Affinage

SPAG6

Sperm-associated antigen 6 · UniProt O75602

Length
509 aa
Mass
55.5 kDa
Annotated
2026-06-10
55 papers in source corpus 27 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPAG6 is an armadillo-repeat protein that functions as a structural scaffold of the central apparatus of motile cilia and flagella, where it stabilizes the C1 microtubule and organizes the projections that confer axonemal asymmetry (PMID:8636214). First defined through the Chlamydomonas orthologue PF16, SPAG6 localizes specifically to the C1 microtubule, and its loss eliminates the C1 microtubule and paralyzes the flagellum, a phenotype rescued by re-expression (PMID:8636214); the armadillo repeats act as a single structural unit required for axonemal assembly (PMID:10913963). The human and mouse proteins localize to the sperm flagellum and decorate cytoplasmic microtubules in transfected cells (PMID:10493827, PMID:10684790). SPAG6 builds a central-apparatus interaction network, binding PF20/SPAG16 and PF6 and being required for the stable assembly of both partners in the axoneme (PMID:12391165, PMID:15827353). Beyond the axoneme, SPAG6 associates with the centrosome and cytoplasmic microtubules to control ciliogenesis, basal-foot orientation and epithelial planar cell polarity, with loss causing reduced and disorganized ciliary beating and loss of Vangl2 polarity (PMID:25333478), and to support centrosome polarization during immunological synapse formation (PMID:27169488). SPAG6 regulates cell proliferation, adhesion, motility and microtubule acetylation, and its deletion produces supernumerary centrosomes and defective primary cilia (PMID:26585507). During spermiogenesis it stabilizes acrosomal SPINK2 and modulates AKAP4 and SPAG16L levels, and compound loss with its paralogue causes infertility with defective acrosome, manchette and flagellar sheath formation (PMID:32216237, PMID:40777416). In hematological malignancies SPAG6 acts as a pro-survival, pro-proliferative factor, suppressing apoptosis through PTEN/PI3K/AKT, TRAIL/FADD, AMPK/mTOR/ULK1 autophagy, AKT/FOXO cell-cycle, and ROS/GSTP1/JNK signaling, and its expression is controlled by promoter methylation and a STAT1 feedback loop (PMID:25405588, PMID:28393201, PMID:29749435, PMID:33000212, PMID:37681349, PMID:39508041).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Established the founding mechanistic role: SPAG6's orthologue PF16 is a dedicated structural component of the C1 microtubule whose absence collapses the central apparatus and abolishes motility.

    Evidence Insertional mutagenesis, transformation rescue, and immunogold EM in Chlamydomonas

    PMID:8636214

    Open questions at the time
    • Did not resolve which armadillo repeats mediate assembly
    • No direct binding partners identified at this stage
  2. 2000 High

    Defined the structural logic of assembly by showing the armadillo repeats function as a single unit, with the first repeat necessary but not sufficient and the C-terminus dispensable.

    Evidence Site-directed mutagenesis and deletion-construct rescue in pf16 mutants

    PMID:10913963

    Open questions at the time
    • No atomic structure of the repeat unit
    • Binding determinants for partner proteins not mapped
  3. 1999 Medium

    Extended the central-apparatus role to mammals by showing human and mouse SPAG6 localize to the sperm flagellum and associate with microtubules.

    Evidence cDNA cloning and immunofluorescence on permeabilized sperm and transfected COS-1 cells

    PMID:10493827 PMID:10684790

    Open questions at the time
    • Localization in somatic motile cilia not addressed
    • No functional knockout yet
  4. 2005 High

    Resolved how SPAG6 organizes the central apparatus by demonstrating it bridges PF20/SPAG16 and PF6 and is required for their stable assembly, defining a PF6–SPAG6–PF20 network.

