E3 ubiquitin-protein ligase HERC1 (HECT domain & RCC1-like domain-containing protein 1, p532, p619, HERC1)

Function

• role in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity & its ability to bind clathrin
• acts as a GEF for Arf & Rab, by exchanging bound GDP for free GTP
• binds phosphatidylinositol-4,5-bisphosphate, which is required for GEF activity
• may also act as a E3 ubiquitin-protein ligase
• interacts with TSC2; interaction is inhibited by TSC1
• interacts with PKM2, ARF1 & ARF6
• forms a ternary complex with clathrin heavy chain (CLTC) & HSPA1A
• protein degradation; protein ubiquitination
• phosphorylated upon DNA damage, probably by ATM or ATR

Structure

• contains 1 B30.2/SPRY domain
• contains 1 HECT domain (E6AP-type E3 ubiquitin-protein ligase domain)
• contains 14 RCC1 repeats
• contains 11 WD repeats

Compartment

• peripheral membrane
• cytoplasm
• Golgi
• recruited onto actin-rich surface protrusions

Expression

widely expressed

More general terms

• E3 ubiquitin ligase
• WD repeat protein family
• phosphoprotein
• guanine nucleotide exchange factor

Database

• OMIM: https://mirror.omim.org/entry/605109
• UniProt: http://www.uniprot.org/uniprot/Q15751.html