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FLASH GENE
Symbol ITGAM contributors: mct/npt - updated : 22-12-2017
HGNC name integrin, alpha M (complement component 3 receptor 3 subunit)
HGNC id 6149
Location 16p11.2      Physical location : 31.271.287 - 31.344.211
Synonym name
  • integrin, alpha M (complement component receptor 3, alpha; also known as CD11b (p170), macrophage antigen alpha polypeptide)
  • cell differentiation antigen CD11b (p170),165/95kD,CR3 receptor, identified by antibodies Mo1, Mac-1
  • macrophage antigen alpha polypeptide
  • neutrophil adherence receptor alpha-M subunit
  • CD11 antigen-like family member B
  • leukocyte adhesion receptor MO1
  • Synonym symbol(s) CD11B, CR3A, MAC-1, MAC1A, MGC117044, MO1A, SLEB6
    DNA
    TYPE functioning gene
    STRUCTURE 72.93 kb     30 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure two consensus binding sites for Sp1, a GATA motif, and a purine-rich sequence that presents potential binding sites for members of the ETS family of genes (Pahl 1992)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    30 - 4742 - 1152 - 2016 27534550
    - - 4745 - 1153 - 2016 27534550
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   moderately
     thymus   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Lymphoid/Immunenatural killer
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal large extracellular domain
  • a sevenfold repeated structure with putative cation-binding motifs in the three of four C terminal repeats
  • an I domain (VWFa domain) inserted between the second and third repeats ligand binding
  • a single transmembrane segment (1TM)
  • a short conserved cytoplasmic domain
  • conjugated GlycoP
    mono polymer heteromer , dimer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to rattus Itgam (73.59 pc)
    homolog to murine Itgam (74.65 pc)
    Homologene
    FAMILY
  • integrin alpha chain family
  • CATEGORY adhesion , immunity/defense , antigen , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • cell surface adhesion receptor mediating cell-adhesion to extra cellular matrix or to other cells,through hetero dimerization and connecting to the cytoskeleton and various signaling molecules within cells
  • playing an important role in osteoclastogenesis
  • differential involvement of ITGAX and ITGAM in adhesion and subsequent cytoskeletal changes in monocytes exposed to different conditions indicates the importance of each integrin in distinct responses during inflammation (Georgakopoulos 2008)
  • marked differences in the signaling requirements for expression of ENPP3 and ITGAM versus CD63 expression and histamine release in human basophils
  • role of ITGAM in maintaining autoreactive B cell tolerance
  • ITGAM-mediated atrial polymorphonuclear neutrophils (PMN) infiltration linked to the formation of fibrosis, which promotes the initiation and propagation of atrial fibrillation (AF)
  • plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of adipose tissue macrophages (ATMs)
  • novel role for ITGAM in the regulation of soluble beta-amyloid (APP) clearance independent of phagocytosis
  • function of ITGAM in antibody responses and the role of CD11b as a vital regulator of class switch recombination (CSR)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    text phagocytosis of complement-opsonized micro-organism
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • dimerizing with ITGB2 in to form a leukocyte-specific integrin
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mn2+ throught the A domain
  • Ca2+
  • protein
  • binds to BCAP31, a member of a novel class of sorting proteins regulating cellular anterograde transport
  • interacting with BST1
  • new function for WAS in the control of neutrophil polarity via crosstalk between ITGAM and microtubules
  • TLR4-mediated expression of ITGAM in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis
  • PRKCA promotes the downregulation of VSIG4 and upregulation of ITGAM expression and TNF and IL6 production, a mechanism that may promote inflammation
  • regulates IL13 activity in macrophages by directly interacting with IL13RA1
  • crucial role of GABPA in myeloid cell differentiation and ITGAM/CD11b is a novel GABPA target gene
  • binds to ligands to regulate leukocyte adhesion and migration across the endothelium or epithelium
  • FOLR2 is a novel ITGAM/ITGB2 regulator for trafficking and homing of a subset of macrophages on collagen
  • cell & other
  • unstimulated endothelial cells
  • REGULATION
    Other genetic inactivation of ITGAM promotes IL13-induced JAK/STAT activation in macrophages, resulting in enhanced polarization along the alternative activation pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP nonsynonymous coding SNP rs1143679 in exon 3 is strongly associated with increased risk of SLE
    Candidate gene
    Marker
  • monocyte-platelet aggregates and ITGAM expression are markers for thrombogenicity in atrial fibrillation
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    potential of ITGAM as a therapeutic target in colorectal cancer
    ANIMAL & CELL MODELS
  • high-fat diet-induced insulin resistance was significantly reduced in CD11b-deficient mice