Affinage

SPAG5

Sperm-associated antigen 5 · UniProt Q96R06

Length
1193 aa
Mass
134.4 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPAG5 (Astrin/hMAP126) is a microtubule-associated protein essential for mitotic spindle organization and cell cycle progression, with additional roles in spermatogenesis-related outer dense fiber assembly, autophagy regulation, and multiple oncogenic signaling pathways. SPAG5 localizes to spindle microtubules during mitosis and is phosphorylated by CDK1 (p34cdc2); its C-terminal domain is required for spindle targeting, and truncation causes defective spindle organization and Sertoli cell apoptosis in rats (PMID:11549262, PMID:16816335, PMID:16211599). Transcriptionally, SPAG5 is driven by YAP/TAZ/TEAD and MYC while being repressed by the p53-p21 axis, and its protein is stabilized by USP14-mediated de-ubiquitination (PMID:33230261, PMID:39164278, PMID:30955859, PMID:31957155). SPAG5 activates PI3K/AKT signaling through interaction with CEP55, stabilizes FOXM1 to drive MMP2 expression, enhances c-MYC transcriptional activity via MYCBP binding, modulates β-catenin signaling, and suppresses autophagy through the PI3K/Akt/mTOR pathway (PMID:30089483, PMID:32668328, PMID:30736840, PMID:30249289, PMID:38807081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 Medium

    Identification of SPAG5 as a novel mitotic spindle protein that interacts with p29 and is phosphorylated by CDK1 established its basic identity as a cell-cycle-regulated microtubule-associated factor, while parallel discovery of its Odf1-binding leucine zipper domain connected it to sperm outer dense fiber biology.

    Evidence Yeast two-hybrid, immunofluorescence localization, in vitro CDK1 kinase assay, and leucine zipper domain mapping in two independent studies

    PMID:11468777 PMID:11549262

    Open questions at the time
    • CDK1 phosphorylation sites not mapped
    • in vivo significance of p29 interaction unknown
    • Odf1 interaction not confirmed by co-IP
  2. 2002 High

    Genetic knockout of Spag5 in mice revealed no spermatogenesis or fertility defect, demonstrating functional redundancy and raising the question of which processes genuinely require SPAG5.

    Evidence Homologous recombination knockout in mice with systematic fertility and spermatogenesis analysis

    PMID:11884588

    Open questions at the time
    • Compensating gene(s) not identified
    • mitotic phenotype in somatic tissues of knockout mice not examined
  3. 2006 High

    Demonstration that SPAG5 binds microtubules in somatic cells but associates with outer dense fibers (not axonemal microtubules) in spermatids established its cell-type-dependent function, while a natural truncating mutation in rats proved the C-terminal spindle-targeting domain is essential for Sertoli cell mitosis.

    Evidence Immunoelectron microscopy, in vitro microtubule-binding assay, positional cloning of hgn rat mutation, immunohistochemistry of mutant testes

    PMID:16211599 PMID:16816335

    Open questions at the time
    • Structural basis of C-terminal spindle targeting not resolved
    • whether human SPAG5 mutations cause male infertility not tested
  4. 2012 Medium

    Localization of SPAG5 to photoreceptor basal bodies with Usher syndrome proteins NINLisoB and USH2AisoB suggested a postmitotic ciliary trafficking role beyond its known mitotic function.

    Evidence Immunofluorescence co-localization and protein interaction analysis in retinal tissue

    PMID:23351521

    Open questions at the time
    • No functional assay for SPAG5 in ciliary trafficking performed
    • interaction with USH2A not confirmed by reciprocal co-IP
    • relevance to Usher syndrome pathogenesis not established
  5. 2014 High

    Discovery that ORP8 recruits SPAG5 to ER membranes and that SPAG5 is required for ORP8- and oxysterol-mediated G2/M arrest placed SPAG5 as an effector in lipid-sensing cell cycle control.

