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FLASH GENE
Symbol SPP1 contributors: mct/shn - updated : 22-04-2016
HGNC name secreted phosphoprotein 1
HGNC id 11255
Location 4q22.1      Physical location : 88.896.801 - 88.904.562
Synonym name
  • secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1)
  • osteopontin/immunoglobulin alpha 1 heavy chain constant region fusion protein; secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1)
  • early T-lymphocyte activation 1
  • nephropontin/uropontin
  • bone sialoprotein 1
  • SPP1/CALPHA1 fusion
  • arginin-glycin-aspartic acid (RGD) containing glycoprotein
  • osteopontin/immunoglobulin alpha 1 heavy chain constant region fusion protein
  • urinary stone protein
  • osteopontin
  • osteopontin-C
  • osteopontin-D
  • nephropontin
  • early T-lymphocyte activation 1
    • Synonym symbol(s) OPN, BNSP, BSPI, ETA-1, OSTP, MGC110940, SPP-1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    text SIBLINGs share many common features, such as their tandem gene location
    STRUCTURE 7.76 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure
  • TP53 responsive element
  • AP-1 binding site involved in UTP-induced transcription
  • functional HNF1 binding sites in the promoter region
    • MAPPING cloned Y linked Y status confirmed
    Map cen - D4S2462 - D4S1542 - SPP1 - D4S2929 - D4S1563 - qter
    regionally located closely linked to IBSP
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1616 34 300 - 1990 1974876
  • isoform b
    • 7 splicing 1641 38 314 - 1990 1974876
  • insertion of 14 AAs at residue 58
  • isoform a
    • 6 splicing 1560 - 287 - 1990 1974876
  • isoform c
    • 8 splicing 1823 - 327 - -
    5 splicing 1511 - 273 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels    
    Digestiveintestinesmall intestine   
    Nervousbrain   highly
     spinal cord    
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
     chondrocyte
    Blood/Hematopoieticerythroblast
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Lymphoid/Immunemacrophage
    Lymphoid/ImmuneT cell
    cell lineage bone cells and decidua cells (
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • RGD attachment motif and aspartate-serine region homolog to the repeated motif ARSAM found on MEPE
  • 38 AA domain within the N terminal thrombin fragment (binding site for ITGA4B1)
  • an Arg-Gly-Asp (RGD) cell adhesion motif-mediating interactions with several integrins
  • phosphorylation and other modification of the highly conserved C-terminal region of SPP1 inhibits its interaction with the alpha-V/beta-3-integrin
    • conjugated GlycoP
    isoforms Precursor
    HOMOLOGY
    interspecies ortholog to Spp1, Mus musculus
    ortholog to spp1, Danio rerio
    ortholog to Spp1, Rattus norvegicus
    ortholog to SPP1, Pan troglodytes
    Homologene
    FAMILY
  • osteopontin family
    • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text extracellular matrix
    basic FUNCTION
  • RGD-containing extracellular matrix protein involved in ossification, mineralization of matrix, inflammation and immunity to infectious diseases
  • role for in tissue remodeling (
  • ligand of CD44, of ITGA5B3 and ITGA4B1 and major hepatocyte growth factor transcriptional target
  • involved in intestinal immune homeostasis
  • involved in post-traumatic tissue repair but not in axonal injury in the peripheral nervous system
  • may act as a novel regulator of myelination and remyelination in central nervous system
  • multifunctional protein implicated in mammary development, neoplastic change, and metastasis
  • macrophage-derived matricellular glycoprotein, inhibiting axon outgrowth
  • could be involved in chronic myelogenous leukemia (CML) stem cell biology
  • having a crucial role in allergic airway disease through regulation of dendritic cell subsets
  • playing a critical role in the process of bone remodeling
  • mediating phosphorylation or activation of multiple proteins including Rac-1 GTPase and the actin-binding protein, adducin, in erythroblasts
  • cytokine highly expressed during bone remodeling and having pro-inflammatory effects
  • modulates multiple signaling events in erythroblasts, influences Ca2+ efflux, and plays an important role in F-actin filament formation
  • plays a pivotal role not only in the development, but also in the function of Invariant natural killer T cells
  • may play an important role in facilitating calcium pyrophosphate dihydrate crystal formation in articular cartilage
  • required for the effects of mechanical stress on bone
  • has an important role in the effects of unloading-induced alterations of differentiation of bone marrow into osteoblasts and osteoclasts
  • plays an important role in regulating lymphocyte adhesion and cytokine production associated with inflammatory processes and autoimmune diseases
  • enhancing angiogenesis through PI3K/AKT and ERK-mediated pathways with VEGF acting as a positive feedback signal
  • enhances angiogenesis directly through PI3K/AKT- and ERK-mediated pathways with VEGF acting as a positive feedback signal
  • have potent proinflammatory functions
  • Dental Bud Stem Cells (DBSCs) differentiation toward osteoblastic lineage was enhanced when cells were grown on fibronectin (FN1), vitronectin (VTN), and osteopontin (SPP1)
