Human Gene TUBA1A (uc009zlf.4) Description and Page Index
  Description: Homo sapiens tubulin, alpha 1a (TUBA1A), transcript variant 2, mRNA.
RefSeq Summary (NM_001270399): Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to the mouse and rat Tuba1 genes. Northern blot studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q. Mutations in this gene cause lissencephaly type 3 (LIS3) - a neurological condition characterized by microcephaly, intellectual disability, and early-onset epilepsy caused by defective neuronal migration. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017].
Transcript (Including UTRs)
   Position: hg19 chr12:49,578,578-49,583,107 Size: 4,530 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg19 chr12:49,578,793-49,582,202 Size: 3,410 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:49,578,578-49,583,107)mRNA (may differ from genome)Protein (451 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsH-INV
HGNCHPRDLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: TBA1A_HUMAN
DESCRIPTION: RecName: Full=Tubulin alpha-1A chain; AltName: Full=Alpha-tubulin 3; AltName: Full=Tubulin B-alpha-1; AltName: Full=Tubulin alpha-3 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.
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
TISSUE SPECIFICITY: Expressed at a high level in fetal brain.
PTM: Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (TTCP) and tubulin tyrosine ligase (TTL), respectively (By similarity).
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: Acetylation of alpha-tubulins at Lys-40 stabilizes microtubules and affects affinity and processivity of microtubule motors. This modification has a role in multiple cellular functions, ranging from cell motility, cell cycle progression or cell differentiation to intracellular trafficking and signaling (By similarity).
DISEASE: Defects in TUBA1A are the cause of lissencephaly type 3 (LIS3) [MIM:611603]. LIS is characterized by a smooth brain surface due to the absence (agyria) or reduction (pachygyria) of surface convolutions. It is often associated with psychomotor retardation and seizures. LIS3 features include agyria or pachygyria or laminar heterotopia, severe mental retardation, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem.
SIMILARITY: Belongs to the tubulin family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TUBA1A
CDC HuGE Published Literature: TUBA1A
Positive Disease Associations: Lipoproteins, HDL
Related Studies:
  1. Lipoproteins, HDL
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: TUBA1A
Diseases sorted by gene-association score: lissencephaly 3* (1679), lissencephaly with cerebellar hypoplasia* (283), tubulinopathy-associated dysgyria* (202), lissencephaly (33), pachygyria (16), hydranencephaly (14), distal hereditary motor neuropathy, type ii (8), microlissencephaly (7), congenital nervous system abnormality (5), heterotopia, periventricular (5), miller-dieker lissencephaly syndrome (5), epileptic encephalopathy, early infantile, 15 (3), physical disorder (1), microcephaly (1), intellectual disability (1), retinitis pigmentosa (0)
* = 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: 890.35 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 7433.44 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 -381.94905-0.422 Picture PostScript Text
3' UTR -50.40215-0.234 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
IPR002452 - 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

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 Q71U36
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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:0005198 structural molecule activity
GO:0005200 structural constituent of cytoskeleton
GO:0005515 protein binding
GO:0005525 GTP binding
GO:0019904 protein domain specific 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:0030705 cytoskeleton-dependent intracellular transport
GO:0051301 cell division
GO:0097711 ciliary basal body docking

