Affinage

ITGA2

Integrin alpha-2 · UniProt P17301

Round 2 corrected
Length
1181 aa
Mass
129.3 kDa
Annotated
2026-04-28
130 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGA2 encodes the alpha-2 subunit of integrin α2β1, the principal collagen receptor on platelets and many other cell types, mediating direct adhesion to collagen types I–VIII as well as thrombospondin and echovirus 1 (PMID:2546619, PMID:8118028, PMID:8240284). Ligand recognition is conferred by the I-domain (residues ~140–359), whose MIDAS motif coordinates a divalent cation and engages the GFOGER collagen motif through three surface loops, with a collagen glutamate completing metal coordination; ligand binding induces conformational changes that propagate to the domain's opposite pole, coupling adhesion to outside-in signaling (PMID:7523399, PMID:9353312, PMID:10778855). Collagen engagement of α2β1 activates constitutively associated Src/Lyn kinases, leading to Syk, PLCγ2, and FAK phosphorylation that drive platelet spreading, and in epithelial and cancer cells signals through FAK/AKT, RhoA/p38 MAPK, STAT3, and ERK1/2 to promote proliferation, EMT, migration, and chemoresistance (PMID:11038351, PMID:12615912, PMID:31818309, PMID:34113124). ITGA2 expression is transcriptionally regulated by BACH1, HOXD3, TEAD1, and EZH2, is induced by VEGF on endothelial cells to support angiogenesis and lymphangiogenesis, and nuclear ITGA2 additionally inhibits NHEJ DNA repair by blocking DNA-PKcs recruitment to the Ku70/80 heterodimer (PMID:37311571, PMID:9391074, PMID:15132990, PMID:35998796).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 High

    Cloning and antibody-blocking experiments established that VLA-2 (α2β1) is a collagen receptor on platelets and that the α2 subunit harbors a unique ~191-residue I-domain homologous to vWF A-domains, identifying the likely collagen-binding module.

    Evidence cDNA cloning/sequencing of α2 subunit and monoclonal antibody 6F1 blocking of platelet–collagen adhesion

    PMID:2545729 PMID:2546619

    Open questions at the time
    • I-domain collagen-binding function was inferred by homology, not yet demonstrated directly
    • β1 subunit contribution to ligand binding was unknown
  2. 1994 High

    Chimeric constructs, mutagenesis, and recombinant I-domain binding assays demonstrated that the I-domain alone is necessary and sufficient for collagen recognition, mapping critical residues (Asp-151, Asp-254, Thr-221) and showing α2β1 binds all collagen types I–VIII.

    Evidence Human/bovine α2 chimeras, site-directed mutagenesis, recombinant I-domain collagen-binding assay, systematic antibody blocking across 8 collagen types

    PMID:7511592 PMID:7523399 PMID:8118028

    Open questions at the time
    • Atomic-resolution structure of I-domain not yet available
    • Role of divalent cations in binding was debated
  3. 1997 High

    The crystal structure of the free I-domain revealed a Rossmann fold with a MIDAS motif coordinating Mg²⁺, resolving how divalent cations participate in collagen recognition and predicting a collagen glutamate would complete metal coordination.

    Evidence X-ray crystallography of the α2 I-domain; recombinant I-domain competition of platelet adhesion

    PMID:9184414 PMID:9353312

    Open questions at the time
    • Ligand-bound structure not yet solved
    • Conformational changes upon collagen binding uncharacterized
  4. 2000 High

    The co-crystal structure of the I-domain with a triple-helical GFOGER collagen peptide proved that collagen glutamate completes MIDAS coordination and showed that ligand binding propagates conformational changes to the opposite pole, providing a structural basis for affinity regulation and outside-in signaling.

    Evidence X-ray crystallography of I-domain–collagen peptide complex

    PMID:10778855

    Open questions at the time
    • Mechanism coupling C-terminal conformational shift to β1 subunit activation undetermined
    • Full ectodomain structure with β1 unavailable
  5. 2001 High

    Identification of the outside-in signaling cascade downstream of α2β1 engagement—constitutive Src/Lyn association, Syk and PLCγ2 phosphorylation, FAK activation, and intracellular Ca²⁺ mobilization—established the receptor as an autonomous signaling entity independent of GPVI.

