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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
General
guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS)
phosphoprotein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
WD repeat protein family
Properties
SIZE: entity length = 4861 aa
MW = 532 kD
COMPARTMENT: cytoplasm
golgi
MOTIF: RCC1 repeat {371-420}
RCC1 repeat {421-475}
WD repeat {441-483}
RCC1 repeat {476-528}
WD repeat {506-545}
RCC1 repeat {529-578}
RCC1 repeat {580-631}
RCC1 repeat {633-682}
WD repeat {660-699}
RCC1 repeat {683-735}
glutamate-rich region {1349-1378}
MOTIF: glutamate residue (SEVERAL)
Ser phosphorylation site {S1514}
Ser phosphorylation site {S1517}
Ser phosphorylation site {S1521}
B30.2/SPRY {2002-2193}
WD repeat {3426-3465}
WD repeat {3484-3522}
WD repeat {3524-3572}
WD repeat {3580-3619}
WD repeat {3624-3663}
MOTIF: Thr phosphorylation site {T3628}
Ser phosphorylation site {S3631}
Thr phosphorylation site {T3643}
WD repeat {3667-3713}
WD repeat {3745-3784}
RCC1 repeat {3996-4044}
RCC1 repeat {4046-4099}
RCC1 repeat {4101-4151}
RCC1 repeat {4153-4203}
RCC1 repeat {4205-4256}
RCC1 repeat {4258-4308}
WD repeat {4287-4325}
RCC1 repeat {4310-4360}
HECT domain {4501-4848}
MOTIF: Thr phosphorylation site {T4786}
Ser phosphorylation site {S4790}
cysteine residue {C4811}
Database Correlations
OMIM 605109
UniProt Q15751
PFAM correlations
References
UniProt :accession Q15751