A8KBH6
Gene name |
prkcb (prkcb1) |
Protein name |
Protein kinase C beta type |
Names |
PKC-B , PKC-beta , EC 2.7.11.13 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
xtr:100038043 |
EC number |
2.7.10.1: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with P10721)
The c-Kit receptor protein-tyrosine kinase is tightly regulated in normal cells, whereas deregulated c-Kit kinase activity is implicated in the pathogenesis of human cancers. Crystal structures of c-Kit kinase reveal a manner in which the small juxtamembrane domain functions to maintain the kinase in an autoinhibited state. Insertion of this autoinhibitory domain into the cleft between the kinase N- and C-lobes flips the DFG motif into its off state, thereby inducing the activation loop to fold back over from its extended conformation in the active kinase where it binds as a pseudosubstrate at the kinase-active center.
Autoinhibitory domains (AIDs)
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
480-503 (Activation loop from InterPro)
Target domain |
338-660 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta) |
Relief mechanism |
|
Assay |
|
480-503 (Activation loop from InterPro)
Target domain |
338-660 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Slater SJ et al. (2002) "Regulation of PKC alpha activity by C1-C2 domain interactions", The Journal of biological chemistry, 277, 15277-85
- Jones AC et al. (2020) "Hypothesis: Unifying model of domain architecture for conventional and novel protein kinase C isozymes", IUBMB life, 72, 2584-2590
- Kirwan AF et al. (2003) "Inhibition of protein kinase C catalytic activity by additional regions within the human protein kinase Calpha-regulatory domain lying outside of the pseudosubstrate sequence", The Biochemical journal, 373, 571-81
- Steinberg SF (2008) "Structural basis of protein kinase C isoform function", Physiological reviews, 88, 1341-78
- Sommese RF et al. (2017) "The Role of Regulatory Domains in Maintaining Autoinhibition in the Multidomain Kinase PKCα", The Journal of biological chemistry, 292, 2873-2880
- Pears CJ et al. (1990) "Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation", European journal of biochemistry, 194, 89-94
- Smith MK et al. (1990) "Specificities of autoinhibitory domain peptides for four protein kinases. Implications for intact cell studies of protein kinase function", The Journal of biological chemistry, 265, 1837-40
- 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
- Wagner J et al. (2009) "Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes", Journal of medicinal chemistry, 52, 6193-6
Autoinhibited structure
Activated structure
1 structures for A8KBH6
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-A8KBH6-F1 | Predicted | AlphaFoldDB |
No variants for A8KBH6
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for A8KBH6 | |||||
No associated diseases with A8KBH6
No regional properties for A8KBH6
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for A8KBH6 | |||
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.1 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| 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. |
9 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 H3T6 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 serine kinase activity | Catalysis of the reactions |
| zinc ion binding | Binding to a zinc ion (Zn). |
9 GO annotations of biological process
| Name | Definition |
|---|---|
| adaptive immune response | An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory). |
| 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. |
| B cell activation | The change in morphology and behavior of a mature or immature B cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific. |
