Affinage

ITGB3

Integrin beta-3 · UniProt P05106

Length
788 aa
Mass
87.1 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGB3 (integrin β3/GPIIIa/CD61) is the β-subunit of integrin heterodimers that transduce extracellular adhesion cues into intracellular signaling controlling platelet aggregation, cell migration, invasion, and tissue remodeling (PMID:2477081, PMID:21622897). Surface display of the receptor is conditional: GPIIIa must assemble with pro-GPIIb in the ER as an obligatory prerequisite for heterodimer maturation, and unassembled GPIIIa is retained intracellularly (PMID:2477081); mutations disrupting subunit-interface contacts or disulfide bonding in the cysteine-rich region abolish surface expression of both αIIbβ3 and αvβ3, causing Glanzmann's thrombasthenia (PMID:10233432, PMID:20020534). Engagement of αvβ3 drives outside-in signaling principally through focal adhesion kinase (FAK), which couples the receptor to integrin endocytosis and extracellular-vesicle uptake, to β-catenin nuclear translocation during mechanosensing, and to PI3K/AKT- and JNK-dependent outputs (PMID:32848136, PMID:34996170, PMID:28600799). Across multiple cancers, ITGB3 sustains TGF-β signaling, EMT, and metastasis, and engages additional effector axes including PI3K-Akt-mTOR/STMN1, c-SRC/STAT3, NF-κB, and EGFL7-KLF2 amplification loops (PMID:21622897, PMID:29383126, PMID:32152220, PMID:32191808). ITGB3 abundance is set at several levels: transcriptionally by HOXB5 and by a G9A/P300/glucocorticoid-receptor activator complex, translationally by hypoxia, and post-translationally by ITCH-mediated ubiquitylation; a promoter variant raising β3 expression in megakaryocytes enhances SERT trafficking to the platelet membrane and elevates blood serotonin (PMID:33456563, PMID:29449539, PMID:29383126, PMID:37760946, PMID:30535103). Beyond hemostasis and cancer, ITGB3 acts as a uPAR-linked effector of calcineurin-NFATC signaling in podocyte injury, regulates cortical network excitability by balancing synaptic versus extrasynaptic mGluR5 signaling, and is transiently expressed on T cells where it pairs with CD103 at the immune synapse to potentiate TCR signaling and antitumor cytotoxicity (PMID:31127093, PMID:36035754, PMID:38561495).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    Established that GPIIIa cannot reach the cell surface alone, defining heterodimer assembly with pro-GPIIb as the gatekeeping step for receptor biogenesis.

    Evidence Pulse-chase with subunit-specific antibodies in human megakaryocytes and complementation in the LAMA-84 cell line

    PMID:2477081

    Open questions at the time
    • Did not define the ER chaperones or quality-control machinery enforcing retention
    • Does not address αvβ3 assembly requirements
  2. 1991 High

    Determined that GPIIIa is phosphorylated on threonine by CaM kinase II, but at stoichiometry too low to regulate bulk fibrinogen-receptor function.

    Evidence 32Pi metabolic labeling of platelets plus in vitro phosphorylation of purified GPIIb-IIIa and phosphoamino acid analysis

    PMID:1650365

    Open questions at the time
    • Physiological role of the low-stoichiometry phosphorylation not resolved
    • Specific phosphoacceptor residues not mapped
  3. 1992 Medium

    Mapped the ligand-binding and subunit-interface regions of GPIIIa by proteolytic dissection, providing the first domain-level structure-function framework.

    Evidence Limited proteolysis of purified GPIIb/IIIa with multiple proteinases and immunochemical fragment mapping

    PMID:1546968

    Open questions at the time
    • No crystal structure confirmation at the time
    • Boundaries inferred from protease accessibility rather than direct contact mapping
  4. 2010 High

    Connected disease mutations to receptor assembly defects and identified specific β3 residues governing the αIIb β-propeller/β3 β-I domain interface.

    Evidence Site-directed mutagenesis and COS-7 surface expression assays combined with free-energy analysis on the solved αIIbβ3 crystal structure

    PMID:10233432 PMID:20020534 PMID:8132570

    Open questions at the time
    • Does not address how interface defects are sensed by ER quality control
    • Some variants (e.g. Sra) alter glycosylation without affecting function, leaving structural consequences unexplained
  5. 2004 Medium

    Identified a platelet-surface signaling partnership in which F11R/JAM-A associates with GPIIIa during platelet activation.

    Evidence Co-immunoprecipitation from activated platelets with functional aggregation, secretion, calcium and actin assays

    PMID:15344881

    Open questions at the time
    • Single co-IP without reciprocal validation
    • Direct versus indirect nature of the association not established
  6. 2017 Medium

    Defined αvβ3 as the receptor coupling laminin engagement to MSC paracrine secretion through branched JNK and PI3K/AKT outputs.

