P43490 (NAMPT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nicotinamide phosphoribosyltransferase
Short name=NAmPRTase
Short name=Nampt
EC=2.4.2.12

Alternative name(s):
Pre-B-cell colony-enhancing factor 1
Short name=Pre-B cell-enhancing factor
Visfatin

Gene names

Name:	NAMPT
Synonyms:	PBEF, PBEF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway By similarity.
Catalytic activity	Nicotinamide D-ribonucleotide + diphosphate = nicotinamide + 5-phospho-alpha-D-ribose 1-diphosphate.
Enzyme regulation	Inhibited by FK866. FK866 competes for the same binding site as nicotinamide, but due to its very low dissociation rate, it is essentially an irreversible inhibitor. Ref.8
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; nicotinamide D-ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide: step 1/1.
Subunit structure	Homodimer. Ref.8
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.
Sequence similarities	Belongs to the NAPRTase family.
Caution	Was originally (Ref.1) thought to be a cytokine which acts on early B-lineage precursor cells, by enhancing the effect of IL-7 and SCF on pre-B-cell colony formation.
Sequence caution	The sequence AAQ96862.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence EAL24400.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Glycosyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NAD biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway NAD metabolic process Traceable author statement. Source: Reactome cell-cell signaling Traceable author statement Ref.1. Source: ProtInc nicotinamide metabolic process Traceable author statement. Source: Reactome positive regulation of cell proliferation Traceable author statement Ref.1. Source: ProtInc positive regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay PubMed 19727662. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 23001182. Source: BHF-UCL signal transduction Traceable author statement Ref.1. Source: ProtInc water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	cytokine activity Traceable author statement Ref.1. Source: ProtInc nicotinamide phosphoribosyltransferase activity Inferred from electronic annotation. Source: EC nicotinate phosphoribosyltransferase activity Inferred from electronic annotation. Source: InterPro nicotinate-nucleotide diphosphorylase (carboxylating) activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 491

491

Nicotinamide phosphoribosyltransferase

PRO_0000205863

Regions

Region

311 – 313

3

Nicotinamide ribonucleotide binding

Region

353 – 354

2

Nicotinamide ribonucleotide binding

Sites

Binding site

196

1

Diphosphate

Binding site

219

1

Nicotinamide ribonucleotide

Binding site

247

1

Diphosphate

Binding site

311

1

Diphosphate

Binding site

384

1

Nicotinamide ribonucleotide; via amide nitrogen

Binding site

392

1

Nicotinamide ribonucleotide

Natural variations

Natural variant

176

1

L → S in a colorectal cancer sample; somatic mutation. Ref.9

VAR_036614

Experimental info

Mutagenesis

219

1

D → N or S: No effect on activity towards nicotinamide. Alters specificity, so that the enzyme acquires activity towards nicotinic acid. Ref.8

Mutagenesis

247

1

H → A: Reduces activity towards nicotinamide. Ref.8

Mutagenesis

311

1

R → D: Reduces activity towards nicotinamide. Ref.8

Secondary structure

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491

Helix Strand Turn

Details...

