Affinage

Showing SGTA — VPU is a alias.

SGTA

Small glutamine-rich tetratricopeptide repeat-containing protein alpha · UniProt O43765

Length
313 aa
Mass
34.1 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SGTA is a TPR-motif cochaperone that governs the cytosolic triage of nascent and mislocalized membrane proteins, capturing exposed hydrophobic transmembrane domains and arbitrating their fate between productive membrane delivery and proteasomal degradation (PMID:23129660, PMID:25179605). It functions as a holdase that recognizes exposed hydrophobicity on mislocalized membrane proteins and maintains them in a non-ubiquitylated state, directly antagonizing BAG6-mediated ubiquitylation and promoting substrate deubiquitination — an activity independent of its TPR motifs and thus of Hsp70/Hsp90 engagement (PMID:23129660, PMID:25179605). SGTA is itself a component of the BAG6 complex: its noncanonical ubiquitin-like-binding domain engages the unconventional UBL domain of UBL4A, while BAG6's N-terminal UBL domain also binds SGTA, with UBL4A and BAG6 competing for mutually exclusive SGTA binding (PMID:23246001, PMID:23533635). Through its dimerization domain SGTA forms a high-affinity electrostatic complex with the Get5/UBL4A UBL domain in the GET/TRC tail-anchored protein targeting pathway, and it is recruited to ribosomes synthesizing membrane proteins before the transmembrane domain emerges, complementing SRP by masking hydrophobic signals and reducing co-translational ubiquitination (PMID:23142665, PMID:32216016). SGTA also tunes substrate access to the proteasome by binding the 19S ubiquitin receptor Rpn13 via its TPR domain (PMID:26169395). Independently of its membrane-protein triage role, SGTA binds Hsp70 and Hsp90 and acts at an early Hsp70-mediated step of the steroid receptor chaperone cycle to negatively regulate androgen, glucocorticoid, and progesterone receptor activity, abrogating FKBP52-mediated receptor potentiation (PMID:24753260). SGTA is further required for mitotic chromosome congression, acting with BAG6 and Hsp70 in prometaphase, where its depletion causes misaligned chromosomes and mitotic arrest (PMID:16777091). The TPR domain additionally serves as a docking site for multiple viral proteins, including HIV-1 Vpu and Gag (PMID:18759457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 Medium

    Establishing SGTA's existence and architecture answered what kind of protein it is — a conserved, ubiquitously expressed TPR-repeat protein found in both nucleus and cytoplasm — providing the structural framework for all later mechanism.

    Evidence cDNA cloning, FISH mapping, Northern blot, and yeast two-hybrid/in vitro binding to parvovirus NS1 in rat and human cells

    PMID:9557704 PMID:9740675

    Open questions at the time
    • No cellular function assigned beyond viral protein binding
    • TPR-motif binding partners and their specificity undefined
  2. 2003 Medium

    Domain-resolved mapping of client binding showed individual TPR motifs recognize distinct partner sequences (myostatin signal peptide via TPR3, GHR UbE motif via TPR1), framing SGTA as a modular chaperone-like adaptor rather than a single-ligand binder.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, and deletion mutagenesis of SGTA TPR motifs with myostatin and growth hormone receptor

    PMID:12735788 PMID:14623262

    Open questions at the time
    • Functional consequence of these interactions for client processing not established
    • No demonstration of holdase or chaperone activity
  3. 2006 High

    Linking SGTA to Hsp90/Hsp70 and to mitosis showed it is a bona fide cochaperone with an essential cellular role, as its depletion blocks chromosome congression and triggers apoptosis through a BAG6- and Hsp70-associated complex.

    Evidence RNAi with live-cell imaging, reciprocal co-IP with MS identification of BAG6 and Hsp70, BAG6-depletion epistasis, and Hsp90 co-IP with localization shifts upon geldanamycin

    PMID:16580629 PMID:16777091

    Open questions at the time
    • Molecular mechanism by which SGTA-BAG6 promotes congression unknown
    • Whether mitotic and chaperone roles are mechanistically linked unresolved
  4. 2008 High

    The crystal structure of the SGTA TPR domain defined the physical platform for partner binding and showed the TPR alone is sufficient (if less efficient) to bind viral Vpu and reduce particle release, localizing function to a defined module.

