PaperBLAST

PaperBLAST Hits for SwissProt::A0A125YS36 Vacuolar transporter chaperone complex subunit 2; SPX-dependent polyphosphate polymerase VTC subunit 2; Vacuolar membrane polyphosphate polymerase accessory subunit 2; PolyP polymerase (Toxoplasma gondii (strain ATCC 50611 / Me49)) (1308 a.a., MKFSKQLSAQ...)

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>SwissProt::A0A125YS36 Vacuolar transporter chaperone complex subunit 2; SPX-dependent polyphosphate polymerase VTC subunit 2; Vacuolar membrane polyphosphate polymerase accessory subunit 2; PolyP polymerase (Toxoplasma gondii (strain ATCC 50611 / Me49))
MKFSKQLSAQADLRYLNEYISYKDLKKAIKVITGSDVQVCTVQDVVSNFRQTNALTGSIF
RPPESRFQELLNHELDKINSFSKREVEAILDQLAVALVIMWRLHAALTLLRLAPDSPGYA
EAQALLKRLEQREQEIRNALVVYPQKRGRATEQDKAGSPSSNPRCRGVSDEPSSSSEERE
LGAEGDDFSSAGGKTSSRGEGDAKRRQGDEDGGEGEQDDAKRSVAEALILLEKDVLEVEG
VLEAQSQEIVFLDSFVRLNFTGFRKITKKYDKHNQSSAASWYMSRVVRQDFMNLNFTLLL
TRLARCYVALRSLRRRLGEQQQQSLSISPADDPSKAASVKEDRSTVGSFSQSLGPEGARL
STYKRTGGSDEGEQRREPRFSLAARSRGSRDCREDIKVTKYLIAPDELMKVKVLILKHLP
LLAAGGIPMDDSVLCPFENSSQAVAAEDFSAALEAAASLLRTSGTASDKREARQSLGGSR
VPTWEVYLDNEEFTYYTNTRTRRDSPDSCRGVAPSRRVVRVRWQGLPSLNSAGRQVALEL
SRPDSSIADPQEDITTPLASNAPDVASSAFTVILRQKQLLQLLHGLITPSKLLDQLMDEM
EASAAGVATGEGANATAASHRTGARGAANRGEGSGGGGGNRGSDDRAVALTKQKRKADML
QVLQTVWDAVQQRGVSPSVRTWFYRTEFMSEDGVAWISVDEDIRFSREMNRTPPANQWIR
SETEALSTDDVHPFPWGLLDVSFLVRDNGVALPQHAVQQAKDFHPLVGRDDLEDFVADLR
GLSTLTEVPGFSLFAHGTAYFYTPRLQALQARMSGYEQAVHLIPLWLQYTTNAEFDDDAS
QVFDEATEGGKGKKADRTSVGQSRLGRNQGDSAERGQRAGSPGGLSRPRVCHRGSVIDVV
HQGTSASLVHDLQASAQVSPPTSSGVDQLGNSHRPSVSESRHPSAPALSVLASAPSLPMP
APPLLEVSPFQSGARGLLTQPLLDDGDRMAGERQSASRGGAPTPSQSWLLTGARYWRRYC
NCFSLSGSAGRRRRSMSCLFPWSQRSSARRIHPVGPRSMVAGGVTSGPSVRVEPKTFFAN
ERTLLQWMNTAVLIATISITLMNFGNPVGRIAGLLMSPVAVFFIGYSFWVYLRRARALER
KEPIAYNDKLGPSILVVTLMLSLSAVIALNLLYHEGEAQLPITPQNSSTSTAPSLPPSPH
ALPLLSQLNVSHSQAAYKAPSAPNATVNAGGYSVADVPAPDFSLSHPATAYAAATALAAA
EAAAAAGPVSFAGAPERAVHAHVTEAMTHAASAETAAAEGARVTAGAK

Running BLASTp...

Found 28 similar proteins in the literature:

VTC2_TOXGM / A0A125YS36 Vacuolar transporter chaperone complex subunit 2; SPX-dependent polyphosphate polymerase VTC subunit 2; Vacuolar membrane polyphosphate polymerase accessory subunit 2; PolyP polymerase from Toxoplasma gondii (strain ATCC 50611 / Me49) (see paper)
100% identity, 100% coverage

• function: Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain vtc4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation. The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen. PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase. The VTC complex also plays a role in vacuolar membrane fusion.
  subunit: The VTC core complex is an integral membrane heterooligomer composed of at least the catalytic subunit vtc4 and the accessory subunits vtc1 and vtc2. vtc1 is a small membrane protein without hydrophilic domain. Vtc2 and vtc4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in vtc4 is the catalytic domain.
  disruption phenotype: The VTC2 locus is refractory to knockout, and may be essential. Partial disruption of the gene results in reduced polyP accumulation.

VTC1_SCHPO / Q9UR17 Vacuolar transporter chaperone complex subunit 1; Negative regulator of cdc42; SPX-dependent polyphosphate polymerase VTC subunit 1; Vacuolar membrane polyphosphate polymerase accessory subunit 1; PolyP polymerase from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see 2 papers)
nrf1 GTPase regulator Nrf1 from Schizosaccharomyces pombe (see 3 papers)
SPBC21B10.04c GTPase regulator Nrf1 (predicted) from Schizosaccharomyces pombe
42% identity, 8% coverage

• function: Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain vtc4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation. The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen. PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase. Vtc1 contributes only 3 transmembrane domains to the complex. The VTC complex also plays a role in vacuolar membrane fusion (By similarity). Involved in the control of cell polarity (PubMed:10628977).
  subunit: The VTC core complex is an integral membrane heterooligomer composed of at least the catalytic subunit vtc4 and the accessory subunits vtc1 and vtc2. vtc1 is a small membrane protein without hydrophilic domain. Vtc2 and vtc4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in vtc4 is the catalytic domain (By similarity). Vtc1 interacts with GTP-bound Ras-like cdc42, which is subsequently inactivated (PubMed:10628977).
  disruption phenotype: Defects in endocytosis.
• CharProtDB Source (per GeneDB): GeneDB_Spombe
• Proteasome regulation of petite-negativity in fission yeast.
  Amberg, bioRxiv : the preprint server for biology 2024
  • “...involved in cell-cell communication in N. crassa O13791 slt1 0.57 0.036 Schizosaccharomyces specific protein Slt1 Q9UR17 nrf1 0.57 0.028 vacuolar transporter chaperone (VTC) complex, GTPase regulator subunit Nrf1 P27584 gpa1 0.58 0.009 G-protein alpha subunit O14363 rpl102 0.58 0.003 60S ribosomal protein L10a P79081 SPAC1002.07c 0.58...”
• Dataset describing the genome wide effects on transcription resulting from alterations in the relative levels of the bZIP transcription factors Atf1 and Pcr1 in Schizosaccharomyces pombe
  Basu, Data in brief 2022
  • “...vesicle-mediated transport SPAC15A10.05c mug182 NADHX epimerase SPAC4G9.12 idn1 gluconokinase SPBC23G7.16 ctr6 vacuolar copper exporter Ctr6 SPBC21B10.04c nrf1 vacuolar transporter chaperone (VTC) complex, GTPase regulator subunit Nrf1 SPCC965.06 osr2 potassium channel, beta subunit, aldo-keto reductase SPNCRNA.906 snR30 non-coding RNA SPAC823.17 tom6 mitochondrial TOM complex subunit Tom6 SPAC688.16...”
  • “...SPAC1F8.03c str3 plasma membrane heme transmembrane transporter Str3 SPAC1F8.05 isp3 spore wall structural constituent Isp3 SPBC21B10.04c nrf1 vacuolar transporter chaperone (VTC) complex, GTPase regulator subunit Nrf1 SPBC215.11c SPBC215.11c aldo/keto reductase, unknown biological role SPBC11B10.10c pht1 histone H2A variant H2A.Z Pht1 SPAC4F8.10c stg1 SM22/transgelin-like actin modulating protein...”

