Human Gene TUBB3 (uc002fpf.2) Description and Page Index
  Description: Homo sapiens tubulin, beta 3 class III (TUBB3), transcript variant 1, mRNA.
RefSeq Summary (NM_006086): This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010].
Transcript (Including UTRs)
   Position: hg19 chr16:89,985,259-90,002,505 Size: 17,247 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr16:89,985,667-90,002,212 Size: 16,546 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDGene Alleles
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:89,985,259-90,002,505)mRNA (may differ from genome)Protein (797 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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Wikipedia

-  Comments and Description Text from UniProtKB
  ID: TBB3_HUMAN
DESCRIPTION: RecName: Full=Tubulin beta-3 chain; AltName: Full=Tubulin beta-4 chain; AltName: Full=Tubulin beta-III;
FUNCTION: 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.
SUBUNIT: Dimer of alpha and beta chains.
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
TISSUE SPECIFICITY: Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues.
DOMAIN: The highly acidic C-terminal region may bind cations such as calcium.
PTM: Some glutamate residues at the C-terminus are polyglutamylated. This modification occurs exclusively on glutamate residues and results in polyglutamate chains on the gamma-carboxyl group. Also 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) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. The precise function of such modifications is still unclear but they regulate the assembly and dynamics of axonemal microtubules (Probable).
PTM: 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.
DISEASE: Defects in TUBB3 are the cause of congenital fibrosis of extraocular muscles type 3A (CFEOM3A) [MIM:600638]. A 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.
DISEASE: Defects in TUBB3 are the cause of cortical dysplasia complex with other brain malformations (CDCBM) [MIM:614039]. CDCBM is a 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.
SIMILARITY: Belongs to the tubulin family.

-  MalaCards Disease Associations
  MalaCards Gene Search: TUBB3
Diseases sorted by gene-association score: cortical dysplasia, complex, with other brain malformations 1* (1681), fibrosis of extraocular muscles, congenital, 3a* (1231), tukel syndrome* (476), tubulinopathy-associated dysgyria* (350), tubb3-related congenital fibrosis of the extraocular muscles* (200), refractive error (30), ovarian carcinosarcoma (27), ocular motility disease (25), hypotropia (23), cranial nerve disease (23), exotropia (22), paralytic squint (21), physical disorder (20), pineal gland cancer (19), congenital nervous system abnormality (14), amyloid tumor (14), amblyopia (13), tracheomalacia (13), segmental dystonia (13), leukodystrophy, hypomyelinating, 6 (13), peripheral nervous system disease (13), neonatal anemia (12), tracheal disease (12), ptosis, congenital (12), cell type cancer (11), charcot-marie-tooth disease, axonal, type 2k (11), marcus gunn phenomenon (11), strabismus (11), charcot-marie-tooth disease, type 4a (10), moebius syndrome (10), polyneuropathy (10), pathologic nystagmus (10), ptosis (10), female reproductive organ cancer (9), embryonal carcinoma (9), peritoneum cancer (8), pineocytoma (8), exposure keratitis (8), kearns-sayre syndrome (8), duane retraction syndrome (8), pick disease (7), spastic cerebral palsy (7), esotropia (7), chondroid chordoma (7), congenital nystagmus (7), keratopathy (7), odontoma (7), lung cancer (7), twin-to-twin transfusion syndrome (6), spastic diplegia (6), corpus callosum agenesis (6), spinal cord glioma (6), dystonia-12 (6), pineal parenchymal tumor of intermediate differentiation (6), reproductive organ cancer (6), nervous system disease (5), adult medulloblastoma (5), poland syndrome (5), facial nerve disease (5), hypertropia (5), facial paralysis (5), distal arthrogryposis (4), ovarian cancer, somatic (2), corneal disease (2), charcot-marie-tooth disease, type 2e (1), kallmann syndrome (1), central nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -182.80408-0.448 Picture PostScript Text
3' UTR -95.27293-0.325 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013838 - Beta-tubulin_BS
IPR002453 - Beta_tubulin
IPR008280 - Tub_FtsZ_C
IPR000217 - Tubulin
IPR018316 - Tubulin/FtsZ_2-layer-sand-dom
IPR023123 - Tubulin_C
IPR017975 - Tubulin_CS
IPR003008 - Tubulin_FtsZ_GTPase

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)
PF00091 - Tubulin/FtsZ family, GTPase domain
PF03953 - Tubulin C-terminal domain
PF13853 - Olfactory receptor

SCOP Domains:
52490 - Tubulin nucleotide-binding domain-like
55307 - Tubulin C-terminal domain-like
81321 - Family A G protein-coupled receptor-like

ModBase Predicted Comparative 3D Structure on Q13509
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003924 GTPase activity
GO:0005200 structural constituent of cytoskeleton
GO:0005515 protein binding
GO:0005525 GTP binding
GO:0042277 peptide binding