    Evidence X-ray crystallography of the TPR domain, peptide array mapping, GST pull-down, and HIV-1 p24 release assay

    PMID:18759457

    Open questions at the time
    • Contribution of N- and C-terminal regions to binding not structurally defined
    • No structure of full-length SGTA or of client-bound complexes
  5. 2012 High

    A cluster of structural and biochemical studies established SGTA as a BAG6-complex subunit and a GET/TRC-pathway component: its UBL-binding domain engages UBL4A/Get5 to load substrates onto BAG6 and to hand off tail-anchored proteins, defining its place in membrane-protein targeting.

    Evidence NMR of the SGTA UBD–UBL4A interface, crystal structures of yeast and human SGTA dimerization-domain/Get5-UBL complexes, biophysical affinity measurements, and ERAD aggregation assays

    PMID:23142665 PMID:23246001

    Open questions at the time
    • Precise handoff sequence from SGTA to TRC40 not kinetically resolved in vivo
    • Stoichiometry of SGTA dimer within the assembled complex unclear
  6. 2012 High

    Demonstrating that SGTA actively antagonizes BAG6-driven ubiquitylation and promotes deubiquitination of mislocalized proteins reframed it from a passive holdase to an active counterweight that can rescue substrates from degradation, with this activity mapped independently of the TPR/Hsp interactions.

    Evidence Ubiquitination and substrate-stability assays with SGTA gain/loss-of-function, domain deletion, and an ER-delivery rescue experiment using an APC-derived model substrate

    PMID:23129660

    Open questions at the time
    • Whether SGTA recruits a deubiquitinase or shields lysines directly not determined
    • Domain responsible for the anti-ubiquitylation activity not finely mapped
  7. 2013 Medium

    Competition mapping clarified the architecture of substrate triage by showing SGTA binds BAG6 or UBL4A but not both at once, with BAG6's central region holding tail-anchored substrates, defining mutually exclusive complex states.

    Evidence In vitro binding, GST pull-down, competition assays, and yeast heterologous localization with domain deletions of BAG6/UBL4A and Sec61β substrate

    PMID:23533635

    Open questions at the time
    • Regulation of the BAG6-vs-UBL4A switch in cells unknown
    • Functional consequence of each complex state for substrate fate not directly tested in mammalian cells
  8. 2014 High

    Two studies established the kinetic logic of the SGTA–BAG6 competition and extended SGTA's regulatory reach: SGTA delays degradation and promotes aggregation when overexpressed, and at the receptor level it acts at an early Hsp70 step to negatively regulate AR, GR, and PR but not MR or ER.

    Evidence Overexpression/knockdown with ubiquitination and aggregation readouts; yeast and mammalian steroid receptor reporter assays, in vitro Hsp70/Hsp90 binding, and FKBP52 epistasis

    PMID:24753260 PMID:25179605

    Open questions at the time
    • How SGTA discriminates among receptor classes mechanistically unclear
    • Whether membrane-protein triage and receptor regulation share the same SGTA pool not addressed
  9. 2015 Medium

    Identifying the SGTA–Rpn13 interaction connected SGTA to the proteasome end of the pathway, showing it can gate substrate access at the 19S regulatory particle through its TPR domain.

    Evidence Co-IP, TPR point mutagenesis, and Rpn13-fragment overexpression with MLP substrate-level readouts

    PMID:26169395

    Open questions at the time
    • Whether SGTA delivers or withholds substrates at Rpn13 not directly distinguished
    • Structural basis of TPR–Rpn13 binding undefined
  10. 2020 Medium

    Showing SGTA is recruited to ribosomes before TMD emergence revealed it acts co-translationally, complementing SRP by masking hydrophobic signals and reducing co-translational ubiquitination, extending its triage role to the earliest stage of membrane-protein synthesis.

