Affinage

SORBS2

Sorbin and SH3 domain-containing protein 2 · UniProt O94875

Length
1100 aa
Mass
124.1 kDa
Annotated
2026-06-10
56 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SORBS2 (ArgBP2/nArgBP2) is a multi-domain adaptor that operates at two distinct functional poles: assembling cytoskeletal signaling complexes and acting as a post-transcriptional mRNA-stabilizing RNA-binding protein (PMID:9211900, PMID:29548303). As a scaffold, it was first identified as a substrate of Arg/v-Abl tyrosine kinases that localizes to stress fibers in epithelial cells and to cardiac Z-disks via its three C-terminal SH3 domains (PMID:9211900). Its SoHo and SH3 domains nucleate cytoskeletal complexes through direct binding to spectrin, dynamin, synaptojanin, WAVE isoforms, palladin, and alpha-actinin, with a palladin–alpha-actinin–ArgBP2 ternary complex explaining its Z-disc targeting (PMID:15659545, PMID:16125169). SORBS2 bridges c-Abl to the ubiquitin ligase Cbl, promoting phosphorylation-dependent ubiquitination and proteasomal degradation of c-Abl, and its own activities are gated by tyrosine phosphorylation (which destabilizes SH3-mediated oligomers) and by PKA phosphorylation that drives 14-3-3 binding to release alpha-actinin and relieve migration inhibition (PMID:12475393, PMID:25429109, PMID:24475245). Through a WAVE1/PTP-PEST/c-Abl axis it restrains cell adhesion and migration, and its loss promotes invasion across multiple cancers (PMID:18559503). As an RNA-binding protein, SORBS2 binds 3' UTRs and other regions of target transcripts—including WFDC1, IL-17D, RORA, MTUS1, TIMP3, and HK2—to stabilize them, generally enforcing tumor-suppressive programs (PMID:29548303, PMID:31365778, PMID:33311452, PMID:39288625). In the heart, SORBS2 localizes to the intercalated disc and binds beta-tubulin to promote microtubule polymerization and integrin–cytoskeleton coupling; cardiomyocyte loss of Sorbs2 produces arrhythmogenic and dilated cardiomyopathy with disrupted intercalated disc integrity, defective microtubule cross-linking, fibrosis, and broad ion-channel remodeling, while it directly regulates BK and Nav1.5 channels via SH3/SoHo protein interactions and mRNA binding (PMID:32808564, PMID:32143182, PMID:34487812, PMID:35730644, PMID:38362769, PMID:39957251, PMID:40662394). In the nervous system the neuronal isoform localizes with F-actin at spines and supports dendritic complexity and AMPAR-mediated synaptic transmission (PMID:26888934, PMID:38555055).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Established SORBS2 as a kinase-associated adaptor by showing it binds and is phosphorylated by Arg/Abl kinases and partitions between epithelial stress fibers and cardiac Z-disks, defining its dual cytoskeletal compartments.

    Evidence Yeast two-hybrid, reciprocal Co-IP, subcellular fractionation/IF, and in vivo phosphorylation assay

    PMID:9211900

    Open questions at the time
    • Catalytic or downstream consequence of ArgBP2 tyrosine phosphorylation not yet defined
    • No structural basis for SH3-mediated kinase binding
  2. 1999 High

    Defined a neuronal synaptic role by mapping nArgBP2 SH3-domain binding to SAPAP, vinculin, and l-afadin at synapses, extending the scaffold beyond muscle/epithelium.

    Evidence Co-IP from rat brain, yeast two-hybrid domain mapping, IF co-localization

    PMID:10521485

    Open questions at the time
    • Functional consequence at the synapse not tested here
    • Isoform-specific expression not resolved
  3. 2003 High

    Resolved how SORBS2 controls Abl kinase levels by showing it scaffolds c-Abl to Cbl, coupling phosphorylation to ubiquitination and degradation of both c-Abl and itself.

    Evidence Co-IP, in vitro ubiquitination assay, degradation Western blots

    PMID:12475393

    Open questions at the time
    • Cellular contexts in which this degradation pathway dominates not mapped
    • In vivo relevance of self-degradation unknown
  4. 2005 High

    Built the cytoskeletal interactome and assigned Z-disc targeting, showing SoHo binds spectrin and SH3 domains bind dynamin, synaptojanin, WAVE, palladin, and alpha-actinin in a ternary complex.