    Evidence Yeast two-hybrid, co-localization in CHO cells, and immunoblot of Spag6-knockout mouse sperm

    PMID:12391165 PMID:15827353

    Open questions at the time
    • Stoichiometry and architecture of the network not defined
    • Whether interactions are direct in the assembled axoneme unconfirmed
  5. 2014 High

    Broadened SPAG6's role beyond beating to ciliogenesis and tissue polarity, and to centrosome-dependent immune cell function.

    Evidence Spag6-knockout mouse analysis of ependymal/tracheal cilia, Vangl2 distribution, and lymphocyte immunological synapse assays

    PMID:25333478 PMID:27169488

    Open questions at the time
    • Molecular link between SPAG6 and Vangl2 PCP machinery unresolved
    • Mechanism of centrosome polarization control not defined
  6. 2015 Medium

    Identified SPAG6 as a cytoplasmic regulator of centrosome number, cell morphology, motility, and microtubule acetylation, and as a stabilizer of partner proteins in distinct cell types.

    Evidence Spag6-knockout MEF assays with rescue, plus co-IP of prestin in outer hair cells and neuronal migration assays

    PMID:25748314 PMID:26130477 PMID:26585507

    Open questions at the time
    • Direct biochemical basis for tubulin acetylation change unknown
    • Mechanism of centrosome amplification not established
  7. 2019 Medium

    Showed SPAG6 stabilizes acrosomal SPINK2 during spermiogenesis, extending its scaffolding role to acrosome formation.

    Evidence Yeast two-hybrid, co-localization, and knockout-mouse immunoblot/immunofluorescence

    PMID:32216237

    Open questions at the time
    • Functional consequence of SPINK2 loss for fertility addressed only later
    • Direct binding interface not mapped
  8. 2020 Medium

    Reframed SPAG6 as a pro-survival oncogenic factor in hematological malignancies, converging on PTEN/PI3K/AKT, TRAIL/FADD, autophagy, and cell-cycle control of apoptosis.

    Evidence shRNA/siRNA knockdown and overexpression with pharmacological pathway rescue in MDS, leukemia and lymphoma lines plus xenografts

    PMID:25405588 PMID:28393201 PMID:29749435 PMID:30835546 PMID:32537026 PMID:33000212

    Open questions at the time
    • How an axonemal scaffold engages these signaling pathways mechanistically is unclear
    • Most readouts are pathway correlations from a single lab lineage
  9. 2022 Medium

    Connected SPAG6 expression to epigenetic and transcriptional control and to a direct cytoskeletal motor partner driving oncogenic signaling.

    Evidence Co-IP/mass spectrometry of MYO1D, fractionation, and DNMT3b promoter-methylation/luciferase assays

    PMID:35667090 PMID:36398260

    Open questions at the time
    • Whether MYO1D translocation is direct or scaffold-dependent unresolved
    • Context-dependent tumor-suppressor vs oncogene roles not reconciled
  10. 2023 Medium

    Established a STAT1–SPAG6 positive feedback loop and additional apoptosis axes, deepening the transcriptional regulation of SPAG6 in malignancy.

    Evidence ChIP and dual-luciferase assays plus knockdown/overexpression in MPN, and TGF-β/Smad pathway analysis in B-ALL

    PMID:37681349 PMID:38147275

    Open questions at the time
    • B-ALL TGF-β/Smad link is low-confidence pathway correlation
    • Generality of STAT1 feedback across cell types untested
  11. 2025 Medium

    Distinguished SPAG6 from its paralogue SPAG6L, showing antagonistic effects on tubulin acetylation and differential SPINK2 affinity, and confirmed central-apparatus scaffolding by cryoEM.

