Details for: TUBB1

Gene ID: 81027

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TUBB1

Ensembl ID: ENSG00000101162

Description: tubulin beta 1 class VI

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • erythrocyte CL0000232
    CSI 9.94
    rCSI 22.55%
    PRS 94.93
  • promyelocyte CL0000836
    CSI 7.63
    rCSI 11.01%
    PRS 97.13
  • B cell CL0000236
    CSI 5.05
    rCSI 6.76%
    PRS 94.7
  • platelet CL0000233
    CSI 4.41
    rCSI 18.31%
    PRS 93.21
  • megakaryocyte CL0000556
    CSI 4.09
    rCSI 17.74%
    PRS 96
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.42
    rCSI 2.18%
    PRS 96.27
  • primitive red blood cell CL0002355
    CSI 1.4
    rCSI 7.53%
    PRS 96.74
  • erythroblast CL0000765
    CSI 1
    rCSI 2.65%
    PRS 96.16

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TUBB1](/details-gene/81027) (Tubulin Beta 1 Class VI) is a protein-coding gene located on chromosome 20q13.32 that encodes the tubulin beta-1 chain, a critical component of the microtubule cytoskeleton. As a structural constituent of microtubules, [TUBB1](/details-gene/81027) is fundamentally involved in processes requiring cytoskeletal dynamics, including cell division, intracellular transport, and maintenance of cell shape. Expression data highlights its pronounced significance within the hematopoietic system, particularly in cells of the erythroid and megakaryocytic lineages such as [erythrocyte](/details-cell/CL0000232)s, [platelet](/details-cell/CL0000233)s, and their progenitors. Mutations in this gene are associated with congenital macrothrombocytopenia, underscorining its specialized and essential role in platelet formation ([Link](https://doi.org/10.1182/blood-2008-06-162610)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [TUBB1](/details-gene/81027) indicates a highly specialized function within the hematopoietic compartment. The gene shows its highest significance in mature, anucleated cells and their immediate precursors, suggesting a role in the terminal stages of differentiation and cellular function. The most significant expression is observed in the erythroid lineage, including [erythrocyte](/details-cell/CL0000232) (CSI: 9.94), [primitive red blood cell](/details-cell/CL0002355) (CSI: 1.40), and [erythroblast](/details-cell/CL0000765) (CSI: 1.00). This suggests that the [TUBB1](/details-gene/81027) isotype is a key component of the microtubule network required for enucleation and the establishment of the characteristic biconcave shape of red blood cells. Concurrently, [TUBB1](/details-gene/81027) is a defining marker for the megakaryocyte-platelet lineage. Its high significance in [platelet](/details-cell/CL0000233)s (CSI: 4.41), [megakaryocyte](/details-cell/CL0000556)s (CSI: 4.09), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)s (CSI: 2.42) is consistent with its established role in proplatelet formation, a process heavily dependent on microtubule sliding and reorganization. A functional polymorphism in [TUBB1](/details-gene/81027) has been shown to modulate platelet function and structure, influencing cardiovascular disease risk ([Link](https://doi.org/10.1182/blood-2005-02-0723)). Additionally, high significance in [promyelocyte](/details-cell/CL0000836)s (CSI: 7.63) and [B cell](/details-cell/CL0000236)s (CSI: 5.05) suggests a broader role in the cytoskeletal architecture of various hematopoietic cells. ## Pathways and Molecular Function The molecular functions of [TUBB1](/details-gene/81027) are centered on its role as a [Structural constituent of cytoskeleton](/details-ontology/GO:0005200), with associated [Gtp binding](/details-ontology/GO:0005525) and [Gtpase activity](/details-ontology/GO:0003924) essential for the dynamic polymerization and depolymerization of microtubules. Its localization to the [Microtubule](/details-ontology/GO:0005874) and the [Mitotic spindle](/details-ontology/GO:0072686) underpins its involvement in core biological processes. Consistent with its role in hematopoietic cell development, [TUBB1](/details-gene/81027) is annotated to pathways such as [Factors involved in megakaryocyte development and platelet production](/details-pathway/R-HSA-983231) and [Hemostasis](/details-pathway/R-HSA-109582). These annotations directly reflect its high expression significance in [megakaryocyte](/details-cell/CL0000556)s and [platelet](/details-cell/CL0000233)s and its clinical relevance in thrombocytopenia. Furthermore, its involvement in the [Cell cycle, mitotic](/details-pathway/R-HSA-69278) pathway, particularly [M phase](/details-pathway/R-HSA-68886), is a general feature of tubulin proteins and is critical for the proliferation of progenitor cells like the [promyelocyte](/details-cell/CL0000836) and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050). The gene is also implicated in a vast array of other fundamental cellular processes, including [Vesicle-mediated transport](/details-pathway/R-HSA-5653656), [Axon guidance](/details-pathway/R-HSA-422475), and signaling within the [Immune system](/details-pathway/R-HSA-168256), highlighting the ubiquitous importance of the microtubule network it helps form. ## Research Directions The specific expression pattern of [TUBB1](/details-gene/81027) within hematopoietic lineages, coupled with its known role in genetic disorders, provides fertile ground for further investigation. **Proposed Hypotheses:** 1. Given its high significance in [erythrocyte](/details-cell/CL0000232)s and the crucial role of the marginal band of microtubules in red blood cell morphology, we hypothesize that specific post-translational modifications of the [TUBB1](/details-gene/81027) protein are essential for maintaining erythrocyte membrane integrity and flexibility. Deficiencies in these modifications may underlie certain hereditary spherocytoses or other red cell membrane disorders not attributable to canonical membrane protein defects. 2. Based on its critical role in platelet formation, we hypothesize that [TUBB1](/details-gene/81027) acts as a primary scaffold for the recruitment of specific motor proteins (e.g., kinesins and dyneins) that drive the transport of granules and organelles into nascent proplatelets. The specific [TUBB1](/details-gene/81027) isotype may confer unique binding properties or track characteristics for these motors, and disruption of this interaction could be a unifying mechanism for different forms of congenital macrothrombocytopenia. **Experimental Approach to Test Hypothesis 2:** To investigate the role of [TUBB1](/details-gene/81027) as a specific scaffold for motor proteins in [megakaryocyte](/details-cell/CL0000556)s, one could employ a combination of proteomic and cell biology techniques. Differentiating human CD34+ hematopoietic stem cells into mature [megakaryocyte](/details-cell/CL0000556)s *in vitro* would provide a relevant model system. Using proximity-dependent biotinylation (e.g., BioID) with [TUBB1](/details-gene/81027) as the bait, one could identify its specific interactome during proplatelet formation. Candidate motor proteins identified could then be validated by co-immunoprecipitation and high-resolution microscopy. Functional validation would involve CRISPR-Cas9-mediated knockout of [TUBB1](/details-gene/81027) or introduction of mutations that disrupt a putative motor-binding domain, followed by live-cell imaging to track organelle transport and assess defects in proplatelet extension and fragmentation. **Therapeutic Potential:** As a therapeutic target, direct inhibition of [TUBB1](/details-gene/81027) is likely to be poorly tolerated systemically due to the essential role of microtubules in all cells, mirroring the toxicity of conventional tubulin-targeting chemotherapeutics. However, its highly specific role in hematopoiesis suggests potential for more nuanced approaches. For genetic disorders like [TUBB1](/details-gene/81027)-associated macrothrombocytopenia, the therapeutic goal would be functional restoration, not inhibition. This could potentially be achieved via hematopoietic stem cell-based gene therapy to introduce a functional copy of the gene. Furthermore, small molecules that specifically stabilize the [TUBB1](/details-gene/81027) isotype or correct pathogenic conformational changes could represent a viable strategy for treating these rare hematological conditions.

