Affinage

SPAG5

Sperm-associated antigen 5 · UniProt Q96R06

Length
1193 aa
Mass
134.4 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPAG5 (hMAP126/Astrin) is a microtubule-associated mitotic spindle protein that is phosphorylated by p34(cdc2)/CDK1 and localizes to the mitotic spindle in dividing cells while distributing to the endoplasmic reticulum and microtubules in interphase somatic cells (PMID:11549262, PMID:16211599). Its localization and binding partners are cell-type specific: in spermatids and sperm it associates with outer dense fibers through a C-terminal leucine-zipper interaction with ODF1 rather than with axonemal microtubules (PMID:11468777, PMID:16211599), and in interphase cells it can be recruited onto ER membranes by ORP8, downstream of which SPAG5 contributes to oxysterol-mediated G2/M cell cycle accumulation (PMID:24424245). A C-terminal spindle-targeting domain is essential for SPAG5's function in cell division: a natural truncating mutation in rats abolishes spindle formation and causes abnormal Sertoli cell mitosis, apoptosis, and testicular dysplasia, although complete Spag5 knockout in mice leaves spermatogenesis and fertility intact, indicating functional compensation in the germline (PMID:11884588, PMID:16816335). In cancer, SPAG5 acts as a proliferation- and survival-promoting hub: it interacts with CEP55 to activate PI3K/AKT signaling (PMID:30089483), engages MYCBP to amplify c-MYC transcriptional output driving cell-cycle genes (PMID:30736840), stabilizes FOXM1 to upregulate MMP2 and promote metastasis (PMID:32668328), and modulates beta-catenin degradation to repress SCARA5 (PMID:30249289). SPAG5 expression is itself a convergence point of oncogenic transcriptional control, being a direct target of the YAP/TAZ/TEAD (Hippo) axis and, in triple-negative breast cancer, of coordinated YAP, mutant p53, and MYC activity, while the wild-type p53-p21 axis suppresses it (PMID:30955859, PMID:33230261, PMID:39164278). Across multiple disease contexts SPAG5 also regulates PI3K/AKT/mTOR-dependent autophagy and ROS/ferroptosis balance (PMID:41774258, PMID:38807081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 Medium

    Established SPAG5's identity as a cell-cycle-regulated spindle protein by showing it associates with the mitotic spindle and is a CDK1 substrate, linking it to mitotic regulation.

    Evidence Polyclonal antibody immunolocalization and in vitro p34(cdc2) kinase assay

    PMID:11549262

    Open questions at the time
    • In vitro kinase phosphorylation site not mapped
    • Functional consequence of phosphorylation on spindle binding undefined
  2. 2001 Medium

    Identified a tissue-specific binding partner, showing SPAG5 binds the outer dense fiber protein ODF1 via a C-terminal leucine zipper, implicating it in sperm tail structure.

    Evidence Yeast two-hybrid screen with leucine-zipper domain mapping in rat

    PMID:11468777

    Open questions at the time
    • Interaction not biochemically reconstituted
    • Physiological role of ODF1 binding untested
  3. 2002 High

    Tested whether SPAG5 is required for spermatogenesis; null mice were fertile, revealing functional redundancy in the germline despite the ODF1 interaction.

    Evidence Homologous-recombination knockout and phenotypic analysis of null mice

    PMID:11884588

    Open questions at the time
    • Compensating proteins not identified
    • Somatic/mitotic phenotypes not examined in this knockout
  4. 2006 High

    Resolved SPAG5's cell-type-specific localization, distinguishing ER/microtubule association in somatic cells from outer-dense-fiber association in sperm, defining context-dependent function.

    Evidence Immunofluorescence, in vitro microtubule-binding, immuno-EM, and fractionation in rat

    PMID:16211599

    Open questions at the time
    • Microtubule-binding determinant not mapped at residue level
    • Isoform-specific functions unresolved
  5. 2006 High

    Established the C-terminal spindle-targeting domain as essential for cell division, since a natural truncation caused defective Sertoli cell mitosis and testicular dysplasia.

