Affinage

TUBD1

Tubulin delta chain · UniProt Q9UJT1

Length
453 aa
Mass
51.0 kDa
Annotated
2026-06-10
23 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TUBD1 (delta tubulin) is a noncanonical tubulin required for the structural integrity of centriole microtubules and for cilium-dependent signaling in both somatic and germ cells (PMID:32060285, PMID:29290584). In human somatic cells it operates within a centriole biogenesis pathway (CEP295–CEP44–POC1B–TUBE1–TUBD1), where its depletion disturbs centriole microtubule integrity and blocks centriole-to-centrosome conversion (PMID:32060285). Consistent with a role in ciliary function, TUBD1 acts as a positive regulator of primary cilia-dependent Hedgehog signaling, and its loss reduces target-cell sensitivity to Sonic Hedgehog (PMID:29290584). In male germ cells TUBD1 stabilizes meiotic kinetochores, governs spindle polarity and cytokinesis, and partners with the microtubule-severing enzymes KATNAL2 and KATNB1 to remodel the manchette during sperm head shaping (PMID:40586731). Loss of TUBD1 causes male sterility in conditional-knockout mice (PMID:40586731), and a recessive missense allele (p.H210R) causes ciliopathy-like chronic airway disease and perinatal mortality in cattle, establishing TUBD1 as essential for cilia integrity in vivo (PMID:27225349). TUBD1 pre-mRNA processing is itself subject to regulation, with the ILDR1/2–splicing-factor axis altering its alternative splicing (PMID:28785060).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2016 Medium

    Established that functional TUBD1 is essential for cilia integrity in a whole organism, linking the gene to ciliary disease rather than leaving it as an uncharacterized tubulin.

    Evidence Whole-genome sequencing, haplotype analysis, and pathology of homozygous p.H210R calves in two cattle breeds

    PMID:27225349

    Open questions at the time
    • No molecular mechanism for how the H210R substitution impairs ciliary function
    • Does not define the protein-level activity of TUBD1
  2. 2017 Medium

    Placed TUBD1 in a defined signaling context by showing it is a positive regulator of primary cilia-dependent Hedgehog signal transduction.

    Evidence Genome-wide CRISPR loss-of-function screens in two cell types with Hh signaling and neural differentiation validation assays

    PMID:29290584

    Open questions at the time
    • Mechanism by which TUBD1 acts within cilia to promote Hh signaling unresolved
    • Does not distinguish a direct ciliary role from indirect effects on cilium formation
  3. 2017 Medium

    Identified an upstream regulatory layer on TUBD1 expression by showing ILDR1/2 and associated splicing factors control its alternative splicing.

    Evidence Co-immunoprecipitation of ILDR1/2 with TRA2A, TRA2B, SRSF1 and siRNA knockdown with RT-PCR readout of TUBD1 splicing

    PMID:28785060

    Open questions at the time
    • Functional consequence of the altered TUBD1 splice forms not determined
    • Single lab; binding shown by Co-IP without reciprocal or direct interaction validation
  4. 2020 High

    Defined the molecular pathway context of TUBD1 in centriole biogenesis, showing it is required for centriole microtubule integrity and centriole-to-centrosome conversion.

    Evidence siRNA depletion in human somatic cell lines with centriole/centrosome conversion assays and epistasis against CEP295/CEP44/POC1B/TUBE1

    PMID:32060285

    Open questions at the time
    • Biochemical activity of TUBD1 within the centriole lumen not resolved
    • Direct physical interactions among the pathway members not established
  5. 2025 High

    Revealed germ-cell-specific roles, showing TUBD1 stabilizes meiotic kinetochores, controls spindle polarity and cytokinesis, and partners with katanin enzymes for manchette remodeling.

    Evidence Conditional germ-cell knockout mouse with in vivo spermatogenesis and cell-biology readouts of kinetochore stability, spindle polarity, cytokinesis, and manchette remodeling

    PMID:40586731

    Open questions at the time
    • Molecular basis of the TUBD1–KATNAL2/KATNB1 partnership not biochemically dissected
    • Whether kinetochore and manchette functions reflect a shared or distinct molecular activity is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic biochemical activity of delta-tubulin TUBD1 and how it physically integrates into centriole and germ-cell microtubule structures remain undefined.
  • No structural model of TUBD1 in the centriole
  • No direct demonstration of TUBD1 incorporation into microtubule lattices
  • Mechanistic link between somatic centriole role and germ-cell phenotypes untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0005929 cilium 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1474165 Reproduction 1 R-HSA-162582 Signal Transduction 1 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
CEP295CEP44KATNAL2KATNB1POC1BTUBE1
Complex memberships
centriole

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 TUBD1 (delta tubulin) stabilizes kinetochores during male mouse meiosis, enabling meiotic progression, and is required for appropriate spindle polarity and cytokinesis. In haploid cells, TUBD1 works in partnership with microtubule-severing enzymes KATNAL2 and KATNB1 to regulate manchette remodeling and sperm head shaping. Conditional knockout of TUBD1 in male germ cells causes sterility. Conditional knockout mouse model, in vivo spermatogenesis analysis, cell biology assays for kinetochore stability, spindle polarity, cytokinesis, and manchette remodeling The Journal of cell biology High 40586731
2020 Impairment of TUBD1 (along with TUBE1 and POC1B) disturbs the integrity of centriole microtubules and prevents centriole-to-centrosome conversion, placing TUBD1 in a centriole biogenesis pathway (CEP295–CEP44–POC1B–TUBE1–TUBD1) that operates in the centriole lumen and on the cytoplasmic side. siRNA depletion of TUBD1 in human somatic cell lines, centriole structure and centrosome conversion assays, epistasis with CEP295/CEP44/POC1B/TUBE1 Nature communications High 32060285
2017 TUBD1 was identified as a positive regulator of Hedgehog (Hh) signaling involved in ciliary functions. Loss of Tubd1 reduced target cell sensitivity to Sonic Hedgehog, consistent with a role in primary cilia-dependent Hh signal transduction. Genome-wide CRISPR loss-of-function screens in two cell types, validated with multiple Hh signaling and neural differentiation assays Developmental cell Medium 29290584
2016 A missense mutation in TUBD1 (p.H210R) causes high perinatal and juvenile mortality in Braunvieh and Fleckvieh cattle with autosomal recessive inheritance, and homozygous calves suffer from chronic airway disease with pathology consistent with defective respiratory cilia, demonstrating that functional TUBD1 is essential for cilia integrity in vivo. Whole-genome sequencing of cattle populations, haplotype analysis, clinical and pathological examination of homozygous calves BMC genomics Medium 27225349
2017 ILDR1 (and ILDR2) bind splicing factors TRA2A, TRA2B, and SRSF1, and when endogenous ILDR1 and ILDR2 are knocked down, the alternative splicing of TUBD1 is altered, indicating that the ILDR1/2–splicing factor axis regulates TUBD1 pre-mRNA processing. Co-immunoprecipitation of ILDR1/2 with splicing factors, siRNA knockdown of ILDR1/2 in cultured cells with RT-PCR detection of TUBD1 alternative splicing Scientific reports Medium 28785060

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog. Developmental cell 84 29290584
2013 Identification of alternative splicing events regulated by the oncogenic factor SRSF1 in lung cancer. Cancer research 69 24371231
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 46 27346689
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
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 39 19454617
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 24 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) 19 32143512
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
2023 A Genome-Wide Association Study of Metabolic Syndrome in the Taiwanese Population. Nutrients 15 38201907
2020 Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle. Journal of dairy science 15 32197842
2016 Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin. Proteomics 12 27037516
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 6 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

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