Affinage

TUBD1

Tubulin delta chain · UniProt Q9UJT1

Round 2 corrected
Length
453 aa
Mass
51.0 kDa
Annotated
2026-04-28
53 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TUBD1 (delta-tubulin) is a non-canonical tubulin that functions as a core structural and regulatory component of centrioles, centrosomes, and cilia, with specialized roles in spermatogenesis. TUBD1 physically interacts with epsilon-tubulin and gamma-tubulin and is essential for centriole triplet microtubule integrity; in its absence, centrioles form de novo but are unstable and fail to undergo centriole-to-centrosome conversion, operating within a CEP295–CEP44–POC1B–TUBE1–TUBD1 biogenesis pathway (PMID:28906251, PMID:32060285). Through its role in ciliogenesis, TUBD1 is required for Hedgehog signaling, and loss-of-function causes ciliopathy-like airway disease in cattle (PMID:29290584, PMID:27225349). In male germ cells, TUBD1 stabilizes meiotic kinetochores, enables cytokinesis, and cooperates with KATNAL2 and KATNB1 to remodel the manchette for sperm head shaping, with its loss causing male sterility (PMID:40586731, PMID:10620804).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2000 High

    The initial question of where delta-tubulin resides and what it interacts with was resolved: TUBD1 localizes to centrosomes/centrioles independently of microtubules, physically interacts with gamma-tubulin, and in testis associates with the manchette perinuclear ring and centriolar vaults, establishing it as a centriole- and spermatid-associated non-canonical tubulin.

    Evidence Immunofluorescence, co-immunoprecipitation, immunoelectron microscopy, and subcellular fractionation in human and mouse cells and testis

    PMID:10620804 PMID:10753753

    Open questions at the time
    • No loss-of-function data to determine whether TUBD1 is structurally required at centrioles
    • Nature of the gamma-tubulin interaction (direct or bridged) was not resolved
    • Functional significance of nuclear localization in somatic cells remained unclear
  2. 2004 High

    TUBD1's spermatogenic roles were elaborated beyond centrioles: it was shown to be a structural component of intercellular bridges connecting sister spermatogenic cells and of the manchette perinuclear ring, implicating it in both cell cohesion and nuclear shaping during spermatogenesis, with a testis-enriched long isoform.

    Evidence Immunoelectron microscopy and isoform expression analysis (RT-PCR/Western blot) in mouse testis

    PMID:15081367

    Open questions at the time
    • No genetic evidence that TUBD1 is required for intercellular bridge function
    • Mechanism by which TUBD1 contributes to nuclear shaping was unknown
  3. 2016 Medium

    An in vivo loss-of-function phenotype was established: a TUBD1 missense mutation in cattle causes chronic airway disease resembling primary ciliary dyskinesia with high perinatal mortality, demonstrating that TUBD1 is required for functional motile cilia in the respiratory tract.

    Evidence Whole-genome sequencing and haplotype analysis in Braunvieh and Fleckvieh cattle with clinical pathological examination of homozygous calves

    PMID:27225349

    Open questions at the time
    • The specific centriolar or ciliary defect underlying the airway phenotype was not characterized ultrastructurally
    • Whether the same mutation causes human disease was not addressed
  4. 2017 High

    The structural requirement for TUBD1 at centrioles was definitively resolved: TUBD1 and epsilon-tubulin physically interact, and their knockout in human cells eliminates triplet microtubules, causing centriole instability and a futile cycle of de novo centriole formation and disintegration that can be rescued by paclitaxel-mediated microtubule stabilization.

    Evidence CRISPR knockout in human cells, electron microscopy, co-immunoprecipitation, paclitaxel rescue experiments

    PMID:28906251

    Open questions at the time
    • Whether TUBD1 directly incorporates into the centriole wall or acts catalytically was not distinguished
    • Stoichiometry and structure of the TUBD1–TUBE1 complex were not determined
  5. 2017 Medium

    TUBD1 was placed in the Hedgehog signaling pathway: a genome-wide CRISPR screen identified it as a positive regulator of Hh signaling through its ciliary function, linking centriole/cilium integrity to developmental signaling.