    Evidence Pull-downs, Co-IP, RNAi/overexpression phenotyping, targeting assays (two studies)

    PMID:15659545 PMID:16125169

    Open questions at the time
    • Quantitative affinities and competition among partners not measured
    • Direct link between partner binding and a specific signaling output not established
  5. 2008 High

    Demonstrated a migration-suppressive function via a WAVE1/PTP-PEST/c-Abl complex and linked SORBS2 loss to invasion and metastasis in pancreatic cancer.

    Evidence Gain/loss-of-function in cancer lines, migration/adhesion assays, Co-IP, in vivo tumorigenicity

    PMID:18559503

    Open questions at the time
    • Direct enzymatic regulation within the complex not dissected
    • Generalizability across tumor types untested at this stage
  6. 2014 High

    Showed SORBS2 scaffold activity is conformationally gated: tyrosine phosphorylation destabilizes SH3 oligomers and PKA/14-3-3 displaces alpha-actinin, switching its anti-migratory state on and off.

    Evidence Oligomerization Co-IP, in vitro kinase assays, domain/point mutagenesis, 14-3-3 pull-down, migration assays (two studies)

    PMID:24475245 PMID:25429109

    Open questions at the time
    • In vivo phospho-stoichiometry not measured
    • Upstream signals that trigger PKA gating in physiologic settings unknown
  7. 2018 High

    Reframed SORBS2 as a sequence-specific RNA-binding protein that stabilizes WFDC1 and IL-17D transcripts to suppress ovarian cancer invasion and shape the immune microenvironment.

    Evidence RIP, 3' UTR reporter, mRNA stability assays, KD/OE with invasion and immune-polarization readouts

    PMID:29548303

    Open questions at the time
    • RNA-binding domain not yet mapped in this study
    • Relationship between RNA-binding and cytoskeletal roles unresolved
  8. 2020 High

    Mapped the RNA-binding function to the C2H2 zinc finger domain (binding MTUS1 3' UTR) and consolidated SORBS2 as a tumor-suppressive mRNA-stabilizer across additional targets including RORA.

    Evidence RIP, pull-down, transcriptome-wide RNA-seq, domain mapping, stability assays, xenograft (RORA and MTUS1 studies)

    PMID:31365778 PMID:33311452

    Open questions at the time
    • Consensus RNA motif not defined
    • How the zinc finger and SH3 modules are coordinated within one protein not addressed
  9. 2020 High

    Defined SORBS2 as an intercalated-disc and microtubule regulator whose loss causes arrhythmogenic cardiomyopathy and whose overexpression densifies beta-tubulin and disorganizes T-tubules.

    Evidence Global KO mice, echocardiography/ECG, IF/fractionation, beta-tubulin Co-IP, in vitro polymerization, AAV9 overexpression, Ca2+ imaging (two studies)

    PMID:32143182 PMID:32808564

    Open questions at the time
    • Whether microtubule and intercalated-disc defects are causally linked not resolved
    • Direct structural role versus RNA-mediated effect in heart not separated
  10. 2021 High

    Showed SORBS2 directly governs cardiac ion-channel expression and is required for second heart field development, linking its scaffold/RNA functions to electrical and structural heart phenotypes.

    Evidence KO mice with patch-clamp, RT-PCR/Western, RIP/Co-IP for channels; hESC-CM KD with SHH rescue and mouse mutant analysis (two studies)

    PMID:34099102 PMID:34487812

    Open questions at the time
    • Which channel effects are RNA-mediated versus protein-scaffold-mediated not fully separated
    • Direct targets within NOTCH/SHH signaling not identified
  11. 2022 High

    Established the cardiomyocyte-autonomous requirement: conditional adult deletion produces dilated cardiomyopathy with defective microtubule polymerization and a sarcomeric/cytoskeletal interactome.

    Evidence Cardiomyocyte-specific Cre KO mice, echocardiography, contractility assays, AP-proteomics/Co-IP (two studies)

    PMID:35050860 PMID:35730644

    Open questions at the time
    • Functional significance of most proteomic interactors beyond YWHAQ not tested
    • Mechanism of compensatory cytoskeletal upregulation unknown
  12. 2024 High

    Provided the most complete dual-mode dissection in vascular smooth muscle: SORBS2 SH3/SoHo domains bind BK channel subunits while it also binds BK-alpha mRNA, with Nrf2 as an upstream transcriptional activator.

