GPNMB notes

Deep research

• just deep-research-falcon human GPNMB --fallback perplexity-lite failed (providers unavailable,
  2026-10-21). Notes from cached publications, Reactome and UniProt Q14956.

Identity and topology

• Glycoprotein NMB (osteoactivin, DC-HIL, HGFIN); type I transmembrane glycoprotein of the PMEL/NMB family.
  Signal peptide 1-22, extracellular domain 23-498 with RGD cell-attachment motif (64-66), TM, cytoplasmic tail
  520-572 (UniProt).
• "GPNMB belongs to the premelanosome protein (PMEL)/NMB family" PMID:29336782.

Function

• DC-HIL on APCs binds syndecan-4 on activated T cells via heparinase-sensitive saccharides and inhibits T-cell
  activation, cytokine secretion and S-phase entry PMID:19350579.
• ADAM10 sheds the ectodomain; "the shed GPNMB/OA ECD is capable of inducing endothelial cell migration in vitro"
  PMID:20711474.
• EGFR:GPNMB heterodimer recruits BRK downstream of HB-EGF (LINK-A lncRNA study) PMID:26751287.
• Neuroprotective extracellular fragments in ALS/ischaemia models [PMID:22891158, PMID:25010402].
• Biallelic truncating variants cause amyloidosis cutis dyschromica PMID:29336782.

Localization

• Plasma membrane (type I, ECD outside), melanosome membrane (proteomics, PMID:12643545, 17081065), early endosome
  membrane (PMID:29336782); ectodomain shed to extracellular space.
• Conclusion: PM with ECD exposed (antibody-drug conjugate target), plus melanosome/endosome pools and shed ECD.