S_TK_XExtension to Ser/Thr-type protein kinases |
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| SMART accession number: | SM00133 |
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| Description: | |
| Interpro abstract (IPR000961): | Protein kinases are a group of enzymes that possess a catalytic subunit which transfers the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine specific and tyrosine specific (PUBMED:3291115). Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens. Protein kinases play a role in a mulititude of cellular processes, including division, proliferation, apoptosis, and differentiation (PUBMED:12368087). Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved (PUBMED:15078142), leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases (PUBMED:15320712). This domain is found in a large variety of protein kinases with different functions and dependencies. Protein kinase C, for example, is a calcium-activated, phospholipid-dependent serine- and threonine-specific enzyme. It is activated by diacylglycerol which, in turn, phosphorylates a range of cellular proteins. This domain is most often found associated with IPR000719. |
| GO process: | protein amino acid phosphorylation (GO:0006468) |
| GO function: | protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524) |
| Family alignment: |
There are 2719 S_TK_X domains in 2713 proteins in SMART's nrdb database.
Click on the following links for more information.
- Evolution (species in which this domain is found)
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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes - Disease (disease genes where sequence variants are found in this domain)
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SwissProt sequences and OMIM curated human diseases associated with missense mutations within the S_TK_X domain.
Protein Disease Protein kinase C gamma type (SRS)(SMART) OMIM:176980: PROTEIN KINASE C, GAMMA; PRKCG Rhodopsin kinase precursor (SRS)(SMART) OMIM:180381: Oguchi disease-2
OMIM:258100: - Metabolism (metabolic pathways involving proteins which contain this domain)
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Click the image to view the interactive version of the map in iPath% proteins involved KEGG pathway ID Description 6.60 map04010 MAPK signaling pathway 4.74 map04720 Long-term potentiation 4.74 map04910 Insulin signaling pathway 4.64 map04530 Tight junction 4.49 map04914 Progesterone-mediated oocyte maturation 4.20 map04310 Wnt signaling pathway 4.20 map04540 Gap junction 3.42 map04510 Focal adhesion 3.42 map04012 ErbB signaling pathway 3.37 map04020 Calcium signaling pathway 3.37 map04916 Melanogenesis 3.37 map04150 mTOR signaling pathway 3.13 map04210 Apoptosis 2.78 map04740 Olfactory transduction 2.59 map04370 VEGF signaling pathway 2.59 map05214 Glioma 2.59 map05223 Non-small cell lung cancer 2.25 map04670 Leukocyte transendothelial migration 2.25 map04730 Long-term depression 2.00 map05221 Acute myeloid leukemia 1.95 map04742 Taste transduction 1.95 map04912 GnRH signaling pathway 1.95 map04340 Hedgehog signaling pathway 1.66 map04350 TGF-beta signaling pathway 1.42 map04070 Phosphatidylinositol signaling system 1.42 map04650 Natural killer cell mediated cytotoxicity 1.17 map05222 Small cell lung cancer 1.17 map05213 Endometrial cancer 1.17 map04662 B cell receptor signaling pathway 1.17 map05212 Pancreatic cancer 1.17 map04630 Jak-STAT signaling pathway 1.17 map05220 Chronic myeloid leukemia 1.17 map04920 Adipocytokine signaling pathway 1.17 map04664 Fc epsilon RI signaling pathway 1.17 map05210 Colorectal cancer 1.17 map04620 Toll-like receptor signaling pathway 1.17 map05215 Prostate cancer 1.17 map04660 T cell receptor signaling pathway 1.17 map05211 Renal cell carcinoma 1.17 map05218 Melanoma 0.83 map04810 Regulation of actin cytoskeleton 0.83 map04360 Axon guidance 0.29
map00632Benzoate degradation via CoA ligation 0.29
