G2Cdb::Gene report

Gene id
G00001927
Gene symbol
AP2S1 (HGNC)
Species
Homo sapiens
Description
adaptor-related protein complex 2, sigma 1 subunit
Orthologue
G00000678 (Mus musculus)

Databases (8)

Curated Gene
OTTHUMG00000070491 (Vega human gene)
Gene
ENSG00000042753 (Ensembl human gene)
1175 (Entrez Gene)
1089 (G2Cdb plasticity & disease)
AP2S1 (GeneCards)
Literature
602242 (OMIM)
Marker Symbol
HGNC:565 (HGNC)
Protein Sequence
P53680 (UniProt)

Literature (20)

Pubmed - other

  • A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein.

    Byland R, Vance PJ, Hoxie JA and Marsh M

    Cell Biology Unit, MRC-Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom.

    During the assembly of enveloped viruses viral and cellular components essential for infectious particles must colocalize at specific membrane locations. For the human and simian immunodeficiency viruses (HIV and SIV), sorting of the viral envelope proteins (Env) to assembly sites is directed by trafficking signals located in the cytoplasmic domain of the transmembrane protein gp41 (TM). A membrane proximal conserved GYxxØ motif mediates endocytosis through interaction with the clathrin adaptor AP-2. However, experiments with SIV(mac239) Env indicate the presence of additional signals. Here we show that a conserved C-terminal dileucine in HIV(HxB2) also mediates endocytosis. Biochemical and morphological assays demonstrate that the C-terminal dileucine motif mediates internalization as efficiently as the GYxxØ motif and that both must be removed to prevent Env internalization. RNAi experiments show that depletion of the clathrin adaptor AP-2 leads to increased plasma membrane expression of HIV Env and that this adaptor is required for efficient internalization mediated by both signals. The redundancy of conserved endocytosis signals and the role of the SIV(mac239) Env GYxxØ motif in SIV pathogenesis, suggest that these motifs have functions in addition to endocytosis, possibly related to Env delivery to the site of viral assembly and/or incorporation into budding virions.

    Funded by: Medical Research Council: MC_U122665002, U.1226.00.003.00001.01(65002); NIAID NIH HHS: AI-49784, R01 AI049784

    Molecular biology of the cell 2007;18;2;414-25

  • Large-scale mapping of human protein-protein interactions by mass spectrometry.

    Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T and Figeys D

    Protana, Toronto, Ontario, Canada.

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

    Molecular systems biology 2007;3;89

  • Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2.

    Batonick M, Favre M, Boge M, Spearman P, Höning S and Thali M

    Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.

    The envelope glycoprotein (Env) of HIV-1 interacts with the clathrin-associated adaptor complex AP-2 during the late phase of the viral replication cycle. Upon its synthesis, Env, therefore, is retrieved from the cellular surface unless internalization is inhibited by viral Gag. Here we demonstrate that not only Env, but also HIV-1 Gag, specifically binds to AP-2. Gag-AP-2 association was found to depend on tyrosine residue 132 and valine residue 135 at the matrix-capsid junction in the Gag polyprotein. Results of a morphological analysis of viral egress from cells expressing dominant-negative AP-2 suggest an involvement of AP-2 in confining HIV-1 exit to distinct microdomains. Further, particle release from AP-2-mutant cells was enhanced compared to release from wild-type cells but the infectivity of virus released from these cells was moderately reduced. Together these data attribute a role to the AP-2 complex in the regulation of HIV-1 assembly/release.

    Funded by: NIAID NIH HHS: R01 AI047727, R01AI047727-04

    Virology 2005;342;2;190-200

  • Towards a proteome-scale map of the human protein-protein interaction network.

    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 and Vidal M

    Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.

    Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

    Funded by: NCI NIH HHS: R33 CA132073; NHGRI NIH HHS: P50 HG004233, R01 HG001715, RC4 HG006066, U01 HG001715; NHLBI NIH HHS: U01 HL098166

    Nature 2005;437;7062;1173-8

  • Human immunodeficiency virus Nef induces rapid internalization of the T-cell coreceptor CD8alphabeta.

