Affinage

ICAM2

Intercellular adhesion molecule 2 · UniProt P13598

Audit flag: wrong gene
Length
275 aa
Mass
30.7 kDa
Annotated
2026-06-10
87 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ICAM-2 (CD102) is a constitutively expressed two-Ig-domain transmembrane adhesion glycoprotein that serves as a counter-receptor for leukocyte β2 integrins and thereby governs leukocyte trafficking, vascular biology, and immune cell signaling (PMID:2497351, PMID:7561061). It was originally identified as a second ligand for LFA-1 (CD11a/CD18), structurally related to the N-terminal domains of ICAM-1 (PMID:2497351, PMID:1676048), and also binds Mac-1 (CD11b/CD18) through its first Ig domain (PMID:7561061). Crystallographic and structure-guided mutagenesis studies localized the integrin recognition surface to a flat band across domain 1, with Glu-37 coordinating the Mg2+ ion in the LFA-1 I domain (PMID:9153399, PMID:10077629). Its glycosylation state tunes ligand activity: properly glycosylated ICAM-2 bearing Lewis Y presents a glycan-specific ligand for DC-SIGN, while cell-type-specific sialylation reduces its capacity to support leukocyte adhesion (PMID:18155766, PMID:15673159). The short cytoplasmic tail couples ICAM-2 to the actin cytoskeleton through direct, PtdIns(4,5)P2-regulated binding of ERM proteins (ezrin/moesin) at a juxtamembrane positively charged cluster and through binding to alpha-actinin (PMID:9472040, PMID:9705328, PMID:8824270). Outside-in signaling through ICAM-2 drives ezrin tyrosine phosphorylation, PI3K membrane recruitment, and AKT activation to suppress apoptosis, and activates Rac—but not RhoA—to support endothelial migration, tube formation, and vascular barrier integrity (PMID:11825565, PMID:12097408, PMID:15920013, PMID:24593809). At the tissue level ICAM-2 mediates leukocyte crawling and sequential transmigration steps across vascular and epithelial barriers, regulates angiogenesis and eosinophil trafficking, and contributes to NK recognition and T cell costimulation (PMID:10023766, PMID:20861356, PMID:24259506, PMID:18842965, PMID:8717043). In tumor cells, the ICAM-2–alpha-actinin–actin linkage suppresses the metastatic phenotype (PMID:18978946, PMID:24704826). ICAM-2 promoter activity is endothelially programmed by Sp1, GATA, and Ets factors and is down-regulated by inflammatory cytokines (PMID:10574717, PMID:9565596, PMID:10223354). No Mendelian disease link is established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Establishing that LFA-1 has a second cellular ligand answered why LFA-1-dependent adhesion persisted in settings of limited ICAM-1, defining ICAM-2 as a distinct adhesion receptor.

    Evidence Functional cloning, COS cell transfection and cell adhesion assays

    PMID:2497351

    Open questions at the time
    • Did not map the integrin-binding residues
    • Cellular and tissue distribution not yet defined
  2. 1991 High

    Reciprocal blocking and binding to purified LFA-1 confirmed ICAM-2 as a direct, not indirect, LFA-1 ligand and placed it alongside ICAM-1 as accounting for LFA-1 binding to endothelium.

    Evidence Blocking mAb (CBR-IC2/2), immunoprecipitation, cell binding to purified LFA-1

    PMID:1676048

    Open questions at the time
    • An additional LFA-1 ligand on some lines remained unaccounted for
    • Affinity and structural basis of binding undefined
  3. 1995 High

    Mapping ICAM-2 binding to the CD11b A domain broadened its receptor repertoire beyond LFA-1 to include Mac-1, relevant for myeloid adhesion.

    Evidence Adhesion assays with purified integrins, peptide competition, anti-CD11b A-domain blocking

    PMID:7561061

    Open questions at the time
    • Relative physiological contribution of Mac-1 vs LFA-1 binding not resolved
    • Single lab
  4. 1997 High

    The crystal structure defined the molecular architecture of the integrin recognition surface, showing Glu-37 positioned to coordinate the I-domain Mg2+ and distinguishing ICAM-2's binding mode from VCAM-1/fibronectin.

    Evidence X-ray crystallography of extracellular ICAM-2; structure-guided mutagenesis with LFA-1 binding assays

    PMID:10077629 PMID:9153399

    Open questions at the time
    • No co-crystal of the ICAM-2/LFA-1 complex
    • Conformational changes upon binding not captured
  5. 1998 High

    Identifying ERM and alpha-actinin binding to the cytoplasmic tail explained how ICAM-2 physically anchors to the cortical actin cytoskeleton and localizes to microvilli.

    Evidence GST pulldown, co-IP, SPR (KD = 3.3×10^-7 M), PtdIns(4,5)P2 binding, mutagenesis, chimera localization; alpha-actinin affinity pulldown and colocalization

    PMID:8824270 PMID:9472040 PMID:9705328

    Open questions at the time
    • Functional consequence of cytoskeletal coupling not yet defined
    • Crystallographic detail of the FERM-tail interaction came later (PMID 11375520)
  6. 1996 High

    Linking ICAM-2 redistribution into ezrin-rich uropods to NK killing connected the cytoskeletal anchorage to an immune effector function.

    Evidence Ezrin transfection into NK-resistant cells, cytotoxicity assays, confocal localization

    PMID:8717043

    Open questions at the time
    • Downstream signaling from redistributed ICAM-2 not defined
    • NK receptor engaging ICAM-2 not identified here
  7. 2002 High

    Demonstrating that ICAM-2 engagement activates PI3K/AKT and that it fails to activate RhoA established outside-in signaling distinct from ICAM-1 and a pro-survival role.

