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GPNMB (glycoprotein (transmembrane) nmb)

Written2009-10Shyam A Patel, Philip K Lim, Pranela Rameshwar
University of Medicine, Dentistry of New Jersey - New Jersey Medical School,Newark, New Jersey, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesglycoprotein (transmembrane) nmb
Alias_symbol (synonym)NMB
HGFIN
Other aliasosteoactivin
HGNC (Hugo) GPNMB
LocusID (NCBI) 10457
Atlas_Id 40739
Location 7p15.3  [Link to chromosome band 7p15]
Location_base_pair Starts at 23246697 and ends at 23275110 bp from pter ( according to hg19-Feb_2009)  [Mapping GPNMB.png]
Fusion genes
(updated 2016)
AHNAK (11q12.3) / GPNMB (7p15.3)GPNMB (7p15.3) / DDX27 (20q13.13)GPNMB (7p15.3) / NUPL2 (7p15.3)
GPNMB (7p15.3) / TSIX (Xq13.2)SP4 (7p15.3) / GPNMB (7p15.3)

DNA/RNA

Description The GPNMB gene maps (Homo sapiens) on the plus strand of chromosome 7p15 between 23,252,841 and 23,281,254 bp from the promoter and spans 28,414 bp.
Transcription 2 transcript variants:

Variant 1:
- 2775bp, accession #: NM_001005340.1
- the longer transcript
- encodes the longer isoform (isoform a)
- open reading frame from bp 162 to 1880
- 11 exons

Variant 2:
- accession #: NM_002510.2
- undergoes alternative splicing and uses an in-frame splice site
- conserved N- and C-terminals compared to isoform a, but decreased in length

Protein

Note The GPNMB gene, which is the human homolog of murine osteoactivin, encodes a type I transmembrane glycoprotein. It has homology to the melanocyte specific protein precursor pMEL17. GPNMB expression is inversely correlated with aggressiveness of melanoma cell lines. GPNMB is thought to be inversely correlated with metastatic potential, although limited data is available.
Description Two protein isoforms exist: isoform a: 572 a.a. ; isoform b: 560 a.a. .
Expression GPNMB is expressed in osteoclasts, dendritic cells, macrophages, and breast epithelia. Its expression is nearly undetectable in monocytes but increases upon conversion of monocytes to macrophages.
Localisation GPNMB localizes to the plasma membrane, as it is a type I transmembrane glycoprotein. It is also found in melanosomes and membrane-bound vesicles in the cytoplasm.
Function GPNMB is involved in binding to heparin sulfate and integrins. It functions in mineralization of bone and differentiation of osteoblasts. It also functions in cellular adhesion. It is thought to reduce inflammation involving macrophages.
Homology Homo sapiens GPNMB shares sequence homology with mouse and rat sequences. GPNMB shares structural homology with neurokinin 1 (NK1) and can interact with the NK ligand substance P.

Implicated in

Note
  
Entity Breast cancer
Note It is unclear to date whether GPNMB plays a tumor suppressive role or oncogenic role in breast cancer.
Disease In a murine model, osteoactivin (OA) has been associated with enhanced invasiveness of breast cancer cells in vivo, and forced overexpression of OA in weakly bone metastatic cells lines resulted in increased migratory and invasive characteristics in vitro (Rose et al., 2007). Furthermore, analysis of 51 breast cancer cell lines revealed higher osteoactivin expression than normal breast MCF-12A cells and in estrogen receptor negative breast tumors (Rose and Siegel, 2007). However, other studies with non-tumorigenic human breast cancer cells have shown that there was increased migration and evidence of transformation and loss of contact dependency in the absence of GPNMB/HGFIN (Metz et al., 2007).
  
  
Entity Glioblastoma multiforme (GBM)
Note In immunocompromised mice, glioma cells expressing osteoactivin and osteonectin (two strucurally bone-related genes) developed a highly invasive phenotype and invaded the brain along blood vessels when implanted intracranially (Rich et al., 2003).
Disease Evaluation of 50 GBM patient tumor samples revealed that 35 out of 50 samples (70%) were positive for GPNMB wild-type and splice variant transcripts while the remaining 30% were positive for wild-type only (Kuan et al., 2006). This is in contrast to normal brain samples that expressed little or no GPNMB mRNA (Kuan et al., 2006).
Prognosis Detection of GPNMB mRNA and surface membrane protein in glioma cells may potentially be used as a tumor-associated antigen for targeting by therapeutic treatment (Kuan et al., 2006).
  
