Full text data of NAPRT1
NAPRT1
(FHIP)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Nicotinate phosphoribosyltransferase; NAPRTase; 6.3.4.21 (FHA-HIT-interacting protein; Nicotinate phosphoribosyltransferase domain-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Nicotinate phosphoribosyltransferase; NAPRTase; 6.3.4.21 (FHA-HIT-interacting protein; Nicotinate phosphoribosyltransferase domain-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00465085
IPI00465085 Nicotinate phosphoribosyltransferase-like protein nicotinate phosphoribosyltransferase activity, transferase activity, transferring glycosyl groups, pyridine nucleotide biosynthesis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00465085 Nicotinate phosphoribosyltransferase-like protein nicotinate phosphoribosyltransferase activity, transferase activity, transferring glycosyl groups, pyridine nucleotide biosynthesis soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q6XQN6
ID PNCB_HUMAN Reviewed; 538 AA.
AC Q6XQN6; A7BFI3; Q6PJL1; Q6XQN4; Q6XQN5; Q8N5E8; Q9BRG0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JAN-2008, sequence version 2.
DT 22-JAN-2014, entry version 78.
DE RecName: Full=Nicotinate phosphoribosyltransferase;
DE Short=NAPRTase;
DE EC=6.3.4.21;
DE AltName: Full=FHA-HIT-interacting protein;
DE AltName: Full=Nicotinate phosphoribosyltransferase domain-containing protein 1;
GN Name=NAPRT1; Synonyms=FHIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17604275; DOI=10.1074/jbc.M610357200;
RA Hara N., Yamada K., Shibata T., Osago H., Hashimoto T., Tsuchiya M.;
RT "Elevation of cellular NAD levels by nicotinic acid and involvement of
RT nicotinic acid phosphoribosyltransferase in human cells.";
RL J. Biol. Chem. 282:24574-24582(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RA Huang C.-H., Chen H., Chen Y.;
RT "Identification of nicotinate phosphoribosyltransferase as a novel
RT FHA-HIT interaction protein (FHIP).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
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.,
RA Buerckstuemmer T., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION, 3D-STRUCTURE
RP MODELING, AND MUTAGENESIS OF ASP-19; TYR-21; GLY-169; GLY-209;
RP HIS-213; ASP-288; ARG-318; ASN-357; GLY-379; THR-380 AND SER-381.
RX PubMed=21742010; DOI=10.1016/j.biochi.2011.06.033;
RA Galassi L., Di Stefano M., Brunetti L., Orsomando G., Amici A.,
RA Ruggieri S., Magni G.;
RT "Characterization of human nicotinate phosphoribosyltransferase:
RT Kinetic studies, structure prediction and functional analysis by site-
RT directed mutagenesis.";
RL Biochimie 94:300-309(2012).
CC -!- FUNCTION: Catalyzes the conversion of nicotinic acid (NA) to NA
CC mononucleotide (NaMN). Essential for NA to increase cellular NAD
CC levels and prevent oxidative stress of the cells.
CC -!- FUNCTION: Catalyzes the synthesis of beta-nicotinate D-
CC ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate
CC at the expense of ATP (By similarity).
CC -!- CATALYTIC ACTIVITY: Nicotinate + 5-phospho-alpha-D-ribose 1-
CC diphosphate + ATP + H(2)O = beta-nicotinate D-ribonucleotide +
CC diphosphate + ADP + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=44.3 uM for nicotinic acid (in the presence of 3mM ATP);
CC KM=22.1 uM for 5-phosphoribosyl-1-pyrophosphate (in the presence
CC of 3mM ATP);
CC KM=27.3 uM for nicotinic acid (in the presence of inorganic
CC phosphate);
CC KM=38.2 uM for 5-phosphoribosyl-1-pyrophosphate (in the presence
CC of inorganic phosphate);
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; nicotinate D-
CC ribonucleotide from nicotinate: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6XQN6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6XQN6-2; Sequence=VSP_030612;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q6XQN6-3; Sequence=VSP_030610;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the NAPRTase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06284.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH32466.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB242230; BAF75377.1; -; mRNA.
DR EMBL; AY214325; AAP69603.1; -; mRNA.
DR EMBL; AY214326; AAP69604.1; -; mRNA.
DR EMBL; AY214327; AAP69605.1; -; mRNA.
