E3 ubiquitin-protein ligase MARCHF8 (MARCH8)
The protein contains 291 amino acids for an estimated molecular weight of 32965 Da.
E3 ubiquitin-protein ligase that mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. May also promote ubiquitination and endocytosis of TFRC and FAS. (updated: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs3764990 | |
| dbSNP:rs7908745 |
No binding partner found
Biological Process
Adaptive immune response
Antigen processing and presentation of peptide antigen via MHC class II
Immune response
Protein polyubiquitination
The reference OMIM entry for this protein is 613335
Membrane-associated ring-ch finger protein 8; march8
March viii
Mir
DESCRIPTION
MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003; Bartee et al., 2004).CLONING
Kaposi sarcoma-associated herpesvirus (KSHV) modulator of immune recognition (MIR) proteins function as E3 ubiquitin ligases for immune recognition-related molecules. The MIR catalytic domain is a plant homeodomain (PHD) of the BKS (bovine herpesvirus-4, KSHV, and swinepox virus) subclass, or a BKS-PHD domain. By searching databases for proteins containing a BKS-PHD domain, followed by PCR and 5-prime RACE of a human BJAB B-cell cDNA library, Goto et al. (2003) cloned MARCH8, which they designated MIR. The deduced 291-amino acid protein has an N-terminal BKS-PHD domain, followed by 2 transmembrane domains. Both the N and C termini were predicted to be cytoplasmic. RT-PCR analysis detected MIR expression in neonatal brain and in adult lymph node, spleen, and placenta, but not in other tissues examined. It was also detected in monocytes and immature dendritic cells, but not in lymphocytes. Poxviruses and gamma-2 herpesviruses express ubiquitin ligases called K3 proteins that inhibit the surface expression of glycoproteins, including major histocompatibility complex (MHC) class I molecules (see 142800). By searching a database for sequences similar to the functional domains of viral K3 proteins, Bartee et al. (2004) identified 9 human MARCH proteins, including MARCH8. The deduced MARCH8 protein contains a short N terminus, followed by a RING-CH domain and 2 transmembrane domains. MARCH8 shares over 90% identity with MARCH1 (613331) in the RING-CH and transmembrane domains. Real-time PCR analysis detected variable expression of MARCH8 in all human tissues examined, with highest expression in lung. Immunofluorescence analysis showed that epitope-tagged MARCH8 was expressed in a punctate pattern that partly overlapped with endocytic or lysosomal vesicles. Using RT-PCR, De Gassart et al. (2008) detected high MARCH8 expression in immature and mature human dendritic cells and in HeLa and human B-cell lines, with lower expression in monocytes.GENE FUNCTION
Goto et al. (2003) showed that overexpression of MIR in human cells downregulated surface expression of B7-2 (CD86; 601020), a costimulatory molecule for MHC II (see 142860)-mediated antigen presentation. Overexpression of MIR did not downregulate surface expression of MHC I molecules. The BKS-PHD domain of MIR showed ubiquitin ligase activity in an in vitro ubiquitination assay, and downregulation of surface B7-2 required ubiquitination of B7-2 on cytoplasmic lysines, which was followed by lysosomal degradation of B7-2. Mutation analysis revealed that the ubiquitin ligase activity of MIR and downregulation of surface B7-2 required conserved zinc-binding cysteines within the BKS-PHD domain of MIR. Immunoprecipitation analysis revealed that both wildtype MIR and a ligase-dead MIR mutant interacted directly with B7-2. Bartee et al. (2004) showed that the isolated RING-CH domain of MARCH8 functioned as an E3 ubiquitin ligase in a reaction containing ubiquitin, ATP, an E1 ubiquitin-activating enzyme (see UBE1; 314370), and the E2 ubiquitin-conjugating enzyme UBCH2 (UBE2H; 601082) or UBCH5A ( ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 613335 was added.
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).