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    NADK NAD kinase [ Homo sapiens (human) ]

    Gene ID: 65220, updated on 27-Nov-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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    See NADK in Genome Data Viewer
    Location:
    1p36.33
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (1751232..1780514, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (1185650..1214901, complement)
    RS_2024_09 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. Functional annotation of rare gene aberration drivers of pancreatic cancer. Tsang YH, et al. Nat Commun, 2016 Jan 25. PMID 26806015, Free PMC Article
    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. 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
    4. Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis. Meng X, et al. J Cancer Res Clin Oncol, 2024 May 3. PMID 38700533, Free PMC Article
    5. NAD kinase levels control the NADPH concentration in human cells. Pollak N, et al. J Biol Chem, 2007 Nov 16. PMID 17855339

    See all (50) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis.
      Title: Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis.
    2. 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.
    3. NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma.
      Title: NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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)

    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_2024_08

    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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