SII-SWORD/CoKE huggingface dataset:
Fascin-like domain (Fascin-like_dom)
Type: Domain

This entry represents the fascin-like domain, which is found repeated four times in members of the fascin family. This domain adopts a β-trefoil fold .

The fascins are a structurally unique and evolutionarily conserved group of actin cross-linking proteins. Fascins function in the organisation of two major forms of actin-based structures: dynamic, cortical cell protrusions and cytoplasmic microfilament bundles. The cortical structures, which include filopodia, spikes, lamellipodial ribs, oocyte microvilli and the dendrites of dendritic cells, have roles in cell-matrix adhesion, cell interactions and cell migration, whereas the cytoplasmic actin bundles appear to participate in cell architecture . Dictyostelium hisactophilin, another actin-binding protein, is a submembranous pH sensor that signals slight changes of the H+ concentration to actin by inducing actin polymerisation and binding to microfilaments only at pH values below seven . Members of this group are histidine rich, typically contain the repeated motif of HHXH .
Aerobactin siderophore biosynthesis IucA/IucC-like, C-terminal (IucA/IucC-like_C)
Type: Domain

This entry represents the C-terminal domain of this group of proteins which is related to the FhuF iron transporter proteins. FhuF is involved in the reduction of ferric iron in cytoplasmic ferrioxamine B .

Bacteria solve the iron supply problem caused by the insolubility of Fe(3) by synthesizing iron-complexing compounds, called siderophores, and by using iron sources of their hosts, such as haem and iron bound to transferrin and lactoferrin. Escherichia coli, as an example of a Gram-negative bacterium, forms sophisticated Fe(3)-siderophore and haem transport systems across the outer membrane. IucA and IucC catalyse discrete steps in biosynthesis of the siderophore aerobactin from N epsilon-acetyl-N epsilon-hydroxylysine and citrate .

This entry also includes SbnC, SbnE and SbnF from Staphylococcus aureus. They are involved in staphyloferrin B biosynthesis. SbnC is a staphyloferrin B synthase. SbnE is a L-2,3-diaminopropanoate--citrate ligase. SbnF is a 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate synthase .

It also includes Bisucaberin biosynthesis protein C that is involved in the biosynthesis of the siderophore bisucaberin , as well as AnkE which is responsible of the production of NK13650 B via ligation of citrate to the ankD product .
Wings apart-like protein, C-terminal (WAPL_C)
Type: Domain

This entry represents the conserved region of D. melanogaster wings apart-like protein, WAPL. It is involved in the regulation of heterochromatin structure . hWAPL (

), the human homologue, is found to play a role in the development of cervical carcinogenesis, and is thought to have similar functions to Drosophila wapl protein . Malfunction of the hWAPL pathway is thought to activate an apoptotic pathway that consequently leads to cell death .

The WAPL-like proteins can be found in metazoa, fungi and plants.
von Hippel-Lindau disease tumour suppressor, beta/alpha domain (VHL_tumour_suppress_b/a_dom)
Type: Domain

This entry represents both beta and alpha domains of VHL.

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologues are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterised putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF-independent cellular processes. Germline VHL mutations cause renal cell carcinomas, haemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilise microtubules and foster the maintenance of primary cilia. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B .

Von Hippel-Lindau disease tumour suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in β-sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain and, significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL .
Siva (Siva)
Type: Family

Siva binds to the CD27 cytoplasmic tail. It has a DD homology region, a box-B-like ring finger, and a zinc finger-like domain. Overexpression of Siva in various cell lines induces apoptosis, suggesting an important role for Siva in the CD27-transduced apoptotic pathway . Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. Indeed, the unique amphipathic helical region (SAH) present in Siva-1 is required for its binding to BCL-X(L) and sensitising cells to UV radiation. Natural complexes of Siva-1/BCL-X(L) are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis .
AP complex, mu/sigma subunit (AP_mu_sigma_su)
Type: Domain

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer .

This entry represents the small sigma and mu subunits of various adaptins from different AP clathrin adaptor complexes (including AP1, AP2, AP3 and AP4), and the zeta and delta subunits of various coatomer (COP) adaptors. The small sigma subunit of AP proteins have been characterised in several species . The sigma subunit plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The zeta subunit of coatomers (zeta-COP) is required for coatomer binding to Golgi membranes and for coat-vesicle assembly .
TRM13/UPF0224 family, U11-48K-like CHHC zinc finger domain (TRM13/UPF0224_CHHC_Znf_dom)
Type: Domain

This zinc binding domain has four conserved zinc chelating residues in a CHHC pattern and is known as the CHHC U11-48K-type zinc finger.

