Affinage

RIN1

Ras and Rab interactor 1 · UniProt Q13671

Length
783 aa
Mass
84.1 kDa
Annotated
2026-06-10
43 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RIN1 is a multidomain RAS effector that couples activated RAS to membrane trafficking and tyrosine-kinase signaling, thereby controlling receptor endocytosis, cytoskeletal remodeling, and cell adhesion/migration (PMID:11784866, PMID:11703925, PMID:15886098). It binds activated RAS with high affinity (~22 nM) and competes directly with RAF1, and unlike canonical proliferative effectors it inhibits RAS-mediated transformation (PMID:11784866). Through its Vps9-homology domain, RIN1 acts as a guanine-nucleotide exchange factor for RAB5, stimulating Rab5-dependent endosome fusion and driving internalization of activated receptors including EGFR; activated RAS potentiates this GEF activity (PMID:11703925, PMID:12783862). In parallel, RIN1 directly activates ABL tyrosine kinases by binding their SH3 and SH2 domains and stimulating catalytic activity toward CRK/CRKL, with RAS forming a stable RAS–RIN1–ABL2 complex that relieves RIN1 autoinhibition; loss of RIN1 accelerates cell adhesion and motility (PMID:15886098, PMID:9144171). These two outputs are integrated at the receptor level: RIN1 dictates EGFR fate by routing it toward RAB5-driven degradation while ABL activation stabilizes the receptor and restrains macropinocytosis, with degradation requiring the RIN1 PRD–STAM2 interaction (PMID:22976291, PMID:17403676). RIN1 is recruited to ligand-engaged receptors through its SH2 domain binding to phosphorylated EGFR, insulin receptor, and EphA4, and its activity and membrane localization are tuned by PKD phosphorylation of S351 (controlling 14-3-3 binding) and PKA phosphorylation of S291/S292 (promoting RAS binding and blocking TGF-β–induced migration) (PMID:12783862, PMID:16457816, PMID:18723684, PMID:11784866, PMID:27137893). Beyond receptor trafficking, RIN1 acts as a GEF for the mitofusin MFN2 when scaffolded by cytoplasmic Smad2 to promote mitochondrial fusion (PMID:27184078). In the nervous system RIN1 is an inhibitory modulator of neuronal plasticity: it is enriched in forebrain and excitatory neurons, mediates EphA4 endocytosis, and its knockout enhances amygdala LTP and aversive memory, while in sensory and spinal neurons it controls NMDAR subunit switching and TRPV1 surface levels to shape nociception (PMID:12574403, PMID:18723684, PMID:41329672, PMID:42186385). In disease, RIN1 potentiates BCR-ABL oncogenic signaling and is required for BCR-ABL-driven leukemic transformation, with its silencing increasing imatinib sensitivity (PMID:9208849, PMID:21102429).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Established RIN1 as a bifunctional adaptor that physically and enzymatically links ABL tyrosine kinase to activated RAS, defining its core domain architecture.

    Evidence In vitro SH3 binding, co-IP, and tyrosine phosphorylation assays in mammalian cells

    PMID:9144171

    Open questions at the time
    • Functional consequence of ABL–RIN1 binding not yet defined
    • Did not establish how RAS binding regulates RIN1 activity
  2. 1997 High

    Showed RIN1 is a functional partner of oncogenic BCR-ABL, providing the first disease context by demonstrating it accelerates BCR-ABL-induced leukemia.

    Evidence Co-IP from leukemic cells, retroviral transformation, and murine leukemia model

    PMID:9208849

    Open questions at the time
    • Mechanism by which RIN1 potentiates kinase activity not resolved
    • Whether RIN1 is required (not just sufficient) for transformation untested
  3. 2001 High

    Identified RIN1's enzymatic activity as a RAB5 GEF, explaining how a RAS effector drives receptor endocytosis and endosome fusion.

    Evidence In vitro GEF assay with domain deletions plus endosome fusion and EGFR endocytosis assays

    PMID:11703925

    Open questions at the time
    • How RAS potentiation of GEF activity is achieved structurally unknown
    • Receptor specificity of RIN1-driven endocytosis not delineated
  4. 2002 High

    Quantified RIN1–RAS binding and showed it competes with RAF and inhibits transformation, plus identified PKD/14-3-3 control of localization—distinguishing RIN1 from proliferative RAS effectors.

