ID NAMPT_HUMAN Reviewed; 491 AA. AC P43490; A4D0Q9; A4D0R0; Q3KQV0; Q8WW95; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 219. DE RecName: Full=Nicotinamide phosphoribosyltransferase; DE Short=NAmPRTase; DE Short=Nampt; DE EC=2.4.2.12 {ECO:0000250|UniProtKB:Q99KQ4}; DE AltName: Full=Pre-B-cell colony-enhancing factor 1; DE Short=Pre-B cell-enhancing factor; DE AltName: Full=Visfatin; GN Name=NAMPT; Synonyms=PBEF, PBEF1; 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]. RC TISSUE=Blood; RX PubMed=8289818; DOI=10.1128/mcb.14.2.1431-1437.1994; RA Samal B., Sun Y., Stearns G., Xie C., Suggs S., McNiece I.; RT "Cloning and characterization of the cDNA encoding a novel human pre-B-cell RT colony-enhancing factor."; RL Mol. Cell. Biol. 14:1431-1437(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Skin; 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-188, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [8] RP IDENTIFICATION BY MASS 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). RN [9] RP REVIEW. RX PubMed=22462624; DOI=10.1146/annurev-nutr-071811-150746; RA Dahl T.B., Holm S., Aukrust P., Halvorsen B.; RT "Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology RT and pathophysiology."; RL Annu. Rev. Nutr. 32:229-243(2012). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=21741723; DOI=10.1016/j.diabres.2011.06.009; RA Bienertova-Vasku J., Bienert P., Zlamal F., Tomandl J., Tomandlova M., RA Dostalova Z., Vasku A.; RT "Visfatin is secreted into the breast milk and is correlated with weight RT changes of the infant after the birth."; RL Diabetes Res. Clin. Pract. 96:355-361(2012). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-472, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24130902; DOI=10.1371/journal.pone.0078283; RA Romacho T., Villalobos L.A., Cercas E., Carraro R., Sanchez-Ferrer C.F., RA Peiro C.; RT "Visfatin as a novel mediator released by inflamed human endothelial RT cells."; RL PLoS ONE 8:E78283-E78283(2013). RN [14] 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE; PRODUCT RP AND INHIBITOR FK866, ACTIVITY REGULATION, MUTAGENESIS OF ASP-219; HIS-247 RP AND ARG-311, AND SUBUNIT. RX PubMed=16783377; DOI=10.1038/nsmb1105; RA Khan J.A., Tao X., Tong L.; RT "Molecular basis for the inhibition of human NMPRTase, a novel target for RT anticancer agents."; RL Nat. Struct. Mol. Biol. 13:582-588(2006). RN [16] RP VARIANT [LARGE SCALE ANALYSIS] SER-176. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Catalyzes the condensation of nicotinamide with 5- CC phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an CC intermediate in the biosynthesis of NAD. It is the rate limiting CC component in the mammalian NAD biosynthesis pathway. The secreted form CC behaves both as a cytokine with immunomodulating properties and an CC adipokine with anti-diabetic properties, it has no enzymatic activity, CC partly because of lack of activation by ATP, which has a low level in CC