    Evidence αvβ3 blocking antibody plus JNK and PI3K/AKT inhibitors with paracrine factor ELISA

    PMID:28600799

    Open questions at the time
    • Antibody blockade does not exclude contribution of other αv heterodimers
    • Mechanism connecting receptor to divergent kinase arms not detailed
  7. 2011 Medium

    Showed that ITGB3 drives tumor migration/invasion and TGF-β-dependent tumor-initiating-cell self-renewal, placing the receptor upstream of cancer-progression programs.

    Evidence siRNA knockdown with Transwell assays and PI3K-Akt-mTOR/STMN1 analysis; CD49f/CD61 sorting with tumorsphere and in vivo tumorigenicity assays plus TGF-β inhibition

    PMID:21622897 PMID:21996747

    Open questions at the time
    • How ROS upregulates ITGB3 transcription not defined
    • Direct molecular link between β3 and TGF-β receptor activation not resolved
  8. 2017 High

    Established that ITGB3 abundance is set translationally under hypoxia and is required for sustained TGF-β/EMT signaling and metastasis.

    Evidence Polysomal RNA-Seq translatome profiling plus knockdown with apoptosis, migration, EMT readouts and in vivo lung metastasis

    PMID:29383126

    Open questions at the time
    • mTOR-independent translational mechanism not molecularly identified
    • Effector linking β3 to Snail induction unspecified
  9. 2018 High

    Identified multiple transcriptional and signaling inputs setting or transmitting ITGB3 levels in cancer, including a non-catalytic G9A/P300/GR activator complex and NF-κB-linked chemoresistance.

    Evidence ChIP, reciprocal co-IP, luciferase reporters and SET-domain mutants for G9A complex; knockdown with NF-κB pathway and drug-response analysis for mesenchymal lung cancer

    PMID:29449539 PMID:30563517

    Open questions at the time
    • Generality of glucocorticoid-dependent ITGB3 induction beyond gastric cancer untested
    • Mechanism linking β3 to NF-κB activation not defined
  10. 2019 High

    Linked an ITGB3 promoter variant to megakaryocyte-specific β3 expression, SERT membrane trafficking, and blood serotonin, connecting integrin dosage to a neurotransmitter phenotype.

    Evidence Luciferase reporters in hematopoietic cell lines, platelet β3 quantification, SERT trafficking assay, and human association analysis

    PMID:30535103

    Open questions at the time
    • Molecular mechanism by which β3 promotes SERT membrane trafficking unresolved
    • Causality between serotonin elevation and phenotype not established
  11. 2019 High

    Placed ITGB3 as a downstream effector in the miR-30/calcineurin-NFATC/uPAR axis driving podocyte injury.

    Evidence Podocyte-specific miR-30 KO/transgenic mice with ITGB3, calcineurin and NFATC inhibitors and proteinuria readouts

    PMID:31127093

    Open questions at the time
    • Direct uPAR-ITGB3 binding versus signaling crosstalk not dissected
    • Rho GTPase activation mechanism downstream of β3 not detailed
  12. 2020 High

    Defined FAK-dependent outside-in signaling roles for ITGB3 in vesicle endocytosis and in SRC/STAT3 and EGFL7-KLF2 survival circuits.

    Evidence Knockdown/overexpression with reciprocal co-IP (HSPGs, EGFL7), FAK inhibition, ChIP-qPCR, phosphorylation and in vivo models across breast cancer, melanoma and myeloma

    PMID:32152220 PMID:32191808 PMID:32848136

    Open questions at the time
    • Whether a single β3 conformation drives all these effector branches unknown
    • Cell-type determinants selecting among SRC/STAT3, KLF2 and FAK outputs unresolved
  13. 2021 Medium

    Identified HOXB5 as a direct transcriptional activator of ITGB3 in a CXCL12-CXCR4 feedback loop and extended ITGB3 function to placental vascular development and osteoblast differentiation.

    Evidence ChIP and luciferase reporters with in vivo metastasis for HOXB5; morpholino knockdown in sheep conceptus; IL1RN-ITGB3 co-IP with β-catenin/osteogenesis assays

    PMID:33232974 PMID:33456563 PMID:33493267

    Open questions at the time
    • IL1RN-ITGB3 interaction rests on a single co-IP
    • Mechanism by which β3 controls SPP1/NOS3 in placenta not defined
  14. 2022 High

    Expanded ITGB3 regulation and signaling to RGD-mediated suppression by MIIP, ferroptosis evasion via SLC7A11, and neuronal control of mGluR5-dependent network excitability.

    Evidence Co-IP with RGD-motif mutagenesis and β-catenin ubiquitination (MIIP); EV transfer with SLC7A11 stability and MAPK/ERK/ATF4/Nrf2 analysis; Itgb3 KO mice with CRISPRa rescue and mGluR5 pharmacology

    PMID:36035754 PMID:36130933 PMID:36263165

    Open questions at the time
    • Whether synaptic mGluR5 regulation involves canonical integrin adhesion signaling unknown
    • Structural basis of MIIP RGD-mediated inhibition versus ligand activation not contrasted
  15. 2023 Medium

    Established ITCH-mediated ubiquitylation as a post-translational control of ITGB3 stability and pro-invasive activity.