    Evidence Rhodocytin-stimulated liposome-reconstituted α2β1 kinase assays; collagen peptide-stimulated platelet spreading with PLCγ2-KO platelets and PP2 inhibitor

    PMID:11038351 PMID:12615912

    Open questions at the time
    • Adaptor proteins linking Src/Syk to downstream effectors incompletely defined
    • Role of cytoplasmic tail phosphorylation unclear
  6. 1997 High

    VEGF was shown to transcriptionally upregulate α2β1 on endothelial cells, and functional blocking of α2 integrin inhibited VEGF-driven angiogenesis by ~90% in vivo, placing α2β1–collagen interaction as a required step in neovascularization.

    Evidence Flow cytometry, mRNA induction, anti-α2 blocking antibody in vivo angiogenesis assay; extended to lymphangiogenesis in a subsequent study

    PMID:15132990 PMID:9391074

    Open questions at the time
    • Specific intracellular signals linking VEGF-induced α2β1 to endothelial tube formation not fully mapped
  7. 2008 High

    Cooperative signaling through α2β1 (via FAK/p130CAS) and DDR1 (via Pyk2) converging on Rap1 was shown to upregulate N-cadherin in pancreatic cancer, providing a mechanistic link between collagen sensing by α2β1 and EMT.

    Evidence siRNA knockdown of α2β1 and DDR1, signaling pathway inhibitors, in vivo tumor model

    PMID:18362184

    Open questions at the time
    • Rap1 activation mechanism downstream of FAK/p130CAS incompletely characterized
    • Generalizability to other epithelia unconfirmed
  8. 2014 Medium

    Transcriptional and epigenetic regulation of ITGA2 was elaborated: EZH2 directly represses the locus, PARP-1/Ku80 bind CA-repeat promoter elements to enhance transcription, and promoter CpG methylation status controls expression in prostate cancer, establishing ITGA2 as an epigenetically regulated gene.

    Evidence ChIP for EZH2, DNA affinity chromatography for PARP-1/Ku80, bisulfite sequencing in prostate cancer cells, pharmacological inhibition of EZH2

    PMID:20090957 PMID:25549357 PMID:25662931

    Open questions at the time
    • Relative contribution of each epigenetic regulator in different lineages unclear
    • Whether EZH2-mediated repression is H3K27me3-dependent was not confirmed by histone mark ChIP
  9. 2019 Medium

    ITGA2 was found to interact with STAT3, promote its phosphorylation, and thereby transcriptionally upregulate PD-L1, revealing a non-canonical signaling output linking α2β1 to immune evasion.

    Evidence Co-immunoprecipitation (ITGA2–STAT3), RNA-seq, ITGA2 knockdown/overexpression in cancer cells

    PMID:31818309

    Open questions at the time
    • Reciprocal co-IP or proximity ligation not reported
    • Whether STAT3 interaction is direct or bridged by FAK/Src unknown
    • Functional impact on anti-tumor immunity not tested in vivo
  10. 2022 Medium

    Nuclear ITGA2 was shown to inhibit NHEJ DNA repair by blocking DNA-PKcs recruitment to the Ku70/80 heterodimer, linking integrin expression to genome instability and radiation sensitivity in pancreatic cancer.

    Evidence DNA-PKcs/Ku70/Ku80 recruitment assay, NHEJ functional assay, ITGA2 nuclear localization analysis, radiation sensitivity assay

    PMID:35998796

    Open questions at the time
    • Mechanism of ITGA2 nuclear translocation undefined
    • Structural basis of ITGA2–Ku70/80 interaction unknown
    • Not independently replicated
  11. 2023 Medium

    BACH1 and HOXD3 were identified as direct transcriptional activators of ITGA2 by ChIP and reporter assays, with BACH1–ITGA2 signaling through FAK-RAC1-PAK and HOXD3–ITGA2 through ERK1/2, connecting upstream transcription factor programs to α2β1-dependent invasion.

    Evidence ChIP-PCR, dual-luciferase reporter, knockdown/overexpression of BACH1/HOXD3, downstream pathway Western blots

    PMID:32557953 PMID:37311571

    Open questions at the time
    • Whether BACH1 and HOXD3 co-operate or act in distinct contexts is unknown
    • Genomic occupancy validated at single locus only
  12. 2024 Medium

    CRISPR deletion of ITGA2 (with ITGA1) in benign prostate epithelium activated TGFβ1 autocrine signaling and nuclear YAP1, converting cells to a tumorigenic phenotype, while TEAD1 was identified as a transcriptional regulator whose loss phenocopies integrin deletion.