extracellular space and plasma. Plays a role in the modulation of CC circadian clock function. NAMPT-dependent oscillatory production of NAD CC regulates oscillation of clock target gene expression by releasing the CC core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1- CC mediated suppression (By similarity). {ECO:0000250|UniProtKB:Q99KQ4, CC ECO:0000269|PubMed:24130902}. CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-nicotinamide D-ribonucleotide + diphosphate = 5-phospho- CC alpha-D-ribose 1-diphosphate + nicotinamide + H(+); CC Xref=Rhea:RHEA:16149, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017; EC=2.4.2.12; CC Evidence={ECO:0000250|UniProtKB:Q99KQ4}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16151; CC Evidence={ECO:0000250|UniProtKB:Q99KQ4}; CC -!- ACTIVITY REGULATION: Inhibited by FK866. FK866 competes for the same CC binding site as nicotinamide, but due to its very low dissociation CC rate, it is essentially an irreversible inhibitor. CC {ECO:0000269|PubMed:16783377}. CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; nicotinamide D- CC ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and CC nicotinamide: step 1/1. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16783377}. CC -!- INTERACTION: CC P43490; P02792: FTL; NbExp=3; IntAct=EBI-2829310, EBI-713279; CC P43490; Q01628: IFITM3; NbExp=3; IntAct=EBI-2829310, EBI-7932862; CC P43490; P03886: MT-ND1; NbExp=3; IntAct=EBI-2829310, EBI-1246156; CC P43490; P43490: NAMPT; NbExp=5; IntAct=EBI-2829310, EBI-2829310; CC P43490; Q70CQ1-2: USP49; NbExp=3; IntAct=EBI-2829310, EBI-12133829; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24130902}. Cytoplasm CC {ECO:0000250|UniProtKB:Q99KQ4}. Secreted {ECO:0000269|PubMed:21741723}. CC Note=Under non-inflammatory conditions, visfatin predominantly exhibits CC a granular pattern within the nucleus. Secreted by endothelial cells CC upon IL-1beta stimulation. Abundantly secreted in milk, reaching 100- CC fold higher concentrations compared to maternal serum. CC {ECO:0000269|PubMed:21741723, ECO:0000269|PubMed:24130902}. CC -!- TISSUE SPECIFICITY: Expressed in large amounts in bone marrow, liver CC tissue, and muscle. Also present in heart, placenta, lung, and kidney CC tissues. CC -!- SIMILARITY: Belongs to the NAPRTase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ96862.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAL24400.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/43890/NAMPT"; 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; U02020; AAA17884.1; -; mRNA. DR EMBL; AK292851; BAF85540.1; -; mRNA. DR EMBL; AC007032; AAF19249.1; -; Genomic_DNA. DR EMBL; AC007032; AAQ96862.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH236947; EAL24399.1; -; Genomic_DNA. DR EMBL; CH236947; EAL24400.