P70268
SS
Gene name |
Pkn1 (Pkn, Prk1, Prkcl1) |
Protein name |
Serine/threonine-protein kinase N1 |
Names |
EC 2.7.11.13 , Protein kinase C-like 1 , Protein kinase C-like PKN , Protein-kinase C-related kinase 1 , Serine-threonine protein kinase N |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:320795 |
EC number |
2.7.11.13: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
Serine/threonine-protein kinase N1 (PKN1) is a PKC-related serine/threonine protein kinase involved in specific signal transduction responses such as regulation of intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion, and transcription regulation in cells. Its kinase activity is enhanced by fatty acids such as arachidonic acid or the small GTP-binding protein Rho. Residues 455-511 of PKN selectively inhibit the kinase activity of the catalytic fragment of PKN1. Arachidonic acid relieves the catalytic activity of wild-type PKN from autoinhibition by residues 455-511 of PKN.
Autoinhibitory domains (AIDs)
Target domain |
619-878 (Protein kinase domain) |
Relief mechanism |
Ligand binding, PTM |
Assay |
|
Accessory elements
761-784 (Activation loop from InterPro)
Target domain |
619-878 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Yoshinaga C et al. (1999) "Mutational analysis of the regulatory mechanism of PKN: the regulatory region of PKN contains an arachidonic acid-sensitive autoinhibitory domain", Journal of biochemistry, 126, 475-84
- Huang X et al. (2003) "Crystal structure of an inactive Akt2 kinase domain", Structure (London, England : 1993), 11, 21-30
- Truebestein L et al. (2021) "Structure of autoinhibited Akt1 reveals mechanism of PIP(3)-mediated activation", Proceedings of the National Academy of Sciences of the United States of America, 118,
- Lučić I et al. (2018) "Conformational sampling of membranes by Akt controls its activation and inactivation", Proceedings of the National Academy of Sciences of the United States of America, 115, E3940-E3949
Autoinhibited structure
Activated structure
1 structures for P70268
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P70268-F1 | Predicted | AlphaFoldDB |
53 variants for P70268
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388981724 | 16 | L>Q | No | EVA | |
| rs3388995744 | 22 | A>T | No | EVA | |
| rs3388964593 | 28 | A>P | No | EVA | |
| rs3388981772 | 36 | E>* | No | EVA | |
| rs3388999801 | 38 | E>* | No | EVA | |
| rs3388993041 | 58 | N>K | No | EVA | |
| rs3388995218 | 101 | P>L | No | EVA | |
| rs3388992655 | 107 | S>G | No | EVA | |
| rs219613963 | 107 | S>N | No | EVA | |
| rs3388946901 | 118 | P>T | No | EVA | |
| rs3399426434 | 129 | A>D | No | EVA | |
| rs3388964645 | 165 | T>S | No | EVA | |
| rs3388970717 | 175 | T>I | No | EVA | |
| rs3388970769 | 202 | P>L | No | EVA | |
| rs3388992632 | 209 | P>S | No | EVA | |
| rs3388991513 | 246 | K>N | No | EVA | |
| rs3388987428 | 260 | L>S | No | EVA | |
| rs3399266542 | 280 | E>V | No | EVA | |
| rs3399169755 | 282 | P>H | No | EVA | |
| rs3399425953 | 284 | D>E | No | EVA | |
| rs3399063621 | 285 | H>L | No | EVA | |
| rs3398433864 | 288 | G>A | No | EVA | |
| rs224531182 | 289 | R>Q | No | EVA | |
| rs3388995721 | 290 | L>M | No | EVA | |
| rs3388946879 | 332 | R>Q | No | EVA | |
| rs3388946873 | 338 | N>S | No | EVA | |
| rs240235291 | 346 | S>N | No | EVA | |
| rs3388992792 | 374 | R>W | No | EVA | |
| rs3388995781 | 377 | S>R | No | EVA | |
| rs3388976453 | 386 | G>W | No | EVA | |
| rs3388998805 | 483 | I>F | No | EVA | |
| rs3388964573 | 489 | R>M | No | EVA | |
| rs3388991599 | 501 | Q>H | No | EVA | |
| rs3388981745 | 503 | K>E | No | EVA | |
