IRX1

Key takeaways

IRX1 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect IRX1 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of IRX1 from memory before moving on to harder problems.

Reference excerpt

Iroquois-class homeodomain protein IRX-1, also known as Iroquois homeobox protein 1, is a protein that in humans is encoded by the IRX1 gene. All members of the Iroquois (IRO) family of proteins share two highly conserved features, encoding both a homeodomain and a characteristic IRO sequence motif. Members of this family are known to play numerous roles in early embryo patterning. IRX1 has also been shown to act as a tumor suppressor gene in several forms of cancer.

Role in development IRX1 is a member of the Iroquois homeobox gene family. Members of this family play multiple roles during pattern formation in embryos of numerous vertebrate and invertebrate species. IRO genes are thought to function early in development to define large territories, and again later in development for further patterning specification. Experimental data suggest roles for IRX1 in vertebrates may include development and patterning of lungs, limbs, heart, eyes, and nervous system.

Gene

Overview IRX1 is located on the forward DNA strand (see Sense (molecular biology)) of chromosome 5, from position 3596054 - 3601403 at the 5p15.3 location. The human gene product is an 1858 base pair mRNA with 4 predicted exons in humans. Promoter analysis was performed using El Dorado through the Genomatix software page. The predicted promoter region spans 1040 base pairs from position 3595468 through 3595468 on the forward strand of chromosome 5.

Gene neighborhood IRX1 is relatively isolated, with no other protein coding genes found from position 3177835 – 5070004.

Expression Microarray and RNA 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. Moderate to high levels are also indicated in the lung, prostate and stomach. Promoter analysis with the El Dorado program from Genomatix predicted that IRX1 expression is regulated by factors that include E2F cell cycle regulators, NRF1, and ZF5, and brachyury. Expression data from human, mouse, and developing mouse brains are available though the Allen Brain Atlas.

Protein

Properties and characteristics The mature IRX1 protein has 480 amino acid residues, with a molecular mass of 49,600 daltons and an isoelectric point of 5.7. A BLAST search revealed that IRX1 contains two highly conserved domains: a homeodomain and a characteristic IRO motif of unknown function. 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 three alpha helices that comprise the domain. The presence of this well characterized homeodomain strongly suggests that IRX1 acts as a transcription factor. This is further supported by the predicted localization of IRX1 to the nucleus. 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 the Notch receptor protein suggests that it may be involved with protein-protein interaction. In addition to these two characteristic domains, IRX1 contains a third domain from the HARE-HTH superfamily fused to the C-terminal end of the homeodomain. This domain adopts a winged helix-turn-helix fold predicted to bind DNA, and is thought to play a role in recruiting effector activities to DNA. Several forms of post-translational modification are predicted, including SUMOylation, C-mannosylation, and phosphorylation, using bioinformatics tools from ExPASy. Bioinformatic analysis of IRX1 with the NetPhos tool predicted 71 potential phosphorylation sites throughout the protein.

Protein Interactions Potential protein interacting partners for IRX1 were found using computational tools. The STRING database lists nine putative interacting partners supported by text mining evidence, though closer analysis of the results shows little support for most of these predicted interactions. However, it is possible that one of these proteins, CDKN1A, is involved in the predicted regulation of IRX1 by E2F cell cycle regulators.

Conservation

Orthologs 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. Homologous sequences were found in species as distantly related to humans as the pig roundworm Ascaris suum, from the family Ascarididae, using BLAST and the ALIGN tool through the San Diego Super Computer Biology Workbench. The following is a table describing the evolutionary conservation of IRX1.

Paralogs IRX1 is one of six members of the Iroquois-class homeodomain proteins found in humans: IRX2, IRX3, IRX4, IRX5, and IRX6. IRX1, IRX2, and IRX4 are found on human chromosome 5, and their orientation corresponds to that of IRX3, IRX5, and IRX6 found on human chromosome 16. It is thought that the genomic organization of IRO genes in conserved gene clusters allows for coregulation and enhancer sharing during development.

References

Illustrations

Worked examples

Example 1 — a first encounter with IRX1

Start with the simplest possible case. Write down what IRX1 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to IRX1 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about IRX1 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of IRX1

In research: IRX1 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses IRX1 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: IRX1 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 5, Transcription factors, so understanding it makes those chapters shorter.
In everyday life: Look for IRX1 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study IRX1 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what IRX1 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain IRX1 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is IRX1 in simple terms?

Iroquois-class homeodomain protein IRX-1, also known as Iroquois homeobox protein 1, is a protein that in humans is encoded by the IRX1 gene. All members of the Iroquois (IRO) family of proteins share two highly conserved features, encoding both a homeodomain and a characteristic IRO sequence motif.

Why does IRX1 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study IRX1?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on IRX1.