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471070; EAW83382.1; -; Genomic_DNA. DR EMBL; BC072439; AAH72439.1; -; mRNA. DR EMBL; BC106046; AAI06047.1; -; mRNA. DR CCDS; CCDS5737.1; -. DR PIR; A55927; A55927. DR RefSeq; NP_005737.1; NM_005746.3. DR RefSeq; XP_047275655.1; XM_047419699.1. DR RefSeq; XP_054212959.1; XM_054356984.1. DR PDB; 2E5B; X-ray; 2.00 A; A/B=1-491. DR PDB; 2E5C; X-ray; 2.20 A; A/B=1-491. DR PDB; 2E5D; X-ray; 2.00 A; A/B=1-491. DR PDB; 2GVG; X-ray; 2.20 A; A/B/C/D/E/F=1-491. DR PDB; 2GVJ; X-ray; 2.10 A; A/B=1-491. DR PDB; 3DGR; X-ray; 2.10 A; A/B=1-484. DR PDB; 3DHD; X-ray; 2.00 A; A/B=1-484. DR PDB; 3DHF; X-ray; 1.80 A; A/B=1-484. DR PDB; 3DKJ; X-ray; 2.00 A; A/B=1-484. DR PDB; 3DKL; X-ray; 1.89 A; A/B=1-484. DR PDB; 4JNM; X-ray; 2.20 A; A/B=1-491. DR PDB; 4JR5; X-ray; 1.91 A; A/B=1-491. DR PDB; 4KFN; X-ray; 1.60 A; A/B=1-491. DR PDB; 4KFO; X-ray; 1.60 A; A/B=1-491. DR PDB; 4KFP; X-ray; 1.84 A; A/B=1-491. DR PDB; 4L4L; X-ray; 2.12 A; A/B=1-491. DR PDB; 4L4M; X-ray; 2.44 A; A/B=1-491. DR PDB; 4LTS; X-ray; 1.69 A; A/B=1-491. DR PDB; 4LV9; X-ray; 1.81 A; A/B=1-491. DR PDB; 4LVA; X-ray; 1.55 A; A/B=1-491. DR PDB; 4LVB; X-ray; 1.84 A; A/B=1-491. DR PDB; 4LVD; X-ray; 1.75 A; A/B=1-491. DR PDB; 4LVF; X-ray; 1.50 A; A/B=1-491. DR PDB; 4LVG; X-ray; 1.70 A; A/B=1-491. DR PDB; 4LWW; X-ray; 1.64 A; A/B=1-491. DR PDB; 4M6P; X-ray; 1.75 A; A/B=1-491. DR PDB; 4M6Q; X-ray; 2.41 A; A/B=1-491. DR PDB; 4N9B; X-ray; 2.86 A; A/B=1-491. DR PDB; 4N9C; X-ray; 1.75 A; A/B=1-491. DR PDB; 4N9D; X-ray; 1.70 A; A/B=1-491. DR PDB; 4N9E; X-ray; 1.72 A; A/B=1-491. DR PDB; 4O0Z; X-ray; 2.05 A; A/B=1-491. DR PDB; 4O10; X-ray; 1.55 A; A/B=1-491. DR PDB; 4O12; X-ray; 2.50 A; A/B=1-491. DR PDB; 4O13; X-ray; 1.75 A; A/B=1-491. DR PDB; 4O14; X-ray; 1.87 A; A/B=1-491. DR PDB; 4O15; X-ray; 1.80 A; A/B=1-491. DR PDB; 4O16; X-ray; 1.78 A; A=1-491. DR PDB; 4O17; X-ray; 1.82 A; A/B=1-491. DR PDB; 4O18; X-ray; 1.92 A; A/B=1-491. DR PDB; 4O19; X-ray; 1.75 A; A/B=1-491. DR PDB; 4O1A; X-ray; 1.87 A; A/B=1-491. DR PDB; 4O1B; X-ray; 1.65 A; A/B=1-491. DR PDB; 4O1C; X-ray; 2.09 A; A/B=1-491. DR PDB; 4O1D; X-ray; 1.70 A; A/B=1-491. DR PDB; 4O28; X-ray; 2.00 A; A/B=1-491. DR PDB; 4WQ6; X-ray; 1.72 A; A/B=1-491. DR PDB; 5KIT; X-ray; 1.60 A; A/B=1-491. DR PDB; 5LX3; X-ray; 2.10 A; A/B=1-491. DR PDB; 5LX5; X-ray; 1.88 A; A/B=1-491. DR PDB; 5NSD; X-ray; 2.05 A; A/B=1-491. DR PDB; 5U2M; X-ray; 1.89 A; A/B=9-485. DR PDB; 5U2N; X-ray; 1.73 A; A/B=9-485. DR PDB; 5UPE; X-ray; 1.93 A; A/B=1-491. DR PDB; 5UPF; X-ray; 1.69 A; A/B=1-491. DR PDB; 5WI0; X-ray; 2.05 A; A/B=1-491. DR PDB; 5WI1; X-ray; 1.99 A; A/B=1-491. DR PDB; 6ATB; X-ray; 2.53 A; A/B/C/D=1-491. DR PDB; 6AZJ; X-ray; 2.53 A; A/B=8-485. DR PDB; 6B75; X-ray; 2.53 A; A/B/C/D=1-491. DR PDB; 6B76; X-ray; 2.44 A; A/B/C/D=1-491. DR PDB; 6E68; X-ray; 1.50 A; A/B=8-487. DR PDB; 6PEB; X-ray; 2.46 A; A/B/C/D=2-491. DR PDB; 6TA0; X-ray; 1.58 A; A/B=1-491. DR PDB; 6TA2; X-ray; 1.68 A; A/B=1-491. DR PDB; 6TAC; X-ray; 1.60 A; A/B=1-491. DR PDB; 7ENQ; X-ray; 2.20 A; A/B/C/D=1-491. DR PDB; 7PPE; X-ray; 1.86 A; A/B=1-491. DR PDB; 7PPF; X-ray; 2.36 A; A/B=1-491. DR PDB; 7PPG; X-ray; 2.13 