    Evidence Patch-clamp, Co-IP/pull-down, RNA-IP, domain-deletion mutagenesis, Nrf2 ChIP/promoter assay, KO coronary studies

    PMID:38362769

    Open questions at the time
    • Relative contributions of protein versus RNA binding to BK regulation not quantified
    • Whether the same dual mechanism applies to other channels untested
  13. 2025 High

    Extended the cardiac role to integrin–cytoskeleton coupling and fibrosis control and identified GATA4 as a cardiomyocyte transcriptional regulator of SORBS2.

    Evidence AP-MS, cardiomyocyte-specific KO, ECM proteomics, GATA4 ChIP/reporter, histopathology

    PMID:39957251

    Open questions at the time
    • Direct integrin-binding interface not mapped
    • Causal step from integrin remodeling to fibrosis not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SORBS2 partitions and coordinates its scaffold versus RNA-binding activities within a single cell, and what determines its consensus RNA target set, remain unresolved.
  • No unifying model linking cytoskeletal scaffolding and mRNA stabilization
  • No defined RNA-binding consensus motif
  • No structural model integrating SoHo, SH3, and zinc-finger modules

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005856 cytoskeleton 5 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-397014 Muscle contraction 3 R-HSA-1266738 Developmental Biology 1
Partners
ABL2ACTNCBLPALLDSAPAPTUBBWASF1YWHAQ
Complex memberships
ArgBP2–palladin–alpha-actinin complexWAVE1/PTP-PEST/c-Abl signaling complexintercalated disc