    Evidence CRISPR genomic deletion, TGFβ1 neutralization, YAP1 localization, in vivo tumorigenesis assay, TEAD1 knockdown

    PMID:38169150

    Open questions at the time
    • Individual contribution of ITGA2 versus ITGA1 loss not separable in the dual-knockout design
    • Whether TEAD1 directly binds the ITGA2 promoter was not shown by ChIP

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the mechanism of ITGA2 nuclear translocation, the structural basis of α2β1 full-ectodomain interaction with β1, how the I-domain conformational switch is coupled to cytoplasmic signaling, and whether the ITGA2–STAT3 interaction is direct.
  • No full-length α2β1 structure available
  • Nuclear import pathway of ITGA2 uncharacterized
  • STAT3 interaction awaits reciprocal validation and proximity labeling

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 1 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-109582 Hemostasis 4 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-73894 DNA Repair 1
Partners
ITGB1LYNPLCG2PTK2RAB21SRCSTAT3SYK
Complex memberships
integrin α2β1

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The ITGA2 (VLA-2 alpha2 subunit) primary structure was determined from cDNA cloning, revealing a 1,181 amino acid protein with a 191-amino acid inserted I-domain (not found in other integrin alpha chains at the time) homologous to von Willebrand factor A-domains and cartilage matrix protein, suggesting the I-domain as a collagen-binding domain. The protein contains three metal-binding domains and a transmembrane segment with a short 22-amino acid cytoplasmic tail. cDNA library screening, nucleotide sequencing, protein NH2-terminal sequencing The Journal of cell biology High 2545729
1989 GPIa/IIa (integrin alpha2beta1) mediates direct platelet adhesion to collagen independently of plasma adhesive proteins, demonstrated by a blocking monoclonal antibody (6F1) that inhibited collagen-induced platelet aggregation and platelet adhesion to collagen by >95% in the absence of plasma proteins. GPIIb/IIIa mediates indirect collagen interaction via adhesive protein intermediaries. Monoclonal antibody blocking assay, collagen-coated bead agglutination, platelet adhesion assay Blood High 2546619
1994 Integrin alpha2beta1 is a universal platelet collagen receptor mediating adhesion to collagen types I through VIII under both static and flow conditions, as demonstrated by complete inhibition of platelet adhesion to all collagen types by anti-GPIa monoclonal antibody 176D7. Platelet adhesion assay under static and flow conditions with monoclonal antibody blocking Blood High 8118028
1994 The I-domain of ITGA2 (residues 140-359) contains the ligand-binding site for both collagen and echovirus 1. Function-blocking antibodies map to residues 173-259 within the I-domain. Mutations of Asp-151 and Asp-254 block collagen binding, and Asp-160 and Arg-242 are critical for other function-inhibiting antibody epitopes, indicating that collagen and echovirus 1 binding sites are adjacent or overlapping within the I-domain. Interspecies (human/bovine) alpha2 chimeras, site-directed mutagenesis, antibody epitope mapping The Journal of biological chemistry High 7511592
1994 The recombinant I-domain of ITGA2 alone is sufficient for collagen binding in a divalent cation-independent manner, demonstrating the I-domain contains all components necessary for collagen recognition. Thr-221 within the I-domain is critical for collagen binding to both full-length alpha2beta1 and the isolated I-domain fragment; divalent cations regulate binding rather than directly participate in collagen contact. Recombinant I-domain protein binding assay, site-directed mutagenesis (T221 substitution), divalent cation chelation experiments The Journal of biological chemistry High 7523399
1997 The recombinant alpha2 I-domain (residues 145-334) fused to maltose-binding protein binds immobilized collagen type I in a Mg2+-dependent, Ca2+/EDTA-inhibitable manner, and competitively inhibits platelet adhesion to collagen and collagen-induced platelet aggregation (IC50 ~0.7 μM), confirming the I-domain as the collagen-binding site of alpha2beta1. Recombinant protein expression, ELISA-based binding assay, platelet adhesion inhibition, platelet aggregation inhibition Thrombosis and haemostasis High 9184414
1997 Crystal structure of the ITGA2 I-domain determined at high resolution reveals a dinucleotide-binding (Rossmann) fold with a metal ion-dependent adhesion site (MIDAS) motif coordinating Mg2+ at the top of the beta-sheet. A unique C-helix creates a groove around the Mg2+ ion predicted to be the collagen-binding site; modeling suggests a glutamate from collagen coordinates the metal. The echovirus-1 binding site maps to a distinct surface (one edge of the beta-sheet), indicating collagen and virus bind by different mechanisms. X-ray crystallography (high resolution crystal structure) The Journal of biological chemistry High 9353312