VTC1_TRYB2 / Q57UM0 Vacuolar transporter chaperone complex subunit 1; SPX-dependent polyphosphate polymerase VTC subunit 1; Vacuolar membrane polyphosphate polymerase accessory subunit 1; PolyP polymerase from Trypanosoma brucei brucei (strain 927/4 GUTat10.1) (see paper)
XP_846013 vacuolar transporter chaperone, putative from Trypanosoma brucei brucei TREU927
41% identity, 8% coverage

• function: Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain vtc4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation. The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen. PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase. VTC1 contributes only 3 transmembrane domains to the complex. The VTC complex also plays a role in vacuolar membrane fusion.
  subunit: The VTC core complex is an integral membrane heterooligomer composed of at least the catalytic subunit vtc4 and the accessory subunits vtc1 and vtc2. vtc1 is a small membrane protein without hydrophilic domain. Vtc2 and vtc4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in vtc4 is the catalytic domain.
  disruption phenotype: Causes an abnormal morphology of acidocalcisomes, a significant decrease in the amount of polyP and a deficient response to hyposmotic stress.
• Ablation of a small transmembrane protein of Trypanosoma brucei (TbVTC1) involved in the synthesis of polyphosphate alters acidocalcisome biogenesis and function, and leads to a cytokinesis defect.
  Fang, The Biochemical journal 2007
  • GeneRIF: PP(i)-driven H+ pumping deficiency induced by ablation of TbVTC1 induces changes in the protonmotive force of acidocalcisomes, resulting in deficient fusion or budding of the organelles, decreased H+ and Ca2+ content, and decreased synthesis of poly P.

CNAG_00582 vacuolar transporter chaperone 1 from Cryptococcus neoformans var. grubii H99
40% identity, 8% coverage

• The F-Box Protein Fbp1 Regulates Virulence of Cryptococcus neoformans Through the Putative Zinc-Binding Protein Zbp1
  Han, Frontiers in cellular and infection microbiology 2021
  • “...2 CNAG_05216 CAMK protein kinase 1.378940229 1 CNAG_04669 Mitochondrial matrix protein import protein 1.370162857 0 CNAG_00582 Vacuolar transporter chaperone 1 1.369598183 0 CNAG_05817 GDP-mannose transporter 1 1.358720216 0 CNAG_06837 PH domain-containing protein 1.355891304 2 CNAG_05173 DNA-3-methyladenine glycosylase II 1.343807756 0 CNAG_02823 Bloom syndrome protein 1.307827849 2...”

PAS_chr4_0290 Vacuolar transporter chaperon (VTC) involved in distributing V-ATPase and other membrane proteins from Komagataella phaffii GS115
40% identity, 7% coverage

• Effect of Phosphate Starvation on Gene Expression in <i>Komagataella phaffii</i> Cells
  Ishtuganova, Microorganisms 2024
  • “...24 ]. We observed the activation of the KpVTC4 ( PAS_chr2-2_0420 ) and KpVTC1 ( PAS_chr4_0290 ) genes in our study. They encode components of the Vtc4p and Vtc1p chaperone complexes, respectively ( Figure 2 ). 3.3. The Phosphate Starvation Influences Genes Involved in Carbon Metabolism...”

FOIG_07033 vacuolar transporter chaperone 1 from Fusarium odoratissimum NRRL 54006
39% identity, 7% coverage

• RNA Sequencing Reveals that Endoplasmic Reticulum Stress and Disruption of Membrane Integrity Underlie Dimethyl Trisulfide Toxicity against Fusarium oxysporum f. sp. cubense Tropical Race 4
  Zuo, Frontiers in microbiology 2017
  • “...OST4 (FOIG_01070), signal peptidase complex (FOIG_03977 and FOIG_05064), phosphotransferase (FOIG_05811), and vacuolar transporter chaperone 1 (FOIG_07033) ( Figure 5 ). FIGURE 5 Expression profiles of ER-related genes. Repression of DEGs Involved in Steroid Biosynthesis Following DT Exposure The expression of the genes involved in steroid biosynthesis...”

VTC1_YEAST / P40046 Vacuolar transporter chaperone complex subunit 1; Negative regulator of CDC42 protein 1; Phosphate metabolism protein 4; SPX-dependent polyphosphate polymerase VTC subunit 1; Vacuolar membrane polyphosphate polymerase accessory subunit 1; PolyP polymerase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see 9 papers)
TC 9.B.51.1.6 / P40046 VTC1 or PHM4 protein of 129 aas and 3 TMSs from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
NP_010995 Vtc1p from Saccharomyces cerevisiae S288C
YER072W Vacuolar transporter chaperon (VTC) involved in distributing V-ATPase and other membrane proteins; together with other VTC proteins, forms a heterotetrameric complex that associates with the SNARE Nyv1p and the V0 sector of the V-ATPase from Saccharomyces cerevisiae
38% identity, 8% coverage

