Affinage

SPECC1

Cytospin-B · UniProt Q5M775

Length
1068 aa
Mass
118.6 kDa
Annotated
2026-06-10
28 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPECC1 (HCMOGT-1/NSP) is a coiled-coil and calponin homology domain-containing protein implicated in nucleolar RNA metabolism, cell-fate regulation, and epithelial junction integrity (PMID:18763323, PMID:20237420, PMID:34166821). Its isoforms NSP 5a3a and NSP 5a3b physically associate with the nucleolar phosphoprotein B23/NPM1, and NSP 5a3a additionally binds the ribonuclear protein hnRNP-L, linking SPECC1 to ribosome biogenesis and rRNA processing, with this cooperation differing between normal and cancer breast cell models (PMID:18763323, PMID:20237420). Consistent with a role in proliferation/apoptosis control, overexpression of NSP 5a3a triggers apoptosis through a p73-dependent, p53- and caspase-3-independent pathway in head and neck carcinoma cells (PMID:21311098). Beyond its nucleolar interactions, SPECC1 supports the morula-to-blastocyst transition by maintaining tight junction integrity in trophectoderm cells (PMID:34166821) and is required for normal avoidance learning in mice (PMID:22846151). SPECC1 is also recurrently captured as an oncogenic fusion partner: a t(5;17) translocation fuses HCMOGT-1 to PDGFRB, generating a constitutively active fusion kinase in juvenile myelomonocytic leukemia (PMID:15087372). The biochemical activity of the calponin homology and SMC/SbcC ATPase-like motifs has not been functionally characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2004 Medium

    Established SPECC1's first disease link by showing it serves as a chromosomal translocation partner that activates an oncogenic kinase.

    Evidence Molecular cloning of the t(5;17) breakpoint by 5'-RACE with FISH and RT-PCR confirmation in juvenile myelomonocytic leukemia

    PMID:15087372

    Open questions at the time
    • Does not define the normal function of full-length SPECC1
    • Mechanism of fusion-kinase transformation downstream of PDGFRB not addressed
  2. 2008 Medium

    Answered where SPECC1 isoforms act biochemically by demonstrating interaction with the nucleolar protein B23/NPM1 and linking the protein to proliferation and apoptosis.

    Evidence siRNA silencing of HCMOGT-1 plus proteomic and FACS analysis; domain analysis identifying SMC/SbcC ATPase and calponin homology motifs

    PMID:18763323

    Open questions at the time
    • Functional consequence of B23 binding not resolved
    • Activity of identified ATPase/CH domains untested
  3. 2010 Medium

    Extended the nucleolar role by adding hnRNP-L as a partner and a regulator of NSP 5a3a, placing SPECC1 in ribosome biogenesis/rRNA processing.

    Evidence Co-IP/pulldown of NSP 5a3a with B23 and hnRNP-L, siRNA silencing, and differential expression analysis in normal vs cancer breast cells

    PMID:20237420

    Open questions at the time
    • Direct involvement in specific rRNA processing steps not demonstrated
    • Basis of normal-vs-cancer differential cooperation unknown
  4. 2010 Low

    Tested the functional output of SPECC1 by showing overexpression drives apoptosis through a defined p73-dependent pathway.

    Evidence Overexpression of NSP 5a3a in HN30, FaDu and WI38 cells with apoptosis quantification and p73/p53/caspase-3 pathway analysis

    PMID:21311098

    Open questions at the time
    • No genetic rescue or reconstitution to confirm specificity
    • How NSP 5a3a engages the p73 axis is unknown
  5. 2012 Medium

    Revealed an in vivo physiological role by linking SPECC1 loss to a specific cognitive deficit.

    Evidence Gene-trap mouse mutant phenotyped in an automated home-cage avoidance learning assay

    PMID:22846151

    Open questions at the time
    • Molecular/cellular basis of the learning defect not defined
    • Neuronal localization or partners not identified
  6. 2021 Medium

    Identified a developmental role by showing SPECC1 maintains trophectoderm tight junctions during the morula-to-blastocyst transition.

