Affinage

ITGA2

Integrin alpha-2 · UniProt P17301

Length
1181 aa
Mass
129.3 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGA2 encodes the alpha2 subunit of integrin alpha2beta1 (GPIa/IIa, VLA-2, CD49b), a heterodimeric cell-surface receptor whose principal function is direct, high-affinity binding to collagen and related matrix ligands to mediate cell adhesion, signaling, and motility (PMID:2545729, PMID:2546619, PMID:8118028). The collagen-binding activity resides in a unique 191-residue I-domain insert (~residues 140–359) homologous to von Willebrand factor A domains; the recombinant I-domain alone is sufficient for collagen binding, with Asp-151, Asp-254 and Thr-221 critical for ligand contact, and this isolated-domain binding is divalent-cation-independent in contrast to the Mg2+-dependence of the intact receptor (PMID:2545729, PMID:7511592, PMID:7523399, PMID:9184414). On platelets, alpha2beta1 is the major universal receptor for collagen types I–VIII under both static and flow conditions and additionally binds thrombospondin at a distinct, ion-independent site (PMID:2546619, PMID:8118028, PMID:8240284). Ligand engagement triggers outside-in signaling through a constitutively associated Src/Lyn module, leading to Cas, Syk and PLCgamma2 phosphorylation and Ca2+ mobilization, as revealed by the snake-venom agonist rhodocytin (PMID:11038351). Beyond platelets, ITGA2 drives leukocyte trafficking and inflammatory function—homing of memory CD4 T-cell precursors to bone marrow and IL-7-cooperative Th17 osteoclastogenesis—and in epithelial and cancer cells it controls adhesion, migration, invasion, EMT and stemness through FAK/AKT, RhoA-p38 MAPK, STAT3–PD-L1 and PI3K/AKT signaling (PMID:23897120, PMID:26408663, PMID:31818309, PMID:29743821, PMID:34113124, PMID:34179312). A non-canonical nuclear pool of ITGA2 inhibits non-homologous end-joining by restraining DNA-PKcs recruitment to the Ku70/80 heterodimer, sensitizing cells to radiotherapy (PMID:35998796). ITGA2 expression is set by transcriptional regulators including TEAD1, BACH1, and PARP-1/Ku80 binding to a CA-repeat promoter element, by enhancer chromatin looping, and by epigenetic CpG methylation and EZH2-mediated repression (PMID:17669516, PMID:20090957, PMID:25549357, PMID:25662931, PMID:37311571, PMID:38169150, PMID:40321134). Coding polymorphisms define the HPA-5 platelet alloantigen system (Glu505Lys) and the C807T variant that scales receptor surface density (PMID:7913826, PMID:10468872).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Establishing the primary structure of the alpha2 subunit revealed a unique I-domain insert not present in other integrin alpha chains, immediately implicating a dedicated ligand-binding module.

    Evidence cDNA cloning with direct N-terminal protein sequencing and domain analysis

    PMID:2545729

    Open questions at the time
    • Sequence alone did not prove which residues contact collagen
    • No structural model of the I-domain at this stage
  2. 1989 High

    It was unknown whether GPIa/IIa was a true functional collagen receptor; antibody blockade showed it directly mediates platelet adhesion and aggregation on collagen independently of plasma proteins.

    Evidence Monoclonal antibody (6F1) inhibition of platelet adhesion/aggregation and collagen-bead agglutination

    PMID:2546619

    Open questions at the time
    • Did not localize the binding site within the subunit
    • Did not address signaling downstream of adhesion
  3. 1994 High

    The collagen-binding site was localized to the I-domain and specific residues, defining the molecular determinants of ligand recognition and showing the recombinant I-domain alone suffices for cation-independent collagen binding.

    Evidence Interspecies chimeras, site-directed mutagenesis (Asp-151, Asp-254, Thr-221), recombinant I-domain binding and antibody epitope mapping

    PMID:7511592 PMID:7523399

    Open questions at the time
    • Reconciling cation-independence of isolated I-domain with cation-dependence of intact receptor
    • No co-crystal with collagen
  4. 1994 High

    The receptor's ligand breadth and physiological relevance were defined: it is a universal platelet collagen receptor across types I–VIII under static and flow conditions.

    Evidence Platelet adhesion assays across eight collagen types under stasis and shear with antibody (176D7) inhibition

    PMID:8118028

    Open questions at the time
    • Did not resolve signaling consequences of engagement
    • Relative contribution versus other platelet collagen receptors not quantified
  5. 1994 High

    Coding polymorphisms were defined molecularly, linking ITGA2 sequence variation to the HPA-5 alloantigen system and laying groundwork for genotype–phenotype studies.

    Evidence RT-PCR/cDNA sequencing and PCR-RFLP genotyping of the bp1648 A→G (Glu505Lys) variant

    PMID:7913826 PMID:7916494

    Open questions at the time
    • Functional consequence of the substitution on collagen binding not established
    • Clinical alloimmunization outcomes not addressed here
  6. 1999 Medium

    It was unclear whether common ITGA2 variants alter receptor abundance; flow cytometry tied the C807T and HPA-5 alleles to platelet surface receptor density.

    Evidence Flow cytometry of platelet GPIa/IIa with PCR genotyping in blood-donor cohorts

    PMID:10220262 PMID:10468872

    Open questions at the time
    • Association studies do not establish the molecular mechanism of altered density
    • Functional adhesion consequences not directly measured
  7. 1993 Medium

    Ligand specificity beyond collagen was probed; alpha2beta1 was shown to bind thrombospondin at a distinct, divalent-cation-independent site.

