Q8BWW9
SS
Gene name |
Pkn2 (Prk2, Prkcl2) |
Protein name |
Serine/threonine-protein kinase N2 |
Names |
EC 2.7.11.13 , PKN gamma , Protein kinase C-like 2 , Protein-kinase C-related kinase 2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:109333 |
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 |
656-915 (Protein kinase domain) |
Relief mechanism |
Ligand binding, PTM |
Assay |
|
Accessory elements
798-821 (Activation loop from InterPro)
Target domain |
656-915 (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 Q8BWW9
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8BWW9-F1 | Predicted | AlphaFoldDB |
36 variants for Q8BWW9
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388661762 | 30 | A>D | No | EVA | |
| rs3388649350 | 31 | V>G | No | EVA | |
| rs3388664458 | 55 | E>D | No | EVA | |
| rs3388670544 | 87 | K>I | No | EVA | |
| rs3388668004 | 94 | E>* | No | EVA | |
| rs3388649379 | 202 | E>D | No | EVA | |
| rs3388663969 | 223 | R>SE* | No | EVA | |
| rs3388665507 | 224 | H>D | No | EVA | |
| rs3388665469 | 265 | S>G | No | EVA | |
| rs3388655508 | 274 | S>* | No | EVA | |
| rs3413091441 | 289 | S>G | No | EVA | |
| rs226158813 | 300 | A>T | No | EVA | |
| rs259400913 | 310 | M>T | No | EVA | |
| rs31076655 | 315 | N>S | No | EVA | |
| rs3388668582 | 410 | P>S | No | EVA | |
| rs3393803794 | 439 | W>* | No | EVA | |
| rs3388660346 | 441 | S>Y | No | EVA | |
| rs3388655906 | 497 | K>* | No | EVA | |
| rs3388666782 | 559 | D>G | No | EVA | |
| rs3388665482 | 629 | D>E | No | EVA | |
| rs3388660353 | 665 | G>V | No | EVA | |
| rs3388671394 | 668 | G>E | No | EVA | |
| rs3388668599 | 682 | F>S | No | EVA | |
| rs3388666698 | 689 | K>* | No | EVA | |
| rs3388670507 | 694 | A>T | No | EVA | |
| rs3388671353 | 825 | P>T | No | EVA | |
| rs3388663310 | 836 | A>V | No | EVA | |
| rs3388663910 | 839 | W>G | No | EVA | |
| rs3393812119 | 893 | R>I | No | EVA | |
| rs3388655981 | 900 | G>V | No | EVA | |
| rs3388663975 | 951 | S>L | No | EVA | |
| rs31075246 | 964 | I>V | No | EVA | |
| rs218714099 | 967 | E>Q | No | EVA | |
| rs248278710 | 971 | E>D | No | EVA | |
| rs3388649393 | 979 | V>I | No | EVA | |
| rs3388663919 | 980 | A>T | No | EVA |
No associated diseases with Q8BWW9
11 regional properties for Q8BWW9
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 329 - 472 | IPR000008 |
| domain | Protein kinase domain | 656 - 915 | IPR000719 |
| domain | AGC-kinase, C-terminal | 916 - 983 | IPR000961 |
| active_site | Serine/threonine-protein kinase, active site | 777 - 789 | IPR008271 |
| domain | HR1 rho-binding domain | 33 - 110 | IPR011072-1 |
| domain | HR1 rho-binding domain | 121 - 204 | IPR011072-2 |
| domain | HR1 rho-binding domain | 204 - 285 | IPR011072-3 |
| binding_site | Protein kinase, ATP binding site | 662 - 685 | IPR017441 |
| domain | Protein kinase, C-terminal | 936 - 978 | IPR017892 |
| domain | Serine/threonine-protein kinase N, first HR1 domain | 42 - 107 | IPR037313 |
| domain | Serine/threonine-protein kinase N, C2 domain | 389 - 472 | IPR037784 |
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 | |
12 GO annotations of cellular component
| Name | Definition |
|---|---|
| apical junction complex | A functional unit located near the cell apex at the points of contact between epithelial cells, which in vertebrates is composed of the tight junction, the zonula adherens, and desmosomes and in some invertebrates, such as Drosophila, is composed of the subapical complex (SAC), the zonula adherens and the septate junction. Functions in the regulation of cell polarity, tissue integrity and intercellular adhesion and permeability. |
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| 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. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| intermediate filament cytoskeleton | Cytoskeletal structure made from intermediate filaments, typically organized in the cytosol as an extended system that stretches from the nuclear envelope to the plasma membrane. Some intermediate filaments run parallel to the cell surface, while others traverse the cytosol; together they form an internal framework that helps support the shape and resilience of the cell. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| 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. |
| nuclear body | Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins. |
| 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. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| 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. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| diacylglycerol-dependent serine/threonine kinase activity | Catalysis of the reaction |
