Q15274 (NADC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nicotinate-nucleotide pyrophosphorylase [carboxylating]
EC=2.4.2.19

Alternative name(s):
Quinolinate phosphoribosyltransferase [decarboxylating]
Short name=QAPRTase
Short name=QPRTase

Gene names

Name:

QPRT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	297 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the catabolism of quinolinic acid (QA). Ref.5
Catalytic activity	Nicotinate D-ribonucleotide + diphosphate + CO2 = pyridine-2,3-dicarboxylate + 5-phospho-alpha-D-ribose 1-diphosphate.
Enzyme regulation	Activity toward QA is slightly repressed by phosphoribosylpyrophosphate (PRPP) in both a competitive and a non-competitive manner. Ref.5
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; nicotinate D-ribonucleotide from quinolinate: step 1/1.
Subunit structure	Hexamer formed by 3 homodimers. Ref.5
Sequence similarities	Belongs to the nadC/modD family.
Biophysicochemical properties	Kinetic parameters: KM=21 µM for QA (at 0.1 mM PRPP) Ref.5 KM=23 µM for QA (at 0.3 mM PRPP) Vmax=1.2 µM/min/mg enzyme (at 0.3 mM QA and 0.1 mM PRPP) Vmax=0.93 µM/min/mg enzyme (at 0.3 mM QA and 0.3 mM PRPP)

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Coding sequence diversity	Polymorphism
Molecular function	Glycosyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein oligomerization Inferred from direct assay Ref.5. Source: UniProtKB quinolinate catabolic process Inferred from direct assay Ref.1. Source: UniProtKB water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	nicotinate-nucleotide diphosphorylase (carboxylating) activity Inferred from direct assay Ref.5Ref.1. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 297

297

Nicotinate-nucleotide pyrophosphorylase [carboxylating]

PRO_0000155954

Regions

Region

137 – 139

3

Substrate binding

Region

248 – 250

3

Substrate binding By similarity

Region

269 – 271

3

Substrate binding By similarity

Sites

Binding site

102

1

Substrate

Binding site

161

1

Substrate

Binding site

171

1

Substrate

Binding site

201

1

Substrate By similarity

Binding site

222

1

Substrate By similarity

Natural variations

Natural variant

158

1

A → V.
Corresponds to variant rs2303255 [ dbSNP | Ensembl ].

VAR_021915

Natural variant

195

1

T → A. Ref.1 Ref.2 Ref.3
Corresponds to variant rs9932770 [ dbSNP | Ensembl ].

VAR_050219

Experimental info

Mutagenesis

102

1

R → A or Q: Reduced activity. Ref.5

Mutagenesis

138

1

R → Q: Loss of activity. Ref.5

Mutagenesis

139

1

K → A or S: Loss of activity. Ref.5

Mutagenesis

161

1

R → A: Reduced activity. Ref.5

Mutagenesis

161

1

R → Q: Loss of activity. Ref.5

Mutagenesis

171

1

K → A or S: Loss of activity. Ref.5

Sequence conflict

53

1

V → I in AAP35895. Ref.2

Sequence conflict

53

1

V → I in AAH05060. Ref.3

Sequence conflict

170

1

V → L in BAA11242. Ref.1

Sequence conflict

177 – 178

2

AA → PP in BAA11242. Ref.1

Sequence conflict

208

1

A → V in BAA11242. Ref.1

Sequence conflict

235

1

V → A in BAA11242. Ref.1

Sequence conflict

276

1

A → V in BAA11242. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

297

Helix Strand Turn

Details...