    Evidence Genetic screen, ezrin phosphorylation/PIP3/PDK-1/AKT biochemistry, apoptosis assays; ICAM cross-linking with RhoA activity and actin readouts

    PMID:11825565 PMID:12097408

    Open questions at the time
    • Direct molecular link between ezrin phosphorylation and PI3K recruitment not fully resolved
    • Why ICAM-2 cannot activate RhoA mechanistically unexplained
  8. 2005 High

    Knockout mice and deficient endothelial cells showed ICAM-2 drives Rac-dependent angiogenesis, migration, tube formation, and survival, defining an endothelial-autonomous role beyond leukocyte adhesion.

    Evidence ICAM-2 knockout mice and cells, tube formation, in vivo angiogenesis, migration, apoptosis, Rac activity assays

    PMID:15920013

    Open questions at the time
    • The homophilic interaction inferred for tube formation not structurally characterized
    • Upstream activator of Rac downstream of ICAM-2 unspecified
  9. 2014 High

    Domain-mutant rescue established that the ERM-binding site and cytoplasmic tail are required for ICAM-2 to maintain endothelial junctions and barrier function via N-cadherin and Rac-1.

    Evidence Knockout endothelioma lines, full-length vs mutant re-expression, TEER, intravital permeability, Rac-1 assay

    PMID:24593809

    Open questions at the time
    • Mechanism linking ICAM-2 tail to N-cadherin not detailed
    • Whether ligand engagement is required for barrier function unclear
  10. 1999 Medium

    Cytokine-driven transcriptional control via Ets/Erg, Sp1, and GATA sites explained how endothelial ICAM-2 levels are programmed and reduced during inflammation, opposite to ICAM-1.

    Evidence Promoter reporter assays, EMSA, site-directed mutagenesis, GATA-2/Erg transactivation, Northern blot, flow cytometry

    PMID:10223354 PMID:10574717 PMID:9565596

    Open questions at the time
    • Single-lab promoter studies
    • In vivo relevance of each transcription factor not tested genetically
  11. 1999 High

    Knockout and rescue work established that endothelial ICAM-2, redundantly with ICAM-1, is required for transendothelial migration and physiological eosinophil/leukocyte trafficking.

    Evidence ICAM-1-deficient endothelioma + retroviral rescue; ICAM-2 knockout mice in allergic lung model and transmigration assays

    PMID:10023766 PMID:10464174 PMID:9808177

    Open questions at the time
    • Molecular signaling driving the migration step not dissected here
    • Relative ICAM-1/ICAM-2 contribution varies by stimulus
  12. 2013 High

    Multi-knockout intravital and flow imaging dissected ICAM-2's sequential roles in leukocyte crawling, defining crawling as a prerequisite for transcellular diapedesis distinct from the arrest step.

    Evidence Knockout mouse strains and endothelial cell combinations, cell transfer, intravital and flow live imaging

    PMID:19211506 PMID:20861356 PMID:24259506 PMID:24317296

    Open questions at the time
    • Signaling events coordinating crawling-to-diapedesis transition incomplete
    • Stimulus-specificity (IL-1β vs TNF-α) mechanism unresolved
  13. 2008 High

    Defining the ICAM-2–alpha-actinin–actin complex and N-glycosylation requirement showed ICAM-2 acts as a metastasis suppressor through cytoskeletal coupling.

    Evidence Co-IP, competitive peptides, alpha-actinin-binding and glycosylation-site mutants, migration assays, in vivo neuroblastoma metastasis models

    PMID:18978946 PMID:23714211 PMID:24704826

    Open questions at the time
    • alpha-actinin-independent suppressive mechanism not identified
    • How glycosylation contributes independent of alpha-actinin binding unknown
  14. 2007 Medium

    Glycan-specific recognition by DC-SIGN and sialylation-dependent loss of leukocyte support established that ICAM-2 glycoforms determine which partners it engages.

    Evidence Shear-flow adhesion assays, glycosylation manipulation, FUT1 siRNA, isoelectric focusing and neuraminidase treatment

    PMID:15673159 PMID:18155766

    Open questions at the time
    • In vivo relevance of cell-type glycoform differences not tested
    • Single-lab biochemistry
  15. 2022 Medium

    Recent disease-model studies extended ICAM-2/PI3K/AKT signaling to pathological proliferation and metastasis, with m6A methylation identified as an upstream regulator of ICAM2 expression.

    Evidence MeRIP, ChIP, luciferase, knockdown/overexpression in RA-FLS and TNBC models; pull-down and antibody neutralization in vivo

    PMID:36536495 PMID:37620448

    Open questions at the time
    • Generality of m6A regulation beyond RA-FLS untested
    • ICAM2-ICAM1 homophilic/heterophilic interaction in metastasis structurally undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How outside-in ICAM-2 signaling selectively engages Rac and PI3K but not RhoA, and how ligand engagement, glycoform, and cytoskeletal coupling are integrated into a unified signaling mechanism, remains unresolved.
  • No co-crystal of ICAM-2 with any integrin or DC-SIGN partner
  • Mechanism of selective GTPase activation unexplained
  • No human Mendelian disease association established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 1
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-1474244 Extracellular matrix organization 1
Partners
ACTN1CD209EZRICAM1ITGALITGAMITGB2MSN