    Evidence Ribosome association and nascent-chain pulldown assays, co-translational ubiquitination readouts, and RNAi knockdown

    PMID:32216016

    Open questions at the time
    • Recruitment mechanism to the ribosome before TMD exposure unknown
    • Relationship between co-translational SGTA and the post-translational BAG6 complex not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SGTA's multiple roles — co-translational TMD masking, post-translational BAG6-complex triage, proteasomal gating, steroid receptor regulation, and mitotic congression — are partitioned and regulated within a single cell.
  • No model integrating the chaperone, receptor, and mitotic functions
  • Regulatory inputs controlling which SGTA complex assembles are unknown
  • No in vivo demonstration of how substrate commitment between delivery and degradation is decided

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005840 ribosome 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 1 R-HSA-1640170 Cell Cycle 1
Partners
ARBAG6HSP70HSP90RPN13UBL4AVPU
Complex memberships
BAG6 complex (BAG6/UBL4A/TRC35)GET/TRC targeting machinery

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SGTA (SGT) was identified as a novel cellular protein containing three tetratricopeptide repeat (TPR) motifs that interacts with the parvovirus H-1 nonstructural protein NS1. The interaction was demonstrated by yeast two-hybrid and in vitro interaction assays. SGT was detected in both nucleus and cytoplasm of rat cells by immunofluorescence and subcellular fractionation, and was post-translationally modified upon parvovirus infection or NS protein expression. Yeast two-hybrid screen, in vitro interaction assay, immunofluorescence, subcellular fractionation, Western blot Journal of virology Medium 9557704
1998 Human SGTA (hSGT) cDNA was isolated encoding a 313-amino acid protein with three tandem TPR motifs, ubiquitously expressed across human tissues, and mapped to chromosome 19p13. Homologues were identified in S. cerevisiae and C. elegans, establishing evolutionary conservation of the SGT family. cDNA cloning, Northern blot, fluorescence in situ hybridization (FISH), sequence analysis Genomics Medium 9740675
2001 SGTA (Ubp/Vpu-binding protein) localizes to both nucleus and cytoplasm and is loosely associated with microtubules in the cytoplasm (co-fluorescence with tubulin, but not tightly bound by cytoskeletal isolation). Expression of HIV-1 Vpu caused redistribution of SGTA and Gag to the cell periphery, and SGTA interacts with both Vpu and HIV-1 Gag structural protein. Immunofluorescence/confocal microscopy, cytoskeletal isolation, detergent extraction, flotation gradient analysis Virology Medium 11878889
2003 SGTA interacts with the N-terminal signal peptide region of myostatin via its C-terminal third TPR motif. The interaction was identified by yeast two-hybrid and confirmed by GST pull-down and co-immunoprecipitation, suggesting a role for SGTA as a molecular chaperone in myostatin processing/secretion. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, deletion mutagenesis Biochemical and biophysical research communications Medium 14623262
2003 SGTA interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor (GHR) via its first TPR motif. Both precursor and mature forms of GHR interact with SGTA in vivo, and this interaction is independent of the ubiquitin-conjugating system. GST pull-down, co-immunoprecipitation, deletion mutagenesis of SGTA TPR motifs The Biochemical journal Medium 12735788
2006 SARS-CoV 7a protein interacts with SGTA; the interaction was identified by yeast two-hybrid and confirmed by co-immunoprecipitation and co-localization. The second TPR motif of SGTA (aa 125–158) was essential for the interaction with 7a. Yeast two-hybrid, co-immunoprecipitation, co-localization, deletion mutagenesis Biochemical and biophysical research communications Medium 16580632
