Affinage

SORBS2

Sorbin and SH3 domain-containing protein 2 · UniProt O94875

Length
1100 aa
Mass
124.1 kDa
Annotated
2026-04-28
56 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SORBS2 (ArgBP2/nArgBP2) is a multidomain scaffold and RNA-binding protein that organizes signaling complexes at actin stress fibers, cardiac intercalated discs, and neuronal synapses, integrating cytoskeletal dynamics, cell adhesion, mRNA stability, and ion channel regulation. Through its SoHo and SH3 domains, SORBS2 directly binds α-actinin, palladin, spectrin, WAVE isoforms, dynamin, and Abl/Arg kinases to control actin remodeling and suppress cell migration—an anti-migratory function relieved by PKA phosphorylation at Ser-259 and consequent 14-3-3 binding (PMID:25429109, PMID:15659545, PMID:9211900). SORBS2 also functions as an RNA-binding protein: its C2H2 zinc finger and SH3/SoHo domains bind 3′ UTRs of target mRNAs (including WFDC1, IL-17D, RORA, MTUS1, HK2, TIMP3, and BK-α), stabilizing them post-transcriptionally and thereby influencing tumor suppression, glycolysis, and ion channel expression (PMID:29548303, PMID:33311452, PMID:38362769). In the heart, SORBS2 is essential for intercalated disc integrity, microtubule polymerization, and regulation of Na⁺, Ca²⁺, K⁺, and BK channels; cardiomyocyte-specific or global loss of Sorbs2 in mice causes arrhythmogenic or dilated cardiomyopathy with ventricular arrhythmias (PMID:32808564, PMID:35730644, PMID:34487812).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    The foundational question of ArgBP2's molecular identity and cellular context was answered: it was identified as both a binding partner and tyrosine substrate of Abl/Arg kinases that localizes to actin stress fibers and cardiac Z-discs, establishing it as a cytoskeletal adapter protein.

    Evidence Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, and immunofluorescence in fibroblasts and cardiomyocytes

    PMID:9211900

    Open questions at the time
    • Functional consequence of Abl-mediated phosphorylation on ArgBP2 not determined
    • Cardiac-specific role not tested by loss-of-function
  2. 1999 High

    The existence of a brain-specific isoform (nArgBP2) and its placement in the postsynaptic density via SAPAP interaction established SORBS2 as a neuronal scaffold, extending its biology beyond non-neuronal cytoskeletal functions.

    Evidence Co-immunoprecipitation from rat brain lysate, yeast two-hybrid, immunofluorescence at cerebellar synapses

    PMID:10521485

    Open questions at the time
    • No loss-of-function data for neuronal isoform at this stage
    • Synaptic transmission consequences unknown
  3. 2003 High

    ArgBP2 was shown to scaffold a degradation pathway by linking c-Abl to the E3 ligase Cbl, answering how Abl kinase levels are controlled post-translationally via an adapter-dependent ubiquitination mechanism.

    Evidence Co-immunoprecipitation, in vitro kinase assay, ubiquitination and degradation assays

    PMID:12475393

    Open questions at the time
    • In vivo relevance of Cbl-mediated Abl degradation via ArgBP2 not tested
    • Whether other E3 ligases use ArgBP2 as a scaffold unknown
  4. 2005 High

    The scope of SORBS2's interactome was broadened to include spectrin (via SoHo), dynamin, synaptojanin, WAVE isoforms (via SH3), palladin, and α-actinin, with knockdown and overexpression revealing its role in balancing adhesion versus motility at the actin cytoskeleton.

    Evidence Pulldown, co-immunoprecipitation, siRNA knockdown/overexpression in astrocytes; domain mapping with α-actinin and palladin in separate study

    PMID:15659545 PMID:16125169

    Open questions at the time
    • Relative contributions of individual binding partners to migration phenotype not dissected
    • No in vivo loss-of-function at this time
  5. 2008 High

    The anti-migratory function of ArgBP2 was placed in a cancer-relevant signaling context: it suppresses pancreatic cancer cell migration by scaffolding a WAVE1/PTP-PEST/c-Abl complex, and its expression is lost during oncogenic transformation.