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 ICAM-2 was identified as a second ligand for the integrin LFA-1 (CD11a/CD18). ICAM-2 is an integral membrane protein with two immunoglobulin-like domains, closely related to the two N-terminal domains of ICAM-1 (34% identity), and mediates LFA-1-dependent cell adhesion. Functional cloning using a novel ligand-identification method; COS cell transfection and cell adhesion assays Nature High 2497351
1991 A blocking anti-ICAM-2 monoclonal antibody (CBR-IC2/2) totally inhibited binding of ICAM-2+ COS cells to purified LFA-1, confirming ICAM-2 as a direct LFA-1 ligand. ICAM-1 and ICAM-2 together account for all LFA-1-dependent binding to endothelium, but an additional LFA-1 ligand (ICAM-3) was implicated on some cell lines. Monoclonal antibody generation, immunoprecipitation, cell binding assays to purified LFA-1, mAb blocking experiments The Journal of experimental medicine High 1676048
1995 ICAM-2 (CD102) binds to the leukocyte integrin CD11b/CD18 (Mac-1) through the CD11b A domain. A 22-amino acid peptide (P1) derived from the first Ig domain of ICAM-2 also binds to purified CD11b/CD18. Cell adhesion assays with purified integrins, peptide competition, blocking with anti-CD11b A domain antibodies Journal of immunology High 7561061
1993 A synthetic peptide from ICAM-2 spanning residues 21-42 of the first immunoglobulin domain binds to purified CD11a/CD18 (LFA-1) and inhibits adhesion of endothelial cells to this integrin and B lymphoblastoid cell binding to endothelium. Peptide synthesis, binding assay to purified CD11a/CD18, cell adhesion inhibition assays The Journal of biological chemistry High 8349630
1997 Crystal structure of the extracellular region of ICAM-2 was determined. Glu-37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the LFA-1 I domain. The LFA-1 recognition surface is relatively flat and the critical Glu lies in a beta-strand (unlike VCAM-1/fibronectin where critical Asp is in a loop). A bend between domains 1 and 2 and N-linked glycans in domain 2 present the recognition surface to LFA-1. X-ray crystallography of extracellular ICAM-2 Nature High 9153399
1999 Mutagenesis of ICAM-2 based on its crystal structure localized the LFA-1 binding site to a diagonal band across the GFC beta-sheet and CD edge of domain 1, with Glu-37 ligating Mg2+ in the I domain. The binding site is confined to the upper part of domain 1, distinct from the VCAM-1 binding site for alpha4 integrins. Site-directed mutagenesis of ICAM-2 guided by crystal structure; LFA-1 binding assays Proceedings of the National Academy of Sciences of the United States of America High 10077629
1996 ICAM-2 cytoplasmic domain (amino acids 231-254) binds alpha-actinin. The minimal binding region was mapped to ICAM-2 residues 241-248. Colocalization of ICAM-2 and alpha-actinin was demonstrated in Eahy926 cells, suggesting alpha-actinin links ICAM-2 to the actin cytoskeleton. Affinity peptide pulldown from placental lysates, immunoblotting with anti-alpha-actinin, confocal microscopy colocalization, bacterially expressed alpha-actinin fusion proteins The Journal of biological chemistry High 8824270
1998 ERM proteins (ezrin/radixin/moesin) bind to a positively charged amino acid cluster in the juxtamembrane cytoplasmic domain of ICAM-2. GST-fusion of ICAM-2 cytoplasmic domain bound moesin in vitro. E-cadherin chimeras bearing the ICAM-2 cytoplasmic sequence co-concentrated with ERM proteins at microvilli; deletion of the positively charged cluster abolished this. Binding was confirmed by co-immunoprecipitation and site-directed mutagenesis. GST pulldown, co-immunoprecipitation, site-directed mutagenesis, chimeric protein expression in L fibroblasts, confocal microscopy The Journal of cell biology High 9472040
1998 Ezrin interacts directly with ICAM-2 cytoplasmic tail. The interaction was demonstrated by affinity precipitation, microtiter binding assay, co-immunoprecipitation, and surface plasmon resonance (KD = 3.3 × 10^-7 M). PtdIns(4,5)P2 enhanced the ICAM-2-ezrin interaction, and ICAM-2 cytoplasmic tail directly binds PtdIns(4,5)P2. ICAM-2 and ezrin co-localize in microvillar projections of transfected cells. Affinity precipitation, microtiter binding assay, co-immunoprecipitation, surface plasmon resonance, cell transfection with localization analysis The Journal of biological chemistry High 9705328
1996 NK cell-mediated killing depends on ICAM-2 and is regulated by ICAM-2 distribution. In NK-sensitive cells, ICAM-2 is concentrated in uropod-like projections with ezrin. Transfection of ezrin into NK-resistant cells induced uropod formation, redistribution of ICAM-2, and sensitized cells to IL-2-activated killing. Ezrin transfection into NK-resistant cells, NK cytotoxicity assays, confocal microscopy of ICAM-2 and ezrin localization Nature High 8717043
2002 ICAM-2 activates the PI3K/AKT pathway. ICAM-2 induced tyrosine phosphorylation of ezrin and PI3K membrane translocation, resulting in PIP3 production, PDK-1 and AKT activation, and phosphorylation of AKT targets BAD, GSK3, and FKHR. ICAM-2 clustering protected primary human CD19+ cells from TNFα- and Fas-mediated apoptosis. ICAM-2 engagement by its natural receptor LFA-1 on CD4+ T cells specifically induced AKT activity. Genetic screen for PI3K/AKT activators, biochemical assays for ezrin phosphorylation/PI3K translocation/PIP3/PDK-1/AKT activation, apoptosis assays, single-cell analysis Immunity High 11825565
