A Bioinformatics Approach to Identifying Tail‐Anchored Proteins in the Human Genome

Kalbfleisch, Theodore S.; Cambon, A.; Wattenberg, Binks W.

doi:10.1111/j.1600-0854.2007.00661.x

Cited by 126 publications

(133 citation statements)

References 27 publications

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“…As ER association of the pre-CPs was compromised in TRC40 knockdown, such a TA protein on the ER membrane might serve as an acceptor for pre-CPs. Further studies are needed to identify this factor from B400 predicted TA proteins 41 .…”

Section: Discussionmentioning

confidence: 99%

Involvement of Bag6 and the TRC pathway in proteasome assembly

et al. 2013

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The 26S proteasome has an elaborate structure, consisting of 33 different subunits that form the 20S core particle capped by the 19S regulatory particle on either end. Several chaperones that are dedicated to the accurate assembly of this protease complex have been identified, but the mechanisms underlying proteasome biogenesis remain unexplored so far. Here we report that core particle assembly becomes less efficient if the TRC pathway, which mediates insertion of tail-anchored proteins, is defective. We demonstrate that Bag6, a protein in the TRC pathway that is also responsible for the degradation of mislocalized proteins, is not only involved in core particle assembly but also has a key role in efficient regulatory particle assembly by directly associating with precursor regulatory particles. These findings indicate that proteasome assembly is not solely mediated by dedicated chaperones but also depends on general chaperones that preserve protein homeostasis.

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Section: Discussionmentioning

confidence: 99%

Involvement of Bag6 and the TRC pathway in proteasome assembly

et al. 2013

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“…TA proteins are involved in vital cellular processes in all domains of life, such as chaperoning, ubiquitination, signaling, trafficking, and transcript regulation (10)(11)(12)(13). The nascent protein is almost fully translated when the hydrophobic TMD emerges from the ribosome, requiring shielding from the aqueous cytosol to guarantee protein stability, efficient folding, and function (14).…”

mentioning

confidence: 99%

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

Xing

Mehlhorn

Wallmeroth

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

109

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Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al. (2008) Cell 134(4):634-645; Stefanovic S, Hegde RS (2007) Cell 128(6):1147-1159]. This pathway consists of six proteins, with the cytosolic ATPase GET3 chaperoning the newly synthesized TA protein posttranslationally from the ribosome to the endoplasmic reticulum (ER) membrane. Structural and biochemical insights confirmed the potential of pathway components to facilitate membrane insertion, but the physiological significance in multicellular organisms remains to be resolved. Our phylogenetic analysis of 37 GET3 orthologs from 18 different species revealed the presence of two different GET3 clades. We identified and analyzed GET pathway components in Arabidopsis thaliana and found reduced root hair elongation in Atget lines, possibly as a result of reduced SNARE biogenesis. Overexpression of AtGET3a in a receptor knockout (KO) results in severe growth defects, suggesting presence of alternative insertion pathways while highlighting an intricate involvement for the GET pathway in cellular homeostasis of plants.GET pathway | TA proteins | SNAREs | ER membrane | root hairs

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“…1 Newly synthesized TA proteins are released from free ribosomes with the C-terminal hydrophobic region inserted into various membranes, such as the endoplasmic reticulum, chloroplast outer envelope, mitochondrial outer membrane and the peroxisomal membrane. 2 The functional domain of TA proteins orients to the cytosol and the TMD of TA proteins is inserted into membranes posttranslationally.…”

mentioning

confidence: 99%

AtPAP2 is a tail-anchored protein in the outer membrane of chloroplasts and mitochondria

Sun

Carrie

Law

et al. 2012

Plant Signaling & Behavior

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Tail-anchored (TA) proteins possess an N-terminal functional domain and a single transmembrane domain (TMD) at the C-terminus followed by a hydrophilic tail.1 Newly synthesized TA proteins are released from free ribosomes with the C-terminal hydrophobic region inserted into various membranes, such as the endoplasmic reticulum, chloroplast outer envelope, mitochondrial outer membrane and the peroxisomal membrane. 2The functional domain of TA proteins orients to the cytosol and the TMD of TA proteins is inserted into membranes posttranslationally. Sorting of proteins by the C-terminal tail (CT) to their specific intracellular destinations is essential for their functions.3 For instance, overexpression of a C-terminal TMDtruncated AtPAP2 in Arabidopsis abolishes its faster plant growth phenotype. 4 Over 500 proteins in Arabidopsis have been predicted to have TA structures, of which, 130 have had their subcellular localization experimentally confirmed based on either GFP targeting or mass spectrometry.2 Most TA proteins were assigned to the ER and secretory membranes, 27 proteins to mitochondria and 32 proteins to plastids.2,5 These include several isoforms of Tom20 and Tom22 (also known as Tom9) of the mitochondrial outer membrane translocon 6,7 and the GTPase receptors of the outer membrane translocon of plastids, including AtToc33, AtToc34. 5,8Arabidopsis purple acid phosphatase 2 (AtPAP2) is the only plant TA protein shown to be dual-targeted to chloroplasts and mitochondria. 4 It was predicted to carry a putative N-terminal signal peptide, a phosphatase domain and a transmembrane domain (TMD) followed by a short hydrophilic C-terminal tail (CT) (a.a. 614-636) by the TMHMM analysis.4 AtPAP2 was to date, Arabidopsis purple acid phosphatase 2 (AtPAP2) is the only known plant protein that is dual-targeted to chloroplasts and mitochondria by a C-terminal targeting signal. using in vitro organelle import and green fluorescence protein (GFP) localization assays, we showed that AtPAP2 is located on, but not imported across the outer membrane (om) of chloroplasts and mitochondria and exposed its n-terminal enzymatic domain to the cytosol. it was also found that a short stretch of 30 amino acids (a.a.) at the C-terminal region (a.a. 615-644) that contains a stretch of 18 hydrophobic residues, a WYAK motif and 8 hydrophilic residues is sufficient for dual-targeting. mutation of WYAK to WYAE had no effect on dual-targeting ability suggesting that the charge within this flanking region alone is not an important determinant for dual-targeting.AtPAP2 is a tail-anchored protein in the outer membrane of chloroplasts and mitochondria Keywords: purple acid phosphatase, mitochondria, plastid, dual-targeting, outer membrane detected in the membrane fraction using immunoblotting. 4 An in vivo targeting assay using chimeric GFP vectors showed that the C-terminal TMD motif of AtPAP2, but not the predicted N-terminal signal peptide, can direct GFP to both plastids and mitochondria in Arabidopsis PSB-D protoplasts. 4 In transgenic Arabi...

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A Bioinformatics Approach to Identifying Tail‐Anchored Proteins in the Human Genome

Cited by 126 publications

References 27 publications

Involvement of Bag6 and the TRC pathway in proteasome assembly

Involvement of Bag6 and the TRC pathway in proteasome assembly

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

AtPAP2 is a tail-anchored protein in the outer membrane of chloroplasts and mitochondria

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