The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism

Dictyostelium discoideum is a widely studied model organism with both unicellular and multicellular forms in its developmental cycle. The Dictyostelium genome encodes 285 predicted protein kinases, similar to the count of the much more advanced Drosophila. It contains members of most kinase classes shared by fungi and metazoans, as well as many previously thought to be metazoan specific, indicating that they have been secondarily lost from the fungal lineage. This includes the entire tyrosine kinase–like (TKL) group, which is expanded in Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies not present in yeast or metazoa, suggesting that protein kinases have played key roles in the adaptation of Dictyostelium to its habitat. This study offers insights into kinase evolution and provides a focus for signaling analysis in this system.

Named for ABC1 from yeast, and is unrelated to the ABC transporter proteins.
Alpha_kinase A novel protein kinase catalytic domain with a related structure, but no sequence homology, to ePKs.

BROMO
May be involved in protein-protein interactions in transcriptional activation complexes.

PI3Kc
RIO Domain found in eukaryotes and prokaryotes that is related to ePKs.
HATPase_c Domain found in several ATP-binding proteins, including histidine kinases.

HisKA
Dimerisation and phosphoacceptor domain of histidine kinases.
Phosphoinositide 3-kinase isoforms include lipid kinases and protein kinases.

DOMAINS INVOLVED IN G-PROTEIN SIGNALING
ARFGAP Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase Arf. RHOGAP GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
TBC Thought to be a GTPase activator of Rab-like small GTPases.

RasGEF_N Found N-terminal to the RasGEF domain in several exchange factors for Ras-like small GTPase. RasGEF
Guanine nucleotide exchange factor for Ras-like small GTPases.

RGS
Regulator of G Protein Signalling. Promotes GTP hydrolysis by the alpha subunit of heterotrimeric G proteins. roc_domain Ras-like domain of complex proteins.
cor_domain Domain found C-terminal of roc_domain.

PBD
Domain that binds Cdc42p-and/or Rho-like small GTPases.

Ank
Ankyrin repeats are usually involved in protein-protein interactions.
ARM Armadillo repeats mediate protein-protein interactions.

Calpain_III
The function of domain III of calpains is unknown.

FNIP
Named after the pattern of conserved residues. Found only Dictyostelium.
HAMP Named for four of the proteins it is found in: histidine kinases, adenylyl cyclases, methyl binding proteins and phosphatases. Kelch Named after the protein in which it was first identified. Its function is unknown.
LIM Named after Lin-11 Isl-1 Mec-3. Binds two Zn 2+ ; mediates protein-protein interactions. LRR Leucine-rich repeats provide a versatile structural framework for the formation of protein-protein interactions. MORN "Membrane Occupation and Recognition Nexus". Function is unknown.

PQQ
Domain found in several enzymes which utilise pyrrolo-quinoline quinone as a prosthetic group. Function is unknown.

RCC1
Repeated domain found in regulator of chromosome condensation (RCC). Binds to chromatin and acts as a guanine-nucleotide dissociation stimulator for Ran.

WD40
Named for their~40 aa length, and because they often terminate in a WD dipeptide. Mediate protein-protein interactions, including to Gβ and myosin II.

STRUCTURAL MOTIFS
polyN Regions at least 19 aa in length that are at least 90% asparagine.
polyQ Regions at least 19 aa in length that are at least 90% glutamine.
Coiled-coil Regions predicted to dimerize by forming parallel alpha-helices.
AAA ATPase family associated with various activities. Often found in proteins with chaperone-like functions. Acetyltransf Gcn2-related N-actyltransferase. A superfamily that includes histone acetylases and other acetyltransferase enzymes. HECT Homologous to the E6-AP Carboxyl Terminus. E3 ubiquitin-protein ligase.
tRNA-synt_2b tRNA synthetase class II core domain. tRNA synthetases catalyse the attachment of an amino acid to its cognate tRNA. Myotub-related Domain in myotubularin-related proteins. Myotubularin is a lipid phosphatase that dephosphorylates PtdIns(3)P and PtdIns(3,5)P2.
Ribonuc_2-5A An endoribonuclease that cleaves an intron from Hac1 mRNA in humans, which causing it to be more efficiently translated.

DOMAINS MEDIATING PROTEIN-PROTEIN INTERACTIONS
BTB BR-C, ttk and bab. Mediates homomeric, and in some instances heteromeric, dimerization.

FBOX
A motif found in cyclin-F. Serves as a link between a target protein and a ubiquitin-conjugating enzyme. Filamin_repeat These form a rod-like structure in filamin, which is an actin-binding protein.

SH3
Src homology 3. Binds to target proteins through sequences containing proline and hydrophobic amino acids.