    Evidence Saturable binding with purified GPIa/IIa, competition and antibody (6F1) inhibition

    PMID:8240284

    Open questions at the time
    • Single biochemical study without cellular validation
    • Physiological role of TSP binding unresolved
  8. 2001 High

    The outside-in signaling machinery was defined: alpha2beta1 constitutively associates with Src/Lyn and, upon agonist (rhodocytin) engagement, transduces a tyrosine-phosphorylation cascade to Syk/PLCgamma2 and Ca2+ flux.

    Evidence Liposome reconstitution of recombinant receptor, immunoprecipitation, in vitro kinase assays and Western blotting

    PMID:11038351

    Open questions at the time
    • Direct kinase–subunit interaction interface not mapped
    • Relevance to physiological collagen signaling versus venom agonist not fully resolved
  9. 2001 High

    The widely used DX5 antibody antigen was identified as CD49b/ITGA2, establishing the subunit as an NK-cell marker and its loss with IL-2-driven proliferation.

    Evidence Retroviral expression cloning with flow cytometry and antibody competition

    PMID:11466327

    Open questions at the time
    • Functional role of CD49b on NK cells not defined here
  10. 2007 Medium

    Transcriptional and epigenetic control of ITGA2 abundance began to be defined, distinguishing CA-repeat/Sp1 promoter regulation and PARP-1/Ku80 binding from ITGA1 methylation.

    Evidence Bisulfite sequencing, promoter-luciferase reporters, demethylation treatment and transcriptome analysis

    PMID:17669516

    Open questions at the time
    • Causality between factor binding and expression only correlative at this stage
    • Single lineage (megakaryocytic) context
  11. 2010 Medium

    The promoter regulatory logic was refined: PARP-1/Ku80 bind the longer (CA)12 allele with enhanced affinity, enabling ranking of ITGA2 haplotypes by transcriptional activity together with the C-52T Sp1 site.

    Evidence DNA affinity chromatography, ChIP and promoter-luciferase reporter assays

    PMID:20090957

    Open questions at the time
    • In vivo relevance of haplotype ranking not established
    • Single experimental system
  12. 2013 Medium

    An in vivo adhesion function for ITGA2 in immunity was established: CD49b is required for memory CD4 T-cell precursor homing to bone marrow, where collagen II-expressing stroma provide ligand.

    Evidence CD49b-deficient mice, antibody blockade, adoptive transfer and confocal imaging

    PMID:23897120

    Open questions at the time
    • Downstream signaling in homing not dissected
    • Single lab
  13. 2014 Medium

    EZH2 was shown to directly repress ITGA2, and de-repression activates ITGA2-dependent cofilin phosphorylation that constrains colorectal cancer migration—linking chromatin regulation to cytoskeletal control.

    Evidence ChIP, EZH2 inhibition (DZNep/GSK343), siRNA and phospho-cofilin/migration assays

    PMID:25549357

    Open questions at the time
    • Direction of migratory effect appears context-dependent
    • Mechanism linking ITGA2 to cofilin not fully resolved
  14. 2015 Medium

    ITGA2 was shown to act as a pro-migratory/pro-stemness driver in epithelial cancers and inflammatory T cells, with promoter CpG methylation controlling its expression and IL-7R co-engagement amplifying its function.

    Evidence Bisulfite sequencing, siRNA, migration assays (prostate) and flow/adhesion/in vivo blockade with pathway inhibition (Th17)

    PMID:25662931 PMID:26408663

    Open questions at the time
    • Context-dependent pro- vs anti-migratory roles unreconciled
    • Direct signaling intermediates not all defined
  15. 2019 Medium

    Specific oncogenic signaling outputs were mapped: ITGA2 interacts with STAT3 to drive PD-L1, and ADAR1 p110 upregulates ITGA2 to enhance ECM adhesion and metastasis.

    Evidence Co-IP, RNA-seq and functional proliferation/invasion assays (pancreatic); lentiviral gain/loss and orthotopic xenografts (HCC)

    PMID:30798327 PMID:31818309

    Open questions at the time
    • Co-IP without reciprocal/structural validation of ITGA2–STAT3 interaction
    • Direct versus indirect effects on PD-L1 not fully separated
  16. 2021 Medium

    ITGA2 was placed upstream of multiple signaling axes (FAK/AKT, RhoA-p38 MAPK, PI3K/AKT) governing invasion, apoptosis and mechanotransduction, with pharmacological rescue confirming pathway directionality.

    Evidence Antibody blockade (gastric), overexpression/knockdown with MK-2206 rescue (ESCC), and mechanical stretch with siRNA (nucleus pulposus)

    PMID:29743821 PMID:33815660 PMID:34113124

    Open questions at the time
    • Tissue-specific differences in downstream wiring not unified
    • Single lab per context
  17. 2022 Medium

    A non-canonical nuclear role was uncovered: nuclear ITGA2 inhibits NHEJ by restraining DNA-PKcs recruitment to Ku70/80, modulating genome stability and radiosensitivity.

    Evidence Nuclear fractionation, NHEJ activity assay, DNA-PKcs/Ku70/80 immunoprecipitation and radiation sensitivity assays

    PMID:35998796

    Open questions at the time
    • Mechanism of ITGA2 nuclear import unknown
    • Single lab; reciprocal validation of the repair interaction limited
  18. 2023 Medium

    Additional upstream transcriptional regulators were defined—BACH1 directly activates ITGA2 to drive FAK-RAC1-PAK migration, and macrophage-conditioned mesothelial cells upregulate ITGA2 via JNK/Akt to promote adhesion.