Genular Protein ID: 2867369585

Symbol: TBB1_HUMAN

Name: Tubulin beta-1 chain

UniProtKB Accession Codes:

Q9H4B7

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEBI 10 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 11 DrugCentral 1 EMBL 3 Ensembl 1 GO 18 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OGP 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 31 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12665801

Title: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.

PubMed ID: 12665801

DOI: 10.1038/nbt810

PubMed ID: 16371510

Title: Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-dependent kinase Cdk1.

PubMed ID: 16371510

DOI: 10.1091/mbc.e05-07-0621

PubMed ID: 18347012

Title: RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules.

PubMed ID: 18347012

DOI: 10.1074/jbc.m709397200

PubMed ID: 19524510

Title: Evolutionary divergence of enzymatic mechanisms for posttranslational polyglycylation.

PubMed ID: 19524510

DOI: 10.1016/j.cell.2009.05.020

PubMed ID: 20191564

Title: Tumoral and tissue-specific expression of the major human beta-tubulin isotypes.

PubMed ID: 20191564

DOI: 10.1002/cm.20436

PubMed ID: 26875866

Title: Graded control of microtubule severing by tubulin glutamylation.

PubMed ID: 26875866

DOI: 10.1016/j.cell.2016.01.019

PubMed ID: 15956286

Title: The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure.

PubMed ID: 15956286

DOI: 10.1182/blood-2005-02-0723

PubMed ID: 18849486

Title: Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly.

PubMed ID: 18849486

DOI: 10.1182/blood-2008-06-162610

Sequence Information:

  • Length: 451
  • Mass: 50327
  • Checksum: 6A3E5208C1C89AE4
  • Sequence:
    • MREIVHIQIG QCGNQIGAKF WEMIGEEHGI DLAGSDRGAS ALQLERISVY YNEAYGRKYV 
PRAVLVDLEP GTMDSIRSSK LGALFQPDSF VHGNSGAGNN WAKGHYTEGA ELIENVLEVV 
RHESESCDCL QGFQIVHSLG GGTGSGMGTL LMNKIREEYP DRIMNSFSVM PSPKVSDTVV 
EPYNAVLSIH QLIENADACF CIDNEALYDI CFRTLKLTTP TYGDLNHLVS LTMSGITTSL 
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTAQGSQQ YRALSVAELT QQMFDARNTM 
AACDLRRGRY LTVACIFRGK MSTKEVDQQL LSVQTRNSSC FVEWIPNNVK VAVCDIPPRG 
LSMAATFIGN NTAIQEIFNR VSEHFSAMFK RKAFVHWYTS EGMDINEFGE AENNIHDLVS 
EYQQFQDAKA VLEEDEEVTE EAEMEPEDKG H