| rs3388995760 | 540 | S>P | No | EVA | |
| rs3388992977 | 575 | S>F | No | EVA | |
| rs229907588 | 602 | G>S | No | EVA | |
| rs3399169742 | 603 | P>H | No | EVA | |
| rs3388998808 | 611 | K>R | No | EVA | |
| rs3388946923 | 621 | F>I | No | EVA | |
| rs3388995590 | 641 | S>R | No | EVA | |
| rs3388964630 | 642 | G>R | No | EVA | |
| rs3388988361 | 645 | F>C | No | EVA | |
| rs3388995717 | 657 | A>V | No | EVA | |
| rs13471860 | 744 | D>A | No | EVA | |
| rs3388992779 | 754 | T>N | No | EVA | |
| rs3388995545 | 761 | A>V | No | EVA | |
| rs3388998719 | 771 | G>D | No | EVA | |
| rs3388964577 | 782 | T>P | No | EVA | |
| rs3388987432 | 797 | T>M | No | EVA | |
| rs3388987477 | 809 | L>I | No | EVA | |
| rs3388992967 | 812 | M>T | No | EVA | |
| rs3388995241 | 873 | K>R | No | EVA |
No associated diseases with P70268
5 regional properties for P70268
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Calcineurin-like phosphoesterase domain, ApaH type | 235 - 429 | IPR004843 |
| domain | Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase | 203 - 479 | IPR006186 |
| repeat | Tetratricopeptide repeat | 62 - 95 | IPR019734-1 |
| repeat | Tetratricopeptide repeat | 96 - 129 | IPR019734-2 |
| domain | PP5, C-terminal metallophosphatase domain | 176 - 490 | IPR041753 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.13 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
7 GO annotations of cellular component
| Name | Definition |
|---|---|
| cleavage furrow | The cleavage furrow is a plasma membrane invagination at the cell division site. The cleavage furrow begins as a shallow groove and eventually deepens to divide the cytoplasm. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoplasmic vesicle | A vesicle found in the cytoplasm of a cell. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| midbody | A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
13 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| chromatin binding | Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. |
| diacylglycerol-dependent serine/threonine kinase activity | Catalysis of the reaction |
| histone binding | Binding to a histone, any of a group of water-soluble proteins found in association with the DNA of eukaryotic or archaeal chromosomes. They are involved in the condensation and coiling of chromosomes during cell division and have also been implicated in gene regulation and DNA replication. They may be chemically modified (methylated, acetlyated and others) to regulate gene transcription. |
| histone deacetylase binding | Binding to histone deacetylase. |
| histone H3T11 kinase activity | Catalysis of the reaction |
| nuclear androgen receptor binding | Binding to a nuclear androgen receptor. |
| nuclear receptor coactivator activity | A transcription coactivator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound nuclear receptor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction |
| protein kinase C binding | Binding to protein kinase C. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| small GTPase binding | Binding to a small monomeric GTPase. |
15 GO annotations of biological process
| Name | Definition |
|---|---|
| B cell apoptotic process | Any apoptotic process in a B cell, a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity. |
| B cell homeostasis | The process of regulating the proliferation and elimination of B cells such that the total number of B cells within a whole or part of an organism is stable over time in the absence of an outside stimulus. |
| epithelial cell migration | The orderly movement of an epithelial cell from one site to another, often during the development of a multicellular organism. |