2000 Crystal structure of the ITGA2 I-domain in complex with a triple-helical collagen peptide containing the GFOGER motif revealed that three loops on the upper surface of the I-domain coordinate a metal ion and simultaneously engage the collagen triple helix, with a collagen glutamate completing the metal ion coordination sphere. Ligand binding induces conformational changes that propagate from the upper surface to the opposite pole of the domain, providing a structural basis for affinity regulation and signal transduction. X-ray crystallography of I-domain/collagen peptide complex Cell High 10778855
2001 Rhodocytin from snake venom directly binds GPIa/IIa (integrin alpha2beta1) independently of divalent cations, inducing platelet aggregation. Src and Lyn kinases constitutively associate with GPIa/IIa and Src activity increases transiently after rhodocytin stimulation; Src then mediates phosphorylation of p130 Cas. Downstream signals including Syk phosphorylation, PLCgamma2 phosphorylation, and intracellular Ca2+ mobilization are cAMP-sensitive and require actin polymerization/receptor clustering. Rhodocytin-coupled bead binding assay, liposome reconstitution with recombinant GPIa/IIa, in vitro kinase assay, Western blotting of immunoprecipitates, cytochalasin D inhibition The Journal of biological chemistry High 11038351
2003 EMS16, a C-type lectin-like protein from Echis multisquamatus venom, acts as a potent and selective antagonist of integrin alpha2beta1 (GPIa/IIa). Crystal structure at 1.9 Å resolution revealed a heterodimer with domain-swapped central loop architecture and a unique positively-charged electrostatic patch on its concave surface proposed as the interaction site for the ITGA2 I-domain. X-ray crystallography at 1.9 Å resolution, structural analysis of protein-receptor antagonist Biochemistry High 14580195
2003 Integrin alpha2beta1 mediates outside-in signaling during platelet spreading on collagen, activating Src kinases, Syk, SLP-76, PLCgamma2, focal adhesion kinase, and plasma membrane calcium ATPase, leading to filopodia and lamellipodia formation. This signaling is independent of the GPVI-FcR gamma-chain complex, requires intracellular Ca2+, and is abolished by the Src kinase inhibitor PP2 and in PLCgamma2-deficient platelets. Integrin-specific collagen peptide stimulation, tyrosine phosphorylation Western blot, PLCgamma2-deficient platelets, PP2 inhibitor, intracellular Ca2+ chelation, morphological spreading assay The Journal of cell biology High 12615912
1993 GPIa/IIa (integrin alpha2beta1) binds thrombospondin (TSP) in an ion-independent manner with a dissociation constant of 0.69 μM, which is 5.5-fold more favorable than GPIIb/IIIa binding to TSP. This interaction is blocked by anti-GPIa/IIa antibody 6F1 but not by anti-GPIIb/IIIa antibody, suggesting GPIa/IIa is a preferred TSP binding protein on platelets. Saturable binding assay with purified glycoproteins, competition inhibition with antibodies and unlabeled protein The Biochemical journal Medium 8240284
1997 VEGF induces 5-7 fold increased surface expression of integrin alpha2beta1 (and alpha1beta1) on dermal microvascular endothelial cells through induction of alpha2 subunit mRNA. Blocking antibodies against alpha2 integrin partially inhibited EC attachment to collagen I and abolished VEGF-promoted cell spreading on collagen I gels. In vivo, anti-alpha2 antibody combination markedly inhibited VEGF-driven angiogenesis, reducing new vessel cross-sectional area by 90%. Flow cytometry, mRNA induction assay, blocking antibody cell adhesion/spreading assay, in vivo VEGF-driven angiogenesis model Proceedings of the National Academy of Sciences of the United States of America High 9391074
2004 Endorepellin (COOH-terminal domain of perlecan) binds integrin alpha2beta1 on endothelial cells and triggers a signaling cascade including increased cAMP, activation of PKA and FAK, transient activation of p38 MAPK and HSP27 followed by their rapid downregulation, leading to disassembly of actin stress fibers and focal adhesions, and blocking endothelial cell migration and angiogenesis. Ligand binding, cAMP measurement, kinase activity assays, Western blotting of p38/HSP27, actin/focal adhesion immunofluorescence, cell migration assay The Journal of cell biology High 15240572