  
Entity Melanoma
Note Analysis of a cDNA library between lowly and highly metastatic human melanoma showed the preferential expresion of GPNMB in low-metastatic cell lines (Weterman et al., 1995). Additionally, transfection of partial GPNMB cDNA into highly-metastatic melanoma cell line resulted in slower subcutaneous tumor growth in nude mice (Weterman et al., 1995).
Disease A potential therapeutic agent in the treatment of malignant melanomas is an antibody-drug conjugate tartgeting GPNMB (Pollack et al., 2007). Intravenous administration of the immunoconjugate in athymic mice with human melanoma xenografts showed inhibition of tumor growth and complete regression of the tumor (Pollack et al., 2007).
  
  
Entity End-stage kidney disease
Note Macrophages involved in uremia have elevated levels of GPNMB expression. Its role in end-stage kidney disease may relate to its role in soft tissue calcification and arteriosclerosis (Pahl et al., 2009).
  
  
Entity Acute liver injury
Note In normal rat livers, OA was found to be expressed in high levels in Kupffer cells and peritoneal macrophages (Haralanova-Ilieva et al., 2005). Upon induction of acute liver injury after carbon tetrachloride administration, OA expression was upregulated after 2 days and returned to normal levels after 7 days (Haralanova-Ilieva et al., 2005). In normal human liver, OA RNA was not detected while fulminant hepatitis B and C infections, paracetamol intoxication, and liver cirrhosis all resulted in positive OA RNA levels (Haralanova-Ilieva et al., 2005).
  
  
Entity Osteopetrosis
Note OA cDNA was found to be overexpressed 3- to 4-fold in rats with osteopetrotic bones when compared to normal rat long bones (Safadi et al., 2001). Furthermore, OA mRNA was primarily localized in cuboidal osteoblasts lining bone surfaces (Safadi et al., 2001).
Disease Osteopetrosis, also known as marble bone disease, is a rare hereditary disease which results in thickening and hardening of bones due to deficient osteoclast activity (Kumar et al., 2003). OA is expressed at highest levels in primary osteoblasts and thus, may account for the imbalance in activity of osteoblasts and osteoclasts in osteopetrosis (Sadafai et al., 2001).
  

Bibliography

Expression of osteoactivin in rat and human liver and isolated rat liver cells.
Haralanova-Ilieva B, Ramadori G, Armbrust T.
J Hepatol. 2005 Apr;42(4):565-72.
PMID 15763343
 
Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.
Kuan CT, Wakiya K, Dowell JM, Herndon JE 2nd, Reardon DA, Graner MW, Riggins GJ, Wikstrand CJ, Bigner DD.
Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):1970-82.
PMID 16609006
 
Diseases of Bone - Osteopetrosis.
Kumar V, Cotran RS, Robbins SL.
Robbins Basic Pathology (7th Edition). 2003:757.
 
Role of human HGFIN/nmb in breast cancer.
Metz RL, Patel PS, Hameed M, Bryan M, Rameshwar P.
Breast Cancer Res. 2007;9(5):R58.
PMID 17845721
 
Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease.
Pahl MV, Vaziri ND, Yuan J, Adler SG.
Clin J Am Soc Nephrol. 2009 Oct 15. [Epub ahead of print]
PMID 19833906
 
Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB.
Pollack VA, Alvarez E, Tse KF, Torgov MY, Xie S, Shenoy SG, MacDougall JR, Arrol S, Zhong H, Gerwien RW, Hahne WF, Senter PD, Jeffers ME, Lichenstein HS, LaRochelle WJ.
Cancer Chemother Pharmacol. 2007 Aug;60(3):423-35. Epub 2007 Jun 1.
PMID 17541593
 
Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.
Rich JN, Shi Q, Hjelmeland M, Cummings TJ, Kuan CT, Bigner DD, Counter CM, Wang XF.
J Biol Chem. 2003 May 2;278(18):15951-7. Epub 2003 Feb 17.
PMID 12590137
 
