UniProt functional annotation for P43490



	UniProt functional annotation for P43490

UniProt code: P43490.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). {ECO:0000250|UniProtKB:Q99KQ4, ECO:0000269|PubMed:24130902}.

Catalytic activity: Reaction=beta-nicotinamide D-ribonucleotide + diphosphate = 5-phospho- alpha-D-ribose 1-diphosphate + H(+) + nicotinamide; Xref=Rhea:RHEA:16149, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017; EC=2.4.2.12; Evidence={ECO:0000250|UniProtKB:Q99KQ4}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16151; Evidence={ECO:0000250|UniProtKB:Q99KQ4};

Activity 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. {ECO:0000269|PubMed:16783377}.

Pathway: Cofactor biosynthesis; NAD(+) biosynthesis; nicotinamide D- ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide: step 1/1.

Subunit: Homodimer. {ECO:0000269|PubMed:16783377}.

Subcellular location: Nucleus {ECO:0000269|PubMed:24130902}. Cytoplasm {ECO:0000250|UniProtKB:Q99KQ4}. Secreted {ECO:0000269|PubMed:21741723}. Note=Under non-inflammatory conditions, visfatin predominantly exhibits a granular pattern within the nucleus. Secreted by endothelial cells upon IL-1beta stimulation. Abundantly secreted in milk, reaching 100- fold higher concentrations compared to maternal serum. {ECO:0000269|PubMed:21741723, ECO:0000269|PubMed:24130902}.

Tissue specificity: Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.

Similarity: Belongs to the NAPRTase family. {ECO:0000305}.

Sequence caution: Sequence=AAQ96862.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=EAL24400.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). {ECO:0000250\|UniProtKB:Q99KQ4, ECO:0000269\|PubMed:24130902}.


Catalytic activity:		Reaction=beta-nicotinamide D-ribonucleotide + diphosphate = 5-phospho- alpha-D-ribose 1-diphosphate + H(+) + nicotinamide; Xref=Rhea:RHEA:16149, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:33019, ChEBI:CHEBI:58017; EC=2.4.2.12; Evidence={ECO:0000250\|UniProtKB:Q99KQ4}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16151; Evidence={ECO:0000250\|UniProtKB:Q99KQ4};
Activity 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. {ECO:0000269\|PubMed:16783377}.
Pathway:		Cofactor biosynthesis; NAD(+) biosynthesis; nicotinamide D- ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide: step 1/1.
Subunit:		Homodimer. {ECO:0000269\|PubMed:16783377}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:24130902}. Cytoplasm {ECO:0000250\|UniProtKB:Q99KQ4}. Secreted {ECO:0000269\|PubMed:21741723}. Note=Under non-inflammatory conditions, visfatin predominantly exhibits a granular pattern within the nucleus. Secreted by endothelial cells upon IL-1beta stimulation. Abundantly secreted in milk, reaching 100- fold higher concentrations compared to maternal serum. {ECO:0000269\|PubMed:21741723, ECO:0000269\|PubMed:24130902}.
Tissue specificity:		Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.
Similarity:		Belongs to the NAPRTase family. {ECO:0000305}.
Sequence caution:		Sequence=AAQ96862.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=EAL24400.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};