Affinage

TPPP2

Tubulin polymerization-promoting protein family member 2 · UniProt P59282

Length
170 aa
Mass
18.5 kDa
Annotated
2026-06-10
19 papers in source corpus 5 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPPP2 (p18/p25beta) is a member of the tubulin polymerization promoting protein family that functions in spermiogenesis and male fertility rather than in microtubule organization (PMID:30680919). Despite its family membership, TPPP2 does not bind tubulin and does not promote tubulin polymerization or microtubule bundling — activities retained by its paralogs TPPP1 and TPPP3 — and instead distributes homogeneously in the cytosol of transfected cells (PMID:17105200, PMID:28106390). TPPP2 protein localizes to elongating spermatids and mature sperm, and its loss in knockout mice causes male subfertility with reduced sperm count and motility together with mitochondrial structural defects, abnormal electron transfer chain expression, lowered ATP levels, decreased mitochondrial membrane potential, and increased sperm apoptosis (PMID:30680919). During spermiogenesis TPPP2 participates in a cytoplasmic protein network with CFAP65, MNS1, RSPH1, ZPBP1, and SPACA1 (PMID:34231842). Beyond these findings, the molecular mechanism by which TPPP2 supports sperm mitochondrial function has not been resolved in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2006 Medium

    Established that TPPP2, despite belonging to the TPPP family, does not behave like its microtubule-bundling paralogs, raising the question of what distinct function it serves.

    Evidence Recombinant protein characterization, in vitro microtubule bundling assays, and localization of fluorescent constructs in transfected HeLa cells

    PMID:17105200

    Open questions at the time
    • Cytosolic diffuse distribution leaves the native cellular role undefined
    • Tested only in a heterologous HeLa context
  2. 2017 Medium

    Resolved whether TPPP2 retains any tubulin activity, confirming it lacks tubulin binding, polymerization, and bundling capacity and diverges functionally from TPPP1/TPPP3.

    Evidence In vitro tubulin binding and polymerization assays, spectroscopy, and electron microscopy

    PMID:28106390

    Open questions at the time
    • A negative result that does not identify the actual molecular activity of TPPP2
    • No alternative binding partners or substrates identified in this work
  3. 2019 High

    Defined the physiological role of TPPP2 by showing it is expressed in spermatids and sperm and is required for normal sperm number, motility, and mitochondrial integrity, linking TPPP2 to male fertility.

    Evidence Tppp2 knockout mouse with immunolocalization, sperm motility assays, ATP and mitochondrial membrane potential measurements, electron microscopy, and apoptosis assays

    PMID:30680919

    Open questions at the time
    • Whether mitochondrial defects are a direct or downstream consequence of TPPP2 loss is unresolved
    • The molecular activity connecting TPPP2 to ATP production is not established
  4. 2019 Low

    Offered a candidate mechanism by identifying eEF1B as a TPPP2 interactor, hinting at a role in localized translation relevant to mitochondrial function.

    Evidence Co-immunoprecipitation identifying eEF1B as a potential interactor

    PMID:30680919

    Open questions at the time
    • Single Co-IP described as a potential interaction without reciprocal validation
    • No demonstration that TPPP2 influences translation of specific mitochondrial proteins
  5. 2021 Medium

    Placed TPPP2 within a defined cytoplasmic protein network during spermiogenesis, indicating it operates in a multiprotein assembly rather than alone.

    Evidence Endogenous co-immunoprecipitation, immunostaining, and proteomic analysis in mouse testes

    PMID:34231842

    Open questions at the time
    • Direct versus indirect nature of each interaction within the network is undefined
    • Functional consequence of the network for sperm formation is not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular activity of TPPP2 and the mechanism by which it maintains sperm mitochondrial structure and ATP production remain unknown.
  • No biochemical activity assigned after exclusion of tubulin binding
  • No validated mechanistic link between TPPP2 interactors and the mitochondrial phenotype

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1474165 Reproduction 2
Partners
CFAP65EEF1BMNS1RSPH1SPACA1ZPBP1