    Evidence Co-immunoprecipitation, yeast two-hybrid, cell migration/adhesion assays, overexpression/knockdown in pancreatic cancer lines, xenograft

    PMID:18559503

    Open questions at the time
    • Whether ArgBP2 loss is a driver or passenger in transformation not resolved
    • Mechanism of epigenetic silencing not yet identified
  6. 2014 High

    The molecular switch controlling SORBS2's anti-migratory activity was defined: PKA phosphorylation at Ser-259 promotes 14-3-3 binding that blocks α-actinin interaction (mapped to residues 192–228), relieving migration suppression; separately, c-Abl-dependent tyrosine phosphorylation destabilizes ArgBP2 oligomers, tuning its partner affinity.

    Evidence Deletion mutagenesis, co-immunoprecipitation, kinase assay, migration assays; oligomerization analysis by Co-IP and kinase assay

    PMID:24475245 PMID:25429109

    Open questions at the time
    • In vivo validation of PKA/14-3-3 switch not performed
    • Structural basis of oligomerization unknown
  7. 2016 High

    Two major in vivo roles were established simultaneously: in the brain, Sorbs2 knockout reduced dendritic complexity and AMPAR-mediated synaptic transmission causing memory deficits; in the heart, SORBS2 was identified as a target of miR-21-3p whose downregulation contributes to sepsis-induced cardiac dysfunction.

    Evidence Sorbs2 KO mouse with electrophysiology and behavioral assays (brain); antagomiR in vivo with echocardiography (heart)

    PMID:26888934 PMID:27033308

    Open questions at the time
    • Neuronal mechanism linking F-actin/spine remodeling to AMPAR changes not resolved
    • Direct miR-21-3p targeting confirmation by luciferase reporter not explicitly shown
  8. 2018 High

    A paradigm-shifting discovery revealed SORBS2 as an RNA-binding protein that stabilizes target mRNAs (WFDC1, IL-17D) via 3′ UTR binding, expanding its function from purely scaffold/adapter to post-transcriptional regulator; this RNA-binding activity suppresses ovarian cancer invasiveness and modulates immune polarization.

    Evidence RNA immunoprecipitation, mRNA stability assay, luciferase reporter, invasion assays, immune cell polarization assays

    PMID:29548303

    Open questions at the time
    • RNA-binding domain not yet identified
    • Transcriptome-wide target repertoire not defined at this point
  9. 2020 High

    The cardiac role was mechanistically deepened: SORBS2 binds β-tubulin and promotes microtubule polymerization, and Sorbs2 knockout causes arrhythmogenic cardiomyopathy with intercalated disc disruption, right ventricular dilation, and ventricular tachycardia, establishing SORBS2 as essential for cardiac structural and electrical integrity.

    Evidence Co-immunoprecipitation, microtubule polymerization assay, AAV9-mediated overexpression, global KO mouse with echocardiography and ECG

    PMID:32143182 PMID:32808564

    Open questions at the time
    • Whether microtubule defect is the primary driver of arrhythmia versus intercalated disc disruption not resolved
    • Human genetic link to cardiomyopathy not established
  10. 2020 High

    The C2H2 zinc finger domain was identified as a key RNA-binding domain mediating SORBS2's mRNA-stabilizing function (demonstrated for MTUS1 3′ UTR), providing domain-level resolution for its post-transcriptional activity.

    Evidence RNA immunoprecipitation, RNA pulldown, domain-deletion mutagenesis, mRNA stability assay in clear cell renal carcinoma models

    PMID:33311452

    Open questions at the time
    • Whether C2H2-ZnF is sufficient for all mRNA targets or cooperates with SH3/SoHo unknown
    • Structural basis of RNA recognition not determined
  11. 2021 High

    SORBS2's RNA-binding and protein-interaction functions converge on cardiac ion channels: Sorbs2 KO mice show progressive dysfunction of Nav1.5, L-type Ca²⁺, K⁺, and inward-rectifier K⁺ channels, and Sorbs2 physically interacts with RNA and/or protein of these channels, establishing it as a multi-channel regulator.