    Evidence Yeast two-hybrid confirmed by pull-down and co-IP, siRNA knockdown with flow cytometry cell cycle analysis

    PMID:24424245

    Open questions at the time
    • Direct mechanism by which SPAG5 enforces G2/M arrest downstream of ORP8 unknown
    • oxysterol-SPAG5 axis not validated in vivo
  6. 2018 Medium

    Identification of CEP55 as a SPAG5 binding partner that triggers AKT Ser473 phosphorylation, and demonstration that SPAG5 modulates β-catenin degradation to activate TCF4 signaling, revealed two distinct oncogenic signaling axes through which SPAG5 promotes cancer cell growth.

    Evidence Co-IP, phosphorylation assays, PI3K inhibitor rescue in HCC cells; shRNA knockdown with β-catenin/SCARA5 epistasis in HCC

    PMID:30089483 PMID:30249289

    Open questions at the time
    • How SPAG5-CEP55 interaction activates PI3K not biochemically defined
    • mechanism of β-catenin stabilization by SPAG5 not reconstituted
  7. 2019 Medium

    SPAG5 was shown to bind MYCBP to enhance c-MYC transcriptional activity driving cell cycle genes, while the p53-p21 axis was identified as a transcriptional repressor of SPAG5, together defining a regulatory circuit linking tumor suppressors and oncogenes to SPAG5 expression and function.

    Evidence Co-IP and epistasis via MYCBP/c-MYC knockdown in TNBC; MDM2 inhibitor treatment with p53/p21 knockdown in lung adenocarcinoma

    PMID:30736840 PMID:30955859

    Open questions at the time
    • Whether SPAG5 directly stabilizes MYCBP protein or acts transcriptionally not resolved
    • p53-p21 repression mechanism (direct binding vs indirect) not defined
  8. 2020 Medium

    Multiple studies converged to show that SPAG5 transcription is directly driven by YAP/TAZ/TEAD (confirmed by ChIP), that USP14 stabilizes SPAG5 protein via de-ubiquitination, and that SPAG5 stabilizes FOXM1 to upregulate MMP2 and promote metastasis, together defining the transcriptional, post-translational, and downstream effector logic of SPAG5 in cancer.

    Evidence ChIP for YAP/TAZ/TEAD on SPAG5 promoter, USP14 pulldown/co-IP/de-ubiquitination assay, FOXM1 stability assays with in vivo metastasis models

    PMID:31957155 PMID:32668328 PMID:33230261

    Open questions at the time
    • USP14-mediated de-ubiquitination site(s) on SPAG5 not mapped
    • mechanism by which SPAG5 inhibits FOXM1 degradation not biochemically reconstituted
    • relative contributions of YAP vs MYC vs p53 to SPAG5 transcription not quantified
  9. 2022 Medium

    Identification of CLUH as a stable, RNA-independent interactor and SF3B4 as a splicing factor required for proper SPAG5 mRNA maturation expanded the regulatory network controlling SPAG5 protein levels beyond transcription and ubiquitin-mediated turnover.

    Evidence Co-IP and BioID proximity labeling for CLUH; RNA-seq alternative splicing analysis and epistasis for SF3B4

    PMID:35012549 PMID:35853859

    Open questions at the time
    • Functional consequence of CLUH-SPAG5 interaction unknown
    • whether SF3B4-mediated splicing regulation of SPAG5 occurs in normal tissues not tested
  10. 2024 Medium

    SPAG5 was established as an upstream suppressor of autophagy via PI3K/Akt/mTOR, with in vivo relevance in atherosclerosis, while coordinated transcriptional regulation by YAP, mutant p53, and MYC was demonstrated at the SPAG5 promoter in TNBC.