    Evidence ChIP and dual-luciferase reporter with downstream Western blot (lung); mRNA-seq, siRNA and pathway inhibitors with adhesion assay (ovarian)

    PMID:36766725 PMID:37311571

    Open questions at the time
    • Network of overlapping transcriptional regulators not integrated
    • Single lab per study
  19. 2024 Medium

    TEAD1 was identified as a key transcriptional regulator of ITGA1/ITGA2, and combined loss triggers TGFbeta1/YAP1-driven EMT and tumorigenic conversion, revealing a tumor-suppressive facet of these integrins in benign epithelium.

    Evidence CRISPR-Cas9 deletion, co-expression analysis, EMT markers, TGFbeta1 ELISA and in vivo tumorigenicity

    PMID:38169150

    Open questions at the time
    • Reconciliation of pro-tumor vs tumor-suppressor roles across tissues
    • Redundancy between ITGA1 and ITGA2 not separated
  20. 2025 Medium

    Enhancer-level control of ITGA2 was defined: a NONO-dependent enhancer-associated lncRNA loops the ITGA2 enhancer to its promoter and increases H3K27ac to drive expression and vascular smooth muscle proliferation/migration.

    Evidence CUT&Tag, promoter capture Hi-C, CRISPR knockout, CHIRP/RIP and carotid wire-injury model

