ROS1 (human, P08922) curation notes

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UniProt.

Localization

• UniProt SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I membrane protein.
  Large extracellular fibronectin-type-III region is surface-exposed; the kinase domain is
  cytoplasmic.
• Generic GO:0016020 membrane modified to plasma membrane.
• Caveat recorded in the review: oncogenic ROS1 fusions (FIG/GOPC, CD74, SLC34A2) lose the
  transmembrane anchoring and are not plasma-membrane receptors.

Function

• NELL2 is the endogenous ligand; ROS1 "triggers epididymal epithelial differentiation and
  subsequent sperm maturation" (UniProt, by similarity to mouse).
• Substrates: PTPN11 ("Mediates the phosphorylation of PTPN11, an activator of this pathway"),
  VAV3 PMID:11094073, STAT3; downstream PI3K-mTOR, ERK.
• Phosphatase recruitment: "Phosphorylation at Tyr-2274 is required for the interaction with PTPN6".

Review decisions

• Three generic GO:0005515 rows removed per policy (the SHP-1/PTP1B peptide study is represented
  by protein phosphatase binding).
• GO:0004672 modified to the tyrosine-specific kinase terms; GO:1902531 regulation of intracellular signal transduction marked TOO_GENERAL.
• Spermatogenesis and epithelial-development ISS rows kept as non-core tissue outputs.