Gene Symbol: AP1S3
Description: adaptor related protein complex 1 subunit sigma 3
Alias: PSORS15, AP-1 complex subunit sigma-3, adapter-related protein complex 1 subunit sigma-1C, adaptor protein complex AP-1 sigma-1C subunit, adaptor related protein complex 1 sigma 3 subunit, adaptor-related protein complex 1 subunit sigma-1C, clathrin assembly protein complex 1 sigma-1C small chain, golgi adaptor HA1/AP1 adaptin sigma-1C subunit, sigma 1C subunit of AP-1 clathrin
Species: human
Products:     AP1S3

Top Publications

  1. Greenberg M, DeTulleo L, Rapoport I, Skowronski J, Kirchhausen T. A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4. Curr Biol. 1998;8:1239-42 pubmed
    ..Thus, the dileucine motif in HIV-1 is required for CD4 downregulation and for interaction with clathrin adaptor complexes. ..
  2. Wyss S, Berlioz Torrent C, Boge M, Blot G, Honing S, Benarous R, et al. The highly conserved C-terminal dileucine motif in the cytosolic domain of the human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adaptor [correction of adapter]. J Virol. 2001;75:2982-92 pubmed
    ..Finally, the C-terminal dileucine was shown to assist the membrane-proximal Y712 motif in restricting the cell surface expression of Env. ..
  3. Coleman S, Van Damme N, Day J, Noviello C, Hitchin D, Madrid R, et al. Leucine-specific, functional interactions between human immunodeficiency virus type 1 Nef and adaptor protein complexes. J Virol. 2005;79:2066-78 pubmed
    ..This binding likely underlies the unusual ability of Nef to induce the stabilization of these complexes on endosomal membranes, an activity that correlates with enhancement of viral replication. ..
  4. Janvier K, Craig H, Hitchin D, Madrid R, Sol Foulon N, Renault L, et al. HIV-1 Nef stabilizes the association of adaptor protein complexes with membranes. J Biol Chem. 2003;278:8725-32 pubmed
    ..The stabilization of these complexes on membranes may underlie the pleiotropic effects of Nef on protein trafficking within the endosomal system. ..
  5. Checkley M, Luttge B, Freed E. HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol. 2011;410:582-608 pubmed publisher
    ..Here, we review our current understanding of HIV-1 Env glycoprotein trafficking and incorporation into virions. ..
  6. Bresnahan P, Yonemoto W, Ferrell S, Williams Herman D, Geleziunas R, Greene W. A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor. Curr Biol. 1998;8:1235-8 pubmed
    ..Our findings also reveal an evolutionary difference between HIV-1 and HIV-2/SIV in which the Nef proteins utilize structurally distinct motifs for binding cellular adaptors. ..
  7. Berlioz Torrent C, Shacklett B, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P, et al. Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol. 1999;73:1350-61 pubmed
  8. Khalid M, Idichi T, Seki N, Wada M, Yamada Y, Fukuhisa H, et al. Gene Regulation by Antitumor miR-204-5p in Pancreatic Ductal Adenocarcinoma: The Clinical Significance of Direct RACGAP1 Regulation. Cancers (Basel). 2019;11: pubmed publisher
    ..Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of ..
  9. Toda H, Kurozumi S, Kijima Y, Idichi T, Shinden Y, Yamada Y, et al. Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3. J Hum Genet. 2018;63:1197-1210 pubmed publisher
    ..High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-..