• function: Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain VTC4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation (PubMed:19390046). The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen (PubMed:19390046, PubMed:25315834). PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase (PubMed:25315834). VTC1 contributes only 3 transmembrane domains to the complex (Probable). The VTC complex also plays a role in vacuolar membrane fusion (PubMed:10480897, PubMed:11102525, PubMed:11823419, PubMed:12584253). Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation (PubMed:11823419).
  subunit: The VTC core complex is an integral membrane heterooligomer composed of the catalytic subunit VTC4 and the accessory subunits VTC1, VTC2 and VTC3. The complex exists in 2 different sub-complexes: VTC1- VTC2-VCT4 and VCT1-VTC3-VTC4. The VCT1-VTC3-VTC4 subcomplex is mostly found on the vacuolar membrane. The VTC1-VTC2-VCT4 subcomplex is observed in the cell periphery, probably ER and nuclear envelope, but localizes to the vacuole under phosphate starvation. Each subunit contains 3 transmembrane helices. VTC1 is a small membrane protein without hydrophilic domain. VTC2, VTC3 and VTC4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in VTC4 is the catalytic domain, with the essential catalytic lysine replaced by isoleucine and leucine in VTC2 and VTC3, respectively (PubMed:19390046). The core complex associates with the accessory subunit VTC5 (PubMed:27587415). The complex interacts with the v-SNARE NYV1 and with the V(0) subunit of V-ATPase VPH1 (PubMed:11823419).
• substrates: H+
  tcdb comment: This protein corresponds to the C-terminal domain of polyphosphate polymerase (TC# 4..E.1) (Gerasimaitė et al. 2014). VTC proteins influence the vacuolar H+-ATPase (V-ATPase) as well as vacuolar H+ uptake. Like the V-ATPase V0 sectors, VTCs are important factors in vacuolar membrane fusion (Müller et al. 2003)
• The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex
  Guan, Nature communications 2023
  • “...14 , 35 . Protein expression and purification The codon-optimized DNAs of yeast Vtc1 (Uniprot: P40046), Vtc3 (Uniprot: Q02725) and Vtc4 (Uniprot: P47075) were subcloned separately into the pMlink vector 55 . Vtc1 was tagged with a C-terminal HA tag, Vtc3 was tagged with an N-terminal...”
• Knockout of the Hmt1p Arginine Methyltransferase in Saccharomyces cerevisiae Leads to the Dysregulation of Phosphate-associated Genes and Processes
  Chia, Molecular & cellular proteomics : MCP 2018
  • “...Pho8p YLR413W Pho3p Fpr4p Pdr5p Q02725 P25297 P40046 P47075 P32802 P11491 Q06689 P24031 Q06205 P33302 Vacuolar transporter chaperone Inorganic phosphate...”
• Ablation of a small transmembrane protein of Trypanosoma brucei (TbVTC1) involved in the synthesis of polyphosphate alters acidocalcisome biogenesis and function, and leads to a cytokinesis defect
  Fang, The Biochemical journal 2007
  • “...of TbVTC1 (Tb, AAX70699) with S. cerevisiae Phm4/Vtc1 (Sc, P40046) and two orthologues from T. cruzi (Tc, AY304574) and L. major (Lm, CAB 86965). Lines above...”
• Isolation and characterization of Nrf1p, a novel negative regulator of the Cdc42p GTPase in Schizosaccharomyces pombe
  Murray, Genetics 2000
  • “...S. cerevisiae encodes a protein (YER072w; accession no. P40046) that is 78% identical (91% similar) in predicted amino-acid sequence to S. pombe Nrf1p (Figure...”
• Ddi1 is a ubiquitin-dependent protease.
  Yip, Proceedings of the National Academy of Sciences of the United States of America 2020
  • GeneRIF: unlike other shuttling factors, Ddi1 and its homologs contain a conserved helical domain (helical domain of Ddi1, HDD) and a retroviral-like protease (RVP) domain. The RVP domain is probably responsible for cleavage of the precursor of the transcription factor Nrf1 in higher eukaryotes, which results in the up-regulation of proteasomal subunit genes.
• Antifungal Activity of Disalt of Epipyrone A from Epicoccum nigrum Likely via Disrupted Fatty Acid Elongation and Sphingolipid Biosynthesis
  Lee, Journal of fungi (Basel, Switzerland) 2024
  • “...6500HS (General Electric). For reference, nuclei were distinguished with RFP. These proteins include Sit1(YEL065W); Vtc1 (YER072W); Sna3 (YJL151C); Ade17 (YMR120C); Aga1 (YNR044W); Cmk2 (YOL016C); and Sur1 (YPL057C). Figure 8 Quantitative comparison of GFP-tagged protein intensity in presence and absence (control) of disalt of epipyrone A (DEA)....”
  • “...proteins include Ade17 (YMR120C); Aga1 (YNR044W); Cmk2 (YOL016C); Sit1(YEL065W); Sna3 (YJL151C); Sur1 (YPL057C); and Vtc1 (YER072W). **** represents p < 0.0001. Figure 9 Thin-layer chromatography (TLC) reveals accumulation of free fatty acids (FFA) and triacyl glycerides (TAG) in disalt of epipyrone A (DEA)-treated cells. Cells were...”
• Spt4 facilitates the movement of RNA polymerase II through the +2 nucleosomal barrier
  Uzun, Cell reports 2021
  • “...(RNAPII) and TEF-seq (Spt4 and Spt5) reads of example genes transcribed fromthe positive strand, namely, YER072W , YER073W , and YDR381W , in two biological replicates. The dark-blue boxes indicate the transcribed region of the genes (from TSS to PAS), and the blue line indicates the...”
• The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae
  Trilisenko, Cells 2019
  • “...and diphosphoinositol endopolyphosphatase 1.00 0.96 0.46 Subunits of the VTC Complex Involved in Polyphosphate Biosynthesis YER072W VTC1 Regulatory subunit involved in membrane trafficking and vacuolar polyphosphate accumulation 5.48 5.05 2.94 YFL004W VTC2 1.59 1.52 0.98 YPL019C VTC3 1.18 2.51 2.33 YDR089W VTC5 0.78 0.96 0.07 YJL012C...”
• Widespread Cumulative Influence of Small Effect Size Mutations on Yeast Quantitative Traits
  Hua, Cell systems 2018
  • “...YDR245W, YBR036C, YDR221W, YPL192C, YLL014W, YDR508C, YEL001C, YER005W, YDR137W, YDL099W, YGL231C, YHR108W, YMR238W, YAL053W, YIL027C, YER072W, YML038C, YER120W, YEL027W, YIL030C, YDR492W, YJR131W, YMR010W, YHR181W, YPR063C, YIL124W, YLR350W, YJR088C, YBL011W, YML048W, YNL044W, YDR358W, YOR311C, YDR411C, YMR272C, YNL049C, YMR015C, YDL052C, YJR134C, YKL096W, YNL280C, YLR194C, YER113C, YDR077W, YDR055W, YNR021W,...”
• Yeast metabolic and signaling genes are required for heat-shock survival and have little overlap with the heat-induced genes
  Gibney, Proceedings of the National Academy of Sciences of the United States of America 2013
  • “...YDR340W RPL4A BMH1 YIR027C YML107C DAL1 PML39 YER072W YOL153C YFR010W YBL081W YOR170W YLR392C VTC1 YOL153C UBP6 YBL081W YOR170W ART10 Inositol hexakisphosphate...”
• A Whole Genome Screen for Minisatellite Stability Genes in Stationary-Phase Yeast Cells
  Alver, G3 (Bethesda, Md.) 2013
  • “...YMR258C YMR258c EDC3 YEL015w PRM4 YPL156c VPS61 YDR136c YMR304C-A YMR304c-a EFT2 YDR385w PSD2 YGR170w VTC1 YER072w YOL024W YOL024w ELC1 YPL046c PXL1 YKR090w YAP1801 YHR161c YOL079W YOL079w FDC1 YDR539w QCR10 YHR001w-a YAT2 YER024w YOL153C YOL153c FIN1 YDR130c RDS1 YCR106w YBL096C YBL096c YOR170W YOR170w FOB1 YDR110w REC104 YHR157w...”
• The role of the Parkinson's disease gene PARK9 in essential cellular pathways and the manganese homeostasis network in yeast
  Chesi, PloS one 2012
  • “...PPM1 YHR180W YHR180W YJR033C RAV1 YJL053W PEP8 YKR028W SAP190 YIL054W YIL054W YBR231C SWC5 YIL040W APQ12 YER072W VTC1 YLL044W YLL044W YJL004C SYS1 YJR074W MOG1 YJL012C VTC4 YOR199W YOR199W YKL081W TEF4 YMR031W-A YMR031W-A YHR135C YCK1 YIL145C PAN6 YOL018C TLG2 YDR089W YDR089W YDL095W PMT1 YKR001C VPS1 YDR295C HDA2 YLL030C...”
• High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome
  Yu, BMC genomics 2012
  • “...- - - - - - 8.45 - - - - 6.10 - - P YER072W VTC1 B - - - - - - 8.94 - - - - 8.59 - - S YOL049W GSH2 C - 5.42 - - - - - - 6.15 -...”
• More

Q6CDJ7 YALI0B23408p from Yarrowia lipolytica (strain CLIB 122 / E 150)
42% identity, 7% coverage

• Validated Growth Rate-Dependent Regulation of Lipid Metabolism in Yarrowia lipolytica
  Poorinmohammad, International journal of molecular sciences 2022
  • “...extracting the interaction term of the linear model. Contrastingly, the proteins Q6CAQ5 (E3 ubiquitin-protein ligase), Q6CDJ7 (YALI0B23408p), and Q6CHE0 (glycine cleavage system P protein) ( Figure 2 b) exemplify expression changes with similar patterns in both strains, and thus such profiles were not considered in the...”