A; A/B/C/D=1-491. DR PDB; 7PPH; X-ray; 1.74 A; A/B=1-491. DR PDB; 7PPI; X-ray; 2.33 A; A/B/C/D=1-491. DR PDB; 8DSC; X-ray; 1.32 A; A/B=1-491. DR PDB; 8DSD; X-ray; 1.43 A; A/B=1-491. DR PDB; 8DSE; X-ray; 1.43 A; A/B=1-491. DR PDB; 8DSH; X-ray; 2.20 A; A/B=1-491. DR PDB; 8DSI; X-ray; 1.43 A; A/B=1-491. DR PDB; 8DSM; X-ray; 2.75 A; A/B/C/D=1-491. DR PDB; 8DTJ; X-ray; 2.12 A; A/B=1-491. DR PDB; 8F7L; X-ray; 2.20 A; A/B=1-491. DR PDB; 8IVU; X-ray; 2.09 A; A/B/C/D=1-491. DR PDB; 8TM7; X-ray; 1.79 A; A/B=1-491. DR PDB; 8Y55; X-ray; 1.86 A; A/B=1-491. DR PDB; 9IWT; X-ray; 2.02 A; A/B/C/D=1-491. DR AlphaFoldDB; P43490; -. DR MDRepo; P43490; -. DR SASBDB; P43490; -. DR SMR; P43490; -. DR BioGRID; 115438; 156. DR DIP; DIP-29218N; -. DR FunCoup; P43490; 987. DR IntAct; P43490; 52. DR MINT; P43490; -. DR NDEx; IQUERY-CP-NAMPT; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000222553; -. DR BindingDB; P43490; -. DR ChEMBL; CHEMBL1744525; -. DR DrugBank; DB12980; CHS-828. DR DrugBank; DB12731; Daporinad. DR DrugBank; DB05217; Teglarinad chloride. DR DrugCentral; P43490; -. DR GlyGen; P43490; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P43490; -. DR MetOSite; P43490; -. DR PhosphoSitePlus; P43490; -. DR SwissPalm; P43490; -. DR BioMuta; NAMPT; -. DR DMDM; 1172027; -. DR CPTAC; CPTAC-409; -. DR CPTAC; CPTAC-410; -. DR jPOST; P43490; -. DR MassIVE; P43490; -. DR PaxDb; 9606-ENSP00000222553; -. DR PeptideAtlas; P43490; -. DR PRIDE; P43490; -. DR ProteomicsDB; 55638; -. DR Pumba; P43490; -. DR Antibodypedia; 17123; 1026 antibodies from 47 providers. DR DNASU; 10135; -. DR Ensembl; ENST00000222553.8; ENSP00000222553.3; ENSG00000105835.14. DR Ensembl; ENST00000424768.2; ENSP00000390591.2; ENSG00000105835.14. DR Ensembl; ENST00000681255.1; ENSP00000506129.1; ENSG00000105835.14. DR Ensembl; ENST00000681491.1; ENSP00000506540.1; ENSG00000105835.14. DR Ensembl; ENST00000901886.1; ENSP00000571945.1; ENSG00000105835.14. DR Ensembl; ENST00000901887.1; ENSP00000571946.1; ENSG00000105835.14. DR Ensembl; ENST00000921397.1; ENSP00000591456.1; ENSG00000105835.14. DR GeneID; 10135; -. DR KEGG; hsa:10135; -. DR MANE-Select; ENST00000222553.8; ENSP00000222553.3; NM_005746.3; NP_005737.1. DR UCSC; uc003vdq.4; human. DR AGR; HGNC:30092; -. DR ClinPGx; PA162396933; -. DR CTD; 10135; -. DR DisGeNET; 10135; -. DR GeneCards; NAMPT; -. DR HGNC; HGNC:30092; NAMPT. DR HPA; ENSG00000105835; Tissue enhanced (lymphoid). DR MIM; 608764; gene. DR OpenTargets; ENSG00000105835; -. DR VEuPathDB; HostDB:ENSG00000105835; -. DR eggNOG; ENOG502QSGN; Eukaryota. DR GeneTree; ENSGT00940000153456; -. DR HOGENOM; CLU_012550_2_0_1; -. DR InParanoid; P43490; -. DR OMA; TFGFAMK; -. DR OrthoDB; 193380at2759; -. DR PAN-GO; P43490; 2 GO annotations based on evolutionary models. DR PhylomeDB; P43490; -. DR BRENDA; 2.4.2.12; 2681. DR PathwayCommons; P43490; -. DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian expression. DR Reactome; R-HSA-196807; Nicotinate