    Evidence Positional cloning of hgn/hgn rat mutant with marker immunostaining and phenotyping

    PMID:16816335

    Open questions at the time
    • Molecular partners of the spindle-targeting domain not defined
    • Reconciliation with fertile mouse knockout phenotype unresolved
  6. 2013 Low

    Connected SPAG5 to ciliary/basal body biology by placing it in the Usher protein network at photoreceptor basal bodies.

    Evidence Yeast two-hybrid and co-localization in retinal photoreceptors

    PMID:23351521

    Open questions at the time
    • Yeast two-hybrid interaction not biochemically confirmed
    • Functional role at basal bodies untested
    • Relevance to disease unknown
  7. 2014 High

    Showed SPAG5 acts downstream of ORP8 in oxysterol-driven cell cycle control, integrating it into lipid-sensing G2/M regulation at the ER.

    Evidence Yeast two-hybrid, pull-down, reciprocal co-IP, siRNA knockdown, and flow cytometry

    PMID:24424245

    Open questions at the time
    • Mechanism linking ER recruitment to G2/M arrest unresolved
    • Direct binding interface not mapped
  8. 2018 Medium

    Defined an oncogenic mechanism whereby SPAG5-CEP55 binding activates PI3K/AKT to drive HCC growth and metastasis.

    Evidence Co-IP, PI3K/AKT inhibitor rescue, and in vitro/in vivo HCC assays

    PMID:30089483

    Open questions at the time
    • How CEP55 binding triggers AKT Ser473 phosphorylation not mechanistically resolved
    • Single lab without reciprocal structural validation
  9. 2018 Medium

    Linked SPAG5 to Wnt/beta-catenin signaling, showing it represses SCARA5 by modulating beta-catenin degradation to promote HCC.

    Evidence shRNA/overexpression with Western blot of beta-catenin pathway and xenografts

    PMID:30249289

    Open questions at the time
    • Direct effect of SPAG5 on beta-catenin turnover not biochemically demonstrated
    • Mechanism inferred from pathway markers only
  10. 2019 Medium

    Established a SPAG5-MYCBP-c-MYC axis amplifying c-MYC transcriptional output and cell-cycle gene expression in TNBC.

    Evidence Co-IP, Western blot, and siRNA epistasis with functional assays

    PMID:30736840

    Open questions at the time
    • Mechanism by which SPAG5 raises MYCBP levels unknown
    • Direct vs indirect target gene effects not distinguished
  11. 2019 Medium

    Identified the p53-p21 axis as a required suppressor of SPAG5 transcription, defining tumor-suppressor control of SPAG5.

    Evidence Nutlin-3a treatment with p53/p21 knockdown, Western blot, and qRT-PCR

    PMID:30955859

    Open questions at the time
    • Direct vs indirect transcriptional mechanism not resolved
    • p53/p21 binding to SPAG5 locus not demonstrated
  12. 2020 Medium

    Placed SPAG5 as a direct YAP/TAZ/TEAD Hippo-pathway target additionally repressed by miR-10b-3p, defining its upstream transcriptional/post-transcriptional regulation.

    Evidence ChIP/luciferase reporter for TEAD, YAP/TAZ/TEAD knockdown, and miRNA target validation

    PMID:33230261

    Open questions at the time
    • Relative contribution of transcriptional vs miRNA control unquantified
    • Single lab
  13. 2020 Medium

    Defined post-translational stabilization of SPAG5 via the SPAG5-AS1/USP14 axis and downstream AKT/mTOR-driven autophagy suppression in podocytes.

    Evidence Pulldown, RIP, co-IP, ChIP, luciferase, and functional assays under high glucose

    PMID:31957155

    Open questions at the time
    • Direct USP14 deubiquitination of SPAG5 not enzymatically reconstituted
    • Relevance beyond podocytes untested
  14. 2020 Medium

    Established a SPAG5-FOXM1-MMP2 axis driving osteosarcoma metastasis through FOXM1 protein stabilization.