    Evidence Compound knockout mouse genetics with binding-affinity assays (preprint) and cryoEM of the T. brucei central apparatus (preprint)

    PMID:40777416

    Open questions at the time
    • Both findings are preprints awaiting peer review
    • cryoEM is in a non-mammalian organism without mutagenesis validation
    • DUSP1/MAPK interaction in myeloma remains low-confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a structural axonemal scaffold mechanistically rewires intracellular signaling pathways (PI3K/AKT, JNK, MAPK) in non-ciliated cancer cells remains unresolved.
  • No direct biochemical link between SPAG6 scaffolding and PTEN/AKT regulation
  • Reconciliation of tumor-suppressor vs oncogene context not achieved
  • No structure of mammalian SPAG6 or its partner complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 2 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
DUSP1MYO1DPF6PRESTINSPAG16SPINK2TAC1
Complex memberships
axoneme central apparatus (C1 microtubule)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 PF16 (SPAG6 orthologue in Chlamydomonas) contains eight contiguous armadillo repeats and localizes specifically to the C1 microtubule of the central apparatus in flagella; loss of PF16 results in absence of the C1 microtubule and flagellar paralysis, and rescue by transformation restores wild-type motility and ultrastructure. Insertional mutagenesis, cDNA cloning, transformation rescue, immunofluorescence and immunogold electron microscopy with anti-PF16 antibody The Journal of cell biology High 8636214
2000 Functional domain analysis of PF16 demonstrated that the first armadillo repeat is necessary but not sufficient for assembly into the axoneme; the C-terminal 122 amino acids are dispensable for assembly and motility; and the armadillo repeats function as a single structural unit required for PF16 assembly. Site-directed mutagenesis of PF16 locus alleles, deletion constructs transformed into pf16 mutants, motility rescue and ultrastructural analysis Cell motility and the cytoskeleton High 10913963
1999 Human SPAG6 protein, containing eight contiguous armadillo repeats homologous to Chlamydomonas PF16, localizes to the tails of permeabilized human sperm, consistent with a role in the axoneme central apparatus. cDNA cloning, immunofluorescence with anti-SPAG6 antibody on permeabilized human sperm Genomics Medium 10493827
2000 Mouse Spag6 protein (murine SPAG6) localizes to the principal piece of permeabilized sperm tails and co-localizes with microtubules when expressed in COS-1 cells, establishing it as a microtubule-associated axonemal central apparatus protein. Antipeptide antibody immunofluorescence on mouse sperm and COS-1 cells transfected with Spag6 expression construct Biology of reproduction Medium 10684790
2002 Mammalian PF20 (SPAG16) interacts with SPAG6 via its WD repeat domain, as shown by yeast two-hybrid assay; when co-expressed in CHO cells, PF20 co-localizes with SPAG6 on polymerized microtubules; and PF20 protein is markedly reduced in sperm of Spag6-deficient mice, indicating SPAG6 is required for PF20 stability or assembly in the axoneme. Yeast two-hybrid, co-expression in CHO cells with fluorescence microscopy, immunoblotting of Spag6-knockout mouse sperm Molecular and cellular biology High 12391165
2005 Mammalian PF6 (the orthologue of Chlamydomonas PF6, localized to the C1 1a projection) interacts with SPAG6 via a defined fragment, demonstrated by yeast two-hybrid and co-localization in transfected cells; a PF6 fragment corresponding to the SPAG6-binding domain is absent from sperm of SPAG6-deficient mice, establishing PF6–SPAG6–PF20 as a network linking C1 microtubule projections to the central bridge in the axoneme. Yeast two-hybrid, co-transfection and co-localization in mammalian cells, immunoblotting of Spag6-knockout mouse sperm Molecular & cellular proteomics : MCP High 15827353