    Evidence Surface plasmon resonance, competition and transformation assays, in vitro PKD kinase assay, fractionation

    PMID:11784866

    Open questions at the time
    • Upstream signals controlling PKD-mediated S351 phosphorylation in vivo unclear
    • Link between membrane localization and effector output not mechanistically dissected
  5. 2003 High

    Defined the SH2 domain as the receptor-recruitment module, explaining how growth factor stimulation localizes RIN1 to drive EGFR internalization.

    Evidence Co-IP, recruitment microscopy, dominant-negative SH2 expression, internalization assay

    PMID:12783862

    Open questions at the time
    • Phosphotyrosine specificity of the SH2 domain not mapped
    • Whether SH2 binding feeds into GEF or ABL output untested here
  6. 2003 High

    Revealed an in vivo physiological role: RIN1 restrains neuronal plasticity and fear memory, moving it beyond cell-line biochemistry.

    Evidence Neuronal immunolocalization, Rin1 knockout mice, amygdala LTP, fear conditioning

    PMID:12574403

    Open questions at the time
    • Which RIN1 effector activity (RAB5 vs ABL) underlies the plasticity phenotype not separated
    • Synaptic substrate/receptor unknown at this stage
  7. 2005 High

    Reconstituted RIN1 as a direct ABL activator and showed RAS relieves RIN1 autoinhibition, unifying the RAS, ABL, and adhesion outputs into one regulatory logic.

    Evidence In vitro ABL2 kinase assay with purified proteins, co-IP, Rin1 KO cells, migration assays, RNAi

    PMID:15886098

    Open questions at the time
    • Structural basis of RBD-mediated autoinhibition not resolved
    • How RAS binding allosterically opens RIN1 unknown
  8. 2006 Medium

    Extended RIN1 receptor regulation to the insulin receptor and showed it selectively dampens ERK and Akt signaling, indicating pathway-selective control.

    Evidence Retroviral expression of deletion mutants, internalization, co-IP, kinase assays, confocal

    PMID:16457816

    Open questions at the time
    • Single-lab study without independent confirmation
    • Basis for selective ERK/Akt versus JNK/p38 effects not mechanistically explained
  9. 2007 High

    Identified STAM2 as the PRD partner required to route EGFR to degradation, connecting RIN1 to the ESCRT/endosomal sorting machinery.

    Evidence Reciprocal co-IP, RNAi, confocal co-localization, PRD deletion, EGFR degradation assay

    PMID:17403676

    Open questions at the time
    • Whether STAM2 recruitment requires concurrent RAB5 activation untested
    • Generality across other receptors not examined
  10. 2008 High

    Provided the synaptic substrate for RIN1's plasticity role by showing SH2-mediated EphA4 binding and ephrin-triggered EphA4 endocytosis in amygdala neurons.

    Evidence Co-IP from synaptosomes, EphA4 endocytosis assay, Rin1 KO, amygdala LTP

    PMID:18723684

    Open questions at the time
    • Downstream signaling from internalized EphA4 not traced
    • Contribution of ABL versus RAB5 activity to LTP suppression unresolved
  11. 2010 High

    Demonstrated RIN1 is required for BCR-ABL1 transformation and stabilizes a drug-resistant kinase conformation, establishing it as a determinant of imatinib sensitivity.

    Evidence RNAi, Rin1 KO bone marrow transformation with ectopic rescue, kinase activity and imatinib sensitivity assays

    PMID:21102429

    Open questions at the time
    • Structural model of the stabilized BCR-ABL1 conformation not determined
    • Whether RIN1 targeting is therapeutically tractable not yet tested
  12. 2012 High

    Integrated RIN1's dual outputs by showing RAB5 and ABL arms oppositely control EGFR degradation versus macropinocytosis, defining RIN1 as a switch governing receptor fate.

    Evidence RNAi/overexpression of mutants, EGFR degradation and macropinocytosis assays, ABL inhibitor, RIN1-BIN1 co-IP, actin imaging

    PMID:22976291

    Open questions at the time
    • How the balance between the two arms is set in different cell types unclear
    • Role of BIN1 in membrane bending mechanistically undefined
  13. 2014 Medium

    Showed RIN1's RAB5-GEF activity is exploited and used during bacterial infection, broadening its trafficking role to host–pathogen interactions.