    Stove V, Van de Walle I, Naessens E, Coene E, Stove C, Plum J and Verhasselt B

    Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospita, Belgium.

    Human immunodeficiency virus (HIV) Nef is a membrane-associated protein decreasing surface expression of CD4, CD28, and major histocompatibility complex class I on infected cells. We report that Nef strongly down-modulates surface expression of the beta-chain of the CD8alphabeta receptor by accelerated endocytosis, while CD8 alpha-chain expression is less affected. By mutational analysis of the cytoplasmic tail of the CD8 beta-chain, an FMK amino acid motif was shown to be critical for Nef-induced endocytosis. Although independent of CD4, endocytosis of the CD8 beta-chain was abrogated by the same mutations in Nef that affect CD4 down-regulation, suggesting common molecular interactions. The ability to down-regulate the human CD8 beta-chain was conserved in HIV-1, HIV-2, and simian immunodeficiency virus SIVmac239 Nef and required an intact AP-2 complex. The Nef-mediated internalization of receptors, such as CD4, major histocompatibility complex class I, CD28, and CD8alphabeta, may contribute to the subversion of the host immune system and progression towards AIDS.

    Journal of virology 2005;79;17;11422-33

  • PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking.

    Lu W and Ziff EB

    Program in Neuroscience and Physiology, New York University School of Medicine, New York, New York 10016, USA.

    PICK1 and ABP/GRIP bind to the AMPA receptor (AMPAR) GluR2 subunit C terminus. Transfer of the receptor from ABP/GRIP to PICK1, facilitated by GluR2 S880 phosphorylation, may initiate receptor trafficking. Here we report protein interactions that regulate these steps. The PICK1 BAR domain interacts intermolecularly with the ABP/GRIP linker II region and intramolecularly with the PICK1 PDZ domain. Binding of PKCalpha or GluR2 to the PICK1 PDZ domain disrupts the intramolecular interaction and facilitates the PICK1 BAR domain association with ABP/GRIP. Interference with the PICK1-ABP/GRIP interaction impairs S880 phosphorylation of GluR2 by PKC and decreases the constitutive surface expression of GluR2, the NMDA-induced endocytosis of GluR2, and recycling of internalized GluR2. We suggest that the PICK1 interaction with ABP/GRIP is a critical step in controlling GluR2 trafficking.

    Funded by: NIMH NIH HHS: MH067229

    Neuron 2005;47;3;407-21

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses.

    Vendeville A, Rayne F, Bonhoure A, Bettache N, Montcourrier P and Beaumelle B

    UMR 5539 CNRS, Département Biologie-Santé, Case 107, Université Montpellier II, 34095 Montpellier Cedex 5, France.

    The HIV-1 Tat protein is secreted by infected cells. Extracellular Tat can affect bystander uninfected T cells and induce numerous biological responses such as apoptosis and cytokine secretion. Tat is likely involved in several immune disorders during AIDS. Nevertheless, it is not known whether Tat triggers cell responses directly upon binding to signaling receptors at the plasma membrane or after delivery to the cytosol. The pathway that enables Tat to reach the cytosol is also unclear. Here we visualized Tat within T-cell-coated pits and endosomes. Moreover, inhibitors of clathrin/AP-2-mediated uptake such as chlorpromazine, activated RhoA, or dominant-negative mutants of Eps15, intersectin, dynamin, or rab5 impaired Tat delivery to the cytosol by preventing its endocytosis. Molecules neutralizing low endosomal pH or Hsp90 inhibitors abolished Tat entry at a later stage by blocking its endosomal translocation, as directly shown using a cell-free translocation assay. Finally, endosomal pH neutralization prevented Tat from inducing T-cell responses such as NF-kappaB activation, apoptosis, and interleukin secretion, indicating that cytosolic delivery is required for Tat signaling. Hence, Tat enters T cells essentially like diphtheria toxin, using clathrin-mediated endocytosis before low-pH-induced and Hsp90-assisted endosomal translocation. Cell responses are then induced from the cytosol.

    Molecular biology of the cell 2004;15;5;2347-60

  • Molecular architecture and functional model of the endocytic AP2 complex.