    Evidence Patch clamp electrophysiology, RNA-binding assay, co-immunoprecipitation in Sorbs2 KO mice

    PMID:34487812

    Open questions at the time
    • Relative contribution of RNA stabilization versus protein scaffolding to ion channel regulation not dissected
    • Channel-specific binding sites on SORBS2 not mapped
  12. 2022 High

    Cardiomyocyte-specific Sorbs2 deletion demonstrated that the dilated cardiomyopathy phenotype is cell-autonomous, with defective microtubule polymerization and compensatory cytoskeletal remodeling, confirming cardiomyocyte-intrinsic structural roles.

    Evidence Cardiomyocyte-specific Cre-lox KO, echocardiography, cytoskeletal fractionation, skinned myofiber contractility

    PMID:35730644

    Open questions at the time
    • Whether restoring microtubule dynamics rescues the cardiomyopathy not tested
    • Contribution of intercalated disc versus sarcomeric versus microtubule defects not individually dissected
  13. 2024 High

    The RNA-binding function was extended to vascular biology: SORBS2 binds BK channel α-subunit mRNA and protein via its SH3 domain, regulating BK channel expression and coronary vasodilation; Nrf2 was identified as an upstream transcriptional activator of Sorbs2.

    Evidence Patch clamp, Co-IP, RNA-binding assay, domain deletion, Sorbs2 KO mouse vascular reactivity, ChIP for Nrf2

    PMID:38362769

    Open questions at the time
    • Whether Nrf2-SORBS2-BK axis operates in other vascular beds unknown
    • Full RNA targetome in smooth muscle cells not defined
  14. 2025 High

    SORBS2's role in integrin-ECM homeostasis was defined: cardiomyocyte-specific loss alters integrin expression and extracellular matrix composition, exacerbating fibrosis during pathological remodeling; GATA4 was identified as an upstream transcriptional activator.

    Evidence Affinity purification mass spectrometry, cardiomyocyte-specific KO, cardiac fibrosis assay, ChIP/reporter for GATA4

    PMID:39957251

    Open questions at the time
    • Whether SORBS2-integrin axis operates through RNA stabilization or protein scaffolding not resolved
    • Interaction between GATA4 and Nrf2 regulation of SORBS2 not studied

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for SORBS2's dual protein-scaffold and RNA-binding activities; the complete RNA targetome across tissues; whether human SORBS2 mutations cause inherited cardiomyopathy or neurodevelopmental disease; and the mechanism by which SORBS2 simultaneously regulates multiple ion channels.
  • No structural model of SORBS2 or its RNA-binding interface exists
  • No human Mendelian disease linkage established by direct genetic evidence
  • Full tissue-specific RNA targetome not systematically determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 5
Localization
GO:0005856 cytoskeleton 6 GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 3
Partners
ABL1ABL2ACTN1CBLDLGAP1PALLDTUBBWAVE1

