Affinage

NUBP2

Cytosolic Fe-S cluster assembly factor NUBP2 · UniProt Q9Y5Y2

Length
271 aa
Mass
28.8 kDa
Annotated
2026-06-10
10 papers in source corpus 9 papers cited in narrative 10 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

NUBP2 is a MRP/MinD-type P-loop NTPase that acts as an integral centriole component and a negative regulator of centrosome duplication and ciliogenesis (PMID:10486206, PMID:23807208). It functions within a protein network: NUBP2 physically interacts with its paralog NUBP1, and both associate with the minus-end-directed motor KIFC5A such that loss of NUBP1/NUBP2 phenocopies KIFC5A silencing, producing centrosome amplification and multipolar spindles (PMID:16638812). NUBP2 and NUBP1 reside at centrioles throughout the cell cycle and at the basal bodies of primary cilia, and depletion of Nubp2 increases the fraction of ciliated cells — a phenotype reversed by concurrent silencing of KIFC5A, placing NUBP2 in a KIFC5A-dependent regulatory axis (PMID:23807208). NUBP2 also directly and independently binds KATNAL2 isoforms, a katanin-like microtubule-regulatory factor that likewise localizes to centrioles and basal bodies and controls centriole number and ciliogenesis (PMID:26153462). In vivo, this centrosome/cilia function is developmentally essential: conditional loss in neural crest causes craniofacial defects through mesenchymal apoptosis independent of cilia proportion or SHH/FGF/BMP signaling (PMID:31733190), while forebrain-specific deletion causes primary microcephaly with supernumerary centrosomes and cilia and p53-independent cell death (PMID:39867373). In colorectal cancer cells NUBP2 acts upstream of GSK3β phosphorylation to promote proliferation and migration (PMID:38492158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 Medium

    Established the biochemical identity of NUBP2, defining it as a eukaryotic member of the MRP/MinD-type P-loop nucleotide-binding protein family.

    Evidence Sequence motif characterization and phylogenetic analysis with Northern blot expression profiling

    PMID:10486206

    Open questions at the time
    • No functional or enzymatic assay demonstrating NTPase activity
    • No cellular role assigned
  2. 2006 Medium

    Placed NUBP2 in a centrosome-duplication control pathway by showing it interacts with NUBP1 and KIFC5A and that its loss phenocopies KIFC5A silencing.

    Evidence Co-IP and RNAi single/double knockdown with immunofluorescence in mammalian cells

    PMID:16638812

    Open questions at the time
    • Mechanism by which the NUBP1/NUBP2/KIFC5A complex restrains duplication unknown
    • Single lab; NTPase activity not linked to phenotype
  3. 2009 Low

    Identified the N-terminus as a determinant of NUBP2 subcellular localization and nuclear morphology.

    Evidence GFP-fusion live imaging in HeLa cells

    PMID:19263241

    Open questions at the time
    • Single imaging method with no functional follow-up
    • Nuclear accumulation may be a tag artifact; physiological relevance unclear
  4. 2013 High

    Defined NUBP2 as an integral centriole/basal-body component and a negative regulator of ciliogenesis acting through a KIFC5A-dependent axis.

    Evidence RNAi loss-of-function, immunofluorescence and EM localization, and epistatic double silencing across mouse, C. elegans and Chlamydomonas

    PMID:23807208

    Open questions at the time
    • Whether NUBP2 NTPase activity drives ciliogenesis suppression untested
    • CCT/TRiC link demonstrated for NUBP1 but not directly for NUBP2
  5. 2015 Medium

    Expanded the NUBP2 interaction network to KATNAL2, connecting it to katanin-family microtubule regulation of centriole number and cilia.

    Evidence In vivo Co-IP plus shRNAi and immunofluorescence

    PMID:26153462

    Open questions at the time
    • Functional consequence of the NUBP2–KATNAL2 interaction not dissected
    • Single lab
  6. 2019 Medium

    Revealed a developmental survival function distinct from cilia regulation, showing NUBP2 loss kills craniofacial neural crest cells without altering cilia proportion or major morphogen signaling.

    Evidence Wnt1-Cre conditional knockout with ENU screen, complementation, and apoptosis/pathway-marker immunofluorescence

    PMID:31733190

    Open questions at the time
    • Molecular trigger of apoptosis not identified
    • Relationship between centrosome function and cell survival unresolved
  7. 2024 Medium

    Implicated NUBP2 in cancer cell signaling as an upstream modulator of GSK3β phosphorylation governing proliferation and migration.