    Evidence siRNA knockdown in HUVECs and ApoE-/- mice with autophagy inhibitor rescue; ChIP showing MYC recruitment to SPAG5 promoter dependent on YAP and mutant p53

    PMID:38807081 PMID:39164278

    Open questions at the time
    • Direct molecular target through which SPAG5 activates PI3K in the autophagy context not identified
    • whether SPAG5 autophagy regulation is cell-type specific not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct biochemical mechanism by which SPAG5 activates PI3K/AKT signaling, the structural basis of its spindle-targeting domain, and the identity of compensating factors in Spag5-knockout mice remain unresolved.
  • No structural model of SPAG5 or its domain-specific interactions exists
  • PI3K activation mechanism by SPAG5-CEP55 not reconstituted biochemically
  • compensating gene(s) in Spag5-null mice not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 3 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 4 R-HSA-9612973 Autophagy 2 R-HSA-1266738 Developmental Biology 1
Partners
CEP55CLUHFOXM1MYCBPNINLODF1ORP8USP14

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 hMAP126 (SPAG5) was identified as a novel mitotic spindle-associated protein that interacts with p29 in a yeast two-hybrid assay, localizes to the mitotic spindle, and is phosphorylated by p34(cdc2) kinase in vitro, indicating post-translational regulation during mitosis. Yeast two-hybrid, subcellular localization by immunofluorescence, in vitro kinase assay Biochemical and biophysical research communications Medium 11549262
2001 Spag5 encodes a ~200 kDa testicular protein that binds the major outer dense fiber protein Odf1 via a leucine zipper motif located in the C-terminal region; it shares 73% similarity with the mitotic spindle protein Deepest. Yeast two-hybrid, leucine zipper domain mapping Molecular reproduction and development Medium 11468777
2002 Targeted disruption of Spag5 in mice (Spag5-null) showed no detectable spermatogenesis or fertility defect, indicating that Spag5 is dispensable for these processes in vivo, likely due to functional compensation. Homologous recombination knockout, spermatogenesis and fertility analysis Molecular and cellular biology High 11884588
2006 Rat Spag5 localizes to the endoplasmic reticulum and microtubules in somatic cells, confirmed by in vivo localization and in vitro microtubule-binding assays; in contrast, in elongated spermatids and epididymal sperm, a 58 kDa Spag5 form associates with outer dense fibers (ODF) but not axonemal microtubules, demonstrating cell-type-dependent localization and function. Immunofluorescence, in vitro microtubule-binding assay, immunoelectron microscopy, Western blot Molecular reproduction and development High 16211599
2006 A 25 bp duplication insertion in exon 6 of Spag5/astrin in hypogonadic (hgn/hgn) rats produces a truncated Spag5 protein lacking the C-terminal spindle-targeting domain, resulting in defective mitotic spindle organization and apoptotic death of proliferating Sertoli cells, establishing SPAG5 as essential for Sertoli cell proliferation and testis development. Positional cloning, mutant characterization, immunohistochemistry, domain analysis Reproduction (Cambridge, England) High 16816335
2012 SPAG5/Astrin was identified in the retina and found to interact with USH2AisoB interaction partner NINLisoB; SPAG5, USH2AisoB, and NINLisoB colocalize at the basal bodies of photoreceptor cells, connecting SPAG5 to the Usher protein network and suggesting a postmitotic role in microtubule-based ciliary trafficking. Co-localization by immunofluorescence, in situ hybridization, qPCR, protein interaction analysis Cilia Medium 23351521
2014 ORP8 (OSBP-related protein 8) was identified as a binding partner of SPAG5/Astrin by yeast two-hybrid, confirmed by pull-down and co-immunoprecipitation; ORP8 overexpression recruits SPAG5 to ER membranes in interphase cells, and SPAG5 knockdown significantly reduces the G2/M cell cycle arrest induced by both ORP8 overexpression and 25-hydroxycholesterol treatment, placing SPAG5 downstream of ORP8 in oxysterol-mediated cell cycle regulation. Yeast two-hybrid, pull-down, co-IP, cell cycle analysis by flow cytometry, siRNA knockdown Experimental cell research High 24424245
2018 SPAG5 interacts with the centrosomal protein CEP55, and this interaction triggers phosphorylation of AKT at Ser473, activating the PI3K/AKT signaling pathway to promote tumor growth and metastasis in hepatocellular carcinoma; inhibition of PI3K/AKT signaling markedly attenuated SPAG5-mediated cell growth. Co-immunoprecipitation, phosphorylation assay, in vitro and in vivo functional assays, PI3K/AKT inhibitor treatment Molecular cancer Medium 30089483
