High impact information on HERC1

• These observations suggest that p619 is a Brefeldin A-sensitive Golgi protein that functions as a guanine nucleotide exchange factor for ARF1 and, possibly, for members of the Rab family of proteins [1].
• Subcellular localization studies indicate that p619 is located in the cytosol and in the Golgi apparatus [1].
• Localization of p619 in the Golgi is altered by Brefeldin A [1].
• TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase [2].
• The interaction between p532 and clathrin only occurs in the cytosol and is mediated by the formation of an ATP-dependent ternary complex with the heat shock protein, Hsp70 [3].

Biological context of HERC1

• Assignment of the human P532 gene (HERC1) to chromosome 15q22 by fluorescence in situ hybridization [4].
• HERC proteins are characterized by having one or more RCC1-like domains as well as a C-terminal HECT domain in their amino acid sequences [5].
• Six HERC genes have turned up in the human genome which encode two different sorts of polypeptides: while the small HERC proteins possess little more than the two aforementioned domains, the large ones are giant proteins with a plethora of potentially important regions [6].
• Members of the HERC (domain homologous to E6 associated protein carboxy-terminus and RCC1 domain protein) family may function both as guanine nucleotide exchange factors and E3 ubiquitin ligases [7].

Anatomical context of HERC1

• Herein, we show that HERC1 is recruited onto actin-rich surface protrusions in ARF6-transfected HeLa cells upon aluminum fluoride (AlF(4)(-)) treatment [8].
• Here we describe a physical interaction between the HECT domain of HERC1, a giant protein involved in intracellular membrane traffic, and the M2 isoform of glycolytic enzyme pyruvate kinase (M2-PK) [5].

Associations of HERC1 with chemical compounds

• Furthermore, we demonstrate that the activity of HERC1 as a guanine nucleotide release factor requires the presence of PI(4,5)P(2) bound to HERC1's RLD1 [9].
• Interaction between HERC1 and M2-type pyruvate kinase [5].
• The giant protein HERC1 is recruited to aluminum fluoride-induced actin-rich surface protrusions in HeLa cells [8].
• Finally, we suggest a phosphoinositide-binding mechanism whereby HERC1 may translocate to these protrusions [8].
• Requirement of phosphatidylinositol-4,5-bisphosphate for HERC1-mediated guanine nucleotide release from ARF proteins [9].

Regulatory relationships of HERC1

• Previously, it has been shown that the RCC1-like domain 1 (RLD1) of HERC1 stimulates guanine nucleotide dissociation on ARF1 and Rab proteins [9].
• In this study, we have analyzed whether HERC1 may also regulate ARF6 activity [9].

Other interactions of HERC1

• We have identified HERC1 as a TSC2-interacting protein [2].
• Thus, using this continuous LAG gel, it is possible to simultaneously analyze giant proteins, such as HERC1 and dynein, big proteins like clathrin heavy chain and small proteins like ARF [10].

Analytical, diagnostic and therapeutic context of HERC1

• To organize and rank learning needs, HERC staff at Schwab Rehabilitation Hospital first created a universe of all perceived learning needs, which was accomplished through interviews with each staff member [11].

References