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Protein

Tubulin alpha-4A chain

Gene

TUBA4A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167552-MONOMER.
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-380259. Loss of Nlp from mitotic centrosomes.
R-HSA-380270. Recruitment of mitotic centrosome proteins and complexes.
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. Assembly of the primary cilium.
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-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

HGNCiHGNC:12407. TUBA4A.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • microtubule Source: UniProtKB
Complete GO annotation...

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 rs730880029dbSNPEnsembl.1
Natural variantiVAR_072715215R → C in ALS22; displays significantly different distribution in terms of incorporation into microtubules. 1 PublicationCorresponds to variant rs730880028dbSNPEnsembl.1
Natural variantiVAR_072716320R → C in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant rs730880025dbSNPEnsembl.1
Natural variantiVAR_072717320R → H in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant rs730880026dbSNPEnsembl.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 rs368743618dbSNPEnsembl.1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Neurodegeneration

Organism-specific databases

DisGeNETi7277.
MalaCardsiTUBA4A.
MIMi616208. phenotype.
OpenTargetsiENSG00000127824.
PharmGKBiPA162407391.

Chemistry databases

ChEMBLiCHEMBL2095182.
DrugBankiDB06772. Cabazitaxel.
DB01179. Podofilox.
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

Keywords - PTMi

Acetylation, Nitration, Phosphoprotein

Proteomic databases

EPDiP68366.
MaxQBiP68366.
PaxDbiP68366.
PeptideAtlasiP68366.
PRIDEiP68366.

2D gel databases

DOSAC-COBS-2DPAGEP68366.
OGPiP05215.

PTM databases

iPTMnetiP68366.
PhosphoSitePlusiP68366.
SwissPalmiP68366.

Miscellaneous databases

PMAP-CutDBP68366.

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.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi113128. 212 interactors.
IntActiP68366. 48 interactors.
MINTiMINT-1394538.
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.
OMAiSEGREDM.
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.
InterProiIPR002452. Alpha_tubulin.
IPR008280. Tub_FtsZ_C.
IPR000217. Tubulin.
IPR018316. Tubulin/FtsZ_2-layer-sand-dom.
IPR023123. Tubulin_C.
IPR017975. Tubulin_CS.
IPR003008. Tubulin_FtsZ_GTPase.
[Graphical view]
PANTHERiPTHR11588. PTHR11588. 1 hit.
PfamiPF00091. Tubulin. 1 hit.
PF03953. Tubulin_C. 1 hit.
[Graphical view]
PRINTSiPR01162. ALPHATUBULIN.
PR01161. TUBULIN.
SMARTiSM00864. Tubulin. 1 hit.
SM00865. Tubulin_C. 1 hit.
[Graphical view]
SUPFAMiSSF52490. SSF52490. 1 hit.
SSF55307. SSF55307. 1 hit.
PROSITEiPS00227. TUBULIN. 1 hit.
[Graphical view]

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 rs730880029dbSNPEnsembl.1
Natural variantiVAR_072715215R → C in ALS22; displays significantly different distribution in terms of incorporation into microtubules. 1 PublicationCorresponds to variant rs730880028dbSNPEnsembl.1
Natural variantiVAR_072716320R → C in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant rs730880025dbSNPEnsembl.1
Natural variantiVAR_072717320R → H in ALS22; displays significantly lower levels of dimer assembly. 1 PublicationCorresponds to variant rs730880026dbSNPEnsembl.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 rs368743618dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Tubulin entry

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.

3D structure databases

ProteinModelPortaliP68366.
SMRiP68366.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113128. 212 interactors.
IntActiP68366. 48 interactors.
MINTiMINT-1394538.
STRINGi9606.ENSP00000248437.

Chemistry databases

ChEMBLiCHEMBL2095182.
DrugBankiDB06772. Cabazitaxel.
DB01179. Podofilox.
DB00541. Vincristine.

PTM databases

iPTMnetiP68366.
PhosphoSitePlusiP68366.
SwissPalmiP68366.

Polymorphism and mutation databases

DMDMi55977476.

2D gel databases

DOSAC-COBS-2DPAGEP68366.
OGPiP05215.

Proteomic databases

EPDiP68366.
MaxQBiP68366.
PaxDbiP68366.
PeptideAtlasiP68366.
PRIDEiP68366.

Protocols and materials databases

DNASUi7277.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7277.
DisGeNETi7277.
GeneCardsiTUBA4A.
HGNCiHGNC:12407. TUBA4A.
HPAiCAB004621.
CAB005887.
HPA039247.
HPA043684.
HPA063394.
MalaCardsiTUBA4A.
MIMi191110. gene.
616208. phenotype.
neXtProtiNX_P68366.
OpenTargetsiENSG00000127824.
PharmGKBiPA162407391.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167552-MONOMER.
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-380259. Loss of Nlp from mitotic centrosomes.
R-HSA-380270. Recruitment of mitotic centrosome proteins and complexes.
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. Assembly of the primary cilium.
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-983189. Kinesins.
SIGNORiP68366.

Miscellaneous databases

ChiTaRSiTUBA4A. human.
GeneWikiiTUBA4A.
GenomeRNAii7277.
PMAP-CutDBP68366.
PROiP68366.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127824.
CleanExiHS_TUBA4A.
ExpressionAtlasiP68366. baseline and differential.
GenevisibleiP68366. HS.

Family and domain databases

Gene3Di1.10.287.600. 1 hit.
3.30.1330.20. 1 hit.
3.40.50.1440. 1 hit.
InterProiIPR002452. Alpha_tubulin.
IPR008280. Tub_FtsZ_C.
IPR000217. Tubulin.
IPR018316. Tubulin/FtsZ_2-layer-sand-dom.
IPR023123. Tubulin_C.
IPR017975. Tubulin_CS.
IPR003008. Tubulin_FtsZ_GTPase.
[Graphical view]
PANTHERiPTHR11588. PTHR11588. 1 hit.
PfamiPF00091. Tubulin. 1 hit.
PF03953. Tubulin_C. 1 hit.
[Graphical view]
PRINTSiPR01162. ALPHATUBULIN.
PR01161. TUBULIN.
SMARTiSM00864. Tubulin. 1 hit.
SM00865. Tubulin_C. 1 hit.
[Graphical view]
SUPFAMiSSF52490. SSF52490. 1 hit.
SSF55307. SSF55307. 1 hit.
PROSITEiPS00227. TUBULIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTBA4A_HUMAN
AccessioniPrimary (citable) accession number: P68366
Secondary accession number(s): A8MUB1, B3KNQ6, P05215
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: November 2, 2016
This is version 138 of the entry and version 1 of the sequence. [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

Miscellaneous

This tubulin does not have a C-terminal tyrosine.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.