map00562Inositol phosphate metabolism 0.24 map04111 Cell cycle - yeast This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with S_TK_X domain which could be assigned to a KEGG orthologous group, and not all proteins containing S_TK_X domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of S_TK_X domains in PDB
PDB code Main view Title 1apm 
2.0 angstrom refined crystal structure of the catalytic subunit of camp-dependent protein kinase complexed with a peptide inhibitor and detergent 1atp 
2.2 angstrom refined crystal structure of the catalytic subunit of camp-dependent protein kinase complexed with mnatp and a peptide inhibitor 1bkx 
A binary complex of the catalytic subunit of camp-dependent protein kinase and adenosine further defines conformational flexibility 1bx6 
Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of camp- dependent protein kinase 1cdk 
Camp-dependent protein kinase catalytic subunit (e.c.2.7.1.37) (protein kinase a) complexed with protein kinase inhibitor peptide fragment 5-24 (pki(5-24) isoelectric variant ca) and mn2+ adenylyl imidodiphosphate (mnamp-pnp) at ph 5.6 and 7c and 4c 1cmk 
Crystal structures of the myristylated catalytic subunit of camp-dependent protein kinase reveal open and closed conformations 1ctp 
Structure of the mammalian catalytic subunit of camp- dependent protein kinase and an inhibitor peptide displays an open conformation 1fmo 
Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of camp-dependent protein kinase complexed with the peptide inhibitor pki(5-24) and adenosine 1fot 
Structure of the unliganded camp-dependent protein kinase catalytic subunit from saccharomyces cerevisiae 1gzk 
Molecular mechanism for the regulation of protein kinase b/ akt by hydrophobic motif phosphorylation 1gzn 
Structure of pkb kinase domain 1gzo 
Structure of protein kinase b unphosphorylated 1j3h 
Crystal structure of apoenzyme camp-dependent protein kinase catalytic subunit 1jbp 
Crystal structure of the catalytic subunit of camp- dependent protein kinase complexed with a substrate peptide, adp and detergent 1jlu 
Crystal structure of the catalytic subunit of camp- dependent protein kinase complexed with a phosphorylated substrate peptide and detergent 1l3r 
Crystal structure of a transition state mimic of the catalytic subunit of camp-dependent protein kinase 1mrv 
Crystal structure of an inactive akt2 kinase domain 1mry 
Crystal structure of an inactive akt2 kinase domain 1o6k 
Structure of activated form of pkb kinase domain s474d with gsk3 peptide and amp-pnp 1o6l 
Crystal structure of an activated akt/protein kinase b (pkb- pif chimera) ternary complex with amp-pnp and gsk3 peptide 1omw 
Crystal structure of the complex between g protein-coupled receptor kinase 2 and heterotrimeric g protein beta 1 and gamma 2 subunits 1q24 
Pka double mutant model of pkb in complex with mgatp 1q61 
Pka triple mutant model of pkb 1q62 
Pka double mutant model of pkb 1q8t 
The catalytic subunit of camp-dependent protein kinase (pka) in complex with rho-kinase inhibitor y-27632 1q8u 
The catalytic subunit of camp-dependent protein kinase in complex with rho-kinase inhibitor h-1152p 1q8w 
The catalytic subunit of camp-dependent protein kinase in complex with rho-kinase inhibitor fasudil (ha-1077) 1rdq 
Hydrolysis of atp in the crystal of y204a mutant of camp- dependent protein kinase 1re8 
Crystal structure of camp-dependent protein kinase complexed with balanol analog 2 1rej 
Crystal structure of camp-dependent protein kinase complexed with balanol analog 1 1rek 
Crystal structure of camp-dependent protein kinase complexed with balanol analog 8 1smh 
Protein kinase a variant complex with completely ordered n- terminal helix 1stc 
Camp-dependent protein kinase, alpha-catalytic subunit in complex with staurosporine 1sve 
Crystal structure of protein kinase a in complex with azepane derivative 1 1svg 
Crystal structure of protein kinase a in complex with azepane derivative 4 1svh 
Crystal structure of protein kinase a in complex with azepane derivative 8 1syk 
