Affinage

SSX2IP

Afadin- and alpha-actinin-binding protein · UniProt Q9Y2D8

Length
614 aa
Mass
71.2 kDa
Annotated
2026-06-10
13 papers in source corpus 9 papers cited in narrative 9 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

SSX2IP (hMsd1) is a centriolar satellite protein that governs centrosome maturation, microtubule anchoring, and ciliogenesis (PMID:23816619, PMID:25833712). Delivered to the centrosome in a centriolar satellite-dependent manner, it accumulates at spindle poles via Dynein and binds the γ-tubulin ring complex (γ-TuRC) together with the satellite protein PCM-1, and its loss prevents γ-TuRC loading onto centrosomes, reducing microtubule nucleation and causing spindle assembly failure, pericentriolar material fragmentation, and chromosome segregation errors (PMID:23816619). By anchoring microtubule minus ends at the centrosome it organizes interphase microtubules, sets mitotic spindle length and orientation, and is required for proper centriole assembly and duplication, with its depletion trapping satellites near the centrosome and producing faulty centriole structures (PMID:25833712). SSX2IP functions downstream of Wdr8, which localizes to the proximal mother centriole and is required to recruit SSX2IP to the mitotic centrosome (PMID:26545777). At the basal body, SSX2IP acts as a targeting factor for ciliary membrane proteins, recruiting Cep290 and enabling BBSome entry, Rab8 accumulation, somatostatin receptor 3 delivery, and axoneme elongation, and its orthologs are required for ciliogenesis and left-right asymmetry (PMID:24356449, PMID:24397932). Originally identified as a nuclear binding partner of the cancer-testis antigen SSX2 through its N-terminus (PMID:12007189), SSX2IP also associates with the LIM-domain adaptor Wtip during Xenopus neural tube closure (PMID:34710136), and in cancer it engages FANCI to promote proliferation and migration (PMID:39533770) and mediates extracellular-vesicle export of cisplatin to confer drug resistance (PMID:41827805).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2002 Medium

    Established the first molecular partner of SSX2IP, defining it as an SSX2-interacting nuclear protein and naming the gene.

    Evidence Yeast two-hybrid screen with GST pull-down confirmation and immunofluorescence of transfected cells

    PMID:12007189

    Open questions at the time
    • Functional consequence of the SSX2 interaction undefined
    • No endogenous validation beyond transfected cells
    • Binding region on SSX2IP not mapped
  2. 2013 High

    Answered what SSX2IP does at the centrosome by showing it binds the γ-TuRC and is required for its loading, establishing SSX2IP as a centrosome maturation factor.

    Evidence Quantitative proteomics, immunodepletion in Xenopus egg extracts, reciprocal co-IP, and morpholino/siRNA knockdown across medaka and somatic cells

    PMID:23816619

    Open questions at the time
    • Direct versus indirect γ-TuRC binding not resolved
    • How Dynein-dependent pole accumulation is regulated unclear
  3. 2013 High

    Extended SSX2IP function to the cilium, defining it as a basal-body targeting factor that recruits Cep290 and enables BBSome/Rab8-dependent ciliary cargo delivery.

    Evidence siRNA knockdown with immunofluorescent readouts of Cep290, BBSome, Rab8, and somatostatin receptor 3 in human and murine ciliated cells

    PMID:24356449

    Open questions at the time
    • Direct binding partner among Cep290/BBSome not biochemically mapped
    • Mechanism linking satellite delivery to basal-body targeting unresolved
  4. 2014 High

    Connected the centrosomal and ciliary roles by showing satellite-dependent delivery and γ-tubulin binding anchor microtubules, controlling spindle orientation and conserved ciliogenesis.

    Evidence siRNA depletion, co-IP for γ-tubulin, and zebrafish morpholino knockdown with left-right asymmetry readouts

    PMID:24397932

    Open questions at the time
    • Molecular basis of microtubule anchoring not structurally defined
    • Link between spindle and ciliary functions mechanistically separate
  5. 2015 High

    Resolved how microtubule anchoring impacts centriole biogenesis, showing it is required for proper centriole assembly and constrains satellite positioning.

    Evidence siRNA knockdown with superresolution and electron microscopy, Plk4 overexpression epistasis, and hydroxyurea arrest

    PMID:25833712

    Open questions at the time
    • Mechanism coupling anchoring to centriole structural integrity unknown
    • Single lab
  6. 2015 Medium

    Placed SSX2IP in a hierarchy by identifying Wdr8 as an upstream partner required for SSX2IP recruitment to the mitotic centrosome.

