| 2000 |
NORPEG (RAI14) encodes a ~110 kDa protein with six ankyrin repeats and a long coiled-coil domain; when transiently expressed in COS-7 cells as a FLAG fusion, it localizes to the cytoplasm in thread-like projections reminiscent of the cytoskeleton, and the expressed protein shows resistance to solubilization by Triton X-100 and KCl, consistent with cytoskeletal association. |
Transient expression of FLAG-fusion protein in COS-7 cells, confocal immunofluorescence, detergent fractionation |
The Journal of biological chemistry |
Medium |
11042181
|
| 2006 |
NORPEG (RAI14) subcellular localization is cell-density dependent: it is predominantly nuclear in non-confluent ARPE-19 cells but shifts to cytoplasmic/cytoskeletal localization in confluent cultures. A conserved monopartite nuclear localization signal (PKKRKAP, residues 270–276) was identified; deletion and mutation analysis showed this NLS is indispensable for nuclear targeting. |
Confocal immunofluorescence with polyclonal antibody, GFP-fusion protein expression, deletion and point mutation analysis, expression in ARPE-19 and COS-7 cells |
Biochemical and biophysical research communications |
High |
16729964
|
| 2013 |
RAI14 is an actin-binding protein expressed at the ectoplasmic specialization (ES) in rat testis; it co-associates with the actin cross-linking protein palladin. RNAi knockdown of Rai14 in Sertoli cells in vitro disrupted F-actin organization and perturbed tight junction-permeability barrier function; in vivo knockdown caused defects in spermatid polarity, adhesion, and transport via changes in F-actin organization and protein mis-localization at the apical ES. |
RNAi knockdown in vitro and in vivo, co-immunoprecipitation/binding assays with actin and palladin, immunofluorescence, tight junction permeability assays |
PloS one |
High |
23565266
|
| 2013 |
RAI14 binds directly to both F-actin and palladin (an actin cross-linking/bundling protein) in the testis, functioning as a regulator of actin filament bundle integrity at the ectoplasmic specialization during spermatogenesis. |
Co-immunoprecipitation, immunofluorescence co-localization, functional RNAi studies |
Spermatogenesis |
Medium |
23885305
|
| 2018 |
RAI14 knockdown in gastric cancer cells inhibited proliferation, migration, and invasion, and promoted apoptosis by downregulating Bcl-2 and upregulating Bax; the mechanism was linked to inhibition of Akt pathway activation, and overexpression of RAB31 rescued the reduced proliferation caused by RAI14 knockdown, placing RAB31 downstream of RAI14. |
siRNA knockdown, cell proliferation/migration/invasion assays, flow cytometry apoptosis, Western blot, Akt pathway activation with IGF-1, RAB31 rescue experiments |
OncoTargets and therapy |
Medium |
30349303
|
| 2018 |
RAI14 promotes mTOR-mediated NF-κB inflammatory signaling in U87 glioblastoma cells; RAI14 knockdown attenuated pro-inflammatory cytokine production via inhibition of the IKK/NF-κB pathway, and mTOR inhibitor (everolimus) reduced NF-κB activity and IKKα/β phosphorylation through RAI14 signaling. RAI14 also enhanced mTOR-mediated NF-κB activation under chemical hypoxia. |
siRNA knockdown, mTOR inhibitor (everolimus) treatment, Western blot for IKK/NF-κB pathway components, LPS/TNF-α and CoCl2 stimulation models |
Cellular and molecular neurobiology |
Medium |
30554401
|
| 2019 |
RAI14 knockdown in breast cancer cells inhibits proliferation, migration, and invasion by regulating cell cycle and EMT through the Akt/Cyclin D1 axis and modulating MMP2, MMP9, and ZEB1/E-cadherin/Vimentin pathway. |
siRNA knockdown, cell proliferation/migration/invasion assays, Western blot for pathway markers |
Journal of Cancer |
Low |
31772666
|
| 2020 |
RAI14 silencing in esophageal cancer cells induces apoptosis and cell cycle arrest; RAI14 activates the STAT3 pathway, upregulates Mcl-1 and cyclin D1, and inhibits cleaved caspase-3; STAT3 inhibition restored the oncogenic effect of RAI14. |
siRNA knockdown, overexpression, Western blot, STAT3 inhibitor rescue, in vivo xenograft |