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 ArgBP2 (SORBS2) was identified as a binding partner and substrate of Arg and Abl tyrosine kinases; it is phosphorylated on tyrosine in v-Abl-transformed cells and localizes to stress fibers and Z-disks of cardiac sarcomeres, functioning as an adapter to assemble signaling complexes at the actin cytoskeleton. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, in vitro kinase assay The Journal of biological chemistry High 9211900
1999 The neuronal isoform nArgBP2 (encoded by SORBS2) interacts with SAPAP via its third SH3 domain, and also binds vinculin and l-afadin; nArgBP2 co-immunoprecipitates with SAPAP from rat brain and co-localizes with SAPAP at cerebellar synapses, placing it in the postsynaptic density protein network. Co-immunoprecipitation from rat brain lysate, yeast two-hybrid, immunofluorescence co-localization The Journal of biological chemistry High 10521485
2003 ArgBP2 acts as a scaffold linking c-Abl to the ubiquitin ligase Cbl; c-Abl phosphorylates both Cbl and ArgBP2, stabilizing their interaction and facilitating Cbl-mediated ubiquitination and proteasomal degradation of c-Abl and ArgBP2 itself. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, degradation assay The Biochemical journal High 12475393
2005 The SoHo domain of ArgBP2/nArgBP2 interacts with spectrin, and the SH3 domains bind dynamin, synaptojanin, and WAVE isoforms (including WAVE regulatory proteins); knockdown of ArgBP2/nArgBP2 in astrocytes causes redistribution of focal adhesion proteins and increased peripheral actin ruffles, while nArgBP2 overexpression collapses the actin cytoskeleton, demonstrating its role as a scaffold balancing adhesion and motility. Pulldown assay, co-immunoprecipitation, siRNA knockdown with immunofluorescence readout, overexpression Proceedings of the National Academy of Sciences of the United States of America High 15659545
2005 ArgBP2 directly interacts with palladin (via palladin's N-terminal poly-proline sequences binding ArgBP2's first SH3 domain) and with alpha-actinin (via the N-terminal segment of ArgBP2); a three-way complex of ArgBP2, palladin, and alpha-actinin forms in vivo, explaining the Z-disc-specific localization of ArgBP2. In vitro pulldown, co-immunoprecipitation, targeting/localization assays in cells Experimental cell research High 16125169
2005 Human sorbin peptide is generated by alternative splicing from the ArgBP2 (SORBS2) gene locus, with the sorbin N- and C-termini spliced to the 95%-homologous central region. Computational genomic analysis, cDNA sequence analysis Peptides Low 15949647
2008 ArgBP2 suppresses pancreatic cancer cell migration and adhesion by controlling a WAVE1/PTP-PEST/c-Abl signaling complex; ArgBP2 is repressed during oncogenic transformation, and its restoration blocks invasion without affecting proliferation or apoptosis. Co-immunoprecipitation, yeast two-hybrid, cell migration/adhesion assays, overexpression/knockdown in pancreatic cancer cell lines, xenograft Cancer research High 18559503
2009 ArgBP2 interacts with CIP4; both proteins modulate reciprocal tyrosine phosphorylation by c-Abl, both bind WAVE1 directly, and they synergistically increase WAVE1 tyrosine phosphorylation by c-Abl, while CIP4 is dispensable for ArgBP2-induced blockade of 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 (ArgBP2™) containing only three SH3 domains was identified; in epithelial NMuMG cells, ArgBP2 localizes to tight junctions (distinct from vinexin), and a second SH3 domain was identified as important for localization to cell-cell contact sites. Immunofluorescence, mutation analysis, Western blot Medical molecular morphology Medium 22431180
2014 ArgBP2γ binds alpha-actinin via a small region (residues 192–228), and this interaction is required for stress fiber localization and inhibition of cell migration; PKA phosphorylation of ArgBP2γ at Ser-259 promotes 14-3-3 binding, which blocks alpha-actinin interaction and relieves the anti-migratory effect. Domain mapping by deletion mutagenesis, co-immunoprecipitation, immunofluorescence, cell migration assay, kinase assay The Journal of biological chemistry High 25429109