Biological Process:
GO:0000278 mitotic cell cycle
GO:0007010 cytoskeleton organization
GO:0007017 microtubule-based process
GO:0007411 axon guidance
GO:0030182 neuron differentiation

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005856 cytoskeleton
GO:0005874 microtubule
GO:0015630 microtubule cytoskeleton
GO:0030424 axon
GO:0030425 dendrite
GO:0043025 neuronal cell body
GO:0070062 extracellular exosome
GO:0071944 cell periphery


-  Descriptions from all associated GenBank mRNAs
  AK311630 - Homo sapiens cDNA, FLJ18672.
AK024232 - Homo sapiens cDNA FLJ14170 fis, clone NT2RP2002105, highly similar to Melanocyte-stimulating hormone receptor.
FZ428591 - JP 2011500004-A/4: Methods For Assaying MC1R Variants And Mitochondrial Markers In Skin Samples.
HI565108 - Sequence 4 from Patent EP2217730.
JD037162 - Sequence 18186 from Patent EP1572962.
JD120095 - Sequence 101119 from Patent EP1572962.
AK225902 - Homo sapiens mRNA for Melanocyte stimulating hormone receptor variant, clone: FCC120B12.
AK054666 - Homo sapiens cDNA FLJ30104 fis, clone BNGH41000169, highly similar to Melanocyte-stimulating hormone receptor.
JD131735 - Sequence 112759 from Patent EP1572962.
JD414417 - Sequence 395441 from Patent EP1572962.
BC007856 - Homo sapiens melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor), mRNA (cDNA clone MGC:14337 IMAGE:4298428), complete cds.
JD393188 - Sequence 374212 from Patent EP1572962.
JD516915 - Sequence 497939 from Patent EP1572962.
JD370440 - Sequence 351464 from Patent EP1572962.
JD384017 - Sequence 365041 from Patent EP1572962.
JD421320 - Sequence 402344 from Patent EP1572962.
JD165766 - Sequence 146790 from Patent EP1572962.
JD344382 - Sequence 325406 from Patent EP1572962.
BC080622 - Homo sapiens melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor), mRNA (cDNA clone MGC:99464 IMAGE:6267157), complete cds.
JD334836 - Sequence 315860 from Patent EP1572962.
X67594 - H.sapiens mRNA for MSH receptor.
JD382811 - Sequence 363835 from Patent EP1572962.
JD437414 - Sequence 418438 from Patent EP1572962.
BC020171 - Homo sapiens cDNA clone IMAGE:3543976, **** WARNING: chimeric clone ****.
JD435218 - Sequence 416242 from Patent EP1572962.
JD435727 - Sequence 416751 from Patent EP1572962.
CU675837 - Synthetic construct Homo sapiens gateway clone IMAGE:100018880 5' read MC1R mRNA.
DQ893267 - Synthetic construct clone IMAGE:100005897; FLH195777.01X; RZPDo839G02152D melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) (MC1R) gene, encodes complete protein.
DQ896597 - Synthetic construct Homo sapiens clone IMAGE:100011057; FLH195773.01L; RZPDo839G02151D melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) (MC1R) gene, encodes complete protein.
BT006971 - Homo sapiens tubulin, beta, 4 mRNA, complete cds.
JD104461 - Sequence 85485 from Patent EP1572962.
JD077454 - Sequence 58478 from Patent EP1572962.
JD548905 - Sequence 529929 from Patent EP1572962.
AK292219 - Homo sapiens cDNA FLJ77784 complete cds.
LF384493 - JP 2014500723-A/191996: Polycomb-Associated Non-Coding RNAs.
AK314616 - Homo sapiens cDNA, FLJ95457, highly similar to Homo sapiens tubulin, beta, 4 (TUBB4), mRNA.
AK307201 - Homo sapiens cDNA, FLJ97149.
AK058140 - Homo sapiens cDNA FLJ25411 fis, clone TST03333, highly similar to TUBULIN BETA-3 CHAIN.
AK223039 - Homo sapiens mRNA for tubulin, beta, 4 variant, clone: JTH08432.
BC000748 - Homo sapiens tubulin, beta 3, mRNA (cDNA clone MGC:2411 IMAGE:2823044), complete cds.
BC003021 - Homo sapiens tubulin, beta 3, mRNA (cDNA clone MGC:4055 IMAGE:2823044), complete cds.
BC064975 - Homo sapiens tubulin, beta 3, mRNA (cDNA clone IMAGE:6152050), with apparent retained intron.
CU674384 - Synthetic construct Homo sapiens gateway clone IMAGE:100018303 5' read TUBB3 mRNA.
AB590840 - Synthetic construct DNA, clone: pFN21AE1913, Homo sapiens TUBB3 gene for tubulin, beta 3, without stop codon, in Flexi system.
KJ893021 - Synthetic construct Homo sapiens clone ccsbBroadEn_02415 TUBB3 gene, encodes complete protein.
AF427491 - Homo sapiens class III beta tubulin mRNA, complete cds.
U47634 - Human beta-tubulin class III isotype (beta-3) mRNA, complete cds.
S62643 - beta-tubulin {EST} [human, mRNA Partial, 300 nt].
AK122757 - Homo sapiens cDNA FLJ16289 fis, clone OCBBF2009920, highly similar to TUBULIN BETA-3 CHAIN.
BC001678 - Homo sapiens tubulin, beta 3, mRNA (cDNA clone IMAGE:2821278), partial cds.
AK127418 - Homo sapiens cDNA FLJ45510 fis, clone BRTHA2020910, highly similar to Tubulin beta-4 chain.
BC047518 - Homo sapiens tubulin, beta 3, mRNA (cDNA clone IMAGE:5276469), partial cds.
JD025413 - Sequence 6437 from Patent EP1572962.
JD474669 - Sequence 455693 from Patent EP1572962.
LF328861 - JP 2014500723-A/136364: Polycomb-Associated Non-Coding RNAs.
LF331432 - JP 2014500723-A/138935: Polycomb-Associated Non-Coding RNAs.
DQ587200 - Homo sapiens piRNA piR-54312, complete sequence.
LF375197 - JP 2014500723-A/182700: Polycomb-Associated Non-Coding RNAs.
JD080012 - Sequence 61036 from Patent EP1572962.
LF375198 - JP 2014500723-A/182701: Polycomb-Associated Non-Coding RNAs.
JD404707 - Sequence 385731 from Patent EP1572962.
JD187688 - Sequence 168712 from Patent EP1572962.
JD123353 - Sequence 104377 from Patent EP1572962.
JD121867 - Sequence 102891 from Patent EP1572962.
LF375199 - JP 2014500723-A/182702: Polycomb-Associated Non-Coding RNAs.
MA620070 - JP 2018138019-A/191996: Polycomb-Associated Non-Coding RNAs.
MA564438 - JP 2018138019-A/136364: Polycomb-Associated Non-Coding RNAs.
MA567009 - JP 2018138019-A/138935: Polycomb-Associated Non-Coding RNAs.
MA610774 - JP 2018138019-A/182700: Polycomb-Associated Non-Coding RNAs.
MA610775 - JP 2018138019-A/182701: Polycomb-Associated Non-Coding RNAs.
MA610776 - JP 2018138019-A/182702: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04540 - Gap junction
hsa05130 - Pathogenic Escherichia coli infection