DR EMBL; BC006284; AAH06284.2; ALT_INIT; mRNA.
DR EMBL; BC032466; AAH32466.1; ALT_INIT; mRNA.
DR RefSeq; NP_660202.3; NM_145201.5.
DR UniGene; Hs.493164; -.
DR ProteinModelPortal; Q6XQN6; -.
DR SMR; Q6XQN6; 16-522.
DR STRING; 9606.ENSP00000401508; -.
DR PhosphoSite; Q6XQN6; -.
DR DMDM; 166221824; -.
DR PaxDb; Q6XQN6; -.
DR PRIDE; Q6XQN6; -.
DR Ensembl; ENST00000426292; ENSP00000390949; ENSG00000147813.
DR Ensembl; ENST00000449291; ENSP00000401508; ENSG00000147813.
DR GeneID; 93100; -.
DR KEGG; hsa:93100; -.
DR UCSC; uc003yym.4; human.
DR CTD; 93100; -.
DR GeneCards; GC08M144656; -.
DR HGNC; HGNC:30450; NAPRT1.
DR HPA; HPA023739; -.
DR HPA; HPA024017; -.
DR MIM; 611552; gene.
DR neXtProt; NX_Q6XQN6; -.
DR PharmGKB; PA142671293; -.
DR eggNOG; COG1488; -.
DR HOVERGEN; HBG062439; -.
DR InParanoid; Q6XQN6; -.
DR KO; K00763; -.
DR BRENDA; 2.4.2.11; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR UniPathway; UPA00253; UER00457.
DR ChiTaRS; NAPRT1; human.
DR GenomeRNAi; 93100; -.
DR NextBio; 77980; -.
DR PRO; PR:Q6XQN6; -.
DR ArrayExpress; Q6XQN6; -.
DR Bgee; Q6XQN6; -.
DR CleanEx; HS_NAPRT1; -.
DR Genevestigator; Q6XQN6; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0004516; F:nicotinate phosphoribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004514; F:nicotinate-nucleotide diphosphorylase (carboxylating) activity; IEA:InterPro.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019674; P:NAD metabolic process; TAS:Reactome.
DR GO; GO:0006769; P:nicotinamide metabolic process; TAS:Reactome.
DR GO; GO:0019358; P:nicotinate nucleotide salvage; IEA:InterPro.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR InterPro; IPR007229; Nic_PRibTrfase-Fam.
DR InterPro; IPR006405; Nic_PRibTrfase_pncB.
DR InterPro; IPR002638; Quinolinate_PRibosylTrfase_C.
DR Pfam; PF04095; NAPRTase; 2.
DR PIRSF; PIRSF000484; NAPRT; 1.
DR SUPFAM; SSF51690; SSF51690; 2.
DR TIGRFAMs; TIGR01513; NAPRTase_put; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Ligase;
KW Phosphoprotein; Polymorphism; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 538 Nicotinate phosphoribosyltransferase.
FT /FTId=PRO_0000315681.
FT MOD_RES 537 537 Phosphoserine.
FT VAR_SEQ 469 481 Missing (in isoform 3).
FT /FTId=VSP_030610.
FT VAR_SEQ 517 517 Y -> YQVGGGGPPCHSALCAPALTLPTAPVLCSL (in
FT isoform 2).
FT /FTId=VSP_030612.
FT VARIANT 57 57 A -> V (in dbSNP:rs896950).
FT /FTId=VAR_038275.
FT MUTAGEN 19 19 D->A: Complete loss of activity.
FT MUTAGEN 21 21 Y->A: Partial loss of activity in the
FT presence of ATP, complete loss in the
FT absence of ATP.
FT MUTAGEN 169 169 G->A: Partial loss of activity.
FT MUTAGEN 209 209 G->A: Partial loss of activity.
FT MUTAGEN 213 213 H->A: Partial loss of activity.
FT MUTAGEN 288 288 D->A: Partial loss of activity.
FT MUTAGEN 318 318 R->A: Partial loss of activity in the
FT presence of ATP, almost complete loss in
FT the absence of ATP.
FT MUTAGEN 357 357 N->A: Small loss of activity.
FT MUTAGEN 379 379 G->A: Complete loss of activity.
FT MUTAGEN 380 380 T->A: Partial loss of activity.
FT MUTAGEN 381 381 S->A: Partial loss of activity.