2002 ICAM-1 cross-linking activates RhoA and induces stress fiber formation and c-fos/rhoA transcription in endothelial cells. In contrast, ICAM-2 cross-linking does NOT activate RhoA or alter actin cytoskeletal organization in HUVECs, despite both ICAM-1 and ICAM-2 localizing with moesin in apical microvilli at baseline. ICAM cross-linking with antibodies, RhoA activity assay, actin staining, transcription reporter assays, confocal microscopy Journal of immunology High 12097408
2005 Endothelial ICAM-2 regulates angiogenesis. ICAM-2-deficient mice and ICAM-2-deficient endothelial cells show impaired angiogenesis in vitro and in vivo. ICAM-2 supports homophilic interaction (involved in tube formation), supports cell migration, protects against apoptosis (serum deprivation, anti-Fas, staurosporine), and activates the small GTPase Rac, which is required for tube formation and migration. ICAM-2 knockout mice, ICAM-2-deficient endothelial cells, in vitro tube formation assay, in vivo angiogenesis assay, cell migration assay, apoptosis assays, Rac GTPase activity assay Blood High 15920013
2014 ICAM-2 regulates endothelial barrier function and vascular permeability through a pathway involving N-cadherin, ERM proteins, and Rac-1 signaling. ICAM-2 lacking ERM-binding site or cytoplasmic tail failed to restore junctions and Rac-1 activation in ICAM-2-deficient cells. In vivo, thrombin-induced vascular permeability was increased in ICAM-2-deficient mice. siRNA knockdown, ICAM-2 knockout endothelioma lines, re-expression of full-length vs. mutant ICAM-2, transendothelial electrical resistance, intravital fluorescence microscopy for permeability, Rac-1 activity assay Cell communication and signaling High 24593809
1998 TNF-α and IL-1β down-regulate ICAM-2 expression at the transcriptional level in HUVECs (to ~50% of control surface expression; mRNA reduced to ~40% of control). Inflammatory cytokines reduce ICAM-2 promoter activity. ICAM-2 localizes mainly at endothelial cell junctions and this junctional expression is markedly decreased by cytokine treatment. IFN-γ had no effect on ICAM-2 expression. Flow cytometry, Northern blotting, ICAM-2 promoter reporter assays in HUVECs, immunocytochemistry Cell adhesion and communication Medium 10223354
1999 TNF-α-mediated down-regulation of the ICAM-2 promoter involves three Ets transcription factor binding sites (EBS). Two of these EBS are involved in TNF-α-induced down-regulation. The Ets family member Erg is constitutively expressed in HUVECs, binds the EBS, and transactivates the ICAM-2 promoter. TNF-α down-regulates Erg protein levels, and ICAM-2 and Erg expression are co-regulated in an ex vivo artery model. Site-directed mutagenesis of ICAM-2 promoter, EMSA, Erg cDNA transactivation assays in HeLa and HUVEC, Western blotting for Erg protein, ex vivo artery model Journal of cell science Medium 10574717
1998 ICAM-2 promoter activity in endothelial cells requires Sp1 motif at -194 and GATA motifs at -145 and -53 (each contributing 61-78% of activity). Mutation of an 8-bp palindrome at -268 also reduced activity by 70%. Specific binding of endothelial nuclear proteins to these sites was demonstrated. GATA-2 overexpression transactivated the ICAM-2 promoter 3-4-fold in COS cells. Promoter reporter gene assays, site-directed mutagenesis, gel shift (EMSA) analysis, GATA-2 transactivation assays The Journal of biological chemistry Medium 9565596
1998 ICAM-1 and ICAM-2 (but not PECAM-1, VCAM-1, or E-selectin) are essential for transendothelial migration of T cells. In the absence of ICAM-1, only ICAM-2 mediates transendothelial migration. This was established using ICAM-1-deficient endothelioma cells and rescue by retroviral transfer of wild-type ICAM-1. ICAM-1-deficient endothelioma cells from knockout mice, retroviral rescue with wild-type ICAM-1, transendothelial migration assay, blocking antibodies European journal of immunology High 9808177
1999 Endothelial ICAM-1 and ICAM-2 are equally required for transendothelial migration of thymocytes and T lymphoma cells, in addition to CD4+ memory T cells, demonstrating that this requirement is not T cell subset-specific. ICAM-1-deficient endothelioma cells, transendothelial migration assay with different T cell populations International immunology Medium 10464174
1999 ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium and delayed eosinophil transmigration into the airway lumen during allergic lung inflammation, resulting in prolonged heightened airway hyperresponsiveness. This phenotype is due to lack of ICAM-2 on non-hematopoietic (endothelial) cells; ICAM-2 deficiency on endothelial cells reduces eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing but is required for megakaryocyte progenitor numbers. ICAM-2 knockout mice, allergic lung disease model, in vitro eosinophil transmigration assay, bone marrow analysis Immunity High 10023766