2014 In Spag6-deficient mice, ependymal and tracheal cilia show reduced beat frequency, unsynchronized beating, reduced cilia density, and randomized basal foot orientation; planar cell polarity protein Vangl2 distribution is lost in tracheal epithelial cells, demonstrating that SPAG6 regulates not only ciliary motility but also ciliogenesis, axoneme orientation, and epithelial planar cell polarity. Spag6 knockout mouse analysis: high-speed video microscopy of cilia beat, scanning/transmission electron microscopy, immunofluorescence for basal feet orientation and Vangl2 distribution PloS one High 25333478
2014 SPAG6 deficiency in mice leads to impaired immunological synapse formation due to loss of centrosome polarization and failure of actin clearance at the synaptic cleft in lymphocytes, resulting in defective CTL function and reduced humoral immunity (germinal centers, class-switched antibody); SPAG6 is associated with the centrosome in lymphocytes. Bone marrow reconstitution, immunofluorescence for centrosome polarization and actin distribution in lymphocytes, CTL killing assays, antibody production assays in Spag6-knockout mice Scientific reports High 27169488
2014 SPAG6 silencing in myeloid leukemia cells (SKM-1 and K562) induces apoptosis via activation of caspase-3, -9, and -8, and upregulates p53 and PTEN expression at mRNA and protein levels; SPAG6-shRNA xenograft mice showed inhibited tumor growth and increased apoptosis. shRNA lentiviral knockdown, flow cytometry, CCK-8 assay, Western blot, RT-PCR, NOD/SCID xenograft model International journal of oncology Medium 25405588
2015 Spag6-deficient mouse embryonic fibroblasts proliferate more slowly, have larger surface area, reduced motility (chemotaxis and wound healing), reduced adhesion with non-polarized F-actin distribution, multiple centrosomes, reduced primary cilia formation, and increased sensitivity to paclitaxel; re-expression of SPAG6 rescues abnormal cell morphology; SPAG6 selectively increases acetylated tubulin levels. MEF isolation from Spag6-knockout embryos, proliferation assays, wound healing/chemotaxis assays, immunofluorescence for F-actin and tubulin, primary cilia quantification, rescue by SPAG6 re-expression Scientific reports High 26585507
2015 Overexpression of Spag6 in cortical neurons delays neuronal migration rate and decreases neurite number and length, as assayed by in utero electroporation, identifying a role for SPAG6 in regulating neuronal migration through cytoskeletal remodeling. In utero electroporation of mouse embryonic cortex, immunofluorescence and quantitative analysis of neuronal position and neurite morphology Journal of molecular neuroscience : MN Medium 26130477
2015 SPAG6 co-immunoprecipitates with prestin in outer hair cells (OHCs); Spag6-knockout mice show reduced prestin expression at both protein and mRNA levels and abnormal OHC morphology, indicating SPAG6 is required for prestin stability and normal OHC mechanosensory function. Co-immunoprecipitation, Western blot, real-time PCR, immunofluorescence in Spag6-knockout mice Neuroscience letters Medium 25748314
2017 SPAG6 regulates apoptosis in SKM-1 MDS cells via the TRAIL signaling pathway: SPAG6 knockdown activates the TRAIL pathway and increases interaction between FADD and TRAIL death receptors, while high SPAG6 expression suppresses TRAIL signaling; SPAG6 does not affect expression of TRAIL death receptors except FADD. shRNA lentiviral knockdown, flow cytometry, CCK-8 assay, Western blot, co-immunoprecipitation for FADD–death receptor interaction Oncology reports Medium 28393201
