Table 2.
Functions of Selected Lineage-Specific Protein Clusters in Five Eukaryotes
| Name of the cluster | Species (no. of members) | Biological functions and other comments |
| Transcription regulation | ||
| AP2-like DNA-binding proteins | At(117) | Plant-specific transcription factors with multiple roles in stress and ethylene response and development (Riechmann et al. 2000). |
| MYB-like DNA-binding proteins | At(100, 48) | HTH-domain-containing transcription factors with diverse roles in development and regulation of various environmental responses (Riechmann et al. 2000). |
| WRKY-like DNA-binding proteins | AT(68) | DNA-binding proteins involved in regulation of development and pathogen response. |
| RF-A family of nucleic acid-binding proteins (OB fold) | At(47) | An expansion involving the conserved archaeo-eukaryotic replication factor A that is present in a single copy in other eukaryotic lineages (Wold 1997). |
| Viv1/PVAL-like transcription factors | AT(41) | Plant-specific transcription factors involved in abscisic acid response, seed differentiation, and development (Riechmann et al. 2000). |
| Nuclear hormone receptors | Ce (66, 43, 26, 26, and other small clusters) | Zn-dependent DNA-binding proteins typified by vertebrate steroid receptors. Many of the C. elegans members of this family may function independently of ligands, and characterized members like odr-7 have roles in cell-type differentiation (Sluder et al. 1999). |
| C4DM+Zn-finger-containing proteins | Dm(82) | Transcription factors typified by the Zeste-white 5 family. Consist of a DNA-binding C2H2-finger and C4DM, a predicted Zn-dependent protein–protein interaction domain (Lander et al. 2001). |
| SAZ-type Myb domain-containing proteins | Dm(40) | A specialized version of the MYB DNA-binding domain typified by transcription factors, such as Stonewall, Adf-1, and Zeste. |
| POZ+Zn-finger | Dm(55) | A class of DNA-binding, chromatin-associated transcription factors, such as Broad-complex, Lola, and trithorax-like consist of a specific version of the POZ domain fused to a C2H2-finger. |
| C6 finger-containing proteins | Sp(4) | Gal4-like C6 Zn fingers are among the most common transcription factors in the ascomycete fungi. |
| Pathogen/stress response | ||
| AP-ATPases | AT(150, 29, 17) | Plant disease-resistance loci products, typically consist of a TIR and an AP-ATPase domain combined with leucine-rich repeats (LRRs) (Hulbert et al. 2001). |
| Pepsin-like proteases | At(51), Ce(16) | Secreted proteases that could be involved in extracellular regulatory proteolytic cascades. |
| Subtilisin-like proteases | At(57) | Secreted proteases that could be involved in extracellular regulatory proteolytic cascades. |
| Papain-like proteases | At(14) | Thiol proteases that could be involved in stress responses and in germination. |
| Metalloproteases containing CUB domains | Ce(23) | Membrane-associated metalloproteases that could be involved in proteolytic cascades on the cell surface. |
| C-type lectins | Ce(115, 42) Dm(28) | Extracellular proteins containing adhesion modules potentially involved in recognition of specific pathogen surface molecules. |
| Chitinases | Ce(33) Dm(17) | Enzymes potentially involved in hydrolysis of cell walls of fungal pathogens. |
| Toll-like receptors | Dm(8) | Key receptors of the anti-pathogen response pathways. |
| CUB-domain proteins | Ce(40) | Extracellular adhesion proteins. |
| P450 hydroxylases | At(124, 34, 33, 28) Dm(83) Ce(46, 16) | Oxidoreductases involved in detoxification of diverse xenobiotics through hydroxylation (Nelson 1999; Tijet et al. 2001). |
| PRI-domain proteins | At(24) Ce(40) | Secreted proteins that could function as inhibitors of enzymes or adhesion molecules. |
| Cell wall mannoproteins | Sc(11) | Involved in cold shock and anoxic stress response. |
| α-helical peroxidases | At(73) | Enzymes generating nascent oxygen as part of the oxidative defense mechanisms. |
| Signaling | ||
| Concanavalin-like lectins | At(43) | Some of these lectins are fused to kinases as extracellular receptor domains and probably function as carbohydrate receptors. |
| PPR-module proteins | AT(194, 195) | α-superhelical proteins that could function as protein–protein interaction scaffolds in various contexts. |
| Calcium-dependent protein kinases | AT(44) | The principal transducers of Ca+ + signaling that mediate this pathway in various contexts. |
