SII-SWORD/CoKE huggingface dataset:
Prion, copper binding octapeptide repeat region (Prion_copper_b_octapeptide)
Type: Repeat

Prion protein (PrP-c) is a small glycoprotein found in high quantity in the brain of animals infected with certain degenerative neurological diseases, such as sheep scrapie and bovine spongiform encephalopathy (BSE), and the human dementias Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP-c is encoded in the host genome and is expressed both in normal and infected cells. During infection, however, the PrP-c molecule become altered (conformationally rather than at the amino acid level) to an abnormal isoform, PrP-sc. In detergent-treated brain extracts from infected individuals, fibrils composed of polymers of PrP-sc, namely scrapie-associated fibrils or prion rods, can be evidenced by electron microscopy. The precise function of the normal PrP isoform in healthy individuals remains unknown. Several results, mainly obtained in transgenic animals, indicate that PrP-c might play a role in long-term potentiation, in sleep physiology, in oxidative burst compensation (PrP can fix four Cu2+ through its octarepeat domain), in interactions with the extracellular matrix (PrP-c can bind to the precursor of the laminin receptor, LRP), in apoptosis and in signal transduction (costimulation of PrP-c induces a modulation of Fyn kinase phosphorylation) .

The normal isoform, PrP-c, is anchored at the cell membrane, in rafts, through a glycosyl phosphatidyl inositol (GPI); its half-life at the cell surface is 5 h, after which the protein is internalised through a caveolae-dependent mechanism and degraded in the endolysosome compartment. Conversion between PrP-c and PrP-sc occurs likely during the internalisation process.

The N-terminal region of the prion protein includes the N-terminal, positively charged polybasic region and the octapeptide repeat (OR) region. The latter, represented by this entry, has been shown to bind to copper, which has been related with novel inter-domain interaction. Both are important for the conversion of PrP-c into PrP-sc . The number and organisation of the repeats varies and is thought to be related to phenotypic variation. In this way, the insertion of four or more octapeptide repeats has been proved to be pathogenic, while smaller repeat insertions have an unclear pathogenicity. In any case, the presence of this insertion repeat in the protein may slightly increase risk of developing sporadic CJD .
Mitochondrial import receptor subunit Tom22, fungi (Tom22_fungi)
Type: Family

Tom22 is a central component of the TOM (Translocase of Outer Membrane) complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with tom20, it functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the translocation pore .
Antitermination protein N, arginine-rich motif (Antiterm_prot_N_Arg-rich)
Type: Family

Antitermination proteins positively regulate expression of bacteriophage early and late gene operons . Bacterial host RNA polymerase is modified by these antitermination proteins to a terminator-resistant form that transcribes through termination sites that would otherwise prevent expression of the regulated genes.

Enterobacteria phage lambda antitermination protein N is essential for the expression of two phage early operons which are critical for phage development. This entry represents the RNA-binding arginine-rich motif (also known as N36) which forms a complex with boxB RNA by binding tightly to the major groove of the boxB hairpin via hydrophobic and electrostatic interactions forming a bent α helix .
Rickettsia surface antigen, 120kDa (Rickettsia_antigen_120kDa)
Type: Family

This domain family is found in bacteria, and is approximately 40 amino acids in length. This family is a Rickettsia surface antigen of 120kDa which may be used as an antigen for immune response against the bacterial species .
Uncharacterised protein family Atu4866 (Uncharacterised_Atu4866)
Type: Family

The function of the proteins in this entry is not known, though Atu4866 from Agrobacterium tumefaciens has been structurally characterised. Atu4866 adopts a streptavidin-like fold and has a β-barrel/sandwich which is formed by eight antiparallel β-strands . Atu4866 has a potential ligand-binding site where it has a stretch of conserved residues on the surface.
Transcription factor Aft1, osmotic stress domain (TF_Aft1_OSM)
Type: Domain

This region is found in the transcription factor Aft1 which is required for a wide range of stress responses. The OSM domain has been shown to be involved in the osmotic stress response .
Tachystatin B (Tachystatin_B)
Type: Family