2006 SGTA interacts with Hsp90alpha and Hsp90beta. Disruption of the SGTA–Hsp90beta interaction by geldanamycin (Hsp90 inhibitor) increased nuclear localization of SGTA in HeLa cells. Nuclear import of SGTA was also significantly increased during staurosporine-induced apoptosis, indicating that subcellular localization of SGTA is linked to Hsp90 engagement and apoptotic state. Co-immunoprecipitation, confocal microscopy, Western blot of fractionated cells, pharmacological inhibition Biochemical and biophysical research communications Medium 16580629
2006 Human SGTA (hSGT) is required for progression through cell division; RNAi-mediated depletion of hSGT causes prometaphase arrest with persistent misaligned chromosomes near spindle poles, followed by apoptosis. SGTA interacts with Bag-6/Bat-3/Scythe and Hsp70 (confirmed by co-immunoprecipitation of Flag-hSGT and mass spectrometry), and these interactions occur in prometaphase. Bag-6 depletion phenocopies hSGT depletion (misaligned chromosomes and mitotic arrest), suggesting the hSGT–Bag-6 complex has a role in chromosome congression. RNAi knockdown, live-cell imaging (histone H2A-YFP), co-immunoprecipitation, mass spectrometry, truncation mutant analysis Experimental cell research High 16777091
2008 The crystal structure of the TPR domain of human SGTA was determined, revealing typical TPR domain features. The TPR domain of SGTA is sufficient to bind HIV-1 Vpu and to reduce HIV-1 p24 secretion from cells, although less efficiently than full-length SGTA, indicating the N- and/or C-terminus also contribute. The SGTA binding site on Vpu was mapped by peptide array and confirmed by GST pull-down. X-ray crystallography, GST pull-down, peptide array, p24 ELISA (particle release assay) Biochemistry High 18759457
2012 SGTA is a component of the Bag6 (BAG6/Ubl4A/Trc35) complex and cooperates with Bag6 to prevent aggregation of dislocated ERAD substrates. Using NMR spectroscopy and biochemical assays, SGTA was shown to contain a noncanonical ubiquitin-like-binding domain (UBD) that binds an unconventional ubiquitin-like domain in Ubl4A (at least partly via electrostatic interactions), thereby recruiting SGTA to Bag6 and enhancing substrate loading onto Bag6 to prevent formation of nondegradable protein aggregates. NMR spectroscopy, biochemical binding assays, co-immunoprecipitation, ERAD substrate aggregation assays Cell reports High 23246001
2012 SGTA actively antagonizes BAG6-mediated ubiquitination of mislocalized proteins and promotes their deubiquitination, reversing BAG6 pro-degradation activity. This SGTA-mediated deubiquitination is independent of SGTA's TPR motifs (and thus independent of Hsp70/Hsp90 chaperone interactions). Increasing steady-state SGTA levels specifically stabilizes a model mislocalized membrane protein (from amyloid precursor protein), an effect negated by restoring efficient ER delivery. Ubiquitination assays, Western blot of substrate stability, SGTA overexpression and knockdown, domain deletion analysis Proceedings of the National Academy of Sciences of the United States of America High 23129660
2012 The dimerization domain of SGTA (yeast Sgt2) forms a complex with the UBL domain of Get5/UBL4A in the GET/TRC pathway for tail-anchored (TA) protein targeting. Crystal structures of both yeast and human UBD/UBL interfaces were determined, showing the interaction is mediated by electrostatics and has high-affinity with rapid kinetics, providing a refined model for SGTA's role in TA protein handoff. X-ray crystallography, biophysical studies (ITC, SPR or equivalent), biochemical interaction assays Cell reports High 23142665