M7XMX5 Vacuolar transporter chaperone 4 from Rhodotorula toruloides (strain NP11)
36% identity, 8% coverage

• Adaptation of Proteome and Metabolism in Different Haplotypes of Rhodosporidium toruloides during Cu(I) and Cu(II) Stress
  Cavelius, Microorganisms 2023
  • “...n.d. 2.17 Vacuolar transporter chaperone 2 M7WMK7 64.00 17.05 n.d. n.d. Vacuolar transporter chaperone 4 M7XMX5 n.d. 2.26 n.d. n.d. Mitochondrial inner membrane metallopeptidase Oma1 M7X2Q6 down n.d. down down A0A0K3C9S0 down 0.46 n.d. n.d. Mitochondrial outer membrane protein IML2 M7X0Q4 n.d. up down down A0A2T0A031...”

AFUA_1G09540 vacuolar transporter chaperon Vtc1, putative from Aspergillus fumigatus Af293
37% identity, 8% coverage

• The Influence of <i>Aspergillus fumigatus</i> Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility
  Delbaje, Journal of fungi (Basel, Switzerland) 2024
  • “...3) 1.9383 AFUA_4G06330 (C6 transcription factor) 12.169 Protein ppoC /WT (CSP) * AFUA_4G10130 (alpha-amylase) 12.271 AFUA_1G09540 (vacuolar transporter chaperon Vtc1) 11.797 AFUA_7G06750 (phosphoglycerate mutase) 9.2397 AFUA_7G04020 (lipase) 8.2124 AFUA_8G05360 (FAS1 domain-containing protein) 8.0016 AFUA_5G09130 (polysaccharide deacetylase) 7.1757 AFUA_1G12040 (chitin synthase export chaperone) 6.4859 AFUA_8G00230 (verruculogen synthase)...”

P78810 Vacuolar transporter chaperone complex subunit 4 from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
39% identity, 8% coverage

• Proteasome regulation of petite-negativity in fission yeast.
  Amberg, bioRxiv : the preprint server for biology 2024
  • “...mrpl4 0.41 0.036 mitochondrial ribosomal protein subunit L29 O74512 wtf14 0.42 0.031 wtf element Wtf14 P78810 vtc4 0.43 0.010 vacuolar transporter chaperone (VTC) complex subunit Vtc4 P00046 cyc1 0.43 0.006 cyc1 cytochrome c O14249 SPAC6G10.03c 0.43 0.030 mitochondrial cardiolipin-specific phospholipase Cld1 Q9HDU3 gal10 0.44 0.047 UDP-glucose...”

VTC4_YEAST / P47075 Vacuolar transporter chaperone complex subunit 4; Phosphate metabolism protein 3; Polyphosphate kinase; SPX-dependent polyphosphate polymerase VTC subunit 4; Vacuolar membrane polyphosphate polymerase catalytic subunit; PolyP polymerase; EC 2.7.4.1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see 12 papers)
NP_012522, YJL012C Vacuolar membrane protein involved in vacuolar polyphosphate accumulation; functions as a regulator of vacuolar H+-ATPase activity and vacuolar transporter chaperones; involved in non-autophagic vacuolar fusion from Saccharomyces cerevisiae
NP_012522 Vtc4p from Saccharomyces cerevisiae S288C
36% identity, 8% coverage

• function: Catalytic subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain VTC4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation (PubMed:19390046). The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen (PubMed:19390046, PubMed:25315834). PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase (PubMed:25315834). The VTC complex also plays a role in vacuolar membrane fusion (PubMed:11102525, PubMed:11823419, PubMed:12584253). Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation (PubMed:11823419). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7); these are important intracellular signaling molecules. Inositol polyphosphate binding promotes vacuolar polyphosphate synthesis (PubMed:27080106). The VTC complex is required for microautophagy. It is a constituent of autophagic tubes and is required for scission of microautophagic vesicles from these tubes (PubMed:17079729).
  catalytic activity: [phosphate](n) + ATP = [phosphate](n+1) + ADP (RHEA:19573)
  cofactor: Mn(2+)
  subunit: The VTC core complex is an integral membrane heterooligomer composed of the catalytic subunit VTC4 and the accessory subunits VTC1, VTC2 and VTC3. The complex exists in 2 different sub-complexes: VTC1- VTC2-VCT4 and VCT1-VTC3-VTC4. The VCT1-VTC3-VTC4 subcomplex is mostly found on the vacuolar membrane. The VTC1-VTC2-VCT4 subcomplex is observed in the cell periphery, probably ER and nuclear envelope, but localizes to the vacuole under phosphate starvation. Each subunit contains 3 transmembrane helices. VTC1 is a small membrane protein without hydrophilic domain. VTC2, VTC3 and VTC4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in VTC4 is the catalytic domain, with the essential catalytic lysine replaced by isoleucine and leucine in VTC2 and VTC3, respectively (PubMed:19390046). The core complex associates with the accessory subunit VTC5 (PubMed:27587415). The complex interacts with the v-SNARE NYV1 and with the V(0) subunit of V-ATPase VPH1 (PubMed:11823419).
  disruption phenotype: Leads to a decrease in intracellular arginine, consistent with a role for polyP in vacuolar arginine storage.
• Identification of the Genetic Requirements for Zinc Tolerance and Toxicity in Saccharomyces cerevisiae
  Zhao, G3 (Bethesda, Md.) 2020
  • “...PTC7 YMR264W CUE1 Cellular transport, transport facilities and transport routes (32) YBR127C VMA2 YFL004W VTC2 YJL012C VTC4 YLR261C VPS63 YCL038C ATG22 YGL212W VAM7 YJL024C APS3 YLR262C YPT6 YCR037C PHO87 YGL095C VPS45 YJL154C VPS35 YLR268W SEC22 YDL100C GET3 YGR105W VMA21 YJL198W PHO90 YLR396C VPS33 YDR089W VTC5 YHL031C...”
• The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in Saccharomyces cerevisiae
  Trilisenko, Cells 2019
  • “...YFL004W VTC2 1.59 1.52 0.98 YPL019C VTC3 1.18 2.51 2.33 YDR089W VTC5 0.78 0.96 0.07 YJL012C VTC4 Vacuolar membrane polyphosphate polymerase 0.97 1.48 1.90 Phosphate Transport YFR034C PHO4 Activates transcription in response to phosphate limitation; function is regulated by phosphate availability 0.82 0.81 0.52 YML123C PHO84...”
• The role of PCNA as a scaffold protein in cellular signaling is functionally conserved between yeast and humans
  Olaisen, FEBS open bio 2018
  • “...Cox23 Cytochrome c oxidaseassembly factor Cox23 2 YHR137W Aro9 Aromatic amino acid aminotransferase 2 1 YJL012C Vtc4 Vacuolar transporter chaperone 4 42 YJL090C Dpb11 DNA replication regulator Dpb11 10 YKL028W Tfa1 Transcription initiation factor IIE subunit alpha 11 YKL103C Ape1 Vacuolar aminopeptidase 1 14 YKR026C Gcn3...”
• Analysis of COPII Vesicles Indicates a Role for the Emp47-Ssp120 Complex in Transport of Cell Surface Glycoproteins
  Margulis, Traffic (Copenhagen, Denmark) 2016
  • “...21 30 Plasma membrane H+-ATPase YOR270C Vph1 7 22 Subunit a of vacuolar-ATPase V0 domain YJL012C Vtc4 5 20 Vacuolar membrane polyphosphate polymerase YDR135C Ycf1 0 11 Vacuolar glutathione S-conjugate transporter...”
• The role of the Parkinson's disease gene PARK9 in essential cellular pathways and the manganese homeostasis network in yeast
  Chesi, PloS one 2012
  • “...SAP190 YIL054W YIL054W YBR231C SWC5 YIL040W APQ12 YER072W VTC1 YLL044W YLL044W YJL004C SYS1 YJR074W MOG1 YJL012C VTC4 YOR199W YOR199W YKL081W TEF4 YMR031W-A YMR031W-A YHR135C YCK1 YIL145C PAN6 YOL018C TLG2 YDR089W YDR089W YDL095W PMT1 YKR001C VPS1 YDR295C HDA2 YLL030C RRT7 YJL029C VPS53 YPR179C HDA3 YIL047C SYG1 YPL019C...”
• High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome
  Yu, BMC genomics 2012
  • “...- 3.98 - - - - - 3.63 - - - - - - P YJL012C VTC4 B - - - - - - 8.45 - - - - 6.10 - - P YER072W VTC1 B - - - - - - 8.94 - - -...”
• Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases
  Lonetti, The Journal of biological chemistry 2011
  • “...2). It has recently been found that Vtc4 (YJL012C; also known as Phm3), corresponding to subunit four of the vacuolar transporter chaperone complex, functions...”
• Identification of direct target genes using joint sequence and expression likelihood with application to DAF-16
  Yu, PloS one 2008
  • “...HIS1 YER055C HOR2 YER062C VTC1 YER072W VTC2 YFL004W SPL2 * YHR136C PHO12 * YHR215W VTC4 YJL012C PHO86 * YJL117W PHO84 * YML123C PHM7 YOL084W CTF19 YPL018W VTC3 YPL019C KRE29 YER038C SWC3 YAL011W YAR069C YAR069C YAR070C YAR070C KRE2 YDR483W MNN1 YER001W ARO9 YHR137W REC107 YJR021C YJR039W YJR039W...”
• More
• Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase.
  Hothorn, Science (New York, N.Y.) 2009 (PubMed)
  • GeneRIF: results define Vtc4p* as a polyP-synthesizing enzyme
• The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex
  Guan, Nature communications 2023
  • “...purification The codon-optimized DNAs of yeast Vtc1 (Uniprot: P40046), Vtc3 (Uniprot: Q02725) and Vtc4 (Uniprot: P47075) were subcloned separately into the pMlink vector 55 . Vtc1 was tagged with a C-terminal HA tag, Vtc3 was tagged with an N-terminal 3Flag, and Vtc4 was tagged with a...”
• Altered proteome in translation initiation fidelity defective eIF5^G31R mutant causes oxidative stress and DNA damage
  Ram, Scientific reports 2022
  • “...P46992 TOH1 1.7233 0.0489 15 P32528 DUR1,2 1.7275 0.0011 16 Q02725 VTC3 1.7513 0.0068 17 P47075 VTC4 1.8045 0.0040 18 P40159 YNL208W 1.8591 0.0191 19 Q04432 HSP31 1.8778 0.0026 20 P22943 HSP12 1.8912 0.0252 21 P43585 VTC2 1.9087 0.0453 22 P12962 CAF20 1.9685 0.0059 23 Q12123...”
• Knockout of the Hmt1p Arginine Methyltransferase in Saccharomyces cerevisiae Leads to the Dysregulation of Phosphate-associated Genes and Processes
  Chia, Molecular & cellular proteomics : MCP 2018
  • “...YLR413W Pho3p Fpr4p Pdr5p Q02725 P25297 P40046 P47075 P32802 P11491 Q06689 P24031 Q06205 P33302 Vacuolar transporter chaperone Inorganic phosphate transporter...”
• The macro domain as fusion tag for carrier-driven crystallization
  Wild, Protein science : a publication of the Protein Society 2017
  • “...cerevisiae Vtc3; Q02725) and ScVtc4 (S. cerevisiae Vtc4; P47075) and including a secondary structure assignment calculated with the program DSSP48 and based on...”
• Positively-charged semi-tunnel is a structural and surface characteristic of polyphosphate-binding proteins: an in-silico study
  Wei, PloS one 2015
  • “...three-subunit components with actin-like structure. not reported PPK4 (vacuolar transporter chaperone, VTC4) Saccharomyces cerevisiae (NP_012522.2, P47075) membrane transport and vesicular traffic. one SPX domain (IPR004331) at the N terminus, DUF202 (IPR003807) and VTC domain (IPR018966). polyP-winding tunnel-shaped pocket with nucleotide-and phosphate-binding structures, formed mainly by antiparallel...”