Tachystatin B is an antimicrobial chitin binding peptide and consists of two isotopes B1 and B2. Both structures contain a short antiparallel β sheet with an inhibitory cysteine knot motif. Tyr(14) and Arg(17) are thought to be the essential residues for chitin binding .
Domain of unknown function DUF3686 (DUF3686)
Type: Domain

This entry represents an N-terminal domain associated with ATPases and some uncharacterised proteins; it is approximately 450 amino acids in length and contains two conserved sequence motifs: DVF and SPNGED.
Arabinofuranosyltransferase AftA, C-terminal (ArabinofuranosylTrfase_AftA_C)
Type: Domain

The arabinofuranosyltransferase enzyme AftA is involved in cell wall arabinan biosynthesis in bacteria . It catalyses the addition of the first key arabinofuranosyl residue from the sugar donor beta-D-arabinofuranosyl-1-monophosphoryldecaprenol to the galactan domain of the cell wall, thus priming the galactan for further elaboration by the arabinofuranosyltransferases. As this enzyme is important for cell growth and is found in some important pathogens, such as Mycobacterium tuberculosis, it represents a potential target for the devlopment of new antibacterial drugs.

This entry represents the C-terminal domain of AftA.
Aleutian mink disease parvovirus non-structural protein 1-3 (ADV_NS1-3)
Type: Domain

This entry represents a domain found in Aleutian mink disease parvovirus (ADV) non-structural protein 1-3 (NS1-3). It is approximately 50 amino acids in length. ADV utilizes caspase activity to cleave its major non-structural protein (NS1), enable the localization of this protein to the nucleus and facilitate virus replication . The smaller NS2/3 are also encoded during viral infection and are essential for the replication of the virus .
Domain of unknown function DUF3642, lipoprotein (DUF3642_lipo)
Type: Domain

This domain is found in proteins which are major virulence factors from Gram-negative bacteria and is approximately 60 amino acids in length. There is a single completely conserved Y residue that may be functionally important.
Bacteriophage phiX174, GpK (Phage_phiX174_GpK)
Type: Family

This family of proteins is found in the microviridae (isometric ssDNA phages) and are approximately 60 amino acids in length. The function of these proteins are unknown. In phi X174 site-directed mutagenesis of gene K produces small plaques on su- hosts. The mutant phage has an identical latent period, but a more reduced burst size than that of the wild-type phi X174. The reduced burst size in the gene K mutant suggests that the gene K protein, although not essential, has a role in increasing infectivity by increasing the burst size three to six fold .
Arabinofuranosyltransferase AftA, N-terminal (ArabinofuranosylTrfase_AftA_N)
Type: Domain

The arabinofuranosyltransferase enzyme AftA is involved in cell wall arabinan biosynthesis in bacteria . It catalyses the addition of the first key arabinofuranosyl residue from the sugar donor beta-D-arabinofuranosyl-1-monophosphoryldecaprenol to the galactan domain of the cell wall, thus priming the galactan for further elaboration by the arabinofuranosyltransferases. As this enzyme is important for cell growth and is found in some important pathogens, such as Mycobacterium tuberculosis, it represents a potential target for the devlopment of new antibacterial drugs.

This entry represents the N-terminal domain of AftA, which is predicted to contain 11 transmembrane helices.
Acyl-CoA dehydrogenase, C-terminal (Acyl-CoA_dehydrogenase_C)
Type: Domain

This entry represents the C-terminal α helical domain of some bacterial Acyl-CoA dehydrogenases. It is found in association with

,

,

. There is a conserved ARRL sequence motif.
Aromatic prenyltransferase, CloQ-type (Prenyltransferase_CloQ)
Type: Family

This entry includes prenyltransferase-like proteins, including:

Aromatic prenyltransferases NovQ from Streptomyces niveus and CloQ from Streptomyces roseochromogenes. They catalyse the transfer of a dimethylallyl group to 4-hydroxyphenylpyruvate to produce the ring A structure in the novobiocin and clorobiocin biosynthesis pathways, respectively .