    Evidence Genome-wide CRISPR screen with Hh signaling and neural differentiation assays in cultured cells

    PMID:29290584

    Open questions at the time
    • Whether TUBD1 loss abolishes cilia entirely or impairs ciliary signaling selectively was not resolved
    • No direct measurement of ciliary structure in TUBD1-depleted cells in this study
  6. 2017 Medium

    Upstream regulation of TUBD1 expression was identified: angulin proteins ILDR1/ILDR2 regulate TUBD1 alternative splicing through interactions with splicing factors TRA2A, TRA2B, and SRSF1, establishing a mechanism controlling TUBD1 isoform production.

    Evidence siRNA knockdown and RT-PCR splicing analysis with co-immunoprecipitation of angulins with splicing factors in cultured cells

    PMID:28785060

    Open questions at the time
    • Functional consequence of altered TUBD1 splicing on centriole or cilia biology was not tested
    • Single-lab finding not independently confirmed
  7. 2020 High

    TUBD1 was positioned within a defined centriole maturation pathway: it functions alongside TUBE1 and POC1B downstream of CEP295 to enable centriole-to-centrosome conversion, and its depletion prevents centrosome maturation even when CEP295 remains centriole-bound.

    Evidence siRNA depletion, epistasis analysis, immunofluorescence, and electron microscopy in human cells

    PMID:32060285

    Open questions at the time
    • Direct biochemical interactions between TUBD1 and POC1B or CEP44 were not demonstrated
    • Whether TUBD1 acts in the centriole lumen, on the cytoplasmic surface, or both remained partially ambiguous
  8. 2025 High

    TUBD1's in vivo roles in mammalian spermatogenesis were comprehensively defined: conditional knockout in mouse germ cells causes sterility through failure to stabilize meiotic kinetochores, defective cytokinesis, and impaired manchette remodeling in cooperation with KATNAL2/KATNB1 for sperm head shaping.

    Evidence Conditional knockout mouse model with immunofluorescence, live imaging, and co-localization studies

    PMID:40586731

    Open questions at the time
    • Biochemical mechanism by which TUBD1 stabilizes kinetochores is not known
    • Whether TUBD1's meiotic function is through its centriolar role or an independent activity is unresolved
    • Relevance to human male infertility has not been tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: whether TUBD1 incorporates directly into the centriole microtubule wall or acts as an assembly factor, the atomic structure of the TUBD1–TUBE1 complex, and whether human TUBD1 mutations cause ciliopathy or male infertility.
  • No high-resolution structural data for TUBD1 or any TUBD1-containing complex
  • No human genetic disease association confirmed
  • Mechanism of TUBD1 action at kinetochores versus centrioles not distinguished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 4 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2 GO:0005634 nucleus 1
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-162582 Signal Transduction 1
Partners
CEP295CEP44KATNAL2KATNB1POC1BTUBE1TUBG1