    Evidence RNAi, Listeria invasion assay, phagosome-lysosome fusion assay in epithelial cells

    PMID:25082076

    Open questions at the time
    • Single-lab study; counterbalancing early/late roles need independent confirmation
    • Host signal triggering RIN1 engagement post-infection unknown
  14. 2015 Medium

    Validated the RIN1–ABL interface as a druggable node by showing both engineered and small-molecule disruption of the interaction suppress BCR-ABL signaling and restore imatinib sensitivity.

    Evidence Co-IP with engineered SH3 mutant and TR-FRET HTS, kinase activity, MAPK assays, proliferation, xenograft

    PMID:25811598 PMID:26321052

    Open questions at the time
    • Compound selectivity and in vivo efficacy beyond initial models unestablished
    • Single-lab validation of each approach
  15. 2016 High

    Uncovered a non-trafficking role: Smad2-scaffolded RIN1 acts as a MFN2 GEF to promote mitochondrial fusion and metabolic output, expanding its GEF repertoire beyond RAB5.

    Evidence Co-IP of Smad2-RIN1-MFN2 complex, MFN2 GTP-exchange assay, mitochondrial imaging, ATP/ROS measurements, RNAi

    PMID:27184078

    Open questions at the time
    • How RIN1 selects RAB5 versus MFN2 substrates not resolved
    • Physiological trigger redirecting RIN1 to mitochondria unclear
  16. 2016 Medium

    Defined PKA phosphorylation of S291/S292 as a regulatory input that enhances RAS binding and blocks TGF-β-driven migration, adding a second phospho-control layer atop PKD/S351.

    Evidence Phosphoproteomics, in vitro PKA assay, RAS pull-down, mutagenesis, migration assay, siRNA

    PMID:27137893

    Open questions at the time
    • Single-lab study
    • Interplay between S291/292 and S351 phosphorylation not examined
  17. 2017 Medium

    Showed a context where RIN1 promotes (rather than inhibits) oncogenic signaling, acting via RAB25 to drive EGFR signaling and tumor cell aggressiveness in renal carcinoma.

    Evidence RIN1-RAB25 co-IP, gain/loss-of-function, RAB25 knockdown rescue, growth/migration/invasion, xenograft

    PMID:28612496

    Open questions at the time
    • Mechanistic depth limited; how RAB25 alters EGFR fate unclear
    • Reconciliation with RIN1's transformation-inhibitory role elsewhere not addressed
  18. 2023 Medium

    Implicated RIN1 in RASopathy pathology by showing it is the dominant HRAS(G12S) effector in Costello syndrome keratinocytes, mislocalizing β1 integrin and impairing its recycling.

    Evidence HRAS-RIN1 co-IP, RAB5A activation assay, integrin endosomal co-localization, RIN1 disruption, surface distribution and spreading assays

    PMID:35981076

    Open questions at the time
    • Single-lab study
    • Whether RIN1 targeting ameliorates Costello syndrome phenotypes untested
  19. 2025 Medium

    Established RIN1 as a regulator of nociceptive signaling by controlling NMDAR subunit composition in spinal neurons and TRPV1 surface levels in DRG neurons.

    Evidence Conditional RIN1 knockouts, synaptic NMDAR composition and TRPV1 surface trafficking assays, RIN1-TRPV1 co-IP, AAV rescue, behavioral nociception

    PMID:41329672 PMID:42186385

    Open questions at the time
    • Single-lab studies
    • Which RIN1 effector arm drives NMDAR subunit switching not separated from RAB5-GEF activity