2014 ArgBP2 forms oligomers through SH3-domain-mediated binding to a specific proline-rich cluster; tyrosine phosphorylation by c-Abl destabilizes these oligomers, and the oligomerization/phosphorylation state regulates the affinity of ArgBP2 for its molecular partners and its cytoskeletal functions in pancreatic cancer cells. Co-immunoprecipitation, in vitro kinase assay, cell-based functional assays PloS one Medium 24475245
2015 MORC2 binds to the ArgBP2 promoter and enhances recruitment of EZH2, which catalyzes H3K27 tri-methylation, leading to transcriptional repression of ArgBP2 in gastric cancer cells. ChIP assay, luciferase reporter, co-immunoprecipitation, Western blot Biochemical and biophysical research communications Medium 26476214
2016 nArgBP2 (the neuronal isoform of SORBS2) co-localizes with F-actin at dendritic spines and growth cones; genetic deletion of Sorbs2 in mice reduces dendritic complexity and decreases AMPAR-mediated miniature EPSC frequency in dentate gyrus granule cells, resulting in deficits in long-term object recognition memory and contextual fear memory. Immunofluorescence, whole-cell patch clamp, Sorbs2 knockout mouse, behavioral assays The Journal of neuroscience High 26888934
2016 Telomere shortening creates a long-distance chromatin loop at the 4q35 locus that regulates SORBS2 transcription via a cis-acting TPE-OLD mechanism in FSHD myoblasts; SORBS2 expression is abnormally activated by short telomeres in FSHD myoblasts but is normally upregulated only upon skeletal muscle differentiation. Chromosome conformation capture (3C) variant, telomere-length measurement, qRT-PCR in patient-derived myoblasts Genome research Medium 26359233
2016 miR-21-3p directly targets SORBS2, repressing its expression; pharmacological inhibition of miR-21-3p (antagomiR) prevents sepsis-associated cardiac dysfunction in LPS-treated mice, and SORBS2 levels are inversely correlated with miR-21-3p in mouse hearts. AntagomiR/agomiR in vivo, qRT-PCR, echocardiography, luciferase reporter (implied by targeting statement) Journal of molecular and cellular cardiology Medium 27033308
2017 SORBS2 localizes at the apical junctional complex of epithelial cells, positioned farther from the membrane than ZO-1 and alternating periodically with myosin IIB; overexpression of GFP-SORBS2 recruits alpha-actinin, vinculin, and N-WASP to junctions, but CRISPR-KO of SORBS2 does not affect barrier function, junction assembly, or actin-dependent junction remodeling. Super-resolution imaging, CRISPR-Cas9 KO, GFP overexpression, TER/dextran flux assay, Ca2+-switch assay PloS one High 28961272
2018 SORBS2 acts as an RNA-binding protein that binds the 3' UTRs of WFDC1 and IL-17D mRNAs, enhancing their stability; this stabilization suppresses ovarian cancer invasiveness and modulates monocyte-to-MDSC and M2-like macrophage polarization to generate a tumor-suppressive immune microenvironment. RNA immunoprecipitation (RIP), mRNA stability assay, luciferase reporter, functional invasion assays, immune cell polarization assays Genome biology High 29548303
2018 HSF1 interacts with MORC2 and together they bind to an ArgBP2 enhancer, promoting PRC2 (EZH2) recruitment, H3K27me3 deposition, and transcriptional repression of ArgBP2 in gastric cancer cells; this HSF1/MORC2-PRC2-ArgBP2 axis drives migration and invasion. ChIP, co-immunoprecipitation, luciferase reporter, siRNA knockdown, migration/invasion assays Biochimica et biophysica acta. Molecular basis of disease Medium 29339121
2019 SORBS2 directly binds the 3' UTR of RORA mRNA, reducing its degradation and stabilizing RORA expression; this SORBS2-RORA axis suppresses HCC tumourigenesis and metastasis. RNA immunoprecipitation, RNA pulldown assay, luciferase reporter, mRNA stability assay, xenograft model Liver international High 31365778
