E3 ubiquitin-protein ligase HACE1 (HACE1)
The protein contains 909 amino acids for an estimated molecular weight of 102342 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs17853353 | |
| dbSNP:rs17857038 |
Biological Process
Cell cycle
Golgi organization
Membrane fusion
Positive regulation of protein catabolic process
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Rac protein signal transduction
Regulation of cell migration
Regulation of transcription, DNA-templated
Transcription, DNA-templated
Ubiquitin-dependent protein catabolic process
Cellular Component
Cytoplasm
Endoplasmic reticulum
Golgi cisterna membrane
Golgi membrane
Nuclear body
Nucleus
The reference OMIM entry for this protein is 610876
Hect domain- and ankyrin repeat-containing e3 ubiquitin protein ligase 1; hace1
Kiaa1320
CLONING
By sequencing clones obtained from a fetal brain cDNA library, Nagase et al. (2000) cloned HACE1, which they designated KIAA1320. RT-PCR ELISA detected moderate expression in all regions of the brain examined and in lung, kidney, testis, and ovary, with low expression in heart, liver, skeletal muscle, pancreas, and spleen. Fernandez et al. (2001) identified a balanced t6;15(q21;q21) translocation in a Wilms tumor (194070) from a 6-month old infant. By database analysis of the chromosome 6q21 breakpoint region, Anglesio et al. (2004) identified HACE1. The predicted 909-amino acid protein has a calculated molecular mass of about 103 kD and contains 6 N-terminal ankyrin repeats and a C-terminal HECT domain. Northern blot analysis of human tissues detected a 4.6-kb transcript with strong expression in heart, brain, placenta, pancreas, and adult and fetal kidney. By subcellular fractionation and immunofluorescence studies in NIH3T3 fibroblasts, the authors found that HACE1 localized primarily to endoplasmic reticulum and the cytoplasm with small amounts of endogenous protein present in other fractions.GENE FUNCTION
By in vitro and in vivo studies, Anglesio et al. (2004) showed that HACE1 has ubiquitin ligase activity, utilizing UBCH7 (UBE2L3; 603721) as a candidate partner E2 enzyme. HACE1 associated with ubiquitinated proteins and components of the 26S proteasomal complex (see 602706), indicating that at least some proteins targeted for ubiquitination by HACE1 are degraded by the proteasome. Zhang et al. (2007) demonstrated that the E3 ubiquitin ligase HACE1 is frequently downregulated in human tumors and maps to a region of chromosome 6q21 implicated in multiple human cancers. Genetic inactivation of HACE1 in mice resulted in the development of spontaneous, late-onset cancer. A second hit from either environmental triggers or genetic heterozygosity of another tumor suppressor, p53 (191170), markedly increased tumor incidence in a Hace1-deficient background. Reexpression of HACE1 in human tumor cells directly abrogated in vitro and in vivo tumor growth, whereas downregulation of HACE1 via siRNA allowed nontumorigenic human cells to form tumors in vivo. Mechanistically, the tumor suppressor function of HACE1 is dependent on its E3 ligase activity, and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1 (168461). Thus, Zhang et al. (2007) concluded that HACE1 is a candidate chromosome 6q21 tumor suppressor gene involved in multiple cancers.GENE STRUCTURE
Anglesio et al. (2004) determined that the HACE1 gene contains 24 exons.MAPPING
By sequence and database analysis of the chromosome 6q21 breakpoint reported by Fernandez et al. (2001), Anglesio et al. (2004) mapped the HACE1 gene to 50 kB downstream from the breakpoint. Zhang et al. (2007) noted that this region is frequently deleted in a wide spectrum of tumor types.MOLECULAR GENETICS
Anglesio et al. (2004) analyzed the chromosome 6q21 breakpoint of a nonconstitutional t(6;15)(q21;q21) rearrangement in a sporadic Wilms tumor. Although the HACE1 locus was not directly interrupted by the translocation in the index Wilms case, HACE1 expression was markedly lower in tumor tissue compared with adjacent normal kidney. HACE1 expression was virtually undetectable in the SK-NEP-1 Wilms tumor cell line and in 4 of 5 additional primary Wilms tumor cases compared with pa ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for HACE1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610876 was added.