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RIN1 partitions its GEF activity among RAB5, MFN2, and other targets, and how phosphorylation, RAS binding, and partner scaffolds combinatorially select among its receptor-degradation, ABL-activation, and metabolic outputs in a given cell, remains unresolved.
  • No structural model of full-length autoinhibited versus RAS-bound RIN1
  • Cell-type rules governing inhibitory versus oncogenic RIN1 outputs undefined
  • Integration of S351 and S291/292 phospho-control not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ABL1ABL2EGFRHRASMFN2RAB5ASMAD2STAM2
Complex memberships
RAS-RIN1-ABL2 complexSmad2-RIN1-MFN2 complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 RIN1 binds to the ABL SH3 domain via a proline-rich sequence and is directly tyrosine phosphorylated by c-ABL; RIN1 also encodes a functional SH2 domain. Full-length RIN1 interacts with activated RAS in mammalian cells through its C-terminal effector-binding domain. In vitro SH3-domain binding assay, co-immunoprecipitation, tyrosine phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 9144171
1997 RIN1 potentiates BCR-ABL oncogenic activity and accelerates BCR-ABL-induced leukemia; this requires tyrosine phosphorylation of RIN1 and binding to ABL SH2 and SH3 domains. RIN1 is tyrosine phosphorylated and associated with BCR-ABL in human and murine leukemic cells. Co-immunoprecipitation from leukemic cells, retroviral transformation assay in hematopoietic cells, murine leukemia model Immunity High 9208849
2001 The Vps9-homology domain of RIN1 is necessary and sufficient for binding to GDP-bound Rab5A and Vps21p, and RIN1 stimulates Rab5 guanine nucleotide exchange, Rab5A-dependent endosome fusion, and EGF receptor-mediated endocytosis. Activated RAS potentiates all three of these RIN1-mediated activities. In vitro GEF assay, endosome fusion assay, EGF receptor endocytosis assay, domain-deletion analysis Developmental cell High 11703925
2002 RIN1 binds activated RAS with Kd ~22 nM, directly competing with RAF1 for RAS binding. RIN1 inhibits RAS-mediated cellular transformation (distinguishing it from other RAS effectors). RIN1 binds 14-3-3 proteins through serine 351, and phosphorylation of S351 by protein kinase D (PKD/PKCmu) in vitro and in vivo controls 14-3-3 binding and RIN1 membrane localization. S351A mutation shifts RIN1 to the plasma membrane and enhances RAS transformation blockade. Surface plasmon resonance (Kd measurement), competition binding assay, focus formation/transformation assay, co-immunoprecipitation, in vitro kinase assay, subcellular fractionation Molecular and cellular biology High 11784866
2003 The SH2 domain of RIN1 mediates ligand-dependent binding to tyrosine-phosphorylated EGFR intracellular domain, recruits RIN1 to plasma membrane and endosomes upon EGF stimulation, and is required for EGFR internalization. Expression of the SH2 domain alone substantially impaired EGF internalization without affecting transferrin internalization. Co-immunoprecipitation, light microscopy/subcellular recruitment, dominant-negative SH2 domain expression, internalization assay The Journal of biological chemistry High 12783862
2003 RIN1 is preferentially expressed in postnatal forebrain neurons where it localizes in dendrites and is physically associated with RAS. Rin1 knockout mice show enhanced amygdala LTP and elevated amygdala-dependent aversive memory, indicating RIN1 is an inhibitory modulator of neuronal plasticity in fear memory formation. Immunolocalization in neurons, Rin1 gene knockout mice, amygdala LTP electrophysiology, fear conditioning behavioral assays The Journal of neuroscience High 12574403
