tubulin alpha-3D chain; alpha-tubulin 3D; contains:, detyrosinated tubulin alpha-3D chain (TUBA3D)

Function

• tubulin is the major constituent of microtubules
• it binds two moles of GTP, one at an exchangeable site on the beta chain & one at a non-exchangeable site on the alpha chain
• some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group
• polyglutamylation plays a role in microtubule severing by spastin (SPAST)
• SPAST preferentially recognizes & acts on microtubules decorated with short polyglutamate tails
• severing activity by SPAST increases as the number of glutamates per tubulin increases from 1 to 8, but decreases beyond this glutamylation threshold
• some glutamate residues at the C-terminus are monoglycylated due to the absence of functional TTLL10
• monoglycylation is mainly limited to tubulin incorporated into axonemes (cilia & flagella)
• both polyglutamylation & monoglycylation can,coexist on the same protein on adjacent residues, & lowering glycylation levels increases polyglutamylation,
• acetylation of alpha chains at Lys-40 is located inside the microtubule lumen.
• this modification correlates with microtubule stability, intracellular transport & ciliary assembly
• methylation of alpha chains at Lys-40 is found in mitotic microtubules & is required for normal mitosis & cytokinesis
• nitration of Tyr-450 is irreversible & interferes with normal dynein intracellular distribution
• undergoes a tyrosination/detyrosination cycle, the cyclic removal & re-addition of a C-terminal Tyr by the enzymes tubulin tyrosine carboxypeptidase (VASH1 or VASH2) & tubulin tyrosine ligase (TTL), respectively
• tubulin alpha-3D chain tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 & DCTN1 (putative)
• tyrosination regulates initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (putative)
• detyrosinated tubulin alpha-3D chain: detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis:
• detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator
• detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac & skeletal muscle
• in cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction
• detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules & mechanical resistance to

Structure

belongs to the tubulin family,

Compartment

cytoplasm, cytoskeleton

Expression

expressed in the cornea, sclera, & peripheral blood

Pathology

• mutations of the TUBA3D gene result in keratoconus 9

More general terms

• tubulin alpha-1A chain

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=113457
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7278
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:113457
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7278
• OMIM: https://mirror.omim.org/entry/617878
• OMIM: https://mirror.omim.org/entry/617928
• UniProt: http://www.uniprot.org/uniprot/P0DPH8.html