Osteoactivin promotes breast cancer metastasis to bone.
Rose AA, Pepin F, Russo C, Abou Khalil JE, Hallett M, Siegel PM.
Mol Cancer Res. 2007 Oct;5(10):1001-14.
PMID 17951401
 
Osteoactivin/HGFIN: is it a tumor suppressor or mediator of metastasis in breast cancer?
Rose AA, Siegel PM.
Breast Cancer Res. 2007;9(6):403.
PMID 18086324
 
Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts.
Safadi FF, Xu J, Smock SL, Rico MC, Owen TA, Popoff SN.
J Cell Biochem. 2001;84(1):12-26.
PMID 11746512
 
nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts.
Weterman MA, Ajubi N, van Dinter IM, Degen WG, van Muijen GN, Ruitter DJ, Bloemers HP.
Int J Cancer. 1995 Jan 3;60(1):73-81.
PMID 7814155
 

Citation

This paper should be referenced as such :
Patel, SA ; Lim, PK ; Rameshwar, P
GPNMB (glycoprotein (transmembrane) nmb)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):765-767.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GPNMBID40739ch7p15.html


External links

Nomenclature
HGNC (Hugo)GPNMB   4462
Cards
AtlasGPNMBID40739ch7p15
Entrez_Gene (NCBI)GPNMB  10457  glycoprotein nmb
AliasesHGFIN; NMB
GeneCards (Weizmann)GPNMB
Ensembl hg19 (Hinxton)ENSG00000136235 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000136235 [Gene_View]  chr7:23246697-23275110 [Contig_View]  GPNMB [Vega]
ICGC DataPortalENSG00000136235
TCGA cBioPortalGPNMB
AceView (NCBI)GPNMB
Genatlas (Paris)GPNMB
WikiGenes10457
SOURCE (Princeton)GPNMB
Genetics Home Reference (NIH)GPNMB
Genomic and cartography
GoldenPath hg38 (UCSC)GPNMB  -     chr7:23246697-23275110 +  7p15.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GPNMB  -     7p15.3   [Description]    (hg19-Feb_2009)
EnsemblGPNMB - 7p15.3 [CytoView hg19]  GPNMB - 7p15.3 [CytoView hg38]
Mapping of homologs : NCBIGPNMB [Mapview hg19]  GPNMB [Mapview hg38]
OMIM604368   
Gene and transcription
Genbank (Entrez)AF322909 AI952217 AJ505015 AK292078 AK296779
RefSeq transcript (Entrez)NM_001005340 NM_002510
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GPNMB
Cluster EST : UnigeneHs.190495 [ NCBI ]
CGAP (NCI)Hs.190495
Alternative Splicing GalleryENSG00000136235
Gene ExpressionGPNMB [ NCBI-GEO ]   GPNMB [ EBI - ARRAY_EXPRESS ]   GPNMB [ SEEK ]   GPNMB [ MEM ]
Gene Expression Viewer (FireBrowse)GPNMB [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10457
GTEX Portal (Tissue expression)GPNMB
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14956   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ14956  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ14956
Splice isoforms : SwissVarQ14956
PhosPhoSitePlusQ14956
Domaine pattern : Prosite (Expaxy)PKD (PS50093)   
Domains : Interpro (EBI)PKD/Chitinase_dom    PKD_dom   
Domain families : Pfam (Sanger)PKD (PF00801)   
Domain families : Pfam (NCBI)pfam00801   
Domain families : Smart (EMBL)PKD (SM00089)  
Conserved Domain (NCBI)GPNMB
DMDM Disease mutations10457
Blocks (Seattle)GPNMB
SuperfamilyQ14956
Human Protein AtlasENSG00000136235
Peptide AtlasQ14956
HPRD05081
IPIIPI00940949   IPI00001592   IPI00909401   IPI00910425   IPI00979896   IPI01015913   IPI00470529   IPI01020806   IPI00383519   
Protein Interaction databases
DIP (DOE-UCLA)Q14956
IntAct (EBI)Q14956
FunCoupENSG00000136235
BioGRIDGPNMB
STRING (EMBL)GPNMB
ZODIACGPNMB
Ontologies - Pathways
QuickGOQ14956