| Plant-specific protein kinases | At(316) | Involved in various signaling pathways, such as hormone response, disease resistance, and development. Often fused to various other domains, including Apple, LRRs, and bulb lectins. |
| Octicosapeptide module proteins | At(72, 17, 14) | A Ca+ +-binding signaling module; some are fused to VTV1-like DNA-binding domains and GAF domains (Ponting 1996). |
| NPH-3-like, plant-specific POZ-domain proteins | At(30) | Specialized POZ domains, some of which are involved in plant light response signaling. |
| PP2C phosphatases | At(20) | Phosphoserine phosphatases that function in diverse signlaing pathways, e.g., abscisic acid signaling. |
| Worm-specific S/T kinases | Ce(65) | A distinct, nematode-specific branch of the casein kinase family. |
| Receptor guanylate cyclases fused to protein kinases | Ce(13, 12) | Potential receptors of secreted peptide first messengers by analogy to mating pheromone receptors of sea urchins. |
| Worm-specific domains | Ce(42) | Uncharacterized domain probably involved in specific protein–protein interactions; some are fused to SET, caspase, kinase, and PHD domains. |
| POZ-domain proteins | Ce(26, 29) | Often fused to MATH domains, possibly function as chromatin-associated adaptors. |
| Insulin-like peptides | Ce(11) | Probably function as nematode-specific peptide hormones or growth factors. |
| Sec14-domain proteins | Dm(23) | Probably participate in regulation of protein trafficking and vesicular cargo loading. |
| SET-domain proteins with an inserted metal-chelating module | Dm(10) | Protein methyltransferases containing a divergent SET domain with a characteristic insert of a metal-chelating module. Probable regulators of chromatin dynamics. |
| Geko-domain proteins | Dm(8, 17) | A large family of Drosophila-specific cysteine-rich proteins, the only characterized member, Geko, is involved in olfaction. The LSC might be functionally coupled to the correspondingly expanded olfactory receptor families. |
| Ubiquitin signaling/protein unfolding and degradation | ||
| F-box proteins | At(251, 64, 41, 23) Ce(111, 46, 21) | Specificity-defining E3 subunits of ubiquitin ligases; fused to several other domains that might act as scaffolds for the assembly of the ubiquitinating enzyme complexes (Kipreos and Pagano 2000). |
| RING-finger proteins | At(74, 16, 12) | The majority of the RING fingers in the LSCs are of the RING-H2 category; probably function as specific E3-ligases |
| U-box proteins | At(21, 18) | RING-finger derivatives that probably mediate multiubiquitination of specific targets. |
| Ubiquitin-domain proteins | At(11) | Probably utilized similarly to ubiquitin, but could specifically conjugate with different proteins. |
| Adenoviral-type proteases | At(117) | Probably involved in deubiquitination as exemplified by ULP1/SMT4 (Li and Hochstrasser 2000; Nishida et al. 2000). |
| GH3-domain proteins | At(17) | Share a conserved domain with the E1 subunits of ubiquitin ligases; might be negative regulators of the signalosome. |
| MATH-domain proteins | Ce(81) At(73) | Related to the MATH domains of the ubiquitin carboxy-terminal hydrolases and E3-ligases of the TRAF family; could function as adaptors in ubiquitin pathways. |
| Prolyl hydroxylases | Dm(19) At(10) | Hydroxylation of prolines by these enzymes might provide targets for ubiquitination by specific E3-ligases (Aravind and Koonin 2001). |
| Cyclophilin-type peptidyl-prolyl isomerases | Dm(10) | Catalyze isomerization of proline-containing peptide bonds; might function in regulating aggregation of protein complexes. |
| Chemoreceptors and small molecule sensors | ||
| 7-transmembrane olfactory receptors | Ce(264, 228, 122) | Receptors for odorants/environmental chemicals (Dryer 2000; Glusman et al. 2001). |
| Insect-type odorant receptors | Dm(55) | Receptors for odorants/environmental chemicals. |
| Pheromone-binding proteins | Dm(27) | Probably involved in the binding and delivery of odorants to chemoreceptory cells. |
| Patched-type sterol binding membrane proteins | Ce(15) | Bind lipids and sterols in various contexts including stabilization of receptor complexes. |
| Juvenile hormone and other small-molecule-binding proteins | Dm(27) | Probably involved in the binding and delivery of small molecules in the insect haemolymph. |
| Lipid-bind proteins (NLTP) | At(49, 26) | Cysteine-rich α-helical proteins involved in lipid binding and delivery in various contexts and wax deposition. |