    PMID:40321134

    Open questions at the time
    • Generalizability beyond vascular smooth muscle unknown
    • Direct lncRNA–NONO–chromatin contact stoichiometry not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct adhesive, signaling, transcriptional-regulatory, and nuclear DNA-repair-modulating functions of ITGA2 are integrated—and what governs its nuclear versus membrane partitioning across cell types—remains unresolved.
  • No mechanism for ITGA2 nuclear import/trafficking
  • Context-dependent pro- versus anti-tumor activities not unified
  • No high-resolution structure of the intact alpha2beta1–collagen complex in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-109582 Hemostasis 3 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 1
Partners
DNA-PKCSITGB1KU70/80LYNNONOSRCSTAT3
Complex memberships
integrin alpha2beta1 (GPIa/IIa, VLA-2)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 ITGA2 (VLA-2 alpha 2 subunit, GPIa) encodes a 1,181 amino acid protein with a signal peptide, long extracellular domain (1,103 aa), transmembrane domain, and short cytoplasmic segment (22 aa). The sequence contains three metal-binding domains (DXDXDGXXD), 20 cysteine residues, and a unique 191-amino acid I-domain insert (residues ~140-359) not found in other integrin alpha chains at the time, with homology to von Willebrand factor A1/A3 domains and cartilage matrix protein—regions associated with collagen binding. cDNA cloning, direct NH2-terminal protein sequencing, sequence analysis The Journal of cell biology High 2545729
1989 GPIa/IIa (integrin alpha2beta1, ITGA2/ITGB1) directly mediates platelet adhesion to collagen independently of plasma adhesive proteins. Monoclonal antibody 6F1 against GPIa/IIa blocked >95% of collagen-induced platelet adhesion in the absence of plasma and nearly completely inhibited collagen-induced platelet aggregation, establishing GPIa/IIa as a direct collagen receptor. Monoclonal antibody inhibition of platelet adhesion and aggregation assays; 6F1 affinity-purified GPIa/IIa complex; collagen-coated bead agglutination assay Blood High 2546619
1994 The I-domain of ITGA2 (residues 140–359) contains the collagen-binding site of integrin alpha2beta1. Mutations of Asp-151 and Asp-254 block alpha2beta1 binding to collagen, while a small region (residues 173–259) within the I-domain is recognized by function-blocking anti-alpha2 monoclonal antibodies (6F1, RMAC11, 12F1, AA10) that block both collagen and echovirus 1 binding. 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 alpha2 subunit is sufficient for collagen binding, and this binding is divalent cation-independent (unlike full-length integrin binding). Thr-221 within the I-domain is a critical residue for collagen binding to both alpha2beta1 and the isolated I-domain fragment. Recombinant I-domain expression, collagen-binding assay, site-directed mutagenesis (Thr-221), divalent cation chelation experiments The Journal of biological chemistry High 7523399
1994 GPIa/IIa (integrin alpha2beta1) is a major and universal platelet receptor mediating adhesion to collagen types I–VIII under both static conditions and flow. Monoclonal antibody 176D7 against GPIa (ITGA2) completely inhibited platelet adhesion to all collagen types tested under stasis and flow conditions. Platelet adhesion assays to multiple collagen types under static and flow conditions; monoclonal antibody inhibition studies Blood High 8118028
1994 The HPA-5 alloantigen system on GPIa/IIa (ITGA2) is caused by an A→G polymorphism at base pair 1648 of the GPIa coding sequence, resulting in a Glu/Lys substitution at amino acid position 505 of the mature protein (HPA-5a = Glu505; HPA-5b = Lys505). RT-PCR, cDNA sequencing, allele-specific restriction enzyme analysis (Mnl I PCR-ASRA) British journal of haematology High 7913826
1994 The Br (HPA-5) polymorphism of GPIa is encoded by a single base change at position 1648 on platelet GPIa mRNA, causing an amino acid substitution at position 505 of mature GPIa. This polymorphism is located within a 144 bp exon of the GPIa (ITGA2) gene flanked by two introns (~1.7 and ~1.9 kb). PCR of genomic DNA, RFLP analysis with MnlI endonuclease, correlation with serological MAIPA typing Thrombosis and haemostasis High 7916494
1997 The recombinant alpha2 I-domain (residues D145–S334) fused to maltose-binding protein binds immobilized collagen type I in a concentration-dependent and Mg2+-dependent manner (inhibited by EDTA or Ca2+ but sustained in Mg2+), and the I-domain alone can inhibit platelet adhesion to collagen and collagen-induced platelet aggregation (IC50 ~0.7 µM for both), confirming the I-domain as the collagen-binding site of alpha2beta1. Recombinant I-domain expression and purification, ELISA binding assay, platelet adhesion inhibition assay, platelet aggregation inhibition assay Thrombosis and haemostasis High 9184414
1999 The C807T dimorphism (TTC/TTT in codon 224) of the GPIa (ITGA2) cDNA is associated with variation in GPIa/IIa receptor density on the platelet surface, with the 807T allele associated with higher GPIa/IIa surface density. Flow cytometry for platelet GPIa/IIa levels; PCR genotyping of C807T polymorphism British journal of haematology Medium 10468872
1999 Both the 807C/T and HPA-5 polymorphisms of GPIa (ITGA2) independently correlate with GPIa/IIa molecule number on the platelet surface, with 807T and HPA-5b alleles associated with increased receptor density. The two polymorphisms are genetically linked (HPA-5b linked to ~15.8% of 807C alleles). Flow cytometry for platelet GPIa/IIa levels; PCR-RFLP genotyping; 159 blood donors Transfusion Medium 10220262