    Evidence siRNA/overexpression, phospho-kinase array, CHIR-99021 rescue, and subcutaneous tumor model in colorectal cancer cells

    PMID:38492158

    Open questions at the time
    • Direct molecular link between NUBP2 and GSK3β not defined
    • Connection to its centrosome role unexamined
  8. 2024 Low

    Identified NUBP2 as a direct pharmacological target whose engagement alters VNN1 membrane localization and oxidative stress/fibrosis responses.

    Evidence Drug-target binding assays with ISP I, LX-2 cell assays, VNN1 membrane fractionation, and BDL/CCl4 fibrosis models

    PMID:40177065

    Open questions at the time
    • Binding assay details and binding site not specified
    • Mechanism linking NUBP2 to VNN1 trafficking unknown
  9. 2025 Medium

    Demonstrated that the centrosome/cilia regulatory role of NUBP2 is essential for neurogenesis, with its loss causing primary microcephaly via supernumerary centrosomes and p53-independent cell death.

    Evidence Emx1-Cre conditional knockout, neurosphere cultures, centrosome/cilia immunofluorescence, p53 epistasis, and human variant complementation (preprint)

    PMID:39867373

    Open questions at the time
    • p53-independent death pathway not identified
    • Preprint; human disease link based on variant complementation not yet peer-reviewed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NUBP2's nucleotide-binding activity mechanistically restrains centriole duplication and ciliogenesis, and how this reconciles with its roles in cell survival, GSK3β signaling, and VNN1 trafficking, remains unresolved.
  • No demonstrated catalytic NTPase activity tied to phenotype
  • No structural model of the NUBP1/NUBP2/KIFC5A/KATNAL2 assembly
  • Unclear whether disparate roles share a common centrosome-based mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005929 cilium 2
Pathway
R-HSA-1640170 Cell Cycle 1 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
KATNAL2KIFC5ANUBP1