2004 VEGF-A promotes lymphangiogenesis via induction of alpha1 and alpha2 integrin expression on lymphatic endothelial cells. Anti-alpha2 integrin blocking antibodies suppressed VEGF-A-induced lymphatic endothelial cord formation and haptotactic migration toward collagen I in vitro, and systemic blockade of alpha2 integrin inhibited VEGF-A-driven lymphangiogenesis in vivo. Integrin expression profiling, blocking antibody tube formation assay, haptotaxis assay, in vivo lymphangiogenesis model FASEB journal High 15132990
2006 Rab21 small GTPase associates with the cytoplasmic domains of alpha-integrin chains including alpha2, regulating endosomal trafficking of beta1-integrins. Knockdown of Rab21 impairs integrin-mediated cell adhesion and motility, while overexpression stimulates migration and cancer cell adhesion to collagen; a point mutation in the alpha-integrin cytoplasmic domain that abolishes Rab21 association prevents Rab21-induced adhesion. Co-immunoprecipitation, siRNA knockdown, overexpression, point mutagenesis of cytoplasmic domain, cell adhesion and motility assays The Journal of cell biology High 16754960
2007 The ITGA2 gene locus on chromosome 5q11.2 is regulated by epigenetic mechanisms distinct from the neighboring ITGA1. During thrombopoietin-induced megakaryocyte differentiation, ITGA1 undergoes rapid progressive CpG methylation but ITGA2 does not, establishing that ITGA2 expression is maintained in the megakaryocyte lineage through a methylation-independent mechanism. In vitro methylation of ITGA1 promoter suppresses its transcription. Sodium bisulfite genomic sequencing, promoter-luciferase reporter assays, 5-aza-2'-deoxycytidine treatment, primary cord blood megakaryocyte differentiation Biochimica et biophysica acta Medium 17669516
2008 Collagen I signaling through integrin alpha2beta1 and discoidin domain receptor 1 (DDR1) cooperatively up-regulates N-cadherin in pancreatic cancer cells, promoting EMT. Alpha2beta1 integrin propagates signals through FAK and the p130CAS scaffold, while DDR1 acts through Pyk2/p130CAS; both pathways converge and require Rap1 (but not Rho GTPases) for N-cadherin upregulation. Knockdown of alpha2beta1 prevents collagen I-induced N-cadherin upregulation. siRNA knockdown of alpha2beta1 and DDR1, signaling pathway inhibitors, Western blotting, in vivo mouse tumor model The Journal of cell biology High 18362184
2010 PARP-1 and Ku80/70 bind specifically and with enhanced affinity to longer (CA)12 repeat alleles in the 5'-regulatory region of ITGA2 (beginning at -605), as demonstrated by DNA affinity chromatography and chromatin immunoprecipitation. This enhanced binding correlates with increased ITGA2 transcriptional activity, identifying PARP-1 and Ku80/70 as transcriptional co-regulators of ITGA2 expression. DNA affinity chromatography, chromatin immunoprecipitation (ChIP), promoter-reporter assays with different CA repeat length alleles PloS one Medium 20090957
2011 Alpha2-integrin (ITGA2) expression is upregulated on stiffer extracellular matrices during osteogenic induction of mesenchymal stem cells, and siRNA knockdown of alpha2-integrin downregulates osteogenic differentiation markers through ROCK, FAK, and ERK1/2 signaling pathways, placing alpha2-integrin upstream of ROCK/FAK/ERK1/2 mechanotransduction during osteogenesis. siRNA knockdown, polyacrylamide hydrogel stiffness system, Western blot of ROCK/FAK/ERK1/2 activity, osteogenic differentiation markers Journal of bone and mineral research Medium 20939067
2014 EZH2 epigenetically represses ITGA2 expression, and when EZH2 is inhibited (genetically or pharmacologically with DZNep or GSK343), de-repressed ITGA2 signaling increases cofilin phosphorylation at Serine 3 (inactivating cofilin), thereby reducing actin remodeling and cell migration in colorectal cancer cells. ChIP confirmed EZH2 directly regulates the ITGA2 locus. EZH2 siRNA knockdown, pharmacological inhibition (DZNep, GSK343), chromatin immunoprecipitation (ChIP), cofilin phosphorylation Western blot, cell migration assay PloS one Medium 25549357
2015 ITGA2 expression is regulated by CpG methylation of its promoter in prostate cancer cells. Demethylated ITGA2 promoter correlates with higher ITGA2 expression and increased cell migratory potential. siRNA knockdown of ITGA2 in highly migratory PC3 and 22Rv1 cells reduced migration in scratch assays, confirming ITGA2 promotes cell migration in prostate cancer. Bisulfite sequencing of ITGA2 promoter CpG island, qPCR, siRNA knockdown, scratch wound healing assay The Prostate Medium 25662931
2015 Human Th17 cells co-express IL-7R and integrin alpha2beta1 (CD49b); IL-7 increases Th17 adhesion to collagen via alpha2beta1. Co-engagement of IL-7R and alpha2beta1 cooperatively enhances IL-17 production and osteoclastogenic activity through JAK/PI3K/AKT and MAPK/ERK pathways. In vivo blockade of alpha2beta1 with neutralizing mAb inhibited IL-7-induced bone loss by reducing Th17 cell numbers and IL-17/RANKL production. Integrin blocking antibody, co-engagement of receptors, cytokine production ELISA, in vivo bone loss model with antibody blockade, pathway inhibitor studies Journal of immunology Medium 26408663