    Collins BM, McCoy AJ, Kent HM, Evans PR and Owen DJ

    Cambridge Institute for Medical Research, University of Cambridge, Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Hills Road, United Kingdom.

    AP2 is the best-characterized member of the family of heterotetrameric clathrin adaptor complexes that play pivotal roles in many vesicle trafficking pathways within the cell. AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) complexed with the polyphosphatidylinositol headgroup mimic inositolhexakisphosphate at 2.6 A resolution. Two potential polyphosphatidylinositide binding sites are observed, one on alpha and one on mu2. The binding site for Yxxphi endocytic motifs is buried, indicating that a conformational change, probably triggered by phosphorylation in the disordered mu2 linker, is necessary to allow Yxxphi motif binding. A model for AP2 recruitment and activation is proposed.

    Cell 2002;109;4;523-35

  • Association of Trk neurotrophin receptors with components of the cytoplasmic dynein motor.

    Yano H, Lee FS, Kong H, Chuang J, Arevalo J, Perez P, Sung C and Chao MV

    Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, Departments of Cell Biology , New York, New York 10016, USA.

    Nerve growth factor (NGF) initiates its trophic effects by long-range signaling through binding, internalization, and transport of a ligand-receptor complex from the axon terminal to the cell body. However, the mechanism by which retrograde transport of NGF takes place has not been elucidated. Here we describe an interaction between the Trk receptor tyrosine kinase and a 14 kDa light chain of cytoplasmic dynein. After transfection in human embryonic kidney 293 cells, this 14 kDa dynein light chain was found to bind to TrkA, TrkB, and TrkC receptors. Mapping experiments indicated that the 14 kDa dynein light chain binds to the distal region of the TrkA juxtamembrane domain. Coimmunoprecipitation experiments in vivo indicate that Trk receptors are in a complex with the 14 kDa light chain and 74 kDa intermediate chain of dynein. Confirming the physiological relevance of this association, a marked accumulation of Trk with the 14 kDa and the 74 kDa dynein components was observed after ligation of the sciatic nerve. The association of Trk receptors with components of cytoplasmic dynein suggests that transport of neurotrophins during vesicular trafficking may occur through a direct interaction of the Trk receptor with the dynein motor machinery.

    Funded by: NEI NIH HHS: EY11307, R01 EY011307; NICHD NIH HHS: HD233-5; NINDS NIH HHS: NS21072

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2001;21;3;RC125

  • Clathrin coat construction in endocytosis.

    Pearse BM, Smith CJ and Owen DJ

    Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK. bulbeck@mrc-lmb.cam.acuk

    Electron cryomicroscopy of the clathrin coat and X-ray crystallography of parts of the clathrin heavy chain combine to give a detailed picture of the clathrin molecule, assembled as a cage. Recently determined domain structures of other components of the endocytic machinery, particularly the mu2 subunit and the alpha-appendage domain of the AP2 adaptor complex, provide important information on the sequence of recognition events involved in the dynamic process of clathrin coat assembly.

    Current opinion in structural biology 2000;10;2;220-8

  • The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module.

    Rosenthal JA, Chen H, Slepnev VI, Pellegrini L, Salcini AE, Di Fiore PP and De Camilli P

    Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.

    Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries. Epsin 1 and 2 are most similar in their NH(2)-terminal region, which represents a module (epsin NH(2) terminal homology domain, ENTH domain) found in a variety of other proteins of the data base. The multiple DPW motifs, typical of the central region of epsin 1, are only partially conserved in epsin 2. Both proteins, however, interact through this central region with the clathrin adaptor AP-2. In addition, we show here that both epsin 1 and 2 interact with clathrin. The three NPF motifs of the COOH-terminal region of epsin 1 are conserved in the corresponding region of epsin 2, consistent with the binding of both proteins to Eps15. Epsin 2, like epsin 1, is enriched in brain, is present in a brain-derived clathrin-coated vesicle fraction, is concentrated in the peri-Golgi region and at the cell periphery of transfected cells, and partially colocalizes with clathrin. High overexpression of green fluorescent protein-epsin 2 mislocalizes components of the clathrin coat and inhibits clathrin-mediated endocytosis. The epsins define a new protein family implicated in membrane dynamics at the cell surface.

