Human Gene TUBB4A (uc002mfg.1)
  Description: Homo sapiens tubulin, beta 4A class IVa (TUBB4A), mRNA.
RefSeq Summary (NM_006087): This gene encodes a member of the beta tubulin family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene cause hypomyelinating leukodystrophy-6 and autosomal dominant torsion dystonia-4. Alternate splicing results in multiple transcript variants encoding different isoforms. A pseudogene of this gene is found on chromosome X. [provided by RefSeq, Jan 2014].
Transcript (Including UTRs)
   Position: hg19 chr19:6,494,330-6,502,330 Size: 8,001 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg19 chr19:6,495,175-6,502,223 Size: 7,049 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:6,494,330-6,502,330)mRNA (may differ from genome)Protein (444 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TBB4A_HUMAN
DESCRIPTION: RecName: Full=Tubulin beta-4A chain; AltName: Full=Tubulin 5 beta; AltName: Full=Tubulin beta-4 chain;
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.
SUBUNIT: Dimer of alpha and beta chains.
INTERACTION: P22736:NR4A1; NbExp=2; IntAct=EBI-355007, EBI-721550;
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
TISSUE SPECIFICITY: Major isotype in brain, where it represents 46% of all beta-tubulins.
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).
SIMILARITY: Belongs to the tubulin family.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TUBB4A
Diseases sorted by gene-association score: leukodystrophy, hypomyelinating, 6* (1687), dystonia 4, torsion, autosomal dominant* (1590), dystonia 4* (148), dystonia (26), hypomyelinating leukodystrophy (25), leukodystrophy (20), torsion dystonia 4 (19), spasmodic dysphonia (11), leukodystrophy, hypomyelinating, 5 (9), hereditary dystonia (8), hypomyelinating leukoencephalopathy (7)
* = 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
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 616.58 RPKM in Brain - Cerebellum
Total median expression: 3559.49 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.70107-0.240 Picture PostScript Text
3' UTR -161.25845-0.191 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:
PF00091 - Tubulin/FtsZ family, GTPase domain
PF03953 - Tubulin C-terminal domain

SCOP Domains:
52490 - Tubulin nucleotide-binding domain-like
55307 - Tubulin C-terminal domain-like

ModBase Predicted Comparative 3D Structure on P04350
FrontTopSide
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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 orthologNo orthologNo orthologNo orthologNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
     SGD
     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:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005525 GTP binding

Biological Process:
GO:0000086 G2/M transition of mitotic cell cycle
GO:0007010 cytoskeleton organization
GO:0007017 microtubule-based process
GO:0010389 regulation of G2/M transition of mitotic cell cycle
GO:0031115 negative regulation of microtubule polymerization
GO:0097711 ciliary basal body docking