    Evidence Co-IP of ITCH with ITGB3, ubiquitylation analysis, and proliferation/invasion rescue in ectopic endometrial stromal cells

    PMID:37760946

    Open questions at the time
    • Ubiquitylated lysine residues and chain type not mapped
    • Whether ITCH targets cell-surface or intracellular β3 pools unclear
  16. 2024 High

    Revealed non-canonical contexts: transient CD61 expression at the T-cell immune synapse potentiating TCR signaling, and PEX3-dependent plasmalogen metabolism controlling ITGB3 membrane localization in cardiac repair.

    Evidence Live synaptic imaging with CD61/CD103/TCR colocalization and cytotoxicity assays; cardiomyocyte-specific Pex3 KO with lipidomics, membrane fractionation and AKT/GSK3β analysis

    PMID:38561495 PMID:38951640

    Open questions at the time
    • How CD61 mechanistically modulates TCR proximal signaling not defined
    • Lipid-dependent mechanism positioning β3 at the plasma membrane not molecularly resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single β3 subunit selects among its diverse outside-in effector branches (FAK, SRC/STAT3, β-catenin, NF-κB, mGluR5) in a cell-type- and ligand-specific manner.
  • No unifying conformational or partner-selection model across tissues
  • Relationship between phosphorylation, ubiquitylation and effector choice unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098631 cell adhesion mediator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-109582 Hemostasis 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-168256 Immune System 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
CD103EGFL7F11RIL1RNITCHITGA2BITGAVMIIP
Complex memberships
αIIbβ3 (GPIIb-IIIa)αvβ3 integrin

