Protein kinase N1

PDB rendering based on 1cxz.

Available structures
PDB	1CXZ, 1URF, 2RMK

Identifiers

Symbols

PKN1; DBK; MGC46204; PAK-1; PAK1; PKN; PKN-ALPHA; PRK1; PRKCL1

External IDs

OMIM: 601032 MGI: 108022 HomoloGene: 48130 GeneCards: PKN1 Gene

EC number

2.7.11.13

Gene Ontology
Molecular function	• nucleotide binding • chromatin binding • protein kinase activity • protein serine/threonine kinase activity • protein kinase C activity • protein kinase C binding • protein binding • ATP binding • GTP-Rho binding • ligand-dependent nuclear receptor transcription coactivator activity • ligand-dependent nuclear receptor transcription coactivator activity • histone kinase activity (H3-T11 specific) • histone binding • histone deacetylase binding • Rac GTPase binding • androgen receptor binding
Cellular component	• intracellular • nucleus • cytoplasm • endosome • plasma membrane • cytoplasmic membrane-bounded vesicle
Biological process	• regulation of transcription, DNA-dependent • protein phosphorylation • hyperosmotic response • signal transduction • activation of JUN kinase activity • chromatin modification • regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor • regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor • histone H3-T11 phosphorylation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
14.54 – 14.58 Mb

Chr 8:
86.19 – 86.22 Mb

PubMed search

[1]

[2]

Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene.^[1]^[2]

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.^[2]

Interactions

Protein kinase N1 has been shown to interact with Phospholipase D1,^[3] Phosphoinositide-dependent kinase-1,^[4] Vimentin,^[5] AKAP9,^[6] CCDC85B,^[7] Actinin, alpha 1,^[8] NEFL,^[9] NEUROD2^[10] and RHOA.^[11]^[12]^[13]

References

^ Bartsch JW, Mukai H, Takahashi N, Ronsiek M, Fuchs S, Jockusch H, Ono Y (Jun 1998). "The protein kinase N (PKN) gene PRKCL1/Prkcl1 maps to human chromosome 19p12-p13.1 and mouse chromosome 8 with close linkage to the myodystrophy (myd) mutation". Genomics 49 (1): 129–132. doi:10.1006/geno.1997.5208. PMID 9570957.
^ ^a ^b "Entrez Gene: PKN1 protein kinase N1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5585.
^ Oishi, K; Takahashi M, Mukai H, Banno Y, Nakashima S, Kanaho Y, Nozawa Y, Ono Y (May. 2001). "PKN regulates phospholipase D1 through direct interaction". J. Biol. Chem. (United States) 276 (21): 18096–18101. doi:10.1074/jbc.M010646200. ISSN 0021-9258. PMID 11259428.
^ Balendran, A; Biondi R M, Cheung P C, Casamayor A, Deak M, Alessi D R (Jul. 2000). "A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1". J. Biol. Chem. (UNITED STATES) 275 (27): 20806–20813. doi:10.1074/jbc.M000421200. ISSN 0021-9258. PMID 10764742.
^ Matsuzawa, K; Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M (May. 1997). "Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN". Biochem. Biophys. Res. Commun. (UNITED STATES) 234 (3): 621–625. doi:10.1006/bbrc.1997.6669. ISSN 0006-291X. PMID 9175763.
^ Takahashi, M; Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (Jun. 1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. (UNITED STATES) 274 (24): 17267–17274. doi:10.1074/jbc.274.24.17267. ISSN 0021-9258. PMID 10358086.
^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514.
^ Feng, Shuju; Reséndiz Julio C, Christodoulides Nicolaos, Lu Xin, Arboleda David, Berndt Michael C, Kroll Michael H (Jan. 2002). "Pathological shear stress stimulates the tyrosine phosphorylation of alpha-actinin associated with the glycoprotein Ib-IX complex". Biochemistry (United States) 41 (4): 1100–1108. doi:10.1021/bi0156005. ISSN 0006-2960. PMID 11802708.
^ Mukai, H; Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (Apr. 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. (UNITED STATES) 271 (16): 9816–9822. doi:10.1074/jbc.271.16.9816. ISSN 0021-9258. PMID 8621664.
^ Shibata, H; Oda H, Mukai H, Oishi K, Misaki K, Ohkubo H, Ono Y (Dec. 1999). "Interaction of PKN with a neuron-specific basic helix-loop-helix transcription factor, NDRF/NeuroD2". Brain Res. Mol. Brain Res. (NETHERLANDS) 74 (1–2): 126–134. doi:10.1016/S0169-328X(99)00273-9. ISSN 0169-328X. PMID 10640683.
^ Riento, Kirsi; Guasch Rosa M, Garg Ritu, Jin Boquan, Ridley Anne J (Jun. 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Mol. Cell. Biol. (United States) 23 (12): 4219–4229. doi:10.1128/MCB.23.12.4219-4229.2003. ISSN 0270-7306. PMC 156133. PMID 12773565. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=156133.
^ Alberts, A S; Bouquin N, Johnston L H, Treisman R (Apr. 1998). "Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the yeast response regulator protein Skn7". J. Biol. Chem. (UNITED STATES) 273 (15): 8616–8622. doi:10.1074/jbc.273.15.8616. ISSN 0021-9258. PMID 9535835.
^ Flynn, P; Mellor H, Palmer R, Panayotou G, Parker P J (Jan. 1998). "Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif". J. Biol. Chem. (UNITED STATES) 273 (5): 2698–2705. doi:10.1074/jbc.273.5.2698. ISSN 0021-9258. PMID 9446575.