8i6vE / P47075 Cryo-em structure of the polyphosphate polymerase vtc complex(vtc4/vtc3/vtc1) (see paper)
36% identity, 8% coverage

• Ligand: triphosphate (8i6vE)

CNAG_01263, XP_012049426 vacuolar transporter chaperone 4 from Cryptococcus neoformans var. grubii H99
J9VQL2 Vacuolar transporter chaperone 4 from Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487)
36% identity, 8% coverage

• Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans
  Bowring, mBio 2023
  • “...(CNAG_00483) ATGGTATTGCCGACCGTATG CTCTTCGCGATCCACATCTG PHO89 sodium-dependent phosphate transporter (CNAG_05075) GTGCTCGGTAACAGACTGAC ACGCTCGCCAGTTAATCG VTC4 vacuolar chaperone complex 4 (CNAG_01263) GATGCCGTCGGTATGGTTTC TAACAACGCCGCGCAAAG BTA1 betaine lipid synthase (CNAG_02353) CCCATTCCAACGCTTTCTACTCTCA AGCGACTCATCAGGAAGACCCC PHO84 phosphate:H symporter (CNAG_02777) CCTACTCGTTACCGATCAACTG AGTCTCGGGAAGAAGCAATG APH1 phosphate-repressible vacuolar acid phosphatase (CNAG_02944) CCTTCAACTTGAGTGCGCTT ACATCCCGTCCTTGTTCCAT PHO81 cyclin-dependent protein kinase inhibitor (CNAG_02541) AAGAAGGTAGGAAGGGAGAGCGG...”
• IP₇-SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery
  Desmarini, mBio 2020
  • “...XP_012049680 ), CnSyg1 ( XP_012051471 ), CnPho91 ( XP_012049822 ) phosphate transporter, and CnVtc4 ( XP_012049426 ) vacuolar transporter chaperone 4; Saccharomyces cerevisiae ScPho81 (SGDID:S000003465), ScVtc4 (SGDID:S000003549), ScVtc2 (SGDID:S000001890), and ScVtc3 (SGDID:S000005940); Histoplasma capsulatum HcPho81 ( EEH08674 ); Pneumocystis jirovecii PjPho81 ( XP_018228495 ); Candida albicans...”
• Pho4 Is Essential for Dissemination of Cryptococcus neoformans to the Host Brain by Promoting Phosphate Uptake and Growth at Alkaline pH
  Lev, mSphere 2017
  • “...) CNAG_06967 APH2 Phytase CNAG_02681 APH3 Phytase CNAG_06115 APH4 Acid phosphatase VTC4 Vacuolar transporter chaperone CNAG_01263 VTC4 Vacuolar transporter chaperone 4 ( 8 ) NA CNAG_02353 BTA1 Betaine lipid (DGTS) synthase PHO81 Cyclin-dependent kinase inhibitor CNAG_02541 PHO81 Cyclin-dependent protein kinase inhibitor ( 7 ) GDE1 Glycerophosphocholine...”
• Defects in phosphate acquisition and storage influence virulence of Cryptococcus neoformans
  Kretschmer, Infection and immunity 2014
  • “...membrane Polyphosphate storage and processing Vtc4 Ppx1 Ppn1 CNAG_01263 CNAG_04354 CNAG_07629 VTC4 XPP1 EPP1 e155 2e24 1e76 64 26 43 80 44 61 Vacuolar...”
  • “...to the yeast vacuolar transport chaperone Vtc4 (CNAG_01263) for polyphosphate synthesis, as well as candidate orthologs for endopolyphosphatases (EPP1) and...”
• Identification, Culture Characteristics and Whole-Genome Analysis of Pestalotiopsis neglecta Causing Black Spot Blight of Pinus sylvestris var. mongolica
  Yang, Journal of fungi (Basel, Switzerland) 2023
  • “...quality control protease 31.9 gene03868 Scaffold2 PHI:2393 I1R980 Fusarium graminearum - 25.8 gene03896 Scaffold2 PHI:3529 J9VQL2 Cryptococcus neoformans Phosphate Acquisition and Storage 46.9 gene04733 Scaffold3 PHI:2393 I1R980 Fusarium graminearum - 26.8 gene05524 Scaffold3 PHI:7121 B0YCA2 Aspergillus fumigatus Trehalosephosphate synthase subunit 51.9 gene05651 Scaffold3 PHI:2393 I1R980 Fusarium...”