Helix

3 – 9

7

Helix

12 – 26

15

Helix

34 – 37

4

Beta strand

41 – 48

8

Helix

57 – 66

10

Beta strand

70 – 75

6

Beta strand

83 – 93

11

Helix

94 – 127

34

Beta strand

132 – 135

4

Helix

145 – 154

10

Beta strand

166 – 170

5

Helix

172 – 178

7

Helix

181 – 192

12

Turn

193 – 195

3

Beta strand

198 – 204

7

Helix

205 – 213

9

Beta strand

217 – 223

7

Helix

226 – 239

14

Beta strand

243 – 250

8

Turn

253 – 255

3

Helix

256 – 259

4

Beta strand

266 – 268

3

Helix

271 – 274

4

Beta strand

281 – 288

8

Sequences

	Sequence		Length	Mass (Da)
	Q15274 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: E3199814DB9FA0D5	FASTA	297	30,846
	10 20 30 40 50 60 MDAEGLALLL PPVTLAALVD SWLREDCPGL NYAALVSGAG PSQAALWAKS PGVLAGQPFF 70 80 90 100 110 120 DAIFTQLNCQ VSWFLPEGSK LVPVARVAEV RGPAHCLLLG ERVALNTLAR CSGIASAAAA 130 140 150 160 170 180 AVEAARGAGW TGHVAGTRKT TPGFRLVEKY GLLVGGAASH RYDLGGLVMV KDNHVVAAGG 190 200 210 220 230 240 VEKAVRAARQ AADFTLKVEV ECSSLQEAVQ AAEAGADLVL LDNFKPEELH PTATVLKAQF 250 260 270 280 290 PSVAVEASGG ITLDNLPQFC GPHIDVISMG MLTQAAPALD FSLKLFAKEV APVPKIH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and functional expression of the cDNA encoding human brain quinolinate phosphoribosyltransferase." Fukuoka S., Nyaruhucha C.M., Shibata K. Biochim. Biophys. Acta 1395:192-201(1998) [PubMed: 9473669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-195. Tissue: Brain.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-195.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-195. Tissue: Kidney, Muscle and Placenta.
[4]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]	"Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens." Liu H., Woznica K., Catton G., Crawford A., Botting N., Naismith J.H. J. Mol. Biol. 373:755-763(2007) [PubMed: 17868694] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, MUTAGENESIS OF ARG-102; ARG-138; LYS-139; ARG-161 AND LYS-171, FUNCTION, SUBUNIT, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D78177 mRNA. Translation: BAA11242.1.
BT007231 mRNA. Translation: AAP35895.1.
BC005060 mRNA. Translation: AAH05060.1.
BC010033 mRNA. Translation: AAH10033.1.
BC018910 mRNA. Translation: AAH18910.1.

IPI

IPI00300086.

PIR

T46864.

RefSeq

NP_055113.2. NM_014298.3.

UniGene

Hs.513484.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JBM	X-ray	2.00	A/B/C/D/E/F/G/H/I/J/K/L	1-297	[»]
3LAR	X-ray	2.80	A/B/C/D/E/F	1-297	[»]

ProteinModelPortal

Q15274.

SMR

Q15274. Positions 1-289.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15274. 3 interactions.

MINT

MINT-1446481.

STRING

Q15274.

PTM databases

PhosphoSite

Q15274.

Polymorphism databases

DMDM

296439291.

Proteomic databases

PRIDE

Q15274.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000395384; ENSP00000378782; ENSG00000103485.

GeneID

23475.

KEGG

hsa:23475.

UCSC

uc002dto.1. human.

Organism-specific databases

CTD

23475.

GeneCards

GC16P029597.

H-InvDB

HIX0019343.

HGNC

HGNC:9755. QPRT.

MIM

606248. gene.

neXtProt

NX_Q15274.

PharmGKB

PA34096.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15873.

GeneTree

ENSGT00390000002761.

HOGENOM

HBG751540.

HOVERGEN

HBG031727.

InParanoid

Q15274.

OMA

VECRSLE.

PhylomeDB

Q15274.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q15274.

Bgee

Q15274.

CleanEx

HS_QPRT.

Genevestigator

Q15274.

GermOnline

ENSG00000103485. Homo sapiens.

Family and domain databases

InterPro

IPR013785. Aldolase_TIM.
IPR004393. NadC.
IPR002638. Quinolinate_PRibosylTrfase_C.
IPR022412. Quinolinate_PRibosylTrfase_N.
[Graphical view]

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.
G3DSA:3.90.1170.20. G3DSA:3.90.1170.20. 1 hit.

KO

K00767.

Pfam

PF01729. QRPTase_C. 1 hit.
PF02749. QRPTase_N. 1 hit.
[Graphical view]

SUPFAM

SSF51690. Q_phspho_trans. 1 hit.

TIGRFAMs

TIGR00078. NadC. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00627. Niacin.

NextBio

45813.

SOURCE

Search...

Entry information

Entry name

NADC_HUMAN

Accession

Primary (citable) accession number: Q15274
Secondary accession number(s): Q53XW7, Q96G22, Q9BSG6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 18, 2010
Last modified:	January 25, 2012
This is version 110 of the entry and version 3 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.