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Protein

Tubulin alpha-4A chain

Gene

TUBA4A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.

Miscellaneous

This tubulin does not have a C-terminal tyrosine.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi142 – 148GTPSequence analysis7

GO - Molecular functioni

  • GTPase activity Source: InterPro
  • GTP binding Source: UniProtKB-KW
  • protein kinase binding Source: ARUK-UCL
  • structural constituent of cytoskeleton Source: InterPro

GO - Biological processi

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-190840 Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane
R-HSA-190861 Gap junction assembly
R-HSA-2132295 MHC class II antigen presentation
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC
R-HSA-389977 Post-chaperonin tubulin folding pathway
R-HSA-437239 Recycling pathway of L1
R-HSA-5610787 Hedgehog 'off' state
R-HSA-5617833 Cilium Assembly
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-5620924 Intraflagellar transport
R-HSA-5626467 RHO GTPases activate IQGAPs
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-6807878 COPI-mediated anterograde transport
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic
R-HSA-68877 Mitotic Prometaphase
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854518 AURKA Activation by TPX2
R-HSA-8955332 Carboxyterminal post-translational modifications of tubulin
R-HSA-983189 Kinesins
SIGNORiP68366

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin alpha-4A chain
Alternative name(s):
Alpha-tubulin 1
Testis-specific alpha-tubulin
Tubulin H2-alpha
Tubulin alpha-1 chain
Gene namesi
Name:TUBA4A
Synonyms:TUBA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000127824.13
HGNCiHGNC:12407 TUBA4A
MIMi191110 gene
neXtProtiNX_P68366

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Microtubule

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis 22, with or without frontotemporal dementia (ALS22)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:616208
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072714145T → P in ALS22. 1 PublicationCorresponds to variant dbSNP:rs730880029EnsemblClinVar.1
Natural variantiVAR_072715215R → C in ALS22; displays significantly different distribution in terms of incorporation into microtubules. 1 PublicationCorresponds to variant dbSNP:rs730880028EnsemblClinVar.1
Natural variantiVAR_072716320R → C in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant dbSNP:rs730880025EnsemblClinVar.1
Natural variantiVAR_072717320R → H in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant dbSNP:rs730880026EnsemblClinVar.1
Natural variantiVAR_072718383A → T in ALS22; displays significantly different distribution in terms of incorporation into microtubules; destabilizes the microtubule network. 1 PublicationCorresponds to variant dbSNP:rs368743618EnsemblClinVar.1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Neurodegeneration

Organism-specific databases

DisGeNETi7277
MalaCardsiTUBA4A
MIMi616208 phenotype
OpenTargetsiENSG00000127824
PharmGKBiPA162407391

Chemistry databases

ChEMBLiCHEMBL2095182
DrugBankiDB06772 Cabazitaxel
DB05147 CYT997
DB03010 Epothilone B
DB01873 Epothilone D
DB01179 Podofilox
DB05281 S-8184
DB00541 Vincristine

Polymorphism and mutation databases

DMDMi55977476

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000481061 – 448Tubulin alpha-4A chainAdd BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40N6-acetyllysine1 Publication1
Modified residuei48PhosphoserineCombined sources1
Modified residuei83Nitrated tyrosineBy similarity1
Modified residuei432PhosphotyrosineBy similarity1
Modified residuei439PhosphoserineBy similarity1

Post-translational modificationi

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).1 Publication
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 axonemes (cilia and flagella). Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. The precise function of monoglycylation is still unclear (Probable).1 Publication
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.1 Publication
Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.By similarity

Keywords - PTMi

Acetylation, Methylation, Nitration, Phosphoprotein

Proteomic databases

EPDiP68366
MaxQBiP68366
PaxDbiP68366
PeptideAtlasiP68366
PRIDEiP68366

2D gel databases

DOSAC-COBS-2DPAGEiP68366
OGPiP05215

PTM databases

iPTMnetiP68366
PhosphoSitePlusiP68366
SwissPalmiP68366

Miscellaneous databases

PMAP-CutDBiP68366

Expressioni

Gene expression databases

BgeeiENSG00000127824
CleanExiHS_TUBA4A
ExpressionAtlasiP68366 baseline and differential
GenevisibleiP68366 HS

Organism-specific databases

HPAiCAB004621
CAB005887
HPA039247
HPA043684
HPA063394

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CLIP1P306223EBI-351772,EBI-2683569

GO - Molecular functioni

  • protein kinase binding Source: ARUK-UCL

Protein-protein interaction databases

BioGridi113128, 286 interactors
CORUMiP68366
IntActiP68366, 59 interactors
MINTiP68366
STRINGi9606.ENSP00000248437

Structurei

3D structure databases

ProteinModelPortaliP68366
SMRiP68366
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tubulin family.Curated

Phylogenomic databases

eggNOGiKOG1376 Eukaryota
COG5023 LUCA
GeneTreeiENSGT00760000119060
HOGENOMiHOG000165711
HOVERGENiHBG000089
InParanoidiP68366
KOiK07374
OMAiHLHIGQA
OrthoDBiEOG091G0736
PhylomeDBiP68366
TreeFamiTF300314

