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    PKN3 protein kinase N3 [ Homo sapiens (human) ]

    Gene ID: 29941, updated on 14-Nov-2024

    Summary

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    Official Symbol
    PKN3provided by HGNC
    Official Full Name
    protein kinase N3provided by HGNC
    Primary source
    HGNC:HGNC:17999
    See related
    Ensembl:ENSG00000160447 MIM:610714; AllianceGenome:HGNC:17999
    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
    UTDP4-1
    Summary
    Predicted to enable protein serine/threonine kinase activity. Involved in epithelial cell migration. Predicted to be located in Golgi apparatus; cytosol; and nucleus. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in fat (RPKM 3.9), lung (RPKM 3.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PKN3 in Genome Data Viewer
    Location:
    9q34.11
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (128702503..128720916)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (140907265..140925683)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (131464782..131483195)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene dynein 2 intermediate chain 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131430084-131430584 Neighboring gene high mobility group AT-hook 1 pseudogene 4 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131445235-131445871 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131445872-131446509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29088 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29089 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29090 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131449798-131450674 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20348 Neighboring gene SET nuclear proto-oncogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131465059-131465598 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131475223-131475724 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:131475725-131476224 Neighboring gene RNA, 7SL, cytoplasmic 560, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20350 Neighboring gene ZDHHC12 divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131491015-131491846 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:131491847-131492678 Neighboring gene zinc finger DHHC-type palmitoyltransferase 12 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:131494472-131494972 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:131494973-131495473 Neighboring gene zyg-11 related cell cycle regulator Neighboring gene small nucleolar RNA U13

    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 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. Identification and characterization of PKNbeta, a novel isoform of protein kinase PKN: expression and arachidonic acid dependency are different from those of PKNalpha. Oishi K, et al. Biochem Biophys Res Commun, 1999 Aug 11. PMID 10441506
    2. Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions dynamics and attenuates endothelial cell activation. Möpert K, et al. Eur J Cell Biol, 2012 Sep. PMID 22609186
    3. PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase. Leenders F, et al. EMBO J, 2004 Aug 18. PMID 15282551, Free PMC Article
    4. PKN3 is the major regulator of angiogenesis and tumor metastasis in mice. Mukai H, et al. Sci Rep, 2016 Jan 8. PMID 26742562, Free PMC Article
    5. A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18. Dibus M, et al. Int J Mol Sci, 2020 Oct 20. PMID 33092266, Free PMC Article

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18.
      Title: A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18.
    2. a novel interaction of p130Cas with Ser/Thr kinase PKN3, is reported.
      Title: The interaction of p130Cas with PKN3 promotes malignant growth.
    3. Steady-state kinetic analysis revealed that PKN1-3 follows a sequential ordered Bi-Bi kinetic mechanism, where peptide substrate binding is preceded by ATP binding. This kinetic mechanism was confirmed by additional kinetic studies for product inhibition and affinity of small molecule inhibitors.
      Title: Enzyme kinetics and distinct modulation of the protein kinase N family of kinases by lipid activators and small molecule inhibitors.
    4. PKN3 is the major regulator of angiogenesis in humans and mice and tumor metastasis in mice.
      Title: PKN3 is the major regulator of angiogenesis and tumor metastasis in mice.
    5. PKN3 can be considered a novel protein implicated in remodeling the actin-adherens junction, possibly by linking ICAM-1-signaling with actin/AJ dynamics.
      Title: Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions dynamics and attenuates endothelial cell activation.
    6. PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It
      Title: Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.
    7. PKN3 might represent a preferred target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of phosphoinositide 3-kinase
      Title: PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium,diacylglycerol-dependent serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables diacylglycerol-dependent, calcium-independent serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables small GTPase binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in epithelial cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi apparatus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein kinase N3
    Names
    protein kinase PKN-beta
    protein-kinase C-related kinase 3
    NP_001304855.1
    NP_037487.2
    XP_005252003.1
    XP_006717143.1
    XP_016870138.1
    XP_016870139.1
    XP_047279234.1
    XP_047279235.1
    XP_054218798.1
    XP_054218799.1
    XP_054218800.1
    XP_054218801.1

    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_001317926.2 → NP_001304855.1  serine/threonine-protein kinase N3 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the penultimate exon, compared to variant 1, resulting in a novel 3' coding region and shorter 3' UTR. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL441992
      Conserved Domains (6) summary
      cd11622
      Location:13 → 78
      HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N
      cd11632
      Location:97 → 170
      HR1_PKN3_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3
      smart00220
      Location:559 → 811
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl00087
      Location:170 → 230
      HR1; Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases
      cl14603
      Location:328 → 410
      C2; C2 domain
      cl21453
      Location:559 → 815
      PKc_like; Protein Kinases, catalytic domain

    2. NM_013355.5 → NP_037487.2  serine/threonine-protein kinase N3 isoform 1

      See identical proteins and their annotated locations for NP_037487.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL441992
      Consensus CDS
      CCDS6908.1
      UniProtKB/Swiss-Prot
      Q6P5Z2, Q9UM03
      Related
      ENSP00000291906.4, ENST00000291906.5
      Conserved Domains (6) summary
      PTZ00263
      Location:555 → 879
      PTZ00263; protein kinase A catalytic subunit; Provisional
      cd11622
      Location:13 → 78
      HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N
      cd11632
      Location:97 → 170
      HR1_PKN3_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3
      cd05589
      Location:559 → 884
      STKc_PKN; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N
      cl00087
      Location:170 → 230
      HR1; Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases
      cl14603
      Location:328 → 410
      C2; C2 domain

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      128702503..128720916
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017014650.2 → XP_016870139.1  serine/threonine-protein kinase N3 isoform X4

    2. XM_047423278.1 → XP_047279234.1  serine/threonine-protein kinase N3 isoform X4

    3. XM_005251946.4 → XP_005252003.1  serine/threonine-protein kinase N3 isoform X2

      Conserved Domains (6) summary
      PTZ00263
      Location:552 → 876
      PTZ00263; protein kinase A catalytic subunit; Provisional
      cd11622
      Location:10 → 75
      HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N
      cd11632
      Location:94 → 167
      HR1_PKN3_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3
      cl00087
      Location:167 → 227
      HR1; Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases
      cl14603
      Location:325 → 407
      C2; C2 domain
      cl21453
      Location:556 → 881
      PKc_like; Protein Kinases, catalytic domain

    4. XM_006717080.4 → XP_006717143.1  serine/threonine-protein kinase N3 isoform X1

      Conserved Domains (6) summary
      cd11622
      Location:20 → 85
      HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N
      cd11632
      Location:104 → 177
      HR1_PKN3_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3
      smart00220
      Location:566 → 825
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd05589
      Location:566 → 891
      STKc_PKN; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N
      cl00087
      Location:177 → 237
      HR1; Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases
      cl14603
      Location:335 → 417
      C2; C2 domain

    5. XM_017014649.3 → XP_016870138.1  serine/threonine-protein kinase N3 isoform X3

    6. XM_047423279.1 → XP_047279235.1  serine/threonine-protein kinase N3 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      140907265..140925683
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054362826.1 → XP_054218801.1  serine/threonine-protein kinase N3 isoform X4

    2. XM_054362825.1 → XP_054218800.1  serine/threonine-protein kinase N3 isoform X3

    3. XM_054362823.1 → XP_054218798.1  serine/threonine-protein kinase N3 isoform X1

    4. XM_054362824.1 → XP_054218799.1  serine/threonine-protein kinase N3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6P5Z2.1 GenPept UniProtKB/Swiss-Prot:Q6P5Z2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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