MIPOL1

Key takeaways

MIPOL1 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect MIPOL1 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of MIPOL1 from memory before moving on to harder problems.

Reference excerpt

MIPOL1 (Mirror Image Polydactyly 1), also known as CCDC193 (Coiled-coil domain containing 193), is a protein that in humans is encoded by the MIPOL1 gene. Mutation of this gene is associated with mirror-image polydactyly (also known as Laurin-Sandrow syndrome.) in humans, which is a rare genetic condition characterized by mirror-image duplication of digits.

Gene MIPOL1 is also known as CCDC193 (Coiled-coil domain containing 193).

Locus The MIPOL1 gene is located at 14q13.3-q21.1 on the plus strand, spanning base pairs 37,197,888 to 37,579,207 (in the human GRCh38 primary assembly, length: 381,320 base pairs), consisting of 15 exons and 11 introns. Some notable genes in its neighborhood include SLC25A21 (mutation of this gene causes synpolydactyly) and FOXA1.

mRNA MIPOL1 has at least 15 known splice isoforms produced by alternative splicing.

Protein

Properties The unmodified MIPOL1 protein isoform 1 in humans has an isoelectric point of 5.6 and molecular weight 51.5 kDa. Relative to other human proteins, MIPOL1 consists of unusually low amounts of Proline and Glycine and higher amounts of Glutamic acid and Glutamine.

Isoforms There are at least three known isoforms of this protein in humans produced by alternative splicing: isoform 1, of length 442 amino acids, isoform 2 of length 261 amino acids and isoform 3 of length 169 amino acids.

Domains and motifs MIPOL1 contains two coiled-coil domains in its C-terminus at positions 107 – 212 and 253 – 435 (shown in Fig.1). A bipartite nuclear localization signal is predicted at position 128 – 143.

Post-translational modifications The following post-translational modifications are predicted using bioinformatics tools for MIPOL1. Multiple phosphorylation sites are predicted for this protein, that are conserved in close orthologs, including a Casein kinase 1 (CK1) site, three Casein kinase 2 (CK2) sites, and three NEK2 sites.

Structure The exact structure of the MIPOL1 has not yet been characterized. Homology-based and de novo predictions of its tertiary structure suggest that it may consist of inter-twined alpha helices, forming coiled-coil domains (see Fig.4.).

Sub-cellular localization Immunofluorescence imaging in the human U2OS cell line (bone Osteosarcoma epithelial cells) shows localization in the cytosol. Immunohistochemistry imaging of human prostate tissue also suggests cytosolic localization. A bipartite nuclear localization signal is predicted at position 128 – 143, which is highly conserved in mammalian orthologs (see Fig.2.), indicating possible localization in the nucleus.

Gene regulation The predicted promoter sequence for this gene spans from base pair 37196852 to 37198126 (1,275 bp) and has multiple predicted binding sites for transcription factors such as GATA binding factors, SMAD3, TP63 and NRF1.

Gene Expression MIPOL1 is ubiquitously expressed at low levels in humans, with highest expression in the prostate.

Transcript regulation The RNA secondary structure is stabilized by multiple stem loops that have been predicted (using bioinformatics tools), and conserved across closely related species. Multiple binding targets are found for microRNAs such as MIR3163 and MIR190a, that could silence these regions on the mRNA and inhibit translation.

Clinical significance The MIPOL1 gene is an autosomal dominant gene. It is one of six genes in humans causing non-syndromic polydactyly (i.e. polydactyly occurring as a separate event with no other associated anomalies). Mutation of this gene is associated with mirror-image polydactyly (also known as Laurin-Sandrow syndrome) in humans, which is a rare genetic condition characterized by mirror-image duplication of digits in hands and feet. This gene has also been associated with central nervous system development, and the loss of this gene can cause craniofacial defects and agenesis of the corpus callosum. The gene is shown to function as a tumor suppressor in nasopharyngeal carcinoma (NPC), through the up-regulation of the p21 (WAF1/CIP1) and p27 (proteins that are both cyclin-dependent kinases that are linked with tumor suppression via cell cycle arrest) pathways. Another study investigating the role of MIPOL1 gene in cancer progression reported that MIPOL1 was downregulated in NPC tumor tissues, and that artificially re-expressing the gene caused tumor suppression by down-regulating angiogenic factors and reducing the phosphorylation of metastasis associated proteins like AKT, p65 and FAK14. MIPOL1 interacts with another well-known tumor-suppressing gene, RhoB and this interaction was confirmed to enhance RhoB activity. In a study of pediatric high grade glioma (pHGG), MIPOL1 gene was found to be down-regulated 2.4-fold in the high vascularity tumors The protein is known to interact with Replicase polyprotein 1ab in SARS-CoV2, which is a protein involved in the transcription and replication of viral RNAs.

Interacting proteins This protein is known to interact with multiple human proteins, verified via two-hybrid screening. A few notable examples include: LATS2: Negatively regulates YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting cell proliferation and promoting apoptosis. ZGPAT (Zinc finger CCCH-type with G patch domain-containing protein): A transcription repressor that negatively regulates expression of EGFR, a gene involved in cell proliferation, survival and migration, suggesting that it may act as a tumor suppressor. RCOR3 (REST Corepressor 3): A protein that may act as a component of a co-repressor complex that represses transcription It also interacts with viral proteins such as: Replicase polyprotein 1ab (SARS-CoV2): A multifunctional protein involved in the transcription and replication of viral RNAs. Protein E7 (Human Papillomavirus): Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle.

Origin and evolution The earliest known ortholog of this protein appeared around 948 million years ago in Trichoplax adhaerens in phylum Placozoa in kingdom Animalia. The next most distant orthologs appear in phylum Cnidaria, around 824 million years ago.

… excerpt ends here. Continue reading the full article.

Illustrations

MIPOL1: Chromosome 14 diagram with MIPOL1 gene locus marked in red[9] — Chromosome 14 diagram with MIPOL1 gene locus marked in red[9]

Worked examples

Example 1 — a first encounter with MIPOL1

Start with the simplest possible case. Write down what MIPOL1 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 MIPOL1 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 MIPOL1 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 MIPOL1

In research: MIPOL1 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 MIPOL1 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: MIPOL1 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 14, Proteins, so understanding it makes those chapters shorter.
In everyday life: Look for MIPOL1 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 MIPOL1 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what MIPOL1 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 MIPOL1 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is MIPOL1 in simple terms?

MIPOL1 (Mirror Image Polydactyly 1), also known as CCDC193 (Coiled-coil domain containing 193), is a protein that in humans is encoded by the MIPOL1 gene. Mutation of this gene is associated with mirror-image polydactyly (also known as Laurin-Sandrow syndrome.) in humans, which is a rare genetic co…

Why does MIPOL1 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 MIPOL1?

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 MIPOL1.