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NADK NAD kinase [ Homo sapiens (human) ]

Gene ID: 65220, updated on 3-Apr-2024

Summary

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Official Symbol
NADKprovided by HGNC
Official Full Name
NAD kinaseprovided by HGNC
Primary source
HGNC:HGNC:29831
See related
Ensembl:ENSG00000008130 MIM:611616; AllianceGenome:HGNC:29831
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NADK1; dJ283E3.1
Summary
NADK catalyzes the transfer of a phosphate group from ATP to NAD to generate NADP, which in its reduced form acts as an electron donor for biosynthetic reactions (Lerner et al., 2001 [PubMed 11594753]).[supplied by OMIM, Mar 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 24.4), spleen (RPKM 23.0) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
1p36.33
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (1751232..1780514, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (1185650..1214901, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (1682671..1711470, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene cyclin dependent kinase 11A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 32 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1655889-1656728 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1660738-1661238 Neighboring gene ribosomal protein S7 pseudogene Neighboring gene solute carrier family 35 member E2A (pseudogene) Neighboring gene uncharacterized LOC112268218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 89 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1684563-1685092 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1691433-1692390 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1705547-1706048 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 90 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 33 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 34 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 35 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 36 Neighboring gene Sharpr-MPRA regulatory region 14484 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:1721473-1721656 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 38 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 91 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 39 Neighboring gene G protein subunit beta 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1757447-1758350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 40 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 41 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1782535-1783035 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1783210-1784022 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 42 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 43 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 44 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:1798007-1798184 Neighboring gene Sharpr-MPRA regulatory region 3728 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1820039-1820538 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 92 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 93 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 94 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 95 Neighboring gene GNB1 divergent transcript

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma. Schild T, et al. Cell Rep, 2021 Jun 15. PMID 34133937
  2. Direct stimulation of NADP(+) synthesis through Akt-mediated phosphorylation of NAD kinase. Hoxhaj G, et al. Science, 2019 Mar 8. PMID 30846598, Free PMC Article
  3. Functional annotation of rare gene aberration drivers of pancreatic cancer. Tsang YH, et al. Nat Commun, 2016 Jan 25. PMID 26806015, Free PMC Article
  4. Significance of Ser-188 in human mitochondrial NAD kinase as determined by phosphomimetic and phosphoresistant amino-acid substitutions. Kawabata Y, et al. Biochem Biophys Res Commun, 2015 Dec 25. PMID 26577408
  5. NADPH regulates human NAD kinase, a NADP⁺-biosynthetic enzyme. Ohashi K, et al. Mol Cell Biochem, 2011 Sep. PMID 21526340

See all (45) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation.
    Title: G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation.
  2. NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma.
    Title: NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma.
  3. These data indicate that Akt-mediated phosphorylation of NADK stimulates its activity to increase NADP(+) production through relief of an autoinhibitory function inherent to its amino terminus.
    Title: Direct stimulation of NADP(+) synthesis through Akt-mediated phosphorylation of NAD kinase.
  4. Data indicate metabolic enzymes NAD kinase and ketohexokinase as candidate metabolic gene targets, and the chromatin remodeling protein INO80C as a tumor suppressor in KRAS(MUT) colorectal tumor xenograft.
    Title: Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers.
  5. Depletion of wild-type NADK in pancreatic ductal adenocarcinoma cells attenuates cancer cell growth.
    Title: Functional annotation of rare gene aberration drivers of pancreatic cancer.
  6. Taken together, this indicates that Ser-188 (and perhaps the other residues) is an important phosphorylation site that can downregulate the NAD kinase activity of this critical enzyme.
    Title: Significance of Ser-188 in human mitochondrial NAD kinase as determined by phosphomimetic and phosphoresistant amino-acid substitutions.
  7. Using purified human NAD kinase, we revealed a sigmoidal kinetic behavior toward ATP and the inhibitory effects of NADPH and NADH
    Title: NADPH regulates human NAD kinase, a NADP⁺-biosynthetic enzyme.
  8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  9. NAD kinase levels control the NADPH concentration in human cells
    Title: NAD kinase levels control the NADPH concentration in human cells.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC1900, FLJ13052, FLJ37724, FLJ54695, FLJ77769, FLJ78247, FLJ78307, DKFZp686L22239

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables NAD+ kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables NAD+ kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ATP metabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in NAD metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in NADP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in phosphorylation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
NAD kinase
Names
poly(P)/ATP NAD kinase
NP_001185922.1
NP_001185923.1
NP_001185924.1
NP_001340570.1
NP_001340571.1
NP_075394.3
XP_011540311.1
XP_016857633.1
XP_047284587.1
XP_047284603.1
XP_047284612.1
XP_054194383.1
XP_054194384.1
XP_054194385.1
XP_054194386.1
XP_054194387.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001198993.2 → NP_001185922.1  NAD kinase isoform 1

