Pseudokinase

Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life.wikipedia
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Protein kinase

protein kinasestransmembranekinases
Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life.
Protein kinases are also found in bacteria and plants, and include the pseudokinase sub-family, which exhibit unusual features including atypical nucleotide binding and weak, or no, catalytic activity and are part of a much larger pseudoenzyme group of 'degraded' enzyme relatives that are found throughout life, where they take an active participation in mechanistic cellular signaling.

Pseudoenzyme

pseudoenzymeslack the active site residuespseudoenzyme analysis
Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A, which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix.
The most intensively analyzed, and certainly the best understood pseudoenzymes in terms of cellular signalling functions are probably the pseudokinases, the pseudoproteases and the pseudophosphatases.

Kinome

Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Several pseudokinase-containing families are found in the human kinome, including the Tribbles pseudokinases, which are at the interface between kinase and ubiquitin E3 ligase signalling. A comprehensive evolutionary analysis confirms that pseudokinases group into multiple subfamilies, and these are found in the annotated kinome of organisms across the kingdoms of life, including prokaryotes, archaea and all eukaryotic lineages with an annotated proteome; this data is searchable in ProKino (http://vulcan.cs.uga.edu/prokino/about/browser).
Although the primary sequence of protein kinases shows substantial divergence between unrelated eukaryotes, and amino acid differences in catalytic motifs have permitted their separation of kinomes into canonical and pseudokinase subtypes, the variation found in the amino acid motifs adjacent to the site of actual phosphorylation of substrates by eukaryotic kinases is much smaller.

Protein phosphatase

phosphoprotein phosphataseprotein phosphatases
Examples of membrane-spanning protein phosphatases containing both active (phosphatase) and inactive (pseudophosphatase) domains linked in tandem are known, conceptually similar to the kinase and pseudokinase domain polypeptide structure of the JAK pseudokinases.

Signal transduction

signaling pathwayssignaling cascadesignal transduction pathways
Pseudokinases have both physiological (signal transduction) and pathophysiological functions.

Pathophysiology

pathophysiologicalpathophysiologicpathophysiologist
Pseudokinases have both physiological (signal transduction) and pathophysiological functions.

Ubiquitin ligase

E3 ubiquitin ligaseE3 ligaseubiquitin ligases
Several pseudokinase-containing families are found in the human kinome, including the Tribbles pseudokinases, which are at the interface between kinase and ubiquitin E3 ligase signalling.

Biological target

drug targettargettherapeutic target
The human pseudokinases (and their pseudophosphatase cousins) are implicated in a wide variety of diseases, which has made them potential drug targets and antitargets).

Antitarget

off-target
The human pseudokinases (and their pseudophosphatase cousins) are implicated in a wide variety of diseases, which has made them potential drug targets and antitargets).

FAM20A

Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A, which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix.

Adenosine triphosphate

ATPadenosine triphosphate (ATP)adenosine 5'-triphosphate
Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A, which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix.

Glutamic acid

glutamateL-glutamateGlu
Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A, which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix.

Glutamine

GlnL-glutamine L -glutamine
Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A, which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix.

Periodontal disease

periodontitisgum diseaseperiodontal diseases
FAM20A is implicated in periodontal disease, and serves to control the catalytic activity of FAM20C, an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein.

FAM20C

FAM20A is implicated in periodontal disease, and serves to control the catalytic activity of FAM20C, an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein.

Phosphorylation

phosphorylatedphosphorylatephosphorylates
FAM20A is implicated in periodontal disease, and serves to control the catalytic activity of FAM20C, an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein.

Golgi apparatus

GolgiGolgi complextrans-Golgi network
FAM20A is implicated in periodontal disease, and serves to control the catalytic activity of FAM20C, an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein.

Casein

sodium caseinatemicellar caseincasein protein
FAM20A is implicated in periodontal disease, and serves to control the catalytic activity of FAM20C, an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein.

Proteome

proteomesproteomicprotein expression
A comprehensive evolutionary analysis confirms that pseudokinases group into multiple subfamilies, and these are found in the annotated kinome of organisms across the kingdoms of life, including prokaryotes, archaea and all eukaryotic lineages with an annotated proteome; this data is searchable in ProKino (http://vulcan.cs.uga.edu/prokino/about/browser).

Protein kinase A

PKAcAMP-dependent protein kinasecyclic AMP-dependent protein kinase
PKA acts as a model for understanding protein kinase biology, with the position of the conserved residues helping to distinguish the active protein kinase and inactive pseudokinase members of the human kinome.

TRIB2

TRIB2 is a pseudokinase member of the (pseudoenzyme) class of signaling/scaffold proteins, possessing little vestigial catalytic output in vitro.

Enamel-renal syndrome

This gene encodes a protein - the Golgi apparatus associated secretory pathway pseudokinase.

CAMK

Ca2+/calmodulin-dependent protein kinaseCaMKIICa 2+ /calmodulin-dependent protein kinase