P04350 · TBB4A_HUMAN
- ProteinTubulin beta-4A chain
- GeneTUBB4A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids444 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 11 | GTP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 69 | GTP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 69 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 138 | GTP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 142 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 143 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 144 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 204 | GTP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 226 | GTP (UniProtKB | ChEBI) | ||||
Sequence: N |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | axoneme | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | intercellular bridge | |
Cellular Component | internode region of axon | |
Cellular Component | microtubule | |
Cellular Component | microtubule cytoskeleton | |
Cellular Component | mitotic spindle | |
Cellular Component | myelin sheath | |
Cellular Component | neuronal cell body | |
Cellular Component | nucleus | |
Molecular Function | calcium ion binding | |
Molecular Function | GTP binding | |
Molecular Function | GTPase activity | |
Molecular Function | structural constituent of cytoskeleton | |
Biological Process | microtubule cytoskeleton organization | |
Biological Process | mitotic cell cycle | |
Biological Process | negative regulation of microtubule polymerization |
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTubulin beta-4A chain
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP04350
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Dystonia 4, torsion, autosomal dominant (DYT4)
- Note
- DescriptionA form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT4 is characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait.
- See alsoMIM:128101
Natural variants in DYT4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069798 | 2 | R>G | in DYT4; dbSNP:rs587776983 |
Leukodystrophy, hypomyelinating, 6 (HLD6)
- Note
- DescriptionA neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen.
- See alsoMIM:612438
Natural variants in HLD6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069799 | 249 | D>N | in HLD6; dbSNP:rs483352809 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_069798 | 2 | in DYT4; dbSNP:rs587776983 | |||
Sequence: R → G | ||||||
Natural variant | VAR_052673 | 155 | in dbSNP:rs1053262 | |||
Sequence: I → M | ||||||
Natural variant | VAR_069799 | 249 | in HLD6; dbSNP:rs483352809 | |||
Sequence: D → N | ||||||
Natural variant | VAR_026044 | 365 | in dbSNP:rs1053267 | |||
Sequence: A → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 398 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000048252 | 1-444 | UniProt | Tubulin beta-4A chain | |||
Sequence: MREIVHLQAGQCGNQIGAKFWEVISDEHGIDPTGTYHGDSDLQLERINVYYNEATGGNYVPRAVLVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDAVLDVVRKEAESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEFPDRIMNTFSVVPSPKVSDTVVEPYNATLSVHQLVENTDETYCIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCLRFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDAKNMMAACDPRHGRYLTVAAVFRGRMSMKEVDEQMLSVQSKNSSYFVEWIPNNVKTAVCDIPPRGLKMAATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVSEYQQYQDATAEEGEFEEEAEEEVA | |||||||
Modified residue (large scale data) | 55 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 72 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 75 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 78 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 95 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 166 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 168 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 172 | UniProt | Phosphoserine; by CDK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 172 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 232 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 234 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 274 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 275 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 278 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 281 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 310 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 335 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 338 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 339 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 340 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 436 | UniProt | 5-glutamyl polyglutamate | ||||
Sequence: E |
Post-translational modification
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).
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).
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.
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.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P04350 | LRRK2 Q5S007 | 6 | EBI-355007, EBI-5323863 | |
BINARY | P04350 | NR4A1 P22736 | 2 | EBI-355007, EBI-721550 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 1-4 | MREI motif | ||||
Sequence: MREI |
Domain
The highly acidic C-terminal region may bind cations such as calcium.
The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
Sequence similarities
Belongs to the tubulin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length444
- Mass (Da)49,586
- Last updated2006-04-18 v2
- ChecksumF7429D057C11A3F5
Computationally mapped potential isoform sequences
There are 12 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAQ5BHG7 | A0AAQ5BHG7_HUMAN | TUBB4A | 161 | ||
M0R1I1 | M0R1I1_HUMAN | TUBB4A | 372 | ||
M0R0M1 | M0R0M1_HUMAN | TUBB4A | 93 | ||
M0R0X0 | M0R0X0_HUMAN | TUBB4A | 103 | ||
M0R2T4 | M0R2T4_HUMAN | TUBB4A | 104 | ||
M0R2D3 | M0R2D3_HUMAN | TUBB4A | 340 | ||
M0R278 | M0R278_HUMAN | TUBB4A | 489 | ||
M0QY37 | M0QY37_HUMAN | TUBB4A | 109 | ||
M0QY85 | M0QY85_HUMAN | TUBB4A | 107 | ||
M0QX14 | M0QX14_HUMAN | TUBB4A | 110 | ||
M0QZL7 | M0QZL7_HUMAN | TUBB4A | 495 | ||
M0QYM7 | M0QYM7_HUMAN | TUBB4A | 374 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 269 | in Ref. 1; CAA25318 | ||||
Sequence: G → A | ||||||
Sequence conflict | 283 | in Ref. 1; CAA25318 | ||||
Sequence: A → G | ||||||
Sequence conflict | 432 | in Ref. 1; CAA25318 | ||||
Sequence: E → Q |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X00734 EMBL· GenBank· DDBJ | CAA25318.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK075307 EMBL· GenBank· DDBJ | BAG52106.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471139 EMBL· GenBank· DDBJ | EAW69078.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC006570 EMBL· GenBank· DDBJ | AAH06570.1 EMBL· GenBank· DDBJ | mRNA | ||
BC013683 EMBL· GenBank· DDBJ | AAH13683.1 EMBL· GenBank· DDBJ | mRNA |