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Assembly between pro-GPIIb and GPIIIa (ITGB3) is an obligatory prerequisite for maturation of the heterodimer and its expression on the cell surface; unassociated GPIIIa is retained intracellularly and not surface-exposed. Pulse-chase experiments with antibodies specific for GPIIIa or GPIIb in human megakaryocytes; LAMA-84 megakaryocytic cell line expressing only pro-GPIIb showed no surface expression of GPIIIa until GPIIb processing occurred upon GPIIIa co-expression Blood High 2477081
1991 GPIIIa (ITGB3) is phosphorylated in platelets predominantly on threonine; Ca2+/calmodulin-dependent kinase II can phosphorylate purified GPIIIa to ~0.5 mol P/mol in vitro; stoichiometry in intact platelets is very low (~0.01–0.03 mol P/mol), suggesting phosphorylation does not affect bulk fibrinogen-receptor function but may affect a subpopulation. Metabolic 32Pi labeling of intact platelets; in vitro phosphorylation of purified GPIIb-IIIa by PKC and CaM kinase II; phosphoamino acid analysis The Journal of biological chemistry High 1650365
1992 Limited proteolysis of isolated GPIIb/IIIa heterodimer mapped a ligand-binding region to GPIIIa residues 100–220 and identified GPIIIa residues 217–421 as involved in the subunit interface; the GPIIIa N-terminal (1–52) and core (423–622) domains are compact, while the intervening region is proteolysis-susceptible. Limited proteolysis of purified GPIIb/IIIa with proteinases of different specificities followed by protein-chemical and immunochemical analysis of peptide fragments The Biochemical journal Medium 1546968
1994 A C→T point mutation at position 2004 in GPIIIa creates an Arg636→Cys substitution that introduces an unpaired cysteine in the cysteine-rich domain, alters N-linked glycosylation (detected as molecular weight shift reversed by EndoH), and creates the Sra alloantigen epitope; despite this, surface expression of GPIIb-IIIa and platelet aggregation are unaffected. PCR-amplified GPIIIa mRNA sequencing; allele-specific recombinant GPIIIa expression; anti-Sra alloantibody reactivity assay; Endoglycosidase H treatment; SDS-PAGE; platelet aggregation assay The Journal of biological chemistry High 8132570
1999 A homozygous Cys542→Arg substitution in GPIIIa disrupts disulfide bond formation in the cysteine-rich core region, resulting in a slightly slower-migrating GPIIIa by Western blot and trace levels of both GPIIb and GPIIIa at the platelet surface (type I Glanzmann's thrombasthenia), and also reduces αvβ3 surface expression. Western blotting; flow cytometry with mAbs to GPIIb, GPIIIa, GPIIb-IIIa and αv; PCR-SSCP and direct sequencing; allele-specific restriction enzyme analysis (HinP1I site introduced by mutation) British journal of haematology Medium 10233432
2004 F11R (JAM-1) forms a complex with integrin GPIIIa (ITGB3) on platelet surfaces following F11R crosslinking, coincident with F11R dimerization and phosphorylation; this association is part of the signaling cascade leading to platelet aggregation and secretion. Co-immunoprecipitation of F11R with GPIIIa from activated platelets; functional assays (aggregation, granule secretion); calcium measurements; actin assembly assays Journal of receptor and signal transduction research Medium 15344881
2010 Several missense mutations in ITGB3 (e.g., C38Y, M118R, G221D) prevent αIIbβ3 complex expression at the COS-7 cell surface; a K253M substitution of β3 defines a key role of K253 in the interaction between the αIIb β-propeller and β3 β-I domains, as revealed by free energy analysis on the resolved αIIbβ3 crystal structure. Site-directed mutagenesis; transient expression in COS-7 cells; flow cytometry; structural free energy analysis on solved αIIbβ3 structure; molecular modeling Human mutation High 20020534
2011 ROS upregulate ITGB3 expression in colorectal cancer cells, and surface expression as αvβ3 heterodimer is required for ITGB3-mediated migration and invasion; ITGB3 promotes aggressive phenotype through the PI3K-Akt-mTOR pathway and upregulation of STMN1. 2D-electrophoresis proteomics; knockdown of ITGB3 by siRNA in SW620 and H2O2-treated SW480 cells; Transwell migration/invasion assays; Western blot; ROS measurement Molecular & cellular proteomics : MCP Medium 21622897
2011 Integrin β3 (CD61) signaling is required for sustaining active TGFβ signaling and self-renewal of breast tumor-initiating cells in the MMTV-Her2/neu model; pharmacological inhibition of TGFβ signaling suppressed TIC self-renewal and clonogenicity. CD49f/CD61 surface marker sorting; tumorsphere formation assay; in vivo tumorigenicity; TGFβ pathway inhibition; gene expression profiling Oncogene Medium 21996747