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ArgBP2 (SORBS2) was identified as a novel Arg/Abl-binding protein that physically associates with and is a substrate of Arg and v-Abl tyrosine kinases; it is phosphorylated on tyrosine in v-Abl-transformed cells. ArgBP2 contains three C-terminal SH3 domains and localizes to stress fibers in epithelial cells and to Z-disks in cardiac muscle cells. Yeast two-hybrid screen, co-immunoprecipitation, subcellular fractionation/immunofluorescence, in vivo phosphorylation assay The Journal of biological chemistry High 9211900
1999 nArgBP2 (neural isoform of SORBS2) binds to the proline-rich region of SAPAP via its third SH3 domain, co-immunoprecipitates with SAPAP from rat brain extract, and colocalizes with SAPAP at synapses in cerebellum. nArgBP2 also binds vinculin and l-afadin. Co-immunoprecipitation from rat brain, yeast two-hybrid, immunofluorescence co-localization The Journal of biological chemistry High 10521485
2003 ArgBP2 (SORBS2) acts as a scaffold linking c-Abl to the ubiquitin ligase Cbl. Phosphorylation of both Cbl and ArgBP2 by c-Abl stabilizes their interaction, facilitating Cbl-mediated ubiquitination and subsequent proteasomal degradation of c-Abl and ArgBP2 itself. Co-immunoprecipitation, in vitro ubiquitination assay, Western blot for degradation The Biochemical journal High 12475393
2005 The N-terminal sorbin homology (SoHo) domain of ArgBP2/nArgBP2 (SORBS2) interacts with spectrin. The C-terminal SH3 domains bind dynamin, synaptojanin, and WAVE isoforms (including WAVE2) and WAVE regulatory proteins. Knockdown of ArgBP2/nArgBP2 in astrocytes redistributes focal adhesion proteins and increases peripheral actin ruffles; nArgBP2 overexpression collapses the actin cytoskeleton. Pull-down assays, Co-immunoprecipitation, RNAi knockdown with immunofluorescence readout, overexpression phenotyping Proceedings of the National Academy of Sciences of the United States of America High 15659545
2005 ArgBP2 (SORBS2) directly interacts with palladin (via palladin's N-terminal poly-proline sequences binding to the first C-terminal SH3 domain of ArgBP2) and with alpha-actinin (via the N-terminal segment of ArgBP2). A three-way complex of ArgBP2–palladin–alpha-actinin forms in vivo, explaining ArgBP2's Z-disc-specific localization. In vitro pull-down assays, co-immunoprecipitation, targeting/localization assays in cells Experimental cell research High 16125169
2008 ArgBP2 (SORBS2) controls pancreatic cancer cell adhesion and migration via a WAVE1/PTP-PEST/c-Abl signaling complex. Loss of ArgBP2 during oncogenic transformation promotes invasion and metastasis; re-expression restores adhesion and reduces tumorigenicity. Pancreatic cancer cell line gain/loss-of-function, migration/adhesion assays, yeast two-hybrid for new interactors, co-immunoprecipitation of WAVE1/PTP-PEST/c-Abl complex, in vivo tumorigenicity assay Cancer research High 18559503
2009 CIP4 was identified as a new ArgBP2 (SORBS2) interacting protein. ArgBP2 and CIP4 modulate each other's tyrosine phosphorylation via c-Abl, and both directly interact with WAVE1; they act synergistically to increase WAVE1 tyrosine phosphorylation by c-Abl. CIP4 overexpression is deleterious for the ArgBP2-induced blockade of cancer cell migration. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, cell migration assay Cancer letters Medium 19631450
2012 A novel short isoform of ArgBP2 (SORBS2), termed ArgBP2γ, was identified. In epithelial NMuMG cells, ArgBP2 localizes to tight junctions; the second SH3 domain is required for this localization. ArgBP2 induces anchorage-dependent ERK activation in NIH3T3 cells. RT-PCR/cDNA cloning, immunofluorescence, mutation analysis of SH3 domains, ERK activation assay Medical molecular morphology Medium 22431180
2014 ArgBP2 (SORBS2) inhibits cell migration as a component of alpha-actinin-containing stress fibers. A small region (residues 192–228) in ArgBP2γ mediates direct binding to alpha-actinin and is essential for stress fiber localization and anti-migratory effects. PKA phosphorylation of Ser-259 in ArgBP2γ promotes 14-3-3 binding, which blocks alpha-actinin interaction and thereby relieves migration inhibition. Western blot expression analysis, immunofluorescence, domain-deletion/point-mutation mapping, kinase assay (PKA), 14-3-3 pull-down, migration assay The Journal of biological chemistry High 25429109