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Delta-tubulin (TUBD1) localizes to centrosomes/centrioles independently of microtubules in human cells, with a distinct localization pattern from gamma-tubulin and epsilon-tubulin. Gamma-tubulin co-immunoprecipitates with delta-tubulin, indicating a physical interaction. In testis, delta-tubulin associates with the manchette perinuclear ring and centriolar vaults in elongating spermatids. Immunofluorescence localization, co-immunoprecipitation, cell fractionation Nature cell biology High 10620804
2000 Mouse delta-tubulin (TUBD1 ortholog) is highly expressed in testis, localizes to the perinuclear ring of the manchette, centriolar vaults, and principal piece of sperm flagellum in elongating spermatids. In somatic cell lines, delta-tubulin is both cytoplasmic and nuclear, does not co-localize with microtubules, and is enriched at spindle poles during mitosis. Gamma-tubulin co-immunoprecipitates with delta-tubulin. Immunofluorescence, subcellular fractionation, co-immunoprecipitation, immunoelectron microscopy Current biology High 10753753
2004 Delta-tubulin exists as two isoforms (long and short); the long isoform is predominantly expressed in testis. Delta-tubulin is a structural component of intercellular bridges connecting sister spermatogenic cells and of the perinuclear ring of the manchette, implicating it in nuclear shaping and spermatogenic cell cohesion during spermatogenesis. Immunofluorescence, immunoelectron microscopy, isoform expression analysis by RT-PCR/Western blot Developmental biology High 15081367
2017 Delta-tubulin (TUBD1) and epsilon-tubulin physically interact with each other. In delta-tubulin and epsilon-tubulin null mutant human cells, centrioles lack triplet microtubules and fail to undergo centriole maturation. Aberrant centrioles form de novo each cell cycle but are unstable and do not persist, leading to a futile cycle of centriole formation and disintegration. Centriole disintegration can be suppressed by paclitaxel treatment, indicating that triplet microtubule integrity is required for centriole inheritance. CRISPR knockout, immunofluorescence, electron microscopy, co-immunoprecipitation, paclitaxel rescue eLife High 28906251
2020 Impairment of TUBD1 (along with TUBE1 and POC1B) disturbs centriole microtubule integrity and prevents centriole-to-centrosome conversion, even when CEP295 is still bound to centrioles. TUBD1 functions in the CEP295–CEP44–POC1B–TUBE1–TUBD1 centriole biogenesis pathway, acting in the centriole lumen and on the cytoplasmic side, and is essential for centriole maturation. siRNA depletion, immunofluorescence, electron microscopy, epistasis analysis Nature communications High 32060285
2017 In a genome-wide CRISPR screen, TUBD1 was identified as a positive regulator of Hedgehog (Hh) signaling, specifically involved in ciliary functions. Loss of TUBD1 reduced pathway sensitivity in signaling and neural differentiation assays, consistent with a role in primary cilia required for Hh signal transduction. Genome-wide CRISPR screen, Hh signaling assays, neural differentiation assays Developmental cell Medium 29290584
2017 ILDR1 and ILDR2 (angulin proteins) regulate alternative pre-mRNA splicing of TUBD1 through binding to splicing factors TRA2A, TRA2B, and SRSF1. siRNA knockdown of endogenous ILDR1 and ILDR2 in cultured cells alters the alternative splicing pattern of TUBD1 (and IQCB1), establishing these angulin proteins as upstream regulators of TUBD1 isoform production. siRNA knockdown, RT-PCR splicing analysis, co-immunoprecipitation of angulin proteins with splicing factors Scientific reports Medium 28785060
2016 A missense mutation in TUBD1 (p.H210R) is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh cattle, with homozygous calves developing chronic airway disease resembling primary ciliary dyskinesia, demonstrating that TUBD1 loss-of-function causes defective cilia in the respiratory tract in vivo. Whole-genome sequencing, haplotype analysis, clinical pathological examination of homozygous calves BMC genomics Medium 27225349
2025 Conditional knockout of TUBD1 in mouse male germ cells causes sterility. TUBD1 stabilizes kinetochores during male meiosis, enabling meiotic progression, and is required for appropriate spindle polarity and cytokinesis. In haploid cells, TUBD1 works in partnership with the microtubule-severing enzymes KATNAL2 and KATNB1 to regulate manchette remodeling and sperm head shaping. Conditional knockout mouse model, immunofluorescence, live imaging, co-localization studies The Journal of cell biology High 40586731