2018 SPAG6 silencing in SKM-1 cells increases PTEN expression and reduces AKT phosphorylation, leading to apoptosis via Mcl-1 downregulation, cytochrome c release, and increased caspase-9; the PI3K inhibitor LY294002 synergistically enhances this apoptosis; SPAG6-regulated PTEN expression is caspase-independent; SPAG6 knockdown is associated with DNMT1 downregulation, suggesting SPAG6 may control PTEN expression via DNA methylation. shRNA lentiviral knockdown, Western blot, flow cytometry, PI3K inhibitor treatment, pan-caspase inhibitor treatment, in vivo xenograft model International journal of oncology Medium 29749435
2019 SPAG6 knockdown in SKM-1 cells inhibits cell proliferation by mediating G1-to-S cell cycle arrest, upregulating p27Kip1, and regulating the AKT/FOXO signaling pathway. shRNA knockdown, CCK-8, FACS cell cycle analysis, RT-qPCR, Western blot DNA and cell biology Medium 30835546
2019 SPAG6 interacts with SPINK2 (serine protease inhibitor Kazal-type 2) in the acrosome of round spermatids; SPAG6 is expressed in the acrosome during spermatogenesis (postnatal days 16–28); in SPAG6-knockout mice, SPINK2 expression and acrosomal localization are absent, indicating SPAG6 stabilizes SPINK2 during acrosome formation. Yeast two-hybrid, co-localization in CHO cells by immunofluorescence, Western blot and immunofluorescence in Spag6-knockout mice Zhonghua nan ke xue = National journal of andrology Medium 32216237
2020 SPAG6 silencing in SKM-1 cells induces autophagic cell death via the AMPK/mTOR/ULK1 pathway: knockdown upregulates p-AMPK and p-ULK1 and downregulates p-mTOR; autophagy inhibition with chloroquine or 3-methyladenine decreases SPAG6-knockdown-mediated apoptosis; AMPK inhibition (Compound C) attenuates both autophagy and apoptosis. shRNA lentiviral knockdown, Western blot, flow cytometry, autophagy inhibitor and AMPK inhibitor pharmacological experiments Oncology letters Medium 32537026
2020 SPAG6 promotes proliferation and inhibits apoptosis in Burkitt lymphoma cells via the PTEN/PI3K/AKT pathway: SPAG6 knockdown increases PTEN and reduces p-AKT, while PTEN siRNA or PTEN inhibitor SF1670 reverses the anti-proliferative and pro-apoptotic effects of SPAG6 depletion both in vitro and in vivo. shRNA/siRNA knockdown and overexpression, Western blot, flow cytometry, PTEN inhibitor treatment, in vivo xenograft Oncology reports Medium 33000212
2022 SPAG6 interacts with MYO1D (myosin 1D) as identified by co-immunoprecipitation and mass spectrometry; SPAG6 overexpression promotes translocation of MYO1D from cytosol to cell membrane, upregulating EGFR family expression and thereby activating PI3K/AKT and ERK signaling to promote AML cell proliferation and migration. Immunoprecipitation, mass spectrometry, Western blot for MYO1D localization (membrane vs. cytosol fractionation), in vitro proliferation/migration assays, in vivo xenograft Blood advances Medium 35667090
2023 SPAG6 knockdown in MPN cell lines promotes apoptosis, reduces G1-to-S cell cycle progression, and is associated with downregulated STAT1; forced SPAG6 expression promotes clone formation and G1-to-S progression; chromatin immunoprecipitation shows STAT1 binds the SPAG6 promoter, and dual-luciferase assay shows STAT1 promotes SPAG6 transcription, establishing a positive feedback between SPAG6 and STAT1. shRNA knockdown, overexpression, FACS cell cycle analysis, ChIP assay, dual-luciferase reporter assay, Western blot Cancer science Medium 37681349
