AP1S2 explained

AP-1 complex subunit sigma-2 is a protein that in humans is encoded by the AP1S2 gene.^{[1] [2] [3]}

Function

Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as the small subunit of this complex and is a member of the adaptin protein family. Transcript variants utilizing alternative polyadenylation signals exist for this gene.^[3]

Pathology

Mutations of the AP1S2 gene cause the Pettigrew syndrome,^[4] which is characterized by mental retardation and additional highly variable features, including choreoathetosis, hydrocephalus, Dandy–Walker malformation, seizures, and iron or calcium deposition in the brain.^[5]

References

Further reading

• Kirchhausen T . Clathrin . Annual Review of Biochemistry . 69 . 699–727 . 2000 . 10966473 . 10.1146/annurev.biochem.69.1.699 .
• Geyer M, Fackler OT, Peterlin BM . Structure--function relationships in HIV-1 Nef . EMBO Reports . 2 . 7 . 580–5 . July 2001 . 11463741 . 1083955 . 10.1093/embo-reports/kve141 .
• Bénichou S, Benmerah A . [The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway] . Médecine/Sciences . 19 . 1 . 100–6 . January 2003 . 12836198 . 10.1051/medsci/2003191100 . free .
• Kirchhausen T, Davis AC, Frucht S, Greco BO, Payne GS, Tubb B . AP17 and AP19, the mammalian small chains of the clathrin-associated protein complexes show homology to Yap17p, their putative homolog in yeast . The Journal of Biological Chemistry . 266 . 17 . 11153–7 . June 1991 . 10.1016/S0021-9258(18)99141-6 . 2040623 . free .
• Craig HM, Pandori MW, Guatelli JC . Interaction of HIV-1 Nef with the cellular dileucine-based sorting pathway is required for CD4 down-regulation and optimal viral infectivity . Proceedings of the National Academy of Sciences of the United States of America . 95 . 19 . 11229–34 . September 1998 . 9736718 . 21624 . 10.1073/pnas.95.19.11229 . 1998PNAS...9511229C . free .
• Bresnahan PA, Yonemoto W, Ferrell S, Williams-Herman D, Geleziunas R, Greene WC . A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor . Current Biology . 8 . 22 . 1235–8 . November 1998 . 9811606 . 10.1016/S0960-9822(07)00517-9 . free . 1998CBio....8.1235B .
• 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 . Current Biology . 8 . 22 . 1239–42 . November 1998 . 9811611 . 10.1016/S0960-9822(07)00518-0 . free . 1998CBio....8.1239G .
• Berlioz-Torrent C, Shacklett BL, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P, Dokhelar MC, Benarous R . 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 . Journal of Virology . 73 . 2 . 1350–61 . February 1999 . 9882340 . 103959 . 10.1128/JVI.73.2.1350-1361.1999.
• Wyss S, Berlioz-Torrent C, Boge M, Blot G, Höning S, Benarous R, Thali M . 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] . Journal of Virology . 75 . 6 . 2982–92 . March 2001 . 11222723 . 115924 . 10.1128/JVI.75.6.2982-2992.2001 .
• Doray B, Ghosh P, Griffith J, Geuze HJ, Kornfeld S . Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network . Science . 297 . 5587 . 1700–3 . September 2002 . 12215646 . 10.1126/science.1075327 . 2002Sci...297.1700D . 8810528 .
• Janvier K, Craig H, Hitchin D, Madrid R, Sol-Foulon N, Renault L, Cherfils J, Cassel D, Benichou S, Guatelli J . HIV-1 Nef stabilizes the association of adaptor protein complexes with membranes . The Journal of Biological Chemistry . 278 . 10 . 8725–32 . March 2003 . 12486136 . 10.1074/jbc.M210115200 . free .
• Coleman SH, Van Damme N, Day JR, Noviello CM, Hitchin D, Madrid R, Benichou S, Guatelli JC . Leucine-specific, functional interactions between human immunodeficiency virus type 1 Nef and adaptor protein complexes . Journal of Virology . 79 . 4 . 2066–78 . February 2005 . 15681409 . 546596 . 10.1128/JVI.79.4.2066-2078.2005 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . Huda Zoghbi . 2005Natur.437.1173R . 4427026 .
• Coleman SH, Hitchin D, Noviello CM, Guatelli JC . HIV-1 Nef stabilizes AP-1 on membranes without inducing ARF1-independent de novo attachment . Virology . 345 . 1 . 148–55 . February 2006 . 16253302 . 10.1016/j.virol.2005.09.045 . free .

Notes and References

1. Takatsu H, Sakurai M, Shin HW, Murakami K, Nakayama K . Identification and characterization of novel clathrin adaptor-related proteins . The Journal of Biological Chemistry . 273 . 38 . 24693–700 . September 1998 . 9733768 . 10.1074/jbc.273.38.24693 . free .
2. Tarpey PS, Stevens C, Teague J, Edkins S, O'Meara S, Avis T, Barthorpe S, Buck G, Butler A, Cole J, Dicks E, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, West S, Widaa S, Yates A, Catford R, Butler J, Mallya U, Moon J, Luo Y, Dorkins H, Thompson D, Easton DF, Wooster R, Bobrow M, Carpenter N, Simensen RJ, Schwartz CE, Stevenson RE, Turner G, Partington M, Gecz J, Stratton MR, Futreal PA, Raymond FL . Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation . American Journal of Human Genetics . 79 . 6 . 1119–24 . December 2006 . 17186471 . 1698718 . 10.1086/510137 .
3. Web site: Entrez Gene: AP1S2 adaptor-related protein complex 1, sigma 2 subunit.
4. Huo L, Teng Z, Wang H, Liu X . A novel splice site mutation in AP1S2 gene for X-linked mental retardation in a Chinese pedigree and literature review . Brain and Behavior . 9 . 3 . e01221 . March 2019 . 30714330 . 6422709 . 10.1002/brb3.1221 .
5. Web site: Pettigrew syndrome . Universal Protein Resource (UniProt) .