
Compositional biasi379 – 46183Ala-richAdd
BLAST

Sequence similaritiesi

Belongs to the TALE/IRO homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG315186.
GeneTreeiENSGT00750000117365.
HOGENOMiHOG000234546.
HOVERGENiHBG006180.
InParanoidiP81067.
OMAiGPISDSK.
OrthoDBiEOG7RV9HC.
PhylomeDBiP81067.
TreeFamiTF319371.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR003893. Iroquois_homeo.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00548. IRO. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P81067-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSFPQLGYQY IRPLYPPERP GAAGGGGGGS SAGGRSGPGA GASELAASGS
60 70 80 90 100
LSNVLSSVYG APYAAAAAAA AAAQGYGAFL PYATELPIFP QLGAQYELKD
110 120 130 140 150
SPGVQHPATA AAFPHPHPAF YPYGQYQFGD PSRPKNATRE STSTLKAWLN
160 170 180 190 200
EHRKNPYPTK GEKIMLAIIT KMTLTQVSTW FANARRRLKK ENKMTWAPRS
210 220 230 240 250
RTDEEGNAYG SEREEEDEEE DEEESKRELE MEEEELAGEE EDTGGEGLAD
260 270 280 290 300
DDEDEEIDLE NLDSAAAGSE LTLAGAAHRN GDFGLGPISD CKTSDSDDSS
310 320 330 340 350
EGLEDRPLSV LSLAPPPPPV ARAPASPPSP PSSLDPCAPA PAPSSALQKP
360 370 380 390 400
KIWSLAETAT SPDNPRRSPP GAGGSPPGAA VAPPTLQLSP AAAAAAAAAH
410 420 430 440 450
RLVSAPLGKF PAWTNRPFPG PPAGPRPHPL SMLGSAPQHL LGLPGAAGHP
460 470 480 490 500
AAAAAAYARP AEPESGTDRC SALEVEKKLL KTAFQPVPRR PQNHLDAALV

LSALSSS
Length:507
Mass (Da):52,693
Last modified:November 3, 2009 - v2
Checksum:i04FD67E8F5C29AB6
GO
Isoform 2 (identifier: P81067-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     468-507: DRCSALEVEK...ALVLSALSSS → GDKKNIAVVP...NFSTIFKSLY

Note: No experimental confirmation available.

Show »
Length:522
Mass (Da):54,893
Checksum:i65929DB6FC66C07E
GO

Sequence cautioni

The sequence CAA75233.1 differs from that shown. Reason: Frameshift at positions 239 and 254. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti494 – 4941H → R in CAA75233. (PubMed:9486539)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei468 – 50740DRCSA…ALSSS → GDKKNIAVVPWKWRKSYSRQ LSSRCQGGHRTIWTLLWSYQ LSPRLNFSTIFKSLY in isoform 2. 1 PublicationVSP_038351Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y15001 mRNA. Translation: CAA75233.1. Frameshift.
AK143023 mRNA. Translation: BAE25251.1.
CH466525 Genomic DNA. Translation: EDL11081.1.
BC085500 mRNA. Translation: AAH85500.1.
CCDSiCCDS57630.1. [P81067-2]
CCDS57631.1. [P81067-1]
RefSeqiNP_001240751.1. NM_001253822.1. [P81067-2]
NP_032419.2. NM_008393.3. [P81067-1]
UniGeneiMm.238044.

Genome annotation databases

EnsembliENSMUST00000093312; ENSMUSP00000091002; ENSMUSG00000031734. [P81067-2]
ENSMUST00000175795; ENSMUSP00000135488; ENSMUSG00000031734. [P81067-1]
GeneIDi16373.
KEGGimmu:16373.
UCSCiuc009msu.2. mouse. [P81067-1]
uc009msv.2. mouse. [P81067-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y15001 mRNA. Translation: CAA75233.1. Frameshift.
AK143023 mRNA. Translation: BAE25251.1.
CH466525 Genomic DNA. Translation: EDL11081.1.
BC085500 mRNA. Translation: AAH85500.1.
CCDSiCCDS57630.1. [P81067-2]
CCDS57631.1. [P81067-1]
RefSeqiNP_001240751.1. NM_001253822.1. [P81067-2]
NP_032419.2. NM_008393.3. [P81067-1]
UniGeneiMm.238044.

3D structure databases

ProteinModelPortaliP81067.
SMRiP81067. Positions 139-188.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiP81067.

Proteomic databases

PRIDEiP81067.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000093312; ENSMUSP00000091002; ENSMUSG00000031734. [P81067-2]
ENSMUST00000175795; ENSMUSP00000135488; ENSMUSG00000031734. [P81067-1]
GeneIDi16373.
KEGGimmu:16373.
UCSCiuc009msu.2. mouse. [P81067-1]
uc009msv.2. mouse. [P81067-2]

Organism-specific databases

CTDi79191.
MGIiMGI:1197522. Irx3.

Phylogenomic databases

eggNOGiNOG315186.
GeneTreeiENSGT00750000117365.
HOGENOMiHOG000234546.
HOVERGENiHBG006180.
InParanoidiP81067.
OMAiGPISDSK.
OrthoDBiEOG7RV9HC.
PhylomeDBiP81067.
TreeFamiTF319371.

Miscellaneous databases

NextBioi289504.
PROiP81067.
SOURCEiSearch...

Gene expression databases

BgeeiP81067.
CleanExiMM_IRX3.
GenevestigatoriP81067.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR003893. Iroquois_homeo.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00548. IRO. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of the vertebrate Iroquois homeobox gene family with overlapping expression during early development of the nervous system."
    Bosse A., Zulch A., Becker M.B., Torres M., Gomez-Skarmeta J.-L., Modolell J., Gruss P.
    Mech. Dev. 69:169-181(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE.
  2. "Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart."
    Christoffels V.M., Keijser A.G.M., Houweling A.C., Clout D.E.W., Moorman A.F.M.
    Dev. Biol. 224:263-274(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE.
    Strain: FVB/N.
    Tissue: Embryonic heart.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Lung.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6.
    Tissue: Eye.
  6. "Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification."
    Bellefroid E.J., Kobbe A., Gruss P., Pieler T., Gurdon J.B., Papalopulu N.
    EMBO J. 17:191-203(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  7. "A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube."
    Briscoe J., Pierani A., Jessell T.M., Ericson J.
    Cell 101:435-445(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  8. "Expression of two novel mouse Iroquois-class homeobox genes during neurogenesis."
    Cohen D.R., Cheng C.W., Cheng S.H., Hui C.-C.
    Mech. Dev. 91:317-321(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  9. "Analysis of embryonic motoneuron gene regulation: derepression of general activators function in concert with enhancer factors."
    Lee S.K., Jurata L.W., Funahashi J., Ruiz E.C., Pfaff S.L.
    Development 131:3295-3306(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR.
  10. "The prepattern transcription factor Irx3 directs nephron segment identity."
    Reggiani L., Raciti D., Airik R., Kispert A., Braendli A.W.
    Genes Dev. 21:2358-2370(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiIRX3_MOUSE
AccessioniPrimary (citable) accession number: P81067
Secondary accession number(s): Q3UPZ3, Q5U3K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 3, 2009
Last modified: February 4, 2015
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.