Helix

11 – 13

3

Beta strand

14 – 16

3

Helix

17 – 24

8

Beta strand

30 – 39

10

Beta strand

56 – 58

3

Helix

62 – 69

8

Helix

77 – 91

15

Helix

98 – 108

11

Beta strand

114 – 118

5

Beta strand

124 – 126

3

Beta strand

132 – 138

7

Helix

139 – 141

3

Helix

144 – 147

4

Helix

149 – 153

5

Helix

156 – 180

25

Helix

186 – 188

3

Beta strand

189 – 192

4

Turn

195 – 197

3

Helix

201 – 211

11

Turn

212 – 214

3

Beta strand

217 – 220

4

Helix

222 – 230

9

Beta strand

234 – 236

3

Helix

247 – 251

5

Helix

255 – 257

3

Helix

258 – 268

11

Beta strand

270 – 272

3

Beta strand

274 – 277

4

Helix

283 – 288

6

Helix

289 – 294

6

Helix

296 – 299

4

Beta strand

308 – 311

4

Helix

317 – 331

15

Beta strand

338 – 340

3

Beta strand

348 – 352

5

Helix

358 – 370

13

Helix

375 – 377

3

Beta strand

378 – 383

6

Helix

384 – 387

4

Turn

392 – 396

5

Beta strand

397 – 406

10

Beta strand

409 – 412

4

Helix

421 – 423

3

Beta strand

431 – 434

4

Beta strand

440 – 443

4

Helix

447 – 450

4

Beta strand

452 – 454

3

Beta strand

459 – 463

5

Helix

473 – 479

7

Sequences

	Sequence		Length	Mass (Da)
	P43490 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 6BF07B631B589AC0	FASTA	491	55,521
	10 20 30 40 50 60 MNPAAEAEFN ILLATDSYKV THYKQYPPNT SKVYSYFECR EKKTENSKLR KVKYEETVFY 70 80 90 100 110 120 GLQYILNKYL KGKVVTKEKI QEAKDVYKEH FQDDVFNEKG WNYILEKYDG HLPIEIKAVP 130 140 150 160 170 180 EGFVIPRGNV LFTVENTDPE CYWLTNWIET ILVQSWYPIT VATNSREQKK ILAKYLLETS 190 200 210 220 230 240 GNLDGLEYKL HDFGYRGVSS QETAGIGASA HLVNFKGTDT VAGLALIKKY YGTKDPVPGY 250 260 270 280 290 300 SVPAAEHSTI TAWGKDHEKD AFEHIVTQFS SVPVSVVSDS YDIYNACEKI WGEDLRHLIV 310 320 330 340 350 360 SRSTQAPLII RPDSGNPLDT VLKVLEILGK KFPVTENSKG YKLLPPYLRV IQGDGVDINT 370 380 390 400 410 420 LQEIVEGMKQ KMWSIENIAF GSGGGLLQKL TRDLLNCSFK CSYVVTNGLG INVFKDPVAD 430 440 450 460 470 480 PNKRSKKGRL SLHRTPAGNF VTLEEGKGDL EEYGQDLLHT VFKNGKVTKS YSFDEIRKNA 490 QLNIELEAAH H

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor." Samal B., Sun Y., Stearns G., Xie C., Suggs S., McNiece I. Mol. Cell. Biol. 14:1431-1437(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Skin.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents." Khan J.A., Tao X., Tong L. Nat. Struct. Mol. Biol. 13:582-588(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE; PRODUCT AND INHIBITOR FK866, ENZYME REGULATION, MUTAGENESIS OF ASP-219; HIS-247 AND ARG-311, SUBUNIT.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-176.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U02020 mRNA. Translation: AAA17884.1.
AK292851 mRNA. Translation: BAF85540.1.
AC007032 Genomic DNA. Translation: AAF19249.1.
AC007032 Genomic DNA. Translation: AAQ96862.1. Sequence problems.
CH236947 Genomic DNA. Translation: EAL24399.1.
CH236947 Genomic DNA. Translation: EAL24400.1. Sequence problems.
CH471070 Genomic DNA. Translation: EAW83382.1.
BC072439 mRNA. Translation: AAH72439.1.
BC106046 mRNA. Translation: AAI06047.1.

IPI

IPI00018873.

PIR

A55927.

RefSeq

NP_005737.1. NM_005746.2.

UniGene

Hs.489615.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E5B	X-ray	2.00	A/B	1-491	[»]
2E5C	X-ray	2.20	A/B	1-491	[»]
2E5D	X-ray	2.00	A/B	1-491	[»]
2GVG	X-ray	2.20	A/B/C/D/E/F	1-491	[»]
2GVJ	X-ray	2.10	A/B	1-491	[»]
3DGR	X-ray	2.10	A/B	1-484	[»]
3DHD	X-ray	2.00	A/B	1-484	[»]
3DHF	X-ray	1.80	A/B	1-484	[»]
3DKJ	X-ray	2.00	A/B	1-484	[»]
3DKL	X-ray	1.89	A/B	1-484	[»]

ProteinModelPortal

P43490.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29218N.

IntAct

P43490. 4 interactions.

MINT

MINT-4530953.

STRING

9606.ENSP00000222553.

PTM databases

PhosphoSite

P43490.

Polymorphism databases

DMDM

1172027.

Proteomic databases

PaxDb

P43490.

PRIDE

P43490.

Protocols and materials databases

DNASU

10135.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222553; ENSP00000222553; ENSG00000105835.
ENST00000354289; ENSP00000346242; ENSG00000105835.

GeneID

10135.

KEGG

hsa:10135.

UCSC

uc003vdq.3. human.

Organism-specific databases

CTD

10135.

GeneCards

GC07M105888.

HGNC

HGNC:30092. NAMPT.

HPA

CAB034349.

MIM

608764. gene.

neXtProt

NX_P43490.

PharmGKB

PA162396933.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1488.

HOGENOM

HOG000216546.

HOVERGEN

HBG000336.

InParanoid

P43490.

KO

K03462.

OMA

WYPSTVA.

OrthoDB

EOG40K7ZQ.

PhylomeDB

P43490.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_24941. Circadian Clock.

UniPathway

UPA00253; UER00890.

Gene expression databases

ArrayExpress

P43490.

Bgee

P43490.

CleanEx

HS_NAMPT.

Genevestigator

P43490.

GermOnline

ENSG00000105835. Homo sapiens.

Family and domain databases

InterPro

IPR015977. Nic_PRibTrfase-like.
IPR016471. Nicotinamide_PRibTrfase.
IPR002638. Quinolinate_PRibosylTrfase_C.
[Graphical view]

PANTHER

PTHR11098:SF2. PTHR11098:SF2. 1 hit.

Pfam

PF04095. NAPRTase. 1 hit.
[Graphical view]

PIRSF

PIRSF005943. NMPRT. 1 hit.

SUPFAM

SSF51690. Q_phspho_trans. 1 hit.

ProtoNet

Search...

Other

BindingDB

P43490.

ChEMBL

CHEMBL1744525.

ChiTaRS

NAMPT. human.

EvolutionaryTrace

P43490.

GenomeRNAi

10135.

NextBio

38341.

SOURCE

Search...

Entry information

Entry name

NAMPT_HUMAN

Accession

Primary (citable) accession number: P43490
Secondary accession number(s): A4D0Q9 , A4D0R0, Q3KQV0, Q8WW95

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.