The CHHC U11-48K-type zinc finger is found only in eukaryotes. It has been identified in spliceosomal U11-48K proteins, tRNA methyl-transferases TRM13 and gametocyte specific factors (GTSF). The CHHC U11-48K-type zinc finger (~30 residues) is present in a single copy in U11-48k AND TRM13, whereas GTSF contains two repeats separated by a short linker. The CHHC U11-48K-type zinc finger may function as a RNA recognition and binding module .

The CHHC U11-48K-type zinc finger contains four invariant Cys and His residues with a consensus sequence of C-x(5,7)-H-x(7,9)-H-x(3,4)-C. It stochiometrically binds zinc ions in a one-to-one ratio. The structure of the CHHC U11-48K-type zinc finger consists of a β hairpin followed by a helix. the zinc ion is coordinated by Cys and His residues from the β hairpin and by His and Cys residues from the helix, respectively. The helical region has an α-helical conformation that is interrupted in the middle by a single pi-helical turn .
CDKN3 domain (CDKN3)
Type: Domain

This entry represents a domain found in cyclin-dependent kinase inhibitor 3 or kinase associated phosphatase proteins from several mammalian species. The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner . This domain is also found in the probable protein tyrosine phosphatase type IVA A from Dictyostelium discoideum.

This entry contains both eukaryotic and bacterial proteins.
Dynein family light intermediate chain (Dynein_light_int_chain)
Type: Family

This entry consists of several eukaryotic dynein light intermediate chain proteins. The light intermediate chains (LICs) of cytoplasmic dynein consist of multiple isoforms, which undergo post-translational modification to produce a large number of species. DLIC1 is known to be involved in assembly, organisation, and function of centrosomes and mitotic spindles when bound to pericentrin . DLIC2 is a subunit of cytoplasmic dynein 2 that may play a role in maintaining Golgi organisation by binding cytoplasmic dynein 2 to its Golgi-associated cargo .
Flagellar biosynthesis protein, FliO (Flagellar_biosynth_FliO)
Type: Family

FliO is an essential component of the flagellum-specific protein export apparatus . It is an integral membrane protein that acts as an assembly chaperone for the flagellar protein FliP. It is crucial, although not strictly required, for efficient FliP assembly and, thus flagellar assembly and function . FliO is a short protein found in flagellar biosynthesis operons, and which contains a highly hydrophobic N-terminal sequence followed generally by two basic amino acids. This region is reminiscent of but distinct from the twin-arginine translocation signal sequence. Some instances of this gene have been named "FliZ" but phylogenetic tree building supports a single FliO family.
Actin interacting protein 3-like, C-terminal (AIP3-like_C)
Type: Domain

This entry represents the C-terminal domain of actin interacting protein 3 (also known as Bud6 in budding yeasts). Bud6 is an actin- and formin-interacting protein. The N-terminal half of Bud6 is a microtubule binding domain required for its localisation and for its function in cortical capture of astral microtubule ends. The C-terminal half (residues 489-788) directly facilitates actin filament assembly by the formin Bni1 and is required for NPF (nucleation-promoting factor) activity. The domain represented in this entry (residues 365-776) is overlapped with the C-terminal half of Bud6 in this study . This entry also includes proteins from animals.
GCF, C-terminal (GCFC_dom)
Type: Domain

This entry represents the C-terminal domain of GCF2 its homologues , as well as in a number of other proteins including Tuftelin-interacting protein 11 . While the function of the domain is unknown, some of the proteins it is found in are reported to be involved in pre-mRNA splicing . This domain is also found in Sip1, a septin interacting protein .
Ribosome biogenesis protein Alb1 (Ribosome_bgen_Alb1)
Type: Family

Alb1 is a nuclear shuttling factor involved in ribosome biogenesis .
Geminin/Multicilin (Geminin/Multicilin)
Type: Family

Geminin and multicilin belong to the geminin family.

