ID NADC_HUMAN Reviewed; 297 AA. AC Q15274; Q53XW7; Q96G22; Q9BSG6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 201. DE RecName: Full=Nicotinate-nucleotide pyrophosphorylase [carboxylating]; DE EC=2.4.2.19 {ECO:0000269|PubMed:17868694, ECO:0000269|PubMed:24038671, ECO:0000269|PubMed:9473669}; DE AltName: Full=Quinolinate phosphoribosyltransferase [decarboxylating]; DE Short=QAPRTase; DE Short=QPRTase; GN Name=QPRT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND RP VARIANT ALA-195. RC TISSUE=Brain; RX PubMed=9473669; DOI=10.1016/s0167-4781(97)00143-7; RA Fukuoka S., Nyaruhucha C.M., Shibata K.; RT "Characterization and functional expression of the cDNA encoding human RT brain quinolinate phosphoribosyltransferase."; RL Biochim. Biophys. Acta 1395:192-201(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-195. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-195. RC TISSUE=Kidney, Muscle, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, RP MUTAGENESIS OF ARG-102; ARG-138; LYS-139; ARG-161 AND LYS-171, FUNCTION, RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, RP PATHWAY, AND SUBUNIT. RX PubMed=17868694; DOI=10.1016/j.jmb.2007.08.043; RA Liu H., Woznica K., Catton G., Crawford A., Botting N., Naismith J.H.; RT "Structural and kinetic characterization of quinolinate RT phosphoribosyltransferase (hQPRTase) from homo sapiens."; RL J. Mol. Biol. 373:755-763(2007). RN [6] {ECO:0007744|PDB:4KWV, ECO:0007744|PDB:4KWW} RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) IN APO FORM AND IN COMPLEX WITH RP INHIBITOR PHT, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, RP AND SUBUNIT. RX PubMed=24038671; DOI=10.1002/prot.24406; RA Malik S.S., Patterson D.N., Ncube Z., Toth E.A.; RT "The crystal structure of human quinolinic acid phosphoribosyltransferase RT in complex with its inhibitor phthalic acid."; RL Proteins 82:405-414(2014). RN [7] {ECO:0007744|PDB:5AYX, ECO:0007744|PDB:5AYY, ECO:0007744|PDB:5AYZ} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN APO FORM; IN COMPLEX WITH RP QUINOLINATE AND IN COMPLEX WITH NICOTINATE MONONUCLEOTIDE, SUBUNIT, AND RP MUTAGENESIS OF 1-MET--GLU-4; 1-MET--LEU-8; 1-MET--LEU-9; 1-MET--LEU-10 AND RP 1-MET--PRO-12. RX PubMed=26805589; DOI=10.1038/srep19681; RA Youn H.S., Kim T.G., Kim M.K., Kang G.B., Kang J.Y., Lee J.G., An J.Y., RA Park K.R., Lee Y., Im Y.J., Lee J.H., Eom S.H.; RT "Structural Insights into the Quaternary Catalytic Mechanism of Hexameric RT Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD RT Biosynthesis."; RL Sci. Rep. 6:19681-19681(2016). RN [8] RP VARIANT [LARGE SCALE ANALYSIS] ALA-195, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: Involved in the catabolism of quinolinic acid (QA). CC {ECO:0000269|PubMed:17868694, ECO:0000269|PubMed:24038671, CC ECO:0000269|PubMed:9473669}. CC -!- CATALYTIC ACTIVITY: CC Reaction=CO2 + diphosphate + nicotinate beta-D-ribonucleotide = 5- CC phospho-alpha-D-ribose 1-diphosphate + 2 H(+) + quinolinate; CC Xref=Rhea:RHEA:12733, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:29959, ChEBI:CHEBI:33019, ChEBI:CHEBI:57502, CC ChEBI:CHEBI:58017; EC=2.4.2.19; CC Evidence={ECO:0000269|PubMed:17868694, ECO:0000269|PubMed:24038671, CC ECO:0000269|PubMed:9473669}; CC -!