    Evidence Mass spectrometry, co-IP, sequential siRNA knockdown epistasis, and superresolution microscopy

    PMID:26545777

    Open questions at the time
    • Direct interaction interface not mapped
    • Single lab
    • Whether Wdr8 acts in ciliary as well as spindle context untested
  7. 2021 Medium

    Identified a developmental role beyond the centrosome, linking SSX2IP to the LIM adaptor Wtip in neural tube closure.

    Evidence Targeted proximity biotinylation, co-expression aggregation assay, and double morpholino knockdown in Xenopus embryos

    PMID:34710136

    Open questions at the time
    • Direct biochemical interaction not deeply characterized
    • Mechanism connecting Wtip to junction remodeling unclear
    • Single lab
  8. 2024 Medium

    Defined a pro-tumorigenic axis in which SSX2IP engages and positively regulates FANCI to drive proliferation and migration.

    Evidence Co-IP, siRNA knockdown, FANCI overexpression rescue, proliferation/migration assays, and xenograft in breast cancer cells

    PMID:39533770

    Open questions at the time
    • Interaction not biochemically characterized in depth
    • Mechanism of FANCI expression regulation unknown
    • Single lab
  9. 2026 Medium

    Established a chemoresistance function, showing miR-625-3p-regulated SSX2IP mediates extracellular-vesicle export of cisplatin.

    Evidence Luciferase reporter assay, mass spectrometry, high-speed confocal microscopy, cell death ELISA, and in vitro/in vivo assays in ovarian cancer cells

    PMID:41827805

    Open questions at the time
    • Molecular mechanism of EV-based cisplatin loading undefined
    • Link between centrosomal function and EV export unexplored
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SSX2IP's core centrosomal/ciliary anchoring activity mechanistically relates to its disparate nuclear, developmental, and cancer functions remains unresolved.
  • No structural model of γ-TuRC or microtubule binding
  • Unclear whether SSX2, Wtip, FANCI, and EV-export functions share a common molecular activity
  • Direct versus scaffold-mediated nature of most interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Complex memberships
centriolar satelliteγ-tubulin ring complex (γ-TuRC)