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NUBP2 encodes a short-form MRP/MinD-type P-loop NTPase with conserved ATP/GTP-binding motifs (P-loop motif A and A') and two additional conserved NUBP/MRP motifs (alpha and beta), establishing it as a member of a new eukaryotic nucleotide-binding protein family related to prokaryotic MinD/MRP proteins. Phylogenetic analysis, sequence motif characterization, Northern blot Genomics Medium 10486206
2006 NUBP2 physically interacts with NUBP1, and both interact with minus-end-directed motor KIFC5A; knockdown of Nubp1 alone or double knockdown of Nubp1+Nubp2 phenocopies KIFC5A silencing (centrosome amplification, multipolar spindles), placing NUBP2 in a common regulatory pathway controlling centrosome duplication in mammalian cells. Co-immunoprecipitation (Co-IP), RNAi knockdown, immunofluorescence microscopy Journal of cell science Medium 16638812
2009 GFP-fusion localization experiments in HeLa cells showed that NUBP2 with GFP fused to the N-terminus induces nuclear accumulation, while the N-terminal region of NUBP2 contributes to nuclear morphology, indicating the N-terminus is a determinant of subcellular localization. GFP-fusion protein live imaging in HeLa cells Molecular biology reports Low 19263241
2013 NUBP2 (together with NUBP1) are integral components of centrioles throughout the cell cycle and localize to basal bodies of primary cilia; RNAi-mediated downregulation of Nubp2 in quiescent NIH 3T3 cells markedly increases the number of ciliated cells, establishing Nubp2 as a negative regulator of ciliogenesis. Simultaneous double silencing of Nubp1 + KIFC5A restores ciliogenesis to control levels, placing NUBP2 in a regulatory axis with KIFC5A. RNAi silencing, immunofluorescence microscopy, electron microscopy, genetic epistasis (double silencing) Cellular and molecular life sciences : CMLS High 23807208
2013 NUBP1 (but not NUBP2 explicitly) interacts with members of the CCT/TRiC molecular chaperone complex, which localizes to the basal body independently of NUBP1, NUBP2, or KIFC5A, suggesting CCT/TRiC chaperone activity is involved in the NUBP-regulated ciliogenesis pathway. Co-immunoprecipitation, immunofluorescence Cellular and molecular life sciences : CMLS Low 23807208
2015 NUBP2 directly and independently interacts with KATNAL2 isoforms (katanin-like 2 proteins), as shown by in vivo co-immunoprecipitation; KATNAL2 localizes to centrioles and basal bodies, and shRNAi silencing of Katnal2 increases centriole numbers and reduces ciliogenesis, linking NUBP2 to the KATNAL2 regulatory network governing MT dynamics and ciliogenesis. Co-immunoprecipitation (in vivo), shRNAi, immunofluorescence, cell biology assays Cellular and molecular life sciences : CMLS Medium 26153462
2019 Conditional ablation of Nubp2 in neural crest cells (Wnt1-Cre) causes craniofacial defects due to marked apoptosis in the craniofacial mesenchyme, without changes in the proportion of ciliated cells or alterations in SHH, FGF, or BMP signaling markers, indicating that the craniofacial phenotype is not driven by ciliogenesis dysregulation but by a distinct survival function of NUBP2 in neural crest cells. Conditional knockout (Wnt1-Cre; Nubp2), ENU forward genetic screen, exome sequencing, complementation assay, immunofluorescence for pathway markers and apoptosis Developmental biology Medium 31733190
2024 NUBP2 knockdown in colorectal cancer cells reduces proliferation, increases apoptosis, and impairs migration; NUBP2 knockdown or overexpression significantly changes phosphorylation levels of GSK3β, and the GSK3β inhibitor CHIR-99021 reverses the malignant phenotype induced by NUBP2 overexpression, placing NUBP2 upstream of GSK3β phosphorylation in CRC cell signaling. siRNA knockdown, overexpression, Human Phospho-Kinase Array, pharmacological rescue (CHIR-99021), in vivo subcutaneous tumor model Molecular and cellular biochemistry Medium 38492158
2024 ISP I (isovalerylspiramycin I) directly targets NUBP2 and, through this interaction, increases the membrane localization of VNN1 (vascular non-inflammatory molecule-1), thereby inhibiting oxidative stress and fibrosis in hepatic stellate cells and in vivo liver fibrosis models. Drug-target binding assays, cell-based assays (LX-2 cells), in vivo BDL rat and CCl4 mouse models, membrane fractionation/localization of VNN1 Journal of pharmaceutical analysis Low 40177065
2025 Conditional deletion of Nubp2 from the forebrain (Emx1-Cre) causes severe primary microcephaly accompanied by supernumerary centrosomes and cilia, increased canonical and non-canonical cell death, and alterations in proliferation and cellular migration; loss of p53 fails to rescue microcephaly, indicating that the centrosome/cilia regulatory role of NUBP2 is essential for proper neurogenesis and that cell death is not solely p53-dependent. Conditional knockout (Emx1-Cre; Nubp2 flox/flox), neurosphere cultures, immunofluorescence for centrosomes/cilia, genetic epistasis (p53 deletion), human patient variant analysis with complementation medRxiv / bioRxivpreprint Medium 39867373

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT-based processes in mammalian cells. Cellular and molecular life sciences : CMLS 31 26153462
2006 Motor protein KIFC5A interacts with Nubp1 and Nubp2, and is implicated in the regulation of centrosome duplication. Journal of cell science 29 16638812
2013 The nucleotide-binding proteins Nubp1 and Nubp2 are negative regulators of ciliogenesis. Cellular and molecular life sciences : CMLS 24 23807208
1999 Two novel mouse genes--Nubp2, mapped to the t-complex on chromosome 17, and Nubp1, mapped to chromosome 16--establish a new gene family of nucleotide-binding proteins in eukaryotes. Genomics 17 10486206
2009 Comparison of intracellular localization of Nubp1 and Nubp2 using GFP fusion proteins. Molecular biology reports 11 19263241
2023 Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker. Frontiers in oncology 6 37810966
2019 Nubp2 is required for cranial neural crest survival in the mouse. Developmental biology 2 31733190
2024 Isovalerylspiramycin I alleviates liver injury and liver fibrosis by targeting the nucleotide-binding protein 2 (NUBP2)-vascular non-inflammatory molecule-1 (VNN1) pathway. Journal of pharmaceutical analysis 1 40177065
2025 NUBP2 deficiency disrupts the centrosome-check point in the brain and causes primary microcephaly. medRxiv : the preprint server for health sciences 0 39867373
2024 Abnormal upregulation of NUBP2 contributes to cancer progression in colorectal cancer. Molecular and cellular biochemistry 0 38492158

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