| B cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a B 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. |
| 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. |
| positive regulation of canonical NF-kappaB signal transduction | Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling. |
| 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 transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
18 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 |
| P04409 | PRKCA | Protein kinase C alpha type | Bos taurus (Bovine) | EV SS |
| P05128 | PRKCG | Protein kinase C gamma type | Bos taurus (Bovine) | SS |
| P05126 | PRKCB | Protein kinase C beta type | Bos taurus (Bovine) | SS |
| P13677 | inaC | Protein kinase C, eye isozyme | Drosophila melanogaster (Fruit fly) | SS |
| P05130 | Pkc53E | Protein kinase C, brain isozyme | Drosophila melanogaster (Fruit fly) | SS |
| P17252 | PRKCA | Protein kinase C alpha type | Homo sapiens (Human) | EV |
| P05129 | PRKCG | Protein kinase C gamma type | Homo sapiens (Human) | SS |
| P05771 | PRKCB | Protein kinase C beta type | Homo sapiens (Human) | SS |
| 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 |
| P05696 | Prkca | Protein kinase C alpha type | Rattus norvegicus (Rat) | SS |
| P63319 | Prkcg | Protein kinase C gamma type | Rattus norvegicus (Rat) | SS |
| P68403 | Prkcb | Protein kinase C beta type | Rattus norvegicus (Rat) | SS |
| P90980 | pkc-2 | Protein kinase C-like 2 | Caenorhabditis elegans | SS |
| Q5BKK4 | sgk1 | Serine/threonine-protein kinase Sgk1 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | PR |
| Q7SY24 | prkcbb | Protein kinase C beta type | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MRGARGAWDL | LCVLLVLLRG | QTATSQPSAS | PGEPSPPSIH | PAQSELIVEA | GDTLSLTCID |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PDFVRWTFKT | YFNEMVENKK | NEWIQEKAEA | TRTGTYTCSN | SNGLTSSIYV | FVRDPAKLFL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VGLPLFGKED | SDALVRCPLT | DPQVSNYSLI | ECDGKSLPTD | LTFVPNPKAG | ITIKNVKRAY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| HRLCVRCAAQ | RDGTWLHSDK | FTLKVRAAIK | AIPVVSVPET | SHLLKKGDTF | TVVCTIKDVS |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TSVNSMWLKM | NPQPQHIAQV | KHNSWHRGDF | NYERQETLTI | SSARVDDSGV | FMCYANNTFG |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SANVTTTLKV | VEKGFINISP | VKNTTVFVTD | GENVDLVVEY | EAYPKPEHQQ | WIYMNRTSAN |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KGKDYVKSDN | KSNIRYVNQL | RLTRLKGTEG | GTYTFLVSNS | DASASVTFNV | YVNTKPEILT |
| 430 | 440 | 450 | 460 | 470 | 480 |
| YDRLINGMLQ | CVAEGFPEPT | IDWYFCTGAE | QRCTTPVSPV | DVQVQNVSVS | PFGKLVVQSS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| IDSSVFRHNG | TVECKASNDV | GKSSAFFNFA | FKGNNKEQIQ | AHTLFTPLLI | GFVVAAGAMG |
| 550 | 560 | 570 | 580 | 590 | 600 |
| IIVMVLTYKY | LQKPMYEVQW | KVVEEINGNN | YVYIDPTQLP | YDHKWEFPRN | RLSFGKTLGA |
| 610 | 620 | 630 | 640 | 650 | 660 |
| GAFGKVVEAT | AYGLIKSDAA | MTVAVKMLKP | SAHLTEREAL | MSELKVLSYL | GNHMNIVNLL |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GACTVGGPTL | VITEYCCYGD | LLNFLRRKRD | SFIFSKQEEQ | AEAALYKNLL | HSTEPSCDSS |
| 730 | 740 | 750 | 760 | 770 | 780 |
| NEYMDMKPGV | SYVVPTKTDK | RRSARIDSYI | ERDVTPAIME | DDELALDLDD | LLSFSYQVAK |
| 790 | 800 | 810 | 820 | 830 | 840 |
| GMAFLASKNC | IHRDLAARNI | LLTHGRITKI | CDFGLARDIR | NDSNYVVKGN | ARLPVKWMAP |
| 850 | 860 | 870 | 880 | 890 | 900 |
| ESIFSCVYTF | ESDVWSYGIF | LWELFSLGSS | PYPGMPVDSK | FYKMIKEGFR | MVSPEHAPAE |
| 910 | 920 | 930 | 940 | 950 | 960 |
| MYDVMKTCWD | ADPLKRPTFK | QVVQLIEKQI | SDSTKHIYSN | LANCNPNPEN | PVVVDHSVRV |
| 970 | |||||
| NSVGSSASST | QPLLVHEDA |