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SSX2IP was identified as a direct binding partner of SSX2 via yeast two-hybrid screening, and the interaction was confirmed by GST pull-down assay in vitro. SSX2IP interacts with the N-terminal moiety of SSX2. SSX2IP colocalizes with SSX2 in the nucleus of transfected cells. Yeast two-hybrid, GST pull-down assay, immunofluorescence of transfected cells Genes, chromosomes & cancer Medium 12007189
2013 SSX2IP accumulates at spindle poles in a Dynein-dependent manner in Xenopus egg extracts, interacts with the γ-tubulin ring complex (γ-TuRC) and centriolar satellite protein PCM-1. Immunodepletion of SSX2IP impedes γ-TuRC loading onto centrosomes, leading to reduced microtubule nucleation and spindle assembly failure. In medaka blastomeres and somatic cells, SSX2IP knockdown causes fragmentation of pericentriolar material and chromosome segregation errors, establishing SSX2IP as a centrosome maturation and maintenance factor. Quantitative proteomics, immunodepletion in Xenopus egg extracts, co-immunoprecipitation, morpholino knockdown in medaka embryos, siRNA knockdown in somatic cells The Journal of cell biology High 23816619
2013 SSX2IP localizes to the basal body of primary cilia in human and murine ciliated cells. siRNA knockdown of SSX2IP in human cells reduces recruitment of Cep290 to both centriolar satellites and the basal body, drastically reduces entry of the BBSome and Rab8 accumulation at the ciliary base, limits targeting of the ciliary membrane protein somatostatin receptor 3, and significantly reduces axoneme length. SSX2IP is thus a targeting factor for ciliary membrane proteins that cooperates with Cep290, the BBSome, and Rab8. siRNA knockdown, immunofluorescence, localization studies in human and murine ciliated cells Molecular biology of the cell High 24356449
2014 hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the γ-tubulin complex. Depletion of hMsd1/SSX2IP leads to disorganized interphase microtubules and misoriented mitotic spindles with reduced length, establishing SSX2IP as a microtubule-anchoring protein. Knockdown of the zebrafish orthologue causes ciliary defects and disturbed left-right asymmetry, confirming a conserved role in ciliogenesis. siRNA knockdown, co-immunoprecipitation, immunofluorescence, zebrafish morpholino knockdown EMBO reports High 24397932
2015 hMsd1/SSX2IP-mediated microtubule anchoring to the centrosome is essential for proper centriole assembly and duplication. Upon hMsd1/SSX2IP knockdown, centriolar satellites become stuck at the microtubule minus end near the centrosome and accumulate centrosomal proteins ectopically. Microtubule structures (even when not properly anchored) are still required for satellite aggregation. Superresolution and electron microscopy revealed faulty centriole structures under these conditions. SSX2IP-depleted cells are insensitive to Plk4 overproduction-induced ectopic centriole formation but accelerate centrosome reduplication upon hydroxyurea arrest. siRNA knockdown, superresolution microscopy, electron microscopy, Plk4 overexpression epistasis, hydroxyurea arrest Molecular biology of the cell High 25833712
2015 Wdr8 constitutively localizes to the proximal end of the mother centriole and forms a complex with hMsd1/SSX2IP identified by mass spectrometry. Wdr8 depletion reduces recruitment of hMsd1/SSX2IP to the mitotic centrosome (but not vice versa), and knockdown of either protein produces similar spindle defects (shortened and misoriented spindle microtubules), placing Wdr8 upstream of hMsd1/SSX2IP in centrosome function. Mass spectrometry, co-immunoprecipitation, siRNA knockdown, superresolution microscopy, immunofluorescence Biochemical and biophysical research communications Medium 26545777
2021 Targeted proximity biotinylation identified SSX2IP as a binding partner of the N-terminal domain of Wtip (a LIM-domain adaptor). Physical association was confirmed and the two proteins formed mixed aggregates upon overexpression. Double depletion of Wtip and SSX2IP in Xenopus embryos disrupted neural tube closure, indicating a functional interaction during neurulation and cell junction remodeling. Targeted proximity biotinylation (BirA-anti-GFP), co-expression aggregation assay, double morpholino knockdown in Xenopus embryos PloS one Medium 34710136
2024 SSX2IP physically interacts with FANCI (FA Complementation Group I) as confirmed by co-immunoprecipitation. SSX2IP positively regulates FANCI expression, and FANCI overexpression partially rescues the anti-proliferative and anti-migratory effects of SSX2IP knockdown in breast cancer cells, placing SSX2IP upstream of FANCI in a pro-tumorigenic pathway. Co-immunoprecipitation, siRNA knockdown, overexpression rescue, functional proliferation/migration assays, xenograft Cell biology international Medium 39533770
2026 SSX2IP was confirmed as a direct transcriptional/functional target of miR-625-3p by reporter assays, and its upregulation promotes cisplatin export via extracellular vesicles in ovarian cancer cells, thereby enhancing cisplatin resistance. Mass spectrometry and high-speed confocal microscopy supported SSX2IP's role in mediating EV-based cisplatin secretion. Luciferase reporter assay, mass spectrometry, high-speed confocal microscopy, cell death ELISA, in vitro and in vivo functional assays Cancers Medium 41827805

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP. PloS one 63 23826132
2013 The centriolar satellite protein SSX2IP promotes centrosome maturation. The Journal of cell biology 60 23816619
2013 The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone. Molecular biology of the cell 55 24356449
2002 The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP. Genes, chromosomes & cancer 54 12007189
2014 Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation. EMBO reports 38 24397932
2015 Centriolar satellite- and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly. Molecular biology of the cell 26 25833712
2013 SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma. Journal of translational medicine 25 23452395
2015 The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation. Biochemical and biophysical research communications 17 26545777
2007 SSX2IP: an emerging role in cancer. Biochemical and biophysical research communications 15 17904521
2021 Identification of the centrosomal maturation factor SSX2IP as a Wtip-binding partner by targeted proximity biotinylation. PloS one 12 34710136
2022 MiRNA-181b-5p Modulates Cell Proliferation, Cell Cycle, and Apoptosis by Targeting SSX2IP in Acute Lymphoblastic Leukemia. Turkish journal of haematology : official journal of Turkish Society of Haematology 9 35658330
2026 MicroRNA-625-3p Increases Chemosensitivity in Ovarian Cancer Cells Through Decreasing SSX2IP-Mediated Cisplatin Export in Extracellular Vesicles. Cancers 0 41827805
2024 SSX2IP promotes cell proliferation and migration in breast cancer by regulating FANCI. Cell biology international 0 39533770

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