Affinage

SGO2

Shugoshin 2 · UniProt Q562F6

Length
1265 aa
Mass
144.7 kDa
Annotated
2026-06-10
13 papers in source corpus 10 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SGO2 (Shugoshin-2) is an inner centromere protein that coordinates chromosome segregation by protecting centromeric cohesin and correcting kinetochore–microtubule attachments during meiosis and perturbed mitosis (PMID:17485487, PMID:20889715, PMID:24192037). Its centromeric recruitment is directed by mitotic kinases: Aurora B and BUB1 establish localization in human cells (PMID:17485487), while in mouse oocytes MPS1 activity is required for centromeric targeting and cohesin protection and BUB1 activity dictates whether SGO2 is deposited at the centromere versus the pericentromere/arms (PMID:28947820). Once localized, Aurora B phosphorylates two distinct regions of SGO2 — the N-terminal coiled-coil and the middle region — to separately license PP2A binding (which shields centromeric cohesin from cleavage) and MCAK recruitment (which corrects erroneous attachments and promotes congression) (PMID:20889715, PMID:24192037). SGO2 additionally silences the spindle assembly checkpoint through direct Mad2 binding and limits bivalent stretching by restraining Aurora C activity in oocytes (PMID:24192037), and anchors SET/TAF1 at the inner centromere to sustain local Aurora B activity by inhibiting PP2A, supporting bi-orientation in a tension-sensitive manner (PMID:31527146). In meiosis I mouse oocytes SGO2 is dispensable as a separase inhibitor, that role being covered independently by securin and cyclin B1–CDK1 (PMID:40267054). Beyond its centromeric functions, SGO2 physically interacts with RAB1A and inhibits its ubiquitination to promote prostate cancer cell proliferation (PMID:36566018).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2007 High

    Established SGO2 as an inner-centromere protein required to position the kinetochore depolymerase MCAK, linking it to attachment-error correction rather than only cohesion.

    Evidence siRNA depletion, immunofluorescence, Co-IP and live-cell imaging in human cells

    PMID:17485487

    Open questions at the time
    • Did not resolve how SGO2 itself is recruited at the molecular level
    • PP2A association noted but its functional consequence not dissected
  2. 2007 Medium

    Defined SGO2's meiotic localization dynamics, showing differential co-localization with cohesin subunits and tension-dependent redistribution within centromeres.

    Evidence Immunofluorescence co-localization with RAD21/REC8 in male mouse meiosis

    PMID:17205076

    Open questions at the time
    • No functional manipulation
    • Mechanism of tension-sensing redistribution unknown
  3. 2010 High

    Resolved how SGO2 partitions its dual functions: distinct Aurora B phosphosites separately gate PP2A and MCAK binding, coupling one scaffold to both cohesin protection and congression.

    Evidence In vitro kinase assay, phosphosite mutagenesis, Co-IP, siRNA rescue in HeLa cells

    PMID:20889715

    Open questions at the time
    • Structural basis of dual binding not defined
    • Did not address meiotic context
  4. 2010 Medium

    Connected SGO2 loss to age-related cohesin decline in oocytes, supporting its cohesin-protective role and excluding a checkpoint-failure explanation.

    Evidence Immunofluorescence of chromosome spreads from aged vs young mouse oocytes

    PMID:20817533

    Open questions at the time
    • Correlative rather than causal
    • Did not test whether restoring SGO2 rescues cohesin
  5. 2013 High

    Dissected SGO2's multiple oocyte functions, separating PP2A-dependent cohesin protection from PP2A-independent congression, K-fiber, and bivalent-stretching roles via Mad2, MCAK, and Aurora C.

    Evidence Oocyte knockout/depletion, Co-IP of PP2A/Mad2/MCAK, dominant-negative Aurora C, rescue, live imaging

    PMID:24192037

    Open questions at the time
    • How a single protein coordinates these parallel activities spatially unresolved
    • Aurora C inhibition mechanism not structurally defined
  6. 2017 High

    Identified the kinase hierarchy targeting SGO2 in oocytes, showing MPS1 is essential for centromeric localization and cohesin protection while BUB1 directs pericentromeric pools.

    Evidence MPS1 inhibitor, BUB1 kinase-dead knock-in mice, immunofluorescence, cohesin protection assay

    PMID:28947820

    Open questions at the time
    • Molecular receptor for the MPS1-dependent centromeric pool not identified
    • How centromeric vs pericentromeric pools functionally differ unresolved
  7. 2017 Medium

    Revealed a Mad2-independent, Sgo2-dependent APC/C-inhibitory anaphase-delay pathway in fission yeast, distinguishing it from the canonical SAC.