2001 Rhodocytin from Calloselasma rhodostoma venom directly binds to GPIa/IIa (integrin alpha2beta1, ITGA2) independently of divalent cations, induces platelet aggregation, and activates GPIa/IIa-associated Src and Lyn kinases. Src constitutively associates with GPIa/IIa and its activity transiently increases after rhodocytin stimulation, leading to Cas tyrosine phosphorylation; downstream signals include Syk and PLCγ2 phosphorylation and Ca2+ mobilization. Anti-GPIa mAb blockade, rhodocytin-coupled bead binding assay, liposome-reconstitution with recombinant GPIa/IIa, GPIa immunoprecipitation, in vitro kinase assay, Western blotting, cytochalasin D inhibition The Journal of biological chemistry High 11038351
2001 DX5 monoclonal antibody recognizes CD49b (ITGA2, alpha2 integrin, VLA-2), as identified by retrovirus-mediated expression cloning from an NK cell cDNA library. Binding of DX5 to NK cells and CD49b transfectants is blocked by other anti-CD49b mAbs. CD49b expression on NK cells is progressively lost upon IL-2-driven proliferation. Retrovirus-mediated expression cloning; transfection and flow cytometry; antibody competition assays Journal of immunology High 11466327
2003 EMS16, a C-type lectin-like protein from Echis multisquamatus venom, is a potent and selective inhibitor of GPIa/IIa (integrin alpha2beta1). Its crystal structure at 1.9 Å resolution reveals a heterodimer with domain swapping of the central loop and a unique positively charged electrostatic patch on the concave surface that may interact with the I-domain of GPIa/IIa. X-ray crystallography at 1.9 Å resolution; structural analysis Biochemistry High 14580195
1993 GPIa/IIa (integrin alpha2beta1, ITGA2) specifically binds thrombospondin (TSP) in an ion-independent manner (Kd = 0.69 µM), whereas GPIIb/IIIa binding to TSP is divalent cation-dependent. Anti-GPIa/IIa antibody 6F1 inhibits GPIa/IIa binding to TSP; GPIa/IIa and GPIIb/IIIa bind to distinct sites on TSP. Saturable binding assay with purified GPIa/IIa and GPIIb/IIIa; competition experiments; antibody inhibition; ion dependence experiments The Biochemical journal Medium 8240284
2007 The ITGA2 promoter is regulated by transcription factors including Sp1 (at SNP C-52T binding site). PARP-1 and Ku80/70 bind specifically and with enhanced affinity to the longer (CA)12 repeat allele in the 5'-regulatory region of ITGA2, coinciding with enhanced alpha2beta1 expression. A CpG-rich ITGA1 promoter region is selectively methylated in megakaryocytic cells, but ITGA2 promoter methylation does not change during megakaryocyte differentiation—indicating distinct epigenetic regulation for ITGA1 vs. ITGA2. Bisulfite genomic sequencing, promoter-luciferase reporter assay, transcriptome analysis, 5-aza-2'-deoxycytidine treatment Biochimica et biophysica acta Medium 17669516
2010 PARP-1 and Ku80/70 bind specifically and with enhanced affinity to the longer (CA)12 repeat allele in the 5'-regulatory region of ITGA2 (beginning at -605). This enhanced binding correlates with increased ITGA2/alpha2beta1 expression. Together with SNP C-52T (Sp1 binding site), four ITGA2 haplotypes can be ranked for transcriptional activity: (CA)12/-52C > (CA)11/-52C > (CA)11/-52T > (CA)10/-52T. DNA affinity chromatography, chromatin immunoprecipitation (ChIP), promoter-luciferase reporter assays PloS one Medium 20090957
2013 CD49b (ITGA2) is required for migration of memory CD4 T-cell precursors from blood into the bone marrow sinusoidal endothelium. CD49b-deficient or CD49b-blocked memory CD4 T-cell precursors fail to home to the bone marrow. In the marrow, memory CD4 T cells contact stromal cells expressing collagen II (a ligand for CD49b). CD49b-deficient mice, antibody blockade, adoptive transfer, in vivo migration assays, confocal imaging of stromal cell interactions Immunology and cell biology Medium 23897120
2014 EZH2 epigenetically regulates ITGA2 expression (via chromatin immunoprecipitation-confirmed direct targeting), and de-repression of ITGA2 following EZH2 inhibition (genetic or pharmacological with DZNep and GSK343) activates ITGA2 signaling to increase cofilin phosphorylation at Ser3, thereby reducing colorectal cancer cell migration. siRNA knockdown, pharmacological EZH2 inhibition (DZNep, GSK343), chromatin immunoprecipitation, western blotting for phospho-cofilin, cell migration assays PloS one Medium 25549357
2015 ITGA2 promoter CpG island methylation inversely regulates ITGA2 expression in prostate cancer: highly methylated in non-invasive LNCaP cells (low expression) and hypomethylated in highly metastatic PC3 and 22Rv1 cells (high expression). siRNA knockdown of ITGA2 reduces prostate cancer cell migration. Bisulfite sequencing of ITGA2 promoter CpG island, qPCR, siRNA knockdown, cell migration scratch assay The Prostate Medium 25662931
2015 Human Th17 cells co-express IL-7R and the collagen-binding integrin alpha2beta1 (CD49b/ITGA2). IL-7 increases Th17 adhesion to collagen via alpha2beta1. Co-engagement of IL-7R and alpha2beta1 cooperatively enhances IL-17 production and osteoclastogenic function via JAK/PI3K/AKT and MAPK/ERK pathways. Blockade of alpha2beta1 with a neutralizing mAb inhibited IL-7-induced bone loss in vivo. Flow cytometry, adhesion assays to collagen, neutralizing antibody blockade in vivo, ELISA for IL-17, osteoclast differentiation assay, signaling pathway inhibition Journal of immunology Medium 26408663
2019 ITGA2 interacts with STAT3 (demonstrated by co-immunoprecipitation) and upregulates STAT3 phosphorylation, which transcriptionally increases PD-L1 expression in pancreatic cancer cells. ITGA2 overexpression promotes cancer cell proliferation and invasion; ITGA2 knockdown inhibits these processes. Co-immunoprecipitation, Western blot, RT-qPCR, RNA-seq, MTS assay, colony formation assay, transwell assay, immunohistochemistry Journal of experimental & clinical cancer research Medium 31818309
2018 Blockade of ITGA2 with a specific antibody induces apoptosis in ITGA2-overexpressing gastric cancer cells by upregulating RhoA-p38 MAPK signaling and promoting expression of Bim, Apaf-1, and Caspase-9. At lower doses, anti-ITGA2 antibody inhibits gastric cancer cell migration by downregulating N-WASP, PAK, and LIMK, thereby impairing actin organization. Anti-ITGA2 antibody treatment, Western blot, flow cytometry apoptosis assay, cell migration assay Biological procedures online Medium 29743821
