background:
E3 ubiquitin-protein ligase that may function in cellular proteins degradation. HACE1 has also been shown to be down-regulated in many human tumours and is a putative candidate tumor suppressor.
Function:
E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion. Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division. Specifically interacts with GTP-bound RAC1, mediating ubiquitination and subsequent degradation of active RAC1, thereby playing a role in host defense against pathogens. May also act as a transcription regulator via its interaction with RARB.
Subunit:
Interacts with RARB (By similarity). Interacts with RAB1 (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A or RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-dependent manner. Interacts with RAC1; in a GTP-dependent manner. Interacts with the 26S proteasomal complex through the 20S core proteasomal subunit.
Subcellular Location:
Cytoplasm. Endoplasmic reticulum. A significant portion localizes to the endoplasmic reticulum.
Tissue Specificity:
Expressed in multiple tissues including heart, brain and kidney.
DISEASE:
Note=Defects in HACE1 are a cause of Wilms tumor (WT). WT is a pediatric malignancy of kidney and one of the most common solid cancers in childhood. HACE1 is epigenetically down-regulated in sporadic Wilms tumor. Moreover, a t(5;6)(q21;q21) translocation that truncates HACE1 has been found in a child with bilateral, young-onset Wilms tumor.
Similarity:
Contains 6 ANK repeats.
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
Database links:
Entrez Gene: 527565 Cow
Entrez Gene: 100733867 Guinea pig
Entrez Gene: 100071887 Horse
Entrez Gene: 57531 Human
Entrez Gene: 209462 Mouse
Entrez Gene: 100156102 Pig
Entrez Gene: 361866 Rat
Omim: 610876 Human
SwissProt: F1N6G5 Cow
SwissProt: Q8IYU2 Human
SwissProt: Q3U0D9 Mouse
SwissProt: D3ZBM7 Rat
Unigene: 434340 Human
Unigene: 458633 Mouse
Unigene: 28116 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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