    Evidence siRNA/shRNA knockdown, Western blot for FOXM1 stability, and in vivo metastasis model

    PMID:32668328

    Open questions at the time
    • No direct ubiquitination assay for FOXM1 stabilization
    • Mechanism of SPAG5-FOXM1 interaction undefined
  15. 2022 Medium

    Showed SPAG5 expression depends on SF3B4-mediated splicing, identifying a splicing-level control point for SPAG5 in cervical cancer.

    Evidence RNA-seq splicing analysis, SF3B4 knockdown, and SPAG5 rescue assays

    PMID:35853859

    Open questions at the time
    • Direct SF3B4 binding to SPAG5 pre-mRNA not shown
    • Specificity of splicing effect not established
  16. 2024 Medium

    Linked SPAG5 to redox-dependent cell death, showing it promotes ROS-driven ferroptosis and chemosensitivity in colorectal cancer.

    Evidence Gain/loss-of-function, ROS measurement, ferroptosis and chemosensitivity assays with patient cohort

    PMID:41774258

    Open questions at the time
    • Mechanism by which SPAG5 elevates ROS unknown
    • Connection to mitotic function unclear
  17. 2024 Medium

    Extended SPAG5's PI3K/Akt/mTOR-autophagy role to vascular disease, where SPAG5 silencing activates autophagy and reduces atherosclerosis.

    Evidence Knockdown with PI3K/Akt/mTOR and autophagy readouts, 3-MA rescue, and ApoE-/- mouse model

    PMID:38807081

    Open questions at the time
    • Direct molecular link between SPAG5 and PI3K/Akt activation undefined
    • Cell-autonomous vs systemic effects not separated
  18. 2024 Medium

    Refined SPAG5 transcriptional control in TNBC, showing coordinated YAP, mutant p53, and MYC activity with MYC recruitment to the SPAG5 promoter.

    Evidence siRNA knockdown of YAP/mutant p53/MYC, ChIP at SPAG5 promoter, and in vivo assays

    PMID:39164278

    Open questions at the time
    • Direct interplay among YAP, mutant p53, and MYC at the locus not fully resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SPAG5's core mitotic spindle function mechanistically connects to its diverse oncogenic signaling roles (PI3K/AKT, c-MYC, beta-catenin, FOXM1, ROS/ferroptosis) remains unresolved.
  • No unified model linking spindle role to signaling roles
  • Structural basis of partner interactions undefined
  • Direct enzymatic activities, if any, unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005815 microtubule organizing center 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3
Partners
CEP55FOXM1MYCBPNINLODF1ORP8USH2AUSP14