2019 SORBS2 suppresses HCC metastasis by inhibiting the c-Abl/ERK signaling pathway; MEF2D binds to the SORBS2 promoter to repress its transcription, establishing MEF2D as an upstream regulator of SORBS2. ChIP, luciferase reporter, migration/invasion assays, pathway inhibitor experiments, in vivo metastasis model American journal of cancer research Medium 31911856
2020 SORBS2 binds to β-tubulin and promotes its polymerization (microtubule densification); cardiac overexpression of SORBS2 in mice leads to β-tubulin densification, Junctophilin-2 redistribution, T-tubule disorganization, and Ca2+ handling dysfunction, contributing to heart failure. Co-immunoprecipitation in 293T cells and hESC-CMs, microtubule polymerization assay, AAV9-mediated overexpression in vivo, Ca2+ imaging, echocardiography EBioMedicine High 32143182
2020 Sorbs2 knockout mice develop arrhythmogenic cardiomyopathy (right ventricular dilation, dysfunction, spontaneous ventricular tachycardia, premature death); Sorbs2 protein localizes to the intercalated disc (adhesion junction/desmosome), and its absence disrupts intercalated disc structural integrity and causes profound cardiac electrical remodeling. Global knockout mouse, echocardiography, ECG, immunofluorescence/subcellular fractionation for localization Journal of the American Heart Association High 32808564
2020 SORBS2 binds the 3' UTR of MTUS1 mRNA via its C2H2 zinc finger (Cys2-His2-ZnF) domain, enhancing MTUS1 mRNA stability and thereby suppressing metastasis of clear cell renal cell carcinoma. RNA immunoprecipitation, RNA pulldown, domain-deletion mutagenesis, mRNA stability assay, transcriptome-wide analysis Cell death & disease High 33311452
2021 Sorbs2 knockdown in human embryonic stem cell-derived cardiomyocytes disrupts sarcomeric integrity and reduces cardiomyocyte number; molecular analysis shows decreased second heart field (SHF) marker genes and impaired NOTCH and SHH signaling; exogenous SHH rescues the cardiomyocyte differentiation defect, placing SORBS2 upstream of SHH signaling in SHF development. siRNA knockdown in hESC differentiation model, qRT-PCR, pathway rescue with recombinant SHH, Sorbs2 mouse mutant characterization eLife High 34099102
2021 Sorbs2 knockout mice display progressive abnormalities in voltage-gated Na+ channels, L-type Ca2+ channels, voltage-gated K+ channels, and inward-rectifier K+ channels; Sorbs2 physically interacts with RNA and/or proteins of these ion channels and directly regulates their expression, placing Sorbs2 as a regulator of cardiac ion channel physiology. Patch clamp, Western blot, RNA-binding assay, co-immunoprecipitation, electrophysiology in KO mice Biochimica et biophysica acta. Molecular basis of disease High 34487812
2021 NOVA1 regulates alternative splicing of SORBS2; the resulting SORBS2 isoform promotes migration of colorectal cancer cells via the Notch pathway, establishing NOVA1 as a splicing factor controlling SORBS2 isoform composition and Notch-dependent migration. RNA-seq, qRT-PCR in patient samples and cell lines, in vitro migration assay, pathway analysis Frontiers in cell and developmental biology Medium 34692669
2022 Cardiomyocyte-specific Sorbs2 knockout mice develop dilated cardiomyopathy with progressive systolic dysfunction; within 4 months Sorbs2-cKO hearts show defective microtubule polymerization and compensatory upregulation of cytoskeletal/adapter proteins, indicating that SORBS2 maintains cardiomyocyte structural integrity by supporting microtubule–cytoskeletal interactions. Cardiomyocyte-specific Cre-lox KO, echocardiography, skinned myofiber contractility, Western blot, cytoskeletal fractionation Journal of the American Heart Association High 35730644
2023 ARID5B-PHF2 histone demethylase complex binds the SORBS2 promoter (at H3K36me2 sites) and promotes H3K36 demethylation, thereby activating SORBS2 transcription in ovarian cancer cells. ChIP, co-immunoprecipitation, luciferase reporter, histone methylation analysis Pathology, research and practice Medium 37948999
