PKN1 protein kinase N1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKN1provided by HGNC
Official Full Name: protein kinase N1provided by HGNC
Primary source: HGNC:HGNC:9405
See related: Ensembl:ENSG00000123143 MIM:601032; AllianceGenome:HGNC:9405
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DBK; PKN; PAK1; PRK1; PAK-1; PRKCL1; PKN-ALPHA
Summary: The protein encoded by this gene belongs to the protein kinase C superfamily. This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. This kinase can be activated by phospholipids and by limited proteolysis. The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in spleen (RPKM 39.4), fat (RPKM 30.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.12

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (14433306..14471859)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (14559936..14598492)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (14544118..14582671)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer.
Title: Upregulation of PKN1 as a Prognosis Biomarker for Endometrial Cancer.
Cyclin-dependent kinase 1-mediated phosphorylation of protein kinase N1 promotes anchorage-independent growth and migration.
Title: Cyclin-dependent kinase 1-mediated phosphorylation of protein kinase N1 promotes anchorage-independent growth and migration.
Novel roles of PRK1 and PRK2 in cilia and cancer biology.
Title: Novel roles of PRK1 and PRK2 in cilia and cancer biology.
Characterization of the novel cardiolipin binding regions identified on the protease and lipid activated PKC-related kinase 1
Title: Characterization of the novel cardiolipin binding regions identified on the protease and lipid activated PKC-related kinase 1.
Secretory carcinoma of the skin associated with the presence of novel NFIX-PKN1 translocation.
Title: Secretory Carcinoma of the Skin: Report of 6 Cases, Including a Case With a Novel NFIX-PKN1 Translocation.
PKN1 transduces androgen-responsiveness to serum response factor in prostate neoplasms
Title: Protein Kinase N1 control of androgen-responsive serum response factor action provides rationale for novel prostate cancer treatment strategy.
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.
Pkn1 is not required for tumorigenesis initiated by loss of Pten. Triple knockout of Pten, Pkn1, and Pkn2 in mouse prostate results in squamous cell carcinoma, an uncommon but therapy-resistant form of prostate cancer.
Title: The protein kinase C super-family member PKN is regulated by mTOR and influences differentiation during prostate cancer progression.
PKN1 activity was up-regulated by the active RhoA mutant (G14V) and suppressed by RhoA T19N. PKN1 siRNA interrupted the ability of RhoA to promote ESC proliferation and DNA synthesis. The effect of RhoA on ESC proliferation is mediated by activation of the PKN1-cyclin D1 pathway in vitro.
Title: RhoA promotes epidermal stem cell proliferation via PKN1-cyclin D1 signaling.
TXA2-mediated neoplastic responses in prostate adenocarcinoma PC-3 cells occur through a PRK1/PRK2-dependent mechanism.
Title: Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer.

Submit: New GeneRIF Correction See all GeneRIFs (31)

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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Application of HIV-1 Tat transmembrane transport peptide to cells induces PKN1 gene and slightly represses two genes, ZCD1 and BSG	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables diacylglycerol-dependent serine/threonine kinase activity	EXP Inferred from Experiment more info	PubMed
enables diacylglycerol-dependent serine/threonine kinase activity	TAS Traceable Author Statement more info
enables histone H3T11 kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone binding	IDA Inferred from Direct Assay more info	PubMed
enables histone deacetylase binding	IDA Inferred from Direct Assay more info	PubMed
enables nuclear androgen receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor coactivator activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor coactivator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase C 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 protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in B cell homeostasis	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hyperosmotic response	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in post-translational protein modification	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of androgen receptor signaling pathway	TAS Traceable Author Statement more info
involved_in regulation of cell motility	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of germinal center formation	IEA Inferred from Electronic Annotation more info
involved_in regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal system process	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in spleen development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cleavage furrow	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase N1

Names: protease-activated kinase 1; protein kinase C-like 1; protein kinase C-like PKN; protein kinase C-related kinase 1; protein kinase PKN-alpha; serine-threonine kinase N; serine/threonine protein kinase N

NP_002732.3

EC 2.7.11.13

NP_998725.1

EC 2.7.11.13

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)

NM_002741.5 → NP_002732.3 serine/threonine-protein kinase N1 isoform 2

See identical proteins and their annotated locations for NP_002732.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon at the 5' end compared to variant 1, which includes a part of the coding region. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1.

Source sequence(s)

AC008569

Consensus CDS

CCDS42513.1

UniProtKB/Swiss-Prot

A8K7W5, B2R9R4, B3KVN3, Q15143, Q16512, Q504U4, Q8IUV5, Q9UD44

Related

ENSP00000242783.7, ENST00000242783.11

Conserved Domains (6) summary

cd08687
Location:389 → 476

C2_PKN-like; C2 domain in Protein kinase C-like (PKN) proteins

cd11622
Location:46 → 98

HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N

cd11630
Location:121 → 196

HR1_PKN1_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1

cd11636
Location:205 → 278

HR1_PKN1_3; Third Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1

smart00220
Location:615 → 874

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05589
Location:615 → 939

STKc_PKN; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N
NM_213560.3 → NP_998725.1 serine/threonine-protein kinase N1 isoform 1

See identical proteins and their annotated locations for NP_998725.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC008569

Consensus CDS

CCDS42514.1

UniProtKB/Swiss-Prot

Q16512

Related

ENSP00000343325.4, ENST00000342216.8

Conserved Domains (6) summary

cd08687
Location:395 → 482

C2_PKN-like; C2 domain in Protein kinase C-like (PKN) proteins

cd11622
Location:52 → 104

HR1_PKN_1; First Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N

cd11630
Location:127 → 202

HR1_PKN1_2; Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1

cd11636
Location:211 → 284

HR1_PKN1_3; Third Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1

smart00220
Location:621 → 880

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05589
Location:621 → 945

STKc_PKN; Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N