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 TPPP2 (p18/p25beta) was found to be a more structurally ordered protein compared to TPPP1/p25 and TPPP3/p20, and unlike TPPP1 and p20, TPPP2 (p18) does not cross-link microtubules and distributes homogeneously within the cytosol of transfected HeLa cells rather than associating with microtubule bundles. Recombinant protein characterization, in vitro microtubule bundling assays, transfection of HeLa cells with fluorescent constructs, electron microscopy Biochemistry Medium 17105200
2017 TPPP2 does not bind tubulin and does not promote tubulin polymerization or microtubule bundling, in contrast to TPPP1 and TPPP3 which retain these activities; this establishes that TPPP2 has markedly reduced/absent microtubule-binding and bundling capacity within the TPPP family. Biochemical tubulin binding and polymerization assays, bioinformatics, spectroscopic analysis, electron microscopy Biochemistry Medium 28106390
2019 TPPP2 protein localizes to elongating spermatids (stages IV-VIII of the seminiferous epithelial cycle) and in mature sperm in the epididymis; knockout of Tppp2 in mice causes male subfertility with decreased sperm count and motility, increased mitochondrial structural abnormalities (irregular mitochondria lacking lamellar cristae), abnormal expression of electron transfer chain molecules, lower ATP levels, decreased mitochondrial membrane potential, and increased apoptotic index in sperm. Immunolocalization, Tppp2 knockout mouse model, sperm motility assays, ATP measurement, mitochondrial membrane potential assay, electron microscopy, apoptosis assays Journal of cellular and molecular medicine High 30680919
2019 TPPP2 interacts with eukaryotic translation elongation factor 1 beta (eEF1B), suggesting TPPP2 may affect translation of specific proteins relevant to sperm mitochondrial function. Co-immunoprecipitation / protein interaction assay (identified as potential interactive protein) Journal of cellular and molecular medicine Low 30680919
2021 TPPP2 forms part of a cytoplasmic protein network with CFAP65, MNS1, RSPH1, ZPBP1, and SPACA1 during spermiogenesis, as shown by endogenous co-immunoprecipitation and immunostaining in mouse testes. Endogenous immunoprecipitation, immunostaining, proteomic analysis Human molecular genetics Medium 34231842
1997 The protein encoded by the p25beta locus (an alias for TPPP2) contains a conserved chromodomain in the N-terminal region and a heterochromatin binding domain in the C-terminal region; antibodies specific to the C-terminal domain (amino acids 70-185) show nucleoplasmic, heterochromatin, and centromeric staining in immunofluorescence, while N-terminal-specific antibodies show no staining; the protein associates with centromeres most prominently at anaphase. cDNA cloning, affinity-purified antibodies with domain-specific immunofluorescence, metaphase chromosome spreads Chromosoma Low 9169582

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Tubulin polymerization promoting proteins (TPPPs): members of a new family with distinct structures and functions. Biochemistry 83 17105200
1997 Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis. Chromosoma 61 9169582
2013 Scanning of novel cancer/testis proteins by human testis proteomic analysis. Proteomics 55 23436708
2020 A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine. Genetics, selection, evolution : GSE 44 33292187
2019 Deficiency of TPPP2, a factor linked to oligoasthenozoospermia, causes subfertility in male mice. Journal of cellular and molecular medicine 44 30680919
2021 CFAP65 is required in the acrosome biogenesis and mitochondrial sheath assembly during spermiogenesis. Human molecular genetics 36 34231842
2000 Identification of an alpha-helical epitope region on the PM/Scl-100 autoantigen with structural homology to a region on the heterochromatin p25beta autoantigen using immobilized overlapping synthetic peptides. Journal of molecular medicine (Berlin, Germany) 32 10759029
2019 Comparative proteomic analysis of high- and low-fertile buffalo bull spermatozoa for identification of fertility-associated proteins. Reproduction in domestic animals = Zuchthygiene 30 30820981
2012 Genetic architecture of resilience of executive functioning. Brain imaging and behavior 23 22711244
2023 Bull Sperm SWATH-MS-Based Proteomics Reveals Link between High Fertility and Energy Production, Motility Structures, and Sperm-Oocyte Interaction. Journal of proteome research 21 37782577
2017 Tubulin Binding and Polymerization Promoting Properties of Tubulin Polymerization Promoting Proteins Are Evolutionarily Conserved. Biochemistry 21 28106390
1998 Immunological characterization of heterochromatin protein p25beta autoantibodies and relationship with centromere autoantibodies and pulmonary fibrosis in systemic scleroderma. Journal of molecular medicine (Berlin, Germany) 18 9462868
2022 Quantitative phosphoproteomics analyses reveal the regulatory mechanisms related to frozen-thawed sperm capacitation and acrosome reaction in yak (Bos grunniens). Frontiers in physiology 15 36277216
2018 Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes. Molecular genetics and genomics : MGG 13 29948331
2015 On the tubulin polymerization promoting proteins of zebrafish. Biochemical and biophysical research communications 8 25576359
2012 A fish-specific member of the TPPP protein family? Journal of molecular evolution 6 23053195
2025 Identification of reproductive performance in Bali-polled bulls using computer-assisted semen analysis and plasma seminal proteomics. Veterinary world 4 40041504
2025 Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders. medRxiv : the preprint server for health sciences 1 40766128
2025 Diverse Roles of Tubulin Polymerization Promoting Protein 3 (TPPP3) in Human Health and Disease. Cells 0 41148789

Missed literature

Know a paper Affinage missed for TPPP2? Flag it for the maintainers and the community.

No submissions yet.