2014 ArgBP2 (SORBS2) forms oligomers via SH3-domain binding to a specific proline-rich cluster. Tyrosine phosphorylation by c-Abl destabilizes these oligomers. The phosphorylation/oligomerization state modulates which binding partners ArgBP2 associates with, thereby controlling its cytoskeletal and anti-migratory functions in pancreatic cancer cells. Co-immunoprecipitation oligomerization assay, in vitro kinase assay, domain mutagenesis, cell migration assay in MiaPaCa-2 cells PloS one Medium 24475245
2015 MORC2 binds to the ArgBP2 (SORBS2) promoter and recruits EZH2, which promotes tri-methylation of H3K27, leading to transcriptional repression of ArgBP2 in gastric cancer cells. ChIP assay, promoter cloning/reporter assay, Western blot, siRNA knockdown Biochemical and biophysical research communications Medium 26476214
2015 SORBS2 transcription is regulated by a telomere position effect over long distance (TPE-OLD): telomere shortening at the 4q35 locus promotes a chromatin loop that cis-activates SORBS2 transcription, demonstrated using chromosome conformation capture (3C) methods in FSHD myoblasts. Modified chromosome conformation capture (3C), qRT-PCR, myoblast cell culture with variable telomere lengths Genome research Medium 26359233
2016 Genetic deletion of Sorbs2 in mice leads to reduced dendritic complexity and decreased frequency of AMPAR-mediated miniature spontaneous EPSCs in dentate gyrus granule cells. nArgBP2 (neuronal SORBS2 isoform) colocalizes with F-actin at dendritic spines and growth cones in hippocampal neurons. Sorbs2 knockout mice, morphological analysis of dendrites, whole-cell patch-clamp electrophysiology (mEPSC recording), immunofluorescence co-localization The Journal of neuroscience High 26888934
2016 SoHo proteins CAP/ponsin and ArgBP2 (SORBS2) interact with the cytoplasmic domain of atypical cadherin Fat1 via a proline-rich type II PXXP motif in Fat1 binding to the SH3 domains of ArgBP2/CAP. Knockdown of Fat1 abolishes endogenous ponsin-2 localization to cellular leading edges. Yeast two-hybrid, pull-down assays, siRNA knockdown with immunofluorescence Biochemical and biophysical research communications Medium 26903299
2017 SORBS2 localizes to the apical junctional complex (AJC) in epithelial cells, positioned farther from the membrane than ZO-1, alternating periodically with myosin IIB. Overexpression of GFP-SORBS2 recruits alpha-actinin, vinculin, and N-WASP to cellular junctions. However, CRISPR-Cas9 knockout of SORBS2 did not alter junction assembly, barrier function, or actin-dependent junction remodeling. Super-resolution imaging, GFP-SORBS2 overexpression with immunofluorescence, CRISPR-Cas9 KO, transepithelial resistance measurement, Ca2+-switch and Latrunculin-B washout assays PloS one Medium 28961272
2018 HSF1 directly interacts with MORC2 and together they bind to the ArgBP2 (SORBS2) enhancer, recruiting PRC2 (particularly EZH2), which catalyzes H3K27me3 and represses ArgBP2 transcription in gastric cancer cells. HSF1/MORC2-induced cancer cell migration and invasion depend on ArgBP2 and EZH2. Co-immunoprecipitation (HSF1-MORC2), ChIP assay, reporter assay, siRNA/overexpression functional rescue, migration/invasion assays Biochimica et biophysica acta. Molecular basis of disease Medium 29339121
2018 SORBS2 functions as an RNA-binding protein that binds the 3' UTR of WFDC1 and IL-17D mRNAs, enhancing their stability. This stabilization suppresses ovarian cancer invasiveness and promotes a tumor-suppressive immune microenvironment (affecting monocyte-to-MDSC and M2 macrophage polarization). RNA immunoprecipitation (RIP), 3' UTR reporter assay, mRNA stability assay, SORBS2 KD/OE with invasion and immune polarization readouts Genome biology High 29548303
2019 SORBS2 binds the 3' UTR of RORA mRNA and reduces its degradation, thereby stabilizing RORA transcript in hepatocellular carcinoma cells. This post-transcriptional regulation of RORA mediates SORBS2's tumor-suppressive anti-proliferative and anti-metastatic effects. RNA immunoprecipitation (RIP), RNA pull-down assay, luciferase reporter assay, mRNA stability assay, in vivo xenograft Liver international High 31365778