    See identical proteins and their annotated locations for NP_001185922.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) has an alternate 5' UTR compared to variant 1. Variants 1, 2 and 5 encode the same isoform (1).
    Source sequence(s)
    AL031282, BC001709, BC024219, BM842058, CN349189
    Consensus CDS
    CCDS30565.1
    UniProtKB/Swiss-Prot
    A6NNN3, A8K296, B7Z434, F5GXR5, O95544, Q5QPS4, Q9H2P2, Q9H931
    UniProtKB/TrEMBL
    A8K6D4, A8K6R3
    Related
    ENSP00000344340.3, ENST00000341991.7
    Conserved Domains (1) summary
    cl28462
    Location:96 → 433
    pnk; inorganic polyphosphate/ATP-NAD kinase; Provisional

  2. NM_001198994.2 → NP_001185923.1  NAD kinase isoform 2

    See identical proteins and their annotated locations for NP_001185923.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and CDS compared to variant 1. The resulting isoform (2) has two additional internal segments, as compared to isoform 1.
    Source sequence(s)
    AF250320, AL031282, BC001709, BM842058
    Consensus CDS
    CCDS55562.1
    UniProtKB/Swiss-Prot
    O95544
    Related
    ENSP00000367890.1, ENST00000378625.5
    Conserved Domains (1) summary
    cl01255
    Location:202 → 578
    DAGK_cat; Diacylglycerol kinase catalytic domain

  3. NM_001198995.1 → NP_001185924.1  NAD kinase isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) lacks three exons from the 5' end and has an alternate 5' exon compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus, as compared to isoform 1.
    Source sequence(s)
    AK296722, AL031282, BC001709, BM842058
    Consensus CDS
    CCDS55561.1
    UniProtKB/TrEMBL
    A0A0A0MR98, A8K6R3
    Related
    ENSP00000339727.5, ENST00000342348.9
    Conserved Domains (1) summary
    cl01255
    Location:66 → 401
    DAGK_cat; Diacylglycerol kinase catalytic domain

  4. NM_001353641.2 → NP_001340570.1  NAD kinase isoform 1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 5 encode the same isoform (1).
    Source sequence(s)
    AL031282
    Consensus CDS
    CCDS30565.1
    UniProtKB/Swiss-Prot
    A6NNN3, A8K296, B7Z434, F5GXR5, O95544, Q5QPS4, Q9H2P2, Q9H931
    UniProtKB/TrEMBL
    A8K6D4, A8K6R3
    Conserved Domains (1) summary
    cl28462
    Location:96 → 433
    pnk; inorganic polyphosphate/ATP-NAD kinase; Provisional

  5. NM_001353642.2 → NP_001340571.1  NAD kinase isoform 4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (6) uses and alternate splice site which results in the use of an alternate start codon compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AL031282
    UniProtKB/TrEMBL
    A8K6D4, A8K6R3
    Conserved Domains (1) summary
    cl28462
    Location:9 → 346
    pnk; inorganic polyphosphate/ATP-NAD kinase; Provisional

  6. NM_023018.5 → NP_075394.3  NAD kinase isoform 1

    See identical proteins and their annotated locations for NP_075394.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes variant 1 isoform (1). Variants 1, 2 and 5 encode the same isoform (1).
    Source sequence(s)
    AK023114, AL031282, BC001709, BM842058
    Consensus CDS
    CCDS30565.1
    UniProtKB/Swiss-Prot
    A6NNN3, A8K296, B7Z434, F5GXR5, O95544, Q5QPS4, Q9H2P2, Q9H931
    UniProtKB/TrEMBL
    A8K6D4, A8K6R3
    Related
    ENSP00000341679.5, ENST00000341426.9
    Conserved Domains (1) summary
    cl28462
    Location:96 → 433
    pnk; inorganic polyphosphate/ATP-NAD kinase; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    1751232..1780514 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047428631.1 → XP_047284587.1  NAD kinase isoform X1

    UniProtKB/Swiss-Prot
    A6NNN3, A8K296, B7Z434, F5GXR5, O95544, Q5QPS4, Q9H2P2, Q9H931

  2. XM_011542009.3 → XP_011540311.1  NAD kinase isoform X2

    See identical proteins and their annotated locations for XP_011540311.1

    Conserved Domains (1) summary
    cl01255
    Location:68 → 330
    DAGK_cat; Diacylglycerol kinase catalytic domain

  3. XM_047428656.1 → XP_047284612.1  NAD kinase isoform X5

  4. XM_017002144.3 → XP_016857633.1  NAD kinase isoform X3

  5. XM_047428647.1 → XP_047284603.1  NAD kinase isoform X4

RNA

  1. XR_946747.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    1185650..1214901 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054338408.1 → XP_054194383.1  NAD kinase isoform X1

  2. XM_054338409.1 → XP_054194384.1  NAD kinase isoform X2

  3. XM_054338412.1 → XP_054194387.1  NAD kinase isoform X5

  4. XM_054338410.1 → XP_054194385.1  NAD kinase isoform X3

  5. XM_054338411.1 → XP_054194386.1  NAD kinase isoform X4

RNA

  1. XR_008486152.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95544.1 GenPept UniProtKB/Swiss-Prot:O95544

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