FT CONFLICT 155 155 L -> V (in Ref. 2; AAP69603/AAP69604/
FT AAP69605).
FT CONFLICT 224 224 V -> A (in Ref. 1; BAF75377).
FT CONFLICT 246 246 A -> T (in Ref. 1; BAF75377).
FT CONFLICT 375 375 V -> A (in Ref. 1; BAF75377).
SQ SEQUENCE 538 AA; 57578 MW; 26DF39885CBB1C9B CRC64;
MAAEQDPEAR AAARPLLTDL YQATMALGYW RAGRARDAAE FELFFRRCPF GGAFALAAGL
RDCVRFLRAF RLRDADVQFL ASVLPPDTDP AFFEHLRALD CSEVTVRALP EGSLAFPGVP
LLQVSGPLLV VQLLETPLLC LVSYASLVAT NAARLRLIAG PEKRLLEMGL RRAQGPDGGL
TASTYSYLGG FDSSSNVLAG QLRGVPVAGT LAHSFVTSFS GSEVPPDPML APAAGEGPGV
DLAAKAQVWL EQVCAHLGLG VQEPHPGERA AFVAYALAFP RAFQGLLDTY SVWRSGLPNF
LAVALALGEL GYRAVGVRLD SGDLLQQAQE IRKVFRAAAA QFQVPWLESV LIVVSNNIDE
EALARLAQEG SEVNVIGIGT SVVTCPQQPS LGGVYKLVAV GGQPRMKLTE DPEKQTLPGS
KAAFRLLGSD GSPLMDMLQL AEEPVPQAGQ ELRVWPPGAQ EPCTVRPAQV EPLLRLCLQQ
GQLCEPLPSL AESRALAQLS LSRLSPEHRR LRSPAQYQVV LSERLQALVN SLCAGQSP
//
ID PNCB_HUMAN Reviewed; 538 AA.
AC Q6XQN6; A7BFI3; Q6PJL1; Q6XQN4; Q6XQN5; Q8N5E8; Q9BRG0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JAN-2008, sequence version 2.
DT 22-JAN-2014, entry version 78.
DE RecName: Full=Nicotinate phosphoribosyltransferase;
DE Short=NAPRTase;
DE EC=6.3.4.21;
DE AltName: Full=FHA-HIT-interacting protein;
DE AltName: Full=Nicotinate phosphoribosyltransferase domain-containing protein 1;
GN Name=NAPRT1; Synonyms=FHIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17604275; DOI=10.1074/jbc.M610357200;
RA Hara N., Yamada K., Shibata T., Osago H., Hashimoto T., Tsuchiya M.;
RT "Elevation of cellular NAD levels by nicotinic acid and involvement of
RT nicotinic acid phosphoribosyltransferase in human cells.";
RL J. Biol. Chem. 282:24574-24582(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RA Huang C.-H., Chen H., Chen Y.;
RT "Identification of nicotinate phosphoribosyltransferase as a novel
RT FHA-HIT interaction protein (FHIP).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
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.,
RA Buerckstuemmer T., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION, 3D-STRUCTURE
RP MODELING, AND MUTAGENESIS OF ASP-19; TYR-21; GLY-169; GLY-209;
RP HIS-213; ASP-288; ARG-318; ASN-357; GLY-379; THR-380 AND SER-381.
RX PubMed=21742010; DOI=10.1016/j.biochi.2011.06.033;
RA Galassi L., Di Stefano M., Brunetti L., Orsomando G., Amici A.,
RA Ruggieri S., Magni G.;
RT "Characterization of human nicotinate phosphoribosyltransferase:
RT Kinetic studies, structure prediction and functional analysis by site-
RT directed mutagenesis.";
RL Biochimie 94:300-309(2012).
CC -!- FUNCTION: Catalyzes the conversion of nicotinic acid (NA) to NA
CC mononucleotide (NaMN). Essential for NA to increase cellular NAD
CC levels and prevent oxidative stress of the cells.
CC -!- FUNCTION: Catalyzes the synthesis of beta-nicotinate D-
CC ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate
CC at the expense of ATP (By similarity).
