| 1996 |
PF16 (Chlamydomonas orthologue of SPAG6) contains eight contiguous armadillo repeats and localizes specifically to the C1 microtubule of the central apparatus in flagella; loss of PF16 results in paralyzed flagella and missing C1 microtubule in isolated axonemes |
Insertional mutagenesis, gene cloning, transformation rescue, immunofluorescence, immunogold electron microscopy |
The Journal of cell biology |
High |
8636214
|
| 1999 |
Human SPAG6 encodes an armadillo repeat-containing protein localizing to the tails of permeabilized human sperm, consistent with a role in the flagellar axoneme central pair |
cDNA cloning, antibody generation, immunofluorescence localization of permeabilized sperm |
Genomics |
Medium |
10493827
|
| 2000 |
Murine SPAG6 (Spag6) localizes to the principal piece of mouse sperm tails and co-localizes with microtubules when expressed in COS-1 cells, supporting its role as an axoneme central apparatus component |
Antipeptide antibody, immunofluorescence in sperm and COS-1 cells |
Biology of reproduction |
Medium |
10684790
|
| 2000 |
The first armadillo repeat of PF16 is necessary but not sufficient for assembly into the axoneme; the C-terminal 122 amino acids are dispensable; the armadillo repeats act as a single functional unit required for PF16 assembly and flagellar motility rescue |
Deletion construct generation, transformation rescue assays in pf16 Chlamydomonas mutants |
Cell motility and the cytoskeleton |
High |
10913963
|
| 2002 |
SPAG6 (mammalian PF16 orthologue) physically interacts with PF20 (mammalian WD repeat protein); when co-expressed, PF20 colocalizes with SPAG6 on polymerized microtubules; PF20 is markedly reduced in sperm from SPAG6-deficient mice |
Yeast two-hybrid, co-expression in CHO cells with fluorescence microscopy, immunocytochemistry, western blot of Spag6-null mouse sperm |
Molecular and cellular biology |
High |
12391165
|
| 2005 |
SPAG6 physically interacts with the mammalian orthologue of Chlamydomonas PF6, which is localized to the axoneme central apparatus C1 microtubule 1a projection; PF6 fragment that interacts with SPAG6 is absent from SPAG6-deficient mouse sperm; SPAG6, PF6, and PF20 form a network linking central apparatus components |
Yeast two-hybrid, co-transfection and co-localization in cells, immunocytochemistry, western blot of Spag6-null sperm |
Molecular & cellular proteomics |
High |
15827353
|
| 2014 |
SPAG6 deficiency in mice reduces cilia beat frequency in tracheal epithelial cells, disrupts synchronized cilia beat, reduces cilia density in ependymal and tracheal cells, randomizes basal feet orientation, and disrupts planar cell polarity (Vangl2 distribution), indicating SPAG6 regulates ciliogenesis, axoneme orientation, and epithelial cell polarity |
Knockout mouse model, high-speed video microscopy, immunofluorescence, electron microscopy |
PloS one |
High |
25333478
|
| 2014 |
SPAG6 silencing in myeloid cell lines (SKM-1, K562) inhibits proliferation and induces apoptosis via activation of caspase-3, -9, and -8, and upregulation of p53 and PTEN |
shRNA lentiviral knockdown, flow cytometry, CCK-8 assay, western blot, xenograft mouse model |
International journal of oncology |
Medium |
25405588
|
| 2015 |
SPAG6-deficient mouse embryonic fibroblasts (MEFs) show slower proliferation, larger surface area, reduced motility, reduced adhesion, non-polarized F-actin, multiple centrosomes, reduced primary cilia, and increased sensitivity to paclitaxel; SPAG6 selectively increases acetylated tubulin levels; re-expression rescues abnormal morphology |
MEF isolation from Spag6-null mice, rescue transfection, wound-healing assay, chemotactic analysis, immunofluorescence, paclitaxel sensitivity assay |
Scientific reports |
High |
26585507
|
| 2015 |
SPAG6 overexpression in developing cortical neurons delays neuronal migration rate and decreases neurite number and length, indicating a role in microtubule-dependent neuronal migration |
In utero electroporation overexpression in mouse cortex |
Journal of molecular neuroscience |
Medium |
26130477
|
| 2015 |
SPAG6 is expressed in outer hair cells (OHCs) of the cochlea and co-immunoprecipitates with prestin; SPAG6-deficient mice show reduced prestin expression at both protein and mRNA levels and abnormal OHC morphology |
Immunofluorescence, co-immunoprecipitation, western blot, real-time PCR, Spag6-null mouse model |
Neuroscience letters |
Medium |
25748314
|
| 2016 |
SPAG6 is associated with the centrosome in lymphocytes; SPAG6 deficiency impairs immunological synapse formation by disrupting centrosome polarization and actin clearance at the synaptic cleft, leading to defective CTL function and humoral immunity |
Bone marrow reconstitution, immunofluorescence, functional assays of CTL activity, germinal center analysis in Spag6-null mice |
Scientific reports |
Medium |
27169488
|
| 2017 |
SPAG6 knockdown in SKM-1 cells inhibits proliferation and affects cell cycle G1-to-S transition via upregulation of p27Kip1 and regulation of the AKT/FOXO pathway |
shRNA knockdown, western blot, FACS cell cycle analysis, RT-qPCR, CCK-8 assay |
DNA and cell biology |
Medium |
30835546
|
| 2017 |