    Funded by: NCI NIH HHS: CA46128; NINDS NIH HHS: NS1024-01, NS36251; ...

    The Journal of biological chemistry 1999;274;48;33959-65

  • 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.

    Berlioz-Torrent C, Shacklett BL, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P, Dokhelar MC and Benarous R

    CJF 97/03 INSERM, Interactions Moléculaires, Hôte-Pathogène, Institut Cochin de Génétique Moléculaire, 75014 Paris, France.

    The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the envelope glycoprotein. Flow cytometry and confocal microscopy studies showed that this motif is a major determinant of the cell surface expression of the CD8-HTLV chimera. The YXXO motif also plays a key role in subcellular distribution of the envelope of lentiviruses HIV-1 and SIV. However, these viruses, which encode TM proteins with a long cytoplasmic domain, have additional determinants distal to the YXXO motif that participate in regulating cell surface expression. We have also used the yeast two-hybrid system and in vitro binding assays to demonstrate that all three retroviral YXXO motifs interact with the micro1 and micro2 subunits of AP complexes and that the C-terminal regions of HIV-1 and SIV TM proteins interact with the beta2 adaptin subunit. The TM-CDs of HTLV-1, HIV-1, and SIV also interact with the whole AP complexes. These results clearly demonstrate that the cell surface expression of retroviral envelope glycoproteins is governed by interactions with adaptor complexes. The YXXO-based signal is the major determinant of this interaction for the HTLV-1 TM, which contains a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.

    Journal of virology 1999;73;2;1350-61

  • A novel spliced transcript of human CLAPS2 encoding a protein alternative to clathrin adaptor protein AP17.

    Holzmann K, Pöltl A and Sauermann G

    Institute of Tumor Biology-Cancer Research, University of Vienna, Vienna, Austria. klaus.holzmann@univie.ac.at

    Transcripts of genes encoding proteins of clathrin complexes have been reported to undergo tissue-specific alternative splicing. AP17, encoded by human CLAPS2 cDNA, is the small chain of the major clathrin adaptor complex AP-2 associated with mammalian plasma membranes. In this study, two cDNAs were isolated from a cDNA library of human blood cells. Whereas one cDNA encoded AP17, the other cDNA encoded a putative novel protein variant, termed AP17Delta. Both coding regions were completely sequenced. Consisting of 142aa residues, the predicted protein AP17Delta of 12kDa lacks 38aa residues of AP17. Using specific primers for RT-PCR, mRNAs for AP17Delta and AP17 were found in leukocytes and cultured leukemia cells. The finding of a putative intron in a human EST cDNA clone suggests that mRNAs for AP17 and AP17Delta are formed by alternative splicing. In addition, the identity of human and rat AP17 amino acid sequences is demonstrated.

    Gene 1998;220;1-2;39-44

  • Human CLAPS2 encoding AP17, a small chain of the clathrin-associated protein complex: cDNA cloning and chromosomal assignment to 19q13.2-->q13.3.

    Winterpacht A, Endele S, Enklaar T, Fuhry M and Zabel B

    Children's Hospital, University of Mainz, Germany. winni@winni.kinder.klinik.uni-mainz.de

    We have cloned the cDNA for the human homolog of the rat AP17 gene, a small chain of the clathrin-associated protein complex AP-2. The cDNA is highly conserved between rat and human. Human AP17, gene symbol CLAPS2 (clathrin-associated/assembly/adaptor protein, small 3, 17 kDa), was assigned to chromosome region 19q13.2-->q13.3.

    Cytogenetics and cell genetics 1996;75;2-3;132-5

  • Targeting signals and subunit interactions in coated vesicle adaptor complexes.

    Page LJ and Robinson MS

    Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, England.