2021 Cyclic mechanical stretch promotes proliferation and inhibits apoptosis of nucleus pulposus cells via the ITGA2/PI3K/AKT signaling pathway. Downregulation of ITGA2 by RNA interference abrogates stretch-induced PI3K/AKT activation and blocks stretch-induced COL2A1 expression and cell proliferation. Cyclic tensile stress application, microarray gene expression analysis, Western blot, RNA interference (siRNA), MTT assay, flow cytometry Oxidative medicine and cellular longevity Medium 33815660
2022 ITGA2 localizes to the nucleus in pancreatic cancer cells and inhibits the non-homologous end joining (NHEJ) DNA repair pathway by restraining recruitment of DNA-PKcs to the Ku70/80 heterodimer during DNA damage response, thereby sensitizing cells to radiotherapy. Nuclear fractionation, TCGA data analysis (genome stability parameters), NHEJ activity assay, DNA-PKcs/Ku70/80 immunoprecipitation, radiation sensitivity assays Cancer letters Medium 35998796
2021 ITGA2 overexpression promotes esophageal squamous cell carcinoma cell invasion and migration via FAK/AKT pathway activation and EMT induction. Treatment with AKT inhibitor MK-2206 rescues the ESCC progression caused by ITGA2 overexpression, placing ITGA2 upstream of FAK/AKT in this context. siRNA knockdown, overexpression, Western blot, Transwell assay, wound healing assay, xenograft tumor model, AKT inhibitor (MK-2206) rescue experiment OncoTargets and therapy Medium 34113124
2023 BACH1 transcription factor directly binds the upstream promoter region of ITGA2 (confirmed by ChIP and dual-luciferase reporter assay) to transcriptionally activate ITGA2 expression, and the BACH1-ITGA2 axis promotes lung adenocarcinoma cell migration and invasion by activating the FAK-RAC1-PAK signaling pathway and regulating cytoskeletal organization. Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, RNA sequencing, Western blot, cell adhesion assay, migration/invasion assays Cancer science Medium 37311571
2022 Elevated ITGA2 expression in intrahepatic cholangiocarcinoma cells promotes clonogenic growth induced by collagen type I. ITGA2 depletion or integrin alpha2beta1-selective inhibitor treatment abolishes robust iCCA cell interaction with collagen type I and blocks collagen type I-induced colony growth (3–6 fold enhancement). ITGA2 siRNA depletion, integrin alpha2beta1-selective inhibitor, cell adhesion assay, colony formation assay in 4 iCCA cell lines vs. non-cancerous cholangiocyte line Scientific reports Medium 36575207
2024 Loss of both ITGA1 and ITGA2 (via genomic deletion or TEAD1 loss) activates epithelial-to-mesenchymal transition in benign prostate epithelial cells via enhanced secretion and autocrine activation of TGFβ1 and nuclear targeting of YAP1, converting cells to tumorigenic in vivo. TEAD1 is identified as a key transcriptional regulator of ITGA1 and ITGA2 expression. Genomic deletion (CRISPR-Cas9), in vitro invasion assays, in vivo tumorigenicity assay, genome-wide co-expression analysis, EMT marker Western blot, TGFβ1 ELISA Advanced science Medium 38169150
2020 ITGA2 promotes breast cancer stemness and metastasis downstream of miR-206 (direct miR-206 target). ITGA2 knockdown suppresses mammosphere formation, pluripotency marker expression, cell cycling (G1 arrest), migration, and invasion, and reduces lung metastasis. ITGA2 overexpression reverses miR-206-induced G1 arrest. RNA-seq reveals ITGA2 regulates CCND1 (cell cycle) and ACLY (lipid metabolism) as downstream targets. siRNA knockdown, miRNA overexpression/inhibition, RNA sequencing, mammosphere formation assay, flow cytometry cell cycle analysis, Transwell migration/invasion, lung metastasis in vivo model Genes & diseases Medium 34179312
2019 ADAR1 p110 enhances adhesion of hepatocellular carcinoma cells to extracellular matrix by upregulating ITGA2 at both mRNA and protein levels. ADAR1 p110 overexpression promotes HCC metastasis in an orthotopic xenograft mouse model, and positive correlation between ADAR1 and ITGA2 was confirmed in patient HCC specimens. Lentivirus-mediated ADAR1 overexpression/knockdown, in vitro cell adhesion assay, Western blot, RT-PCR, orthotopic xenograft mouse model, IHC of patient samples Medical science monitor Medium 30798327
2021 miR-99a-3p suppresses PTC metastasis by targeting GRP94; GRP94 overexpression reverses miR-99a-3p inhibition of metastasis. The miR-99a-3p/GRP94 axis exerts its effect by inhibiting the expression and cytoplasmic relocation of ITGA2, implicating ITGA2 localization (cytoplasmic vs. membrane) as functionally important for metastasis. miRNA overexpression/inhibition, siRNA knockdown, subcellular fractionation/localization, EMT markers, invasion assay, in vivo xenograft model Acta biochimica et biophysica Sinica Low 34687203
2023 In ovarian cancer metastasis, macrophage-stimulated mesothelial cells upregulate ITGA2 expression via JNK and Akt signaling pathways; knockdown of ITGA2 in macrophage-conditioned mesothelial cells significantly reduces ovarian cancer cell adhesion to mesothelial cells. mRNA sequencing, siRNA knockdown, signaling pathway inhibition (JNK, Akt inhibitors), cell adhesion assay Cells Medium 36766725
2025 LncRNA-ITGA2 is an enhancer-associated lncRNA that, in a NONO-dependent manner, mediates chromatin looping interactions between the ITGA2 enhancer and ITGA2 promoter, increases H3K27 acetylation at both the enhancer and promoter, and thereby upregulates ITGA2 expression to promote vascular smooth muscle cell proliferation and migration. CUT&Tag, promoter capture Hi-C, microarray, CRISPR-Cas9 knockout of lncRNA-ITGA2 and NONO, RNA sequencing, chromatin immunoprecipitation sequencing (ChIP-seq), CHIRP, RIP, carotid artery wire injury mouse model Circulation research Medium 40321134