2009 ICAM-2, JAM-A, and PECAM-1 act sequentially to mediate neutrophil transmigration in response to IL-1β but not TNF-α stimulation. When TNF-α direct stimulation of neutrophils is blocked, TNF-α-induced neutrophil transmigration becomes dependent on these molecules. Analysis of neutrophil arrest sites in ICAM-2-/-, JAM-A-/-, and PECAM-1-/- mice showed sequential roles. ICAM-2-/-, JAM-A-/-, PECAM-1-/- mice, cell-transfer technique, fluorescence intravital microscopy of cremaster venules Blood High 19211506
2010 Endothelial ICAM-2 (but not VCAM-1) mediates T cell polarization and crawling on BBB endothelium. T cell arrest is mediated by ICAM-1 and VCAM-1, while T cell polarization and crawling require ICAM-1 and ICAM-2. This dissects sequential roles: arrest (ICAM-1/VCAM-1) then crawling (ICAM-1/ICAM-2) prior to diapedesis. Wild-type, ICAM-1-/-, ICAM-2-/-, and ICAM-1/ICAM-2 double-deficient primary mouse brain microvascular endothelial cells; live cell imaging under physiological flow conditions Journal of immunology High 20861356
2013 β2 integrin-mediated neutrophil crawling on endothelial ICAM-1 and ICAM-2 is a prerequisite for transcellular neutrophil diapedesis across the inflamed BBB. In the absence of crawling, neutrophils undergo only paracellular diapedesis. Crawling is mediated by endothelial ICAM-1 and ICAM-2 and neutrophil LFA-1 and Mac-1. Wild-type, CD11a-/-, CD11b-/-, CD18-null neutrophils with wild-type, JAM-A-/-, ICAM-1-null, ICAM-2-/-, ICAM-1/ICAM-2-double-null endothelial cells; live-cell imaging under physiological flow Journal of immunology High 24259506
2013 ICAM-2 has functional roles in luminal neutrophil crawling in vivo: blockade of ICAM-2 reduced crawling velocity, increased stop-start crawling profile, prolonged neutrophil interaction at EC junctions prior to TEM, and reduced overall extravasation. Some ICAM-2-dependent functions are mediated through Mac-1 ligation. Real-time in vivo confocal microscopy of neutrophil-vessel interactions; functional and genetic ICAM-2 blockade; Mac-1 pharmacological inhibition Journal of cell science High 24317296
2007 DC-SIGN on dendritic cells binds to the Lewis Y (LeY) glycan epitope on ICAM-2 on endothelial cells to mediate DC rolling and adhesion on endothelium under shear flow. The interaction is strictly glycan-specific; ICAM-2 on CHO cells serves as a DC-SIGN ligand only when properly glycosylated. FUT1 directs LeY expression; FUT1 silencing reduces DC rolling/adhesion. DC-SIGN/ICAM-2 adhesion assays under shear flow, CHO cell transfection with ICAM-2 ± glycosylation, FUT1 siRNA knockdown, antibody blocking Molecular immunology High 18155766
2004 Sialylation of platelet ICAM-2 impairs its ability to support leukocyte adhesion. Platelet ICAM-2 is more acidic than endothelial ICAM-2 due to cell-specific N-linked glycosylation (sialylation). Platelet ICAM-2 supports 50% less T cell adhesion via LFA-1 and no DC adhesion via DC-SIGN compared to endothelial ICAM-2. Neuraminidase treatment abolished these differences. Isoelectric focusing, N-glycanase/neuraminidase treatment, purified protein adhesion assays, T cell and DC adhesion to immobilized ICAM-2 Inflammation Medium 15673159
2001 Crystals of the complex between the radixin FERM domain and the full-length 28-residue cytoplasmic tail of ICAM-2 were obtained, with data collected to 2.60 Å resolution, establishing the structural basis for ERM-ICAM-2 interaction. X-ray crystallography of radixin FERM domain / ICAM-2 cytoplasmic tail complex Acta crystallographica. Section D, Biological crystallography Medium 11375520
1999 Soluble ICAM-2Fc and a peptide from the first Ig domain of ICAM-2 (P1) can activate integrin affinity in T lymphocytes, inducing CD11/CD18-dependent adhesion to immobilized ICAMs. The activation is energy-, divalent cation-, temperature-, and cytoskeleton-dependent. ICAM-2Fc is a more potent activator of integrin affinity than ICAM-1Fc or ICAM-3Fc. T lymphocyte adhesion assays to purified ICAMs, soluble ICAM-Fc binding assays, cytoskeletal inhibitors, kinase inhibitors Journal of immunology Medium 10352278
1995 An ICAM-2 peptide (residues 21-42) activates NK cell migration (up to 215% of control), induces F-actin polymerization at the leading edge, increases phosphorylation of 150- and 35-kDa proteins, and this migration activation is inhibited by anti-CD11a monoclonal antibodies. This effect is mediated through CD11a/CD18 ligation without receptor recycling. Boyden chamber migration assay, F-actin staining, phosphotyrosine immunoblotting, anti-CD11a blocking antibodies, receptor recycling assay The Journal of biological chemistry Medium 7721764
2008 ICAM-2 forms a complex with alpha-actinin and actin in neuroblastoma cells, linking the membrane to the actin cytoskeleton. ICAM-2 expression limited cell motility, redistributed actin fibers in vitro, and suppressed disseminated tumor formation in vivo in a metastatic neuroblastoma model. Co-immunoprecipitation, competitive peptide assays, in vitro cell migration assay, actin fiber staining, in vivo metastasis model PloS one High 18978946
