P68366 · TBA4A_HUMAN
- ProteinTubulin alpha-4A chain
- GeneTUBA4A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids448 (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.
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 11 | GTP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 71 | GTP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 71 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 140 | GTP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 144 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 145 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 179 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 206 | GTP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 228 | GTP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 254 | |||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoskeleton | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | microtubule | |
Cellular Component | microtubule cytoskeleton | |
Molecular Function | GTP binding | |
Molecular Function | hydrolase activity | |
Molecular Function | metal ion binding | |
Molecular Function | protein kinase binding | |
Molecular Function | structural constituent of cytoskeleton | |
Biological Process | microtubule cytoskeleton organization | |
Biological Process | mitotic cell cycle |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTubulin alpha-4A chain
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP68366
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Amyotrophic lateral sclerosis 22, with or without frontotemporal dementia (ALS22)
- Note
- DescriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS22 may develop frontotemporal dementia.
- See alsoMIM:616208
Natural variants in ALS22
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_072714 | 145 | T>P | in ALS22; dbSNP:rs730880029 | |
VAR_072715 | 215 | R>C | in ALS22; displays significantly different distribution in terms of incorporation into microtubules; dbSNP:rs730880028 | |
VAR_072716 | 320 | R>C | in ALS22; displays significantly lower levels of dimer assembly; dbSNP:rs730880025 | |
VAR_072717 | 320 | R>H | in ALS22; displays significantly lower levels of dimer assembly; dbSNP:rs730880026 | |
VAR_072718 | 383 | A>T | in ALS22; displays significantly different distribution in terms of incorporation into microtubules; destabilizes the microtubule network; dbSNP:rs368743618 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_072714 | 145 | in ALS22; dbSNP:rs730880029 | |||
Sequence: T → P | ||||||
Natural variant | VAR_072715 | 215 | in ALS22; displays significantly different distribution in terms of incorporation into microtubules; dbSNP:rs730880028 | |||
Sequence: R → C | ||||||
Natural variant | VAR_072716 | 320 | in ALS22; displays significantly lower levels of dimer assembly; dbSNP:rs730880025 | |||
Sequence: R → C | ||||||
Natural variant | VAR_072717 | 320 | in ALS22; displays significantly lower levels of dimer assembly; dbSNP:rs730880026 | |||
Sequence: R → H | ||||||
Natural variant | VAR_072718 | 383 | in ALS22; displays significantly different distribution in terms of incorporation into microtubules; destabilizes the microtubule network; dbSNP:rs368743618 | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 323 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, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000048106 | 1-448 | UniProt | Tubulin alpha-4A chain | |||
Sequence: MRECISVHVGQAGVQMGNACWELYCLEHGIQPDGQMPSDKTIGGGDDSFTTFFCETGAGKHVPRAVFVDLEPTVIDEIRNGPYRQLFHPEQLITGKEDAANNYARGHYTIGKEIIDPVLDRIRKLSDQCTGLQGFLVFHSFGGGTGSGFTSLLMERLSVDYGKKSKLEFSIYPAPQVSTAVVEPYNSILTTHTTLEHSDCAFMVDNEAIYDICRRNLDIERPTYTNLNRLISQIVSSITASLRFDGALNVDLTEFQTNLVPYPRIHFPLATYAPVISAEKAYHEQLSVAEITNACFEPANQMVKCDPRHGKYMACCLLYRGDVVPKDVNAAIAAIKTKRSIQFVDWCPTGFKVGINYQPPTVVPGGDLAKVQRAVCMLSNTTAIAEAWARLDHKFDLMYAKRAFVHWYVGEGMEEGEFSEAREDMAALEKDYEEVGIDSYEDEDEGEE | |||||||
Modified residue | 40 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 48 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 48 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 83 | UniProt | 3'-nitrotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 94 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 103 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 158 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 223 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 224 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 225 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 232 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 237 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 262 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 271 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 272 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 277 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 282 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 287 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 312 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 319 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 340 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 357 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 361 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 379 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 399 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 432 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 439 | UniProt | Phosphoserine | ||||
Sequence: S |
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.
Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.
Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.
Although this tubulin does not encode a C-terminal tyrosine, a C-terminal tyrosine can be added post-translationally by the tubulin tyrosine ligase (TTL) (PubMed:35482892).
It can then undergo a detyrosination cycle by the tubulin tyrosine carboxypeptidase (MATCAP1/KIAA0895L) (PubMed:35482892).
It can then undergo a detyrosination cycle by the tubulin tyrosine carboxypeptidase (MATCAP1/KIAA0895L) (PubMed:35482892).
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
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. Interacts with CFAP157 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P68366 | APP P05067 | 3 | EBI-351772, EBI-77613 | |
BINARY | P68366 | CLIP1 P30622 | 3 | EBI-351772, EBI-2683569 | |
BINARY | P68366 | POC5 Q8NA72 | 5 | EBI-351772, EBI-2561090 | |
BINARY | P68366 | TBCB Q99426 | 2 | EBI-351772, EBI-764356 | |
BINARY | P68366 | TCP11L2 Q8N4U5 | 6 | EBI-351772, EBI-11897462 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 1-4 | MREC motif | ||||
Sequence: MREC |
Domain
The MREC motif may be critical for tubulin autoregulation.
Sequence similarities
Belongs to the tubulin family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P68366-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length448
- Mass (Da)49,924
- Last updated1987-08-13 v1
- ChecksumC00ED90A183FE8F2
P68366-2
- Name2
- Differences from canonical
- 1-15: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_055194 | 1-15 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X06956 EMBL· GenBank· DDBJ | CAA30026.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT006731 EMBL· GenBank· DDBJ | AAP35377.1 EMBL· GenBank· DDBJ | mRNA | ||
AK054731 EMBL· GenBank· DDBJ | BAG51418.1 EMBL· GenBank· DDBJ | mRNA | ||
AK299958 EMBL· GenBank· DDBJ | BAH13182.1 EMBL· GenBank· DDBJ | mRNA | ||
AY895018 EMBL· GenBank· DDBJ | AAW65371.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC068946 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC114803 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471063 EMBL· GenBank· DDBJ | EAW70718.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70719.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC009238 EMBL· GenBank· DDBJ | AAH09238.1 EMBL· GenBank· DDBJ | mRNA |