CC -!- CATALYTIC ACTIVITY: Nicotinate + 5-phospho-alpha-D-ribose 1-
CC diphosphate + ATP + H(2)O = beta-nicotinate D-ribonucleotide +
CC diphosphate + ADP + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=44.3 uM for nicotinic acid (in the presence of 3mM ATP);
CC KM=22.1 uM for 5-phosphoribosyl-1-pyrophosphate (in the presence
CC of 3mM ATP);
CC KM=27.3 uM for nicotinic acid (in the presence of inorganic
CC phosphate);
CC KM=38.2 uM for 5-phosphoribosyl-1-pyrophosphate (in the presence
CC of inorganic phosphate);
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; nicotinate D-
CC ribonucleotide from nicotinate: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6XQN6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6XQN6-2; Sequence=VSP_030612;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q6XQN6-3; Sequence=VSP_030610;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the NAPRTase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06284.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH32466.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB242230; BAF75377.1; -; mRNA.
DR EMBL; AY214325; AAP69603.1; -; mRNA.
DR EMBL; AY214326; AAP69604.1; -; mRNA.
DR EMBL; AY214327; AAP69605.1; -; mRNA.
DR EMBL; BC006284; AAH06284.2; ALT_INIT; mRNA.
DR EMBL; BC032466; AAH32466.1; ALT_INIT; mRNA.
DR RefSeq; NP_660202.3; NM_145201.5.
DR UniGene; Hs.493164; -.
DR ProteinModelPortal; Q6XQN6; -.
DR SMR; Q6XQN6; 16-522.
DR STRING; 9606.ENSP00000401508; -.
DR PhosphoSite; Q6XQN6; -.
DR DMDM; 166221824; -.
DR PaxDb; Q6XQN6; -.
DR PRIDE; Q6XQN6; -.
DR Ensembl; ENST00000426292; ENSP00000390949; ENSG00000147813.
DR Ensembl; ENST00000449291; ENSP00000401508; ENSG00000147813.
DR GeneID; 93100; -.
DR KEGG; hsa:93100; -.
DR UCSC; uc003yym.4; human.
DR CTD; 93100; -.
DR GeneCards; GC08M144656; -.
DR HGNC; HGNC:30450; NAPRT1.
DR HPA; HPA023739; -.
DR HPA; HPA024017; -.
DR MIM; 611552; gene.
DR neXtProt; NX_Q6XQN6; -.
DR PharmGKB; PA142671293; -.
DR eggNOG; COG1488; -.
DR HOVERGEN; HBG062439; -.
DR InParanoid; Q6XQN6; -.
DR KO; K00763; -.
DR BRENDA; 2.4.2.11; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR UniPathway; UPA00253; UER00457.
DR ChiTaRS; NAPRT1; human.
DR GenomeRNAi; 93100; -.
DR NextBio; 77980; -.
DR PRO; PR:Q6XQN6; -.
DR ArrayExpress; Q6XQN6; -.
DR Bgee; Q6XQN6; -.
DR CleanEx; HS_NAPRT1; -.
DR Genevestigator; Q6XQN6; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0004516; F:nicotinate phosphoribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004514; F:nicotinate-nucleotide diphosphorylase (carboxylating) activity; IEA:InterPro.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019674; P:NAD metabolic process; TAS:Reactome.
DR GO; GO:0006769; P:nicotinamide metabolic process; TAS:Reactome.
DR GO; GO:0019358; P:nicotinate nucleotide salvage; IEA:InterPro.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR InterPro; IPR007229; Nic_PRibTrfase-Fam.
DR InterPro; IPR006405; Nic_PRibTrfase_pncB.
DR InterPro; IPR002638; Quinolinate_PRibosylTrfase_C.
DR Pfam; PF04095; NAPRTase; 2.
DR PIRSF; PIRSF000484; NAPRT; 1.
DR SUPFAM; SSF51690; SSF51690; 2.
DR TIGRFAMs; TIGR01513; NAPRTase_put; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Ligase;
KW Phosphoprotein; Polymorphism; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 538 Nicotinate phosphoribosyltransferase.
FT /FTId=PRO_0000315681.
FT MOD_RES 537 537 Phosphoserine.
FT VAR_SEQ 469 481 Missing (in isoform 3).
FT /FTId=VSP_030610.
FT VAR_SEQ 517 517 Y -> YQVGGGGPPCHSALCAPALTLPTAPVLCSL (in
FT isoform 2).
FT /FTId=VSP_030612.
FT VARIANT 57 57 A -> V (in dbSNP:rs896950).
FT /FTId=VAR_038275.