2023 SPAG6 knockdown in B-ALL cell lines inhibits proliferation and promotes apoptosis via the TGF-β/Smad signaling pathway. Lentiviral knockdown, cell proliferation assays, flow cytometry for apoptosis, Western blot for TGF-β/Smad pathway components International journal of hematology Low 38147275
2016 TAC1 protein interacts with SPAG6 as shown by yeast two-hybrid; when co-transfected with SPAG6 in CHO cells, TAC1 localizes to microtubules rather than remaining diffusely cytoplasmic, indicating SPAG6 directs TAC1 to microtubules. Yeast two-hybrid, co-transfection and immunofluorescence co-localization in CHO and COS-1 cells, Western blot Zhonghua nan ke xue = National journal of andrology Low 29282908
2022 DNMT3b-mediated hypermethylation of the SPAG6 promoter leads to SPAG6 downregulation in lung squamous cell carcinoma; restored SPAG6 expression inhibits STAT1 and STAT3 transcription, reversing JAK/STAT pathway activation and suppressing malignant cell phenotype. Bisulfite sequencing, DNMT3b functional assays, dual-luciferase assay for STAT1/STAT3 transcription, CCK-8/EdU/Transwell assays American journal of translational research Medium 36398260
2024 SPAG6 overexpression in AML cells reduces ROS and malondialdehyde levels and promotes GSTP1 expression; elevated GSTP1 forms a complex with JNK, reducing p-JNK and inhibiting JNK pathway activation, thereby attenuating the pro-apoptotic effects of daunorubicin; SPAG6 knockdown diminishes mitochondrial membrane potential and increases apoptosis. TMT proteomics after SPAG6 knockdown, CCK-8, flow cytometry for ROS and apoptosis, Western blot, in vivo xenograft, IHC Frontiers in pharmacology Medium 39508041
2025 SPAG6 directly interacts with DUSP1 (dual-specificity phosphatase 1) in multiple myeloma cells, and SPAG6 modulates downstream MAPK/ERK pathway activity by regulating DUSP1 activity; SPAG6 overexpression promotes proliferation, migration, and apoptosis resistance, while knockdown has opposite effects. Transcriptome sequencing, co-immunoprecipitation (implied from 'directly interacts'), RNA interference, overexpression, cell proliferation/apoptosis/migration assays Frontiers in pharmacology Low 40535772
2025 Both SPAG6 and SPAG6L bind SPINK2, but SPAG6 has approximately 10-fold higher binding affinity than SPAG6L; SPAG6 modulates testicular AKAP4 and SPAG16L levels; compound Spag6−/−;Spag6l+/− males are infertile with defective spermiogenesis (abnormal chromatin condensation, malformed acrosome and manchette, disorganized mitochondrial sheath and fibrous sheath); SPAG6 suppresses tubulin acetylation whereas SPAG6L enhances it, indicating antagonistic roles in microtubule regulation. Compound knockout mouse genetics, histological and ultrastructural analysis, binding affinity assays for SPINK2, Western blot for AKAP4 and SPAG16L, acetylated tubulin immunoblotting bioRxivpreprint Medium 40777416
2023 The SPAG6 c.900 T>C variant in exon 7 generates a new splice acceptor site that inhibits exon 7 skipping, thereby promoting Sertoli cell growth and maintaining normal blood-testis barrier function; the variant is associated with semen quality traits in pigs. RNA-seq analysis, Sanger sequencing, splice site reporter assay, Sertoli cell culture assays for growth and blood-testis barrier function Animal genetics Medium 37211688
2025 CryoEM of the Trypanosoma brucei flagellum central apparatus identified PF16 (SPAG6 orthologue) as a structural scaffold critical for central apparatus assembly and axonemal asymmetry; PF16 is stably associated with the C1/C2 microtubules. Cryogenic electron microscopy (cryoEM) structural analysis bioRxivpreprint Medium