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nature medicine 648 23624599
1989 The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain. The Journal of cell biology 332 2545729
1989 Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood 279 2546619
1994 Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin). Blood 196 8118028
2001 Cutting edge: the mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (alpha 2 integrin, very late antigen-2). Journal of immunology (Baltimore, Md. : 1950) 185 11466327
2014 Genome-wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT-ROBO, ITGA2 and MET signaling. International journal of cancer 180 24500968
1994 Identification of putative ligand binding sites within I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29). The Journal of biological chemistry 161 7511592
1994 Direct binding of collagen to the I domain of integrin alpha 2 beta 1 (VLA-2, CD49b/CD29) in a divalent cation-independent manner. The Journal of biological chemistry 151 7523399
1997 Polymorphisms of the human platelet antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GPIIb/IIIa), von Willebrand factor (GPIb/IX), and collagen (GPIa/IIa) are not correlated with an increased risk for stroke. Stroke 108 9227689
2019 Overexpressed ITGA2 promotes malignant tumor aggression by up-regulating PD-L1 expression through the activation of the STAT3 signaling pathway. Journal of experimental & clinical cancer research : CR 96 31818309
2006 Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 82 16951342
2015 Human uterine leiomyoma stem/progenitor cells expressing CD34 and CD49b initiate tumors in vivo. The Journal of clinical endocrinology and metabolism 73 25658015
2000 Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA-5 alloantigens. British journal of haematology 69 10997989
2018 Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer. Biological procedures online 62 29743821
1994 Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing. Thrombosis and haemostasis 60 7916494
1999 The GPIa C807T dimorphism associated with platelet collagen receptor density is not a risk factor for myocardial infarction. British journal of haematology 59 10468872
2021 The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA-RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis. Oncogene 58 34274947
2011 Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets 56 21591983
2020 Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition. Cancers 55 32824235
2014 EZH2 regulates cofilin activity and colon cancer cell migration by targeting ITGA2 gene. PloS one 55 25549357
2019 ITGA2 as a potential nanotherapeutic target for glioblastoma. Scientific reports 53 30996239
2020 ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis. Genes & diseases 52 34179312
2001 Rhodocytin induces platelet aggregation by interacting with glycoprotein Ia/IIa (GPIa/IIa, Integrin alpha 2beta 1). Involvement of GPIa/IIa-associated src and protein tyrosine phosphorylation. The Journal of biological chemistry 52 11038351
2015 Epigenetic silencing of ITGA2 by MiR-373 promotes cell migration in breast cancer. PloS one 51 26258411
2014 IFN-γ induces aberrant CD49b⁺ NK cell recruitment through regulating CX3CL1: a novel mechanism by which IFN-γ provokes pregnancy failure. Cell death & disease 48 25375377
2018 Coexpression of UCA1 and ITGA2 in pancreatic cancer cells target the expression of miR-107 through focal adhesion pathway. Journal of cellular physiology 43 30569514
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
2018 Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages. Frontiers in immunology 38 30510554
1999 The number of platelet glycoprotein Ia molecules is associated with the genetically linked 807 C/T and HPA-5 polymorphisms. Transfusion 38 10220262
2018 CD49b defines functionally mature Treg cells that survey skin and vascular tissues. The Journal of experimental medicine 37 30355617
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
2005 DX5/CD49b-positive T cells are not synonymous with CD1d-dependent NKT cells. Journal of immunology (Baltimore, Md. : 1950) 37 16177083
2006 Functional specialization of memory Th cells revealed by expression of integrin CD49b. Journal of immunology (Baltimore, Md. : 1950) 36 16818752
2002 Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men. European heart journal 36 11812069
1998 Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in three North American populations reveals genetic association between nucleotide 807C/T and amino acid 505 Glu/Lys (HPA-5) dimorphisms. Thrombosis and haemostasis 36 9759626
2004 Real-time PCR genotyping of human platelet alloantigens HPA-1, HPA-2, HPA-3 and HPA-5 is superior to the standard PCR-SSP method. Transfusion medicine (Oxford, England) 32 15569237
2015 miR-128 modulates hepatocellular carcinoma by inhibition of ITGA2 and ITGA5 expression. American journal of translational research 31 26550456
2020 HOXD3 was negatively regulated by YY1 recruiting HDAC1 to suppress progression of hepatocellular carcinoma cells via ITGA2 pathway. Cell proliferation 29 32557953
2010 An unexpected twist in alopecia areata pathogenesis: are NK cells protective and CD49b+ T cells pathogenic? Experimental dermatology 29 20653774
2002 Increased platelet-collagen interaction associated with double homozygosity for receptor polymorphisms of platelet GPIa and GPIIIa. Arteriosclerosis, thrombosis, and vascular biology 29 12482840
2015 Regulation of the ITGA2 gene by epigenetic mechanisms in prostate cancer. The Prostate 28 25662931
2009 Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis. Journal of autoimmunity 28 19880290
2006 Enhanced frequency of CD18- and CD49b-expressing T cells in peripheral blood of asthmatic patients correlates with disease severity. International archives of allergy and immunology 28 16601351
2021 Cyclic Mechanical Stretch Ameliorates the Degeneration of Nucleus Pulposus Cells through Promoting the ITGA2/PI3K/AKT Signaling Pathway. Oxidative medicine and cellular longevity 27 33815660
2015 Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss. Journal of immunology (Baltimore, Md. : 1950) 26 26408663
2003 Structural characterization of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus. Biochemistry 26 14580195
1999 Simultaneous genotyping of human platelet antigens (HPA) 1 through 6 using new sequence-specific primers for HPA-5. Transfusion 26 10604254
2021 Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells. Cancer immunology research 25 33619119
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 25 31428583
2016 Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2. Scientific reports 25 27094978
2020 microRNA-30a arbitrates intestinal-type early gastric carcinogenesis by directly targeting ITGA2. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 24 32112274