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 hMAP126/SPAG5 is a mitotic spindle-associated protein that is post-translationally modified and phosphorylated by p34(cdc2) kinase in vitro, and its subcellular distribution localizes to the mitotic spindle. Polyclonal antibody immunolocalization; in vitro kinase assay with p34(cdc2) Biochemical and biophysical research communications Medium 11549262
2001 Rat Spag5 (ortholog of human SPAG5) encodes a ~200 kDa testicular protein that interacts strongly with Odf1 (the 27 kDa major outer dense fiber protein) via a leucine zipper motif in the C-terminal region of SPAG5; the downstream leucine zipper is specifically required for this interaction. Yeast two-hybrid interaction screen; leucine zipper mutagenesis/domain mapping Molecular reproduction and development Medium 11468777
2002 Disruption of the Spag5 gene in mice by homologous recombination (Spag5-null mice) does not impair spermatogenesis or fertility, indicating that any role of Spag5 in spermatogenesis is compensated by other proteins. Gene targeting by homologous recombination; phenotypic analysis of null mice Molecular and cellular biology High 11884588
2006 In somatic cells, rat Spag5 localizes to the endoplasmic reticulum and microtubules (including a 58 kDa microtubule-associated isoform confirmed by in vitro MT-binding assays), whereas in elongated spermatids and epididymal sperm it associates with outer dense fibers but not axonemal microtubules — demonstrating cell-type-specific localization and function. Immunofluorescence; in vitro microtubule-binding assay; immuno-electron microscopy; Western blotting of fractionated cells Molecular reproduction and development High 16211599
2006 A duplicated 25 bp insertion mutation in exon 6 of the Spag5 gene in hypogonadic (hgn/hgn) rats produces a truncated Spag5 protein lacking the primary spindle-targeting domain at the C-terminus, leading to defective spindle formation, abnormal mitosis of Sertoli cells, apoptotic Sertoli cell death, and testicular dysplasia — establishing that the C-terminal spindle-targeting domain is essential for SPAG5 function in cell division. Positional cloning; sequencing; immunostaining with Sertoli and germ cell markers; phenotypic analysis of mutant rats Reproduction (Cambridge, England) High 16816335
2012 SPAG5/Astrin localizes to centrosomal/basal body structures in photoreceptor cells of the retina and interacts with USH2AisoB interaction partner NINLisoB; SPAG5 was identified as interacting with USH2AisoB and NINLisoB at basal bodies postmitotically, connecting it to the Usher protein network involved in cilium function. Yeast two-hybrid; co-localization by immunofluorescence in retinal photoreceptors; in situ hybridization; quantitative PCR Cilia Low 23351521
2014 SPAG5/Astrin physically interacts with ORP8 (OSBP-related protein 8), confirmed by yeast two-hybrid, pull-down, and co-immunoprecipitation; overexpressed ORP8 recruits SPAG5 onto ER membranes in interphase cells; SPAG5 knockdown significantly reduces ORP8-overexpression- and 25-hydroxycholesterol-induced G2/M cell cycle accumulation, placing SPAG5 downstream of ORP8 in oxysterol-mediated cell cycle regulation. Yeast two-hybrid; pull-down assay; co-immunoprecipitation; siRNA knockdown; cell cycle analysis by flow cytometry Experimental cell research High 24424245
2018 SPAG5 physically interacts with centrosomal protein CEP55, and this interaction triggers phosphorylation of AKT at Ser473, activating PI3K/AKT signaling to promote hepatocellular carcinoma cell growth and metastasis; inhibition of PI3K/AKT markedly attenuates SPAG5-mediated cell growth. Co-immunoprecipitation; in vitro and in vivo functional assays; PI3K/AKT inhibitor treatment; miR-363-3p luciferase reporter assay Molecular cancer Medium 30089483
2018 SPAG5 promotes HCC progression by downregulating SCARA5 through modulating β-catenin degradation, engaging the β-catenin/TCF4 signaling pathway; SCARA5 expression is inversely correlated with SPAG5 in HCC tissues. shRNA knockdown; overexpression; cell proliferation/apoptosis assays; Western blot for β-catenin pathway components; in vivo xenograft Journal of experimental & clinical cancer research : CR Medium 30249289
