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Details on Person UniProt:P04350 TUBB4A

Class:IdReferenceGeneProduct:65693
_chainChangeLogchain:1-444 added on Fri February 6 2015
_displayNameUniProt:P04350 TUBB4A
_timestamp2024-11-03 20:21:48
chainchain:1-444
checksumF7429D057C11A3F5
commentFUNCTION Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.COFACTOR Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.INTERACTION Major isotype in brain, where it represents 46% of all beta-tubulins. In the brain, highest expression levels in the cerebellum, followed by putamen and white matter. Moderate levels in testis. Very low levels, if any, in other tissues.DOMAIN The highly acidic C-terminal region may bind cations such as calcium.DOMAIN The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.PTM Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).PTM Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.PTM Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the tubulin family.
descriptionrecommendedName: Tubulin beta-4A chain alternativeName: Tubulin 5 beta alternativeName: Tubulin beta-4 chain
geneNameTUBB4A
TUBB4
TUBB5
identifierP04350
isSequenceChangedFALSE
keywordCytoplasm
Cytoskeleton
Direct protein sequencing
Disease variant
Dystonia
GTP-binding
Isopeptide bond
Leukodystrophy
Magnesium
Metal-binding
Microtubule
Nucleotide-binding
Phosphoprotein
Proteomics identification
Reference proteome
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
nameTUBB4A
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8958324] ENSEMBL:ENSG00000104833 TUBB4A [Homo sapiens]
secondaryIdentifierTBB4A_HUMAN
B3KQP4
Q969E5
sequenceLength444
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:190588] TUBB4A [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:392778] TUBB4A unfolded [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:392789] TUBB4A folding intermediate [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:5610435] TUBB4A [axonemal microtubule] [Homo sapiens]
[EntityWithAccessionedSequence:8867397] Polyglycyl-TUBB4A [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8867425] Polyglutamyl-TUBB4A [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8957610] TUBB4A [extracellular region] [Homo sapiens]
[EntityWithAccessionedSequence:9648034] TUBB4A [spindle] [Homo sapiens]
[EntityWithAccessionedSequence:9962318] TUBB4A [cilium] [Homo sapiens]
(referenceSequence)[ModifiedResidue:8867379] L-isoglutamyl-polyglutamic acid at unknown position
[ModifiedResidue:8867420] L-isoglutamyl-polyglycine at unknown position
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No pathways have been reviewed or authored by UniProt:P04350 TUBB4A (65693)