2017 ITGB3 is translationally activated under hypoxia in breast cancer cells (mTOR-independent mechanism), and is required for sustained TGF-β pathway activation and induction of Snail/EMT markers; ITGB3 knockdown increased apoptosis, reduced migration, and significantly reduced lung metastasis in mice. Polysomal RNA-Seq (translatome profiling); ITGB3 knockdown; apoptosis assays; TGF-β pathway reporter; EMT marker analysis; in vivo lung metastasis mouse model Oncotarget High 29383126
2018 G9A promotes ITGB3 expression in gastric cancer by forming a transcriptional activator complex with P300 and glucocorticoid receptor (GR) at the ITGB3 promoter, an effect dependent on dexamethasone but independent of G9A's SET domain methyltransferase activity. Chromatin immunoprecipitation (ChIP); co-immunoprecipitation of G9A/P300/GR complex; luciferase reporter assay; ITGB3 overexpression/knockdown; in vitro and in vivo invasion/metastasis assays; SET domain mutant constructs Cell death & disease High 29449539
2018 ITGB3 depletion sensitizes mesenchymal lung cancer cells to conventional chemotherapeutic drugs by modulating the NF-κB signaling pathway. ITGB3 knockdown; cell viability assays; NF-κB signaling pathway analysis; large-scale transcriptome and drug-response dataset correlation Molecular cancer Medium 30563517
2019 ITGB3 promoter variant rs55827077 (C allele) enhances ITGB3 promoter activity specifically during megakaryocyte differentiation, leading to greater integrin β3 protein expression, enhanced SERT trafficking from cytosol to platelet plasma membrane, and elevated serotonin blood levels. Luciferase reporter assays in K-562 and HEL 92.1.7 hematopoietic cell lines; ITGB3 sequencing; platelet integrin β3 protein quantification; SERT trafficking assay; association analysis in 176 autistic individuals Human molecular genetics High 30535103
2020 ITGB3 facilitates uptake of small extracellular vesicles in breast cancer cells through interaction with heparan sulfate proteoglycans (HSPGs) and integrin endocytosis; this requires activation of focal adhesion kinase (FAK), which is necessary for endocytosis-mediated internalization of vesicles. ITGB3 knockdown/overexpression; vesicle uptake assays; Co-IP of ITGB3 with HSPGs; FAK inhibition; endocytosis inhibitor experiments Nature communications High 32848136
2020 In melanoma tumor-repopulating cells, ITGB3 activates c-SRC, which phosphorylates STAT3; STAT3 transcriptionally suppresses RIG-I, thereby decreasing STAT1 activation and conferring resistance to IFN-α-induced apoptosis. ITGB3/c-SRC/STAT3 knockdown; ChIP-qPCR for STAT3 binding to RIG-I promoter; Co-IP of SHP-1 with STAT1; Western blot; apoptosis assays; in vivo tumor models Journal for immunotherapy of cancer High 32152220
2020 EGFL7 binds to and activates ITGB3 on multiple myeloma cells, causing ITGB3 phosphorylation and focal adhesion kinase activation; ITGB3 overexpression upregulates KLF2 transcription factor, which in turn enhances EGFL7 transcription, establishing an EGFL7-ITGB3-KLF2 amplification loop supporting MM cell survival. ITGB3 and EGFL7 overexpression/knockdown; ITGB3 phosphorylation assay; FAK activation measurement; KLF2 reporter; neutralizing antibody treatment; in vivo mouse transplantation model Blood advances High 32191808
2019 miR-30 family deficiency activates calcineurin-NFATC signaling, which in turn activates uPAR-ITGB3 signaling in podocytes, leading to Rho GTPase activation, synaptopodin downregulation and podocyte injury; ITGB3 inhibition, calcineurin inhibition, or NFATC inhibition each reduces the effects of miR-30 knockdown. Podocyte-specific miR-30 KO and transgenic mice; ITGB3 inhibitor treatment; calcineurin/NFATC inhibitors; uPAR/ITGB3 pathway measurement; proteinuria readout; LPS model Cell death & disease High 31127093
2021 HOXB5 transcriptionally activates ITGB3 expression by directly binding to the ITGB3 promoter (chromatin immunoprecipitation + luciferase assay), promoting colorectal cancer metastasis; CXCL12 upregulates HOXB5 via ERK/ETS1 pathway, creating a CXCL12-HOXB5-CXCR4 positive feedback loop. Chromatin immunoprecipitation (ChIP); luciferase reporter assay; HOXB5 overexpression/knockdown; in vivo lung and liver metastasis models Theranostics High 33456563
