Protein-coding gene / tubulin protein · BEGINNER LESSON
TUBA4A
TUBA4A is a human gene that encodes tubulin alpha-4A, an alpha-tubulin protein that helps build microtubules. It is a microtubule subunit with a distinctive C-terminal tail and has been linked to several neurodevelopmental and neurodegenerative disorders when mutated.
What TUBA4A is
TUBA4A is the gene for tubulin alpha-4A, a protein found in humans. Tubulin proteins are the basic building blocks of microtubules, which are long tube-like parts of the cell cytoskeleton; the cytoskeleton is the internal support framework of a cell. Alpha-tubulin and beta-tubulin join as a heterodimer, meaning a two-part complex made of different proteins, and these dimers assemble into microtubules. TUBA4A is one of the major tubulins used in this process.
[2] In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration - Scientific Reports [3] www.uniprot.org › uniprotkb › TBA4A_HUMANTUBA4A - Tubulin alpha-4A chain - Homo sapiens (Human ...
What is measured or distinguished
Researchers describe TUBA4A by its amino-acid sequence, especially its structured core and its C-terminal tail, the tail end of the protein. Compared with other alpha-tubulins, TUBA4A has a distinct tail that naturally lacks the usual terminal tyrosine and ends with glutamate, making it non-tyrosinated. Sources also report distinctive biochemical behavior, altered post-translational modification patterns, and enriched expression in tissues including the nervous system.
[1] TUBA4A: The Tale of an Unconventional Tubulin - PMC [3] www.uniprot.org › uniprotkb › TBA4A_HUMANTUBA4A - Tubulin alpha-4A chain - Homo sapiens (Human ...
How it works
Microtubules grow when GTP-bound tubulin dimers add to the end of the microtubule. GTP stands for guanosine triphosphate, a small molecule that helps power or regulate many cell processes. In the tubulin dimer, GTP binding is important for polymerization, which means joining many subunits into a larger structure. TUBA4A appears to stabilize microtubules in two ways: its core domain lowers the tendency of microtubules to fall apart, and its non-tyrosinated tail makes them less sensitive to depolymerases, proteins that promote breakdown. One source also notes that the tail’s shape can reduce the efficiency of tyrosine ligation by tubulin tyrosine ligase (TTL), the enzyme that normally adds tyrosine to tubulin tails.
[1] TUBA4A: The Tale of an Unconventional Tubulin - PMC [2] In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration - Scientific Reports [3] www.uniprot.org › uniprotkb › TBA4A_HUMANTUBA4A - Tubulin alpha-4A chain - Homo sapiens (Human ...
Why mutations matter
Mutations in TUBA4A have been linked to disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), ataxia, Parkinson’s disease, and other tubulinopathies, which are disorders caused by abnormal tubulin genes. Reported changes may alter TUBA4A structure, GTP binding, assembly into stable tubulin complexes, protein levels, or the balance between tyrosinated and detyrosinated microtubules. These disruptions can affect microtubule behavior and may interfere with axonal transport, the movement of materials along neuron extensions.
[1] TUBA4A: The Tale of an Unconventional Tubulin - PMC [2] In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration - Scientific Reports
Limitations and evidence level
Some claims are based on modeling studies rather than direct experiments, so they are predictions about how certain mutations might affect TUBA4A. The sources also describe multiple mutation types and disease links, but not every variant has the same strength of evidence. A few statements concern biochemical behavior in cells or purified systems, which may not capture all features of living tissue.
[1] TUBA4A: The Tale of an Unconventional Tubulin - PMC [2] In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration - Scientific Reports [3] www.uniprot.org › uniprotkb › TBA4A_HUMANTUBA4A - Tubulin alpha-4A chain - Homo sapiens (Human ...
SEE THE IDEA
TUBA4A in microtubule assembly
Encodes tubulin alpha-4A protein.
Two different tubulin proteins pair up with GTP at their interface.
Dimers add to form long cellular tubes.
TUBA4A core and tail help limit breakdown; mutations can disturb this.
Gene -> protein subunit -> tubulin dimer -> microtubule -> cell support and transport; mutations can weaken the chain.
TUBA4A makes a tubulin subunit that helps build microtubules, and changes in its sequence can alter assembly and stability.
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Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.