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005874 microtubule
GO:0005881 cytoplasmic microtubule
GO:0015630 microtubule cytoskeleton
GO:0036464 cytoplasmic ribonucleoprotein granule
GO:0043209 myelin sheath
GO:0045121 membrane raft
GO:0055037 recycling endosome
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BC057823 - Homo sapiens cDNA clone IMAGE:5303872, containing frame-shift errors.
K00557 - human alpha-tubulin mRNA, 3' end.
AK057842 - Homo sapiens cDNA FLJ25113 fis, clone CBR05706, highly similar to TUBULIN ALPHA-1 CHAIN.
BC006468 - Homo sapiens tubulin, alpha 1a, mRNA (cDNA clone MGC:2321 IMAGE:3528520), complete cds.
BC050637 - Homo sapiens tubulin, alpha 1a, mRNA (cDNA clone MGC:60126 IMAGE:6050536), complete cds.
AF141347 - Homo sapiens hum-a-tub2 alpha-tubulin mRNA, complete cds.
AK297775 - Homo sapiens cDNA FLJ53765 complete cds, highly similar to Tubulin alpha chain.
AF141348 - Homo sapiens hum-a-tub1 alpha-tubulin mRNA, partial cds.
JD120994 - Sequence 102018 from Patent EP1572962.
JD147033 - Sequence 128057 from Patent EP1572962.
AK289483 - Homo sapiens cDNA FLJ77713 complete cds, highly similar to Homo sapiens tubulin, alpha 3 (TUBA3), mRNA.
AK298838 - Homo sapiens cDNA FLJ53743 complete cds, highly similar to Tubulin alpha-3 chain.
DQ890579 - Synthetic construct clone IMAGE:100003209; FLH164104.01X; RZPDo839C09162D tubulin, alpha 3 (TUBA3) gene, encodes complete protein.
KJ892437 - Synthetic construct Homo sapiens clone ccsbBroadEn_01831 TUBA1A gene, encodes complete protein.
KR709985 - Synthetic construct Homo sapiens clone CCSBHm_00008725 TUBA1A (TUBA1A) mRNA, encodes complete protein.
KR709986 - Synthetic construct Homo sapiens clone CCSBHm_00008726 TUBA1A (TUBA1A) mRNA, encodes complete protein.
KR709987 - Synthetic construct Homo sapiens clone CCSBHm_00008730 TUBA1A (TUBA1A) mRNA, encodes complete protein.
KR709988 - Synthetic construct Homo sapiens clone CCSBHm_00008734 TUBA1A (TUBA1A) mRNA, encodes complete protein.
EU176481 - Synthetic construct Homo sapiens clone IMAGE:100011334; FLH164103.01L; RZPDo839C02253D tubulin, alpha 1a (TUBA1A) gene, encodes complete protein.
AB590174 - Synthetic construct DNA, clone: pFN21AE1483, Homo sapiens TUBA1A gene for tubulin, alpha 1a, without stop codon, in Flexi system.
JD440596 - Sequence 421620 from Patent EP1572962.
JD026159 - Sequence 7183 from Patent EP1572962.
JD026858 - Sequence 7882 from Patent EP1572962.
JD317441 - Sequence 298465 from Patent EP1572962.
JD036090 - Sequence 17114 from Patent EP1572962.
JD027868 - Sequence 8892 from Patent EP1572962.
JD033115 - Sequence 14139 from Patent EP1572962.
JD025802 - Sequence 6826 from Patent EP1572962.
JD029721 - Sequence 10745 from Patent EP1572962.
JD029285 - Sequence 10309 from Patent EP1572962.
JD027061 - Sequence 8085 from Patent EP1572962.
JD035518 - Sequence 16542 from Patent EP1572962.
JD024485 - Sequence 5509 from Patent EP1572962.
CU675419 - Synthetic construct Homo sapiens gateway clone IMAGE:100019466 5' read TUBA1A mRNA.
DQ589802 - Homo sapiens piRNA piR-56914, complete sequence.
JD032220 - Sequence 13244 from Patent EP1572962.
JD035670 - Sequence 16694 from Patent EP1572962.
JD034886 - Sequence 15910 from Patent EP1572962.
JD236714 - Sequence 217738 from Patent EP1572962.

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

BioCarta from NCI Cancer Genome Anatomy Project
h_mta3Pathway - Downregulated of MTA-3 in ER-negative Breast Tumors

Reactome (by CSHL, EBI, and GO)

Protein Q71U36 (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-389972 alpha-tubulin:GTP + Cofactor B -> alpha-tubulin:GTP: Cofactor B
R-HSA-389978 alpha-tubulin:GTP + Cofactor E -> alpha-tubulin:GTP:Cofactor E
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-8955712 TTCP hydrolyzes the terminal L-Tyr residue from alpha-tubulin
R-HSA-8955706 TTL ligates L-Tyr to the carboxy terminus of alpha-tubulin
R-HSA-389963 alpha-tubulin:GTP:Cofactor B +Cofactor E -> alpha-tubulin:GTP: Cofactor E +Cofactor B
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: A8K0B8, NM_001270399, NP_006000, P04687, P05209, Q71U36, TBA1A_HUMAN, TUBA3, uc009zlf.3
UCSC ID: uc009zlf.4
RefSeq Accession: NM_001270399
Protein: Q71U36 (aka TBA1A_HUMAN)
CCDS: CCDS8781.1, CCDS58227.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TUBA1A:
tubulin-ov (Tubulinopathies Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001270399.1
exon count: 4CDS single in 3' UTR: no RNA size: 2490
ORF size: 1356CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2431.00frame shift in genome: no % Coverage: 99.44
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.