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 PF16 encodes a protein with armadillo repeats and localizes to a single microtubule of the central apparatus in Chlamydomonas flagella. The Journal of cell biology 153 8636214
2017 SPAG6 and L1TD1 are transcriptionally regulated by DNA methylation in non-small cell lung cancers. Molecular cancer 97 28093071
2002 A sperm-associated WD repeat protein orthologous to Chlamydomonas PF20 associates with Spag6, the mammalian orthologue of Chlamydomonas PF16. Molecular and cellular biology 73 12391165
1999 cDNA cloning and characterization of a human sperm antigen (SPAG6) with homology to the product of the Chlamydomonas PF16 locus. Genomics 67 10493827
2005 Dissecting the axoneme interactome: the mammalian orthologue of Chlamydomonas PF6 interacts with sperm-associated antigen 6, the mammalian orthologue of Chlamydomonas PF16. Molecular & cellular proteomics : MCP 62 15827353
2000 Sperm antigen 6 is the murine homologue of the Chlamydomonas reinhardtii central apparatus protein encoded by the PF16 locus. Biology of reproduction 55 10684790
2010 The Armadillo repeat protein PF16 is essential for flagellar structure and function in Plasmodium male gametes. PloS one 54 20886115
2014 Sperm-associated antigen 6 (SPAG6) deficiency and defects in ciliogenesis and cilia function: polarity, density, and beat. PloS one 47 25333478
2015 Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis. Scientific reports 35 26585507
2020 Patients with severe asthenoteratospermia carrying SPAG6 or RSPH3 mutations have a positive pregnancy outcome following intracytoplasmic sperm injection. Journal of assisted reproduction and genetics 34 32124190
2014 Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice. PloS one 27 25393619
2022 Homozygous SPAG6 variants can induce nonsyndromic asthenoteratozoospermia with severe MMAF. Reproductive biology and endocrinology : RB&E 26 35232447
2016 Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice. Scientific reports 26 27169488
2014 SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis. International journal of oncology 26 25405588
2021 Delayed fractional dosing with RTS,S/AS01 improves humoral immunity to malaria via a balance of polyfunctional NANP6- and Pf16-specific antibodies. Med (New York, N.Y.) 25 35590199
2019 Upregulation of SPAG6 in Myelodysplastic Syndrome: Knockdown Inhibits Cell Proliferation via AKT/FOXO Signaling Pathway. DNA and cell biology 25 30835546
2018 SPAG6 silencing induces apoptosis in the myelodysplastic syndrome cell line SKM‑1 via the PTEN/PI3K/AKT signaling pathway in vitro and in vivo. International journal of oncology 20 29749435
2017 Spag6 Mutant Mice Have Defects in Development and Function of Spiral Ganglion Neurons, Apoptosis, and Higher Sensitivity to Paclitaxel. Scientific reports 20 28819108
2015 Spag6 Negatively Regulates Neuronal Migration During Mouse Brain Development. Journal of molecular neuroscience : MN 18 26130477
2000 Defining functional domains within PF16: a central apparatus component required for flagellar motility. Cell motility and the cytoskeleton 18 10913963
2023 Genome sequencing of Pakistani families with male infertility identifies deleterious genotypes in SPAG6, CCDC9, TKTL1, TUBA3C, and M1AP. Andrology 17 38073178
2020 SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway. Oncology letters 17 32537026
2020 SPAG6 promotes cell proliferation and inhibits apoptosis through the PTEN/PI3K/AKT pathway in Burkitt lymphoma. Oncology reports 16 33000212
2019 Distribution of sperm antigen 6 (SPAG6) and 16 (SPAG16) in mouse ciliated and non-ciliated tissues. Journal of molecular histology 16 30911868
2017 SPAG6 regulates cell apoptosis through the TRAIL signal pathway in myelodysplastic syndromes. Oncology reports 16 28393201
2022 Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression. Blood advances 14 35667090
2022 DNMT3b-mediated SPAG6 promoter hypermethylation affects lung squamous cell carcinoma development through the JAK/STAT pathway. American journal of translational research 14 36398260
2013 Lineage-specific duplications of Muroidea Faim and Spag6 genes and atypical accelerated evolution of the parental Spag6 gene. Journal of molecular evolution 13 24071998
2015 Expression of prestin in OHCs is reduced in Spag6 gene knockout mice. Neuroscience letters 10 25748314