metabolism. DR Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR SABIO-RK; P43490; -. DR SignaLink; P43490; -. DR SIGNOR; P43490; -. DR UniPathway; UPA00253; UER00890. DR Agora; ENSG00000105835; -. DR BioGRID-ORCS; 10135; 214 hits in 1155 CRISPR screens. DR ChiTaRS; NAMPT; human. DR EvolutionaryTrace; P43490; -. DR GeneWiki; Nicotinamide_phosphoribosyltransferase; -. DR GenomeRNAi; 10135; -. DR Pharos; P43490; Tchem. DR PRO; PR:P43490; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P43490; protein. DR Bgee; ENSG00000105835; Expressed in blood and 198 other cell types or tissues. DR ExpressionAtlas; P43490; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; EXP:UniProtKB. DR GO; GO:0005125; F:cytokine activity; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0047280; F:nicotinamide phosphoribosyltransferase activity; IMP:ARUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IDA:BHF-UCL. DR GO; GO:0009435; P:NAD+ biosynthetic process; IBA:GO_Central. DR GO; GO:0034355; P:NAD+ biosynthetic process via the salvage pathway; IEA:Ensembl. DR GO; GO:0006741; P:NADP+ biosynthetic process; IEA:Ensembl. DR GO; GO:1901847; P:nicotinate metabolic process; TAS:Reactome. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:ARUK-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd01569; PBEF_like; 1. DR FunFam; 3.20.20.70:FF:000080; Nicotinamide phosphoribosyltransferase; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR041529; DUF5598. DR InterPro; IPR041525; N/Namide_PRibTrfase. DR InterPro; IPR016471; Nicotinamide_PRibTrfase. DR InterPro; IPR036068; Nicotinate_pribotase-like_C. DR NCBIfam; NF006629; PRK09198.1; 1. DR PANTHER; PTHR43816; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; 1. DR PANTHER; PTHR43816:SF1; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; 1. DR Pfam; PF18127; NAMPT_N; 1. DR Pfam; PF04095; NAPRTase; 1. DR PIRSF; PIRSF005943; NMPRT; 1. DR SUPFAM; SSF51690; Nicotinate/Quinolinate PRTase C-terminal domain-like; 1. DR PDBsum; 2E5B; -. DR PDBsum; 2E5C; -. DR PDBsum; 2E5D; -. DR PDBsum; 2GVG; -. DR PDBsum; 2GVJ; -. DR PDBsum; 3DGR; -. DR PDBsum; 3DHD; -. DR PDBsum; 3DHF; -. DR PDBsum; 3DKJ; -. DR PDBsum; 3DKL; -. DR PDBsum; 4JNM; -. DR PDBsum; 4JR5; -. DR PDBsum; 4KFN; -. DR PDBsum; 4KFO; -. DR PDBsum; 4KFP; -. DR PDBsum; 4L4L; -. DR PDBsum; 4L4M; -. DR PDBsum; 4LTS; -. DR PDBsum; 4LV9; -. DR PDBsum; 4LVA; -. DR PDBsum; 4LVB; -. DR PDBsum; 4LVD; -. DR PDBsum; 4LVF; -. DR PDBsum; 4LVG; -. DR PDBsum; 4LWW; -. DR PDBsum; 4M6P; -. DR PDBsum; 4M6Q; -. DR PDBsum; 4N9B; -. DR PDBsum; 4N9C; -. DR PDBsum; 4N9D; -. DR PDBsum; 4N9E; -. DR PDBsum; 4O0Z; -. DR PDBsum; 4O10; -. DR PDBsum; 4O12; -. DR PDBsum; 4O13; -. DR PDBsum; 4O14; -. DR PDBsum; 4O15; -. DR PDBsum; 4O16; -. DR PDBsum; 4O17; -. DR PDBsum; 4O18; -. DR PDBsum; 4O19; -. DR PDBsum; 4O1A; -. DR PDBsum; 4O1B; -. DR PDBsum; 4O1C; -. DR PDBsum; 4O1D; -. DR PDBsum; 4O28; -. DR PDBsum; 4WQ6; -. DR PDBsum; 5KIT; -. DR PDBsum; 5LX3; -. DR PDBsum; 5LX5; -. DR PDBsum; 