2012 The HERV-K(HML-2) Rec protein interacts with SGTA via the SGTA TPR motif, as shown by yeast two-hybrid, co-immunoprecipitation, pull-down, and co-localization. This interaction occurs in the cytoplasm and nucleoli. Rec interference with SGTA (a known negative regulator of androgen receptor, AR) resulted in up to 5-fold increase in AR transcriptional activity, and Rec-enhanced AR activity was used to transactivate HERV-K LTR. Yeast two-hybrid, co-immunoprecipitation, pull-down assay, co-localization, AR reporter assay International journal of cancer Medium 22733359
2013 BAG6's N-terminal ubiquitin-like (UBL) domain is essential for binding to SGTA. The UBL domain of UBL4A (a second subunit of the BAG6 complex) also competes with BAG6 for SGTA binding, such that SGTA can bind either BAG6 or UBL4A but not both simultaneously. The large central region of BAG6 (not its UBL or BAG domains) provides a binding site for tail-anchored protein substrates such as Sec61β. In vitro binding assays, GST pull-down, yeast heterologous subcellular localization assay, deletion mutagenesis PloS one Medium 23533635
2014 SGTA and the BAG6 complex compete for cytosolic mislocalized membrane proteins (MLPs) by recognition of exposed hydrophobicity. SGTA maintains MLPs in a non-ubiquitylated state, opposing BAG6-mediated ubiquitylation. When SGTA is overexpressed, proteasomal degradation of aberrant MLPs is delayed, steady-state MLP levels increase, and aggregation is promoted. Overexpression and knockdown, Western blot for ubiquitination and substrate levels, aggregation assays, cell biology assays Journal of cell science Medium 25179605
2014 SGTA specifically associates with and negatively regulates androgen receptor (AR), glucocorticoid receptor (GR), and progesterone receptor (PR) activity, but has no effect on mineralocorticoid or estrogen receptors, in both yeast and mammalian reporter assays. SGTA knockdown/deletion enhances receptor activity; overexpression suppresses it. SGTA binds directly to Hsp70 and Hsp90 in vitro with similar affinities but predominantly precipitates with Hsp70 from cell lysates. SGTA overexpression completely abrogates FKBP52-mediated receptor regulation, placing SGTA at an early Hsp70-mediated step in the chaperone cycle. Yeast and mammalian reporter assays, siRNA knockdown, overexpression, in vitro binding assays, co-immunoprecipitation The Journal of biological chemistry High 24753260
2015 SGTA binds to the C-terminal region of the proteasomal ubiquitin receptor Rpn13 via its TPR domain. SGTA overexpression increases steady-state levels of mislocalized membrane proteins (MLPs), and this effect depends on the SGTA–Rpn13 interaction: overexpression of the Rpn13 SGTA-binding region or point mutations in the SGTA TPR domain that disrupt Rpn13 binding both substantially reduce MLP levels. This indicates SGTA can regulate substrate access to the proteasomal core at the 19S regulatory particle. Co-immunoprecipitation, point mutagenesis, overexpression, Western blot for MLP substrate levels Journal of cell science Medium 26169395
2020 SGTA is selectively recruited to ribosomes synthesizing diverse membrane proteins, including those on the co-translational SRP-dependent ER delivery pathway. SGTA is recruited before the transmembrane domain (TMD) of nascent membrane proteins emerges from the ribosome. For co-translational pathway clients with multiple hydrophobic signals, SGTA reduces co-translational ubiquitination, complementing SRP function by masking TMDs during synthesis until ER translocon engagement. Ribosome association assay, nascent chain pulldown, ubiquitination assay, RNA interference knockdown EMBO reports Medium 32216016

