CD63 notes

Deep research providers were unavailable in this environment (just deep-research-falcon human CD63 --fallback perplexity-lite failed: no provider configured). Research done from the 29 cached
publications and the UniProt record (P08962).

Topology and localization (key for surface-accessibility questions)

• Tetraspanin: four transmembrane helices, large glycosylated second extracellular loop, cytoplasmic
  N- and C-termini; C-terminal GYEVM lysosomal targeting motif. UniProt: "Multi-pass membrane protein".
• Steady state is mostly intracellular: lysosome membrane, late endosome membrane, MVB/intraluminal
  vesicles, melanosomes, platelet dense granules, azurophil granules, Weibel-Palade bodies.
  PMID:10793155
• A functional plasma-membrane/cell-surface pool exists and increases on degranulation (classic
  platelet/basophil activation marker) PMID:1993697;
  surface TIMP1 binding PMID:16917503 and surface association with beta1 integrin and VEGFR2
  PMID:23632027 confirm extracellular-loop exposure.
• Released on exosomes (canonical exosome marker; many IDA/HDA rows).

Functions

• Cell-surface binding partner for TIMP1, promoting beta1 integrin activation, survival and migration
  [PMID:16917503, PMID:24635319].
• Bridges VEGFR2 and beta1 integrin, required for VEGFR2 activation and internalization
  PMID:23632027.
• ESCRT-independent sorting of the PMEL luminal domain into ILVs; melanosome maturation PMID:21962903.
• Limits surface abundance of the colonic H+-K+-ATPase PMID:15647390.

Curation decisions

• Protein-binding rows: TIMP1 rows modified to signaling receptor activity (CD63 is the cell-surface
  receptor for TIMP1); EspZ, retroviral env FRET-PLA methods paper and HuRI TMEM80 rows removed as
  uninformative.
• Broad location terms (lysosome, late endosome, MVB, membrane, vesicle, extracellular region) modified
  to the specific compartments already carried experimentally.