2018 SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modulation of β-catenin degradation, thereby activating β-catenin/TCF4 signaling; SPAG5 and SCARA5 expression are inversely correlated in HCC tissues. shRNA knockdown, overexpression, in vitro/in vivo functional assays, Western blot, co-expression analysis Journal of experimental & clinical cancer research Medium 30249289
2019 SPAG5 interacts with c-MYC binding protein (MYCBP) in triple-negative breast cancer, increasing MYCBP protein levels and thereby enhancing c-MYC transcriptional activity, which drives expression of c-MYC target genes including CDC20, CDC25C, BRCA1, BRCA2, and RAD51; knockdown of MYCBP or c-MYC abolished SPAG5-induced cell-cycle progression and proliferation. Co-immunoprecipitation, overexpression, knockdown, c-MYC transcriptional activity assay, in vitro and in vivo functional assays Journal of hematology & oncology Medium 30736840
2019 SPAG5 promotes gastric cancer cell progression by activating the Wnt/β-catenin/Survivin axis; SPAG5 knockdown inhibited proliferation in vivo and in vitro, and SPAG5-mediated effects required Survivin expression downstream of β-catenin. shRNA knockdown, overexpression, Western blot, in vivo xenograft, epistasis rescue assay Experimental cell research Low 30904482
2019 p53-p21 axis transcriptionally suppresses SPAG5 expression in lung adenocarcinoma; restoration of p53 via MDM2 inhibitor Nutlin-3a reduced SPAG5 levels only in wild-type p53 cells, and knockdown of p53 or p21 attenuated Nutlin-3a-induced SPAG5 repression. MDM2 inhibitor treatment, p53/p21 knockdown, RT-PCR, Western blot Biochemical and biophysical research communications Medium 30955859
2020 SPAG5 is a direct transcriptional target of YAP/TAZ/TEAD (Hippo pathway effectors) in breast cancer; depletion of YAP, TAZ, or TEAD strongly reduced SPAG5 expression, pharmacological targeting of YAP/TAZ reduced SPAG5, and SPAG5 depletion impaired cancer cell cycle progression, proliferation, and migration. Additionally, SPAG5 is directly targeted at the post-transcriptional level by miR-10b-3p. ChIP, siRNA knockdown, pharmacological inhibition, luciferase reporter assay, cell functional assays Cell death and differentiation Medium 33230261
2020 SPAG5-AS1 (lncRNA) interacts with ubiquitin-specific peptidase USP14, leading to de-ubiquitination and stabilization of SPAG5 protein; additionally, SPAG5-AS1 acts as a ceRNA sponging miR-769-5p to regulate YY1, which transcriptionally upregulates both SPAG5-AS1 and SPAG5; elevated SPAG5 inhibits autophagy and promotes apoptosis in podocytes via the AKT/mTOR pathway. Pulldown, RIP, co-IP, ChIP, luciferase reporter assay, flow cytometry, Western blot Cell proliferation Medium 31957155
2020 SPAG5 promotes breast cancer cell proliferation and invasion by upregulating Wnt3 expression and increasing β-catenin/TCF4 transcriptional activity; inhibition of Wnt3 or β-catenin reversed SPAG5-mediated oncogenic effects. siRNA knockdown, overexpression, luciferase reporter assay, functional cell assays Clinical and experimental pharmacology & physiology Low 30854682
2020 SPAG5 promotes osteosarcoma metastasis via the SPAG5-FOXM1-MMP2 axis; SPAG5 stabilizes FOXM1 protein by inhibiting its degradation, thereby increasing FOXM1-driven MMP2 expression and promoting EMT and lung metastasis in vivo. siRNA knockdown, overexpression, in vivo metastasis model, Western blot, functional invasion assays The international journal of biochemistry & cell biology Medium 32668328
2022 CLUH interacts stably and RNA-independently with SPAG5 in cytosolic granular structures, identified by co-IP and BioID proximity labeling in mammalian cells. Co-immunoprecipitation, BioID proximity labeling, fluorescence imaging BMC biology Medium 35012549
2022 Splicing factor SF3B4 promotes SPAG5 expression by enabling proper pre-mRNA splicing; SF3B4 knockdown leads to retained introns and reduced SPAG5 mRNA maturation, and SPAG5 deficiency impairs the oncogenic effects of SF3B4 overexpression in cervical cancer cells. RNA-seq, alternative splicing analysis, knockdown/overexpression, in vitro and in vivo functional assays Cell death discovery Medium 35853859
2024 SPAG5 knockdown activates autophagy in HUVECs and in ApoE-/- mouse aorta by inhibiting the PI3K/Akt/mTOR signaling pathway, resulting in reduced atherosclerotic plaque formation; autophagy inhibitor 3-MA reversed the protective effects of SPAG5 silencing, establishing SPAG5 as an upstream regulator of autophagy via PI3K/Akt/mTOR. siRNA knockdown, mouse AS model, Western blot, flow cytometry, GFP-LC3 imaging, autophagy inhibitor rescue BMC cardiovascular disorders Medium 38807081
2024 In TNBC, high SPAG5 expression is regulated by coordinated activity of YAP, mutant p53, and MYC; depletion of YAP or mutant p53 reduced SPAG5 expression and MYC recruitment to the SPAG5 promoter, and MYC targeting reduced SPAG5 expression and TNBC tumorigenicity in a SPAG5-expression-dependent manner. ChIP, siRNA knockdown, promoter analysis, in vitro/in vivo functional assays Cell death & disease Medium 39164278