Aging |
Medium |
32957082
|
| 2021 |
Rai14 knockout (via CRISPR/Cas9) in mice did not disrupt spermatogenesis, fertility, sperm parameters, F-actin organization at the ectoplasmic specialization, or ES junction morphology — in contrast to results from siRNA knockdown in rats. This negative result indicates Rai14 is dispensable for mouse spermatogenesis. |
CRISPR/Cas9 knockout, CASA sperm analysis, histology, immunofluorescence, TEM, TUNEL assay |
PeerJ |
Medium |
33643708
|
| 2022 |
The deubiquitinase STAMBP physically interacts with RAI14 and stabilizes it by suppressing K48-linked ubiquitination of RAI14, preventing its proteasomal degradation; STAMBP knockdown reduces RAI14 protein levels and suppresses TNBC tumor growth in vitro and in vivo. |
Immunoprecipitation-mass spectrometry, co-immunoprecipitation, siRNA knockdown, ubiquitination assays (K48-linked), in vitro and in vivo tumor growth assays |
Experimental & molecular medicine |
High |
36434041
|
| 2022 |
RAI14 affects the transcriptional expression of FBXO32 (an E3 ubiquitin ligase for c-MYC) and thereby regulates the stability of c-MYC protein in melanoma cells; RAI14 expression affects proliferation and invasion of melanoma cells. |
RAI14 overexpression/knockdown, Western blot for FBXO32 and c-MYC, cell proliferation and invasion assays |
International journal of molecular sciences |
Low |
36233342
|
| 2023 |
RAI14 interacts with Invariant chain (Ii/CD74) as identified by yeast two-hybrid screening, confirmed by co-immunoprecipitation; RAI14 localizes to membrane ruffles and macropinosomes. Depletion of RAI14 in antigen-presenting cells delays MHC II internalization and reduces macropinocytic activity. RAI14 also binds myosin II, suggesting RAI14, Ii, and myosin II cooperate to coordinate macropinocytosis and cell motility. |
Yeast two-hybrid screening, co-immunoprecipitation, immunofluorescence localization, RAI14 depletion with functional macropinocytosis and MHC II internalization assays, myosin II binding assay |
Frontiers in immunology |
High |
37545539
|
| 2025 |
RA-induced RAI14 upregulation in renal fibroblasts promotes fibroblast-to-myofibroblast transition; RAI14 binds and stabilizes TRIOBP by preventing HECTD1-mediated ubiquitination and degradation of TRIOBP. This stabilization enhances F-actin assembly and cytoskeletal tension, leading to YAP nuclear translocation and activation of profibrotic transcriptional programs. Genetic ablation of RAI14 significantly attenuates renal fibrosis in vivo. |
Spatial metabolomics, single-cell transcriptomics, co-immunoprecipitation (RAI14-TRIOBP interaction), ubiquitination assays (HECTD1-mediated), F-actin assembly assays, YAP nuclear translocation assays, RAI14 genetic knockout in vivo fibrosis model |
Cellular signalling |
High |
41242366
|
| 2025 |
RNASEH2C enhances TRAF3IP1 expression to promote lysosomal degradation of RAI14, suppressing the mTOR pathway; HSC70 and CMTM6 play opposing roles in RAI14 degradation. RAI14 functions as a skeletal protein that facilitates macropinocytosis of MHC II molecules and tumor-associated antigen in macrophages, thereby activating Th1 cells in hepatocellular carcinoma. |
Single-cell RNA sequencing, immunoblotting, immunofluorescence, immunoprecipitation, flow cytometry, in vitro and mouse tumor models |
Cell death & disease |
Medium |
41361104
|
| 2025 |
RAI14, EPHA2, and PHACTR4 are components of the Wnt/PCP pathway identified by BioID proximity interactomics with key PCP components (ROR1, ROR2, VANGL2, DVL3, PRICKLE1); loss-of-function of rai14 in zebrafish disrupted convergent extension, orientation of lateral organ cells, and migration of melanoma cells (Wnt/PCP-dependent processes). Mechanistically, RAI14 connects the receptor complex to effector actomyosin. |
BioID proximity-dependent biotinylation interactomics, zebrafish loss-of-function (convergent extension, lateral organ orientation, melanoma cell migration assays) |
bioRxivpreprint |
Medium |
bio_10.1101_2025.01.15.633117
|