2014 The interaction of ICAM-2 with alpha-actinin through its cytoplasmic domain is required for ICAM-2 to confer a non-metastatic phenotype in neuroblastoma cells in vivo. ICAM-2 variants with mutated alpha-actinin-binding domains inhibited cell adhesion, migration, and colony growth in vitro similarly to WT, but unlike WT failed to completely suppress disseminated tumor development in vivo. Both alpha-actinin-dependent and alpha-actinin-independent mechanisms contribute to ICAM-2 function. In silico domain analysis, site-directed mutagenesis of alpha-actinin-binding domain, co-precipitation assays, cell migration and adhesion assays, in vivo metastasis model Oncogene High 24704826
2013 N-glycosylation of ICAM-2 is required for complete suppression of metastatic potential in neuroblastoma cells. Hypo- or non-glycosylated ICAM-2 variants (alanine substitutions at N47, N82, N105, N153, N178, N187) significantly attenuated but did not abolish ICAM-2's ability to suppress metastatic properties. Glycosylation status did not affect ICAM-2 interaction with alpha-actinin. Site-directed mutagenesis of N-linked glycosylation sites, cell migration assay, anchorage-independent growth, F-actin distribution, co-immunoprecipitation with alpha-actinin, in vivo metastasis model BMC cancer Medium 23714211
2022 ICAM2 promotes RA-FLS proliferation, migration, and invasion via the ICAM2/PI3K/AKT/p300 pathway. ATT inhibits METTL3-mediated N6-methyladenosine (m6A) methylation of ICAM2 mRNA in RA-FLSs, thereby suppressing ICAM2 expression and downstream signaling. p300 directly facilitates METTL3 transcription, forming a feedback loop with ICAM2. RNA-seq, siRNA knockdown, plasmid overexpression, methylated RNA immunoprecipitation (MeRIP), chromatin immunoprecipitation (ChIP), luciferase reporter, cell proliferation/migration/invasion assays, CIA mouse model Clinical and translational medicine Medium 36536495
2023 ICAM2 promotes leptomeningeal metastasis of TNBC by mediating adhesion to and trans-BCB migration across the blood-CSF barrier via homophilic or heterophilic interaction with ICAM1 in choroid plexus epithelial cells. ICAM2 also conferred cancer stem cell properties. Neutralizing ICAM2 attenuated LM progression in vivo. Proteomic analysis, pull-down assay, antibody neutralization, in vitro trans-BCB migration assay, in vivo spinal cord colonization model Oncogene Medium 37620448
2008 Epithelial ICAM-2 (but not ICAM-3) is expressed on bronchial epithelium and together with ICAM-1 mediates T cell egression across the bronchial epithelium via LFA-1. Blocking both ICAM-1 and ICAM-2 inhibited egression by ~70%, and LFA-1/ICAM interactions on the basolateral epithelium enable recognition of interepithelial junctions but not adhesion/polarization per se. In vitro trans-epithelial migration assay, blocking antibodies against ICAM-1, ICAM-2, ICAM-3, LFA-1; step analysis of adhesion, polarization, and diapedesis FASEB journal Medium 18842965
1998 LFA-1/ICAM-1 or LFA-1/ICAM-2 interactions deliver a negative regulatory signal for Th2 cytokine production. Blocking LFA-1/ICAM-1 or LFA-1/ICAM-2 interactions increased Th2 cytokines (IL-4, IL-5) 15- to 40-fold; combined blockade of both led to 100- to 1,000-fold increase, demonstrating synergistic Th2-suppressive roles. T cells from DO11.10 TCR transgenic mice stimulated by dendritic cells; blocking monoclonal antibodies to LFA-1, ICAM-1, ICAM-2; cytokine ELISAs Journal of immunology Medium 9820482
1997 ICAM-2 provides a costimulatory signal for T cell stimulation by allogeneic class II MHC in an LFA-1-dependent manner. ICAM-2 transfection on MHC II-expressing L cells enhanced T cell proliferation similarly to ICAM-1. ICAM-2-stimulated T cells mounted a secondary allogeneic response, whereas T cells stimulated without ICAM-1/-2 did not, suggesting ICAM-2 prevents anergy. ICAM-2 transfection into MHC II+ L cells, mixed lymphocyte reaction, thymidine incorporation, secondary stimulation assays Scandinavian journal of immunology Medium 9122613
2010 ICAM-2 (Icam2) is expressed on hemogenic endothelium during embryonic hematopoiesis and marks the transition from hemangioblast to hemogenic endothelium. Its expression persists on fetal liver hematopoietic progenitors. Sequential CD40 then Icam2 expression defines progressive steps in blood specification from mesoderm. Embryonic stem cell differentiation in serum-free culture, in vitro and in vivo lineage analysis, cell surface marker characterization, hematopoietic progenitor assays Stem cells Medium 20506544
2008 Downregulation of ICAM2 by siRNA enhanced radiosensitivity of OSCC cells with increased apoptosis via AKT phosphorylation (Ser473) and caspase-3 activation. Overexpression of ICAM2 conferred resistance to X-ray irradiation, suggesting ICAM2 promotes cell survival through AKT signaling. siRNA knockdown, ICAM2 overexpression, X-ray irradiation, apoptosis assays, Western blot for phospho-AKT and caspase-3 British journal of cancer Medium 18349842
1991 ICAM-2 peptide 2 (residues spanning a specific region) mediates lymphocyte adhesion through both CD11/CD18 (β2 integrin) and CD49d/CD29 (VLA-4) integrins. Blocking both anti-CD18 and anti-CD29 antibodies together caused near-complete inhibition of cell attachment to the peptide. Synthetic ICAM-2 peptides, cell attachment assays, blocking monoclonal antibodies to CD11/CD18 and CD49d/CD29 FEBS letters Low 1709118