Ontology : AmiGOosteoblast differentiation  negative regulation of cytokine production  positive regulation of protein phosphorylation  integrin binding  protein binding  plasma membrane  integral component of plasma membrane  cell adhesion  signal transduction  cell-cell signaling  heparin binding  negative regulation of cell proliferation  integral component of membrane  bone mineralization  positive regulation of cell migration  positive regulation of protein autophosphorylation  negative regulation of tumor necrosis factor production  regulation of tissue remodeling  chemoattractant activity  negative regulation of T cell proliferation  melanosome  syndecan binding  regulation of angiogenesis  receptor agonist activity  negative regulation of T cell activation  positive chemotaxis  positive regulation of ERK1 and ERK2 cascade  negative regulation of neuron death  negative regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBIosteoblast differentiation  negative regulation of cytokine production  positive regulation of protein phosphorylation  integrin binding  protein binding  plasma membrane  integral component of plasma membrane  cell adhesion  signal transduction  cell-cell signaling  heparin binding  negative regulation of cell proliferation  integral component of membrane  bone mineralization  positive regulation of cell migration  positive regulation of protein autophosphorylation  negative regulation of tumor necrosis factor production  regulation of tissue remodeling  chemoattractant activity  negative regulation of T cell proliferation  melanosome  syndecan binding  regulation of angiogenesis  receptor agonist activity  negative regulation of T cell activation  positive chemotaxis  positive regulation of ERK1 and ERK2 cascade  negative regulation of neuron death  negative regulation of G1/S transition of mitotic cell cycle  
REACTOMEQ14956 [protein]
REACTOME PathwaysR-HSA-8857538 [pathway]   
NDEx NetworkGPNMB
Atlas of Cancer Signalling NetworkGPNMB
Wikipedia pathwaysGPNMB
Orthology - Evolution
OrthoDB10457
GeneTree (enSembl)ENSG00000136235
Phylogenetic Trees/Animal Genes : TreeFamGPNMB
HOVERGENQ14956
HOGENOMQ14956
Homologs : HomoloGeneGPNMB
Homology/Alignments : Family Browser (UCSC)GPNMB
Gene fusions - Rearrangements
Fusion : MitelmanGPNMB/DDX27 [7p15.3/20q13.13]  
Fusion : MitelmanGPNMB/NUPL2 [7p15.3/7p15.3]  [t(7;7)(p15;p15)]  
Fusion : MitelmanSP4/GPNMB [7p15.3/7p15.3]  [t(7;7)(p15;p15)]  
Fusion: TCGAGPNMB 7p15.3 DDX27 20q13.13 SKCM
Fusion: TCGAGPNMB 7p15.3 NUPL2 7p15.3 BRCA
Fusion: TCGASP4 7p15.3 GPNMB 7p15.3 GBM
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGPNMB [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GPNMB
dbVarGPNMB
ClinVarGPNMB
1000_GenomesGPNMB 
Exome Variant ServerGPNMB
ExAC (Exome Aggregation Consortium)GPNMB (select the gene name)
Genetic variants : HAPMAP10457
Genomic Variants (DGV)GPNMB [DGVbeta]
DECIPHERGPNMB [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGPNMB 
Mutations
ICGC Data PortalGPNMB 
TCGA Data PortalGPNMB 
Broad Tumor PortalGPNMB
OASIS PortalGPNMB [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGPNMB  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGPNMB
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GPNMB
DgiDB (Drug Gene Interaction Database)GPNMB
DoCM (Curated mutations)GPNMB (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPNMB (select a term)
intoGenGPNMB
NCG5 (London)GPNMB
Cancer3DGPNMB(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604368   
Orphanet
MedgenGPNMB
Genetic Testing Registry GPNMB
NextProtQ14956 [Medical]
TSGene10457
GENETestsGPNMB
Target ValidationGPNMB
Huge Navigator GPNMB [HugePedia]
snp3D : Map Gene to Disease10457
BioCentury BCIQGPNMB
ClinGenGPNMB
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10457
Chemical/Pharm GKB GenePA28845
Clinical trialGPNMB
Miscellaneous
canSAR (ICR)GPNMB (select the gene name)
Probes
Litterature
PubMed62 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGPNMB
EVEXGPNMB
GoPubMedGPNMB
iHOPGPNMB
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 30 11:07:57 CEST 2017

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