More Information


  1. Twelves S, Mostafa A, Dand N, Burri E, Farkas K, Wilson R, et al. Clinical and genetic differences between pustular psoriasis subtypes. J Allergy Clin Immunol. 2019;143:1021-1026 pubmed publisher
    ..Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations...
  2. Moghaddas F, Masters S. Monogenic autoinflammatory diseases: Cytokinopathies. Cytokine. 2015;74:237-46 pubmed publisher
    ..IFN) and the interferonopathies, with mutations in the sensors STING and MDA5, the upstream signalling regulator AP1S3, and a downstream inhibitor of IFN signalling, ISG15...
  3. Mahil S, Twelves S, Farkas K, Setta Kaffetzi N, Burden A, Gach J, et al. AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production. J Invest Dermatol. 2016;136:2251-2259 pubmed publisher
    ..We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource...
  4. de Jesus A, Goldbach Mansky R. Newly recognized Mendelian disorders with rheumatic manifestations. Curr Opin Rheumatol. 2015;27:511-9 pubmed publisher
    ..Mutations in ADA2, TRNT1 and COPA, AP1S3, and TNFRSF11A cause complex syndromes; loss-of-function mutations in enzymes and molecules are linked to the ..
  5. Arakawa A, Vollmer S, Besgen P, Galinski A, Summer B, Kawakami Y, et al. Unopposed IL-36 Activity Promotes Clonal CD4+ T-Cell Responses with IL-17A Production in Generalized Pustular Psoriasis. J Invest Dermatol. 2018;138:1338-1347 pubmed publisher
    ..Mutations in the IL-36 antagonist IL36RN, in CARD14 or AP1S3 provide genetic evidence for autoinflammatory etiology but cannot explain its pathogenesis completely...
  6. Rukova B, Staneva R, Hadjidekova S, Stamenov G, Milanova V, Toncheva D. Whole genome methylation analyses of schizophrenia patients before and after treatment. Biotechnol Biotechnol Equip. 2014;28:518-524 pubmed
    ..i>ZNF311) and male schizophrenia patients with complete remission and control male pool after treatment (AP1S3, C16orf59, KCNK15, LOC146336, MGC16384, XRN2) that potentially could be ..
  7. Li X, Niu Y, Cheng M, Chi X, Liu X, Yang W. AP1S3 is required for hepatitis C virus infection by stabilizing E2 protein. Antiviral Res. 2016;131:26-34 pubmed publisher
    ..Here, we identified adaptor protein complex 1 sigma 3 subunit (AP1S3) as a dependency factor for the efficient HCV infection in hepatoma cells. AP1S3 silencing in cultivated Huh7.5...
  8. Kim Y, Choi H, Lee J, Han B, Shin C, Cho N. Replication of Caucasian loci associated with bone mineral density in Koreans. Osteoporos Int. 2013;24:2603-10 pubmed publisher
    ..The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta)...
  9. Santos da Silva E, Mulinge M, Perez Bercoff D. The frantic play of the concealed HIV envelope cytoplasmic tail. Retrovirology. 2013;10:54 pubmed publisher
    ..It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms. ..
  10. Setta Kaffetzi N, Simpson M, Navarini A, Patel V, Lu H, Allen M, et al. AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking. Am J Hum Genet. 2014;94:790-7 pubmed publisher
    ..Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit ?1C, in 15 unrelated individuals with a severe autoinflammatory skin ..
  11. Benichou S, Benmerah A. [The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]. Med Sci (Paris). 2003;19:100-6 pubmed
    ..In addition, these viral factors represent valuable tools to study the pathway they are perturbing. ..
  12. Kulpa D, Del Cid N, Peterson K, Collins K. Adaptor protein 1 promotes cross-presentation through the same tyrosine signal in major histocompatibility complex class I as that targeted by HIV-1. J Virol. 2013;87:8085-98 pubmed publisher
    ..Thus, we provide evidence for two separable cross-presentation pathways, only one of which is targeted by HIV...
  13. Coleman S, Hitchin D, Noviello C, Guatelli J. HIV-1 Nef stabilizes AP-1 on membranes without inducing ARF1-independent de novo attachment. Virology. 2006;345:148-55 pubmed
    ..We conclude that Nef stabilizes AP complexes on endosomal membranes after ARF1-dependent attachment. This stabilization may facilitate coat formation and stimulate the trafficking of multiple cellular proteins. ..
  14. Craig H, Pandori M, Guatelli J. Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity. Proc Natl Acad Sci U S A. 1998;95:11229-34 pubmed
    ..The data also suggest that an influence on the distribution of cellular transmembrane proteins may mechanistically unite two previously distinct properties of Nef: down-regulation of CD4 and enhancement of viral infectivity. ..
  15. Boehm M, Bonifacino J. Adaptins: the final recount. Mol Biol Cell. 2001;12:2907-20 pubmed
    ..Finally, we extend our survey to adaptin-related proteins such as the GGAs and stonins, which contain domains homologous to the adaptins. ..
  16. Roeth J, Williams M, Kasper M, Filzen T, Collins K. HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail. J Cell Biol. 2004;167:903-13 pubmed
    ..In sum, our evidence suggests that binding of AP-1 to the Nef-MHC-I complex is an important step required for inhibition of antigen presentation by HIV. ..
  17. Hirst J, Lindsay M, Robinson M. GGAs: roles of the different domains and comparison with AP-1 and clathrin. Mol Biol Cell. 2001;12:3573-88 pubmed
    ..Together with results from other studies, our findings suggest that the GGAs act as monomeric adaptors, with the four domains involved in cargo selection, membrane localization, clathrin binding, and accessory protein recruitment. ..
  18. Kirchhausen T, Davis A, Frucht S, Greco B, Payne G, Tubb B. AP17 and AP19, the mammalian small chains of the clathrin-associated protein complexes show homology to Yap17p, their putative homolog in yeast. J Biol Chem. 1991;266:11153-7 pubmed
    ..The yeast sequence predicts Yap17p, a protein with 147 amino acids and a Mr of 17,373 that is slightly more related to the mammalian AP17 chain than to its AP19 counterpart. ..