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Protein

Tubulin beta-4A chain

Gene

TUBB4A

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi140 – 146GTPSequence analysis7

GO - Molecular functioni

  • calcium ion binding Source: CAFA
  • GTPase activity Source: InterPro
  • GTP binding Source: GO_Central
  • structural constituent of cytoskeleton Source: GO_Central

GO - Biological processi

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (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
SIGNORiP04350

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin beta-4A chain
Alternative name(s):
Tubulin 5 beta
Tubulin beta-4 chain
Gene namesi
Name:TUBB4A
Synonyms:TUBB4, TUBB5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000104833.10
HGNCiHGNC:20774 TUBB4A
MIMi602662 gene
neXtProtiNX_P04350

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

Dystonia 4, torsion, autosomal dominant (DYT4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:128101
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0697982R → G in DYT4. 1 PublicationCorresponds to variant dbSNP:rs587776983EnsemblClinVar.1
Leukodystrophy, hypomyelinating, 6 (HLD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:612438
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069799249D → N in HLD. 1 PublicationCorresponds to variant dbSNP:rs483352809EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dystonia, Leukodystrophy

Organism-specific databases

DisGeNETi10382
MalaCardsiTUBB4A
MIMi128101 phenotype
612438 phenotype
OpenTargetsiENSG00000104833
Orphaneti139441 Hypomyelination with atrophy of basal ganglia and cerebellum
98805 Primary dystonia, DYT4 type
PharmGKBiPA134949465

Chemistry databases

ChEMBLiCHEMBL3838
DrugBankiDB05147 CYT997
DB03010 Epothilone B
DB01873 Epothilone D
DB06042 ZEN-012

Polymorphism and mutation databases

BioMutaiTUBB4A
DMDMi93141323

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000482521 – 444Tubulin beta-4A chainAdd BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei172Phosphoserine; by CDK11 Publication1
Modified residuei4365-glutamyl polyglutamateBy 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
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.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein

Proteomic databases

EPDiP04350
MaxQBiP04350
PaxDbiP04350
PeptideAtlasiP04350
PRIDEiP04350
ProteomicsDBi51702
TopDownProteomicsiP04350

2D gel databases

OGPiP04350
REPRODUCTION-2DPAGEiIPI00023598

PTM databases

iPTMnetiP04350
PhosphoSitePlusiP04350
SwissPalmiP04350

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000104833 Expressed in 135 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_TUBB4
ExpressionAtlasiP04350 baseline and differential
GenevisibleiP04350 HS

Organism-specific databases

HPAiCAB010768
HPA043640
HPA046280

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

Protein-protein interaction databases

BioGridi115655, 78 interactors
IntActiP04350, 58 interactors
MINTiP04350
STRINGi9606.ENSP00000264071

Structurei

3D structure databases

ProteinModelPortaliP04350
SMRiP04350
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The highly acidic C-terminal region may bind cations such as calcium.

Sequence similaritiesi

Belongs to the tubulin family.Curated

Phylogenomic databases

eggNOGiKOG1375 Eukaryota
COG5023 LUCA
GeneTreeiENSGT00760000119061
HOGENOMiHOG000165710
HOVERGENiHBG000089
InParanoidiP04350
KOiK07375
OMAiTGAYQGD
OrthoDBiEOG091G06U2
PhylomeDBiP04350
TreeFamiTF300298

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
IPR013838 Beta-tubulin_BS
IPR002453 Beta_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
PTHR11588:SF256 PTHR11588:SF256, 1 hit
PfamiView protein in Pfam
PF00091 Tubulin, 1 hit
PF03953 Tubulin_C, 1 hit
PRINTSiPR01163 BETATUBULIN
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
PS00228 TUBULIN_B_AUTOREG, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 12 potential isoforms that are computationally mapped.Show allAlign All

P04350-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MREIVHLQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLERINVY
60 70 80 90 100
YNEATGGNYV PRAVLVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN
110 120 130 140 150
WAKGHYTEGA ELVDAVLDVV RKEAESCDCL QGFQLTHSLG GGTGSGMGTL
160 170 180 190 200
LISKIREEFP DRIMNTFSVV PSPKVSDTVV EPYNATLSVH QLVENTDETY
210 220 230 240 250
CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL RFPGQLNADL
260 270 280 290 300
RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQMFDAKNMM
310 320 330 340 350
AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LSVQSKNSSY FVEWIPNNVK
360 370 380 390 400
TAVCDIPPRG LKMAATFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG
410 420 430 440
EGMDEMEFTE AESNMNDLVS EYQQYQDATA EEGEFEEEAE EEVA
Length:444
Mass (Da):49,586
Last modified:April 18, 2006 - v2
Checksum:iF7429D057C11A3F5
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R042M0R042_HUMAN
Tubulin beta chain
TUBB4A
144Annotation score:
M0R1I1M0R1I1_HUMAN
Tubulin beta chain
TUBB4A
74Annotation score:
M0R2D3M0R2D3_HUMAN
Tubulin beta-4A chain
TUBB4A
155Annotation score:
M0QYM7M0QYM7_HUMAN
Tubulin beta-4A chain
TUBB4A
160Annotation score:
M0R0X0M0R0X0_HUMAN
Tubulin beta-4A chain
TUBB4A
103Annotation score:
M0QY85M0QY85_HUMAN
Tubulin beta-4A chain
TUBB4A
107Annotation score:
M0QY37M0QY37_HUMAN
Tubulin beta-4A chain
TUBB4A
109Annotation score:
M0QX14M0QX14_HUMAN
Tubulin beta-4A chain
TUBB4A
110Annotation score:
M0R278M0R278_HUMAN
Tubulin beta-4A chain
TUBB4A
167Annotation score:
M0QZL7M0QZL7_HUMAN
Tubulin beta-4A chain
TUBB4A
157Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti269G → A in CAA25318 (PubMed:6462917).Curated1
Sequence conflicti283A → G in CAA25318 (PubMed:6462917).Curated1
Sequence conflicti432E → Q in CAA25318 (PubMed:6462917).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0697982R → G in DYT4. 1 PublicationCorresponds to variant dbSNP:rs587776983EnsemblClinVar.1
Natural variantiVAR_052673155I → M1 PublicationCorresponds to variant dbSNP:rs1053262Ensembl.1
Natural variantiVAR_069799249D → N in HLD. 1 PublicationCorresponds to variant dbSNP:rs483352809EnsemblClinVar.1
Natural variantiVAR_026044365A → V1 PublicationCorresponds to variant dbSNP:rs1053267Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00734 Genomic DNA Translation: CAA25318.1
AK075307 mRNA Translation: BAG52106.1
CH471139 Genomic DNA Translation: EAW69078.1
BC006570 mRNA Translation: AAH06570.1
BC013683 mRNA Translation: AAH13683.1
CCDSiCCDS12168.1
PIRiA02972 UBHU5B
RefSeqiNP_001276052.1, NM_001289123.1
NP_001276056.1, NM_001289127.1
NP_001276058.1, NM_001289129.1
NP_001276059.1, NM_001289130.1
NP_001276060.1, NM_001289131.1
NP_006078.2, NM_006087.3
UniGeneiHs.110837

