VASH1
Function
Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869, PubMed:31171830, PubMed:31235910, PubMed:31235911, PubMed:31270470). Critical for spindle function and accurate chromosome segregation during mitosis since microtubule detyronisation regulates mitotic spindle length and postioning (PubMed:31171830). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).
Post-translational modifications
2 major forms (42 and 36 kDa) and 2 minors (32 and 27 kDa) may be processed by proteolytic cleavage (PubMed:16488400). The largest form (42 kDa) seems to be secreted and the other major form (63 kDa) seems to accumulate within the cells or pericellular milieu (PubMed:16488400). Polypeptide consisting of Met-77 to Arg-318 may correspond to the 27 kDa form and that consisting of Met-77 to Val-365 may correspond to the 36 kDa form (PubMed:16488400).
Ubiquitinated in vitro.
Sequence Similarities
Belongs to the transglutaminase-like superfamily. Vasohibin family.
Tissue Specificity
Preferentially expressed in endothelial cells (PubMed:15467828, PubMed:16707096). Highly expressed in fetal organs (PubMed:15467828). Expressed in brain and placenta, and at lower level in heart and kidney (PubMed:15467828). Highly detected in microvessels endothelial cells of atherosclerotic lesions (PubMed:16707096).
Cellular localization
- Cytoplasm
- Secreted
- Mainly localizes in the cytoplasm (PubMed:27879017). Some fraction is secreted via a non-canonical secretion system; interaction with SVBP promotes secretion (PubMed:27879017).
Alternative names
KIAA1036, VASH, VASH1, Tubulinyl-Tyr carboxypeptidase 1, Tubulin carboxypeptidase 1, Tyrosine carboxypeptidase 1, Vasohibin-1, TTCP 1