2019 SORBS2 suppresses HCC metastasis by inhibiting the c-Abl/ERK signaling pathway. MEF2D was identified as an upstream transcriptional regulator that binds the SORBS2 promoter and reduces SORBS2 expression. OE/KD of SORBS2, ERK phosphorylation assays, in vivo metastasis assay, MEF2D promoter binding by ChIP/reporter assay American journal of cancer research Medium 31911856
2020 SORBS2 knockout mice develop arrhythmogenic cardiomyopathy phenotypes including right ventricular dilation, dysfunction, spontaneous ventricular tachycardia, and premature death. Sorbs2 protein localizes to the intercalated disc (adhesion junction/desmosome) and its absence disrupts structural integrity of the intercalated disc and causes cardiac electrical remodeling. Sorbs2 global KO mice, echocardiography, electrocardiography, immunofluorescence/subcellular fractionation, histopathology, patch-clamp Journal of the American Heart Association High 32808564
2020 SORBS2 (via its C2H2 zinc finger domain) directly binds to the 3' UTR of MTUS1 mRNA in clear cell renal cell carcinoma, increasing MTUS1 mRNA stability and thereby suppressing metastasis. RNA immunoprecipitation, pull-down assay, transcriptome-wide analysis (RNA-seq), domain mapping, mRNA stability assay, migration/invasion assay Cell death & disease High 33311452
2020 SORBS2 interacts with β-tubulin and promotes its polymerization in 293T cells and hESC-derived cardiomyocytes. In vivo cardiac overexpression of SORBS2 causes β-tubulin densification, redistribution of Junctophilin 2, T-tubule disorganization, and Ca2+ handling dysfunction leading to cardiac dysfunction. Co-immunoprecipitation (SORBS2–β-tubulin), AAV9-mediated cardiac overexpression in mice, tubulin polymerization assay, T-tubule staining, confocal Ca2+ imaging, echocardiography EBioMedicine High 32143182
2021 Sorbs2 loss-of-function leads to progressive cardiac ion channel remodeling: Sorbs2 KO mice display reduced expression/function of voltage-gated Na+ channels, L-type Ca2+ channels, voltage-gated K+ channels, and inward-rectifier K+ channels. Sorbs2 physically interacts with the RNAs and/or proteins of important cardiac ion channels and directly regulates their expression in vitro. Sorbs2 KO mice, patch-clamp electrophysiology, electrocardiography, molecular biological approaches (RT-PCR, Western blot), RNA immunoprecipitation/protein co-IP for ion channel interactions Biochimica et biophysica acta. Molecular basis of disease High 34487812
2021 SORBS2 knockdown in hESC-derived cardiomyocytes disrupts sarcomeric integrity and reduces cardiomyocyte number. It impairs second heart field (SHF) development by decreasing SHF marker gene expression and impairing NOTCH and SHH signaling. Exogenous SHH rescues SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2 mouse mutants develop atrial septal defects linked to impaired posterior SHF. SORBS2 KD in hESC differentiation model, qRT-PCR, immunofluorescence, SHH rescue experiment, Sorbs2 mouse mutant analysis eLife High 34099102
2021 The NOVA1 splicing factor inhibits a specific SORBS2 alternative splicing isoform; loss of this regulation induces migration of colorectal cancer cells via the Notch pathway. RNA-seq, qRT-PCR, NOVA1 knockdown/overexpression, cell migration assays, pathway analysis Frontiers in cell and developmental biology Medium 34692669
2022 Cardiomyocyte-specific knockout of Sorbs2 in adult mice results in progressive dilated cardiomyopathy with systolic dysfunction, atrial enlargement, and congestive heart failure. Early remodeling involves defective microtubule polymerization and compensatory upregulation of cytoskeletal/adapter proteins, suggesting Sorbs2 strengthens microtubule–cytoskeletal cross-link interactions in cardiomyocytes. Cardiomyocyte-specific Cre-mediated Sorbs2 KO mice, echocardiography, electrophysiology, skinned myofiber contractility assay, Western blot, immunofluorescence Journal of the American Heart Association High 35730644
2022 SORBS2 interacts with alpha-actinin, β-tubulin, MYH7, FLNA, MYBPC3, YWHAQ (14-3-3), and DES in cardiomyocyte/myocardial tissue, as demonstrated by proteomics and co-immunoprecipitation. SORBS2 interaction with YWHAQ negatively affects the cell cycle. Affinity purification proteomics, co-immunoprecipitation, immunofluorescence Aging Medium 35050860
