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FLASH GENE
Symbol ICAM1 contributors: mct - updated : 25-08-2016
HGNC name intercellular adhesion molecule 1
HGNC id 5344
Corresponding disease
FCNC1 candidiasis familial chronic mucocutaneous, 1
Location 19p13.2      Physical location : 10.381.516 - 10.397.291
Synonym name
  • Ig superfamily cell differentiation antigen CD54, 90kD, identified by antibodies RR1/1, LB-2, 7F7, 8F5, WEHI-CAMI, OKT27, F2B1.8, Myl3, 84H10
  • human rhinovirus receptor
  • major group rhinovirus receptor
  • CD54 antigen
  • cell surface glycoprotein P3.58
  • Synonym symbol(s) CD54, BB2, ICA1, P3.58, ICAM-1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 15.78 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • promoter contains several cis-active regulatory elements including 2 Ets binding sites (EBSs) located at positions -158 and -138 relatively to the AUG, and functional cooperation between STAT1 and ETS1 to optimize ICAM1 gene transcription(
  • MAPPING cloned Y linked Y status confirmed
    Physical map
    LOC162993 19p13.2 hypothetical protein LOC162993 UBE2L4 19q13.1-q13.2 ubiquitin-conjugating enzyme E2L 4 FBXL12 19p13.2 F-box and leucine-rich repeat protein 12 PIN1 19p13.2 protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1 UBL5 19p13.3 ubiquitin-like 5 LOC390888 19 similar to 60S ribosomal protein L10 (QM protein homolog) OLFM2 19p13.2 olfactomedin 2 COL5A3 19p13.2 collagen, type V, alpha 3 RDH8 19p13.2-p13.3 retinol dehydrogenase 8 (all-trans) LOC388502 19 similar to Complement C3 precursor LOC388503 19 similar to Complement C3-1 LOC147740 19p13.2 similar to complement C3 protein (GPC3) precursor FLJ11286 19p13.2 hypothetical protein FLJ11286 ANGPTL6 19p13.2 angiopoietin-like 6 PPAN 19p13 peter pan homolog (Drosophila) P2RY11 19p13.2 purinergic receptor P2Y, G-protein coupled, 11 EIF3S4 19p13.2 eukaryotic translation initiation factor 3, subunit 4 delta, 44kDa DNMT1 19p13.2 DNA (cytosine-5-)-methyltransferase 1 EDG5 19p13.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 5 LOC388504 19 LOC388504 MRPL4 19p13.2 mitochondrial ribosomal protein L4 ICAM1 19p13.3-p13.2 intercellular adhesion molecule 1 (CD54), human rhinovirus receptor ICAM4 19p13.2-cen intercellular adhesion molecule 4, Landsteiner-Wiener blood group ICAM5 19p13.2 intercellular adhesion molecule 5, telencephalin LOC388505 MGC19604 19p13.2 similar to RIKEN cDNA B230118G17 gene RAVER1 19p13.2 RAVER1 ICAM3 19p13.3-p13.2 intercellular adhesion molecule 3 TYK2 19p13.2 tyrosine kinase 2 CDC37 19p13.2 CDC37 cell division cycle 37 homolog (S. cerevisiae) PDE4A 19p13.2 phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila) KEAP1 19p13.2 kelch-like ECH-associated protein 1 EDG8 19p13.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 8 AUTL4 19p13.2 AUT-like 4, cysteine endopeptidase (S. cerevisiae) FLJ12949 19p13.2 hypothetical protein FLJ12949 CDKN2D 19p13.2 cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) AP1M2 19p13.2 adaptor-related protein complex 1, mu 2 subunit CTL2 19p13.1 adaptor-related protein complex 1, mu 2 subunit ILF3 19p13 interleukin enhancer binding factor 3, 90kDa QTRT1 19p13.3 queuine tRNA-ribosyltransferase 1 (tRNA-guanine transglycosylase) DNM2 19p13.2 dynamin 2
    RNA
    TRANSCRIPTS type messenger
    text alternatively spliced isoforms that are functional, and play key roles during the progression of CNS inflammation (PMID: 20371120)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 3249 55.2 532 - 2001 11390397
    - - - - - - 2010 20529672
  • also called mICAM1
  • membranous form
  • on exosomes exhibits potent immune modulatory activity
  • on exosomes was functional in leukocyte adhesion and exhibits
  • immune modulatory activity
    - - - - - - 2010 20529672
  • also called sICAM1
  • soluble form
  • cannot exert potent immune modulatory activity due to its low affinity for leukocyte function-associated antigen-1 (LFA-1) or membrane attack complex-1
  • increased levels in the serum of patients with inflammations, infections, and cancer, indicating that it may be a useful parameter for the diagnosis and evaluation of these pathologic conditions