    Evidence Fission yeast genetic epistasis, double mutants, anaphase timing

    PMID:28178520

    Open questions at the time
    • Ortholog system; mammalian conservation untested
    • Biochemical mechanism of APC/C inhibition not defined
  8. 2019 Medium

    Showed SGO2 anchors SET/TAF1 at the inner centromere to locally inhibit PP2A and sustain Aurora B activity, linking SGO2 to tension-sensitive attachment correction.

    Evidence Co-IP, SET overexpression/depletion, kinetochore tension assay, immunofluorescence

    PMID:31527146

    Open questions at the time
    • Single lab; reciprocal validation in other systems lacking
    • How SET levels are tuned by tension mechanistically unclear
  9. 2022 Medium

    Extended SGO2 function beyond mitosis/meiosis by showing it stabilizes RAB1A through inhibition of its ubiquitination to drive prostate cancer cell growth.

    Evidence Co-IP, mass spectrometry, ubiquitination assay, siRNA knockdown, rescue

    PMID:36566018

    Open questions at the time
    • Single study; mechanism of ubiquitination inhibition not defined
    • Whether this is centromere-related or a distinct cytoplasmic pool unknown
  10. 2025 High

    Refuted an essential separase-inhibitory role for SGO2 in meiosis I, showing securin and cyclin B1–CDK1 each independently suppress separase.

    Evidence Separase biosensor, mouse oocyte knockout/perturbation, live imaging

    PMID:40267054

    Open questions at the time
    • Significance of SGO2 destruction during meiosis I unexplained
    • Does not address SGO2's cohesin-protective (PP2A) function
  11. 2025 Medium

    Demonstrated that BUB1 kinase activity sets SGO2's centromeric versus arm localization, with elevated BUB1 in hybrid oocytes causing cohesin over-protection and segregation failure.

    Evidence Hybrid mouse cross, SGO2 immunofluorescence, BUB1 activity assay, segregation assays (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular basis of BUB1-dependent positioning not fully defined
  12. 2025 Medium

    Defined the temporal window of SGO2–PP2A cohesin protection, showing it operates in meiosis I but not at metaphase II, and that kinetochore individualization enables meiosis II cleavage.

    Evidence Securin/cyclin B1 KO mice, structure-function assays, separase monitoring (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • How protection is switched off between meiotic divisions mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single SGO2 scaffold spatially and temporally integrates PP2A-mediated cohesin protection, MCAK/SET-mediated attachment correction, Mad2-mediated checkpoint silencing, and its non-centromeric RAB1A function remains unresolved.
  • No structural model coupling the distinct phospho-regulated binding interfaces
  • Whether centromeric and cytoplasmic SGO2 functions share regulation is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005694 chromosome 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1474165 Reproduction 4 R-HSA-1640170 Cell Cycle 3
Complex memberships
inner centromere