AFUA_2G09040, Afu2g09040 vacuolar transporter chaperone (Vtc4), putative from Aspergillus fumigatus Af293
31% identity, 9% coverage

• Lipid Biosynthesis as an Antifungal Target
  Pan, Journal of fungi (Basel, Switzerland) 2018
  • “...A. nidulans A. fumigatus [ 51 ] AFUA_3G12320 Lipase/Serine esterase S. cerevisiae [ 57 ] AFUA_2G09040 Vacuolar transporter chaperone (Vtc4) Ustilago maydis Candida [ 53 , 54 ] * Fungi tested means that fungi listed here are already well described in literature and the researchers have...”
• Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach
  Kaltdorf, Frontiers in molecular biosciences 2016
  • “...protein AFUA_2G17650 0.523 2.921 2.795 DUF907 domain protein AFUA_2G17300 n.s. 4.050 1.057 GSH Glutathione S-transferase AFUA_2G09040 n.s. 1.360 1.053 Vacuolar transporter chaperone (Vtc4) AFUA_2G04010 n.s. 1.125 1.182 SUC Alpha,alpha-trehalose-phosphate synthase subunit ESSENTIAL GENES AFUA_3G14440 0.916 1.174 n.s. Cytochrome c oxidase family protein AFUA_4G10480 n.s. 2.375 1.812...”
  • “...protein AFUA_2G17300 261 220 481 14 Glutathione S-transferase AFUA_1G17010 261 220 481 14 Glutathione S-transferase AFUA_2G09040 307 195 502 15 Vacuolar transporter chaperone (Vtc4) AFUA_2G04010 220 302 522 16 Alpha, alpha-trehalose-phosphate synthase subunit AFUA_6G12950 220 302 522 16 Trehalose-phosphate synthase/phosphatase complex subunit Tps1, putative B I...”
• Functional characterization of the Aspergillus fumigatusPHO80 homologue
  de, Fungal genetics and biology : FG & B 2008 (PubMed)
  • “...(phoDPHO84), Afu7g06350 (phoEPHO89), Afu4g06020 (phoCPHO81), and Afu2g09040 (vacuolar transporter Vtc4) as more expressed both in the phoBPHO80 mutant...”
  • “...Afu4g03610 Phosphate:H + symporter ( phoD PHO84 ) Afu2g09040 Vacuolar transporter chaperone Vtc4 Afu4g06020 Cyclin dependent kinase inhibitor, Nuc2 ( phoC PHO81...”

B7GCM8 SPX domain-containing protein from Phaeodactylum tricornutum (strain CCAP 1055/1)
29% identity, 10% coverage

• Comparative Proteomic Analysis of the Diatom Phaeodactylum tricornutum Reveals New Insights Into Intra- and Extra-Cellular Protein Contents of Its Oval, Fusiform, and Triradiate Morphotypes
  Chuberre, Frontiers in plant science 2022
  • “...Predicted protein NA Phatr3_J49296 B7GA48 Predicted protein NA Phatr3_J41518 B7GEF5 Predicted protein Methyltransferase activity Phatr3_J50019 B7GCM8 Predicted protein NA Phatr3_J47667 B7G4H1 Predicted protein Sodium-dependent phosphate transmembrane transporter activity Phatr3_J47412 B7G3A5 Predicted protein Nucleic acid binding Phatr3_J48827 B7G8I4 Predicted protein NA Phatr3_J46547 B7G1L3 Predicted protein Serine-type endopeptidase...”

O13718 Vacuolar transporter chaperone complex subunit 2 from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
29% identity, 9% coverage

• Proteasome regulation of petite-negativity in fission yeast.
  Amberg, bioRxiv : the preprint server for biology 2024
  • “...1 Q9UUB1 rib4 0.32 0.025 6,7-dimethyl-8-ribityllumazine synthase O94435 mug35 0.34 0.034 Schizosaccharomyces specific protein Mug35 O13718 vtc2 0.35 0.006 vacuolar transporter chaperone (VTC) complex polyphosphate synthetase subunit Vtc2/3 O14463 trx1 0.35 0.040 cytosolic thioredoxin Trx1 Q9UTK3 SPAC1486.06 0.35 0.021 nicotinate phosphoribosyltransferase Npt1 Q9P544 SPAC1635.01 0.35 0.008...”

XP_002295322 predicted protein from Thalassiosira pseudonana CCMP1335
30% identity, 8% coverage

• Quantitative Proteomics Reveals Common and Specific Responses of a Marine Diatom Thalassiosira pseudonana to Different Macronutrient Deficiencies
  Chen, Frontiers in microbiology 2018
  • “...XP_002292372 2 1.57 Phosphatidylserine decarboxylase XP_002295759 8 2.94 Polyphosphate allocation Vacuolar transporter chaperone 4 (VTC4) XP_002295322 27 3.63 N containing lipids synthesis Betaine aldehyde dehydrogenase XP_002295797 8 1.58 Si deficiency (-Si vs. Control) Transport Silicic acid transporter (SIT1) XP_002290700 3 8.62 Silicic acid transporter (SIT2) XP_002295920...”

BC1G_14169 hypothetical protein from Botrytis cinerea B05.10
27% identity, 9% coverage

• Genome-wide transcriptional profiling of Botrytis cinerea genes targeting plant cell walls during infections of different hosts
  Blanco-Ulate, Frontiers in plant science 2014
  • “...CE12 RG acetylesterases 1 BC1G_14009 XyG backbone GH3 -Glucosidases 6 BC1G_03179, BC1G_07110, BC1G_07622, BC1G_10231, BC1G_11439, BC1G_14169 GH12 XyG-specific -glucanases 1 BC1G_00594 GH16, GH16|CBM18 Glucanases and XyG transglucosylase/hydrolases 11 BC1G_00409, BC1G_02932, BC1G_04948, BC1G_07945, BC1G_08924, BC1G_09991 Xylan backbone GH10, GH11, GH10|CBM1, GH11|CBM1 -Xylanases 5 BcXyn11A, BC1G_00576, BC1G_01778, BC1G_03590...”

S8GSS4 VTC domain-containing protein from Toxoplasma gondii (strain ATCC 50611 / Me49)
30% identity, 8% coverage

• Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins
  Li, Parasites & vectors 2022
  • “...20 S8FBJ7 Membrane protein, putative GGRQIENGGEDAAVND 936951 16 Q6GV23 Rhomboid-like protease 5 EQPPTGDYKRRALASP 5166 16 S8GSS4 Vacuolar transporter chaperone (VTC) domain-containing protein VGSQESGQARERDDREATE 136154 19 S8GRC2 Uncharacterized protein [Basic Local Alignment Search Tool (BLAST): organic solute transporter ostalpha protein] DGRREASEDPSVSANPHPTDSARTTSPSADDQ 5889 32 SAPGQEPQSPRGNADPRPSG 10151034 20 S7WII9...”

