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Protein

Tubulin beta-3 chain

Gene

TUBB3

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. TUBB3 plays a critical role in proper axon guidance and mantainance.1 Publication

Regions

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

GO - Molecular functioni

GO - Biological processi

  • axon guidance Source: UniProtKB
  • microtubule-based process Source: InterPro
  • mitotic cell cycle Source: Ensembl

Keywordsi

LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-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-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
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-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-8955332 Carboxyterminal post-translational modifications of tubulin
R-HSA-983189 Kinesins
SIGNORiQ13509

Names & Taxonomyi

Protein namesi
Recommended name:
Tubulin beta-3 chain
Alternative name(s):
Tubulin beta-4 chain
Tubulin beta-III
Gene namesi
Name:TUBB3
Synonyms:TUBB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000258947.6
HGNCiHGNC:20772 TUBB3
MIMi602661 gene
neXtProtiNX_Q13509

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

Fibrosis of extraocular muscles, congenital, 3A (CFEOM3A)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy.
See also OMIM:600638
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06275862R → Q in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs864321714EnsemblClinVar.1
Natural variantiVAR_062759262R → C in CFEOM3A; affects heterodimers formation; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs267607162EnsemblClinVar.1
Natural variantiVAR_062760262R → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs864321716EnsemblClinVar.1
Natural variantiVAR_062761302A → T in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs267607163EnsemblClinVar.1
Natural variantiVAR_062762380R → C in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs864321717EnsemblClinVar.1
Natural variantiVAR_062763410E → K in CFEOM3A; severe phenotype with congenital facial weakness; lower extremity weakness and sensory loss in the second to third decade of life in one patient; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs267607165EnsemblClinVar.1
Natural variantiVAR_062764417D → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures. 1 PublicationCorresponds to variant dbSNP:rs267607164EnsemblClinVar.1
Natural variantiVAR_062765417D → N in CFEOM3A; some patients with lower extremity weakness and sensory loss in the second to third decade of life; also found in patients without CFEOM3A who developed polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs267607164EnsemblClinVar.1
Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved.
See also OMIM:614039
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066206178T → M in CDCBM1; can form tubulin heterodimers that are properly incorporated into microtubules; the microtubules are less stable than wild-type. 1 PublicationCorresponds to variant dbSNP:rs747480526EnsemblClinVar.1
Natural variantiVAR_066207205E → K in CDCBM1; does not form tubulin heterodimers; patient fibroblasts show no major alterations in the microtubule network, but the microtubules are less stable than wild-type. 1 PublicationCorresponds to variant dbSNP:rs878853257EnsemblClinVar.1
Natural variantiVAR_066208302A → V in CDCBM1; does not form tubulin heterodimers. 1 PublicationCorresponds to variant dbSNP:rs878853258Ensembl.1
Natural variantiVAR_066209323M → V in CDCBM1; reduced heterodimers formation. 1 PublicationCorresponds to variant dbSNP:rs878853256Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10381
GeneReviewsiTUBB3
MalaCardsiTUBB3
MIMi600638 phenotype
614039 phenotype
OpenTargetsiENSG00000258947
Orphaneti45358 Congenital fibrosis of extraocular muscles
300570 Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation
PharmGKBiPA134953867

Chemistry databases

ChEMBLiCHEMBL2597
DrugBankiDB05147 CYT997
DB03010 Epothilone B
DB01873 Epothilone D
DB04845 Ixabepilone
DB06042 ZEN-012
GuidetoPHARMACOLOGYi2752

Polymorphism and mutation databases

BioMutaiTUBB3
DMDMi20455526

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000482501 – 450Tubulin beta-3 chainAdd BLAST450

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei172Phosphoserine; by CDK11 Publication1
Modified residuei4385-glutamyl polyglutamateBy similarity1
Modified residuei444PhosphoserineBy 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

EPDiQ13509
MaxQBiQ13509
PaxDbiQ13509
PeptideAtlasiQ13509
PRIDEiQ13509
ProteomicsDBi59510
TopDownProteomicsiQ13509-1 [Q13509-1]

2D gel databases

OGPiQ13509

PTM databases

iPTMnetiQ13509
PhosphoSitePlusiQ13509
SwissPalmiQ13509

Expressioni

Tissue specificityi

Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues.2 Publications

Gene expression databases

BgeeiENSG00000258947
CleanExiHS_TUBB3
HS_TUBB4
ExpressionAtlasiQ13509 baseline and differential
GenevisibleiQ13509 HS

Organism-specific databases

HPAiHPA043640
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

Show more details

Protein-protein interaction databases

BioGridi115654, 261 interactors
DIPiDIP-31505N
IntActiQ13509, 147 interactors
MINTiQ13509
STRINGi9606.ENSP00000320295

Structurei

3D structure databases

ProteinModelPortaliQ13509
SMRiQ13509
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
InParanoidiQ13509
KOiK07375
OrthoDBiEOG091G06U2
PhylomeDBiQ13509
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