Crystal structure of e230q mutant of camp-dependent protein kinase reveals unexpected apoenzyme conformation 1szm 
Dual binding mode of bisindolylmaleimide 2 to protein kinase a (pka) 1veb 
Crystal structure of protein kinase a in complex with azepane derivative 5 1xh4 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xh5 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xh6 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xh7 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xh8 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xh9 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xha 
Crystal structures of protein kinase b selective inhibitors in complex with protein kinase a and mutants 1xjd 
Crystal structure of pkc-theta complexed with staurosporine at 2a resolution 1ydr 
Structure of camp-dependent protein kinase, alpha-catalytic subunit in complex with h7 protein kinase inhibitor 1-(5- isoquinolinesulfonyl)-2-methylpiperazine 1yds 
Structure of camp-dependent protein kinase, alpha-catalytic subunit in complex with h8 protein kinase inhibitor [n-(2- methylamino)ethyl]-5-isoquinolinesulfonamide 1ydt 
Structure of camp-dependent protein kinase, alpha-catalytic subunit in complex with h89 protein kinase inhibitor n-[2- (4-bromocinnamylamino)ethyl]-5-isoquinoline 1ym7 
G protein-coupled receptor kinase 2 (grk2) 1zrz 
Crystal structure of the catalytic domain of atypical protein kinase c-iota 2acx 
Crystal structure of g protein coupled receptor kinase 6 bound to amppnp 2bcj 
Crystal structure of g protein-coupled receptor kinase 2 in complex with galpha-q and gbetagamma subunits 2c1a 
Structure of camp-dependent protein kinase complexed with isoquinoline-5-sulfonic acid (2-(2-(4-chlorobenzyloxy) ethylamino)ethyl)amide 2c1b 
Structure of camp-dependent protein kinase complexed with (4r,2s)-5'-(4-(4-chlorobenzyloxy)pyrrolidin-2- ylmethanesulfonyl)isoquinoline 2cpk 
Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase 2erz 
Crystal structure of c-amp dependent kinase (pka) bound to hydroxyfasudil 2esm 
Crystal structure of rock 1 bound to fasudil 2etk 
Crystal structure of rock 1 bound to hydroxyfasudil 2etr 
Crystal structure of rock i bound to y-27632 2f2u 
Crystal structure of the rho-kinase kinase domain 2f7e 
Pka complexed with (s)-2-(1h-indol-3-yl)-1-(5-isoquinolin-6- yl-pyridin-3-yloxymethyl-etylamine 2f7x 
Protein kinase a bound to (s)-2-(1h-indol-3-yl)-1-[5-((e)-2- pyridin-4-yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine 2f7z 
Protein kinase a bound to (r)-1-(1h-indol-3-ylmethyl)-2-(2- pyridin-4-yl-[1,7]naphtyridin-5-yloxy)-ehylamine 2gfc 
Camp-dependent protein kinase pka catalytic subunit with pki-5-24 2gnf 
Protein kinase a fivefold mutant model of rho-kinase with y- 2gng 
Protein kinase a fivefold mutant model of rho-kinase 2gnh 
Pka five fold mutant model of rho-kinase with h1152p 2gni 
Pka fivefold mutant model of rho-kinase with inhibitor fasudil (ha1077) 2gnj 
Pka three fold mutant model of rho-kinase with y-27632 2gnl 
Pka threefold mutant model of rho-kinase with inhibitor h- 1152p 2gu8 
Discovery of 2-pyrimidyl-5-amidothiophenes as novel and potent inhibitors for akt: synthesis and sar studies 2h9v 
Structural basis for induced-fit binding of rho-kinase to the inhibitor y27632 2i0e 
Structure of catalytic domain of human protein kinase c beta ii complexed with a bisindolylmaleimide inhibitor 2jdo 
Structure of pkb-beta (akt2) complexed with isoquinoline-5- sulfonic acid (2-(2-(4-chlorobenzyloxy) ethylamino)ethyl) amide 2jdr 
Structure of pkb-beta (akt2) complexed with the inhibitor a- 2jds 
Structure of camp-dependent protein kinase complexed with a- 2jdt 
Structure of pka-pkb chimera complexed with isoquinoline-5- sulfonic acid (2-(2-(4-chlorobenzyloxy) ethylamino)ethyl) amide 2jdv 
Structure of pka-pkb chimera complexed with a-443654 2jed 
The crystal structure of the kinase domain of the protein kinase c theta in complex with nvp-xaa228 at 2.32a resolution. 2oh0 
Crystal structure of protein kinase a in complex with pyridine-pyrazolopyridine based inhibitors 2ojf 