2019 ITGA2 interacts with STAT3 (demonstrated by co-immunoprecipitation) and up-regulates STAT3 phosphorylation, which transcriptionally increases PD-L1 expression in cancer cells. Knockdown of ITGA2 inhibited cancer cell proliferation and invasion, while ITGA2 overexpression promoted these processes. RNA-seq confirmed ITGA2 transcriptionally regulates PD-L1. Co-immunoprecipitation (ITGA2-STAT3 interaction), Western blot (STAT3 phosphorylation), RNA-seq, RT-qPCR, functional assays (MTS, colony formation, transwell) Journal of experimental & clinical cancer research Medium 31818309
2018 Blockade of ITGA2 with a specific antibody induces apoptosis in gastric cancer cells by upregulating RhoA-p38 MAPK signaling to promote Bim, Apaf-1 and Caspase-9 expression (without affecting Ras or Bax/Bcl-2). ITGA2 blockade also inhibits cell migration by downregulating N-WASP, PAK, and LIMK to impede actin organization. Anti-ITGA2 antibody treatment, apoptosis assay, Western blot for RhoA/p38/Bim/Apaf-1/Caspase-9/N-WASP/PAK/LIMK, cell migration assay Biological procedures online Medium 29743821
2020 Exosomal ITGA2 derived from castration-resistant prostate cancer cells can be transferred to androgen receptor-positive recipient cells, promoting proliferation, migration, invasion and epithelial-mesenchymal transition. These effects were reversed by ITGA2 knockdown in donor cells or inhibition of exosomal uptake by methyl-β-cyclodextrin, and reproduced by ectopic ITGA2 overexpression in recipient cells. Exosome co-incubation, ITGA2 knockdown, ectopic overexpression, methyl-β-cyclodextrin inhibition, EMT marker Western blot, cell migration/invasion assays Cancers Medium 32824235
2020 ITGA2 overexpression in ovarian cancer promotes cell proliferation and mediates paclitaxel resistance by activating AKT phosphorylation, which in turn phosphorylates FoxO1, preventing FoxO1-mediated transcription of pro-apoptotic genes. ITGA2 overexpression/knockdown, Western blot for AKT and FoxO1 phosphorylation, paclitaxel sensitivity assay, cell proliferation assay Aging Medium 32202508
2021 Cyclic mechanical stretch promotes nucleus pulposus cell proliferation and inhibits apoptosis via the ITGA2/PI3K/AKT signaling pathway. Gene expression profiling identified 31 differentially expressed genes in this pathway after stretch; siRNA knockdown of ITGA2 and AKT confirmed that the PI3K/AKT pathway mediates stretch-induced COL2A1 expression and cell proliferation. Cyclic tensile stress system, gene expression microarray, siRNA knockdown of ITGA2 and AKT, Western blot, cell proliferation and apoptosis assays Oxidative medicine and cellular longevity Medium 33815660
2021 ITGA2 overexpression in esophageal squamous cell carcinoma activates FAK/AKT signaling and promotes EMT. ITGA2 silencing inhibits FAK/AKT phosphorylation and suppresses EMT markers, while ITGA2 overexpression activates this pathway. Treatment with AKT inhibitor MK-2206 repressed ITGA2-overexpression-driven ESCC progression, establishing FAK/AKT as the downstream pathway. ITGA2 knockdown/overexpression, Western blot for FAK/AKT/EMT markers, AKT inhibitor MK-2206, tumor xenograft model OncoTargets and therapy Medium 34113124
2022 ITGA2 inhibits the non-homologous end joining (NHEJ) DNA repair pathway by restraining the recruitment of DNA-PKcs to the Ku70/80 heterodimer during the DNA damage response, conferring sensitivity to radiotherapy in pancreatic cancer. Nuclear ITGA2 overexpression correlates with genome instability parameters in TCGA data. DNA-PKcs/Ku70/Ku80 recruitment assay, NHEJ activity assay, ITGA2 nuclear localization analysis, TCGA correlation analysis, radiation sensitivity assay Cancer letters Medium 35998796
2022 Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma cells. Depletion of ITGA2 or treatment with an integrin alpha2beta1-selective inhibitor abolished robust interaction of iCCA cells with collagen type I and blocked collagen type I-induced colony growth enhancement (3-6 fold), confirming a functional collagen type I-integrin alpha2 axis in cholangiocarcinoma. ITGA2 siRNA knockdown, integrin alpha2beta1-selective inhibitor, collagen binding assay, clonogenic growth assay Scientific reports Medium 36575207
2023 BACH1 directly binds to the upstream sequence of the ITGA2 promoter to transcriptionally activate ITGA2 expression. The BACH1-ITGA2 axis promotes lung adenocarcinoma cell migration and invasion through activation of the FAK-RAC1-PAK signaling pathway and cytoskeletal regulation, as demonstrated by ChIP and dual-luciferase reporter assays. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, BACH1/ITGA2 knockdown/overexpression, RNA-seq, FAK-RAC1-PAK pathway Western blot, cell adhesion and migration assays Cancer science Medium 37311571