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005874 microtubule
GO:0005929 cilium
GO:0005930 axoneme
GO:0033269 internode region of axon
GO:0042995 cell projection
GO:0043025 neuronal cell body
GO:0043209 myelin sheath
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK075307 - Homo sapiens cDNA FLJ90826 fis, clone Y79AA1001530, highly similar to Tubulin beta-4 chain.
BC013683 - Homo sapiens tubulin, beta 4, mRNA (cDNA clone MGC:18193 IMAGE:4155617), complete cds.
LP896126 - Sequence 990 from Patent EP3253886.
BC006570 - Homo sapiens tubulin, beta 4, mRNA (cDNA clone MGC:4270 IMAGE:3603726), complete cds.
AK095202 - Homo sapiens cDNA FLJ37883 fis, clone BRSTN2010569, highly similar to TUBULIN BETA-2 CHAIN.
JD055552 - Sequence 36576 from Patent EP1572962.
JD072808 - Sequence 53832 from Patent EP1572962.
JD513780 - Sequence 494804 from Patent EP1572962.
JD459841 - Sequence 440865 from Patent EP1572962.
JD318155 - Sequence 299179 from Patent EP1572962.
JD132946 - Sequence 113970 from Patent EP1572962.
AK294102 - Homo sapiens cDNA FLJ52536 complete cds, highly similar to Tubulin beta-4 chain.
JD439517 - Sequence 420541 from Patent EP1572962.
JD199922 - Sequence 180946 from Patent EP1572962.
AK295917 - Homo sapiens cDNA FLJ53341 complete cds, highly similar to Tubulin beta-4 chain.
JD527356 - Sequence 508380 from Patent EP1572962.
JD390807 - Sequence 371831 from Patent EP1572962.
AK293503 - Homo sapiens cDNA FLJ55189 complete cds, highly similar to Tubulin beta-4 chain.
JD416961 - Sequence 397985 from Patent EP1572962.
JD404021 - Sequence 385045 from Patent EP1572962.
JD394533 - Sequence 375557 from Patent EP1572962.
JD130576 - Sequence 111600 from Patent EP1572962.
JD323233 - Sequence 304257 from Patent EP1572962.
JD136481 - Sequence 117505 from Patent EP1572962.
KJ898197 - Synthetic construct Homo sapiens clone ccsbBroadEn_07591 TUBB4A gene, encodes complete protein.
EU831818 - Synthetic construct Homo sapiens clone HAIB:100066847; DKFZo008G0221 tubulin, beta 4 protein (TUBB4) gene, encodes complete protein.
EU831895 - Synthetic construct Homo sapiens clone HAIB:100066924; DKFZo004G0222 tubulin, beta 4 protein (TUBB4) gene, encodes complete protein.
AB590868 - Synthetic construct DNA, clone: pFN21AE1910, Homo sapiens TUBB4 gene for tubulin, beta 4, without stop codon, in Flexi system.
JD471470 - Sequence 452494 from Patent EP1572962.
DQ587200 - Homo sapiens piRNA piR-54312, complete sequence.
LF331432 - JP 2014500723-A/138935: Polycomb-Associated Non-Coding RNAs.
LF328861 - JP 2014500723-A/136364: Polycomb-Associated Non-Coding RNAs.
JD474669 - Sequence 455693 from Patent EP1572962.
CU675455 - Synthetic construct Homo sapiens gateway clone IMAGE:100017280 5' read TUBB4 mRNA.
JD129009 - Sequence 110033 from Patent EP1572962.
JD269458 - Sequence 250482 from Patent EP1572962.
JD406049 - Sequence 387073 from Patent EP1572962.
JD404946 - Sequence 385970 from Patent EP1572962.
MA567009 - JP 2018138019-A/138935: Polycomb-Associated Non-Coding RNAs.
MA564438 - JP 2018138019-A/136364: 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 P04350 (Reactome details) participates in the following event(s):

R-HSA-380272 Plk1-mediated phosphorylation of Nlp
R-HSA-380283 Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome
R-HSA-380294 Loss of C-Nap-1 from centrosomes
R-HSA-380311 Recruitment of Plk1 to centrosomes
R-HSA-380455 Recruitment of CDK11p58 to the centrosomes
R-HSA-380303 Dissociation of Phospho-Nlp from the centrosome
R-HSA-5626220 C2CD3 binds the mother centriole
R-HSA-389980 unfolded actin/tubulin associates with prefoldin
R-HSA-380508 Translocation of NuMA to the centrosomes
R-HSA-2574845 AJUBA binds centrosome-associated AURKA
R-HSA-8853405 TPX2 binds AURKA at centrosomes
R-HSA-3000319 BORA binds PLK1 and AURKA
R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation
R-HSA-3000310 AURKA phosphorylates PLK1
R-HSA-5626223 C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole
R-HSA-5626681 Recruitment of transition zone proteins
R-HSA-5626227 CP110 and CEP97 dissociate from the centriole
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-380316 Association of NuMA with microtubules
R-HSA-8853419 TPX2 promotes AURKA autophosphorylation
R-HSA-5626228 The distal appendage proteins recruit TTBK2
R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
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-5626699 MARK4 binds ODF2 in the centriole
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-5617816 RAB3IP stimulates nucleotide exchange on RAB8A
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-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-8854518 AURKA Activation by TPX2
R-HSA-380287 Centrosome maturation
R-HSA-5617833 Cilium Assembly
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-68877 Mitotic Prometaphase
R-HSA-69275 G2/M Transition
R-HSA-1852241 Organelle biogenesis and maintenance
R-HSA-8955332 Carboxyterminal post-translational modifications of tubulin
R-HSA-390466 Chaperonin-mediated protein folding
R-HSA-391251 Protein folding
R-HSA-68886 M Phase
R-HSA-453274 Mitotic G2-G2/M phases
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: B3KQP4, NM_006087, NP_006078, P04350, Q969E5, TBB4A_HUMAN, TUBB4, TUBB5, uc002mff.1
UCSC ID: uc002mfg.1
RefSeq Accession: NM_006087
Protein: P04350 (aka TBB4A_HUMAN)
CCDS: CCDS12168.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TUBB4A:
hsp (Hereditary Spastic Paraplegia Overview)
tubb4a-leuk (TUBB4A-Related Leukodystrophy)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_006087.2
exon count: 4CDS single in 3' UTR: no RNA size: 2318
ORF size: 1335CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1812.00frame shift in genome: no % Coverage: 98.66
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.