Family and domain databases

Gene3Di1.10.287.600, 1 hit
3.30.1330.20, 1 hit
3.40.50.1440, 1 hit
InterProiView protein in InterPro
IPR002452 Alpha_tubulin
IPR008280 Tub_FtsZ_C
IPR000217 Tubulin
IPR018316 Tubulin/FtsZ_2-layer-sand-dom
IPR037103 Tubulin/FtsZ_C_sf
IPR036525 Tubulin/FtsZ_GTPase_sf
IPR023123 Tubulin_C
IPR017975 Tubulin_CS
IPR003008 Tubulin_FtsZ_GTPase
PANTHERiPTHR11588 PTHR11588, 1 hit
PfamiView protein in Pfam
PF00091 Tubulin, 1 hit
PF03953 Tubulin_C, 1 hit
PRINTSiPR01162 ALPHATUBULIN
PR01161 TUBULIN
SMARTiView protein in SMART
SM00864 Tubulin, 1 hit
SM00865 Tubulin_C, 1 hit
SUPFAMiSSF52490 SSF52490, 1 hit
SSF55307 SSF55307, 1 hit
PROSITEiView protein in PROSITE
PS00227 TUBULIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P68366-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRECISVHVG QAGVQMGNAC WELYCLEHGI QPDGQMPSDK TIGGGDDSFT
60 70 80 90 100
TFFCETGAGK HVPRAVFVDL EPTVIDEIRN GPYRQLFHPE QLITGKEDAA
110 120 130 140 150
NNYARGHYTI GKEIIDPVLD RIRKLSDQCT GLQGFLVFHS FGGGTGSGFT
160 170 180 190 200
SLLMERLSVD YGKKSKLEFS IYPAPQVSTA VVEPYNSILT THTTLEHSDC
210 220 230 240 250
AFMVDNEAIY DICRRNLDIE RPTYTNLNRL ISQIVSSITA SLRFDGALNV
260 270 280 290 300
DLTEFQTNLV PYPRIHFPLA TYAPVISAEK AYHEQLSVAE ITNACFEPAN
310 320 330 340 350
QMVKCDPRHG KYMACCLLYR GDVVPKDVNA AIAAIKTKRS IQFVDWCPTG
360 370 380 390 400
FKVGINYQPP TVVPGGDLAK VQRAVCMLSN TTAIAEAWAR LDHKFDLMYA
410 420 430 440
KRAFVHWYVG EGMEEGEFSE AREDMAALEK DYEEVGIDSY EDEDEGEE
Length:448
Mass (Da):49,924
Last modified:August 13, 1987 - v1
Checksum:iC00ED90A183FE8F2
GO
Isoform 2 (identifier: P68366-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.

Show »
Length:433
Mass (Da):48,329
Checksum:i0448FC0BE3F4872A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072714145T → P in ALS22. 1 PublicationCorresponds to variant dbSNP:rs730880029EnsemblClinVar.1
Natural variantiVAR_072715215R → C in ALS22; displays significantly different distribution in terms of incorporation into microtubules. 1 PublicationCorresponds to variant dbSNP:rs730880028EnsemblClinVar.1
Natural variantiVAR_072716320R → C in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant dbSNP:rs730880025EnsemblClinVar.1
Natural variantiVAR_072717320R → H in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant dbSNP:rs730880026EnsemblClinVar.1
Natural variantiVAR_072718383A → T in ALS22; displays significantly different distribution in terms of incorporation into microtubules; destabilizes the microtubule network. 1 PublicationCorresponds to variant dbSNP:rs368743618EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0551941 – 15Missing in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06956 Genomic DNA Translation: CAA30026.1
BT006731 mRNA Translation: AAP35377.1
AK054731 mRNA Translation: BAG51418.1
AK299958 mRNA Translation: BAH13182.1
AY895018 Genomic DNA Translation: AAW65371.1
AC068946 Genomic DNA No translation available.
AC114803 Genomic DNA No translation available.
CH471063 Genomic DNA Translation: EAW70718.1
CH471063 Genomic DNA Translation: EAW70719.1
BC009238 mRNA Translation: AAH09238.1
CCDSiCCDS2438.1 [P68366-1]
CCDS63131.1 [P68366-2]
PIRiA25873
RefSeqiNP_001265481.1, NM_001278552.1 [P68366-2]
NP_005991.1, NM_006000.2 [P68366-1]
UniGeneiHs.75318

Genome annotation databases

EnsembliENST00000248437; ENSP00000248437; ENSG00000127824 [P68366-1]
ENST00000392088; ENSP00000375938; ENSG00000127824 [P68366-2]
GeneIDi7277
KEGGihsa:7277
UCSCiuc002vkt.3 human [P68366-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTBA4A_HUMAN
AccessioniPrimary (citable) accession number: P68366
Secondary accession number(s): A8MUB1, B3KNQ6, P05215
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: May 23, 2018
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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