2024 Genomic deletion or loss of ITGA2 (together with ITGA1) in benign prostate epithelial cells activates TGFβ1 autocrine signaling and nuclear YAP1 targeting, inducing EMT and converting cells to a tumorigenic phenotype in vivo. TEAD1 was identified as a key transcriptional regulator of both ITGA1 and ITGA2 expression; TEAD1 loss phenocopies dual alpha1/alpha2 integrin loss, triggering TGFβ1-driven EMT. CRISPR genomic deletion of ITGA1/ITGA2, TGFβ1 neutralization, YAP1 nuclear localization assay, genome-wide co-expression analysis, in vivo tumorigenesis assay, TEAD1 knockdown Advanced science Medium 38169150
2024 In 3D bioprinted glioma models, ITGA2 expression is significantly elevated compared to 2D models and mediates radiation tolerance through the p-AKT signaling pathway. shRNA-mediated knockdown of ITGA2 reduced radiation tolerance and concomitantly inhibited p-AKT pathway activation in 3D glioma models. 3D bioprinted tumor model, shRNA ITGA2 knockdown, radiation treatment, p-AKT Western blot, differential gene expression profiling Advanced healthcare materials Medium 38288911
2020 ITGA2 knockdown in breast cancer cells suppressed self-renewal (mammosphere formation), pluripotency marker expression, inhibited cell cycling (G1 arrest), compromised migration/invasion, and decreased lung metastasis. ITGA2 overexpression reversed miR-206-caused G1 cell cycle arrest. RNA sequencing revealed ITGA2 regulates CCND1 (cyclin D1) and ACLY (ATP citrate lyase), with CCND1 being required downstream for cell cycle progression and lung colonization. ITGA2 knockdown/overexpression, mammosphere formation assay, cell cycle analysis, RNA sequencing, CCND1/ACLY knockdown rescue experiments, in vivo lung metastasis model Genes & diseases Medium 34179312
2021 ITGA2 overexpression in rheumatoid arthritis PBMCs promotes T cell proliferation, inhibits apoptosis, and induces expression of IL-8, IFN-γ, and TNF-α in Jurkat T cells, demonstrating a functional role for ITGA2 in T cell activation and pro-inflammatory cytokine production. ITGA2 overexpression in Jurkat T cells, cell proliferation assay, apoptosis analysis, cytokine (IL-8, IFN-γ, TNF-α) measurement by ELISA Clinica chimica acta Low 34599900
2010 In the pregnant rat cervix, ITGA2 expression increases progressively over gestation. Mifepristone (progesterone receptor antagonist) increases ITGA2 expression and activates ERK1/2 phosphorylation both in vivo and in primary cervical stromal cells in vitro; inhibition of ERK1/2 abrogated mifepristone-induced ITGA2 upregulation, placing ERK1/2 downstream of progesterone withdrawal in ITGA2 regulation. Rat gestational model, mifepristone treatment, primary cervical stromal cell culture, Western blot for ITGA2/pERK1/2/pFAK, ERK1/2 inhibitor rescue Reproductive sciences Low 20959644
2020 TSPAN1 transcriptionally regulates ITGA2 expression in pancreatic cancer, and epigenetically controls ITGA2 by modulating TET2, DNMT3B, and DNMT1, resulting in hypomethylation of the ITGA2 promoter CpG island. ITGA2 knockdown abolished TSPAN1 overexpression-driven pancreatic cancer cell proliferation and invasion. RNA-seq after TSPAN1 manipulation, DNMT/TET2 expression analysis, CpG methylation analysis, ITGA2 siRNA rescue experiments American journal of cancer research Low 32368389
2020 HOXD3, whose expression is regulated by YY1 recruiting HDAC1, promotes HCC progression by binding the ITGA2 promoter and upregulating ITGA2 expression, thereby activating ERK1/2 signaling to drive proliferation, metastasis, and migration. ChIP-PCR confirmed HOXD3 binding to the ITGA2 promoter; dual luciferase reporter assays confirmed transcriptional activation. ChIP-PCR, dual luciferase reporter assay, HOXD3/ITGA2 knockdown/overexpression, Co-IP (YY1-HDAC1), ERK1/2 Western blot Cell proliferation Medium 32557953
2025 A novel enhancer-associated lncRNA (LncRNA-ITGA2) located at the ITGA2 locus promotes VSMC proliferation and migration by upregulating ITGA2 expression. Mechanistically, LncRNA-ITGA2 binds the ITGA2 enhancer region, increases H3K27 acetylation at both the ITGA2 enhancer and promoter, and interacts with DNA-binding protein NONO which also binds the ITGA2 promoter, thereby mediating enhancer-promoter looping interactions. CRISPR-Cas9 knockout of NONO or LncRNA-ITGA2 validated this regulatory mechanism. CUT&Tag, promoter-capture Hi-C, RNA-seq, CRISPR-Cas9 knockout, ChIP-seq, CHIRP, RIP, H3K27ac ChIP, carotid artery wire injury in vivo model Circulation research Medium 40321134