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Ethiopians and Khoisan share the deepest clades of the human Y-chromosome phylogeny. American journal of human genetics 118 11719903
1999 Microbial Diversity in Sediments Collected from the Deepest Cold-Seep Area, the Japan Trench. Marine biotechnology (New York, N.Y.) 101 10489418
2009 The environmental clade LKM11 and Rozella form the deepest branching clade of fungi. Protist 98 19674933
2002 Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma. Oncology 95 11914602
2019 Large-scale genomic sequence data resolve the deepest divergences in the legume phylogeny and support a near-simultaneous evolutionary origin of all six subfamilies. The New phytologist 91 31665814
2020 SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell proliferation 90 31957155
2007 A clade uniting the green algae Mesostigma viride and Chlorokybus atmophyticus represents the deepest branch of the Streptophyta in chloroplast genome-based phylogenies. BMC biology 87 17222354
2003 Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 78 12457033
2016 Chloroplast phylogenomic analyses reveal the deepest-branching lineage of the Chlorophyta, Palmophyllophyceae class. nov. Scientific reports 72 27157793
2018 SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma. Molecular cancer 71 30089483
2016 miR-539 inhibits prostate cancer progression by directly targeting SPAG5. Journal of experimental & clinical cancer research : CR 70 27037000
2000 Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer. International journal of oncology 68 10601549
2015 Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. Journal of virology 61 26136578
2001 Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 60 11244332
1991 Time of the deepest root for polymorphism in human mitochondrial DNA. Journal of molecular evolution 60 1901367
2020 Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms. Microbiome 59 32482169
2022 An estimate of the deepest branches of the tree of life from ancient vertically evolving genes. eLife 58 35190025
2010 First investigation of the microbiology of the deepest layer of ocean crust. PloS one 58 21079766
2019 SPAG5 upregulation contributes to enhanced c-MYC transcriptional activity via interaction with c-MYC binding protein in triple-negative breast cancer. Journal of hematology & oncology 56 30736840
2001 Cloning and characterization of hMAP126, a new member of mitotic spindle-associated proteins. Biochemical and biophysical research communications 53 11549262
2020 Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens. Molecular biology and evolution 52 32697301
2001 Testicular protein Spag5 has similarity to mitotic spindle protein Deepest and binds outer dense fiber protein Odf1. Molecular reproduction and development 51 11468777
1996 Complete nucleotide sequences of the genes encoding translation elongation factors 1 alpha and 2 from a microsporidian parasite, Glugea plecoglossi: implications for the deepest branching of eukaryotes. Journal of biochemistry 51 9010756
2004 Genomic characterization of thermophilic Geobacillus species isolated from the deepest sea mud of the Mariana Trench. Extremophiles : life under extreme conditions 49 15168170
2018 SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation. Journal of experimental & clinical cancer research : CR 48 30249289
2019 LncRNA LINC00857 regulates lung adenocarcinoma progression, apoptosis and glycolysis by targeting miR-1179/SPAG5 axis. Human cell 47 31667785
2017 Molecular adaptation in the world's deepest-living animal: Insights from transcriptome sequencing of the hadal amphipod Hirondellea gigas. Molecular ecology 47 28429829