Crystal structure of protein kinase a in complex with pyridine-pyrazolopyridine based inhibitors 2qcs 
A complex structure between the catalytic and regulatory subunit of protein kinase a that represents the inhibited state 2qur 
Crystal structure of f327a/k285p mutant of camp-dependent protein kinase 2qvs 
Crystal structure of type iia holoenzyme of camp-dependent protein kinase 2r5t 
2uvx 
Structure of pka-pkb chimera complexed with 7-azaindole 2uvy 
Structure of pka-pkb chimera complexed with methyl-(4-(9h- purin-6-yl)-benzyl)-amine 2uvz 
Structure of pka-pkb chimera complexed with c-phenyl-c-(4-( 9h-purin-6-yl)-phenyl)-methylamine 2uw0 
Structure of pka-pkb chimera complexed with 6-(4-(4-(4- chloro-phenyl)-piperidin-4-yl)-phenyl)-9h-purine 2uw3 
Structure of pka-pkb chimera complexed with 5-methyl-4- phenyl-1h-pyrazole 2uw4 
Structure of pka-pkb chimera complexed with 2-(4-(5-methyl- 1h-pyrazol-4-yl)-phenyl)-ethylamine 2uw5 
Structure of pka-pkb chimera complexed with (r)-2-(4- chloro-phenyl)-2-(4-1h-pyrazol-4-yl)-phenyl)-ethylamine 2uw6 
Structure of pka-pkb chimera complexed with (s)-2-(4- chloro-phenyl)-2-(4-1h-pyrazol-4-yl)-phenyl)-ethylamine 2uw7 
Structure of pka-pkb chimera complexed with 4-(4-chloro- phenyl)-4-(4-(1h-pyrazol-4-yl)-phenyl)-piperidine 2uw8 
Structure of pka-pkb chimera complexed with 2-(4-chloro- phenyl)-2-phenyl-ethylamine 2uw9 
Structure of pkb-beta (akt2) complexed with 4-(4-chloro- phenyl)-4-(4-(1h-pyrazol-4-yl)-phenyl)-piperidine 2uzt 
Pka structures of akt, indazole-pyridine inhibitors 2uzu 
Pka structures of indazole-pyridine series of akt inhibitors 2uzv 
Pka structures of indazole-pyridine series of akt inhibitors 2uzw 
Pka structures of indazole-pyridine series of akt inhibitors 2v55 
2vd5 
Structure of human myotonic dystrophy protein kinase in complex with the bisindoylmaleide inhibitor bim viii 2vnw 
Structure of pka-pkb chimera complexed with (1-(9h-purin-6- yl)piperidin-4-yl)methanamine 2vny 
Structure of pka-pkb chimera complexed with (1-(9h-purin-6- yl)piperidin-4-yl)amine 2vo0 
Structure of pka-pkb chimera complexed with c-(4-(4- chlorophenyl)-1-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)piperidin- 4-yl)methylamine 2vo3 
Structure of pka-pkb chimera complexed with c-(4-(4- chlorophenyl)-1-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)piperidin- 4-yl)methylamine 2vo6 
Structure of pka-pkb chimera complexed with 4-(4- chlorobenzyl)-1-(7h-pyrrolo(2,3-d)pyrimidin-4-yl)piperidin- 4-ylamine 2vo7 
Structure of pka complexed with 4-(4-chlorobenzyl)-1-(7h- pyrrolo(2,3-d)pyrimidin-4-yl)piperidin-4-ylamine 2z7q 
Crystal structure of the n-terminal kinase domain of human rsk-1 bound to amp-pcp 2z7r 
Crystal structure of the n-terminal kinase domain of human rsk1 bound to staurosporine 2z7s 
Crystal structure of the n-terminal kinase domain of human rsk1 bound to purvalnol a 3a60 
3a61 
3a62 
3bwj 
3c4w 
Crystal structure of g protein coupled receptor kinase 1 bound to atp and magnesium chloride at 2.7a 3c4x 
Crystal structure of g protein coupled receptor kinase 1 bound to atp and magnesium chloride at 2.9a 3c4y 
Crystal structure of apo form of g protein coupled receptor kinase 1 at 7.51a 3c4z 
Crystal structure of g protein coupled receptor kinase 1 bound to adp and magnesium chloride at 1.84a 3c50 
Crystal structure of g protein coupled receptor kinase 1 bound to adp and magnesium chloride at 2.6a 3c51 
Crystal structure of g protein coupled receptor kinase 1 bound to adp and magnesium chloride at 3.55a 3cik 
3cqu 
Crystal structure of akt-1 complexed with substrate peptide and inhibitor 3cqw 
Crystal structure of akt-1 complexed with substrate peptide and inhibitor 3d0e 
3d9v 
Crystal structure of rock i bound to h-1152p a di- methylated variant of fasudil 3dnd 
3dne 
3e87 
3e88 
3e8c 
3e8d 
3e8e 
3fhi 
3fjq 
3hdm 
3hdn 
3idb 
3idc 
3iw4 
- Links (links to other resources describing this domain)
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INTERPRO IPR000961