2023 The ARID5B–PHF2 histone demethylase complex binds to the SORBS2 promoter and promotes histone demethylation at H3K36me2, activating SORBS2 transcription and suppressing EMT in ovarian cancer. ChIP assay, promoter binding assay, histone methylation analysis, ARID5B/PHF2 KD with SORBS2 expression readout Pathology, research and practice Medium 37948999
2024 Sorbs2 regulates BK channel (large conductance Ca2+-activated K+ channel) expression and function in coronary smooth muscle cells. The SH3 domain of Sorbs2 is necessary for interaction with BK-α subunits, and both SH3 and SoHo domains interact with BK-β1 subunits. Sorbs2 also binds BK-α mRNA as an RNA-binding protein. Sorbs2 is a transcriptional target of Nrf2, which binds the Sorbs2 promoter. Sorbs2 KO mice display decreased BK channel expression/function and impaired coronary BK channel-mediated vasodilation. Patch-clamp electrophysiology, Co-IP/pull-down for protein interactions, RNA-IP for mRNA binding, domain-deletion mutagenesis, Nrf2 ChIP/promoter assay, Sorbs2 KO mouse coronary artery studies Circulation research High 38362769
2024 SORBS2 directly binds the 3' UTR of HK2 mRNA, enhancing its stability and activating glycolysis in trophoblast cells. SORBS2 overexpression enhances trophoblast migration and proliferation, whereas silencing HK2 abrogates the SORBS2-induced enhancement. RNA immunoprecipitation, mRNA stability assay, HK2 rescue experiment, cell migration/proliferation assays Reproduction (Cambridge, England) Medium 38995729
2024 SORBS2 binds the 3' UTR of TIMP3 mRNA (identified by RIP-seq), enhancing its stability and thereby regulating extracellular matrix degradation to suppress esophageal squamous cell carcinoma tumor progression. RIP-seq, RIP-qPCR, RNA pull-down assay, mRNA stability assay, in vivo/in vitro functional assays with TIMP3 rescue International immunopharmacology Medium 39288625
2024 Sorbs2 regulates seizure activity by modulating AMPAR-mediated excitatory synaptic transmission: knockdown of hippocampal Sorbs2 decreases mEPSC frequency in CA1 pyramidal neurons and reduces expression of AMPAR subunits GluA1 and GluA2, prolonging latency to spontaneous recurrent seizures. Sorbs2 shRNA knockdown in mouse hippocampus, local field potential recording, whole-cell patch-clamp, Western blot for GluA1/GluA2 Neurochemistry international Medium 38555055
2024 TNF-α stimulation in osteoblasts promotes binding between NMT1 (N-myristoyltransferase 1) and Sorbs2, which inhibits protein myristoylation in these cells. Co-immunoprecipitation, mass spectrometry, Click-it myristoylation assay, immunocytochemistry, siRNA knockdown In vivo (Athens, Greece) Medium 38148048
2025 SORBS2 interacts with integrin-cytoskeleton connections in cardiomyocytes (identified by affinity purification mass spectrometry). Cardiomyocyte-specific loss of Sorbs2 in adult mice alters integrin interactions, increases expression of multiple integrins and their associated extracellular matrix components, and exacerbates fibrotic response during pathological cardiac remodeling. SORBS2 expression in cardiomyocytes is regulated by GATA4. Affinity purification mass spectrometry, cardiomyocyte-specific Sorbs2 KO mice, ECM proteomics, Western blot, ChIP/reporter assay for GATA4, histopathology Cardiovascular research High 39957251
2025 SORBS2 regulates TNBC cell gene expression through direct binding to CDS, introns, and 3' UTRs of target mRNAs (identified by LACE-seq). Knockdown of SORBS2 inhibits proliferation, migration, and invasion in TNBC cells; SORBS2 binding targets are linked to Wnt/β-catenin signaling pathways. LACE-seq (RNA-binding site mapping), RNA-seq, siRNA knockdown with proliferation/migration/invasion assays Biochemical and biophysical research communications Medium 40199126
2025 Sorbs2 deficiency reduces Nav1.5 (voltage-gated Na+ channel alpha subunit SCN5A) protein expression in cardiomyocytes in vivo (Sorbs2 KO mice) and in vitro (si-Sorbs2 H9C2 cells), establishing a mechanistic link between Sorbs2 loss and increased susceptibility to ventricular arrhythmias. Sorbs2 KO mice, Western blot, siRNA in H9C2 cells, ECG recording, caffeine-dobutamine stress testing Zhonghua xin xue guan bing za zhi Medium 40662394