FT MUTAGEN 19 19 D->A: Complete loss of activity.
FT MUTAGEN 21 21 Y->A: Partial loss of activity in the
FT presence of ATP, complete loss in the
FT absence of ATP.
FT MUTAGEN 169 169 G->A: Partial loss of activity.
FT MUTAGEN 209 209 G->A: Partial loss of activity.
FT MUTAGEN 213 213 H->A: Partial loss of activity.
FT MUTAGEN 288 288 D->A: Partial loss of activity.
FT MUTAGEN 318 318 R->A: Partial loss of activity in the
FT presence of ATP, almost complete loss in
FT the absence of ATP.
FT MUTAGEN 357 357 N->A: Small loss of activity.
FT MUTAGEN 379 379 G->A: Complete loss of activity.
FT MUTAGEN 380 380 T->A: Partial loss of activity.
FT MUTAGEN 381 381 S->A: Partial loss of activity.
FT CONFLICT 155 155 L -> V (in Ref. 2; AAP69603/AAP69604/
FT AAP69605).
FT CONFLICT 224 224 V -> A (in Ref. 1; BAF75377).
FT CONFLICT 246 246 A -> T (in Ref. 1; BAF75377).
FT CONFLICT 375 375 V -> A (in Ref. 1; BAF75377).
SQ SEQUENCE 538 AA; 57578 MW; 26DF39885CBB1C9B CRC64;
MAAEQDPEAR AAARPLLTDL YQATMALGYW RAGRARDAAE FELFFRRCPF GGAFALAAGL
RDCVRFLRAF RLRDADVQFL ASVLPPDTDP AFFEHLRALD CSEVTVRALP EGSLAFPGVP
LLQVSGPLLV VQLLETPLLC LVSYASLVAT NAARLRLIAG PEKRLLEMGL RRAQGPDGGL
TASTYSYLGG FDSSSNVLAG QLRGVPVAGT LAHSFVTSFS GSEVPPDPML APAAGEGPGV
DLAAKAQVWL EQVCAHLGLG VQEPHPGERA AFVAYALAFP RAFQGLLDTY SVWRSGLPNF
LAVALALGEL GYRAVGVRLD SGDLLQQAQE IRKVFRAAAA QFQVPWLESV LIVVSNNIDE
EALARLAQEG SEVNVIGIGT SVVTCPQQPS LGGVYKLVAV GGQPRMKLTE DPEKQTLPGS
KAAFRLLGSD GSPLMDMLQL AEEPVPQAGQ ELRVWPPGAQ EPCTVRPAQV EPLLRLCLQQ
GQLCEPLPSL AESRALAQLS LSRLSPEHRR LRSPAQYQVV LSERLQALVN SLCAGQSP
//
MIM
611552
*RECORD*
*FIELD* NO
611552
*FIELD* TI
*611552 NICOTINATE PHOSPHORIBOSYLTRANSFERASE DOMAIN-CONTAINING 1; NAPRT1
;;NICOTINIC ACID PHOSPHORIBOSYLTRANSFERASE
read more*FIELD* TX
DESCRIPTION
Nicotinic acid (NA; niacin) is converted by nicotinic acid
phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide
(NaMN), which is then converted to NA adenine dinucleotide (NaAD), and
finally to nicotinamide adenine dinucleotide (NAD), which serves as a
coenzyme in cellular redox reactions and is an essential component of a
variety of processes in cellular metabolism including response to stress
(Hara et al., 2007).
CLONING
Using a candidate sequence of human NAPRT in GenBank (GENBANK AAH06284)
and 5-prime and 3-prime RACE, Hara et al. (2007) cloned a full-length
human NAPRT cDNA. NAPRT encodes a deduced 538-amino acid protein that is
highly conserved. Transfection experiments with recombinant NAPRT in
HepG2 cells, which normally lack NAPRT activity, localized the protein
in the cytosol at the expected enzymatic activity. Northern blot
analysis of mouse tissues showed that NAPRT mRNA is expressed at highest
levels in the small intestine, liver, and kidney.