- ACTIVITY REGULATION: Activity toward QA is slightly repressed by CC phosphoribosylpyrophosphate (PRPP) in both a competitive and a non- CC competitive manner (PubMed:17868694). Competitively inhibited by CC phthalic acid (PHT) (PubMed:24038671). {ECO:0000269|PubMed:17868694, CC ECO:0000269|PubMed:24038671}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=21 uM for QA (at 0.1 mM PRPP) {ECO:0000269|PubMed:17868694}; CC KM=23 uM for QA (at 0.3 mM PRPP) {ECO:0000269|PubMed:17868694}; CC Vmax=1.2 uM/min/mg enzyme (at 0.3 mM QA and 0.1 mM PRPP) CC {ECO:0000269|PubMed:17868694}; CC Vmax=0.93 uM/min/mg enzyme (at 0.3 mM QA and 0.3 mM PRPP) CC {ECO:0000269|PubMed:17868694}; CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; nicotinate D- CC ribonucleotide from quinolinate: step 1/1. CC {ECO:0000269|PubMed:17868694, ECO:0000269|PubMed:24038671, CC ECO:0000269|PubMed:9473669}. CC -!- SUBUNIT: Hexamer formed by 3 homodimers. {ECO:0000269|PubMed:17868694, CC ECO:0000269|PubMed:24038671, ECO:0000269|PubMed:26805589}. CC -!- INTERACTION: CC Q15274; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-739851, EBI-10173507; CC Q15274; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-739851, EBI-11959885; CC Q15274; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-739851, EBI-10171774; CC Q15274; Q9NZ94-2: NLGN3; NbExp=4; IntAct=EBI-739851, EBI-16423037; CC Q15274; Q15274: QPRT; NbExp=3; IntAct=EBI-739851, EBI-739851; CC -!- SIMILARITY: Belongs to the NadC/ModD family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D78177; BAA11242.1; -; mRNA. DR EMBL; BT007231; AAP35895.1; -; mRNA. DR EMBL; BC005060; AAH05060.1; -; mRNA. DR EMBL; BC010033; AAH10033.1; -; mRNA. DR EMBL; BC018910; AAH18910.1; -; mRNA. DR CCDS; CCDS10651.1; -. DR PIR; T46864; T46864. DR RefSeq; NP_001305178.1; NM_001318249.1. DR RefSeq; NP_001305179.1; NM_001318250.1. DR RefSeq; NP_055113.2; NM_014298.4. DR PDB; 2JBM; X-ray; 2.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-297. DR PDB; 4KWV; X-ray; 2.80 A; A/B/C/D/E/F=1-297. DR PDB; 4KWW; X-ray; 2.55 A; A/B/C/D/E/F=1-297. DR PDB; 5AYX; X-ray; 2.80 A; A/B/C/D/E/F=1-297. DR PDB; 5AYY; X-ray; 3.09 A; A/B/C/D/E/F/G/H/I=1-297. DR PDB; 5AYZ; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=1-297. DR PDBsum; 2JBM; -. DR PDBsum; 4KWV; -. DR PDBsum; 4KWW; -. DR PDBsum; 5AYX; -. DR PDBsum; 5AYY; -. DR PDBsum; 5AYZ; -. DR AlphaFoldDB; Q15274; -. DR SMR; Q15274; -. DR BioGRID; 117035; 86. DR IntAct; Q15274; 40. DR STRING; 9606.ENSP00000378782; -. DR DrugBank; DB00627; Niacin. DR DrugCentral; Q15274; -. DR iPTMnet; Q15274; -. DR PhosphoSitePlus; Q15274; -. DR BioMuta; QPRT; -. DR DMDM; 296439291; -. DR EPD; Q15274; -. DR jPOST; Q15274; -. DR MassIVE; Q15274; -. DR MaxQB; Q15274; -. DR PaxDb; 9606-ENSP00000378782; -. DR PeptideAtlas; Q15274; -. DR ProteomicsDB; 60508; -. DR Pumba; Q15274; -. DR Antibodypedia; 26777; 373 antibodies from 26 providers. DR DNASU; 23475; -. DR Ensembl; ENST00000395384.9; ENSP00000378782.4; ENSG00000103485.19. DR Ensembl; ENST00000449759.2; ENSP00000404873.3; ENSG00000103485.19. DR GeneID; 23475; -. DR KEGG; hsa:23475; -. DR MANE-Select; ENST00000395384.9; ENSP00000378782.4; NM_014298.6; NP_055113.3. DR UCSC; uc002dto.4; human. DR AGR; HGNC:9755; -. DR CTD; 23475; -. DR DisGeNET; 23475; -. DR GeneCards; QPRT; -. DR HGNC; HGNC:9755; QPRT. DR HPA; ENSG00000103485; Tissue enhanced (kidney, liver). DR MIM; 606248; gene. DR neXtProt; NX_Q15274; -. DR OpenTargets; ENSG00000103485; -. DR PharmGKB; PA34096; -. DR VEuPathDB; HostDB:ENSG00000103485; -. DR eggNOG; KOG3008; Eukaryota. DR GeneTree; ENSGT00390000002761; -. DR HOGENOM; CLU_039622_1_1_1; -. DR InParanoid; Q15274; -. DR OMA; DIVMCDN; -. DR OrthoDB; 5473389at2759; -. DR PhylomeDB; Q15274; -. DR TreeFam; TF300845; -. DR BioCyc; MetaCyc:HS02508-MONOMER; -. DR BRENDA; 2.4.2.19; 2681. DR PathwayCommons; Q15274; -. DR