    Evidence siRNA knockdown of maternal and zygotic transcripts in zygotes with qRT-PCR, immunocytochemistry, and FITC tight-junction permeability assay

    PMID:34166821

    Open questions at the time
    • Molecular link between SPECC1 and tight junction components not defined
    • Whether this role relates to the nucleolar interactions is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical activity of SPECC1's calponin homology and SMC/SbcC ATPase-like motifs, and how its nucleolar, developmental, and behavioral roles mechanistically connect, remain unresolved.
  • No demonstrated enzymatic or cytoskeletal-binding activity
  • No structural model
  • No unifying mechanism across tissues

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005730 nucleolus 2
Partners
HNRNPLNPM1PDGFRB

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 HCMOGT-1 (SPECC1) was identified as a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia via t(5;17)(q33;p11.2) translocation. The breakpoint in PDGFRB occurred at the same site as all previously reported PDGFRB translocations, resulting in a constitutively activated PDGFRB/HCMOGT-1 fusion kinase. Molecular cloning of translocation breakpoint via 5'-RACE, confirmed by FISH and RT-PCR Cancer research Medium 15087372
2008 SPECC1 protein isoforms NSP 5a3a and NSP 5a3b interact with nucleolar phosphoprotein B23 (NPM1). siRNA silencing of HCMOGT-1 combined with proteomic analysis confirmed this interaction. siRNA silencing of HCMOGT-1 and NPM1 implicated NSP 5a3a and 5a3b in cell proliferation and apoptosis regulation. Sequence analysis identified SMC/SbcC ATPase motif similarity and a calponin homology (CH) domain in the 3B isoforms. siRNA silencing of HCMOGT-1, proteomic analysis, FACS analysis; sequence/domain analysis Cell cycle (Georgetown, Tex.) Medium 18763323
2010 The SPECC1 isoform NSP 5a3a physically interacts with nucleolar protein B23 and with ribonuclear protein hnRNP-L, implicating SPECC1 in ribosome biogenesis and rRNA processing. Additionally, hnRNP-L was identified as a potential regulator of NSP 5a3a expression via siRNA silencing. A differential cooperation between NSP 5a3a, B23, and hnRNP-L was observed comparing normal and cancer breast cell models. Co-immunoprecipitation/pulldown (confirmed interaction with B23 and hnRNP-L), siRNA silencing of NSP 5a3a and hnRNP-L, differential expression analysis in normal vs. cancer breast cell lines Cell cycle (Georgetown, Tex.) Medium 20237420
2010 Overexpression of NSP 5a3a (SPECC1 isoform) in head and neck carcinoma cell lines (HN30, FaDu) and control WI38 cells induced significant apoptosis (~10-13 fold increase). The apoptotic mechanism was identified as p73-dependent and independent of p53 and caspase-3 activity. Overexpression transfection in cancer cell lines, apoptosis quantification, molecular pathway analysis (p73, p53, caspase-3) Oncotarget Low 21311098
2012 A gene-trap mouse mutant of specc1/cytospinB showed a profound and specific delay in avoidance learning compared to control strains, establishing a functional role for SPECC1 in this aspect of cognition. Gene-trap mouse mutant phenotyping using automated home-cage behavioral assay (PhenoTyper) with aversive stimulus paradigm Genes, brain, and behavior Medium 22846151
2021 Specc1 expression increases markedly from the morula stage onward in mouse preimplantation development, with preferential localization in trophectoderm cells. siRNA-mediated knockdown of both maternal and zygotic Specc1 transcripts did not affect development through the morula stage but significantly reduced blastocyst formation and increased tight junction permeability (assessed by FITC uptake), indicating a role for Specc1 in tight junction complex formation during morula-to-blastocyst transition. siRNA injection into 1-cell zygotes, qRT-PCR, immunocytochemistry for localization, FITC uptake assay for tight junction permeability Gene expression patterns : GEP Medium 34166821