Reactome (by CSHL, EBI, and GO)

Protein Q13509 (Reactome details) participates in the following event(s):

R-HSA-389980 unfolded actin/tubulin associates with prefoldin
R-HSA-389970 Actin/tubulin:prefoldin complex associates with CCT/TriC
R-HSA-389954 Hydrolysis of ATP and release of tubulin folding intermediate from CCT/TriC
R-HSA-389961 ADP is exchanged for ATP in the (ADP:CCT/TriC):tubulin complex
R-HSA-389956 Beta-tubulin:GTP + Cofactor A -> Beta-tubulin:GTP: Cofactor A
R-HSA-389969 Beta-tubulin:GTP + Cofactor D -> Beta-tubulin:GTP: Cofactor D
R-HSA-389974 Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E:Cofactor C-> Beta-tubulin:GDP :alpha-tubulin:GTP heterodimer +Cofactor E+ Cofactor D+ Cofactor C+ Pi
R-HSA-8955706 TTL ligates L-Tyr to the carboxy terminus of alpha-tubulin
R-HSA-8955712 TTCP hydrolyzes the terminal L-Tyr residue from alpha-tubulin
R-HSA-389955 Beta-tubulin:GTP: Cofactor A+ Cofactor D -> Beta-tubulin:GTP:Cofactor D + Cofactor A
R-HSA-389976 Beta-tubulin:GTP:Cofactor D+alpha-tubulin:GTP:Cofactor E-> Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E
R-HSA-389964 Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E+ Cofactor C-> Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E:Cofactor C
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC
R-HSA-389977 Post-chaperonin tubulin folding pathway
R-HSA-8955332 Carboxyterminal post-translational modifications of tubulin
R-HSA-390466 Chaperonin-mediated protein folding
R-HSA-391251 Protein folding
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: BT006971, NM_006086, NP_006077, Q13509, Q9BTZ0, Q9BW10, TBB3_HUMAN, TUBB4
UCSC ID: uc002fpf.2
RefSeq Accession: NM_006086
Protein: Q13509 (aka TBB3_HUMAN or TBB4_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TUBB3:
cfeom (Congenital Fibrosis of the Extraocular Muscles)
tubulin-ov (Tubulinopathies Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: BT006971.1
exon count: 5CDS single in 3' UTR: no RNA size: 2394
ORF size: 2394CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3749.00frame shift in genome: no % Coverage: 99.92
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.