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 1511 18200009
2002 Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde. Cell 560 12507430
1992 Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. Journal of virology 491 1433512
1988 A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science (New York, N.Y.) 422 3261888
1988 Identification of a protein encoded by the vpu gene of HIV-1. Nature 296 3043230
2009 Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS pathogens 290 19478868
2006 The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell 276 16564012
1989 Functional role of human immunodeficiency virus type 1 vpu. Proceedings of the National Academy of Sciences of the United States of America 274 2472639
2009 Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants. PLoS pathogens 263 19214216
1989 Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein. Journal of virology 244 2788224
2006 HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane. PLoS pathogens 225 16699598
1996 The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. Journal of virology 221 8794357
1992 Ubiquitin-specific proteases of Saccharomyces cerevisiae. Cloning of UBP2 and UBP3, and functional analysis of the UBP gene family. The Journal of biological chemistry 215 1429680
2009 HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. The Journal of biological chemistry 204 19837671
1988 Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1. The EMBO journal 195 3138113
2006 Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. Journal of virology 171 16873261
2004 Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression. Virology 145 15015498
2010 HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment. Retrovirology 144 20529266
2004 Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Molecular cell 123 15099524
2016 HIV-1 Vpu Mediates HLA-C Downregulation. Cell host & microbe 120 27173934
2014 HIV-1 Vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells. Journal of virology 115 24623433
2012 The human immunodeficiency virus type 1 Nef and Vpu proteins downregulate the natural killer cell-activating ligand PVR. Journal of virology 111 22301152
2013 Vpu binds directly to tetherin and displaces it from nascent virions. PLoS pathogens 108 23633949
1992 Human-immunodeficiency-virus-type-1-encoded Vpu protein is phosphorylated by casein kinase II. European journal of biochemistry 104 1541298
2010 Modulation of HIV-1-host interaction: role of the Vpu accessory protein. Retrovirology 102 21176220
2011 HIV-1 Vpu protein antagonizes innate restriction factor BST-2 via lipid-embedded helix-helix interactions. The Journal of biological chemistry 98 22072710
2007 Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses. Current molecular medicine 88 17346169
2003 The HIV-1 Vpu protein: a multifunctional enhancer of viral particle release. Microbes and infection 86 12941395
1999 A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proceedings of the National Academy of Sciences of the United States of America 84 10077596
2012 SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation. Cell reports 80 23246001
1998 Identification of a novel cellular TPR-containing protein, SGT, that interacts with the nonstructural protein NS1 of parvovirus H-1. Journal of virology 75 9557704
2012 SGTA antagonizes BAG6-mediated protein triage. Proceedings of the National Academy of Sciences of the United States of America 73 23129660
2014 HIV-1 Nef and Vpu are functionally redundant broad-spectrum modulators of cell surface receptors, including tetraspanins. Journal of virology 71 25275127
2019 HIV-1 Vpu is a potent transcriptional suppressor of NF-κB-elicited antiviral immune responses. eLife 66 30717826
2010 Anti-tetherin activities in Vpu-expressing primate lentiviruses. Retrovirology 66 20167081
2017 HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV. Journal of virology 59 28701393
2006 Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest. Experimental cell research 58 16777091
2012 Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2 and CD4 in humanized mice. Journal of virology 56 22357275
2012 The Rec protein of HERV-K(HML-2) upregulates androgen receptor activity by binding to the human small glutamine-rich tetratricopeptide repeat protein (hSGT). International journal of cancer 56 22733359
2012 Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain reveal an interaction that forms a conserved dynamic interface. Cell reports 56 23142665
2005 Identification of a region within the cytoplasmic domain of the subtype B Vpu protein of human immunodeficiency virus type 1 (HIV-1) that is responsible for retention in the golgi complex and its absence in the Vpu protein from a subtype C HIV-1. AIDS research and human retroviruses 55 15929700
2011 Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu. Journal of virology 54 22090097
2012 Two ZnF-UBP domains in isopeptidase T (USP5). Biochemistry 53 22283393
2016 Vpu-Mediated Counteraction of Tetherin Is a Major Determinant of HIV-1 Interferon Resistance. mBio 50 27531907
2018 Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor. Oncoimmunology 49 30288347
2014 SGTA regulates the cytosolic quality control of hydrophobic substrates. Journal of cell science 49 25179605
2008 Role of HIV-1 Vpu protein for virus spread and pathogenesis. Microbes and infection 48 18672082
2006 Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin. Protein science : a publication of the Protein Society 48 16731964
2016 A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers. Molecular therapy : the journal of the American Society of Gene Therapy 46 27480598
2003 Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses. EMBO reports 46 12973300
1994 Cell type-dependence for Vpu function. Journal of medical primatology 45 7966229
2016 Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence. Viruses 44 26950141
