Minor histocompatibility antigen H13 (HM13)
The protein contains 377 amino acids for an estimated molecular weight of 41488 Da.
Catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides (PubMed:11714810). May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein (PubMed:12145199). Involved in the intramembrane cleavage of the integral membrane protein PSEN1 (PubMed:12077416, PubMed:11714810, PubMed:14741365). Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner (PubMed:25239945). May play a role in graft rejection (By similarity). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs1044419 |
Biological Process
In utero embryonic development
Membrane protein proteolysis
Membrane protein proteolysis involved in retrograde protein transport, ER to cytosol
Protein homotetramerization
Signal peptide processing
Cellular Component
Cell surface
Derlin-1 retrotranslocation complex
Endoplasmic reticulum
Endoplasmic reticulum membrane
Integral component of cytoplasmic side of endoplasmic reticulum membrane
Integral component of lumenal side of endoplasmic reticulum membrane
Membrane
Plasma membrane
Rough endoplasmic reticulum
The reference OMIM entry for this protein is 607106
Minor histocompatibility 13; hm13
Histocompatibility 13
Signal peptide peptidase; spp
Intramembrane protease 1; imp1
DESCRIPTION
Signal peptide peptidase, or SPP, catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. Weihofen et al. (2002) identified human SPP as a polytopic membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases.CLONING
Weihofen et al. (2002) cloned and sequenced a human cDNA corresponding to SPP from a HeLa cell cDNA library. The 377-amino acid protein has 7 putative transmembrane regions, 4 potential N-glycosylation sites, YD and LGLGD aspartic protease motifs, and the endoplasmic reticulum (ER) retrieval signal KKXX. In addition to SPP, Weihofen et al. (2002) identified more than 15 proteins that were homologous to human SPP and could be subdivided into at least 5 subfamilies on the basis of phylogenetic tree analysis. The first subfamily comprises proteins with the C-terminal ER retrieval signal KKXX, and includes SPP. Members of this subfamily are potential orthologs and share homology (up to 94% identity) with SPP throughout the whole amino acid sequence. They are found only in higher eukaryotes. The other 4 subfamilies comprise SPP homologs without obvious intracellular localization signals. They are homologous to SPP only in the C-terminal half of the protein and show substantial variation in the N-terminal regions. Potential orthologs of SPP were not found in the genomes of S. cerevisiae and S. pombe, suggesting that SPP function was acquired late in evolution. By searching sequence databases for homologs of Dictyostelium discoideum Impas, which shares homology with presenilin (104311), followed by PCR of lymphocyte and hippocampus cDNA libraries, Grigorenko et al. (2002) cloned HM13, which they called IMP1. RT-PCR detected expression in all organs and tissues examined, with reduced expression in heart and skeletal muscle. Western blot analysis of transfected human embryonic kidney cells showed that IMP1 migrates at an apparent molecular mass of about 45 kD and at a higher mass of about 100 kD.GENE FUNCTION
Lemberg and Martoglio (2002) analyzed requirements of substrates for intramembrane cleavage by SPP. Comparing signal peptides that are substrates with those that are not revealed that helix-breaking residues within the transmembrane region are required for cleavage, and flanking regions can affect processing. Furthermore, the authors determined that signal peptides have to be liberated from the precursor protein by cleavage with signal peptidase in order to become substrates for SPP.GENE STRUCTURE
Grigorenko et al. (2002) determined that the IMP1 gene contains 11 exons.MAPPING
By genomic sequence analysis, Grigorenko et al. (2002) mapped the HM13 gene to chromosome 20. ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 607106 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).