HM13 explained

Minor histocompatibility antigen H13 is a protein that in humans is encoded by the HM13 gene.^{[1] [2] [3]}

Function

The minor histocompatibility antigen 13 is a nonamer peptide that originates from a protein encoded by the H13 gene.^{[4] [5]} The peptide is generated by the cytosol by the proteasome, enters the endoplasmic reticulum (ER) lumen by the transporter associated with antigen processing (TAP) and is presented on the cell surface on H2-D^b major histocompatibility antigen I (MHC I) molecules. The alloreactivity, which leads to transplant rejection in mice, is conferred by Val/Ile polymorphism in the ‘SSV(V/I)GVWYL’ peptide.^[6] The orthologue gene in humans is called HM13. If a related polymorphism exists, and if the HM13 serves as a Minor histocompatibility antigen, however, remains to be addressed.

The protein encoded by the M13/HM13 gene is the signal peptide peptidase (SPP), an ER-resident intramembrane protease.SPP localizes to the endoplasmic reticulum, catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. This 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. The encoded protein is an integral membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. Multiple transcript variants encoding several different isoforms have been found for this gene.

Further reading

• Lemberg MK, Bland FA, Weihofen A, etal . Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes . J. Immunol. . 167 . 11 . 6441–6 . 2002 . 11714810 . 10.4049/jimmunol.167.11.6441. free .
• Deloukas P, Matthews LH, Ashurst J, etal . The DNA sequence and comparative analysis of human chromosome 20 . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . 2001Natur.414..865D . free .
• Grigorenko AP, Moliaka YK, Korovaitseva GI, Rogaev EI . Novel class of polytopic proteins with domains associated with putative protease activity . Biochemistry Mosc. . 67 . 7 . 826–35 . 2002 . 12139484 . 10.1023/A:1016365227942 . 11785597 .
• McLauchlan J, Lemberg MK, Hope G, Martoglio B . Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets . EMBO J. . 21 . 15 . 3980–8 . 2002 . 12145199 . 10.1093/emboj/cdf414 . 126158 .
• Lemberg MK, Martoglio B . Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis . Mol. Cell . 10 . 4 . 735–44 . 2002 . 12419218 . 10.1016/S1097-2765(02)00655-X . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Urny J, Hermans-Borgmeyer I, Gercken G, Schaller HC . Expression of the presenilin-like signal peptide peptidase (SPP) in mouse adult brain and during development . Gene Expr. Patterns . 3 . 5 . 685–91 . 2004 . 12972007 . 10.1016/S1567-133X(03)00094-2 .
• Lehner B, Semple JI, Brown SE, etal . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–67 . 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Moliaka YK, Grigorenko A, Madera D, Rogaev EI . Impas 1 possesses endoproteolytic activity against multipass membrane protein substrate cleaving the presenilin 1 holoprotein . FEBS Lett. . 557 . 1–3 . 185–92 . 2004 . 14741365 . 10.1016/S0014-5793(03)01489-3 . 21770115 . free .
• Soares MR, Bisch PM, Campos de Carvalho AC, etal . Correlation between conformation and antibody binding: NMR structure of cross-reactive peptides from T. cruzi, human and L. braziliensis . FEBS Lett. . 560 . 1–3 . 134–40 . 2004 . 14988012 . 10.1016/S0014-5793(04)00088-2 . 21812894 .
• Friedmann E, Lemberg MK, Weihofen A, etal . Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins . J. Biol. Chem. . 279 . 49 . 50790–8 . 2005 . 15385547 . 10.1074/jbc.M407898200 . free . 2262/89311 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Otsuki T, Ota T, Nishikawa T, etal . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries . DNA Res. . 12 . 2 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Urny J, Hermans-Borgmeyer I, Schaller HC . Cell-surface expression of a new splice variant of the mouse signal peptide peptidase . Biochim. Biophys. Acta . 1759 . 3–4 . 159–65 . 2006 . 16730383 . 10.1016/j.bbaexp.2006.02.007 .
• Loureiro J, Lilley BN, Spooner E, etal . Signal peptide peptidase is required for dislocation from the endoplasmic reticulum . Nature . 441 . 7095 . 894–7 . 2006 . 16738546 . 10.1038/nature04830 . 2006Natur.441..894L . 4346807 .
• Sato T, Nyborg AC, Iwata N, etal . Signal peptide peptidase: biochemical properties and modulation by nonsteroidal antiinflammatory drugs . Biochemistry . 45 . 28 . 8649–56 . 2006 . 16834339 . 10.1021/bi060597g .

Notes and References

1. Weihofen A, Binns K, Lemberg MK, Ashman K, Martoglio B . Identification of signal peptide peptidase, a presenilin-type aspartic protease . Science . 296 . 5576 . 2215–8 . Jun 2002 . 12077416 . 10.1126/science.1070925 . 2002Sci...296.2215W . 45633906 .
2. Nyborg AC, Kornilova AY, Jansen K, Ladd TB, Wolfe MS, Golde TE . Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor . J Biol Chem . 279 . 15 . 15153–60 . Apr 2004 . 14704149 . 10.1074/jbc.M309305200 . free .
3. Web site: Entrez Gene: HM13 histocompatibility (minor) 13.
4. Web site: Entrez Gene: H13 histocompatibility (minor) 13.
5. Snell GD, Cudkowicz G, Bunker HP . Histocompatibility genes of mice. VII. H-13, a new histocompatibility locus in the fifth linkage group . Transplantation . 5 . 3 . 492–503 . Jun 1967 . 5340356. 10.1097/00007890-196705000-00011 . 31345625 .
6. Mendoza LM, Paz P, Zuberi A, Christianson G, Roopenian D, Shastri N . Minors held by majors: the H13 minor histocompatibility locus defined as a peptide/MHC class I complex . Immunity . 7 . 4 . 461–72 . Oct 1997 . 9354467 . 10.1016/S1074-7613(00)80368-4 . free .