XP_001690865 uncharacterized protein from Chlamydomonas reinhardtii
33% identity, 6% coverage

• Critical function of a Chlamydomonas reinhardtii putative polyphosphate polymerase subunit during nutrient deprivation.
  Aksoy, The Plant cell 2014
  • GeneRIF: Data show that introduction of the VACUOLAR TRANSPORTER CHAPERONE1 (VTC1) gene, which encodes a component of a polyphosphate polymerase complex, specifically complements the ars76 mutant phenotypes.

An12g04710 uncharacterized protein from Aspergillus niger
32% identity, 8% coverage

• The transcriptomic signature of RacA activation and inactivation provides new insights into the morphogenetic network of Aspergillus niger
  Kwon, PloS one 2013
  • “...uptake An17g01925 Sat4 transcription factor for RNA polymerase II An16g07220 Tfg2 negative regulator of Cdc42 An12g04710 Vtc1 putative C 2 H 2 zinc-finger transcription factor An04g01500 SUN family protein involved in replication An08g07090 Sim1 similar to A. nidulans transcription factor RosA An16g07890 Ume6 Others hypothetical aspergillosis...”
• Reconstruction of signaling networks regulating fungal morphogenesis by transcriptomics
  Meyer, Eukaryotic cell 2009
  • “...Other signaling processes An15g01560 An04g01500 An08g07090 An16g07890 An12g04710 (3.21) 2.98 0.06 0.04 0.29 0.029 0.044 0.054 0.037 0.031 GTPase-activating...”
  • “...reference 83). Interestingly, we found a downregulation of An12g04710, which displays similarity to the yeast Vtc1p and Nrf1p proteins, which are negative...”

AO090012000979 No description from Aspergillus oryzae RIB40
26% identity, 11% coverage

• Transcriptome analysis of genes and metabolic pathways associated with nicotine degradation in Aspergillus oryzae 112822
  He, BMC genomics 2019
  • “...(AO090011000649, AO090005000455), ribosome assembly protein (AO090701000541), ATP-dependent RNA helicase (AO090023000510), DNA replication licensing factors MCM4 (AO090012000979, AO090011000793), choline dehydrogenases (AO090026000028, AO090003001420, AO090023000847), RNA-dependent RNA polymerase (AO090020000563), and DNA-directed RNA polymerase (AO090012000486) were approved to have much lower transcriptional level in response to nicotine exposure through qRT-PCR....”

VTC4_TRYCC / Q4E409 Vacuolar transporter chaperone complex subunit 4; Polyphosphate kinase; SPX-dependent polyphosphate polymerase VTC subunit 4; Vacuolar membrane polyphosphate polymerase catalytic subunit; PolyP polymerase; EC 2.7.4.1 from Trypanosoma cruzi (strain CL Brener) (see paper)
22% identity, 8% coverage

• function: Component of a polyphosphate synthase complex that utilizes ATP to synthesize and translocate polyphosphate to acidocalcisomes in epimastigotes, insect-stages of Trypanosoma brucei (PubMed:24386955). Catalytic subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain vtc4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation. The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen. PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase. The VTC complex also plays a role in vacuolar membrane fusion (By similarity). Essential for infection and parasite survival in the mammalian host (By similarity).
  catalytic activity: [phosphate](n) + ATP = [phosphate](n+1) + ADP (RHEA:19573)
  cofactor: Mn(2+)
  subunit: The VTC core complex is an integral membrane heterooligomer composed of at least the catalytic subunit vtc4 and the accessory subunits vtc1 and vtc2. vtc1 is a small membrane protein without hydrophilic domain. Vtc2 and vtc4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in vtc4 is the catalytic domain.
  disruption phenotype: Results in growth defects in procyclic forms (PCF) and changes in acidocalcisome morphology and number. The mean number of acidocalcisomes drops by approximately 2-fold, but individual acidocalcisomes are considerably larger and less circular. Also affects cellular polyP and PPi content. Short chain polyP drops almost 2-fold, while PPi nearly doubles.

VTC4_TRYB2 / Q382V9 Vacuolar transporter chaperone complex subunit 4; Polyphosphate kinase; SPX-dependent polyphosphate polymerase VTC subunit 4; Vacuolar membrane polyphosphate polymerase catalytic subunit; PolyP polymerase; EC 2.7.4.1 from Trypanosoma brucei brucei (strain 927/4 GUTat10.1) (see 2 papers)
22% identity, 12% coverage

• function: Component of a polyphosphate synthase complex that utilizes ATP to synthesize and translocate polyphosphate to acidocalcisomes in epimastigotes, insect-stages of Trypanosoma brucei (PubMed:24386955). Catalytic subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain vtc4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation. The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen. PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase. The VTC complex also plays a role in vacuolar membrane fusion (By similarity). Essential for infection and parasite survival in the mammalian host (PubMed:24114837).
  catalytic activity: [phosphate](n) + ATP = [phosphate](n+1) + ADP (RHEA:19573)
  cofactor: Mn(2+)
  subunit: The VTC core complex is an integral membrane heterooligomer composed of at least the catalytic subunit vtc4 and the accessory subunits vtc1 and vtc2. vtc1 is a small membrane protein without hydrophilic domain. Vtc2 and vtc4 are related and have 2 hydrophilic domains that face the cytosol, an N-terminal SPX domain and the central core domain. The central core in vtc4 is the catalytic domain.
  disruption phenotype: Is considerably less virulent in mice (PubMed:24114837). Reduces short chain polyP levels and results in accumulation of PPi (PubMed:24386955).

M7WMK7 Vacuolar transporter chaperone 2 from Rhodotorula toruloides (strain NP11)
25% identity, 9% coverage

• Adaptation of Proteome and Metabolism in Different Haplotypes of Rhodosporidium toruloides during Cu(I) and Cu(II) Stress
  Cavelius, Microorganisms 2023
  • “...n.d. down n.d. Copper P-type ATPase A0A2T0A6Z7 2.81 3.19 n.d. 2.17 Vacuolar transporter chaperone 2 M7WMK7 64.00 17.05 n.d. n.d. Vacuolar transporter chaperone 4 M7XMX5 n.d. 2.26 n.d. n.d. Mitochondrial inner membrane metallopeptidase Oma1 M7X2Q6 down n.d. down down A0A0K3C9S0 down 0.46 n.d. n.d. Mitochondrial outer...”

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How It Works

PaperBLAST builds a database of protein sequences that are linked to scientific articles. These links come from automated text searches against the articles in EuropePMC and from manually-curated information from GeneRIF, UniProtKB/Swiss-Prot, BRENDA, CAZy (as made available by dbCAN), BioLiP, CharProtDB, MetaCyc, EcoCyc, TCDB, REBASE, the Fitness Browser, and a subset of the European Nucleotide Archive with the /experiment tag. Given this database and a protein sequence query, PaperBLAST uses protein-protein BLAST to find similar sequences with E < 0.001.

To build the database, we query EuropePMC with locus tags, with RefSeq protein identifiers, and with UniProt accessions. We obtain the locus tags from RefSeq or from MicrobesOnline. We use queries of the form "locus_tag AND genus_name" to try to ensure that the paper is actually discussing that gene. Because EuropePMC indexes most recent biomedical papers, even if they are not open access, some of the links may be to papers that you cannot read or that our computers cannot read. We query each of these identifiers that appears in the open access part of EuropePMC, as well as every locus tag that appears in the 500 most-referenced genomes, so that a gene may appear in the PaperBLAST results even though none of the papers that mention it are open access. We also incorporate text-mined links from EuropePMC that link open access articles to UniProt or RefSeq identifiers. (This yields some additional links because EuropePMC uses different heuristics for their text mining than we do.)