  • plays a role in inflammation- and tumor-mediated neovascularization
  • with ICAM1, have a dual effect on bone homeostasis, increasing osteoclast activity while lowering osteoblast anabolic activity (PMID: 18979153)
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Digestivemouthtongue  highly
    Endocrinepancreas   highly
    Respiratorylung   moderately
    Urinarykidney   highly
    Visualeyeanterior segmentconjunctiva  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective    
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Lymphoid    
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Cardiovascularendothelial cell
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • a signal sequence
  • an extracellular region with five Ig-like C2-type domains
  • a single transmembrane segment (1TM)
  • a cytoplasmic C terminus, containing a positively charged aminoacid cluster in the juxtamembrane cytoplasmic domain, ERM proteins binding
  • conjugated GlycoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to rattus Icam1 (53.31 pc)
    homolog to murine Icam1 (54.25 pc)
    Homologene
    FAMILY
  • immunoglobulin superfamily of adhesion proteins
  • ICAM family
  • CATEGORY adhesion , antigen
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text type I transmembrane protein
    basic FUNCTION
  • inhibiting interleukin 4 production by naive T cells
  • playing a role in cell to cell mediated immune response
  • clustering in an endothelial actin rich docking structure with VCAM1, MSN, VIL2
  • mediating leukocytes migration into sites of airway inflammation and activation of T cells
  • may be playing an important role for endothelial cell migration, through a pathway regulating endothelial nitric-oxide synthase activation and organization of the actin cytoskeleton
  • playing an essential role of with ITGB2 in mediating EPC (endothelial progenitor cells) recruitment, angiogenesis, and repair to the infarcted myocardium
  • implicated in neutrophil and monocyte-endothelial cell adhesion, processes contributing to myocardial neutrophil infiltration and microvascular coronary slow flow
  • on osteoclast precursors manifested as clusters which localized at the baso-lateral membrane
  • dynamic molecule localized in the apical membrane of the endothelium and clusters upon binding to leukocytes
  • AGER and ICAM1 are a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute trauma-induced inflammatory response
  • functions in leukocyte trafficking, activation, and the formation of the immunological synapse
  • with VCAM1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression
  • inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions
  • expressed by cardiac fibroblasts with SELE and CXC chemokines in response to proinflammatory cytokine stimulation in the infarcted myocardium
  • AGER and ICAM1 differentially regulate leukocyte adhesion in a stimulus-dependent manner
  • role of endothelial cell adhesion molecules SELP, SELE and ICAM1 in leucocyte recruitment induced by exogenous methylglyoxal in diabetes
  • RAC1 is required for ICAM1 clustering, whereas RHOG controls membrane protrusion formation
  • functions to enhance the strength of antigenic stimulation, extend the duration of contact with antigen-presenting cells, and augment cytokine signals, which are all factors that influence peripheral CD8 T-cell differentiation
  • potential dual roles in both promoting the decay of effector responses and programming the sensitivity of memory CD8 T cells to secondary stimuli
  • CELLULAR PROCESS cell life
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • dimer with ITGAL
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand for ITGB2 (CD11A/CD18)
  • interacting with ezrin, EZR and ICAM2 in microvillar projections under phosphatidylinositol-4,5 biphosphate regulation
  • interactions both within the host and between the host and a number of pathogenes
  • interacting with AGER
  • interacting with IFI16 (mediates ICAM1 stimulation by TNF-alpha through the NF-kappaB pathway, thus reinforcing the role of the IFI16 molecule in the inflammation process)
