TUBA4A tubulin alpha 4a [Homo sapiens (human)] - Gene

Summary

Official Symbol: TUBA4Aprovided by HGNC
Official Full Name: tubulin alpha 4aprovided by HGNC
Primary source: HGNC:HGNC:12407
See related: Ensembl:ENSG00000127824 MIM:191110; AllianceGenome:HGNC:12407
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALS22; TUBA1; H2-ALPHA
Summary: Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of 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 and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
Expression: Broad expression in skin (RPKM 72.2), brain (RPKM 48.6) and 20 other tissues See more
Orthologs: all
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Genomic context

Location:: 2q35

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (219249710..219254740, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (219734477..219739787, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (220114432..220119462, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Novel TUBA4A variant causes congenital myopathy with focal myofibrillar disorganisation.
Title: Novel TUBA4A variant causes congenital myopathy with focal myofibrillar disorganisation.
A new genetic cause of spastic ataxia: the p.Glu415Lys variant in TUBA4A.
Title: A new genetic cause of spastic ataxia: the p.Glu415Lys variant in TUBA4A.
In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration.
Title: In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration.
Mice carrying a missense mutation in the Tuba4a gene, and a patient with a monoallelic double missense mutation in the TUBA4A gene displayed macrothrombocytopenia and structural abnormalities in the marginal band of platelets.
Title: An essential role for α4A-tubulin in platelet biogenesis.
The frequency of TUBA4A mutations suggests that TUBA4A is a rare cause of Amotrophic Lateral Sclerosis in Chinese patients.
Title: Screening for TUBA4A mutations in a large Chinese cohort of patients with ALS: re-evaluating the pathogenesis of TUBA4A in ALS.
Data indicate a microRNA-1825/TBCB/TUBA4A pathway as a putative pathogenic cascade in both familial ALS (fALS) and both sporadic (sALS).
Title: Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS.
The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset.
Title: Elevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations.
alphaTubulin expression might be an independent prognostic factor for pancreatic cancer after surgical resection
Title: Increased expression of αTubulin is associated with poor prognosis in patients with pancreatic cancer after surgical resection.
Its mutations were seen in patients with ALS and frontotemporal dementia.
Title: Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients.
TUBA4A mutations are not associated with FTD.
Title: Assessing the role of TUBA4A gene in frontotemporal degeneration.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Amyotrophic lateral sclerosis type 22 MedGen: C4015512 OMIM: 616208 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs

EBI GWAS Catalog

Description
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify tubulin alpha 4a protein (TUBA4A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	env	The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120	PubMed
	env	The binding of HIV-1 gp120 to CD4+-permissive cells increases the level of acetylated alpha-tubulin in a CD4-dependent manner; overexpression of Histone Deacetylase 6 (HDAC6) inhibits the acetylation of alpha-tubulin and prevents HIV-1-cell fusion	PubMed
Envelope surface glycoprotein gp160, precursor	env	Treatment of cells with actin-depolymerizing agents or tubulin polymerization inhibitors largely reduces the percentage of cells with capped HIV-1 Gag and Env, indicating an intact actin and tubulin cytoskeleton is required for efficient assembly of HIV-1	PubMed
Envelope transmembrane glycoprotein gp41	env	Expression of HIV-1 gp41 cytoplasmic domain reduces acetylated tubulin alpha and interferes with virus-cell fusion	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify tubulin alpha 4a protein (TUBA4A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify tubulin alpha 4a protein (TUBA4A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify tubulin alpha 4a protein (TUBA4A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	gag	Treatment of cells with actin-depolymerizing agents or tubulin polymerization inhibitors largely reduces the percentage of cells with capped HIV-1 Gag and Env, indicating an intact actin and tubulin cytoskeleton is required for efficient assembly of HIV-1	PubMed
Rev	rev	HIV-1 Rev interacting protein, tubulin alpha 4a (TUBA4A), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
	rev	Rev acts to depolymerize microtubules that are formed by tubulin, an effect that is observed during HIV-1 infection	PubMed
Tat	tat	HIV-1 Tat K29A, K50R, and K51R lysine mutations downregulate the proportion of soluble tubulin in cells, while the majority of other lysine mutations upregulate the percentage of soluble tubulin compared with the wild-type	PubMed
	tat	HIV-1 Tat causes a dramatic decrease in alpha-tubulin staining, which indicates disruption of the cytoskeleton organization in human intestinal epithelial cells	PubMed
	tat	HIV-1 Tat (specifically, amino acids 38-72), enhances tubulin polymerization and triggers the mitochondrial pathway to induce T cell apoptosis as shown in vitro by the release of cytochrome c from isolated mitochondria	PubMed
	tat	HIV-1 Tat (amino acids 36-39) binds tubulin alpha/beta dimers and polymerized microtubules leading to the alteration of microtubule dynamics and activation of a mitochondria-dependent apoptotic pathway that is facilitated by the Bcl-2 relative Bim	PubMed
integrase	gag-pol	Co-immunoprecipitation shows interaction of HIV-1 IN with alpha-tubulin	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TUBA1__1214 (e-PCR)
- UniSTS:277847

GDB:181260 (e-PCR)
- UniSTS:155228

RH78682 (e-PCR)
- UniSTS:80224

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in microtubule cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in microtubule	IBA Inferred from Biological aspect of Ancestor more info
located_in microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: tubulin alpha-4A chain

Names: tubulin H2-alpha; tubulin alpha-1 chain; tubulin, alpha 1 (testis specific)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029913.1 RefSeqGene

Range

4999..9207

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001278552.2 → NP_001265481.1 tubulin alpha-4A chain isoform 2

See identical proteins and their annotated locations for NP_001265481.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' exon, which results in translation initiation at a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC068946, AK054731, AK299958

Consensus CDS

CCDS63131.1

UniProtKB/TrEMBL

A8JZY9

Related

ENSP00000375938.2, ENST00000392088.6

Conserved Domains (1) summary

PTZ00335
Location:1 → 433

PTZ00335; tubulin alpha chain; Provisional
NM_006000.3 → NP_005991.1 tubulin alpha-4A chain isoform 1

See identical proteins and their annotated locations for NP_005991.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC068946, AK054731, BP346611

Consensus CDS

CCDS2438.1

UniProtKB/Swiss-Prot

A8MUB1, B3KNQ6, P05215, P68366

UniProtKB/TrEMBL

A8JZY9

Related

ENSP00000248437.4, ENST00000248437.9

Conserved Domains (1) summary

PTZ00335
Location:1 → 448

PTZ00335; tubulin alpha chain; Provisional