Palmer RH, Ridden J, Parker PJ (1995). "Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family". Eur. J. Biochem. 227 (1–2): 344–351. doi:10.1111/j.1432-1033.1995.tb20395.x. PMID 7851406.
Chu W, Presky DH, Danho W et al. (1994). "Identification and characterization of DBK, a novel putative serine/threonine protein kinase from human endothelial cells". Eur. J. Biochem. 225 (2): 695–702. doi:10.1111/j.1432-1033.1994.00695.x. PMID 7957185.
Palmer RH, Ridden J, Parker PJ (1995). "Identification of multiple, novel, protein kinase C-related gene products". FEBS Lett. 356 (1): 5–8. doi:10.1016/0014-5793(94)01202-4. PMID 7988719.
Mukai H, Ono Y (1994). "A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase C". Biochem. Biophys. Res. Commun. 199 (2): 897–904. doi:10.1006/bbrc.1994.1313. PMID 8135837.
Palmer RH, Schönwasser DC, Rahman D et al. (1996). "PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163". FEBS Lett. 378 (3): 281–285. doi:10.1016/0014-5793(95)01454-3. PMID 8557118.
Amano M, Mukai H, Ono Y et al. (1996). "Identification of a putative target for Rho as the serine-threonine kinase protein kinase N". Science 271 (5249): 648–650. doi:10.1126/science.271.5249.648. PMID 8571127.
Mukai H, Toshimori M, Shibata H et al. (1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. 271 (16): 9816–9822. doi:10.1074/jbc.271.16.9816. PMID 8621664.
Brown JL, Stowers L, Baer M et al. (1997). "Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway". Curr. Biol. 6 (5): 598–605. doi:10.1016/S0960-9822(02)00546-8. PMID 8805275.
Mukai H, Miyahara M, Sunakawa H et al. (1996). "Translocation of PKN from the cytosol to the nucleus induced by stresses". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10195–10199. doi:10.1073/pnas.93.19.10195. PMC 38360. PMID 8816775. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38360.
Mukai H, Toshimori M, Shibata H et al. (1997). "Interaction of PKN with alpha-actinin". J. Biol. Chem. 272 (8): 4740–4746. doi:10.1074/jbc.272.8.4740. PMID 9030526.
Matsuzawa K, Kosako H, Inagaki N et al. (1997). "Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN". Biochem. Biophys. Res. Commun. 234 (3): 621–625. doi:10.1006/bbrc.1997.6669. PMID 9175763.
Goedert M, Hasegawa M, Jakes R et al. (1997). "Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases". FEBS Lett. 409 (1): 57–62. doi:10.1016/S0014-5793(97)00483-3. PMID 9199504.
Flynn P, Mellor H, Palmer R et al. (1998). "Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif". J. Biol. Chem. 273 (5): 2698–2705. doi:10.1074/jbc.273.5.2698. PMID 9446575.
Bekri S, Adélaïde J, Merscher S et al. (1998). "Detailed map of a region commonly amplified at 11q13→q14 in human breast carcinoma". Cytogenet. Cell Genet. 79 (1–2): 125–131. doi:10.1159/000134699. PMID 9533029.
Zheng-Fischhöfer Q, Biernat J, Mandelkow EM et al. (1998). "Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation". Eur. J. Biochem. 252 (3): 542–552. doi:10.1046/j.1432-1327.1998.2520542.x. PMID 9546672.
Takanaga H, Mukai H, Shibata H et al. (1998). "PKN interacts with a paraneoplastic cerebellar degeneration-associated antigen, which is a potential transcription factor". Exp. Cell Res. 241 (2): 363–372. doi:10.1006/excr.1998.4060. PMID 9637778.
Takahashi M, Mukai H, Toshimori M et al. (1998). "Proteolytic activation of PKN by caspase-3 or related protease during apoptosis". Proc. Natl. Acad. Sci. U.S.A. 95 (20): 11566–11571. doi:10.1073/pnas.95.20.11566. PMC 21681. PMID 9751706. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21681.
Hanger DP, Betts JC, Loviny TL et al. (1998). "New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry". J. Neurochem. 71 (6): 2465–2476. doi:10.1046/j.1471-4159.1998.71062465.x. PMID 9832145.
Takahashi M, Shibata H, Shimakawa M et al. (1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–17274. doi:10.1074/jbc.274.24.17267. PMID 10358086.

