PKN1 is a serine/threonine protein kinase activated by the Rho family of small GTPases, and by fatty acids such as arachidonic and linoleic acids [, ]. It is expressed ubiquitously and is the most abundant PKN isoform in neurons []. PKN1 is implicated in a variety of functions including cytoskeletal reorganization, cardiac cell survival, cell adhesion, and glucose transport, among others [, ]. PKN1 contains three HR1 domains, a C2 domain, and a kinase domain.This entry represents the second HR1 domain of PKN1. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN1 binds the GTPases RhoA, RhoB, and RhoC, and can also interact weakly with Rac [].
This superfamily represents a domain is found in sulfatase-modifying factors (SUMFs) []and Chlamydia serine/threonine-protein kinase pkn1 []. It is also found in iron(II)-dependent oxidoreductase from Mycobacterium [, ]. The structure of this domain is homologous to the complex alpha/beta topology found in sulfatase-modifying factors (SUMF1). SUMF1 is a paralogue of oxoalanine-generating enzyme, also called C(alpha)-formylglycine generating enzyme (FGE). SUMF1 converts newly synthesized inactive sulfatases to their active form by modifying an active site cysteine residue to oxoalanine. Sulfatases are essential for the degradation of sulfate esters, whose catalytic activity is dependent upon an oxoalanine residue []. Defects in SUMF1 or FGE cause multiple sulfatase deficiency (MSD), which leads to the impairment of all sulfatases and to the accumulation of glycoaminoglycans or sulfolipids, causing early infant death [, , ]Known substrates for SUMF1 are: N-acetylgalactosamine-6-sulfate sulfatase (GALNS), arylsulfatase A (ARSA), steroid sulfatase (STS) and arylsulfatase E (ARSE). SUMF1 occurs in the endoplasmic reticulum or its lumen.
This domain is found in sulfatase-modifying factors (SUMFs) []and Chlamydia serine/threonine-protein kinase pkn1 []. It is also found in iron(II)-dependent oxidoreductase from Mycobacterium [, ]. The structure of this domain is homologous to the complex alpha/beta topology found in sulfatase-modifying factors (SUMF1). SUMF1 is a paralogue of oxoalanine-generating enzyme, also called C(alpha)-formylglycine generating enzyme (FGE). SUMF1 converts newly synthesized inactive sulfatases to their active form by modifying an active site cysteine residue to oxoalanine. Sulfatases are essential for the degradation of sulfate esters, whose catalytic activity is dependent upon an oxoalanine residue []. Defects in SUMF1 or FGE cause multiple sulfatase deficiency (MSD), which leads to the impairment of all sulfatases and to the accumulation of glycoaminoglycans or sulfolipids, causing early infant death [, , ]Known substrates for SUMF1 are: N-acetylgalactosamine-6-sulfate sulfatase (GALNS), arylsulfatase A (ARSA), steroid sulfatase (STS) and arylsulfatase E (ARSE). SUMF1 occurs in the endoplasmic reticulum or its lumen.
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of 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. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. 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 [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].This entry contains the PknD family of serine/threonine protein kinases which are found in (for example) C. trachomatis. In conjunction with Pkn1 they may play a role in specific interactions with host proteins during intracellular growth [].