5NSD; -. DR PDBsum; 5U2M; -. DR PDBsum; 5U2N; -. DR PDBsum; 5UPE; -. DR PDBsum; 5UPF; -. DR PDBsum; 5WI0; -. DR PDBsum; 5WI1; -. DR PDBsum; 6ATB; -. DR PDBsum; 6AZJ; -. DR PDBsum; 6B75; -. DR PDBsum; 6B76; -. DR PDBsum; 6E68; -. DR PDBsum; 6PEB; -. DR PDBsum; 6TA0; -. DR PDBsum; 6TA2; -. DR PDBsum; 6TAC; -. DR PDBsum; 7ENQ; -. DR PDBsum; 7PPE; -. DR PDBsum; 7PPF; -. DR PDBsum; 7PPG; -. DR PDBsum; 7PPH; -. DR PDBsum; 7PPI; -. DR PDBsum; 8DSC; -. DR PDBsum; 8DSD; -. DR PDBsum; 8DSE; -. DR PDBsum; 8DSH; -. DR PDBsum; 8DSI; -. DR PDBsum; 8DSM; -. DR PDBsum; 8DTJ; -. DR PDBsum; 8F7L; -. DR PDBsum; 8IVU; -. DR PDBsum; 8TM7; -. DR PDBsum; 8Y55; -. DR PDBsum; 9IWT; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Biological rhythms; Cytokine; Cytoplasm; KW Glycosyltransferase; Nucleus; Phosphoprotein; Proteomics identification; KW Pyridine nucleotide biosynthesis; Reference proteome; Secreted; KW Transferase. FT CHAIN 1..491 FT /note="Nicotinamide phosphoribosyltransferase" FT /id="PRO_0000205863" FT BINDING 196 FT /ligand="diphosphate" FT /ligand_id="ChEBI:CHEBI:33019" FT BINDING 219 FT /ligand="beta-nicotinamide D-ribonucleotide" FT /ligand_id="ChEBI:CHEBI:14649" FT BINDING 247 FT /ligand="diphosphate" FT /ligand_id="ChEBI:CHEBI:33019" FT BINDING 311..313 FT /ligand="beta-nicotinamide D-ribonucleotide" FT /ligand_id="ChEBI:CHEBI:14649" FT BINDING 311 FT /ligand="diphosphate" FT /ligand_id="ChEBI:CHEBI:33019" FT BINDING 353..354 FT /ligand="beta-nicotinamide D-ribonucleotide" FT /ligand_id="ChEBI:CHEBI:14649" FT BINDING 384 FT /ligand="beta-nicotinamide D-ribonucleotide" FT /ligand_id="ChEBI:CHEBI:14649" FT BINDING 392 FT /ligand="beta-nicotinamide D-ribonucleotide" FT /ligand_id="ChEBI:CHEBI:14649" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 188 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 472 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 176 FT /note="L -> S (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036614" FT MUTAGEN 219 FT /note="D->N,S: No effect on activity towards nicotinamide. FT Alters specificity, so that the enzyme acquires activity FT towards nicotinic acid." FT /evidence="ECO:0000269|PubMed:16783377" FT MUTAGEN 247 FT /note="H->A: Reduces activity towards nicotinamide." FT /evidence="ECO:0000269|PubMed:16783377" FT MUTAGEN 311 FT /note="R->D: Reduces activity towards nicotinamide." FT /evidence="ECO:0000269|PubMed:16783377" FT HELIX 11..13 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 14..16 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 17..24 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 30..39 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 62..65 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 66..70 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 77..91 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 98..108 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 114..118 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 132..138 