| hyperosmotic response | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of detection of, or exposure to, a hyperosmotic environment, i.e. an environment with a higher concentration of solutes than the organism or cell. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| negative regulation of B cell proliferation | Any process that stops, prevents or reduces the rate or extent of B cell proliferation. |
| negative regulation of protein phosphorylation | Any process that stops, prevents or reduces the rate of addition of phosphate groups to amino acids within a protein. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| post-translational protein modification | The process of covalently altering one or more amino acids in a protein after the protein has been completely translated and released from the ribosome. |
| regulation of cell motility | Any process that modulates the frequency, rate or extent of cell motility. |
| regulation of germinal center formation | Any process that modulates the frequency, rate, or extent of germinal center formation. |
| regulation of immunoglobulin production | Any process that modulates the frequency, rate, or extent of immunoglobulin production. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| renal system process | A organ system process carried out by any of the organs or tissues of the renal system. The renal system maintains fluid balance, and contributes to electrolyte balance, acid/base balance, and disposal of nitrogenous waste products. In humans, the renal system comprises a pair of kidneys, a pair of ureters, urinary bladder, urethra, sphincter muscle and associated blood vessels; in other species, the renal system may comprise related structures (e.g., nephrocytes and malpighian tubules in Drosophila). |
| spleen development | The process whose specific outcome is the progression of the spleen over time, from its formation to the mature structure. The spleen is a large vascular lymphatic organ composed of white and red pulp, involved both in hemopoietic and immune system functions. |
38 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P24583 | PKC1 | Protein kinase C-like 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| A1A4I4 | PKN1 | Serine/threonine-protein kinase N1 | Bos taurus (Bovine) | SS |
| P83099 | Pkcdelta | Putative protein kinase C delta type homolog | Drosophila melanogaster (Fruit fly) | PR |
| A1Z7T0 | Pkn | Serine/threonine-protein kinase N | Drosophila melanogaster (Fruit fly) | SS |
| Q04759 | PRKCQ | Protein kinase C theta type | Homo sapiens (Human) | PR |
| Q96LW2 | RSKR | Ribosomal protein S6 kinase-related protein | Homo sapiens (Human) | PR |
| Q02156 | PRKCE | Protein kinase C epsilon type | Homo sapiens (Human) | SS |
| P24723 | PRKCH | Protein kinase C eta type | Homo sapiens (Human) | SS |
| Q05655 | PRKCD | Protein kinase C delta type | Homo sapiens (Human) | SS |
| Q16513 | PKN2 | Serine/threonine-protein kinase N2 | Homo sapiens (Human) | EV |
| Q6P5Z2 | PKN3 | Serine/threonine-protein kinase N3 | Homo sapiens (Human) | SS |
| Q16512 | PKN1 | Serine/threonine-protein kinase N1 | Homo sapiens (Human) | EV |
| Q9Z2A0 | Pdpk1 | 3-phosphoinositide-dependent protein kinase 1 | Mus musculus (Mouse) | SS |
| Q02956 | Prkcz | Protein kinase C zeta type | Mus musculus (Mouse) | SS |
| Q62074 | Prkci | Protein kinase C iota type | Mus musculus (Mouse) | SS |
| Q8K045 | Pkn3 | Serine/threonine-protein kinase N3 | Mus musculus (Mouse) | SS |
| Q8BWW9 | Pkn2 | Serine/threonine-protein kinase N2 | Mus musculus (Mouse) | SS |