2024 Sorbs2 is an RNA-binding protein that binds BK channel α-subunit (BK-α) mRNA and protein, regulating BK channel expression and function in coronary smooth muscle cells; the SH3 domain of Sorbs2 is required for interaction with BK-α, while both SH3 and SoHo domains interact with BK-β1; Sorbs2 KO mice show decreased BK channel expression, impaired Ca2+-sensitivity, and defective BK channel-mediated coronary vasodilation; Sorbs2 is a downstream transcriptional target of Nrf2. Patch clamp, co-immunoprecipitation, RNA-binding assay, domain deletion mutagenesis, Sorbs2 KO mouse, ChIP (Nrf2 binding to Sorbs2 promoter), vascular reactivity assay Circulation research High 38362769
2024 SORBS2 directly binds the 3' UTR of HK2 mRNA, stabilizing it and activating aerobic glycolysis, which promotes trophoblast cell migration; SORBS2 expression is reduced in preeclampsia placentas, and silencing HK2 abrogates the pro-migratory effect of SORBS2. RNA immunoprecipitation, mRNA stability assay, overexpression/knockdown in HTR-8/SVneo cells, rescue with HK2 silencing, proliferation and migration assays Reproduction (Cambridge, England) Medium 38995729
2024 SORBS2 directly binds the 3' UTR of TIMP3 mRNA via RIP-seq-identified sites, enhancing TIMP3 mRNA stability; SORBS2 overexpression inhibits ESCC proliferation, migration, invasion, and angiogenesis in vitro and in vivo, and TIMP3 knockdown reverses these effects. RIP-seq, RIP-qPCR, RNA pulldown, mRNA stability assay, xenograft, endothelial tube formation assay International immunopharmacology High 39288625
2024 Sorbs2 deficiency in mice reduces Nav1.5 protein expression in cardiomyocytes; siRNA-mediated Sorbs2 knockdown in H9C2 cells also reduces Nav1.5 protein, and Sorbs2 KO mice show increased susceptibility to ventricular arrhythmias with prolonged QRS and QTc intervals. Western blot, siRNA knockdown, ECG, caffeine-dobutamine stress test in KO mice Zhonghua xin xue guan bing za zhi Medium 40662394
2024 Sorbs2 physically interacts with NMT1 (N-myristoyltransferase 1) in osteoblasts; TNF-α stimulation promotes this interaction and inhibits global protein myristoylation. Co-immunoprecipitation, mass spectrometry, immunocytochemistry, Click-it myristoylation assay In vivo (Athens, Greece) Low 38148048
2024 Sorbs2 downregulation reduces AMPAR subunit GluA1 and GluA2 expression and excitatory synaptic transmission in hippocampal CA1 pyramidal neurons; knockdown of hippocampal Sorbs2 prolongs latency to spontaneous recurrent seizures and reduces seizure activity in a kainic acid TLE mouse model. AAV-mediated Sorbs2 knockdown, whole-cell patch clamp, Western blot, EEG/local field potential recording, behavioral analysis Neurochemistry international Medium 38555055
2025 SORBS2 interacts with integrin-cytoskeleton connections in cardiomyocytes (identified by affinity purification mass spectrometry); cardiomyocyte-specific loss of Sorbs2 alters integrin expression and extracellular matrix composition, leading to an exacerbated fibrotic response during pathological remodeling; SORBS2 expression is regulated by GATA4. Affinity purification mass spectrometry, Cre-lox cardiomyocyte-specific KO, cardiac fibrosis assay, ChIP/reporter for GATA4 Cardiovascular research High 39957251
2016 Fat1 cytoplasmic domain interacts with ArgBP2 (SORBS2) SH3 domains via a proline-rich PXXP motif; this interaction was mapped by mutagenesis in yeast and confirmed by pulldown in cell culture; knockdown of Fat1 causes loss of ponsin-2 at cellular leading edges. Yeast two-hybrid, pulldown assay, mutagenesis, siRNA knockdown with immunofluorescence Biochemical and biophysical research communications Medium 26903299
2022 SORBS2 interacts with multiple sarcomeric/cytoskeletal proteins in myocardial tissue, including α-actinin, β-tubulin, MYH7, FLNA, MYBPC3, YWHAQ, and DES, as identified by proteomics and verified by co-IP; YWHAQ interaction is highlighted as most associated with LVNC pathogenesis. Co-immunoprecipitation, mass spectrometry proteomics, immunofluorescence co-localization Aging Medium 35050860