2005 RIN1 is a direct activator of ABL tyrosine kinases: it binds ABL SH3 and SH2 domains, stimulates ABL2 catalytic activity in immune complexes and in a defined-component in vitro assay with purified ABL-binding domain (ABD), leading to increased phosphorylation of CRK and CRKL. Activated RAS forms a stable RAS-RIN1-ABL2 complex and enhances ABL2 activation. Deletion of the RAS-binding domain (RBD) strongly increases ABL2 activation, suggesting RAS relieves RIN1 autoinhibition. Rin1-/- mammary epithelial cells show accelerated adhesion and increased motility. In vitro ABL2 kinase assay with purified proteins, co-immunoprecipitation, Rin1 knockout mouse cells, cell adhesion and migration assay, RNAi knockdown Current biology : CB High 15886098
2006 RIN1 regulates insulin receptor internalization and signaling: RIN1 expression enhances insulin receptor-mediated and fluid-phase insulin-stimulated endocytosis via its Rab5-GEF and Ras-binding domains; the SH2 domain of RIN1 associates with tyrosine-phosphorylated insulin receptor. RIN1 expression selectively blocks ERK1/2 and Akt1 activation without affecting JNK or p38. Retroviral expression of RIN1 deletion mutants, receptor internalization assay, co-immunoprecipitation, kinase activity assays, confocal microscopy co-localization Experimental cell research Medium 16457816
2007 RIN1 interacts with STAM2 (signal-transducing adaptor molecule 2) via its proline-rich domain (PRD) and STAM2's SH3 domain. This interaction is required for RIN1-accelerated EGFR degradation following EGF stimulation; a RIN1 mutant lacking the PRD (RIN1ΔPRD) neither binds STAM2 nor accelerates EGFR degradation. Co-immunoprecipitation, RNAi knockdown, confocal co-localization (GFP-Rin1 and HA-STAM2), domain-deletion mutagenesis, EGFR degradation assay The Journal of biological chemistry High 17403676
2008 RIN1 (Rin1), expressed specifically in postnatal brain excitatory neurons, interacts with EphA4 receptor tyrosine kinase in synaptosomal fractions via its SH2 domain, mediates EphA4 endocytosis in amygdala neurons following ephrinB3 engagement, and suppresses synaptic plasticity in the amygdala. Co-immunoprecipitation from synaptosomal fractions, EphA4 endocytosis assay in amygdala neurons, Rin1 knockout mice, amygdala LTP electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 18723684
2010 RIN1 silencing decreases BCR-ABL1 kinase activity; RIN1 overexpression increases it. Rin1-/- bone marrow cells are not transformed by BCR-ABL1, ETV6-ABL1, or drug-resistant BCR-ABL1(T315I); rescue by ectopic RIN1 confirms cell-autonomous mechanism. RIN1 silencing increases imatinib sensitivity, consistent with RIN1 stabilizing an activated BCR-ABL1 conformation with reduced drug affinity. RNAi knockdown, Rin1 knockout bone marrow transformation assay, ectopic RIN1 rescue, BCR-ABL1 kinase activity assay, imatinib sensitivity assay Leukemia High 21102429
2012 RIN1 orchestrates EGFR fate by activating RAB5 GTPases (favoring EGFR degradation over recycling) and ABL tyrosine kinases (stabilizing EGFR and inhibiting macropinocytosis). A RIN1(QM) mutant that blocks ABL activation causes EGF-stimulated membrane ruffling, actin remodeling, macropinocytosis (dextran uptake), and EGFR degradation. EGFR activation also promotes RIN1 interaction with BIN1, a membrane-bending protein. RNAi silencing and overexpression of RIN1/mutants, EGFR degradation assay, macropinocytosis (dextran uptake) assay, ABL kinase inhibitor treatment, co-immunoprecipitation (RIN1-BIN1), actin remodeling imaging Journal of cell science High 22976291
2014 RIN1's RAB5-GEF activity is required for efficient Listeria monocytogenes invasion of intestinal epithelial cells (RIN1 is rapidly engaged post-infection) and subsequently facilitates phagosome-lysosome fusion to promote bacterial clearance, performing counterbalancing roles at early and late infection stages. RIN1 RNAi knockdown, L. monocytogenes invasion assay, phagosome-lysosome fusion assay in epithelial cells Traffic (Copenhagen, Denmark) Medium 25082076