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Integrins. Cell and tissue research 1256 19693543
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 Structural basis of collagen recognition by integrin alpha2beta1. Cell 819 10778855
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2013 Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nature medicine 642 23624599
1987 The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. The Journal of biological chemistry 519 3546305
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
1985 Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 421 2933589
1997 Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins. Proceedings of the National Academy of Sciences of the United States of America 417 9391074
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1999 The hookworm platelet inhibitor: functional blockade of integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa (alpha2beta1) inhibits platelet aggregation and adhesion in vitro. The Journal of infectious diseases 40 10191228
2020 Overexpressed ITGA2 contributes to paclitaxel resistance by ovarian cancer cells through the activation of the AKT/FoxO1 pathway. Aging 39 32202508
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2016 Therapeutic reversal of food allergen sensitivity by mature retinoic acid-differentiated dendritic cell induction of LAG3+CD49b-Foxp3- regulatory T cells. The Journal of allergy and clinical immunology 37 28277274
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2002 Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men. European heart journal 36 11812069
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2020 HOXD3 was negatively regulated by YY1 recruiting HDAC1 to suppress progression of hepatocellular carcinoma cells via ITGA2 pathway. Cell proliferation 28 32557953
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2021 Cyclic Mechanical Stretch Ameliorates the Degeneration of Nucleus Pulposus Cells through Promoting the ITGA2/PI3K/AKT Signaling Pathway. Oxidative medicine and cellular longevity 26 33815660
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2015 Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss. Journal of immunology (Baltimore, Md. : 1950) 25 26408663
2019 CD49b, CD87, and CD95 Are Markers for Activated Cancer-Associated Fibroblasts Whereas CD39 Marks Quiescent Normal Fibroblasts in Murine Tumor Models. Frontiers in oncology 24 31428583
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2010 Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population. Journal of human genetics 20 20485444
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2024 Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 38169150
2021 Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis. Oncology letters 15 34055094
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2021 ITGA2 protein is associated with rheumatoid arthritis in Chinese and affects cellular function of T cells. Clinica chimica acta; international journal of clinical chemistry 10 34599900
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