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2). Cancer research 53 15087372
2012 High-throughput phenotyping of avoidance learning in mice discriminates different genotypes and identifies a novel gene. Genes, brain, and behavior 47 22846151
2018 Upregulation of Circular RNA VPS13C-has-circ-001567 Promotes Ovarian Cancer Cell Proliferation and Invasion. Cancer biotherapy & radiopharmaceuticals 40 30376358
2022 Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis. Hematology (Amsterdam, Netherlands) 36 34957935
2019 Circ_SPECC1 enhances the inhibition of miR-526b on downstream KDM4A/YAP1 pathway to regulate the growth and invasion of gastric cancer cells. Biochemical and biophysical research communications 30 31349968
2013 Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity. European journal of human genetics : EJHG 27 23299920
2020 Circ-SPECC1 modulates TGFβ2 and autophagy under oxidative stress by sponging miR-33a to promote hepatocellular carcinoma tumorigenesis. Cancer medicine 26 32627938
2021 Myocardial Infarction Induces Cardiac Fibroblast Transformation within Injured and Noninjured Regions of the Mouse Heart. Journal of proteome research 20 33789425
2020 A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: Potential implications for the SARS-CoV-2 modus operandi. Medical hypotheses 16 32344305
2010 NSP 5a3a's link to nuclear-cyto proteins B23 and hnRNP-L between normal and aberrant breast cell lines. Cell cycle (Georgetown, Tex.) 14 20237420
2024 A novel protein SPECC1-415aa encoded by N6-methyladenosine modified circSPECC1 regulates the sensitivity of glioblastoma to TMZ. Cellular & molecular biology letters 13 39333871
2010 NSP 5a3a: a potential novel cancer target in head and neck carcinoma. Oncotarget 12 21311098
2021 Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target. Frontiers in oncology 9 34796107
2021 Expression patterns and biological function of Specc1 during mouse preimplantation development. Gene expression patterns : GEP 7 34166821
2008 Possible functional role of NSPs in cancer. Cell cycle (Georgetown, Tex.) 7 18763323
2024 Circular RNA SPECC1 promoted tumorigenesis and osimertinib resistance in lung adenocarcinoma via a circular RNA-microRNA network. Journal of thoracic disease 6 39831223
2019 Cancer-testis antigens in canine histiocytic sarcoma and other malignancies. Veterinary and comparative oncology 6 30854786
2025 Exploring the potential mechanisms of sorafenib resistance in hepatocellular carcinoma cell lines based on RNA sequencing. Cancer cell international 4 40082884
2022 Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells. International journal of molecular sciences 4 35806237
2024 SPECC1 as a pan-cancer biomarker: unraveling its role in drug sensitivity and resistance mechanisms. Discover oncology 3 39397181
2023 Interference of the Circular RNA Sperm Antigen With Calponin Homology and Coiled-Coil Domains 1 Suppresses Growth and Promotes Apoptosis of Breast Cancer Cells Partially Through Targeting miR-1236-3p/Chromobox 8 Pathway. Clinical breast cancer 3 38341369
2022 Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma. Frontiers in genetics 3 35222516
2023 circSPECC1 Promotes Proliferation and Migration of LNCaP Prostate Cancer Cells by Affecting Their Epithelial-Mesenchymal Transition. Journal of immunology research 2 37020791
2018 A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report. BMC medical genomics 2 30563523
2024 Prochloraz induced alterations in the expression of mRNA in the reproductive system of male offspring mice. PeerJ 1 39210919
2026 Cell type resolved MR based on brain single cell eQTLs corroborated by single cell RNA sequencing uncovers neuroimmune and vascular programs in intracerebral hemorrhage. Journal of translational medicine 0 41673661
2026 CircSPECC1 attenuates sensitivity to PD-1 blockade through impaired antigen presentation in hepatocellular carcinoma. Cancer letters 0 42097490
2025 Challenging diagnosis in pulmonary nut carcinoma: A report of two cases with different histopathologic and molecular features and a novel NUTM1::SPECC1 gene fusion. Histology and histopathology 0 40152114

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