2015 An engineered ABL SH3 mutant (T79Y) blocks the RIN1–BCR-ABL SH3 interaction via PxxP motifs, represses BCR-ABL autophosphorylation and downstream signaling pathways, and increases imatinib sensitivity in resistant CML cell lines in vitro and in vivo. Co-immunoprecipitation (SH3-RIN1 interaction), BCR-ABL kinase activity assay, cell proliferation assay, xenograft mouse model Cancer letters Medium 26321052
2015 A TR-FRET-based HTS identified small molecules that disrupt RIN1 binding to ABL, blocking RIN1-dependent stimulation of ABL kinase. Five confirmed compounds decrease MAPK1/3 phosphorylation (a RIN1-dependent ABL signaling indicator) in CML K562 cells and lower BCR-ABL1 kinase activity. TR-FRET binding assay, HTS of 444,743 compounds, cellular MAPK1/3 phosphorylation assay, BCR-ABL kinase activity assay PloS one Medium 25811598
2016 Smad2 forms a cytoplasmic complex with RIN1 and MFN2 (mitofusin2). Inactive cytoplasmic Smad2 recruits RIN1 to act as a GEF for MFN2-GTPase, promoting mitochondrial fusion, ATP synthesis, and suppression of superoxide production. This is distinct from TGF-β-induced nuclear Smad2/3 transcriptional activity. Co-immunoprecipitation (Smad2-RIN1-MFN2 complex), GTP exchange assay for MFN2, mitochondrial morphology imaging, ATP and ROS measurements, RNAi knockdown Molecular cell High 27184078
2016 PGE2-dependent PKA phosphorylation of RIN1 at Ser291 and Ser292 promotes RIN1 binding to activated RAS and abrogates TGF-β-induced RAS/RAF/ERK signaling activation and downstream cellular migration. Ser291/292Ala mutant RIN1 fails to bind activated RAS and fails to block TGF-β-induced migration. Global phosphoproteomics, in vitro PKA phosphorylation, co-immunoprecipitation/pull-down with RAS, RIN1 mutant overexpression, cell migration assay, siRNA knockdown Journal of cellular physiology Medium 27137893
2016 RIN1 interacts with RAB25 GTPase and activates EGFR signaling in clear cell renal cell carcinoma; knockdown of RAB25 eliminates RIN1-driven increases in cell proliferation, migration, and invasion. Co-immunoprecipitation (RIN1-RAB25), RIN1 gain- and loss-of-function, RAB25 knockdown rescue assay, in vitro cell growth/migration/invasion, in vivo xenograft Cancer science Medium 28612496
2023 In Costello syndrome keratinocytes expressing HRAS(Gly12Ser), RIN1 is the quantitatively most prominent high-affinity effector of active HRAS. HRASGly12Ser strongly increases RIN1-dependent RAB5A activation and HRAS-RIN1-ABL1/2 signaling, redirects β1 integrin to RAB5/EEA1-positive early endosomes, impairs integrin recycling, and reduces β1 integrin surface distribution. RIN1 disruption reverses β1 integrin intracellular accumulation. Co-immunoprecipitation (HRAS-RIN1), RAB5A activation assay, confocal co-localization of β1 integrin with endosomal markers, RIN1 siRNA/disruption, integrin surface distribution assay, cell spreading assay Human molecular genetics Medium 35981076
2025 RIN1 dictates synaptic NMDAR subunit composition in spinal cord SOM+ neurons by differentially regulating synaptic trafficking of GluN2B- and GluN2A-containing NMDARs. RIN1 protein levels increase with synapse maturation and drive the developmental GluN2B-to-GluN2A switch; nerve injury-induced RIN1 increase drives a new round of this switch and alters the analgesic efficacy of NMDAR subunit antagonists. Conditional RIN1 knockout in spinal SOM+ neurons, synaptic NMDAR subunit composition analysis, immunofluorescence, behavioral nociception assays, pharmacological NMDAR antagonist sensitivity testing PLoS biology Medium 41329672
2025 RIN1 in dorsal root ganglion neurons interacts with TRPV1 and promotes TRPV1 endocytosis via its Rab5-GEF activity, limiting TRPV1 plasma membrane levels and the duration/magnitude of TRPV1-dependent acute pain responses. Conditional RIN1 knockout in DRG neurons enhances TRPV1 surface accumulation and nociceptive sensitization; AAV-mediated RIN1 re-expression rescues this. Co-immunoprecipitation (RIN1-TRPV1), conditional DRG-specific RIN1 knockout, TRPV1 endocytosis assay, TRPV1 surface distribution assay, nociceptive behavioral assays, AAV rescue experiment Molecular pain Medium 42186385