Geminin inhibits DNA replication by preventing the incorporation of MCM complex into prereplication complex, and is degraded during the mitotic phase of the cell cycle. It has been proposed that geminin inhibits DNA replication during S, G2, and M phases and that geminin destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle . The family also includes multicilin, which is required for multiciliate cell differentiation in diverse tissues . It acts by promoting transcription of genes required for multiciliate cell formation, including FoxJ1 and genes mediating centriole assembly.

Multicilin (also known as Idas) is required for multiciliate cell differentiation in diverse tissues . Multicilin coordinately promotes cell cycle exit, centriole assembly, and FoxJ1 expression . It can form heterodimer with Geminin .
D-proline reductase (dithiol), PrdB protein (D_pro_red_PrdB)
Type: Family

Members of this family form the PrdB subunit, usually a selenoprotein, in the D-proline reductase complex. The usual pathway is conversion of L-protein to D-proline by a racemase, then use of D-proline as an electron acceptor coupled to ATP generation under anaerobic conditions .
Antitoxin ParD (ParD)
Type: Family

ParD is the antitoxin of a bacterial toxin-antitoxin gene pair. The cognate toxin is ParE in

. The family contains several related antitoxins from Cyanobacteria, Proteobacteria and Actinobacteria. Antitoxins of this class carry an N-terminal ribbon-helix-helix domain, RHH, that is highly conserved across all type II bacterial antitoxins, which dimerises with the RHH domain of a second VapB molecule. A hinge section follows the RHH, with an additional pair of flexible α helices at the C terminus. This C terminus is the toxin-binding region of the dimer, and so is specific to the cognate toxin, whereas the RHH domain has the specific function of lying across the RNA-binding groove of the toxin dimer and inactivating the active-site - a more general function of all type II antitoxins .
Glycosyl hydrolase family 26 domain (GH26_dom)
Type: Domain

This entry represents a domain found in the glycosyl hydrolase family 26 members. Glycoside hydrolases (GHs) play a critical role in both eukaryotes and prokaryotes, where they fulfill numerous important functions such as substrate acquisition and the remote remodelling of cell walls and the glycan decorations of glycoproteins. GH family 26 consists mainly of endo-beta-1,4- mannanases (mannanases) (

), although some members of this family display beta- 1,3-xylanase activity. Proteins containing this domain also include the enzyme endogluconase H (

), which catalyses the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans. The family 26 GHs are members of clan GH-A .

The GH26 catalytic domain exhibits the architecture of the classical (β/α)8-barrel folding motif characteristic of a clan-GH-A member. Two Glu residues located respectively on strands β4 and β7 act as the catalytic acid/base and nucleophile in a double-displacement mechanism .
Lysylphosphatidylglycerol synthetase/glycosyltransferase AglD (L-PG_synthase/AglD)
Type: Family

This family contains proteins involved in the addition of lysine to phosphatidylglycerol (lysylphosphatidylglycerol synthetase, L-PG synthase) . L-PG synthase produces lysyl-phosphatidylglycerol (L-PG), the major component of the bacterial membrane and responsible for its positive charge. L-PG synthesis contributes to bacterial virulence as it is involved in the cationic antimicrobial peptides (CAMP) resistance mechanism of the host's immune system (defensins, cathelicidins) and of the competing microorganisms (bacteriocins). This family also includes archaeal glycosyltransferase AglD, involved in S-layer biosynthesis , and a number of uncharacterised proteins.
Type II secretion system protein GspN (T2SS_protein-GspN)
Type: Family

GspN is a cytoplasmic membrane component of the type II secretion system (T2SS). It is present in T2SS operons of a subset of Gram-negative speciesI, such as Aeromonas hydrophila (gene exeN); Erwinia carotovora (gene outN); Klebsiella pneumoniae (gene pulN); or Vibrio cholerae (gene epsN) . The size of the 'N' protein is around 250 amino acids. It apparently contains a single transmembrane domain located in the N-terminal section. The short N-terminal domain is
predicted to be cytoplasmic and the large C-terminal domain periplasmic.