2019 SPAG5 interacts with c-MYC binding protein (MYCBP), increasing MYCBP protein levels and enhancing c-MYC transcriptional activity, which in turn promotes expression of CDC20, CDC25C, BRCA1, BRCA2, and RAD51 in triple-negative breast cancer; knockdown of MYCBP or c-MYC abolishes SPAG5-induced cell-cycle progression and proliferation. Co-immunoprecipitation; Western blot; siRNA knockdown epistasis; in vitro and in vivo functional assays Journal of hematology & oncology Medium 30736840
2019 p53-p21 axis transcriptionally suppresses SPAG5 expression: MDM2 inhibitor Nutlin-3a restores p53/p21 and suppresses SPAG5 in wild-type p53 cells but not p53-null cells; p53 or p21 knockdown attenuates Nutlin-3a-induced repression of SPAG5, establishing p53-p21 as required for SPAG5 repression. MDM2 inhibitor treatment; siRNA knockdown of p53/p21; Western blot; qRT-PCR Biochemical and biophysical research communications Medium 30955859
2020 SPAG5 is a direct transcriptional target of the YAP/TAZ/TEAD axis (Hippo pathway); depletion of YAP, TAZ, or TEAD strongly reduces SPAG5 expression; SPAG5 is also directly targeted post-transcriptionally by miR-10b-3p; SPAG5 depletion impairs cancer cell cycle progression, proliferation, and migration. ChIP/luciferase reporter assays for TEAD binding to SPAG5 promoter; YAP/TAZ/TEAD siRNA knockdown; miR-10b-3p target validation; cell cycle and proliferation assays Cell death and differentiation Medium 33230261
2020 SPAG5-AS1 (a lncRNA neighbor of SPAG5) interacts with USP14, leading to de-ubiquitination and stabilization of SPAG5 protein; YY1 transcriptionally upregulates both SPAG5-AS1 and SPAG5; SPAG5 promotes AKT/mTOR signaling, inhibiting autophagy and aggravating apoptosis in podocytes under high glucose. Pulldown; RIP; co-IP; ChIP; luciferase reporter assay; Western blot; flow cytometry; immunofluorescence Cell proliferation Medium 31957155
2020 SPAG5 promotes osteosarcoma metastasis by stabilizing FOXM1 protein (reducing its degradation), which in turn upregulates MMP2 expression, promoting invasion and migration; SPAG5 silencing inhibits the SPAG5-FOXM1-MMP2 axis and suppresses lung metastasis in vivo. siRNA/shRNA knockdown; Western blot for FOXM1 protein stability; in vitro invasion/migration assays; in vivo metastasis model The international journal of biochemistry & cell biology Medium 32668328
2022 Splicing factor SF3B4 promotes SPAG5 expression by ensuring effective splicing of SPAG5 pre-mRNA; SF3B4 knockdown causes intron retention in SPAG5 pre-mRNA, reducing mature SPAG5 mRNA and protein, and the pro-tumorigenic effects of SF3B4 overexpression in cervical cancer are impaired by SPAG5 deficiency. RNA-seq with alternative splicing analysis; SF3B4 siRNA knockdown; SPAG5 rescue experiments; in vitro and in vivo functional assays Cell death discovery Medium 35853859
2024 SPAG5 promotes ferroptosis in colorectal cancer cells by upregulating intracellular reactive oxygen species (ROS); SPAG5 depletion reduces ROS levels and attenuates ferroptosis, diminishing chemotherapy efficacy; ROS inhibition reverses the chemotherapy-sensitizing effect of SPAG5. SPAG5 overexpression and knockdown; ROS measurement; ferroptosis assays; chemotherapy sensitivity assays in vitro and patient cohort analysis Apoptosis : an international journal on programmed cell death Medium 41774258
2024 In triple-negative breast cancer, high SPAG5 expression is regulated by coordinated activity of YAP, mutant p53, and MYC; depletion of YAP or mutant p53 reduces SPAG5 expression and reduces MYC recruitment to the SPAG5 promoter; MYC targeting reduces SPAG5 expression and TNBC tumorigenicity in a SPAG5-expression-dependent manner. siRNA knockdown of YAP, mutant p53, MYC; ChIP for MYC at SPAG5 promoter; functional cell and in vivo assays; chemotherapy combination experiments Cell death & disease Medium 39164278
2024 SPAG5 knockdown activates autophagy and inhibits PI3K/Akt/mTOR signaling in endothelial cells treated with ox-LDL, reducing atherosclerotic plaque formation in ApoE-/- mice; autophagy inhibitor 3-MA reverses the protective effects of SPAG5 silencing, placing SPAG5 upstream of autophagy via PI3K/Akt/mTOR. siRNA/shRNA knockdown; Western blot for PI3K/Akt/mTOR phosphorylation and autophagy markers; GFP-LC3 puncta assay; 3-MA pharmacological rescue; in vivo ApoE-/- mouse model BMC cardiovascular disorders Medium 38807081

