TMED5

Key takeaways

TMED5 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect TMED5 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of TMED5 from memory before moving on to harder problems.

Reference excerpt

Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene.

Gene

General properties TMED5 (transmembrane emp24 domain-containing protein 5) is also known as p28, p24g2, and CGI-100. The human gene spans 30,775 base pairs over 4 exons and 3 introns for transcript variant 1, 5 exons and 4 introns for transcript variant 2, and it is located on the minus strand of chromosome 1, at 1p22.1.

Expression TMED5 has ubiquitous expression with transcripts detected in 246 tissues. Androgen deprivation led to lower expression in mice splenocytes compared to the control. Human dendritic cells infected with Chlamydia pneumoniae showed an absence of TMED5 expression compared to uninfected dendritic cells which had moderate expression.

mRNA transcript TMED5 has two coding transcript variants and one non-coding transcript variant produced by alternative splicing. Isoform 1 has 4 exons and encodes a protein 229 amino acids. Isoform 2 has 5 exons and encodes a protein with a shorter C-terminus 193 amino acids due to an additional exon causing a frameshift.

Protein

General properties TMED5 contains a signal peptide. After cleavage of the signal peptide, TMED5 isoform 1 is composed of 202 amino acids and has a molecular weight of ~23 kDa. The mature form of isoform 2 is composed of 166 amino acids and has a molecular weight of ~19 kDa. Both isoforms have an isolectric point of approximately 4.6.

Composition Compared to the reference set of human proteins, TMED5 has fewer alanine and proline residues but more aspartic acid and phenylalanine residues. TMED5 isoform 1 has one hydrophobic segment that corresponds with its transmembrane region.

Domains and motifs

TMED5 isoform 1 is a single-pass transmembrane protein and is composed of a lumenal domain, one transmembrane (helical) domain, and a cytoplasmic domain. TMED5 is part of the emp24/gp25L/p24 family/GOLD family protein. TMED5 contains a di-lysine motif and predicted NLS in its cytoplasmic tail.

Structure The structure of TMED5 isoform 1 consists of beta strands making up the lumenal region, disparate coil-coiled regions, alpha helices making up the transmembrane domain, and alpha helices making up some of the cytoplasmic domain.

Post-translational modifications TMED5 has two predicted phosphorylation sites in the cytosolic region, Ser227 and Thr229.

Localization TMED5's predicted location is in the plasma membrane, with an extracellular N-terminus and intracellular C-terminus. TMED5's localization is predicted to be cytoplasmic, but has been found in some tissues to be located in the nucleus.

Interacting proteins The following table provides a list of proteins most likely to interact with TMED5. Not shown in the table are Wnt family proteins which are known to interact with the p24 protein family.

Function and clinical significance TMED5 is a part of the p24 protein family whose general functions are protein trafficking for the secretory pathway. TMED5 is thought to be necessary in the formation of the Golgi into a ribbon. Glycosylphosphatidylinositol-anchored proteins (GPI-AP) depend on p24 cargo receptors for transport from the ER to the Golgi. Knockdown of p24γ2 (a mouse ortholog of TMED5) in mice resulted in impaired transport of GPI-AP. The study concluded that the α-helical region of p24γ2 binds GPI which is necessary to incorporate it into COPII transport vesicles. TMED5 is reported to be necessary for the secretion of Wnt ligands. TMED5 has been found to interact with WNT7B, activating the canonical WNT-CTNNB1/β-catenin signaling pathway. This pathway is linked to numerous cancers because upregulation of the Wnt/β-catenin signaling pathway leads to cytosolic accumulation of β-catenin, promoting cellular proliferation. Research has identified bladder cancer to have a common chromosomal amplification at 1p21-22 and showed significant upregulation of TMED5.

Evolution

Homology

Paralogs TMED5 paralogs include TMED1, TMED2, TMED3, TMED4, TMED6, TMED7, TMED8, TMED9, and TMED10. All paralogs share the conserved transmembrane domain and contain the characteristic GOLD domain as included in the emp24/gp25L/p24 family/GOLD family proteins.

Orthologs TMED5 is found to be conserved in vertebrates, invertebrates, plants and fungi, and there are 243 known organisms that have orthologs with the gene. The following table provides a sample of the ortholog space of TMED5.

References

Illustrations

Worked examples

Example 1 — a first encounter with TMED5

Start with the simplest possible case. Write down what TMED5 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 TMED5 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 TMED5 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 TMED5

In research: TMED5 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 TMED5 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: TMED5 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 1, Proteins, so understanding it makes those chapters shorter.
In everyday life: Look for TMED5 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 TMED5 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what TMED5 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 TMED5 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is TMED5 in simple terms?

Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene. Gene General properties TMED5 (transmembrane emp24 domain-containing protein 5) is also known as p28, p24g2, and CGI-100.

Why does TMED5 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 TMED5?

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 TMED5.