    There are two clathrin-coated vesicle adaptor complexes in the cell, one associated with the plasma membrane and one associated with the TGN. The subunit composition of the plasma membrane adaptor complex is alpha-adaptin, beta-adaptin, AP50, and AP17; while that of the TGN adaptor complex is gamma-adaptin, beta'-adaptin, AP47, and AP19. To search for adaptor targeting signals, we have constructed chimeras between alpha-adaptin and gamma-adaptin within their NH2-terminal domains. We have identified stretches of sequence in the two proteins between amino acids approximately 130 and 330-350 that are essential for targeting. Immunoprecipitation reveals that this region determines whether a construct coassemblies with AP50 and AP17, or with AP47 and AP19. These observations suggest that these other subunits may play an important role in targeting. In contrast, beta- and beta'-adaptins are clearly not involved in this event. Chimeras between the alpha- and gamma-adaptin COOH-terminal domains reveal the presence of a second targeting signal. We have further investigated the interactions between the adaptor subunits using the yeast two-hybrid system. Interactions can be detected between the beta/beta'-adaptins and the alpha/gamma-adaptins, between the beta/beta'-adaptins and the AP50/AP47 subunits, between alpha-adaptin and AP17, and between gamma-adaptin and AP19. These results indicate that the adaptor subunits act in concert to target the complex to the appropriate membrane.

    Funded by: Wellcome Trust

    The Journal of cell biology 1995;131;3;619-30

  • AP17 and AP19, the mammalian small chains of the clathrin-associated protein complexes show homology to Yap17p, their putative homolog in yeast.

    Kirchhausen T, Davis AC, Frucht S, Greco BO, Payne GS and Tubb B

    Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, Massachusetts 02115.

    AP17 and AP19 are the smallest polypeptide chain components of AP-2 and AP-1, the clathrin-associated protein complexes found in coated structures of the plasma membrane and Golgi apparatus of mammalian cells. cDNA clones representing the entire coding sequence of AP17 and AP19 were isolated from rat and mouse brain cDNA libraries, respectively. Determination of their nucleotide sequence predicts proteins of 142 and 158 amino acids with Mr 17,018 and 18,733. A sequence comparison of rat brain AP17 with mouse brain AP19 demonstrates that the small chains are highly related. A computer search for other related proteins has uncovered in yeast a previously unknown gene whose DNA sequence encodes a protein homologous to the small chain of AP complexes. 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.

    The Journal of biological chemistry 1991;266;17;11153-7

  • Serine phosphorylation-independent downregulation of cell-surface CD4 by nef.

    Garcia JV and Miller AD

    Program in molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

    A decline in the T-cell population usually marks the onset of progressive immunological disease in individuals infected with the human immunodeficiency virus (HIV). Because CD4+ cells help to coordinate efficient immune responses, some of the defects in the immune function in advanced cases of AIDS may be explained by the disappearance of these cells. Therefore, an understanding of the mechanisms used by HIV to induce the reduction of CD4+ cells is important. Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4. In all cases we find that cell-surface CD4 expression is inversely related to nef expression. However, nef does not alter steady-state levels of CD4 RNA or CD4 protein. Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism.

    Nature 1991;350;6318;508-11

  • Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2.

    Kirchhausen T, Nathanson KL, Matsui W, Vaisberg A, Chow EP, Burne C, Keen JH and Davis AE

    Department of Anatomy, Harvard Medical School, Boston, MA 02115.

    The clathrin-associated protein complex 2 (AP-2 complex) is a group of proteins associated with clathrin-coated vesicles and believed to interact with cytoplasmic domains of receptors found in the plasma membrane. AP-2 was purified as an assembly of several polypeptide chains (alpha, beta, AP50, and AP17), of which only the alpha and beta chains (100-115 kDa) show significant heterogeneity. We have obtained cDNA clones for two distinct rat brain beta chains. We have also studied the domain organization of bovine brain AP-2 complexes by selective proteolysis. Results of these studies show that the alpha and beta chains have a similar two-domain organization. Their amino-terminal domains are relatively invariant whereas their carboxyl-terminal domains are variable in both sequence and length. We propose that the variable domains select receptors for inclusion in coated vesicles.

    Funded by: NIGMS NIH HHS: R01GM36548-01

    Proceedings of the National Academy of Sciences of the United States of America 1989;86;8;2612-6

Gene lists (6)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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