| histone deacetylase binding | Binding to histone deacetylase. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| RNA polymerase binding | Binding to an RNA polymerase molecule or complex. |
| small GTPase binding | Binding to a small monomeric GTPase. |
13 GO annotations of biological process
| Name | Definition |
|---|---|
| apical junction assembly | The formation of an apical junction, a functional unit located near the cell apex at the points of contact between epithelial cells composed of the tight junction, the zonula adherens junction and the desmosomes, by the aggregation, arrangement and bonding together of its constituents. |
| apoptotic process | A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. |
| cell adhesion | The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. |
| cell cycle | The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. |
| cell division | The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells. |
| cell projection organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a prolongation or process extending from a cell, e.g. a flagellum or axon. |
| epithelial cell migration | The orderly movement of an epithelial cell from one site to another, often during the development of a multicellular organism. |
| 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. |
| positive regulation of cytokinesis | Any process that activates or increases the frequency, rate or extent of the division of the cytoplasm of a cell, and its separation into two daughter cells. |
| positive regulation of mitotic cell cycle | Any process that activates or increases the rate or extent of progression through the mitotic cell cycle. |
| positive regulation of viral genome replication | Any process that activates or increases the frequency, rate or extent of viral genome replication. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of cell motility | Any process that modulates the frequency, rate or extent of cell motility. |
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 |
| Q16512 | PKN1 | Serine/threonine-protein kinase N1 | Homo sapiens (Human) | EV |
| Q6P5Z2 | PKN3 | Serine/threonine-protein kinase N3 | Homo sapiens (Human) | SS |
| Q16513 | PKN2 | Serine/threonine-protein kinase N2 | 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 |
| P70268 | Pkn1 | Serine/threonine-protein kinase N1 | Mus musculus (Mouse) | SS |
| Q8K045 | Pkn3 | Serine/threonine-protein kinase N3 | 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 |
| Q63433 | Pkn1 | Serine/threonine-protein kinase N1 | Rattus norvegicus (Rat) | 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 |
| 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 |
| MASNPDRGEI | LLTELQGDSR | TLPFSENVSA | VQKLDFSDTM | VQQKLDDIKD | RIKREIRKEL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KIKEGAENLR | KVTTDKKNLA | YVDNILKKSN | KKLEELHHKL | QELNAHIVVS | DPEDSTDCPR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TPDTPNSDSR | SSTSNNRLMA | LQKQLDIELK | VKQGAENMIQ | MYSNGSSKDR | KLHGTAQQLL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QDSKTKIEVI | RMQILQAVQT | NELAFDNAKP | VISPLELRME | ELRHHFKIEF | AVAEGAKNVM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| KLLGSGKVTD | RKALSEAQAR | FNESSQKLDL | LKYSLEQRLN | ELPRNHPKSS | VVIEELSLVA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SPTLSPRQSM | LSTQNQYSTL | SKPAALTGTL | EVRLMGCQDI | LENVPGRSKA | TSVALPGWSP |
| 370 | 380 | 390 | 400 | 410 | 420 |
| SDNRSSFMSR | TSKSKSGSSR | NLLKTDDLSN | DVCAVLKLDN | TVVGQTSWKP | ISNQSWDQKF |
| 430 | 440 | 450 | 460 | 470 | 480 |
| TLELDRSREL | EISVYWRDWR | SLCAVKFLRL | EDFLDNQRHG | MCLYLEPQGT | LFAEVTFFNP |
| 490 | 500 | 510 | 520 | 530 | 540 |
| VIERRPKLQR | QKKIFSKQQG | KTFLRAPQMN | INIATWGRLV | RRAIPTVNHS | GTFSPQTPVP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| ATVPVVDARI | PDLAPPASDS | TVTKLDFDLE | PEPPPAPPRA | SSLGETDESS | ELRVLDIPGQ |
| 610 | 620 | 630 | 640 | 650 | 660 |
| GSETVFNIEN | DRNNLRPKSK | SEYELSIPDS | GRSCWGVGEL | DDKRAQQRFQ | FSLQDFRCCA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VLGRGHFGKV | LLAEYKHTNE | MFAIKALKKG | DIVARDEVDS | LMCEKRIFET | VNSVRHPFLV |
| 730 | 740 | 750 | 760 | 770 | 780 |
| NLFACFQTKE | HVCFVMEYAA | GGDLMMHIHT | DVFSEPRAVF | YAACVVLGLQ | YLHEHKIVYR |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DLKLDNLLLD | TEGFVKIADF | GLCKEGMGYG | DRTSTFCGTP | EFLAPEVLTE | TSYTRAVDWW |
| 850 | 860 | 870 | 880 | 890 | 900 |
| GLGVLIYEML | VGESPFPGDD | EEEVFDSIVN | DEVRYPRFLS | TEAISIMRRL | LRRNPERRLG |
| 910 | 920 | 930 | 940 | 950 | 960 |
| AGEKDAEDVK | KHPFFRLTDW | SALMDKKVKP | PFVPTIRGRE | DVSNFDDEFT | SEAPILTPPR |
| 970 | 980 | ||||
| EPRILLEEEQ | EMFHDFDYVA | DWC |