PDB gallery

1cxz: CRYSTAL STRUCTURE OF HUMAN RHOA COMPLEXED WITH THE EFFECTOR DOMAIN OF THE PROTEIN KINASE PKN/PRK1

1urf: HR1B DOMAIN FROM PRK1

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1, LATS2, MAST1, MAST2, STK38, STK38L, CIT, ROCK1, SGK, SGK2, SGK3, Protein kinase B (AKT1, AKT2, AKT3), Ataxia telangiectasia mutated, Mammalian target of rapamycin, EIF-2 kinases (PKR, HRI, EIF2AK3, EIF2AK4), Wee1 (WEE1)

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1, PDK2, PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α (PRKAA1, PRKAA2) · β (PRKAB1, PRKAB2) · γ (PRKAG1, PRKAG2, PRKAG3)

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK, BCKDHA, BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2, IDH3A, IDH3B, IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase (Aurora A kinase, Aurora B kinase)

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK, STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK, IKK2, TBK1, IKBKE, IKBKG, IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A, PRKACG, PRKACB, PRKACA, PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G, PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C, Protein kinase Cζ, PKC alpha, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, PRKCQ, Protein kinase N1, PKN2, PKN3,

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase, Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4, GRK5, GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, MLCK, CASK, CHEK1, CHEK2, DAPK1, DAPK2, DAPK3, STK11, MAPKAPK2, MAPKAPK3, MAPKAPK5, MARK1, MARK2, MARK3, MARK4, MELK, MKNK1, MKNK2, NUAK1, NUAK2, OBSCN, PASK, PHKG1, PHKG2, PIM1, PIM2, PKD1, PRKD2, PRKD3, PSKH1, SNF1LK2, KIAA0999, STK40, SNF1LK, SNRK, SPEG, TSSK2, Kalirin, TRIB1, TRIB2, TRIB3, TRIO, Titin, DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK, MYLK2, MYLK3, MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1, PHKA2, PHKB, PHKG1, PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K, STK19

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1, PLK2, PLK3, PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1, CDK2, CDKL2, CDK3, CDK4, CDK5, CDKL5, CDK6, CDK7, CDK8, CDK9, CDK10, CDC2L5, CRKRS, PCTK1, PCTK2, PCTK3, PFTK1, CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5, RPS6KA4, P70S6 kinase, P70-S6 Kinase 1, RPS6KB2, RPS6KA2, RPS6KA3, RPS6KA1, RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated (MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK12, MAPK15), C-Jun N-terminal (MAPK8, MAPK9, MAPK10), P38 mitogen-activated protein (MAPK11, MAPK13, MAPK14)

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases (MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8) RAFs (ARAF, BRAF, KSR1, KSR2), MLKs (MAP3K12, MAP3K13, MAP3K9, MAP3K10, MAP3K11, MAP3K7, ZAK), CDC7, MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1, TTK, GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors (BMPR1, BMPR1A, BMPR1B, BMPR2), ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

Protein kinase N1

Interactions

References

Further reading