SPAG6 silencing in SKM-1 cells activates the TRAIL signaling pathway and increases interaction between FADD and TRAIL death receptors, promoting apoptosis; high SPAG6 expression suppresses TRAIL-mediated apoptosis without affecting TRAIL death receptor expression |
shRNA lentiviral knockdown, flow cytometry, western blot, CCK-8 assay |
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; PTEN activation by SPAG6 knockdown is caspase-independent; SPAG6 knockdown is associated with DNMT1 downregulation, implying SPAG6 controls PTEN via DNA methylation |
shRNA knockdown, PI3K inhibitor (LY294002), pan-caspase inhibitor (z-VAD-fmk), western blot, flow cytometry, xenograft mouse model |
International journal of oncology |
Medium |
29749435
|
| 2019 |
SPAG6 interacts with SPINK2 (serine protease inhibitor Kazal-type 2) in the acrosome of round spermatids; SPAG6 is required for SPINK2 expression and proper acrosomal localization during spermatogenesis in mice |
Yeast two-hybrid, co-localization in CHO cells, immunofluorescence in Spag6-KO and wild-type mouse testis |
Zhonghua nan ke xue |
Medium |
32216237
|
| 2020 |
SPAG6 silencing triggers autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway; SPAG6 knockdown increases p-AMPK and p-ULK1 while decreasing p-mTOR; autophagy inhibition reduces SPAG6 knockdown-mediated apoptosis; AMPK inhibition attenuates this autophagy |
shRNA knockdown, autophagy inhibitors (chloroquine, 3-MA), AMPK inhibitor (Compound C), western blot, flow cytometry |
Oncology letters |
Medium |
32537026
|
| 2020 |
SPAG6 deficiency in Spag6-null mice causes planar cell polarity defects and hearing loss associated with abnormal stereocilia bundles, basal body positioning, disrupted subapical microtubule meshwork, and misdistributed FZD6 |
Spag6-null mice, auditory brainstem response, immunofluorescence, scanning electron microscopy |
American journal of physiology. Cell physiology |
Medium |
33175573
|
| 2022 |
SPAG6 overexpression in AML promotes translocation of MYO1D from cytosol to cell membrane, thereby upregulating EGFR family expression and activating PI3K/AKT and ERK signaling; SPAG6 physically interacts with MYO1D as shown by co-immunoprecipitation and mass spectrometry |
Immunoprecipitation, mass spectrometry, overexpression/knockdown, western blot, xenograft mouse model |
Blood advances |
Medium |
35667090
|
| 2022 |
DNMT3b-mediated hypermethylation of the SPAG6 promoter in lung squamous cell carcinoma leads to SPAG6 downregulation; SPAG6 regulates the JAK/STAT pathway by inhibiting STAT1 and STAT3 transcription |
Bisulfite sequencing, dual-luciferase assay, KEGG pathway analysis, CCK-8/EdU/Transwell assays, DNMT3b knockdown |
American journal of translational research |
Medium |
36398260
|
| 2023 |
STAT1 protein binds to the SPAG6 promoter and promotes SPAG6 expression; conversely, SPAG6 upregulation correlates with STAT1 expression in MPN, and SPAG6 downregulation reduces STAT1 induction and enhances INF-α sensitivity |
Chromatin immunoprecipitation, dual-luciferase reporter assay, overexpression/knockdown, flow cytometry, western blot, in vivo xenograft |
Cancer science |
Medium |
37681349
|
| 2016 |
TAC1 protein interacts with SPAG6 as determined by yeast two-hybrid; when co-expressed with SPAG6 in CHO cells, TAC1 localizes to microtubules rather than throughout the cell body, showing SPAG6-dependent microtubule targeting of TAC1 |
Yeast two-hybrid, co-transfection and immunofluorescence in CHO and COS-1 cells, western blot |
Zhonghua nan ke xue |
Low |
29282908
|
| 2025 |
SPAG6 physically interacts with SPINK2 with ~10-fold higher affinity than SPAG6L; SPAG6 modulates testicular AKAP4 and SPAG16L levels; SPAG6 suppresses tubulin acetylation (opposite to SPAG6L which enhances it); compound Spag6/Spag6l knockout causes defective spermiogenesis including abnormal acrosome and fibrous sheath |
Compound knockout mouse generation, histology, electron microscopy, binding affinity assay, western blot, tubulin acetylation assay |
bioRxivpreprint |
Medium |
40777416
|
| 2025 |
SPAG6 directly interacts with DUSP1 (dual-specificity phosphatase 1) and modulates downstream MAPK/ERK signaling pathway protein expression by regulating DUSP1 activity, promoting MM cell proliferation and migration |
RNA interference, overexpression, transcriptome sequencing, western blot, proliferation/apoptosis/migration assays |
Frontiers in pharmacology |
Low |
40535772
|
| 2025 |
SPAG6 overexpression in AML cells promotes GSTP1 expression, which reduces ROS levels and forms a GSTP1/JNK complex that reduces p-JNK, thereby inhibiting JNK-mediated apoptosis and attenuating daunorubicin efficacy |
Overexpression/knockdown, flow cytometry (ROS, apoptosis), TMT proteomics, western blot, xenograft model |
Frontiers in pharmacology |
Medium |
39508041
|
| 2025 |
CircMYH9 promotes SPAG6 mRNA stability by recruiting EIF4A3; elevated SPAG6 then suppresses PTEN and activates PI3K/AKT signaling to promote breast cancer cell proliferation, migration, and invasion |
RIP assay (circMYH9–EIF4A3–SPAG6 interaction), mRNA stability assay, overexpression/knockdown, PTEN inhibitor rescue, xenograft model |
Epigenetics |
Medium |
40145872
|