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Developmental cell 245 11703925
2002 The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins. Molecular and cellular biology 122 11784866
2005 RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration. Current biology : CB 99 15886098
1997 Protein binding and signaling properties of RIN1 suggest a unique effector function. Proceedings of the National Academy of Sciences of the United States of America 97 9144171
2000 A consistent pattern of RIN1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage-fusion-bridge cycle model for 11q13 amplification. Genes, chromosomes & cancer 88 10825000
2003 The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis. The Journal of biological chemistry 71 12783862
1997 Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1. Immunity 70 9208849
2008 The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons. Proceedings of the National Academy of Sciences of the United States of America 64 18723684
2003 The RAS effector RIN1 modulates the formation of aversive memories. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 12574403
2016 Activation of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion. Molecular cell 51 27184078
2012 RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to determine the fate of EGFR. Journal of cell science 48 22976291
2007 Rin1 interacts with signal-transducing adaptor molecule (STAM) and mediates epidermal growth factor receptor trafficking and degradation. The Journal of biological chemistry 33 17403676
2007 RIN1 is a breast tumor suppressor gene. Cancer research 32 18089779
2009 Cell proliferation and epidermal growth factor signaling in non-small cell lung adenocarcinoma cell lines are dependent on Rin1. The Journal of biological chemistry 30 19570984
2010 Fear learning and extinction are linked to neuronal plasticity through Rin1 signaling. Journal of neuroscience research 21 19830836
2017 RIN1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25. Cancer science 20 28612496
2012 Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 22249975
2006 Rin1 regulates insulin receptor signal transduction pathways. Experimental cell research 19 16457816
2017 Change of Rin1 and Stathmin in the Animal Model of Traumatic Stresses. Frontiers in behavioral neuroscience 17 28491025
2010 ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1. Leukemia 15 21102429
2001 Cloning and expression of sprint, a Drosophila homologue of RIN1. Mechanisms of development 14 11231087
2014 The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection. Traffic (Copenhagen, Denmark) 12 25082076
2023 Evaluation of the anticancer activity of RIN-1, a Notch signaling modulator, in head and neck squamous cell carcinoma. Scientific reports 9 37607974
2013 RIN1 regulates cell migration through RAB5 GTPases and ABL tyrosine kinases. Communicative & integrative biology 9 24265854
2009 Regulated expression of the Ras effector Rin1 in forebrain neurons. Molecular and cellular neurosciences 9 19837165
2016 Prostaglandin E2-Dependent Phosphorylation of RAS Inhibition 1 (RIN1) at Ser 291 and 292 Inhibits Transforming Growth Factor-β-Induced RAS Activation Pathway in Human Synovial Fibroblasts: Role in Cell Migration. Journal of cellular physiology 8 27137893
2013 The novel Rac effector RIN-1 regulates neuronal cell migration and axon pathfinding in C. elegans. Development (Cambridge, England) 8 23900541
2020 Enhanced apoptosis and decreased ampa receptors are involved in deficit in fear memory in rin1 knockout rats. Journal of affective disorders 6 32174475
2011 RIN1-Ras-ERK pathway plays an important role in carcinogenesis in colon cancer cell line LoVo. Oncology research 6 22812185
2023 Cutaneous manifestations in Costello syndrome: HRAS p.Gly12Ser affects RIN1-mediated integrin trafficking in immortalized epidermal keratinocytes. Human molecular genetics 5 35981076
2020 Role of RIN1 on telomerase activity driven by EGF-Ras mediated signaling in breast cancer. Experimental cell research 5 33069695
2006 Rin1 is a negative regulator of the IL3 receptor signal transduction pathways. Anticancer research 5 16619486
2009 Cloning of a novel splicing variant of RIN1 and its expression in gastric and colon cancer. Oncology research 4 19806790
2025 Exploring the tumor suppressor role of RIN1 in familial thyroid carcinoma. Endocrine-related cancer 3 40116813
2025 RIN1 regulates ferroptosis and nociceptive perception via the Nrf2/HO-1 pathway in chronic constriction injury. Cellular signalling 3 40199450
2015 ABL SH3 mutant inhibits BCR-ABL activity and increases imatinib sensitivity by targeting RIN1 protein in CML cell. Cancer letters 3 26321052
2015 Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1. PloS one 2 25811598
2024 Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana. PloS one 1 38635569
2026 EXPRESS: RIN1 inhibited TRPV1-dependent pain sensitization in a mouse model of bone cancer pain. Molecular pain 0 42186385
2026 Pyramiding nn16 and rin1 alleles to balance plant height and node number at high latitudes. Molecular breeding : new strategies in plant improvement 0 42222010
2025 Neuropathic pain caused contextual fear generalization by reducing RIN1 expression in dorsal hippocampal CA1 pyramidal neurons. Neuropharmacology 0 40835090
2025 RIN1 regulates developmental and pain-related plasticity in spinal synapses via NMDA receptor subunit trafficking. PLoS biology 0 41329672
2016 Rin1 restores host phagocytic activity during invasion by Pseudomonas aeruginosa. Journal of medical microbiology 0 26902911

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