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2000 Delta-tubulin and epsilon-tubulin: two new human centrosomal tubulins reveal new aspects of centrosome structure and function. Nature cell biology 128 10620804
2002 SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Molecular and cellular biology 126 12052866
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2017 Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nature communications 99 28986522
2017 CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog. Developmental cell 83 29290584
2013 Identification of alternative splicing events regulated by the oncogenic factor SRSF1 in lung cancer. Cancer research 69 24371231
2021 SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors. Proceedings of the National Academy of Sciences of the United States of America 64 33536335
2005 HIV-1 Tat protein enhances microtubule polymerization. Retrovirology 51 15691386
2017 Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells. eLife 50 28906251
2016 Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases. American journal of human genetics 45 27346689
2000 Tissue-specific expression and subcellular localisation of mammalian delta-tubulin. Current biology : CB 44 10753753
2004 Delta-tubulin is a component of intercellular bridges and both the early and mature perinuclear rings during spermatogenesis. Developmental biology 41 15081367
2020 CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion. Nature communications 40 32060285
2016 A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle. BMC genomics 39 27225349
2022 In-Depth In Vivo Crosslinking in Minutes by a Compact, Membrane-Permeable, and Alkynyl-Enrichable Crosslinker. Analytical chemistry 38 35575683
2009 Genetic variation in the chromosome 17q23 amplicon and breast cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 38 19454617
2021 Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer. Nature communications 36 34373451
2010 Centrosome-related genes, genetic variation, and risk of breast cancer. Breast cancer research and treatment 36 20508983
2005 HIV-1 Tat, apoptosis and the mitochondria: a tubulin link? Retrovirology 29 15698476
2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. Diabetes care 28 20628086
2020 Circular RNA TUBD1 Acts as the miR-146a-5p Sponge to Affect the Viability and Pro-Inflammatory Cytokine Production of LX-2 Cells through the TLR4 Pathway. Radiation research 23 32097101
2018 Discovery and characterization of the tubercidin biosynthetic pathway from Streptomyces tubercidicus NBRC 13090. Microbial cell factories 20 30153835
2020 Phylogenetic Analysis and Development of Molecular Tool for Detection of Diaporthe citri Causing Melanose Disease of Citrus. Plants (Basel, Switzerland) 18 32143512
2013 Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity. PloS one 18 23826228
2022 Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice. International journal of molecular sciences 17 35806403
2017 Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1. Scientific reports 17 28785060
2020 Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle. Journal of dairy science 15 32197842
2023 A Genome-Wide Association Study of Metabolic Syndrome in the Taiwanese Population. Nutrients 13 38201907
2016 Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin. Proteomics 12 27037516
2020 A conserved acetylation switch enables pharmacological control of tubby-like protein stability. The Journal of biological chemistry 11 33187986
2016 Use of SNP genotypes to identify carriers of harmful recessive mutations in cattle populations. BMC genomics 10 27809787
2017 Genome-wide mRNA analysis reveals a TUBD1 isoform profile as a potential biomarker for diabetic retinopathy development. Experimental eye research 9 28137601
2021 Mining massive genomic data of two Swiss Braunvieh cattle populations reveals six novel candidate variants that impair reproductive success. Genetics, selection, evolution : GSE 5 34915862
2025 Effects of in vitro cytochalasin D and hypoxia on mitochondrial energetics and biogenesis, cell signal status and actin/tubulin/Hsp/MMP entity in air-breathing fish heart. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 1 39864717
2025 Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility. The Journal of cell biology 1 40586731
2025 Identification of Anticancer Targets in Ovarian Cancer Using Genomic Drug Sensitivity Data. International journal of molecular sciences 0 41096794
2025 Plasmodium berghei IMC1j interacts with δ-tubulin to orchestrate subpellicular microtubule organization in ookinetes. mBio 0 41117539
2024 Functional analysis of a panel of molecular markers for diagnosis of systemic lupus erythematosus in rats. Bioscience reports 0 38967046
2016 A proof-of-concept study in engineering synthetic protein for selective recognition of substrate-free polyubiquitin. Proteomics 0 27273999