Reactome; R-HSA-196807; Nicotinate metabolism. DR SignaLink; Q15274; -. DR UniPathway; UPA00253; UER00331. DR BioGRID-ORCS; 23475; 10 hits in 1158 CRISPR screens. DR ChiTaRS; QPRT; human. DR EvolutionaryTrace; Q15274; -. DR GenomeRNAi; 23475; -. DR Pharos; Q15274; Tbio. DR PRO; PR:Q15274; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q15274; Protein. DR Bgee; ENSG00000103485; Expressed in right adrenal gland cortex and 166 other cell types or tissues. DR ExpressionAtlas; Q15274; baseline and differential. DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0004514; F:nicotinate-nucleotide diphosphorylase (carboxylating) activity; IDA:UniProtKB. DR GO; GO:0009435; P:NAD biosynthetic process; IBA:GO_Central. DR GO; GO:0019674; P:NAD metabolic process; TAS:Reactome. DR GO; GO:0034213; P:quinolinate catabolic process; IDA:UniProtKB. DR CDD; cd01572; QPRTase; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR Gene3D; 3.90.1170.20; Quinolinate phosphoribosyl transferase, N-terminal domain; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR004393; NadC. DR InterPro; IPR027277; NadC/ModD. DR InterPro; IPR036068; Nicotinate_pribotase-like_C. DR InterPro; IPR037128; Quinolinate_PRibosylTase_N_sf. DR InterPro; IPR002638; Quinolinate_PRibosylTrfase_C. DR InterPro; IPR022412; Quinolinate_PRibosylTrfase_N. DR NCBIfam; TIGR00078; nadC; 1. DR PANTHER; PTHR32179; NICOTINATE-NUCLEOTIDE PYROPHOSPHORYLASE [CARBOXYLATING]; 1. DR PANTHER; PTHR32179:SF3; NICOTINATE-NUCLEOTIDE PYROPHOSPHORYLASE [CARBOXYLATING]; 1. DR Pfam; PF01729; QRPTase_C; 1. DR Pfam; PF02749; QRPTase_N; 1. DR PIRSF; PIRSF006250; NadC_ModD; 1. DR SUPFAM; SSF51690; Nicotinate/Quinolinate PRTase C-terminal domain-like; 1. DR SUPFAM; SSF54675; Nicotinate/Quinolinate PRTase N-terminal domain-like; 1. DR Genevisible; Q15274; HS. PE 1: Evidence at protein level; KW 3D-structure; Glycosyltransferase; Pyridine nucleotide biosynthesis; KW Reference proteome; Transferase. FT CHAIN 1..297 FT /note="Nicotinate-nucleotide pyrophosphorylase FT [carboxylating]" FT /id="PRO_0000155954" FT REGION 8..12 FT /note="Important for hexamer formation" FT /evidence="ECO:0000269|PubMed:26805589" FT BINDING 102 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0000305|PubMed:17868694, ECO:0000305|PubMed:24038671, FT ECO:0007744|PDB:2JBM, ECO:0007744|PDB:4KWW, FT ECO:0007744|PDB:5AYY" FT BINDING 138..139 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0000305|PubMed:17868694, ECO:0000305|PubMed:24038671, FT ECO:0007744|PDB:2JBM, ECO:0007744|PDB:4KWW, FT ECO:0007744|PDB:5AYY, ECO:0007744|PDB:5AYZ" FT BINDING 160..161 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0000305|PubMed:17868694, ECO:0000305|PubMed:24038671, FT ECO:0007744|PDB:2JBM, ECO:0007744|PDB:4KWW, FT ECO:0007744|PDB:5AYY, ECO:0007744|PDB:5AYZ" FT BINDING 171 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0000305|PubMed:24038671, ECO:0007744|PDB:2JBM, FT ECO:0007744|PDB:4KWW, ECO:0007744|PDB:5AYY, FT ECO:0007744|PDB:5AYZ" FT BINDING 201 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0007744|PDB:5AYZ" FT BINDING 222 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0007744|PDB:5AYZ" FT BINDING 248..250 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0007744|PDB:5AYZ" FT BINDING 270 FT /ligand="quinolinate" FT /ligand_id="ChEBI:CHEBI:29959" FT /evidence="ECO:0000269|PubMed:26805589, FT ECO:0007744|PDB:5AYZ" FT VARIANT 158 FT /note="A -> V (in dbSNP:rs2303255)" FT /id="VAR_021915" FT VARIANT 195 FT /note="T -> A (in dbSNP:rs9932770)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9473669, ECO:0000269|Ref.2, FT