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell structure and function 180 11937713
1997 ArgBP2, a multiple Src homology 3 domain-containing, Arg/Abl-interacting protein, is phosphorylated in v-Abl-transformed cells and localized in stress fibers and cardiocyte Z-disks. The Journal of biological chemistry 119 9211900
2016 miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2. Journal of molecular and cellular cardiology 115 27033308
2005 The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America 81 15659545
2018 The RNA binding protein SORBS2 suppresses metastatic colonization of ovarian cancer by stabilizing tumor-suppressive immunomodulatory transcripts. Genome biology 73 29548303
1999 nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP). The Journal of biological chemistry 73 10521485
2015 SORBS2 transcription is activated by telomere position effect-over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy. Genome research 67 26359233
2003 Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl. The Biochemical journal 58 12475393
2016 Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 26888934
2005 Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton. Experimental cell research 57 16125169
2008 ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity. Cancer research 53 18559503
2019 The RNA-binding protein SORBS2 suppresses hepatocellular carcinoma tumourigenesis and metastasis by stabilizing RORA mRNA. Liver international : official journal of the International Association for the Study of the Liver 45 31365778
2020 Knockout of SORBS2 Protein Disrupts the Structural Integrity of Intercalated Disc and Manifests Features of Arrhythmogenic Cardiomyopathy. Journal of the American Heart Association 35 32808564
2009 ArgBP2 and the SoHo family of adapter proteins in oncogenic diseases. Cell adhesion & migration 35 19262174
2020 LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy. Diabetology & metabolic syndrome 34 32905431
2014 Arg kinase-binding protein 2 (ArgBP2) interaction with α-actinin and actin stress fibers inhibits cell migration. The Journal of biological chemistry 34 25429109
2020 RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability. Cell death & disease 32 33311452
2020 LncRNA H19 Inhibits the Progression of Sepsis-Induced Myocardial Injury via Regulation of the miR-93-5p/SORBS2 Axis. Inflammation 31 32996061
2018 HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in gastric cancer cells. Biochimica et biophysica acta. Molecular basis of disease 29 29339121
2015 Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells. Biochemical and biophysical research communications 28 26476214
2020 Elevated myocardial SORBS2 and the underlying implications in left ventricular noncompaction cardiomyopathy. EBioMedicine 26 32143182
2019 SORBS2, mediated by MEF2D, suppresses the metastasis of human hepatocellular carcinoma by inhibitiing the c-Abl-ERK signaling pathway. American journal of cancer research 24 31911856
2009 CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration. Cancer letters 22 19631450
2022 Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice. Journal of the American Heart Association 21 35730644
2017 Sorbin and SH3 domain-containing protein 2 (SORBS2) is a component of the acto-myosin ring at the apical junctional complex in epithelial cells. PloS one 17 28961272
2012 Cell biological characterization of a multidomain adaptor protein, ArgBP2, in epithelial NMuMG cells, and identification of a novel short isoform. Medical molecular morphology 17 22431180
2021 SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients. eLife 16 34099102
2021 NOVA1-Mediated SORBS2 Isoform Promotes Colorectal Cancer Migration by Activating the Notch Pathway. Frontiers in cell and developmental biology 14 34692669
2022 SORBS2 as a molecular target for atherosclerosis in patients with familial hypercholesterolemia. Journal of translational medicine 12 35590369
2021 Changes in ion channel expression and function associated with cardiac arrhythmogenic remodeling by Sorbs2. Biochimica et biophysica acta. Molecular basis of disease 12 34487812
2013 SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes. BMC cancer 11 24165198
2024 Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes. Circulation research 10 38362769
2023 ARID5B promoted the histone demethylation of SORBS2 and hampered the metastasis of ovarian cancer. Pathology, research and practice 10 37948999
2025 Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition. Cardiovascular research 9 39957251
2014 Oligomerization and phosphorylation dependent regulation of ArgBP2 adaptive capabilities and associated functions. PloS one 9 24475245
2023 MiR-484 promotes nonalcoholic fatty liver disease progression in mice via downregulation of Sorbs2. Obesity (Silver Spring, Md.) 7 37752619
2021 miR-18a-5p Facilitates Malignant Progression of Head and Neck Squamous Cell Carcinoma Cells via Modulating SORBS2. Computational and mathematical methods in medicine 7 34707683
2024 RNA-binding protein SORBS2 increases human trophoblast cell migration via stabilizing HK2 mRNA in preeclampsia. Reproduction (Cambridge, England) 6 38995729
2022 Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes. Frontiers in genetics 6 35242163
2022 The interaction protein of SORBS2 in myocardial tissue to find out the pathogenic mechanism of LVNC disease. Aging 5 35050860
2024 SORBS2-Mediated inhibition of malignant behaviors in esophageal squamous cell carcinoma through TIMP3. International immunopharmacology 4 39288625
2016 Interaction of atypical cadherin Fat1 with SoHo adaptor proteins CAP/ponsin and ArgBP2. Biochemical and biophysical research communications 4 26903299
2005 Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus. Peptides 4 15949647
2025 Understanding the Molecular Mechanisms of SORBS2 in TNBC Lung Metastasis. Biochemical and biophysical research communications 3 40199126
2024 Sorbs2 regulates seizure activity by influencing AMPAR-mediated excitatory synaptic transmission in temporal lobe epilepsy. Neurochemistry international 3 38555055
2022 Advances in the previous two decades in our understanding of the post-translational modifications, functions, and drug perspectives of ArgBP2 and its family members. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 3 36271588
2025 A Novel Missense Variant in SORBS2 Is Causative With Familial Alzheimer's Disease. CNS neuroscience & therapeutics 1 39912518
2025 Impact of Sorbs2 dysfunction on cardiovascular diseases. Biochimica et biophysica acta. Molecular basis of disease 1 40139410
2024 TNF-α-induced Inhibition of Protein Myristoylation Via Binding Between NMT1 and Sorbs2 in Osteoblasts. In vivo (Athens, Greece) 1 38148048
2012 [Expression and localization of ArgBP2 in osteosarcoma MG-63 cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 22394629
2026 Unveiling a new SORBS2::BRAF fusion in papillary thyroid carcinoma: insights from molecular diagnostics. Virchows Archiv : an international journal of pathology 0 41721842
2026 Oxymatrine attenuates melanoma progression and metastasis through SORBS2-mediated suppression of M2 macrophage polarization. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41956023
2026 SORBS2: A Molecular Nexus in Multisystem Diseases Through Scaffold-Mediated Regulation. Journal of cellular and molecular medicine 0 42045927
2025 Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities. Frontiers in genetics 0 39882075
2025 [The impact and potential mechanisms of Sorbs2 on the progression of ventricular arrhythmias in mice]. Zhonghua xin xue guan bing za zhi 0 40662394
2023 Retracted: miR-18a-5p Facilitates Malignant Progression of Head and Neck Squamous Cell Carcinoma Cells via Modulating SORBS2. Computational and mathematical methods in medicine 0 37799418

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