VEGFA has 17 named isoforms from alternative splicing, representing extreme diversity in isoform function.
| Isoform |
UniProt ID |
Length |
Heparin Binding |
Matrix Bound |
Key Feature |
| VEGF206 |
P15692-1 |
206 AA |
Strong |
Yes |
Longest, matrix-bound |
| VEGF189 |
P15692-2 |
189 AA |
Strong |
Yes |
Matrix-bound |
| VEGF165 |
P15692-4 |
165 AA |
Moderate |
Intermediate |
Canonical "VEGF" |
| VEGF121 |
P15692-9 |
121 AA |
None |
No |
Freely diffusible |
| VEGF165B |
P15692-8 |
165 AA |
? |
? |
ANTI-ANGIOGENIC |
UniProt explicitly states for VEGF165B:
"Binds to the KDR receptor but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth" PMID:15520188
This means:
- VEGF165: Pro-angiogenic, promotes tumor growth
- VEGF165B: Anti-angiogenic, inhibits tumor growth
Same length (165 AA), same receptor binding, but opposite biological effects!
Heparin Binding and Matrix Association
The longer isoforms (VEGF189, VEGF206) contain heparin-binding domains and remain matrix-bound, creating:
- Steep gradients - important for vessel sprouting
- Localized signaling - concentrated at source
The shorter isoform (VEGF121) lacks heparin binding:
- Freely diffusible - spreads through tissue
- Broad signaling - less directional
GOA Annotation Status
- 267 total annotations
- NO isoform-specific annotations (no P15692-X identifiers)
- Likely conflates pro-angiogenic (most isoforms) with anti-angiogenic (VEGF165B) functions
Expected Annotation Issues
- Angiogenesis annotations - should specify which isoforms
- "Positive regulation of angiogenesis" - NOT true for VEGF165B
- VEGFR binding - all isoforms bind, but different downstream effects
Key References
- PMID:15520188 - VEGF165B anti-angiogenic properties
- Original VEGF papers describing isoform differences
2026-11-06 ORGANELLES ER batch 4 (endoplasmic reticulum rows)
- Row: GO:0005783 IEA (GO_REF:0000044, SL-0095). Kept KEEP_AS_NON_CORE; summary and reason rewritten, quotes added.
- Source: UniProt "[Isoform L-VEGF189]: Endoplasmic reticulum {ECO:0000269|PubMed:11731620}" (with Golgi). The other isoform lines (VEGF121, VEGF165, VEGF189) say Secreted. The displayed sequence (P15692-13) is L-VEGF189, so the row is not on the wrong isoform, and no source_defects entry was made.
- PMID:11731620 (Huez et al. 2001) was fetched and is abstract-only. In transfected COS-7 cells: PMID:11731620 The abstract does not name the ER.
- Decision: KEEP_AS_NON_CORE on curator deference (curated line from an unread full text). MARK_AS_OVER_ANNOTATED is the close alternative: overexpression data, and the classical isoforms only transit the ER. No lumen row: VEGFA is a secreted protein with no retention signal.