ECO:0007744|PubMed:21269460" FT /id="VAR_050219" FT MUTAGEN 1..12 FT /note="Missing: Forms dimers instead of hexamers." FT /evidence="ECO:0000269|PubMed:26805589" FT MUTAGEN 1..10 FT /note="Missing: Forms dimers instead of hexamers." FT /evidence="ECO:0000269|PubMed:26805589" FT MUTAGEN 1..9 FT /note="Missing: Forms dimers instead of hexamers." FT /evidence="ECO:0000269|PubMed:26805589" FT MUTAGEN 1..8 FT /note="Missing: Forms dimers instead of hexamers." FT /evidence="ECO:0000269|PubMed:26805589" FT MUTAGEN 1..4 FT /note="Missing: No effect on hexamer formation." FT /evidence="ECO:0000269|PubMed:26805589" FT MUTAGEN 102 FT /note="R->A,Q: Reduced activity." FT /evidence="ECO:0000269|PubMed:17868694" FT MUTAGEN 138 FT /note="R->Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:17868694" FT MUTAGEN 139 FT /note="K->A,S: Loss of activity." FT /evidence="ECO:0000269|PubMed:17868694" FT MUTAGEN 161 FT /note="R->A: Reduced activity." FT /evidence="ECO:0000269|PubMed:17868694" FT MUTAGEN 161 FT /note="R->Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:17868694" FT MUTAGEN 171 FT /note="K->A,S: Loss of activity." FT /evidence="ECO:0000269|PubMed:17868694" FT CONFLICT 53 FT /note="V -> I (in Ref. 2; AAP35895 and 3; AAH05060)" FT /evidence="ECO:0000305" FT CONFLICT 170 FT /note="V -> L (in Ref. 1; BAA11242)" FT /evidence="ECO:0000305" FT CONFLICT 177..178 FT /note="AA -> PP (in Ref. 1; BAA11242)" FT /evidence="ECO:0000305" FT CONFLICT 208 FT /note="A -> V (in Ref. 1; BAA11242)" FT /evidence="ECO:0000305" FT CONFLICT 235 FT /note="V -> A (in Ref. 1; BAA11242)" FT /evidence="ECO:0000305" FT CONFLICT 276 FT /note="A -> V (in Ref. 1; BAA11242)" FT /evidence="ECO:0000305" FT HELIX 3..9 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 12..26 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 34..37 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 41..48 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 50..53 FT /evidence="ECO:0007829|PDB:5AYX" FT HELIX 57..66 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 70..75 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 83..93 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 94..127 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 145..154 FT /evidence="ECO:0007829|PDB:2JBM" FT TURN 161..163 FT /evidence="ECO:0007829|PDB:5AYX" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 172..178 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 181..192 FT /evidence="ECO:0007829|PDB:2JBM" FT TURN 193..195 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 198..204 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 205..213 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 217..223 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 226..239 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 243..250 FT /evidence="ECO:0007829|PDB:2JBM" FT TURN 253..255 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 256..259 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 266..268 FT /evidence="ECO:0007829|PDB:2JBM" FT HELIX 271..274 FT /evidence="ECO:0007829|PDB:2JBM" FT STRAND 281..288 FT /evidence="ECO:0007829|PDB:2JBM" SQ SEQUENCE 297 AA; 30846 MW; E3199814DB9FA0D5 CRC64; MDAEGLALLL PPVTLAALVD SWLREDCPGL NYAALVSGAG PSQAALWAKS PGVLAGQPFF DAIFTQLNCQ VSWFLPEGSK LVPVARVAEV RGPAHCLLLG ERVALNTLAR CSGIASAAAA AVEAARGAGW TGHVAGTRKT TPGFRLVEKY GLLVGGAASH RYDLGGLVMV KDNHVVAAGG VEKAVRAARQ AADFTLKVEV ECSSLQEAVQ AAEAGADLVL LDNFKPEELH PTATVLKAQF PSVAVEASGG ITLDNLPQFC GPHIDVISMG MLTQAAPALD FSLKLFAKEV APVPKIH //