2012 Metagenomic analysis of hadopelagic microbial assemblages thriving at the deepest part of Mediterranean Sea, Matapan-Vavilov Deep. Environmental microbiology 46 22827264
2008 Crystal structure of GH13 alpha-glucosidase GSJ from one of the deepest sea bacteria. Proteins 46 18398906
2007 Africans in Yorkshire? The deepest-rooting clade of the Y phylogeny within an English genealogy. European journal of human genetics : EJHG 44 17245408
2004 Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. International journal of oncology 43 14767538
2006 Andalucia (n. gen.)--the deepest branch within jakobids (Jakobida; Excavata), based on morphological and molecular study of a new flagellate from soil. The Journal of eukaryotic microbiology 42 16579813
2002 Psychromonas kaikoae sp. nov., a novel from the deepest piezophilic bacterium cold-seep sediments in the Japan Trench. International journal of systematic and evolutionary microbiology 41 12361254
1998 Evidence for sodium-dependent active urea secretion in the deepest subsegment of the rat inner medullary collecting duct. The Journal of clinical investigation 41 9435315
2016 Bacterial community composition in the water column of the deepest freshwater Lake Baikal as determined by next-generation sequencing. FEMS microbiology ecology 37 27162182
2013 Guidelines for the excision of cutaneous squamous cell cancers in the United Kingdom: the best cut is the deepest. Journal of plastic, reconstructive & aesthetic surgery : JPRAS 37 23352886
2012 Amoeba stages in the deepest branching heteroloboseans, including Pharyngomonas: evolutionary and systematic implications. Protist 33 23021907
2020 SPAG5: An Emerging Oncogene. Trends in cancer 30 32291236
2016 Thermococcus piezophilus sp. nov., a novel hyperthermophilic and piezophilic archaeon with a broad pressure range for growth, isolated from a deepest hydrothermal vent at the Mid-Cayman Rise. Systematic and applied microbiology 30 27638197
2006 Glucosylglycerate biosynthesis in the deepest lineage of the Bacteria: characterization of the thermophilic proteins GpgS and GpgP from Persephonella marina. Journal of bacteriology 30 17189358
2012 The Hadal Amphipod Hirondellea gigas possessing a unique cellulase for digesting wooden debris buried in the deepest seafloor. PloS one 29 22905166
2019 SPAG5 contributes to the progression of gastric cancer by upregulation of Survivin depend on activating the wnt/β-catenin pathway. Experimental cell research 28 30904482
2020 Aberrant transcriptional and post-transcriptional regulation of SPAG5, a YAP-TAZ-TEAD downstream effector, fuels breast cancer cell proliferation. Cell death and differentiation 27 33230261
2006 Rat Spag5 associates in somatic cells with endoplasmic reticulum and microtubules but in spermatozoa with outer dense fibers. Molecular reproduction and development 26 16211599
2002 Targeted disruption of the testicular SPAG5/deepest protein does not affect spermatogenesis or fertility. Molecular and cellular biology 26 11884588
2006 Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immature Sertoli cells in rat hypogonadic (hgn/hgn) testes. Reproduction (Cambridge, England) 24 16816335
2020 Environmental drivers of plankton protist communities along latitudinal and vertical gradients in the oldest and deepest freshwater lake. Environmental microbiology 23 33270368
1995 Histologic grade and cellular proliferation at the deepest invasive portion correlate with the high malignancy of submucosal invasive gastric carcinoma. Oncology 23 7777250
2002 Molecular phylogeny of a circum-global, diverse gastropod superfamily (Cerithioidea: Mollusca: Caenogastropoda): pushing the deepest phylogenetic limits of mitochondrial LSU rDNA sequences. Molecular phylogenetics and evolution 22 11884164