2020 Planar cell polarity defects and hearing loss in sperm-associated antigen 6 (Spag6)-deficient mice. American journal of physiology. Cell physiology 9 33175573
2021 Aberrant expression of SPAG6 may affect the disease phenotype and serve as a tumor biomarker in BCR/ABL1-negative myeloproliferative neoplasms. Oncology letters 8 34820009
2021 SPAG6-silencing enhances decitabine-induced apoptosis and demethylation of PTEN in SKM-1 cells and in a xenograft mouse model. Leukemia & lymphoma 7 33843428
2021 Sperm-associated antigen 6 (Spag6) mutation leads to vestibular dysfunction in mice. Journal of pharmacological sciences 7 34663514
2017 Pf16 and phiPMW: Expanding the realm of Pseudomonas putida bacteriophages. PloS one 7 28877269
2023 SPAG6 regulates cell proliferation and apoptosis via TGF-β/Smad signal pathway in adult B-cell acute lymphoblastic leukemia. International journal of hematology 6 38147275
2015 Gene cloning, sequence analysis and heterologous expression of a novel cold-active lipase from Pseudomonas sp. PF16. Technology and health care : official journal of the European Society for Engineering and Medicine 6 26410312
1992 Cloning and characterization of a highly conserved HMG-like protein (PF16) gene from Plasmodium falciparum. Biochemical and biophysical research communications 6 1731798
2023 Upregulated SPAG6 correlates with increased STAT1 and is associated with reduced sensitivity of interferon-α response in BCR::ABL1 negative myeloproliferative neoplasms. Cancer science 5 37681349
2021 Measurable Residual Disease Monitoring of SPAG6, ST18, PRAME, and XAGE1A Expression in Peripheral Blood May Detect Imminent Relapse in Childhood Acute Myeloid Leukemia. The Journal of molecular diagnostics : JMD 5 34600138
2024 SPAG6 overexpression decreases the pro-apoptotic effect of daunorubicin in acute myeloid leukemia cells through the ROS/JNK MAPK axis in a GSTP1-dependent manner. Frontiers in pharmacology 4 39508041
2023 SPAG6 c.900 T>C affects boar semen quality and blood-testis barrier function by creating a new splice acceptor site. Animal genetics 4 37211688
2024 Target silencing of porcine SPAG6 and PPP1CC by shRNA attenuated sperm motility. Theriogenology 3 38430798
2023 The Function of Spag6 to Repair Brain Edema Damage After Cerebral Ischemic Stroke-reperfusion. Neuroscience 3 37169167
2017 [Expressions of SLC22A14 and SPAG6 proteins in the ejaculated sperm of idiopathic asthenozoospermia patients.]. Zhonghua nan ke xue = National journal of andrology 3 29726644
2025 CircMYH9 promotes the mRNA stability of SPAG6 by recruiting EIF4A3 to facilitate the progression of breast cancer. Epigenetics 2 40145872
2025 SPAG6 Promotes Multiple Myeloma Through Activation of the MAPK/ERK Signaling Pathway. Frontiers in pharmacology 2 40535772
2025 RETRACTED: SPAG6 hypermethylation silences a novel tumor suppressor and inhibits renal cell carcinoma progression via PI3K/AKT/mTOR pathway. PloS one 2 41042741
2021 [Effects of SPAG6 silencing and decitabine treatment on apoptosis and phosphatase and tensin homolog methylation in SKM-1 cells]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 35045671
2019 [The role of SPAG6/SPINK2 protein complex in the formation of sperm acrosome in mice]. Zhonghua nan ke xue = National journal of andrology 1 32216237
1997 Molecular cloning and characterization of a cDNA for the highly conserved HMG-like protein (Pf16) gene of Plasmodium falciparum. Biochemical and biophysical research communications 1 9168969
2026 Role of SPAG6 in regulating physiological functions and tumorigenesis (Review). International journal of oncology 0 41685588
2026 Correction: SPAG6 hypermethylation silences a novel tumor suppressor and inhibits renal cell carcinoma progression via PI3K/AKT/mTOR pathway. PloS one 0 41824384
2025 Two Spag6 genes control sperm formation and male fertility in mice. bioRxiv : the preprint server for biology 0 40777416
2025 The Janus Face of SPAG6: Inducing EMT in Luminal Breast Cancer Cells Amidst Widespread Expression Loss in Breast Tumours. Journal of cellular and molecular medicine 0 41066509
2016 [Interaction between SPAG6 and TAC1 proteins]. Zhonghua nan ke xue = National journal of andrology 0 29282908

Missed literature

Know a paper Affinage missed for SPAG6? Flag it for the maintainers and the community.

No submissions yet.