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vasohibin-1 (VASH1, KIAA1036, VASH)
Function:
- angiogenesis inhibitor
- inhibits migration, proliferation & network formation by endothelial cells as well as angiogenesis
- inhibitory effect is selective to endothelial cells, does not affect the migration of smooth muscle cells or fibroblasts
- does not affect the proliferation of cancer cells in vitro, but inhibits tumor growth & tumor angiogenesis
- acts in an autocrine manner
- inhibits artery neointimal formation & macrophage infiltration
- exhibits heparin-binding activity
- 2 major forms (42 & 36 kD) & 2 minor forms (32 & 27 kD)
- may be processed by proteolytic cleavage
- largest form (42 kD) seems to be secreted, the other major form (63 kD) seems to accumulate within cells or pericellular milieu
- polypeptide consisting of Met-77 to Arg-318 may correspond to the 27 kD form & that consisting of Met-77 to Val-365 may correspond to the 36 kD form
- ubiquitinated in vitro
- interacts with SVBP enhancing VASH1 solubility & secretion & prevents its ubiquitination
Structure:
- belongs to the vasohibin family
- although probably secreted, it lacks a canonical signal sequence
Compartment: secreted
Alternative splicing: named isoforms=2
Expression:
- preferentially expressed in endothelial cells
- highly expressed in fetal organs
- expressed in brain & placenta, & at lower level in heart & kidney
- induced by VEGF
Pathology:
- abundant in microvessels endothelial cells of atherosclerotic lesions
General
endogenous angiogenesis inhibitor
human longevity protein
secreted protein
Properties
SIZE: MW = 41 kD
entity length = 365 aa
COMPARTMENT: extracellular compartment
MOTIF: proteolytic site {29-30}
proteolytic site {76-77}
binding site
SITE: 319-365
FOR-BINDING-OF: heparin
Database Correlations
OMIM 609011
UniProt Q7L8A9
Entrez Gene 22846
Kegg hsa:22846
References
- UniProt :accession Q7L8A9
- PMID: 16488400
- PMID: 488400
- PMID: 16707096
- PMID: 707096
- PMID: 15649403