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FLASH GENE
Symbol GPNMB contributors: mct/npt - updated : 21-02-2018
HGNC name glycoprotein non-metastatic protein B
HGNC id 4462
Corresponding disease
ACDC Amyloidosis cutis dyschromica
Location 7p15.3      Physical location : 23.286.315 - 23.314.728
Synonym name
  • glycoprotein nmb-like protein
  • osteoactivin
  • transmembrane glycoprotein HGFIN
  • Synonym symbol(s) NMB, HGFIN
    DNA
    TYPE functioning gene
    STRUCTURE 29.90 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • single dominant start site around 30 bp downstream of a TATA-like element
  • conserved AP-1 (TGAGTCA) site was identified and the most conserved region contains a consensus M-box element (TCACATGA) for binding of MITF
  • MAPPING cloned Y linked N status provisional
    Physical map
    ASNS 7q21.3 asparagine synthetase LOC392780 7 similar to cardiac leiomodin DRCTNNB1A 7p15.3 similar to cardiac leiomodin C7orf30 7p15.3 chromosome 7 open reading frame 30 WASL 7q31.3 Wiskott-Aldrich syndrome-like IMP-3 7p11 IGF-II mRNA-binding protein 3 LOC392751 7 LOC392751 LOC286031 8p23.1 hypothetical protein LOC286031 LOC392752 7 similar to seven transmembrane helix receptor LOC392753 7 similar to olfactory receptor GA_x6K02T2PVTD-14054886-14053957 OCM 7p13-p11 oncomodulin HYAL4 7q31.3 hyaluronoglucosaminidase 4 SBBI26 7p15.3 SBBI26 protein LOC392642 7 similar to Neuronal protein 3.1 (p311 protein) LOC392643 7 hypothetical gene supported by BC026177 TRA2A 7p15.3 transformer-2 alpha KPI2 7q22.1 transformer-2 alpha NUPL2 7p15 nucleoporin like 2 SPAM1 7q31.3 sperm adhesion molecule 1 (PH-20 hyaluronidase, zona pellucida binding) LOC392644 7 hypothetical gene supported by BC022025; NM_003993 GPNMB 7p15 glycoprotein (transmembrane) nmb LOC90693 7p15.3 alpha-1,3(6)-mannosylglycoprotein beta-1,6-N-acetyl-glucosaminyltransferase-like MIST1 7q22.1 class II bHLH protein MIST1 DKFZP434B0335 7q22.1 DKFZP434B0335 protein C7orf30 7p15.3 chromosome 7 open reading frame 30 IMP-3 7p11 IGF-II mRNA-binding protein 3 LOC392981 7 similar to RIKEN cDNA 6332401O19 gene LOC340277 BRI3 7q22.1 brain protein I3 STK31 7p15.3 serine/threonine kinase 31 LOC55971 7q22.1 insulin receptor tyrosine kinase substrate LOC389473 7 similar to Neuronal protein 3.1 (p311 protein) MGC27348 7p15.3 similar to ribosomal protein S2; 40S ribosomal protein S2 TRA2A 7p15.3 transformer-2 alpha
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2775 63 572 - 2017 28104809
    11 - 2739 - 560 - 2017 28104809
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveesophagus   highly
     mouth   highly
    Lymphoid/Immunethymus   highly
    Nervousbrainlimbic systemhippocampus   Homo sapiens
    Skin/Tegumentskin   highly Homo sapiens
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis   Homo sapiens
    Epithelialbarrier liningretinal pigment epithelium (RPE)  
    Nervouscentral    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Nervousastrocyte Homo sapiens
    Nervousneuron Homo sapiens
    Skin/Tegumentkeratinocyte Homo sapiens
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage melanocytes lineage
    cell lines low metastatic cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one PKD domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Gpnmb
    intraspecies homolog to SILV
    Homologene
    FAMILY
  • PMEL-17 family
  • NMB family
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • co-localized with integrin beta3 and/or beta1 in a hetero-polymeric complex in osteoclasts
  • Type 1 transmembrane glycosylated protein
  • partially localized in melanosomes, lysosomes, and early endosomes
  • basic FUNCTION
  • involved in growth delay and reduction of metastatic potential
  • might be central to malignancies and might also behave as a tumor suppressor
  • intracellular, endosomal/melanosomal compartment specific protein important for melanin biosynthesis and the development of the retinal pigment epithelium and iris
  • playing a role in mature osteoclast function
  • resides in the endocytic pathway of mature osteoclast-like cells and is possibly targeted to the plasma membrane or extracellular space upon osteoclast terminal differentiation
  • required for the differentiation of osteoblast cells
  • osteoclast-derived GPNMB is a novel stimulator of osteoclast activity and bone resorption
  • plays an important role in the regulation of osteoblast differentiation and function
  • GPNMB contributes to the tissue reparative phenotype of M2 macrophages and positively regulates functional activities of mesenchymal stem cells (MSCs)
  • plays important roles in various types of cancer and amyotrophic lateral sclerosis (ALS)
  • might be an inducer for glioma and could enhance matrix metalloproteinase activity through WNT/CTNNB1 pathway to contribute to glioma tumorigenesis
  • GPNMB promotes glioma growth via ATP1A1, ATP1A2, ATP1A3, ATP1A4
  • GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation
  • augments bone mineral deposition by stimulating osteoblast differentiation, and has anti-inflammatory and reparative functions
  • promotes aggressive behaviors such as tumor cell proliferation, migration, and invasion
  • exerts its pro-tumorigenic role both intracellularly and in a paracrine fashion through shedding its extracellular domain
  • implicated in melanosome formation, autophagy, phagocytosis, tissue repair, and negative regulation of inflammation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with TP53 (central role in GPNMB expression, which appears to determine the behavior of the cancer cells)
  • interacting with MITF
  • ADAM10 is a sheddase capable of releasing the GPNMB ectodomain from the surface of breast cancer cells, which induces endothelial cell migration
  • DLX3 and DLX5 proteins were found to activate the GPNMB transcription, whereas, MSX2 suppressed BMP2-induced GPNMB transcription
  • stimulates bone regeneration by inducing osteogenesis and angiogenesis via regulating FGFR1 signaling
  • is a matricellular protein that stimulates osteoblast adhesion through binding to ITGA5, ITGB1 integrin
  • MITF is a critical regulator of GPNMB expression in dendritic cells
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ACDC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in aggressive breast cancers and capable of promoting breast cancer metastasis to bone
    tumoral     --over  
    in epithelial ovarian cancer
    constitutional       gain of function
    in Niemann-Pick type C (NPC) patients, most likely due to glycosphingolipids (GSLs) accumulation
    Susceptibility
    Variant & Polymorphism
    Candidate gene for CYMD (cystoid macular dystrophy)
    Marker
  • is a novel marker for obesity-induced adipose tissue macrophages (ATMs) infiltration and potentiator of interleukin-4 responses
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    may serve as an attractive therapeutic target of cancer treatment
    neurologyneurodegenerative 
    can be a target for therapeutic intervention for suppressing motor neuron degeneration in ALS
    cancerreproductivebreast
    represents an attractive target for therapeutic intervention in breast cancer
    ANIMAL & CELL MODELS
  • Gpnmb deficiency attenuated the dilated cardiomyopathy in muscle lim protein knockout mice but could not prevent cardiac hypertrophy induced by isoprenaline infusion