| IRX1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | IRX1, IRX-5, IRXA1, iroquois homeobox 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM:606197;MGI:1197515;HomoloGene:19065;GeneCards:IRX1;OMA:IRX1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Iroquois-class homeodomain protein IRX-1, also known asIroquois homeobox protein 1, is aprotein that in humans is encoded by theIRX1gene.[5][6] All members of the Iroquois (IRO) family of proteins share two highly conserved features, encoding both ahomeodomain and a characteristic IROsequence motif.[7] Members of this family are known to play numerous roles in early embryo patterning.[5]IRX1 has also been shown to act as atumor suppressor gene in several forms ofcancer.[8][9][10][11]
IRX1 is a member of theIroquois homeobox gene family. Members of this family play multiple roles during pattern formation in embryos of numerous vertebrate and invertebrate species.[5][12] IRO genes are thought to function early in development to define large territories, and again later in development for further patterning specification.[7] Experimental data suggest roles for IRX1 in vertebrates may include development and patterning of lungs, limbs, heart, eyes, and nervous system.[13][14][15][16][17][18]
IRX1 is located on the forward DNA strand (seeSense (molecular biology)) ofchromosome 5, from position 3596054 - 3601403 at the 5p15.3 location.[5] The human gene product is a 1858base pair mRNA with 4 predictedexons in humans.[19] Promoter analysis was performed usingEl Dorado through the Genomatix software page.[20] The predicted promoter region spans 1040 base pairs from position 3595468 through 3595468 on the forward strand of chromosome 5.
IRX1 is relatively isolated, with no other protein coding genes found from position 3177835 – 5070004.[5]
Microarray andRNA seq data suggest that IRX1 is ubiquitously expressed at low levels in adult tissues, with the highest relative levels of expression occurring in the heart, adipose, kidney, and breast tissues.[21][22] Moderate to high levels are also indicated in the lung, prostate and stomach.[22][23] Promoter analysis with theEl Dorado program from Genomatix predicted that IRX1 expression is regulated by factors that includeE2Fcell cycle regulators,NRF1, and ZF5,[24] andbrachyury.[20] Expression data from human, mouse, and developing mouse brains are available though theAllen Brain Atlas.[25]
The mature IRX1 protein has 480amino acid residues, with amolecular mass of 49,600daltons and anisoelectric point of 5.7. ABLAST search revealed that IRX1 contains two highly conserved domains: a homeodomain and a characteristic IRO motif of unknown function.[26] The homeodomain belongs to the TALE (three amino acid loop extension) class of homeodomains, and is characterized by the addition of three extra amino acids between the first and second helix of threealpha helices that comprise the domain.[27] The presence of this well characterized homeodomain strongly suggests that IRX1 acts as atranscription factor. This is further supported by the predicted localization of IRX1 to thenucleus.[28] The IRO motif is a region downstream of the homeodomain that is found only in members of the Iroquois-class homeodomain proteins, though its function is poorly understood. However, its similarity to an internal region of theNotch receptor protein suggests that it may be involved with protein-protein interaction.[7] In addition to these two characteristic domains, IRX1 contains a third domain from the HARE-HTH superfamily[29] fused to theC-terminal end of the homeodomain.[30] This domain adopts a wingedhelix-turn-helix fold predicted to bind DNA, and is thought to play a role in recruiting effector activities to DNA.[29] Several forms ofpost-translational modification are predicted, includingSUMOylation,C-mannosylation, andphosphorylation, usingbioinformatics tools fromExPASy.[31] Bioinformatic analysis of IRX1 with theNetPhos tool predicted 71 potential phosphorylation sites throughout the protein.[32]
Potential protein interacting partners for IRX1 were found using computational tools. TheSTRING database lists nine putative interacting partners supported bytext mining evidence, though closer analysis of the results shows little support for most of these predicted interactions.[33] However, it is possible that one of these proteins,CDKN1A, is involved in the predicted regulation of IRX1 by E2F cell cycle regulators.[20][33]
IRX1 has a high degree of conservation across vertebrate and invertebrate species. The entire protein is more fully conserved through vertebrate species, while only the homeodomain and IRO motif are conserved in more distant homologs.[12]Homologous sequences were found in species as distantly related tohumans as the pig roundwormAscaris suum, from the familyAscarididae, using BLAST and the ALIGN tool through the San Diego Super Computer Biology Workbench.[26] The following is a table describing the evolutionary conservation of IRX1.
| GenusSpecies | Organism Common Name | Divergence from Humans (MYA)[34] | NCBI Protein Accession Number | Sequence identity[26] | Protein Length | Common Gene Name |
|---|---|---|---|---|---|---|
| Homo sapiens[30] | Humans | -- | NP_077313 | 100% | 480 | IRX-1 |
| Pongo abelii[35] | Sumatran Orangutan | 15.7 | XP_002815448 | 99% | 480 | IRX-1 |
| Bos taurus[36] | Cattle | 94.2 | XP_002696496 | 92.3% | 476 | IRX-1 |
| Mus musculus[37] | House Mouse | 92.3 | NP_034703 | 91.5% | 480 | IRX-1 |
| Rattus norvegicus[38] | Brown rat | 92.3 | NP_001100801 | 90.4% | 480 | IRX-1 |
| Gallus gallus[39] | Red Junglefowl | 296 | NP_001025509 | 72.9% | 467 | IRX-1 |
| Xenopus tropicalis[40] | Western clawed frog | 371.2 | NP_001188351 | 68% | 467 | IRX-1 |
| Latimeria chalumnae[41] | West Indian Ocean coelacanth | 441.9 | XP_006002089 | 65.1% | 460 | Irx-1-A-like isoform X1 |
| Danio rerio[42] | Zebrafish | 400.1 | NP_997067 | 61.1% | 426 | Irx-1 isoform 1 |
| Taeniopygia guttata[43] | Zebra finch | 296 | XP_002189063 | 59.7% | 400 | Irx-1-A-like |
| Astyanax mexicanus[44] | Mexican tetra | 400.1 | XP_007254591.1 | 58% | 450 | IRX-1 |
| Ophiophagus hannah[45] | King cobra | 296 | ETE68928 | 54.5% | 387 | Irx-1-A partial |
| Ovis aries[46] | Sheep | 94.2 | XP_004017207 | 43.3% | 260 | IRX-1 |
| Condylura cristata[47] | Star-nosed mole | 94.2 | XP_004678440 | 41.7% | 342 | IRX-1 |
| Branchiostoma floridae[48] | Lancelet | 713.2 | ACF10237.1 | 35.5% | 461 | Iroquois A isoform 1 |
| Strongylocentrotus purpuratus[49] | Purple sea urchin | 742.9 | NP_001123285 | 31.7% | 605 | Iroquois homeobox A |
| Ascaris suum[50] | Pig roundworm | 937.5 | F1KXE6 | 29% | 444 | IRX-1 |
| Caenorhabditis elegans[51] | Nematode roundworm | 937.5 | NP_492533.2 | 28.6% | 377 | IRX-1 |
| Drosophila melanogaster[52] | Fruit fly | 782.7 | NP_524045 | 27% | 717 | Araucan isoform A |
IRX1 is one of six members of the Iroquois-class homeodomain proteins found in humans:IRX2,IRX3,IRX4,IRX5, andIRX6.IRX1,IRX2, andIRX4 are found on human chromosome 5, and their orientation corresponds to that ofIRX3,IRX5, andIRX6 found on humanchromosome 16.[7] It is thought that the genomic organization of IRO genes in conservedgene clusters allows for coregulation andenhancer sharing during development.
This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.