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 855 2497351
1998 Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2. The Journal of cell biology 520 9472040
1991 Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. The Journal of experimental medicine 499 1676048
1998 Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate. The Journal of biological chemistry 271 9705328
2010 Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood-brain barrier endothelium. Journal of immunology (Baltimore, Md. : 1950) 208 20861356
1996 ICAM-2 redistributed by ezrin as a target for killer cells. Nature 200 8717043
1993 Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The American journal of pathology 194 8434643
1994 Characterization of the function of intercellular adhesion molecule (ICAM)-3 and comparison with ICAM-1 and ICAM-2 in immune responses. The Journal of experimental medicine 156 7905020
2009 Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. Blood 153 19211506
2013 β2 integrin-mediated crawling on endothelial ICAM-1 and ICAM-2 is a prerequisite for transcellular neutrophil diapedesis across the inflamed blood-brain barrier. Journal of immunology (Baltimore, Md. : 1950) 148 24259506
1998 LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. Journal of immunology (Baltimore, Md. : 1950) 148 9820482
2010 CXCL17 and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis. Gastroenterology 146 20955708
1994 Differential distribution of intercellular adhesion molecules (ICAM-1, ICAM-2, and ICAM-3) and the MS-1 antigen in normal and diseased human synovia. Their possible pathogenetic and clinical significance in rheumatoid arthritis. Arthritis and rheumatism 133 8129777
1998 T cell interaction with ICAM-1-deficient endothelium in vitro: essential role for ICAM-1 and ICAM-2 in transendothelial migration of T cells. European journal of immunology 132 9808177
2002 Intercellular adhesion molecule (ICAM)-1, but not ICAM-2, activates RhoA and stimulates c-fos and rhoA transcription in endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 114 12097408
2002 Activation of the PKB/AKT pathway by ICAM-2. Immunity 106 11825565
2015 The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues. Current opinion in hematology 104 25427141
1997 Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface. Nature 93 9153399
1995 Intercellular adhesion molecule-2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain. Journal of immunology (Baltimore, Md. : 1950) 82 7561061
2010 Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing. Blood 77 20395417
2000 Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-3 in inflammatory bowel disease. Clinical and experimental immunology 75 10931137
2005 Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis. Blood 74 15920013
1999 Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness. Immunity 74 10023766
1997 Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2. Blood 73 9326242
1998 The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Sp1 and GATA binding sites. The Journal of biological chemistry 68 9565596
1998 Contribution of CD11a/CD18, CD11b/CD18, ICAM-1 (CD54) and -2 (CD102) to human monocyte migration through endothelium and connective tissue fibroblast barriers. European journal of immunology 64 9645379
1993 A peptide from ICAM-2 binds to the leukocyte integrin CD11a/CD18 and inhibits endothelial cell adhesion. The Journal of biological chemistry 61 8349630
2009 Intercellular adhesion molecule 1 (ICAM-1), but not ICAM-2 and -3, is important for dendritic cell-mediated human immunodeficiency virus type 1 transmission. Journal of virology 54 19211748
2020 Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 Differentially Contribute to Peripheral Activation and CNS Entry of Autoaggressive Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis. Frontiers in immunology 53 31993059
1996 Binding of the cytoplasmic domain of intercellular adhesion molecule-2 (ICAM-2) to alpha-actinin. The Journal of biological chemistry 53 8824270
2007 DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through LewisY antigen expressed on ICAM-2. Molecular immunology 50 18155766
2004 DC-SIGN binds to HIV-1 glycoprotein 120 in a distinct but overlapping fashion compared with ICAM-2 and ICAM-3. The Journal of biological chemistry 50 14970226
2013 ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells in vivo. Journal of cell science 48 24317296
1996 CD11a-CD18 and CD102 interactions mediate human myeloma cell growth arrest induced by CD40 stimulation. Cancer research 48 8620513
1992 Expression of endothelial adhesion molecules in vivo. Increased endothelial ICAM-2 expression in lymphoid malignancies. The American journal of pathology 48 1373268
2008 Epithelial ICAM-1 and ICAM-2 regulate the egression of human T cells across the bronchial epithelium. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 47 18842965
1999 Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma. Molecular human reproduction 47 10050664
1994 Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte function-associated molecule 1 in human immunodeficiency virus-mediated syncytia formation. European journal of immunology 44 7916296
1999 Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3. European journal of immunology 43 10427988
1999 T cell interaction with ICAM-1-deficient endothelium in vitro: transendothelial migration of different T cell populations is mediated by endothelial ICAM-1 and ICAM-2. International immunology 43 10464174
1999 Characterisation of the tumour necrosis factor (TNF)-(alpha) response elements in the human ICAM-2 promoter. Journal of cell science 40 10574717
1998 Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium. Cell adhesion and communication 40 10223354
2022 Artemisitene suppresses rheumatoid arthritis progression via modulating METTL3-mediated N6-methyladenosine modification of ICAM2 mRNA in fibroblast-like synoviocytes. Clinical and translational medicine 39 36536495
1999 ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity. Journal of immunology (Baltimore, Md. : 1950) 37 10352278
1992 Isolation, characterization, and expression of mouse ICAM-2 complementary and genomic DNA. Journal of immunology (Baltimore, Md. : 1950) 37 1401904