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 178 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 117 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
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 72 10521485
2018 The RNA binding protein SORBS2 suppresses metastatic colonization of ovarian cancer by stabilizing tumor-suppressive immunomodulatory transcripts. Genome biology 71 29548303
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 64 26359233
2003 Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl. The Biochemical journal 57 12475393
2005 Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton. Experimental cell research 56 16125169
2016 Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 26888934
2008 ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity. Cancer research 52 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 44 31365778
2009 ArgBP2 and the SoHo family of adapter proteins in oncogenic diseases. Cell adhesion & migration 35 19262174
2020 Knockout of SORBS2 Protein Disrupts the Structural Integrity of Intercalated Disc and Manifests Features of Arrhythmogenic Cardiomyopathy. Journal of the American Heart Association 34 32808564
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 33 32905431
2014 Arg kinase-binding protein 2 (ArgBP2) interaction with α-actinin and actin stress fibers inhibits cell migration. The Journal of biological chemistry 33 25429109
2020 LncRNA H19 Inhibits the Progression of Sepsis-Induced Myocardial Injury via Regulation of the miR-93-5p/SORBS2 Axis. Inflammation 30 32996061
2020 RNA-binding protein SORBS2 suppresses clear cell renal cell carcinoma metastasis by enhancing MTUS1 mRNA stability. Cell death & disease 30 33311452
2018 HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in gastric cancer cells. Biochimica et biophysica acta. Molecular basis of disease 28 29339121
2015 Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells. Biochemical and biophysical research communications 27 26476214
2020 Elevated myocardial SORBS2 and the underlying implications in left ventricular noncompaction cardiomyopathy. EBioMedicine 25 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 23 31911856
2009 CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration. Cancer letters 21 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 18 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 16 22431180
2021 SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome patients. eLife 15 34099102
2021 NOVA1-Mediated SORBS2 Isoform Promotes Colorectal Cancer Migration by Activating the Notch Pathway. Frontiers in cell and developmental biology 12 34692669
2021 Changes in ion channel expression and function associated with cardiac arrhythmogenic remodeling by Sorbs2. Biochimica et biophysica acta. Molecular basis of disease 11 34487812
2013 SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes. BMC cancer 11 24165198
2022 SORBS2 as a molecular target for atherosclerosis in patients with familial hypercholesterolemia. Journal of translational medicine 10 35590369
2023 ARID5B promoted the histone demethylation of SORBS2 and hampered the metastasis of ovarian cancer. Pathology, research and practice 9 37948999
2024 Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes. Circulation research 8 38362769
2014 Oligomerization and phosphorylation dependent regulation of ArgBP2 adaptive capabilities and associated functions. PloS one 8 24475245
2025 Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition. Cardiovascular research 7 39957251
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
2023 MiR-484 promotes nonalcoholic fatty liver disease progression in mice via downregulation of Sorbs2. Obesity (Silver Spring, Md.) 6 37752619
2022 Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes. Frontiers in genetics 6 35242163
2024 RNA-binding protein SORBS2 increases human trophoblast cell migration via stabilizing HK2 mRNA in preeclampsia. Reproduction (Cambridge, England) 5 38995729
2022 The interaction protein of SORBS2 in myocardial tissue to find out the pathogenic mechanism of LVNC disease. Aging 4 35050860
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
2024 Sorbs2 regulates seizure activity by influencing AMPAR-mediated excitatory synaptic transmission in temporal lobe epilepsy. Neurochemistry international 2 38555055
2024 SORBS2-Mediated inhibition of malignant behaviors in esophageal squamous cell carcinoma through TIMP3. International immunopharmacology 2 39288625
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 2 36271588
2025 Understanding the Molecular Mechanisms of SORBS2 in TNBC Lung Metastasis. Biochemical and biophysical research communications 1 40199126
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 A Novel Missense Variant in SORBS2 Is Causative With Familial Alzheimer's Disease. CNS neuroscience & therapeutics 0 39912518
2025 Impact of Sorbs2 dysfunction on cardiovascular diseases. Biochimica et biophysica acta. Molecular basis of disease 0 40139410
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