2013 CD49b-dependent establishment of T helper cell memory. Immunology and cell biology 24 23897120
2019 ADAR1 p110 Enhances Adhesion of Tumor Cells to Extracellular Matrix in Hepatocellular Carcinoma via Up-Regulating ITGA2 Expression. Medical science monitor : international medical journal of experimental and clinical research 23 30798327
2015 Both PIGA and PIGL mutations cause GPI-a deficient isolates in the Tk6 cell line. Environmental and molecular mutagenesis 23 25970100
2020 miR-216a-mediated upregulation of TSPAN1 contributes to pancreatic cancer progression via transcriptional regulation of ITGA2. American journal of cancer research 22 32368389
2009 Prevention of embryo loss in non-obese diabetic mice using adoptive ITGA2(+)ISG20(+) natural killer-cell transfer. Reproduction (Cambridge, England) 22 19321657
1997 The integrin alpha 2 beta 1 (GPIa/IIa)-I-domain inhibits platelet-collagen interaction. Thrombosis and haemostasis 22 9184414
2007 Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2. Biochimica et biophysica acta 21 17669516
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
2020 Ropivacaine inhibits proliferation, invasion, migration and promotes apoptosis of papillary thyroid cancer cells via regulating ITGA2 expression. Drug development research 19 32314406
2011 Association between ITGA2 C807T polymorphism and gastric cancer risk. World journal of gastroenterology 19 21734795
2010 Progesterone modulates integrin {alpha}2 (ITGA2) and {alpha}11 (ITGA11) in the pregnant cervix. Reproductive sciences (Thousand Oaks, Calif.) 19 20959644
1994 The human platelet alloantigens, HPA-5(a+, b-) and HPA-5(a-, b+), are associated with a Glu505/Lys505 polymorphism of glycoprotein Ia (the alpha 2 subunit of VLA-2). British journal of haematology 19 7913826
2024 Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38169150
2022 ITGA2 overexpression inhibits DNA repair and confers sensitivity to radiotherapies in pancreatic cancer. Cancer letters 18 35998796
2014 Genetic polymorphism of ITGA2 C807T can increase the risk of ischemic stroke. The International journal of neuroscience 18 24397542
2016 CD4+CD25hiCD127- Treg and CD4+CD45R0+CD49b+LAG3+ Tr1 cells in bone marrow and peripheral blood samples from children with neuroblastoma. Oncoimmunology 17 28123887
2015 Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals. AIDS research and human retroviruses 17 26192268
2021 ITGA2 Overexpression Promotes Esophageal Squamous Cell Carcinoma Aggression via FAK/AKT Signaling Pathway. OncoTargets and therapy 16 34113124
2021 MicroRNA-99a-3p/GRP94 axis affects metastatic progression of human papillary thyroid carcinoma by regulating ITGA2 expression and localization. Acta biochimica et biophysica Sinica 16 34687203
2014 Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals. Balkan medical journal 16 25207168
2024 Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence. International immunopharmacology 15 38640717
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
2018 Formation and phenotypic characterization of CD49a, CD49b and CD103 expressing CD8 T cell populations in human metastatic melanoma. Oncoimmunology 15 30288359
2008 Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L. Journal of immunology (Baltimore, Md. : 1950) 15 18802064
2023 Long non-coding RNA AC018926.2 regulates palmitic acid exposure-compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway. Cell proliferation 14 36720715
2020 CD49a+CD49b+ NK cells induced by viral infection reflect an activated state of conventional NK cells. Science China. Life sciences 14 32335843
2015 Nonclassical CD4+CD49b+ Regulatory T Cells as a Better Alternative to Conventional CD4+CD25+ T Cells To Dampen Arthritis Severity. Journal of immunology (Baltimore, Md. : 1950) 14 26590312
2013 CD49b/CD69-Dependent Generation of Resting T Helper Cell Memory. Frontiers in immunology 14 23847623
2025 Enhancer-Associated LncRNA-ITGA2 Promotes Vascular Remodeling Through ITGA2. Circulation research 13 40321134
2018 Interleukin-4 induces a CD44high /CD49bhigh PC3 subpopulation with tumor-initiating characteristics. Journal of cellular biochemistry 13 29236307
2017 Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia. PloS one 13 29121049
2017 Association of GPIa and COX-2 gene polymorphism with aspirin resistance. Journal of clinical laboratory analysis 12 28948649
2013 Alpha 2 integrin gene (ITGA2) polymorphism in renal transplant recipients with and without drug induced gingival overgrowth. Archives of oral biology 12 24581850
2010 Enhanced binding of poly(ADP-ribose)polymerase-1 and Ku80/70 to the ITGA2 promoter via an extended cytosine-adenosine repeat. PloS one 12 20090957
1993 Interaction of thrombospondin with platelet glycoproteins GPIa-IIa and GPIIb-IIIa. The Biochemical journal 12 8240284
2024 Selumetinib overcomes ITGA2-induced 5-fluorouracil resistance in colorectal cancer. International immunopharmacology 11 38889513
2004 Impact of disparity of minor histocompatibility antigens HA-1, CD31, and CD49b in hematopoietic stem cell transplantation of patients with chronic myeloid leukemia with sibling and unrelated donors. Transplantation 11 15087780
2024 Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway. Advanced healthcare materials 10 38288911
2023 BACH1 promotes lung adenocarcinoma cell metastasis through transcriptional activation of ITGA2. Cancer science 10 37311571
2022 CD49b identifies functionally and epigenetically distinct subsets of lineage-biased hematopoietic stem cells. Stem cell reports 10 35714596
2022 Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma. Scientific reports 10 36575207
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
2020 Overexpression of long non-coding RNA00355 enhances proliferation, chemotaxis, and metastasis in colon cancer via promoting GTF2B-mediated ITGA2. Translational oncology 10 33227664
2014 CD49b, a major marker of regulatory T-cells type 1, predicts the response to antiviral therapy of recurrent hepatitis C after liver transplantation. BioMed research international 10 24575405
2023 Macrophages Promote Ovarian Cancer-Mesothelial Cell Adhesion by Upregulation of ITGA2 and VEGFC in Mesothelial Cells. Cells 9 36766725
2023 ATF4-mediated circTDRD3 promotes gastric cancer cell proliferation and metastasis by regulating the miR-891b/ITGA2 axis and AKT signaling pathway. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 9 37062785
2003 Expression of CD18, CD49b, CD49c and CD49e on lens anterior capsules in human cataracts. Eye (London, England) 9 12802345
2003 Characterization and preliminary crystallographic studies of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus. Journal of biochemistry 9 12944366

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