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q13509-1) [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
MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPSGNYVGDS DLQLERISVY
60 70 80 90 100
YNEASSHKYV PRAILVDLEP GTMDSVRSGA FGHLFRPDNF IFGQSGAGNN
110 120 130 140 150
WAKGHYTEGA ELVDSVLDVV RKECENCDCL QGFQLTHSLG GGTGSGMGTL
160 170 180 190 200
LISKVREEYP DRIMNTFSVV PSPKVSDTVV EPYNATLSIH QLVENTDETY
210 220 230 240 250
CIDNEALYDI CFRTLKLATP TYGDLNHLVS ATMSGVTTSL RFPGQLNADL
260 270 280 290 300
RKLAVNMVPF PRLHFFMPGF APLTARGSQQ YRALTVPELT QQMFDAKNMM
310 320 330 340 350
AACDPRHGRY LTVATVFRGR MSMKEVDEQM LAIQSKNSSY FVEWIPNNVK
360 370 380 390 400
VAVCDIPPRG LKMSSTFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG
410 420 430 440 450
EGMDEMEFTE AESNMNDLVS EYQQYQDATA EEEGEMYEDD EEESEAQGPK
Length:450
Mass (Da):50,433
Last modified:May 2, 2002 - v2
Checksum:i4B9CDE7DBA102949
GO
Isoform 2 (identifier: Q13509-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.

Note: No experimental confirmation available.
Show »
Length:378
Mass (Da):42,433
Checksum:iA190AB5B6264F2AB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti275A → R in AAC52035 (PubMed:9473684).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06275862R → Q in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs864321714EnsemblClinVar.1
Natural variantiVAR_066206178T → M in CDCBM1; can form tubulin heterodimers that are properly incorporated into microtubules; the microtubules are less stable than wild-type. 1 PublicationCorresponds to variant dbSNP:rs747480526EnsemblClinVar.1
Natural variantiVAR_066207205E → K in CDCBM1; does not form tubulin heterodimers; patient fibroblasts show no major alterations in the microtubule network, but the microtubules are less stable than wild-type. 1 PublicationCorresponds to variant dbSNP:rs878853257EnsemblClinVar.1
Natural variantiVAR_062759262R → C in CFEOM3A; affects heterodimers formation; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs267607162EnsemblClinVar.1
Natural variantiVAR_062760262R → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs864321716EnsemblClinVar.1
Natural variantiVAR_062761302A → T in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs267607163EnsemblClinVar.1
Natural variantiVAR_066208302A → V in CDCBM1; does not form tubulin heterodimers. 1 PublicationCorresponds to variant dbSNP:rs878853258Ensembl.1
Natural variantiVAR_066209323M → V in CDCBM1; reduced heterodimers formation. 1 PublicationCorresponds to variant dbSNP:rs878853256Ensembl.1
Natural variantiVAR_062762380R → C in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. 1 PublicationCorresponds to variant dbSNP:rs864321717EnsemblClinVar.1
Natural variantiVAR_062763410E → K in CFEOM3A; severe phenotype with congenital facial weakness; lower extremity weakness and sensory loss in the second to third decade of life in one patient; affects microtubules polymerization and depolymerization rates. 1 PublicationCorresponds to variant dbSNP:rs267607165EnsemblClinVar.1
Natural variantiVAR_062764417D → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures. 1 PublicationCorresponds to variant dbSNP:rs267607164EnsemblClinVar.1
Natural variantiVAR_062765417D → N in CFEOM3A; some patients with lower extremity weakness and sensory loss in the second to third decade of life; also found in patients without CFEOM3A who developed polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs267607164EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0546591 – 72Missing in isoform 2. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U47634 mRNA Translation: AAC52035.1
AF427491 mRNA Translation: AAL28094.1
AK122757 mRNA Translation: BAG53710.1
AK292219 mRNA Translation: BAF84908.1
AC092143 Genomic DNA No translation available.
CH471184 Genomic DNA Translation: EAW66674.1
BC000748 mRNA Translation: AAH00748.1
BC003021 mRNA Translation: AAH03021.2
CCDSiCCDS10988.1 [Q13509-1]
CCDS56012.1 [Q13509-2]
RefSeqiNP_001184110.1, NM_001197181.1 [Q13509-2]
NP_006077.2, NM_006086.3 [Q13509-1]
UniGeneiHs.511743

Genome annotation databases

EnsembliENST00000315491; ENSP00000320295; ENSG00000258947 [Q13509-1]
ENST00000554444; ENSP00000451617; ENSG00000258947 [Q13509-2]
GeneIDi10381
KEGGihsa:10381
UCSCiuc002fph.2 human [Q13509-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTBB3_HUMAN
AccessioniPrimary (citable) accession number: Q13509
Secondary accession number(s): A8K854, Q9BTZ0, Q9BW10
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 2, 2002
Last modified: July 18, 2018
This is version 180 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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