| P23298 | Prkch | Protein kinase C eta type | Mus musculus (Mouse) | PR |
| P16054 | Prkce | Protein kinase C epsilon type | Mus musculus (Mouse) | PR |
| Q02111 | Prkcq | Protein kinase C theta type | Mus musculus (Mouse) | PR |
| P28867 | Prkcd | Protein kinase C delta type | Mus musculus (Mouse) | PR |
| P20444 | Prkca | Protein kinase C alpha type | Mus musculus (Mouse) | SS |
| P63318 | Prkcg | Protein kinase C gamma type | Mus musculus (Mouse) | SS |
| P68404 | Prkcb | Protein kinase C beta type | Mus musculus (Mouse) | SS |
| Q60823 | Akt2 | RAC-beta serine/threonine-protein kinase | Mus musculus (Mouse) | PR |
| P31750 | Akt1 | RAC-alpha serine/threonine-protein kinase | Mus musculus (Mouse) | PR |
| Q9WUA6 | Akt3 | RAC-gamma serine/threonine-protein kinase | Mus musculus (Mouse) | PR |
| Q9ERE3 | Sgk3 | Serine/threonine-protein kinase Sgk3 | Mus musculus (Mouse) | PR |
| Q8QZV4 | Stk32c | Serine/threonine-protein kinase 32C | Mus musculus (Mouse) | PR |
| Q91VJ4 | Stk38 | Serine/threonine-protein kinase 38 | Mus musculus (Mouse) | SS |
| Q7TSE6 | Stk38l | Serine/threonine-protein kinase 38-like | Mus musculus (Mouse) | SS |
| Q64617 | Prkch | Protein kinase C eta type | Rattus norvegicus (Rat) | PR |
| P09216 | Prkce | Protein kinase C epsilon type | Rattus norvegicus (Rat) | PR |
| P09215 | Prkcd | Protein kinase C delta type | Rattus norvegicus (Rat) | PR |
| O08874 | Pkn2 | Serine/threonine-protein kinase N2 | Rattus norvegicus (Rat) | SS |
| Q63433 | Pkn1 | Serine/threonine-protein kinase N1 | Rattus norvegicus (Rat) | SS |
| P34722 | tpa-1 | Protein kinase C-like 1 | Caenorhabditis elegans | PR |
| A7MBL8 | pkn2 | Serine/threonine-protein kinase N2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MAGDAVQSEP | RSWSLLEQLG | LAGADLAAPG | VQQQLELERE | RLKREIRKEL | KLKEGAENLR |
| 70 | 80 | 90 | 100 | 110 | 120 |
| RATTDLGRSL | APVELLLRGS | ARRLDLLHQQ | LQELHAHVVL | PDPAAGSDAT | QSLAEGSPIC |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SSTNLSRVAG | LEKQLAIELK | VKQGAENMIQ | TYSNGSSKDR | KLLLTAQQML | QDSKTKIDII |
| 190 | 200 | 210 | 220 | 230 | 240 |
| RMQLRRALQA | LQAGELESQA | APDEAQGDPE | LGAVELRIEE | LRHHFRVEHA | VAEGAKNVLR |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LLSGAKAPDR | KAVSEAQEKL | TESNQKLGLL | RESLERRLGE | LPADHPKGRL | LREELTAASS |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SAFSAILPGP | FPATHYSTLS | KPAPLTGTLE | VRVVGCKNLP | ETIPWSPPPS | VGASGTPESR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| TPFLSRPARG | LYSRSGSLSG | RSSLRGEAEN | ATEVSTVLKL | DNTVVGQTAW | KPCGPNAWDQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| SFTLELERAR | ELELAVFWRD | QRGLCALKFL | KLEDFLDNER | HEVQLDMEPQ | GCLVAEVTFR |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NPIIERIPRL | QRQKKIFSKQ | QGKAFQRARQ | MNIDVATWVR | LLRRLIPSAV | ATGTFSPNAS |
| 550 | 560 | 570 | 580 | 590 | 600 |
| PGAEIRHTGD | ISMEKLNLGA | DSDSSSQKSP | PGLPSTSCSL | SSPTHESTTS | PELPSETQET |
| 610 | 620 | 630 | 640 | 650 | 660 |
| PGPGLCSPLR | KSPLTLEDFK | FLAVLGRGHF | GKVLLSEFRS | SGELFAIKAL | KKGDIVARDE |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VESLMCEKRI | LAAVTRAGHP | FLVNLFGCFQ | TPEHVCFVME | YSAGGDLMLH | IHSDVFSEPR |
| 730 | 740 | 750 | 760 | 770 | 780 |
| AVFYSACVVL | GLQFLHEHKI | VYRDLKLDNL | LLDTEGYVKI | ADFGLCKEGM | GYGDRTSTFC |
| 790 | 800 | 810 | 820 | 830 | 840 |
| GTPEFLAPEV | LTDTSYTRAV | DWWGLGVLLY | EMLVGESPFP | GDDEEEVFDS | IVNDEVRYPR |
| 850 | 860 | 870 | 880 | 890 | 900 |
| FLSAEAIGIM | RRLLRRNPER | RLGSTERDAE | DVKKQPFFRS | LGWDVLLARR | LPPPFVPTLS |
| 910 | 920 | 930 | 940 | ||
| GRTDVSNFDE | EFTGEAPTLS | PPRDARPLTA | AEQAAFRDFD | FVAGGY |