1993 Intercellular adhesion molecule-2 (ICAM-2) expression on human dendritic cells. Cellular immunology 34 8098673
2001 Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters. Gene therapy 33 11426329
2004 Sialylation of ICAM-2 on platelets impairs adhesion of leukocytes via LFA-1 and DC-SIGN. Inflammation 32 15673159
1992 The expression and role in T cell adhesion of LFA-3 and ICAM-2 on human thyroid cells. Clinical immunology and immunopathology 32 1376653
2008 Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human gammadelta-T cells: implications in the design of gammadelta-T-cell-based immunotherapies for pancreatic cancer. Journal of gastroenterology and hepatology 31 19175829
2004 ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 31 15269165
2002 Binding of LFA-1 (CD11a) to intercellular adhesion molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) triggers transmigration of human immunodeficiency virus type 1-infected monocytes through mucosal epithelial cells. Journal of virology 30 11739669
1995 Activation of natural killer cell migration by leukocyte integrin-binding peptide from intracellular adhesion molecule-2 (ICAM-2). The Journal of biological chemistry 29 7721764
1999 Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily. Proceedings of the National Academy of Sciences of the United States of America 28 10077629
2021 ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo. Frontiers in immunology 27 34484188
1993 EBV peptide epitope sensitization restores human cytotoxic T cell recognition of Burkitt's lymphoma cells. Evidence for a critical role for ICAM-2. Journal of immunology (Baltimore, Md. : 1950) 27 7684421
1992 Expression of the adhesion molecules ICAM-1 and ICAM-2 on tumor cell lines does not correlate with their susceptibility to natural killer cell-mediated cytolysis: evidence for additional ligands for effector cell beta integrins. European journal of immunology 27 1348028
1991 ICAM-2 peptides mediate lymphocyte adhesion by binding to CD11a/CD18 and CD49d/CD29 integrins. FEBS letters 27 1709118
2014 ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling. Cell communication and signaling : CCS 25 24593809
2008 ICAM-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastoma. PloS one 25 18978946
2016 Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 26823454
2020 Increased expression of interferon regulated and antiviral response genes in CD31+/CD102+ lung microvascular endothelial cells from systemic sclerosis patients with end-stage interstitial lung disease. Clinical and experimental rheumatology 19 33253099
2014 Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells. Inflammation 19 24870064
2008 Inhibition of ICAM2 induces radiosensitization in oral squamous cell carcinoma cells. British journal of cancer 19 18349842
1991 The human ICAM2 gene maps to 17q23-25. Genomics 19 1769660
2002 An anti-ICAM-2 (CD102) monoclonal antibody induces immune-mediated regressions of transplanted ICAM-2-negative colon carcinomas. Cancer research 18 12036930
2013 N-glycosylation of ICAM-2 is required for ICAM-2-mediated complete suppression of metastatic potential of SK-N-AS neuroblastoma cells. BMC cancer 16 23714211
2017 Endothelium adhesion molecules ICAM-1, ICAM-2, VCAM-1 and VLA-4 expression in leprosy. Microbial pathogenesis 14 28088473
2014 ICAM-2 confers a non-metastatic phenotype in neuroblastoma cells by interaction with α-actinin. Oncogene 12 24704826
2010 The sequential expression of CD40 and Icam2 defines progressive steps in the formation of blood precursors from the mesoderm germ layer. Stem cells (Dayton, Ohio) 12 20506544
2022 Single cell multi-omic reference atlases of non-human primate immune tissues reveals CD102 as a biomarker for long-lived plasma cells. Communications biology 11 36543997
1997 ICAM-2 provides a costimulatory signal for T cell stimulation by allogeneic class II MHC. Scandinavian journal of immunology 11 9122613
2023 ICAM2 initiates trans-blood-CSF barrier migration and stemness properties in leptomeningeal metastasis of triple-negative breast cancer. Oncogene 9 37620448
2020 Novel MHC-Independent αβTCRs Specific for CD48, CD102, and CD155 Self-Proteins and Their Selection in the Thymus. Frontiers in immunology 7 32612609
2003 Intercellular adhesion molecule-2 (ICAM-2) and Pseudomonas aeruginosa ocular infection. DNA and cell biology 7 14611686
2001 Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of the adhesion protein ICAM-2. Acta crystallographica. Section D, Biological crystallography 7 11375520
2000 CD18/CD54(+CD102), CD2/CD58 pathway-independent killing of lymphokine-activated killer (LAK) cells against glioblastoma cell lines T98G and U373MG. Oncology research 6 11061342
2020 Co-immunostaining of ICAM-1, ICAM-2, and CD31 in Mouse Kidney Glomeruli. Bio-protocol 4 33659333
2019 Increased Expressions of ICAM-2 and ICAM-3 in Pterygium. Current eye research 4 30657707
2012 Expression analysis of intercellular adhesion molecule-2 (ICAM-2) in the context of classical cardiovascular risk factors in acute coronary syndrome patients. Archives of medical science : AMS 4 24482647
2005 Expression of ICAM-1, ICAM-2, NCAM-1 and VCAM-1 by human synovial cells exposed to Borrelia burgdorferi in vitro. Rheumatology international 4 16307273
2005 [Estimation of level of soluble form PECAM-1, ICAM-2 and TNF-alpha, IL-18 in serum patients with chronic myelogenic leukemia]. Przeglad lekarski 4 16521495
1998 Modulation of HLA class I antigen and ICAM-2 on endothelial cells after in vitro infection with human cytomegalovirus. Immunology and cell biology 4 9682965
2025 Proteomics uncovers ICAM2 (CD102) as a novel serum biomarker of proliferative lupus nephritis. Lupus science & medicine 2 40274316
2008 Participation of intercellular adhesion molecule-2 (CD102) in B lymphopoiesis. Immunology letters 1 18680764
2026 ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer. World journal of gastroenterology 0 41693979
2002 [Construction of recombinant human CD59 using ICAM-2 promoter for endothelial-specific expression in xenotransplantation]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 0 12905685

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