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 hSgo2 (Tripin) localizes to the inner centromere and its localization depends on BUB1 and Aurora B kinases. hSgo2 is essential for MCAK to localize to the centromere; depletion of hSgo2 causes MCAK delocalization, leading to uncorrected kinetochore attachment defects and lagging chromosomes. hSgo2 associates with PP2A and is proposed to spatially regulate MCAK activity at the inner centromere/kinetochore. siRNA depletion, immunofluorescence localization, co-immunoprecipitation, live-cell imaging The Journal of cell biology High 17485487
2007 During mammalian meiosis I, SGO2 accumulates at centromeres during diplotene and co-localizes differentially with cohesin subunits RAD21 and REC8 at metaphase I centromeres. During meiosis II and mitosis, SGO2 shows a tension-dependent redistribution within centromeres during chromosome congression. Immunofluorescence, co-localization with cohesin subunits during male mouse meiosis EMBO reports Medium 17205076
2010 Aurora B phosphorylates hSgo2 at its N-terminal coiled-coil region and middle region. These phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, respectively, and are essential for localizing PP2A and MCAK to centromeres. hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesin in HeLa cells. In vitro kinase assay, phosphosite mutagenesis, co-immunoprecipitation, siRNA depletion, immunofluorescence Genes & development High 20889715
2010 In aged mouse oocytes, depletion of Sgo2 accompanies loss of centromeric cohesin, consistent with Sgo2's role in protecting centromeric cohesin during meiosis I. Reduced cohesin is not due to age-related failure of the spindle checkpoint to delay separase-mediated cleavage. Immunofluorescence of chromosome spreads from aged vs. young oocytes, cohesin and Sgo2 quantification Current biology : CB Medium 20817533
2013 In mammalian oocytes, Sgol2 protects centromeric cohesin via its interaction with PP2A; it silences the spindle assembly checkpoint (SAC) via direct binding to Mad2; it promotes chromosome congression, bi-orientation, and K-fiber formation; and it limits bivalent stretching. The K-fiber/bivalent-stretching effects are PP2A-independent and mediated by MCAK recruitment and inhibition of Aurora C kinase activity, respectively. Oocyte knockout/depletion, co-immunoprecipitation (PP2A, Mad2, MCAK), dominant-negative Aurora C, live-cell imaging, rescue experiments eLife High 24192037
2017 In mouse oocyte meiosis I, Mps1 kinase activity is required for Sgo2 localization to the centromere region and for centromeric cohesin protection. Bub1 kinase activity also contributes to Sgo2 localization (preferentially to the pericentromere via H2A-T121 phosphorylation) but is dispensable for cohesin protection when Mps1 is functional. Sgo2 at the centromere (not pericentromere) is the critical pool for protection. Small-molecule kinase inhibition (Mps1 inhibitor), oocyte-specific Bub1 kinase-dead knock-in mice, immunofluorescence, functional cohesin protection assay Nature communications High 28947820
2017 In fission yeast, Sgo2 controls a Mad2-independent, APC/C-inhibitory pathway that delays anaphase onset. This pathway requires Sgo2 and SAC components Bub1, Mph1/Mps1, and Mad3 (first KEN box), but not Mad1 or Mad2. The pathway is terminated when the chromosome passenger complex (CPC) interacts with Klp9/MKLP2. Fission yeast genetic epistasis, double-mutant analysis, spindle checkpoint component deletions, anaphase timing assays Cell reports Medium 28178520
2019 SET/TAF1 localizes to the inner centromere by directly interacting with Sgo2. This interaction maintains Aurora B kinase activity by inhibiting PP2A at the inner centromere, thereby correcting erroneous kinetochore-microtubule attachments. SET levels at centromeres decline with increasing inter-kinetochore distance (tension), contributing to chromosome bi-orientation. Co-immunoprecipitation, immunofluorescence, SET overexpression and depletion, kinetochore tension assay The Journal of cell biology Medium 31527146
2022 SGOL2 physically interacts with RAB1A (validated by mass spectrometry and Co-IP) and inhibits RAB1A ubiquitination, thereby stabilizing RAB1A protein levels and promoting prostate cancer cell proliferation and migration. Co-immunoprecipitation, mass spectrometry, ubiquitination assay, siRNA knockdown, rescue experiments Aging Medium 36566018
2025 SGO2 does not play an essential role as a separase inhibitor during meiosis I in mouse oocytes. Using a separase biosensor, securin and cyclin B1-CDK1 each independently and sufficiently suppress separase activity; SGO2 inhibition of separase is not required. SGO2 is destroyed during meiosis I but this is not linked to essential separase regulation. Separase biosensor, mouse oocyte knockout/perturbation, live imaging of separase activity PLoS biology High 40267054
2025 In mouse hybrid oocytes (M. m. domesticus × M. spicilegus), SGO2 mislocalizes to chromosome arms instead of centromeres due to abnormally elevated BUB1 kinase activity, causing cohesin over-protection and failure of homologous chromosome separation. This establishes that BUB1 activity determines SGO2's centromeric vs. arm targeting in oocytes. Hybrid mouse cross, immunofluorescence of SGO2 localization, BUB1 kinase activity assay, aneuploidy/segregation assays bioRxivpreprint Medium
2025 In mouse oocytes, cohesin is not protected at metaphase II arrest; centromeric cohesin protection by Sgo2-PP2A is operative in meiosis I but not present at metaphase II. Prior kinetochore individualization in meiosis I is required for separase to cleave centromeric cohesin in meiosis II. Knockout mouse models (separase inhibitor elimination via securin/cyclin B1 KO), structure-function assays, separase activity monitoring bioRxivpreprint Medium

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. Current biology : CB 287 20817533
2007 Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments. The Journal of cell biology 115 17485487
2010 Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres. Genes & development 112 20889715
2007 Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis. EMBO reports 73 17205076
2013 Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes. eLife 66 24192037
2017 Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I. Nature communications 55 28947820
2020 CDK1-PLK1/SGOL2/ANLN pathway mediating abnormal cell division in cell cycle may be a critical process in hepatocellular carcinoma. Cell cycle (Georgetown, Tex.) 36 32275843
2017 Identification of a Sgo2-Dependent but Mad2-Independent Pathway Controlling Anaphase Onset in Fission Yeast. Cell reports 15 28178520
2019 Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere. The Journal of cell biology 14 31527146
2022 SGOL2 promotes prostate cancer progression by inhibiting RAB1A ubiquitination. Aging 7 36566018
2025 SGO2 does not play an essential role in separase inhibition during meiosis I in mouse oocytes. PLoS biology 4 40267054
2025 Histone deacetylation as a landmark for Sgo2 relocation from centromeres to subtelomeres during interphase. iScience 0 40520116
2025 Comprehensive Analysis and Experimental Validation of Single-Cell and Transcriptome Sequencing Reveal SGO2 as a Novel Biomarker for Breast Cancer. Breast cancer (Dove Medical Press) 0 41340734

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