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 144..147 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 149..153 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 156..180 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 189..192 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 195..197 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 198..200 FT /evidence="ECO:0007829|PDB:5NSD" FT HELIX 201..211 FT /evidence="ECO:0007829|PDB:8DSC" FT TURN 212..214 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 216..220 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 222..230 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 234..236 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:8F7L" FT HELIX 247..251 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 255..257 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 258..268 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 274..277 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 286..294 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 296..299 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:6B76" FT STRAND 308..311 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 317..331 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:2GVJ" FT STRAND 348..352 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 358..370 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 375..377 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 378..383 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 384..387 FT /evidence="ECO:0007829|PDB:8DSC" FT TURN 392..396 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 397..406 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 409..412 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 418..420 FT /evidence="ECO:0007829|PDB:6AZJ" FT HELIX 421..423 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 424..426 FT /evidence="ECO:0007829|PDB:6E68" FT STRAND 431..434 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 436..438 FT /evidence="ECO:0007829|PDB:9IWT" FT STRAND 440..443 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 447..450 FT /evidence="ECO:0007829|PDB:8DSC" FT STRAND 453..455 FT /evidence="ECO:0007829|PDB:4M6P" FT STRAND 459..463 FT /evidence="ECO:0007829|PDB:8DSC" FT HELIX 473..479 FT /evidence="ECO:0007829|PDB:8DSC" FT TURN 483..485 FT /evidence="ECO:0007829|PDB:8DSC" SQ SEQUENCE 491 AA; 55521 MW; 6BF07B631B589AC0 CRC64; MNPAAEAEFN ILLATDSYKV THYKQYPPNT SKVYSYFECR EKKTENSKLR KVKYEETVFY GLQYILNKYL KGKVVTKEKI QEAKDVYKEH FQDDVFNEKG WNYILEKYDG HLPIEIKAVP EGFVIPRGNV LFTVENTDPE CYWLTNWIET ILVQSWYPIT VATNSREQKK ILAKYLLETS GNLDGLEYKL HDFGYRGVSS QETAGIGASA HLVNFKGTDT VAGLALIKKY YGTKDPVPGY SVPAAEHSTI TAWGKDHEKD AFEHIVTQFS SVPVSVVSDS YDIYNACEKI WGEDLRHLIV SRSTQAPLII RPDSGNPLDT VLKVLEILGK KFPVTENSKG YKLLPPYLRV IQGDGVDINT LQEIVEGMKQ KMWSIENIAF GSGGGLLQKL TRDLLNCSFK CSYVVTNGLG INVFKDPVAD PNKRSKKGRL SLHRTPAGNF VTLEEGKGDL EEYGQDLLHT VFKNGKVTKS YSFDEIRKNA QLNIELEAAH H //