  • is an abundant bone extracellular matrix protein with roles in mineralization, cell adhesion and cell migration, and it has putative consensus sequence sites for cleavage by PCSK5, which may modify its function in bone
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , immunity/defense , inflammation , ossification
    text skeletal development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MMP3 and MMP7 at tumor and wound healing sites for regulation of OPN bioactivity
  • ligand for integrin alpha-V/beta-3/interaction with TP53 (transcription target)
  • integrin alpha v beta 3, integrin alpha 4 beta 1, and integrin alpha v beta 5 (
  • integrin alpha(9)beta(1) (
  • Insulin-like growth factor (IGF)-binding protein-5, IGFBP5 (
  • matrix metalloproteinase-3, MMP3 and matrix metalloproteinase-7, MMP7 (
  • receptor CD44 (
  • IFITM3 and SPP1
  • IFNG and IL27
  • J domain of DNAJB6 is involved in mediating SPP1 suppression
  • induced the proliferation and migration of VSMCs as well as the upregulation of SPP1 via the upregulation of EGR1
  • requirement of FOXC2 for inorganic phosphate (Pi)-induced osteopontin (SPP1) expression and secretion from cancer cells as necessary for the angiogenic response
  • SPP1 can be polymerized by the cross-linking enzyme transglutaminase 2 (TGM2), and polymerization has been shown to enhance the biological activity of SPP1
  • cleavage of SPP1 by PCSK5 may modify the function of SPP1 in bone and/or modulate other enzymatic cleavages of SPP1, leading to alterations in the bone phenotype
    • cell & other
  • stimulating T cell proliferation, T helper cell 1 cytokyne, enhancing IFNG and IL12 production
    • REGULATION
    Other regulated by CBFA1 and ETS1 in the skeletal tissue
    regulated by axon -derived signals
    expression in lymphoid cells depends on the presence of POU2AF1
    regulated by AGT and PDGF via AP-1 activation
    regulated by ETV4, CTNNB, LEF1 and JUN
    modulation of its phosphorylation level by ACP5, that could regulate the extent of degradation such as depth and area at each bone resorption site by triggering osteoclast detachment and facilitate subsequent migration on the bone surface
    its regulation may be directly mediated by ING2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    overexpressed in autoimmune demyelinating disease (multiple sclerosis) and in Dianzani autoimmune/lymphoproliferative disease
    constitutional     --low  
    in Crohn disease of the terminal ileon
    tumoral     --over  
    in breast cancer in progression
    tumoral     --over  
    in chronic myelogenous leukemia (CML) patients because SPP1 is deregulated by BCR-ABL oncogene
    tumoral     --over  
    in glioma
    tumoral     --over  
    in osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis
    tumoral     --over  
    dramatically elevated in hepatocellular carcinoma (HCC) tissues with metastasis and correlates with poorer overall survival and higher recurrence rate
    Susceptibility
  • to systemic lupus erythematosus
  • to glioma
    • Variant & Polymorphism other
  • 707 C->T associated with systemic lupus
  • association between SPP1 promoter polymorphisms and glioma risk
  • rs4754 may be a susceptible factor for Vogt-Koyanagi-Harada disease in a Chinese Han population (
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyimmunodeficiency 
    SPP1 antibody may provide a potential therapeutic target for the treatment of T cell-mediated immune diseases
    allergyasthm 
    important therapeutic target in allergic airway disease
    cancerangiogenesis 
    might be a valuable target for developing novel antiangiogenesis therapy for treatment of cancer
    cancerdigestiveliver
    with S100A6, may be promising diagnostic markers and therapeutic targets for hepatocellular carcinoma
    ANIMAL & CELL MODELS
  • induction of Osteopontin expression is strongly associated with rat ventricular hypertrophy (
  • Osteopontin null mutant mice are fertile but showed a significantly decreased level of debridement, greater disorganization of matrix, and an alteration of collagen fibrillogenesis leading to small diameter collagen fibrils (
  • Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice (
  • Mice deficient in osteopontin gene expression have severely impaired type-1 immunity to viral infection and bacterial infection and do not develop sarcoid-type granulomas (
  • Osteopontin-deficient mice were resistant to progressive autoimmune encephalomyelitis and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma (
  • SLAYGLR sequence of murine osteopontin, is critically involved in the pathogenesis of a murine model of rheumatoid arthritis (
  • OPN- and NKT cell-deficient mice were refractory to Concanavalin A-induced hepatitis (
  • Obese mice lacking osteopontin displayed improved insulin sensitivity in the absence of an effect on diet-induced obesity, body composition, or energy expenditure, and exhibited decreased markers of inflammation, both in adipose tissue and systemically (
  • Periapical bone loss associated with endodontic infection was significantly more severe in OPN-deficient mice compared with wild-type 3 weeks after infection, and was associated with increased areas of inflammation (