2019 High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/β-catenin signalling. Clinical and experimental pharmacology & physiology 21 30854682
2019 p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma. Biochemical and biophysical research communications 21 30955859
2000 Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer. Oncology reports 21 10854531
2022 The splicing factor SF3B4 drives proliferation and invasion in cervical cancer by regulating SPAG5. Cell death discovery 20 35853859
2018 Genome Reduction in Psychromonas Species within the Gut of an Amphipod from the Ocean's Deepest Point. mSystems 20 29657971
2003 Clinical significance of thrombospondin-1 expression in relation to vascular endothelial growth factor and interleukin-10 expression at the deepest invasive tumor site of advanced colorectal carcinoma. International journal of oncology 20 12963968
2022 The interactome of CLUH reveals its association to SPAG5 and its co-translational proximity to mitochondrial proteins. BMC biology 19 35012549
2022 Virioplankton assemblages from challenger deep, the deepest place in the oceans. iScience 19 35942087
2021 MiR-133a-3p attenuates resistance of non-small cell lung cancer cells to gefitinib by targeting SPAG5. Journal of clinical laboratory analysis 19 34057242
2018 Insight Into the Pico- and Nano-Phytoplankton Communities in the Deepest Biosphere, the Mariana Trench. Frontiers in microbiology 19 30319587
2020 SPAG5 promotes osteosarcoma metastasis via activation of FOXM1/MMP2 axis. The international journal of biochemistry & cell biology 16 32668328
2014 OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle. Experimental cell research 16 24424245
2012 The mitotic spindle protein SPAG5/Astrin connects to the Usher protein network postmitotically. Cilia 16 23351521
2010 Novel microbial diversity retrieved by autonomous robotic exploration of the world's deepest vertical phreatic sinkhole. Astrobiology 16 20298146
2023 Phylogenetically and metabolically diverse autotrophs in the world's deepest blue hole. ISME communications 14 37964026
2020 Naringenin Inhibits Cell Migration, Invasion, and Tumor Growth by Regulating circFOXM1/miR-3619-5p/SPAG5 Axis in Lung Cancer. Cancer biotherapy & radiopharmaceuticals 14 32598178
2019 Massive Loss of Olfactory Receptors But Not Trace Amine-Associated Receptors in the World's Deepest-Living Fish (Pseudoliparis swirei). Genes 14 31717379
2017 Dynamics of bacterial class Bacilli in the deepest valley lake of Kashmir-the Manasbal Lake. Microbial pathogenesis 14 28087491
2025 Microbial ecosystems and ecological driving forces in the deepest ocean sediments. Cell 13 40054447
2023 SPAG5, the upstream protein of Wnt and the target of curcumin, inhibits hepatocellular carcinoma. Oncology reports 13 37539742
2012 Organic solutes in the deepest phylogenetic branches of the Bacteria: identification of α(1-6)glucosyl-α(1-2)glucosylglycerate in Persephonella marina. Extremophiles : life under extreme conditions 12 23179593
2022 SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer. DNA and cell biology 11 36264549
2023 Insight into the adaptation mechanisms of high hydrostatic pressure in physiology and metabolism of hadal fungi from the deepest ocean sediment. mSystems 10 38117068
2022 Barriers to gene flow in the deepest ocean ecosystems: Evidence from global population genomics of a cosmopolitan amphipod. Science advances 10 36288308
2021 Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer. Journal of nanobiotechnology 10 34162370
2016 The deepest mitochondrial genome sequenced from Mariana Trench Hirondellea gigas (Amphipoda). Mitochondrial DNA. Part B, Resources 10 33473633
2008 The first "Slit" is the deepest: the secret to a hollow heart. The Journal of cell biology 10 18663138