2021 Loss of ITGB3 in ovine conceptus trophectoderm decreases embryo growth and reduces expression of SPP1 and NOS3 in the placental allantoic membrane, implicating ITGB3 in regulation of placental vascular development. Morpholino antisense oligonucleotide knockdown of ITGB3 in sheep uterus; measurement of embryo growth; qPCR and immunolocalization of SPP1 and NOS3 Biology of reproduction Medium 33232974
2021 IL1RN interacts with ITGB3 (integrin β3) to activate β-catenin signaling, which regulates osteoblast differentiation; IL1RN overexpression promotes osteogenic markers and IL1RN silencing attenuates osteogenesis. Co-immunoprecipitation of IL1RN and ITGB3; IL1RN overexpression/knockdown in MC3T3-E1 and C3H10T1/2 cells; osteogenic staining and marker expression; β-catenin signaling measurement Acta biochimica et biophysica Sinica Medium 33493267
2022 ITGB3 haplo-insufficiency in cortical neurons impairs network excitability by promoting extra-synaptic over synaptic mGluR5 signaling; CRISPR activation of Itgb3 to restore gene dosage rebalanced network excitability as effectively as MPEP (mGluR5 antagonist) blockade. Itgb3 knockout mice; CRISPR activation (CRISPRa) to restore Itgb3 expression; cortical network excitability recording; mGluR5 pharmacological manipulation; biochemical and imaging analyses Molecular therapy. Nucleic acids High 36035754
2022 P-EV (platelet-derived extracellular vesicle)-upregulated ITGB3 increases SLC7A11 expression by enhancing protein stability and activating the MAPK/ERK/ATF4/Nrf2 axis, suppressing ferroptosis and facilitating NPC cell metastasis. EV transfer experiments; ITGB3 overexpression/knockdown; SLC7A11 protein stability assay; MAPK/ERK/ATF4/Nrf2 pathway analysis; ferroptosis assays; NPC xenograft mouse model International journal of biological sciences Medium 36263165
2022 MIIP directly interacts with ITGB3 via an RGD motif, suppresses ITGB3 downstream signaling, reduces β-catenin (via ubiquitin-mediated degradation), decreases VEGFA production and EMT, thereby inhibiting tumor angiogenesis and metastasis of triple-negative breast cancer. Co-immunoprecipitation of MIIP and ITGB3; RGD motif mutagenesis; β-catenin ubiquitination assay; VEGFA expression; in vivo tumor models Cell death & disease High 36130933
2023 ITCH (ubiquitin E3 ligase) interacts with ITGB3 and mediates its ubiquitylation; ITCH overexpression opposes ITGB3-promoted proliferation and invasion of ectopic endometrial stromal cells, suggesting ubiquitination of ITGB3 regulates its stability/activity. Co-immunoprecipitation of ITCH and ITGB3; ubiquitylation analysis; CCK8 proliferation assay; Transwell invasion assay; ITGB3 and ITCH overexpression Biomedicines Medium 37760946
2024 ITGB3 (CD61) is transiently expressed on T cells, pairs with CD103 at synaptic microclusters, and colocalizes with the TCR; CD61 modulates downstream TCR signaling and enhances antitumor cytotoxicity. Live imaging of synaptic microclusters; co-localization of CD61 with CD103 and TCR; TCR signaling pathway analysis; cytotoxicity assays; in vivo tumor growth control experiments Nature immunology High 38561495
2024 PEX3-regulated plasmalogen metabolism activates the AKT/GSK3β signaling pathway via plasma membrane localization of ITGB3, promoting myocardial regenerative repair; cardiomyocyte-specific Pex3 KO disrupts ITGB3 plasma membrane localization. Cardiomyocyte-specific Pex3 KO mice; lipid metabolomics; ITGB3 plasma membrane fractionation; AKT/GSK3β signaling measurement; myocardial regeneration readouts Communications biology Medium 38951640
2017 Laminin (ECM protein) enhances MSC paracrine function (GRO-α, HGF, IL-8 secretion) through αvβ3 integrin (ITGB3), with GRO-α and IL-8 secretion dependent on JNK signaling and HGF secretion dependent on PI3K/AKT signaling downstream of αvβ3. αvβ3 integrin blocking antibody; JNK and PI3K/AKT inhibitors; paracrine factor ELISA; cardiomyocyte apoptosis assay Journal of cellular and molecular medicine Medium 28600799
2018 Osteocytes sense ECM mechanical stiffness via integrin αvβ3 (containing ITGB3), which interacts with FAK to transduce extracellular mechanical stimuli into intracellular signals; FAK triggers cytoplasmic β-catenin signaling and nuclear translocation, affecting gap junction function and mineralization activity. PDMS substrates with varied mechanical stiffness; ITGB3/FAK inhibitor experiments; β-catenin nuclear localization assay; gap junction and mineralization activity measurement ACS applied bio materials Medium 34996170