Genome annotation databases

EnsembliENST00000264071; ENSP00000264071; ENSG00000104833
GeneIDi10382
KEGGihsa:10382
UCSCiuc002mfg.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00734 Genomic DNA Translation: CAA25318.1
AK075307 mRNA Translation: BAG52106.1
CH471139 Genomic DNA Translation: EAW69078.1
BC006570 mRNA Translation: AAH06570.1
BC013683 mRNA Translation: AAH13683.1
CCDSiCCDS12168.1
PIRiA02972 UBHU5B
RefSeqiNP_001276052.1, NM_001289123.1
NP_001276056.1, NM_001289127.1
NP_001276058.1, NM_001289129.1
NP_001276059.1, NM_001289130.1
NP_001276060.1, NM_001289131.1
NP_006078.2, NM_006087.3
UniGeneiHs.110837

3D structure databases

ProteinModelPortaliP04350
SMRiP04350
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115655, 78 interactors
IntActiP04350, 58 interactors
MINTiP04350
STRINGi9606.ENSP00000264071

Chemistry databases

ChEMBLiCHEMBL3838
DrugBankiDB05147 CYT997
DB03010 Epothilone B
DB01873 Epothilone D
DB06042 ZEN-012

PTM databases

iPTMnetiP04350
PhosphoSitePlusiP04350
SwissPalmiP04350

Polymorphism and mutation databases

BioMutaiTUBB4A
DMDMi93141323

2D gel databases

OGPiP04350
REPRODUCTION-2DPAGEiIPI00023598

Proteomic databases

EPDiP04350
MaxQBiP04350
PaxDbiP04350
PeptideAtlasiP04350
PRIDEiP04350
ProteomicsDBi51702
TopDownProteomicsiP04350

Protocols and materials databases

DNASUi10382
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264071; ENSP00000264071; ENSG00000104833
GeneIDi10382
KEGGihsa:10382
UCSCiuc002mfg.2 human

Organism-specific databases

CTDi10382
DisGeNETi10382
EuPathDBiHostDB:ENSG00000104833.10
GeneCardsiTUBB4A
HGNCiHGNC:20774 TUBB4A
HPAiCAB010768
HPA043640
HPA046280
MalaCardsiTUBB4A
MIMi128101 phenotype
602662 gene
612438 phenotype
neXtProtiNX_P04350
OpenTargetsiENSG00000104833
Orphaneti139441 Hypomyelination with atrophy of basal ganglia and cerebellum
98805 Primary dystonia, DYT4 type
PharmGKBiPA134949465
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1375 Eukaryota
COG5023 LUCA
GeneTreeiENSGT00760000119061
HOGENOMiHOG000165710
HOVERGENiHBG000089
InParanoidiP04350
KOiK07375
OMAiTGAYQGD
OrthoDBiEOG091G06U2
PhylomeDBiP04350
TreeFamiTF300298

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of SLC2A4 (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
SIGNORiP04350

Miscellaneous databases

ChiTaRSiTUBB4A human
GeneWikiiTUBB4
GenomeRNAii10382
PROiPR:P04350
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104833 Expressed in 135 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_TUBB4
ExpressionAtlasiP04350 baseline and differential
GenevisibleiP04350 HS

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
IPR013838 Beta-tubulin_BS
IPR002453 Beta_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
PTHR11588:SF256 PTHR11588:SF256, 1 hit
PfamiView protein in Pfam
PF00091 Tubulin, 1 hit
PF03953 Tubulin_C, 1 hit
PRINTSiPR01163 BETATUBULIN
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
PS00228 TUBULIN_B_AUTOREG, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTBB4A_HUMAN
AccessioniPrimary (citable) accession number: P04350
Secondary accession number(s): B3KQP4, Q969E5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: April 18, 2006
Last modified: November 7, 2018
This is version 200 of the entry and version 2 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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