2022 SPAG5 as a novel biomarker and potential therapeutic target via regulating AKT pathway in multiple myeloma. Leukemia & lymphoma 9 35730922
2022 Curcumin Improves Keratinocyte Proliferation, Inflammation, and Oxidative Stress through Mediating the SPAG5/FOXM1 Axis in an In Vitro Model of Actinic Dermatitis by Ultraviolet. Disease markers 9 36118675
2021 SPAG5 Is Involved in Human Gliomagenesis Through the Regulation of Cell Proliferation and Apoptosis. Frontiers in oncology 9 34796102
2020 Diversity hotspot and unique community structure of foraminifera in the world's deepest marine blue hole - Sansha Yongle Blue Hole. Scientific reports 9 32581270
2021 Description of the marine predator Sericomyxa perlucida gen. et sp. nov., a cultivated representative of the deepest branching lineage of vampyrellid amoebae (Vampyrellida, Rhizaria). The Journal of eukaryotic microbiology 8 34152052
2021 CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis. Scientific reports 8 34903799
2020 MSX1 is differentially expressed in the deepest impacted maxillary third molars. The British journal of oral & maxillofacial surgery 8 32381388
2012 From the deepest sea shelf to the uppermost kitchen cabinet shelf: the quest for novel TNF-α inhibitors. Current topics in medicinal chemistry 8 22650373
2024 Targeting of mutant-p53 and MYC as a novel strategy to inhibit oncogenic SPAG5 activity in triple negative breast cancer. Cell death & disease 7 39164278
2020 MicroRNA-367-3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5-mediated Wnt/β-catenin signalling. Clinical and experimental pharmacology & physiology 7 31792998
1997 Single carcinoma cells at the deepest invasive portion correlate with metastatic potential of advanced colorectal carcinoma. International journal of oncology 7 21533496
2023 Maturases and Group II Introns in the Mitochondrial Genomes of the Deepest Jakobid Branch. Genome biology and evolution 6 37029959
2021 Marine signature taxa and core microbial community stability along latitudinal and vertical gradients in sediments of the deepest freshwater lake. The ISME journal 6 34012102
2012 SPAG5 mRNA is over-expressed in peripheral blood leukocytes of patients with Down's syndrome and cryptorchidism. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 6 22773063
2023 SPAG5 promotes the proliferation, migration, invasion, and epithelial-mesenchymal transformation of colorectal cancer cells by activating the PI3K/AKT signaling pathway. The Chinese journal of physiology 4 37929348
2003 Crystallization and preliminary X-ray study of alpha-glucosidase from Geobacillus sp strain HTA-462, one of the deepest sea bacteria. Acta crystallographica. Section D, Biological crystallography 4 12832785
2025 Application of a high-throughput swarm-based deep neural network Algorithm reveals SPAG5 downregulation as a potential therapeutic target in adult AML. Functional & integrative genomics 3 39762615
2024 Fungal Abundance and Diversity in the Mariana Trench, the Deepest Ecosystem on Earth. Journal of fungi (Basel, Switzerland) 3 38248982
2024 SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE-/- mice. BMC cardiovascular disorders 3 38807081
2024 SPAG5 and ASPM play important roles in gastric cancer: An observational study. Medicine 3 38875410
2022 Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis. Molecular biotechnology 3 36346578
2024 Distinct microbial nitrogen cycling processes in the deepest part of the ocean. mSystems 2 38940525
2024 Deep sea treasures - Insights from museum archives shed light on coral microbial diversity within deepest ocean ecosystems. Heliyon 1 38468949
2024 [Biological role of SPAG5 in the malignant proliferation of gastric cancer cells]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 39276045