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3. Cancer research 290 31331909
2013 MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer letters 176 23981581
2011 Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 176 21917754
2011 CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling. Oncogene 139 21996747
2020 ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells. Nature communications 132 32848136
2011 Proteomics identification of ITGB3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. Molecular & cellular proteomics : MCP 111 21622897
2007 Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Human genetics 100 17203304
1989 Biosynthesis and assembly of platelet GPIIb-IIIa in human megakaryocytes: evidence that assembly between pro-GPIIb and GPIIIa is a prerequisite for expression of the complex on the cell surface. Blood 94 2477081
2011 Atorvastatin reduces thrombin generation and expression of tissue factor, P-selectin and GPIIIa on platelet-derived microparticles in patients with peripheral arterial occlusive disease. Thrombosis and haemostasis 87 21614411
1999 The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans. Chest 84 10531147
2016 MiR-30a-5p Suppresses Tumor Metastasis of Human Colorectal Cancer by Targeting ITGB3. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 83 27576787
1991 Phosphorylation of human platelet glycoprotein IIIa (GPIIIa). Dissociation from fibrinogen receptor activation and phosphorylation of GPIIIa in vitro. The Journal of biological chemistry 82 1650365
2019 ITGB3/CD61: a hub modulator and target in the tumor microenvironment. American journal of translational research 72 31934272
2015 Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort. Human mutation 70 25728920
1990 Identification of an abnormal gene for the GPIIIa subunit of the platelet fibrinogen receptor resulting in Glanzmann's thrombasthenia. Blood 69 1967954
2021 CXCL12-mediated HOXB5 overexpression facilitates Colorectal Cancer metastasis through transactivating CXCR4 and ITGB3. Theranostics 58 33456563
2015 miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer. OncoTargets and therapy 58 26445551
2022 Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3. International journal of biological sciences 56 36263165
2018 G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner. Cell death & disease 56 29449539
2007 Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Pharmacogenomics 56 17559347
1994 A point mutation leads to an unpaired cysteine residue and a molecular weight polymorphism of a functional platelet beta 3 integrin subunit. The Sra alloantigen system of GPIIIa. The Journal of biological chemistry 52 8132570
2019 LncRNA-H19 regulates cell proliferation and invasion of ectopic endometrium by targeting ITGB3 via modulating miR-124-3p. Experimental cell research 51 31085188
1992 Proteolytic dissection of the isolated platelet fibrinogen receptor, integrin GPIIb/IIIa. Localization of GPIIb and GPIIIa sequences putatively involved in the subunit interface and in intrasubunit and intrachain contacts. The Biochemical journal 51 1546968
2014 MiR-320a down-regulation mediates bladder carcinoma invasion by targeting ITGB3. Molecular biology reports 48 24443232
2018 Role of miR-223-3p in pulmonary arterial hypertension via targeting ITGB3 in the ECM pathway. Cell proliferation 47 30507047
2017 Hypoxia-mediated translational activation of ITGB3 in breast cancer cells enhances TGF-β signaling and malignant features in vitro and in vivo. Oncotarget 45 29383126
2009 Molecular defects in ITGA2B and ITGB3 genes in patients with Glanzmann thrombasthenia. Journal of thrombosis and haemostasis : JTH 43 19691478
2012 Multiploid CD61+ cells are the pre-dominant cell lineage infected during acute dengue virus infection in bone marrow. PloS one 42 23300812
2014 Arsenic-induced sub-lethal stress reprograms human bronchial epithelial cells to CD61¯ cancer stem cells. Oncotarget 41 24675390
1990 GPIIb and GPIIIa amino acid sequences deduced from human megakaryocyte cDNAs. Molecular biology reports 40 2345548
2018 Large-scale pharmacogenomics based drug discovery for ITGB3 dependent chemoresistance in mesenchymal lung cancer. Molecular cancer 39 30563517
2004 Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A) in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa. Journal of receptor and signal transduction research 39 15344881
2010 Association and gene-gene interaction of SLC6A4 and ITGB3 in autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 38 19588468
2019 MiR-124-3p inhibits the migration and invasion of Gastric cancer by targeting ITGB3. Pathology, research and practice 37 31836324
2004 A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 37 15178823
2017 Insufficient Radiofrequency Ablation Treated Hepatocellular Carcinoma Cells Promote Metastasis by Up-Regulation ITGB3. Journal of Cancer 36 29151962
2010 Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes. European journal of human genetics : EJHG 36 21102624
2005 Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations. American journal of respiratory and critical care medicine 36 15817799
2001 The GPIIIa (beta3 integrin) PlA polymorphism in the early development of coronary atherosclerosis. Atherosclerosis 36 11257275
1997 Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression. Journal of cardiovascular pharmacology 36 9007665
2006 ITGB3 shows genetic and expression interaction with SLC6A4. Human genetics 35 16721604
2017 Extracellular matrix protein laminin enhances mesenchymal stem cell (MSC) paracrine function through αvβ3/CD61 integrin to reduce cardiomyocyte apoptosis. Journal of cellular and molecular medicine 34 28600799
2021 Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel. Blood advances 32 33496739
2007 Chicken thrombocytes express the CD51/CD61 integrin. Veterinary immunology and immunopathology 32 17659354
2010 AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function. Human mutation 31 20020534
2020 Downregulation of RIG-I mediated by ITGB3/c-SRC/STAT3 signaling confers resistance to interferon-α-induced apoptosis in tumor-repopulating cells of melanoma. Journal for immunotherapy of cancer 28 32152220
2016 CD142+/CD61+, CD146+ and CD45+ microparticles predict cardiovascular events in high risk patients following a Mediterranean diet supplemented with nuts. Thrombosis and haemostasis 27 27052787
1999 Homozygous Cys542-->Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia. British journal of haematology 27 10233432
2022 miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation. Molecular medicine (Cambridge, Mass.) 26 36180828
2012 Role of CD61+ cells in thrombocytopenia of dengue patients. International journal of hematology 26 22987294
2001 Automated CD61 immunoplatelet analysis of thrombocytopenic samples. British journal of haematology 26 11260058
2000 Interleukin-6 and interleukin-11 act synergistically with thrombopoietin and stem cell factor to modulate ex vivo expansion of human CD41+ and CD61+ megakaryocytic cells. Haematologica 26 10629587