2006 Vpu and Tsg101 regulate intracellular targeting of the human immunodeficiency virus type 1 core protein precursor Pr55gag. Journal of virology 43 16571793
2021 The extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau. Cell communication and signaling : CCS 40 33933071
2015 Vpu Protein: The Viroporin Encoded by HIV-1. Viruses 40 26247957
2013 HIV-1 Vpu - an ion channel in search of a job. Biochimica et biophysica acta 40 23831603
2015 Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells. PLoS pathogens 39 26172439
2013 The association of BAG6 with SGTA and tail-anchored proteins. PloS one 39 23533635
2007 HIV-1 Vpu inhibits accumulation of the envelope glycoprotein within clathrin-coated, Gag-containing endosomes. Cellular microbiology 38 18076669
2010 HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct mechanisms. Molecular aspects of medicine 37 20858517
2008 Structural and functional characterization of human SGT and its interaction with Vpu of the human immunodeficiency virus type 1. Biochemistry 35 18759457
2003 Structure-function correlates of Vpu, a membrane protein of HIV-1. FEBS letters 35 12972151
2007 The solution structure of the ZnF UBP domain of USP33/VDU1. Protein science : a publication of the Protein Society 34 17766394
1998 Isolation and characterization of human SGT and identification of homologues in Saccharomyces cerevisiae and Caenorhabditis elegans. Genomics 34 9740675
2020 HIV-1 Vpu Downregulates Tim-3 from the Surface of Infected CD4+ T Cells. Journal of virology 33 31941771
2013 SGTA: a new player in the molecular co-chaperone game. Hormones & cancer 33 23818240
2021 Role of Viral Protein U (Vpu) in HIV-1 Infection and Pathogenesis. Viruses 32 34452331
2009 The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability. Cell stress & chaperones 32 19953351
2006 Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT. Biochemical and biophysical research communications 32 16580632
2020 Vpu modulates DNA repair to suppress innate sensing and hyper-integration of HIV-1. Nature microbiology 31 32690953
2010 The Vpu protein: new concepts in virus release and CD4 down-modulation. Current HIV research 31 20201792
2004 Vpu: a multifunctional protein that enhances the pathogenesis of human immunodeficiency virus type 1. Current HIV research 31 15279589
2015 The role of HIV-specific antibody-dependent cellular cytotoxicity in HIV prevention and the influence of the HIV-1 Vpu protein. AIDS (London, England) 30 25396265
2003 Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor. The Biochemical journal 30 12735788
2003 hSGT interacts with the N-terminal region of myostatin. Biochemical and biophysical research communications 30 14623262
2020 HDAC6 ZnF UBP as the Modifier of Tau Structure and Function. Biochemistry 29 33237772
2016 HIV-1 Vpu Antagonizes CD317/Tetherin by Adaptor Protein-1-Mediated Exclusion from Virus Assembly Sites. Journal of virology 29 27170757
2015 Vpu is the main determinant for tetraspanin downregulation in HIV-1-infected cells. Journal of virology 29 25568205
2014 HIV-1 Vpu accessory protein induces caspase-mediated cleavage of IRF3 transcription factor. The Journal of biological chemistry 29 25352594
2006 SGT, a Hsp90beta binding partner, is accumulated in the nucleus during cell apoptosis. Biochemical and biophysical research communications 29 16580629
2001 Association of Vpu-binding protein with microtubules and Vpu-dependent redistribution of HIV-1 Gag protein. Virology 29 11878889
2018 The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28 in CD4+ T cells. Retrovirology 28 29329537
2015 HIV Vpu Interferes with NF-κB Activity but Not with Interferon Regulatory Factor 3. Journal of virology 28 26178989
2022 HIV-1 Vpu restricts Fc-mediated effector functions in vivo. Cell reports 27 36351384
2014 Mechanisms underlying HIV-1 Vpu-mediated viral egress. Frontiers in microbiology 26 24822052
2010 HDAC6 and Ubp-M BUZ domains recognize specific C-terminal sequences of proteins. Biochemistry 26 21090589
2020 Experimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, Modulate In Vivo Susceptibility to Artemisinin and Chloroquine in Plasmodium berghei. Antimicrobial agents and chemotherapy 25 32340987
2014 The cochaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) demonstrates regulatory specificity for the androgen, glucocorticoid, and progesterone receptors. The Journal of biological chemistry 25 24753260
2010 The presence of a vpu gene and the lack of Nef-mediated downmodulation of T cell receptor-CD3 are not always linked in primate lentiviruses. Journal of virology 25 21068258
2016 Cell Surface Downregulation of NK Cell Ligands by Patient-Derived HIV-1 Vpu and Nef Alleles. Journal of acquired immune deficiency syndromes (1999) 24 26656785
2018 The roles of cytosolic quality control proteins, SGTA and the BAG6 complex, in disease. Advances in protein chemistry and structural biology 23 30635083
2011 The HIV-1 Vpu viroporin inhibitor BIT225 does not affect Vpu-mediated tetherin antagonism. PloS one 23 22110710
2008 Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), a candidate gene for polycystic ovary syndrome. Human reproduction (Oxford, England) 23 18332089
2020 The HIV-1 Accessory Protein Vpu Downregulates Peroxisome Biogenesis. mBio 22 32127461
2020 SGTA associates with nascent membrane protein precursors. EMBO reports 22 32216016
2015 Binding of SGTA to Rpn13 selectively modulates protein quality control. Journal of cell science 22 26169395
1998 The genomic organization of Isopeptidase T-3 (ISOT-3), a new member of the ubiquitin specific protease family (UBP). Gene 22 9841226
2005 Vpu-mediated CD4 down-regulation and degradation is conserved among highly divergent SIV(cpz) strains. Virology 21 15823605
2018 Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu. Cell reports 20 29490283
2012 HIV-1 Vpu interference with innate cell-mediated immune mechanisms. Current HIV research 20 22524181

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