GPNMB

The protein encoded by this gene is a type I transmembrane glycoprotein which shows homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB shows expression in the lowly metastatic human melanoma cell lines and xenografts but does not show expression in the highly metastatic cell lines. GPNMB may be involved in growth delay and reduction of metastatic potential. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]GPNMB (Glycoprotein Nmb) is a Protein Coding gene. Diseases associated with GPNMB include Melanoma and Glioblastoma Multiforme. Among its related pathways are Signaling by GPCR and Signaling by PTK6. Gene Ontology (GO) annotations related to this gene include heparin binding and integrin binding. An important paralog of this gene is PMEL.Could be a melanogenic enzyme.

Full Name

Glycoprotein Nmb

Function

Could be a melanogenic enzyme.

Biological Process

Bone mineralization Source: Ensembl
Cell adhesion Source: GO_Central
Cell-cell signaling Source: ParkinsonsUK-UCL
Negative regulation of cell population proliferation Source: ProtInc
Negative regulation of cytokine production Source: ParkinsonsUK-UCL
Negative regulation of G1/S transition of mitotic cell cycle Source: ParkinsonsUK-UCL
Negative regulation of neuron death Source: ParkinsonsUK-UCL
Negative regulation of T cell activation Source: ParkinsonsUK-UCL
Negative regulation of T cell proliferation Source: ParkinsonsUK-UCL
Negative regulation of tumor necrosis factor production Source: Ensembl
Osteoblast differentiation Source: Ensembl
Positive chemotaxis Source: ParkinsonsUK-UCL
Positive regulation of cell migration Source: ParkinsonsUK-UCL
Positive regulation of ERK1 and ERK2 cascade Source: ParkinsonsUK-UCL
Positive regulation of protein autophosphorylation Source: ParkinsonsUK-UCL
Positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
Regulation of angiogenesis Source: ParkinsonsUK-UCL
Regulation of tissue remodeling Source: ParkinsonsUK-UCL
Signal transduction Source: ParkinsonsUK-UCL

Cellular Location

Cell membrane; Early endosome membrane; Melanosome membrane. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Involvement in disease

Increased expression levels in glioblastoma multiforme biopsy samples correlate with poor patient survival prognosis (PubMed:16609006). Has been proposed as a potential target for antibodies coupled to cytotoxic drugs in the context of cancer immunotherapy, including that of melanoma (PubMed:16489096).
Amyloidosis, primary localized cutaneous, 3 (PLCA3):
A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. PLCA3 inheritance is autosomal recessive.

Topology

Extracellular: 23-498
Helical: 499-519
Cytoplasmic: 520-572