INAVA

Key takeaways

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

Reference excerpt

INAVA, sometimes referred to as hypothetical protein LOC55765, is a protein of unknown function that in humans is encoded by the INAVA gene. Less common gene aliases include FLJ10901 and MGC125608.

Gene

Location

In humans, INAVA is located on the long arm of chromosome 1 at locus 1q32.1. It spans from 200,891,499 to 200,915,736 (24.238 kb) on the plus strand.

Gene neighborhood

INAVA is flanked by G protein-coupled receptor 25 (upstream) and maestro heat-like repeat family member 3 (MROH3P), a predicted downstream pseudogene. Ribosomal protein L34 pseudogene 6 (RPL34P6) is further upstream and kinesin family member 21B is further downstream.

Promoter

There are seven predicted promoters for INAVA, and experimental evidence suggests that isoform 1 and 2, the most common isoforms, are transcribed using different promoters. MatInspector, a tool available through Genomatix, was used to predict transcription factor binding sites within potential promoter regions. The transcription factors that are predicted to target the anticipated promoter for isoform 1 are expressed in a range of tissues. The most common tissues of expression are the urogenital system, nervous system and bone marrow. This coincides with expression data for the INAVA protein, which is highly expressed in the kidney and bone marrow. A diagram of the predicted promoter region, with highlighted transcription factor binding sites, is shown to the right. The factors that are predicted to bind to the promoter region of isoform 2 differ, and twelve of the top twenty predicted factors are expressed in blood cells and/or tissues of the cardiovascular system.

Expression C1orf106 is expressed in a wide range of tissues. Expression data from GEO profiles is shown below. The sites of highest expression, are listed in the table. Expression is moderate in the placenta, prostate, testis, lung, salivary glands and dendritic cells. It is low in the brain, most immune cells, the adrenal gland, uterus, heart and adipocytes. Expression data, from various experiments, found on GEO profiles suggests that INAVA expression is up-regulated in several cancers including: lung, ovarian, colorectal and breast.

mRNA

Isoforms Nine putative isoforms are produced from the INAVA gene, seven of which are predicted to encode proteins. Isoform 1 and 2, shown below, are the most common isoforms.

Isoform 1, which is the longest, is accepted as the canonical isoform. It contains ten exons, which encode a protein that is 677 amino acids long, depending on the source. Some sources report that the protein is only 663 amino acids due to the use of a start codon that is forty-two nucleotides downstream. According to NCBI, this isoform has only been predicted computationally. This may be because the Kozak sequence surrounding the downstream start codon is more similar to the consensus Kozak sequence as shown in the table below. Softberry was used to obtain the sequence of the predicted isoform. Isoform 2 is shorter due to a truncated N-terminus. Both isoforms have an alternative polyadenylation site.

miRNA regulation

miRNA-24 was identified as a microRNA that could potentially target INAVA mRNA. The binding site, which is located in the 5' untranslated region is shown.

Protein

General properties Isoform 1, diagramed below, contains a DUF3338 domain, two low complexity regions and a proline rich region. The protein is arginine and proline rich, and has a lower than average amount of asparagine and hydrophobic amino acids, specifically phenylalanine and isoleucine. The isoelectric point is 9.58, and the molecular weight of the unmodified protein is 72.9 kdal. The protein is not predicted to have an N-terminal signal peptide, but there are predicted nuclear localization signals (NLS) and a leucine rich nuclear export signal.

Modifications INAVA is predicted to be highly phosphorylated. Phosphoylation sites predicted by PROSITE are shown in the table below. NETPhos predictions are illustrated in the diagram. Each line points to a predicted phosphorylation site, and connects to a letter which represents either serine (S), threonine (T) or tyrosine (Y).

Structure Coiled-coils are predicted to span from residue 130-160 and 200–260. The secondary composition was predicted to be about 60% random coils, 30% alpha helices and 10% beta sheets.

Interactions The proteins with which the INAVA protein interacts are not well characterized. Text mining evidence suggests INAVA may interact with the following proteins: DNAJC5G, SLC7A13, PIEZO2, MUC19. Experimental evidence, from a yeast two hybrid screen, suggests the INAVA protein interacts with 14-3-3 protein sigma, which is an adaptor protein.

Homology INAVA is well conserved in vertebrates as shown in the table below. Sequences were retrieved from BLAST and BLAT.

A graph of the sequence identity versus the time since divergence for the asterisked entries is shown below. The colors correspond to degree of relatedness (green = closely related, purple = distantly related).

Paralogs Proteins that are considered to be INAVA paralogs are not consistent between databases. A multiple sequence alignment (MSA) of potentially paralogous proteins was made to determine the likelihood of a truly paralogous relationship. The sequences were retrieved from a BLAST search in humans with the C1orf106 protein. The MSA suggests the proteins share a homologous domain, DUF3338, which is found in eukaryotes. A portion of the multiple sequence alignment is shown below. Apart from the DUF domain (boxed in green), there was little conservation. The DUF3338 domain does not have any extraordinary physical properties, however, one notable finding is that each of the proteins in the MSA is predicted to have two nuclear localization signals. The proteins in the MSA are all predicted to localize to the nucleus. A comparison of the physical properties of the proteins was also conducted using SAPS and is shown in the table.

Clinical significance A total of 556 single nucleotide polymorphisms (SNPs) have been identified in the gene region of INAVA, 96 of which are associated with a clinical source. Rivas et al. identified four SNPs, shown in the table below, that may be associated with inflammatory bowel disease and Crohn's disease. According to GeneCards, other disease associations may include multiple sclerosis and ulcerative colitis.

References

External links Human C1orf106 genome location and C1orf106 gene details page in the UCSC Genome Browser.

Illustrations

Worked examples

Example 1 — a first encounter with INAVA

Start with the simplest possible case. Write down what INAVA 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 INAVA 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 INAVA 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 INAVA

In research: INAVA 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 INAVA 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: INAVA is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 1, Uncharacterized proteins, so understanding it makes those chapters shorter.
In everyday life: Look for INAVA 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 INAVA in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what INAVA 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 INAVA out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is INAVA in simple terms?

INAVA, sometimes referred to as hypothetical protein LOC55765, is a protein of unknown function that in humans is encoded by the INAVA gene. Less common gene aliases include FLJ10901 and MGC125608.

Why does INAVA 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 INAVA?

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 INAVA.