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 99 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 92 31665814
2020 SPAG5-AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway. Cell proliferation 91 31957155
2003 Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 78 12457033
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
2022 An estimate of the deepest branches of the tree of life from ancient vertically evolving genes. eLife 63 35190025
2020 Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms. Microbiome 62 32482169
2015 Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. Journal of virology 62 26136578
2001 Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 62 11244332
1991 Time of the deepest root for polymorphism in human mitochondrial DNA. Journal of molecular evolution 60 1901367
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 57 30736840
2020 Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens. Molecular biology and evolution 54 32697301
2001 Cloning and characterization of hMAP126, a new member of mitotic spindle-associated proteins. Biochemical and biophysical research communications 53 11549262
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
2018 SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation. Journal of experimental & clinical cancer research : CR 49 30249289
2004 Genomic characterization of thermophilic Geobacillus species isolated from the deepest sea mud of the Mariana Trench. Extremophiles : life under extreme conditions 49 15168170
2017 Molecular adaptation in the world's deepest-living animal: Insights from transcriptome sequencing of the hadal amphipod Hirondellea gigas. Molecular ecology 48 28429829
2019 LncRNA LINC00857 regulates lung adenocarcinoma progression, apoptosis and glycolysis by targeting miR-1179/SPAG5 axis. Human cell 47 31667785
2012 Metagenomic analysis of hadopelagic microbial assemblages thriving at the deepest part of Mediterranean Sea, Matapan-Vavilov Deep. Environmental microbiology 47 22827264
2008 Crystal structure of GH13 alpha-glucosidase GSJ from one of the deepest sea bacteria. Proteins 47 18398906
2007 Africans in Yorkshire? The deepest-rooting clade of the Y phylogeny within an English genealogy. European journal of human genetics : EJHG 45 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 34 23021907
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 31 27638197
2020 SPAG5: An Emerging Oncogene. Trends in cancer 30 32291236
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
2025 Microbial ecosystems and ecological driving forces in the deepest ocean sediments. Cell 21 40054447
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
2022 Virioplankton assemblages from challenger deep, the deepest place in the oceans. iScience 20 35942087
2018 Genome Reduction in Psychromonas Species within the Gut of an Amphipod from the Ocean's Deepest Point. mSystems 20 29657971
2018 Insight Into the Pico- and Nano-Phytoplankton Communities in the Deepest Biosphere, the Mariana Trench. Frontiers in microbiology 20 30319587
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
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
2023 Phylogenetically and metabolically diverse autotrophs in the world's deepest blue hole. ISME communications 16 37964026
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
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
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
2023 Insight into the adaptation mechanisms of high hydrostatic pressure in physiology and metabolism of hadal fungi from the deepest ocean sediment. mSystems 11 38117068
2022 SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer. DNA and cell biology 11 36264549
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
2021 CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis. Scientific reports 9 34903799
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
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
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 4 36346578
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
2024 Distinct microbial nitrogen cycling processes in the deepest part of the ocean. mSystems 3 38940525
2024 Deep sea treasures - Insights from museum archives shed light on coral microbial diversity within deepest ocean ecosystems. Heliyon 1 38468949
2024 Identification of Lepidapedon oregonense as the current world's deepest trematode. Journal of helminthology 1 38721629
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
2026 SPAG5 promotes ferroptosis and enhances chemotherapy efficacy in locally advanced colorectal cancer via upregulating intracellular ROS levels. Apoptosis : an international journal on programmed cell death 0 41774258
2024 SPAG5 is a potential therapeutic target affecting proliferation, apoptosis, and invasion of esophageal cancer cells. European journal of medical research 0 39696708

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