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
RNA polymerase I-specific transcription initiation factor Rrn10 (Rrn10)
Type: Family

The protein Rrn10 has been identified as a component of the Upstream Activating Factor (UAF), an RNA polymerase I (pol I) specific transcription stimulatory factor .
Bul1, C-terminal (Bul1_C)
Type: Domain

This domain contains the C terminus of Saccharomyces cerevisiae Bul1 and Bul2. Bul1 binds the ubiquitin ligase Rsp5, via an N-terminal PPSY motif (157-160 in

) . The complex containing Bul1 and Rsp5 is involved in intracellular trafficking of the general amino acid permease Gap1 , degradation of Rog1 in cooperation with Bul2 and GSK-3 , and mitochondrial inheritance . Bul2, which is homologous to Bul1, also interacts with Rsp5 . This domain is found C-terminal to

.
Chlorophyll A-B binding protein (Chloroa_b-bind)
Type: Family

The light-harvesting complex (LHC) consists of chlorophylls A and B and the chlorophyll A-B binding protein. LHC functions as a light receptor that captures and delivers excitation energy to photosystems I and II with which it is closely associated. Under changing light conditions, the reversible phosphorylation of light harvesting chlorophyll a/b binding proteins (LHCII) represents a system for balancing the excitation energy between the two photosystems .

The N terminus of the chlorophyll A-B binding protein extends into the stroma where it is involved with adhesion of granal membranes and photo-regulated by reversible phosphorylation of its threonine residues . Both these processes are believed to mediate the distribution of excitation energy between photosystems I and II.

This family also includes the photosystem II protein PsbS, which plays a role in energy-dependent quenching that increases thermal dissipation of excess absorbed light energy in the photosystem .
Type III secretion system regulator LcrR/Chaperone CesD2 (LcrR/CesD2)
Type: Family

LcrR proteins are encoded within type III secretion operons and have been characterised in Yersinia as a regulator of the Low-Calcium Response (LCR). CesD2 of enteropathogenic Escherichia coli is a chaperone for the Type III Secretion Translocator Protein EspD.
Cellulose synthase operon protein D, bacterial (BcsD_bac)
Type: Family

This entry represents Cellulose synthase operon protein D from Komagataeibacter xylinus and similar proteins from Proteobacteria. BcsD has been related with the level of crystalline structure of cellulose . The protein have a octamer pore-like structure with four inner passageways .

An operon encoding 4 proteins required for bacterial cellulose biosynthesis (bcs) in Acetobacter xylinus (Gluconacetobacter xylinus) has been isolated via genetic complementation with strains lacking cellulose synthase activity . Nucleotide sequence analysis showed the cellulose synthase operon to consist of 4 genes, designated bcsA, bcsB, bcsC and bcsD, all of which are required for maximal bacterial cellulose synthesis in A. xylinum.

The calculated molecular mass of the protein encoded by bcsD is 17.3kDa . The function of BcsD is unknown.

Cellulose, an aggregate of unbranched polymers of beta-1,4-linked glucose residues, is the major component of wood and thus paper, and is synthesized by plants, most algae, some bacteria and fungi, and even some animals. The genes that synthesize cellulose in higher plants differ greatly from the well-characterised genes found in Acetobacter and Agrobacterium spp. More correctly designated as "cellulose synthase catalytic subunits", plant cellulose synthase (CesA) proteins are integral membrane proteins, approximately 1,000 amino acids in length. There are a number of highly conserved residues, including several motifs shown to be necessary for processive glycosyltransferase activity .
Spt4/RpoE2 zinc finger (Spt4/RpoE2_Znf)
Type: Domain

This entry consists of several eukaryotic transcription elongation Spt4 proteins as well as archaebacterial RpoE2 . Three transcription-elongation factors Spt4, Spt5, and Spt6 are conserved among eukaryotes and are essential for transcription via the modulation of chromatin structure. Spt4 and Spt5 are tightly associated in a complex, while the physical association of the Spt4-Spt5 complex with Spt6 is considerably weaker. It has been demonstrated that Spt4, Spt5, and Spt6 play roles in transcription elongation in both yeast and humans including a role in activation by Tat. It is known that Spt4, Spt5, and Spt6 are general transcription-elongation factors, controlling transcription both positively and negatively in important regulatory and developmental roles . RpoE2 is one of 13 subunits in the archaeal RNA polymerase. These proteins contain a C4-type zinc finger, and the structure has been solved in . The structure reveals that Spt4-Spt5 binding is governed by an acid-dipole interaction between Spt5 and Spt4, and the complex binds to and travels along the elongating RNA polymerase. The Spt4-Spt5 complex is likely to be an ancient, core component of the transcription elongation machinery.