  • interacting with FLNB (filamin B is required for the lateral mobility of ICAM1 and for ICAM1-induced transmigration of leukocytes)
  • SVEP1 and SRPX2 seemed to act as regulators of ICAM1 and E-selectin shedding and influence the expression of membrane bound adhesion molecules
  • associations at the PNPLA3, RELA, and SH2B3 loci
  • thrombin (thrombin binding region in the sixth EGF like repeat)THBD and ICAM1 were induced with MIF addition in a dose-dependent and time-dependent manner
  • upon clustering of ICAM1, the Rho-guanine nucleotide exchange factor TRIO activates RAC1, prior to activating RHOG, in a filamin-dependent manner
  • ICAM1 and VCAM1, as reflecting endothelial dysfunction biomarkers, play key roles at the early stage of inflammatory response to facilitate leukocytes adhesion and transmigration in vascular endothelial cells
  • ITLN1 inhibition of TNF-induced expression of VCAM1 and ICAM1 is mediated by its down-regulation of ERK/NFKB signaling pathway
  • ITGAL/ICAM1-dependent interactions between T cells and Dendritic cells play a crucial role not only in supporting firm arrest during Ag recognition but also in facilitating the Ag scanning processes
  • HMGB1 promotes an inflammatory response by inducing the expression of ICAM1 and P-selectin via AGER-mediated stimulation of the endoplasmic reticulum stress pathway
  • CLOCK is a positive regulator of ICAM1, and promotes the adhesion of mononuclear cells to endothelial cells
  • increased the cell migration and expression of intercellular adhesion molecule-1 (ICAM1) in human osteosarcoma cells
  • APOM suppressed TNF-induced expression of ICAM1 and VCAM1 through inhibiting the activity of NFKB1
  • NSUN2 upregulates the expression of ICAM1 by methylating ICAM1 mRNA, and this regulatory process impacts on vascular inflammation and allograft arteriosclerosis
  • role of KDM7A in ICAM1 protein stabilization
  • endothelial cell PTPN11 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM1-CDH5 interaction
  • CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTP&
  • 8209;mediated ICAM1 and IL8 mRNA decay
    cell & other
    REGULATION
    induced by upregulated by cytokines
    Other regulated in T cells by phosphotyrosyl phosphatase activity through NFKappaB, ETS and STAT1 dependent signaling pathway
    ubiquitinated and downregulated by MARCH9
    ICAM1 clustering is regulated in an inside-out fashion through the actin cytoskeleton
    IL1A regulates CXCL1, CXCL10, and ICAM1 in network form in oral keratinocytes
    ASSOCIATED DISORDERS
    corresponding disease(s) FCNC1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    during angiogenesis
    constitutional     --over  
    in Alzheimer disease
    tumoral     --low  
    in primary myeloma cells unexpectedly showed constitutively lower expressions than normal bone marrow (BM) plasma cells
    constitutional     --over  
    increased leucocyte adhesion
    constitutional     --over  
    in preeclamptic placenta
    constitutional     --low  
    in N-glycosylation-deficient cells
    Susceptibility
  • to multiple sclerosis susceptibility
  • to type I diabetes
  • to Behcet's disease
  • to ulcerative colitis and Crohn
  • some allele(s) predisposing to cerebral malaria
  • to asthma
  • Variant & Polymorphism SNP , other
  • G/R241 associated with Behcet's disease
  • E/E469 associated with ulcerative colitis and Crohn
  • SNP 241G>A and 469G>A associated with reduced risk for asthma
  • Candidate gene for FCNC1
    Marker
  • can be a useful cellular hypoglycosylation biomarker
  • could be a useful hypoglycosylation biomarker to assess gene complementation of CDG-1 patient cells and to monitor improved glycosylation in response to therapeutic drugs
  • Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheromacardiac
    important potential therapeutic target in myocardial infarction
    immunologyinfectious 
    disrupting ICAM-1 interactions may represent a unique therapeutic target for bolstering immunity in patients with chronic infection
    ANIMAL & CELL MODELS
  • abortive responses and a failure to form a memory T-cell compartment in Icam-1–deficient mice following peptide or protein immunization