| Jacalin-type lectins | At(44) | Might be involved in sugar binding and storage. |
| Hemocyanins | Dm(10) | Copper-dependent oxygen transport proteins. |
| Cyanin family proteins | At(34) | Copper-binding proteins. |
| Ion Channels and Transporters | ||
| Degenerin family channels | Dm(24) | Sodium channels, probably function in tactile reception and related ion-dependent signaling pathways. |
| Potassiumm channels | Ce(15) | Potassium channels of the double pore category, probably function as pH-dependent channels. |
| Innexin-type channels | Ce(20) | Channels related to the Dm Shaking-B protein, might be involved in the formation of gap junctions. |
| cNMP-gated channels | At(21) | Cyclic nucleotide-gated channels containing an intracellular cNMP-binding domain. |
| Amino acid transporters | At(33) | Amino acid transporters of the N-amino acid transporter family. |
| Potassium transporters | At(17) | Belong to the plant tiny root hairfamily; probably involved in potassium uptake. |
| Na-P-transporter-related proteins | Ce(26) | Probably involved in phosphate uptake by symport. |
| Hexose transporters | Sc(15) | Belong to the 12 TM sugar transporter superfamily. |
| ABC transporters | Dm(11, 9, 5) | Transporters containing two ABC-class ATPase domains. |
| Small molecule metabolism | ||
| Lipases | At(106) | A family of phospholipid lipases of the flavodoxin fold; involved in degradation of phosphatidylcholine. Could be involved in metabolizing lipids in germination or degrading lipid membranes of pathogens. |
| 2-OG-Fe dioxygenases | At(67) | Hydroxylases involved in the biosynthesis of numerous plant secondary metabolites, such as gibberellins (Aravind and Koonin 2001). |
| NH2 cinnamoyl/benzoyltransferase | At(56) | Transfers aromatic carboxylic acid groups to diverse targets in the biosynthesis of plant secondary metabolites. |
| Small molecule O-methylases | At(38, 15) | Catalyze the methylation step in the biosynthesis of diverse plant products, such as caffeic acid. |
| Glutathione S-transferases | At(14) Ce(28) Dm(27) | Catalyze the conjugation of electrophilic substrates, particular xenobiotic, to glutathione as part of their transport and detoxification; additionally have peroxidase and small molecule isomerase activities. |
| Predicted secreted small molecule methylases | Ce(32) | Contain specific disulfide bonds; probably catalyze methylation of extracellular small molecules. |
| Integral membrane O-acyltransferases | Ce(151) | A family of membrane-associated acyltransferases closely related to the bacterial membrane associated acyltransferases that acylate macrolide antibiotics and cell surface polysaccharides. |
| Predicted small molecule kinases | Ce(23) Dm(45) | Related to aminoglycoside and lipid kinases; probably involved in phosphorylation of small molecules, such as odorants and/or xenobiotics. |
| Structural/morphological proteins | ||
| Cystine-rich expansions | At(35) | Plant cell-wall glycoproteins. |
| Pectin methylesterases | At(89) | Involved in the biosynthesis of pectins, major structural components of plants. |
| Pectin-associated proteins | At(26) | Four-cysteine α-helical domains, some fused to pectin esterases. |
| Cuticular collagens | Ce(34, 32, 26, 11) | The principal structural component of the nematode cuticle (Johnstone 2000). |
| Major sperm protein family | Ce(32, 10) | The principal structural component of nematode sperms. |
| Insect cuticular proteins | Dm(88) | The principal structural component of the insect cuticle (Andersen et al. 1995). |
| Peritrophin-like proteins | Dm(40) | Insect-specific extracellular matrix proteins. |
| Cell wall glycoproteins | Sc(11) | Protein component of the yeast cell wall. |
| Ecm34p-like proteins | Sc(25) | Protein component of the yeast cell wall. |
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↵The members of each LSC are listed in the Supplementary Material section, in which the LSCs can be identified by their names and the number of members.
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↵Species abbreviations: (At) Arabidopsis thaliana;(Ce) Caenorhabditis elegans; (Dm) Drosophila melanogaster; (Sc) Saccharomyces cerevisiae; (Sp)Schizosaccharomyces pombe. The number of members in each LSC is indicated in parentheses; commas separate distinct LSCs that belong to the same class of paralogous proteins.
