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These proteins modulate the expression of major histocompatibility complex class I molecules (mK3 and kK5) as well as other molecules like ICAM-1 and B7.2 (kK5). Previously, mK3 was shown to ubiquitinate nascent class I molecules, resulting in their rapid degradation, and this process was found to be dependent on TAP and tapasin, endoplasmic reticulum molecules involved in class I assembly. Here, we demonstrate that in murine cells, kK5 does not affect class I expression but does downregulate human B7.2 molecules in a TAP\/tapasin-independent manner. These differences in substrate specificity and TAP\/tapasin dependence between mK3 and kK5 permitted us, using chimeric molecules, to map the sites of mK3 interaction with TAP\/tapasin and to determine the requirements for substrate recognition by mK3. Our findings indicate that mK3 interacts with TAP1 and -2 via their C-terminal domains and with class I molecules via their N-terminal domains. Furthermore, by orienting the RING-CH domain of mK3 appropriately with respect to class I, mK3 binding to TAP\/tapasin, rather than the presence of unique sequences in class I, appears to be the primary determinant of substrate specificity.<\/jats:p>","DOI":"10.1128\/jvi.78.16.8673-8686.2004","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T18:42:49Z","timestamp":1090953769000},"page":"8673-8686","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Model for the Interaction of Gammaherpesvirus 68 RING-CH Finger Protein mK3 with Major Histocompatibility Complex Class I and the Peptide-Loading Complex"],"prefix":"10.1128","volume":"78","author":[{"given":"Xiaoli","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie","family":"Lybarger","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Connors","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted H.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12716"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00047-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00213-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050502"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.3.603"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(02)00005-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200111010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.7.1.379-387.1987"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(02)00120-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1999.tb01290.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00239-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00021-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.11.6686"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.425"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.10.2418"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/35056583"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80752-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8708"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.2.449"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00509-5"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.1427-1440.2003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.7.1638"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5330.1306"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.4049\/jimmunol.125.6.2473","volume":"125","year":"1980","unstructured":"Ozato, K., T. 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