2022 Positive feedback regulation of lncRNA TPT1-AS1 and ITGB3 promotes cell growth and metastasis in pancreatic cancer. Cancer science 23 35534983
2020 The EGFL7-ITGB3-KLF2 axis enhances survival of multiple myeloma in preclinical models. Blood advances 23 32191808
2021 Loss of ITGB3 in ovine conceptuses decreases conceptus expression of NOS3 and SPP1: implications for the developing placental vasculature†. Biology of reproduction 22 33232974
2019 MiR-30 family prevents uPAR-ITGB3 signaling activation through calcineurin-NFATC pathway to protect podocytes. Cell death & disease 22 31127093
2016 Generation and Analysis of GATA2w/eGFP Human ESCs Reveal ITGB3/CD61 as a Reliable Marker for Defining Hemogenic Endothelial Cells during Hematopoiesis. Stem cell reports 22 27746115
2007 CD61 enriches long-term repopulating hematopoietic stem cells. Biochemical and biophysical research communications 22 17983596
2005 Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample. Human genetics 22 15834589
2013 Genetic association and gene-gene interaction analyses suggest likely involvement of ITGB3 and TPH2 with autism spectrum disorder (ASD) in the Indian population. Progress in neuro-psychopharmacology & biological psychiatry 21 23628433
2017 MicroRNA-Mediated Regulation of ITGB3 and CHL1 Is Implicated in SSRI Action. Frontiers in molecular neuroscience 20 29163031
2023 ITGB3 promotes cisplatin resistance in osteosarcoma tumors. Cancer medicine 19 36772869
2013 Genetic variation of ITGB3 is associated with asthma in Chinese Han children. PloS one 19 23451109
2002 Immunohistochemical analysis of beta3 integrin (CD61): expression in pig tissues and human tumors. Histology and histopathology 19 11962738
2021 IL1RN promotes osteoblastic differentiation via interacting with ITGB3 in osteoporosis. Acta biochimica et biophysica Sinica 18 33493267
2021 The long non-coding RNA HOXA11-AS activates ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Cancer cell international 18 34715856
2018 Compliant Substratum Changes Osteocyte Functions: The Role of ITGB3/FAK/β-Catenin Signaling Matters. ACS applied bio materials 18 34996170
2017 Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients. BMC neurology 18 28068952
2017 Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke. European journal of clinical pharmacology 18 28091702
2017 CD61 promotes the differentiation of canine ADMSCs into PGC-like cells through modulation of TGF-β signaling. Scientific reports 18 28256590
2020 Diabetes and Hyperglycemia Affect Platelet GPIIIa Expression. Effects on Adhesion Potential of Blood Platelets from Diabetic Patients under In Vitro Flow Conditions. International journal of molecular sciences 16 32370146
2016 Interaction of CYP2C19, P2Y12, and GPIIIa Variants Associates With Efficacy of Clopidogrel and Adverse Events on Patients With Ischemic Stroke. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 16 27233747
2022 CRISPR-mediated activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling. Molecular therapy. Nucleic acids 15 36035754
2017 Expression of PGR, HBEGF, ITGAV, ITGB3 and SPP1 genes in eutopic endometrium of infertile women with endometriosis during the implantation window: a pilot study. JBRA assisted reproduction 15 28837027
2016 Overexpression of CD61 promotes hUC-MSC differentiation into male germ-like cells. Cell proliferation 15 26840189
2014 Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects. International journal of hematology 15 24474638
2005 Thrombotic thrombocytopenic purpura causing rapid unexpected death: value of CD61 immunohistochemical staining in diagnosis. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 15 15914300
2001 Evaluation of a CD61 MoAb method for enumeration of platelets in thrombocytopenic patients and its impact on the transfusion decision-making process. Transfusion 15 11606818
2024 Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity. Nature immunology 14 38561495
2022 microRNA-25-3p suppresses osteogenic differentiation of BMSCs in patients with osteoporosis by targeting ITGB3. Acta histochemica 14 35777302
2016 Genotype Frequencies of CYP2C19, P2Y12 and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness. International heart journal 14 27488401
2016 Common rs5918 (PlA1/A2) polymorphism in the ITGB3 gene and risk of coronary artery disease. Archives of medical sciences. Atherosclerotic diseases 14 28905013
1988 A Taq 1 polymorphism for the human platelet glycoprotein IIIa gene (GP3A). Nucleic acids research 14 2900503
2020 Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia. Journal of thrombosis and thrombolysis 13 33047245
2019 Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking. Human molecular genetics 13 30535103
1998 Functional characterization of PM6/13, a beta3-specific (GPIIIa/CD61) monoclonal antibody that shows preferential inhibition of fibrinogen binding over fibronectin binding to activated human platelets. Thrombosis and haemostasis 13 9459345
1992 Microsatellite polymorphism in the human platelet glycoprotein IIIa gene (GP3A) on chromosome 17. Nucleic acids research 13 1549507
2024 PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3. Communications biology 12 38951640
2023 ITCH-Mediated Ubiquitylation of ITGB3 Promotes Cell Proliferation and Invasion of Ectopic Endometrial Stromal Cells in Ovarian Endometriosis. Biomedicines 12 37760946
2022 MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer. Cell death & disease 12 36130933
2014 SNPs in microRNA-binding sites in the ITGB1 and ITGB3 3'-UTR increase colorectal cancer risk. Cell biochemistry and biophysics 12 24777809
2013 Genetic association analysis of ITGB3 polymorphisms with age at onset of schizophrenia. Journal of molecular neuroscience : MN 12 23860687
2010 Novel Mutations in the GPIIb and GPIIIa Genes in Glanzmann Thrombasthenia. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 12 21113249
2008 Platelet CD61 expression in vascular calcineurin inhibitor toxicity of renal allografts. Human pathology 12 18234279
2003 Association between the Pl(A) platelet glycoprotein GPIIIa polymorphism and extent of coronary artery disease. International journal of cardiology 12 12714203
1993 Application of GPIIIa gene Taq I polymorphism to determination of carrier status in Glanzmann's thrombasthenia families of Chinese origin. Thrombosis and haemostasis 12 8095357
2023 Reduced expression of Il10, Stat3, Hoxa10, and Itgb3 in the embryo implantation site of rat model with prenatal androgen-induced polycystic ovary syndrome. American journal of reproductive immunology (New York, N.Y. : 1989) 11 37062956
2019 An Evaluation of CD61 Immunohistochemistry in Identification of Vascular Invasion in Follicular Thyroid Neoplasms. Head and neck pathology 11 31218593
2017 Interaction among CYP2C8, GPIIIa and P2Y12 variants increase susceptibility to ischemic stroke in Chinese population. Oncotarget 11 29050321
2009 A1/A2 polymorphism of GpIIIa gene and a risk of aneurysmal subarachnoid haemorrhage. Biochemical and biophysical research communications 11 19345676

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