For every article that mentions a locus tag, a RefSeq protein identifier, or a UniProt accession, we try to select one or two snippets of text that refer to the protein. If we cannot get access to the full text, we try to select a snippet from the abstract, but unfortunately, unique identifiers such as locus tags are rarely provided in abstracts.

PaperBLAST also incorporates manually-curated protein functions:

• Proteins from NCBI's RefSeq are included if a GeneRIF entry links the gene to an article in PubMed^®. GeneRIF also provides a short summary of the article's claim about the protein, which is shown instead of a snippet.
• Proteins from Swiss-Prot (the curated part of UniProt) are included if the curators identified experimental evidence for the protein's function (evidence code ECO:0000269). For these proteins, the fields of the Swiss-Prot entry that describe the protein's function are shown (with bold headings).
• Proteins from BRENDA, a curated database of enzymes, are included if they are linked to a paper in PubMed and their full sequence is known.
• Every protein from the non-redundant subset of BioLiP, a database of ligand-binding sites and catalytic residues in protein structures, is included. Since BioLiP itself does not include descriptions of the proteins, those are taken from the Protein Data Bank. Descriptions from PDB rely on the original submitter of the structure and cannot be updated by others, so they may be less reliable. (For SitesBLAST and Sites on a Tree, we use a larger subset of BioLiP so that every ligand is represented among a group of structures with similar sequences, but for PaperBLAST, we use the non-redundant set provided by BioLiP.)
• Every protein from EcoCyc, a curated database of the proteins in Escherichia coli K-12, is included, regardless of whether they are characterized or not.
• Proteins from the MetaCyc metabolic pathway database are included if they are linked to a paper in PubMed and their full sequence is known.
• Proteins from the Transport Classification Database (TCDB) are included if they have known substrate(s), have reference(s), and are not described as uncharacterized or putative. (Some of the references are not visible on the PaperBLAST web site.)
• Every protein from CharProtDB, a database of experimentally characterized protein annotations, is included.
• Proteins from the CAZy database of carbohydrate-active enzymes are included if they are associated with an Enzyme Classification number. Even though CAZy does not provide links from individual protein sequences to papers, these should all be experimentally-characterized proteins.
• Proteins from the REBASE database of restriction enzymes are included if they have known specificity.
• Every protein with an evidence-based reannotation (based on mutant phenotypes) in the Fitness Browser is included.
• Sequence-specific transcription factors (including sigma factors and DNA-binding response regulators) with experimentally-determined DNA binding sites from the PRODORIC database of gene regulation in prokaryotes.
• Putative transcription factors from RegPrecise that have manually-curated predictions for their binding sites. These predictions are based on conserved putative regulatory sites across genomes that contain similar transcription factors, so PaperBLAST clusters the TFs at 70% identity and retains just one member of each cluster.
• Coding sequence (CDS) features from the European Nucleotide Archive (ENA) are included if the /experiment tag is set (implying that there is experimental evidence for the annotation), the nucleotide entry links to paper(s) in PubMed, and the nucleotide entry is from the STD data class (implying that these are targeted annotated sequences, not from shotgun sequencing). Also, to filter out genes whose transcription or translation was detected, but whose function was not studied, nucleotide entries or papers with more than 25 such proteins are excluded. Descriptions from ENA rely on the original submitter of the sequence and cannot be updated by others, so they may be less reliable.

Except for GeneRIF and ENA, the curated entries include a short curated description of the protein's function. For entries from BioLiP, the protein's function may not be known beyond binding to the ligand. Many of these entries also link to articles in PubMed.

For more information see the PaperBLAST paper (mSystems 2017) or the code. You can download PaperBLAST's database here.

Changes to PaperBLAST since the paper was written:

• November 2023: incorporated PRODORIC and RegPrecise. Many PRODORIC entries were not linked to a protein sequence (no UniProt identifier), so we added this information.
• February 2023: BioLiP changed their download format. PaperBLAST now includes their non-redundant subset. SitesBLAST and Sites on a Tree use a larger non-redundant subset that ensures that every ligand is represented within each cluster. This should ensure that every binding site is represented.
• June 2022: incorporated some coding sequences from ENA with the /experiment tag.
• March 2022: incorporated BioLiP.
• April 2020: incorporated TCDB.
• April 2019: EuropePMC now returns table entries in their search results. This has expanded PaperBLAST's database, but most of the new entries are of low relevance, and the resulting snippets are often just lists of locus tags with annotations.
• February 2018: the alignment page reports the conservation of the hit's functional sites (if available from from Swiss-Prot or UniProt)
• January 2018: incorporated BRENDA.
• December 2017: incorporated MetaCyc, CharProtDB, CAZy, REBASE, and the reannotations from the Fitness Browser.
• September 2017: EuropePMC no longer returns some table entries in their search results. This has shrunk PaperBLAST's database, but has also reduced the number of low-relevance hits.

Many of these changes are described in Interactive tools for functional annotation of bacterial genomes.

Secrets

PaperBLAST cannot provide snippets for many of the papers that are published in non-open-access journals. This limitation applies even if the paper is marked as "free" on the publisher's web site and is available in PubmedCentral or EuropePMC. If a journal that you publish in is marked as "secret," please consider publishing elsewhere.

Omissions from the PaperBLAST Database

Many important articles are missing from PaperBLAST, either because the article's full text is not in EuropePMC (as for many older articles), or because the paper does not mention a protein identifier such as a locus tag, or because of PaperBLAST's heuristics. If you notice an article that characterizes a protein's function but is missing from PaperBLAST, please notify the curators at UniProt or add an entry to GeneRIF. Entries in either of these databases will eventually be incorporated into PaperBLAST. Note that to add an entry to UniProt, you will need to find the UniProt identifier for the protein. If the protein is not already in UniProt, you can ask them to create an entry. To add an entry to GeneRIF, you will need an NCBI Gene identifier, but unfortunately many prokaryotic proteins in RefSeq do not have corresponding Gene identifers.

References

PaperBLAST: Text-mining papers for information about homologs.
M. N. Price and A. P. Arkin (2017). mSystems, 10.1128/mSystems.00039-17.

Europe PMC in 2017.
M. Levchenko et al (2017). Nucleic Acids Research, 10.1093/nar/gkx1005.

Gene indexing: characterization and analysis of NLM's GeneRIFs.
J. A. Mitchell et al (2003). AMIA Annu Symp Proc 2003:460-464.

UniProt: the universal protein knowledgebase.
The UniProt Consortium (2016). Nucleic Acids Research, 10.1093/nar/gkw1099.

BRENDA in 2017: new perspectives and new tools in BRENDA.
S. Placzek et al (2017). Nucleic Acids Research, 10.1093/nar/gkw952.

The EcoCyc database: reflecting new knowledge about Escherichia coli K-12.
I. M. Keeseler et al (2016). Nucleic Acids Research, 10.1093/nar/gkw1003.

The MetaCyc database of metabolic pathways and enzymes.
R. Caspi et al (2018). Nucleic Acids Research, 10.1093/nar/gkx935.

CharProtDB: a database of experimentally characterized protein annotations.
R. Madupu et al (2012). Nucleic Acids Research, 10.1093/nar/gkr1133.

The carbohydrate-active enzymes database (CAZy) in 2013.
V. Lombard et al (2014). Nucleic Acids Research, 10.1093/nar/gkt1178.

The Transporter Classification Database (TCDB): recent advances
M. H. Saier, Jr. et al (2016). Nucleic Acids Research, 10.1093/nar/gkv1103.

REBASE - a database for DNA restriction and modification: enzymes, genes and genomes.
R. J. Roberts et al (2015). Nucleic Acids Research, 10.1093/nar/gku1046.

Deep annotation of protein function across diverse bacteria from mutant phenotypes.
M. N. Price et al (2016). bioRxiv, 10.1101/072470.