GENE FUNCTION
Hara et al. (2007) found that expression of a tagged recombinant NAPRT
demonstrated a 54-kD protein by electrophoresis. The recombinant NAPRT
catalyzed the formation of NaMN in the presence of NA, Mg(2+), and PRPP
(5-phosphoribosyl 1-pyrophosphate). When NAPRT was purified from
nondenaturing gels, the molecular mass was about 110 kD, indicating that
the enzyme may exist as a homodimer. In cells expressing endogenous
NAPRT, the addition of NA but not nicotinamide (Nam) almost doubled
cellular NAD contents and decreased cytotoxicity by hydrogen peroxide.
Both effects were reversed by siRNA knockdown of NAPRT expression. The
results indicated that NAPRT is essential for NA to increase cellular
NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic
analyses revealed that NAPRT but not nicotinamide
phosphoribosyltransferase (NAMPT; 608764) is insensitive to the
physiologic concentration of NAD.
Hara et al. (2007) speculated that loss or downregulation of NAPRT and
the ensuing inability to make NAD may contribute to some of the
clinically observed effects of NA and implies that the vitamin might be
used to treat diseases associated with depletion of NAD pools.
*FIELD* RF
1. Hara, N.; Yamada, K.; Shibata, T.; Osago, H.; Hashimoto, T.; Tsuchiya,
M.: Elevation of cellular NAD levels by nicotinic acid and involvement
of nicotinic acid phosphoribosyltransferase in human cells. J. Biol.
Chem. 282: 24575-24582, 2007.
*FIELD* CD
Alan F. Scott: 10/24/2007
*FIELD* ED
carol: 04/08/2008
carol: 10/25/2007
*RECORD*
*FIELD* NO
611552
*FIELD* TI
*611552 NICOTINATE PHOSPHORIBOSYLTRANSFERASE DOMAIN-CONTAINING 1; NAPRT1
;;NICOTINIC ACID PHOSPHORIBOSYLTRANSFERASE
read more*FIELD* TX
DESCRIPTION
Nicotinic acid (NA; niacin) is converted by nicotinic acid
phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide
(NaMN), which is then converted to NA adenine dinucleotide (NaAD), and
finally to nicotinamide adenine dinucleotide (NAD), which serves as a
coenzyme in cellular redox reactions and is an essential component of a
variety of processes in cellular metabolism including response to stress
(Hara et al., 2007).
CLONING
Using a candidate sequence of human NAPRT in GenBank (GENBANK AAH06284)
and 5-prime and 3-prime RACE, Hara et al. (2007) cloned a full-length
human NAPRT cDNA. NAPRT encodes a deduced 538-amino acid protein that is
highly conserved. Transfection experiments with recombinant NAPRT in
HepG2 cells, which normally lack NAPRT activity, localized the protein
in the cytosol at the expected enzymatic activity. Northern blot
analysis of mouse tissues showed that NAPRT mRNA is expressed at highest
levels in the small intestine, liver, and kidney.
GENE FUNCTION
Hara et al. (2007) found that expression of a tagged recombinant NAPRT
demonstrated a 54-kD protein by electrophoresis. The recombinant NAPRT
catalyzed the formation of NaMN in the presence of NA, Mg(2+), and PRPP
(5-phosphoribosyl 1-pyrophosphate). When NAPRT was purified from
nondenaturing gels, the molecular mass was about 110 kD, indicating that
the enzyme may exist as a homodimer. In cells expressing endogenous
NAPRT, the addition of NA but not nicotinamide (Nam) almost doubled
cellular NAD contents and decreased cytotoxicity by hydrogen peroxide.
Both effects were reversed by siRNA knockdown of NAPRT expression. The
results indicated that NAPRT is essential for NA to increase cellular
NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic
analyses revealed that NAPRT but not nicotinamide
phosphoribosyltransferase (NAMPT; 608764) is insensitive to the
physiologic concentration of NAD.
Hara et al. (2007) speculated that loss or downregulation of NAPRT and
the ensuing inability to make NAD may contribute to some of the
clinically observed effects of NA and implies that the vitamin might be
used to treat diseases associated with depletion of NAD pools.
*FIELD* RF
1. Hara, N.; Yamada, K.; Shibata, T.; Osago, H.; Hashimoto, T.; Tsuchiya,
M.: Elevation of cellular NAD levels by nicotinic acid and involvement
of nicotinic acid phosphoribosyltransferase in human cells. J. Biol.
Chem. 282: 24575-24582, 2007.
*FIELD* CD
Alan F. Scott: 10/24/2007
*FIELD* ED
carol: 04/08/2008
carol: 10/25/2007