Flaviolin linalyltransferase from Streptomyces cinnamonensis. It is involved in the biosynthesis of furanonaphthoquinone I (FNQ I). It catalyses C- and O-prenylations of different phenolic substrates .

5,10-dihydrophenazine-1-carboxylate 9-dimethylallyltransferase from Streptomyces anulatus. It is involved in the biosynthesis of prenylated phenazines. It catalyses the transfer of a dimethylallyl moiety to C-9 of 5,10-dihydrophenazine 1-carboxylate (dihydro-PCA). It is specific for both dimethylallyl diphosphate and dihydro-PCA .
Aluminum-activated malate transporter (ALMT)
Type: Family

This entry represents an malate transporter which has been is identified as being critical for aluminium tolerance in Arabidopsis thaliana . Some family members have been reported to permeable to chloride, nitrate, sulphate and malate .
Borrelia attachment ligand, p66 (Borrelia_attachment_p66)
Type: Family

Borrelia burgdorferi, the agent of Lyme disease, expresses several adhesion molecules that are probably required for initial establishment of infection in mammalian hosts, and for colonization of various tissues within the host.
Bacteriocin class II, aureocin-like (Bacteriocin_II_aureocin-like)
Type: Family

This is a small family of type II bacteriocins usually encoded on a plasmid. Characteristically the members are small, cationic, rich in Lys and Try, and bring about a generalised membrane permeabilisation leading to leakage of ions. The family includes aureocin A, lacticins Q and Z, and BhtB .
Ankyrin-G binding site (Ankyrin-G_BS)
Type: Binding_site

Interactions with ankyrin-G are crucial to the localisation of voltage-gated sodium channels (VGSCs) at the axon initial segment and for neurons to initiate action potentials. This conserved 9-amino acid motif ((V/A)P(I/L)AXXE(S/D)D) is required for ankyrin-G binding and functions to localise sodium channels to a variety of 'excitable' membrane domains both inside and outside of the nervous system . This motif has also been identified in the potassium channel 6TM proteins KCNQ2 and KCNQ3 that correspond to the M channels that exert a crucial influence over neuronal excitability. KCNQ2/KCNQ3 channels are preferentially localised to the surface of axons both at the axonal initial segment and more distally, and this axonal initial segment targeting of surface KCNQ channels is mediated by these ankyrin-G binding motifs of KCNQ2 and KCNQ3 . KCNQ3 is a major determinant of M channel localisation to the AIS, rather than KCNQ2 . Phylogenetic analysis reveals that anchor motifs evolved sequentially in chordates (NaV channel) and jawed vertebrates (KCNQ2/3) .
Bacteriocin class IIc (Bacteriocin_IIc)
Type: Family

This class of bacteriocins was previously described as class V. The members include gassericin A, acidocin B and butyrovibriocin AR10, all of which are hydrophobic cyclical structures . The N- and C-termini are covalently linked, and the circular molecule is resistant to several proteases and peptidases . The immunity protein that protects Lactobacillus gasseri from the toxic effects of its bacteriocin, gassericin A, has been identified. It is found to be a small positively-charged hydrophobic peptide of 53 amino acids containing a putative transmembrane segment - a structure unlike that of the more common immunity proteins as found in

.
ATP synthase, F1 beta subunit (ATP_synth_F1_beta_su)
Type: Domain

F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c. This entry represents the beta subunit of the F1 component.

The NMR solution structure of the protein in SDS micelles was found to contain two helices, an N-terminal amphipathic α-helix and a C-terminal α-helix separated by a large unstructured internal domain. The N-terminal α-helix is the Tom20 receptor binding site whereas the C-terminal α-helix is located upstream of the mitochondrial processing peptidase cleavage site .
Dermonecrotic/RTX toxin, membrane localization domain (Dermonecrotic/RTX_toxin_MLD)
Type: Domain

This is a membrane localization domain found in multiple families of bacterial toxins including all of the clostridial glucosyltransferase toxins and various MARTX toxins (multifunctional-autoprocessing RTX toxins) . In the Pasteurella multocida toxin (PMT, also known as dermonecrotic toxin) C-terminal fragment, structural analysis have indicated that the C1 domain possesses a signal that leads the toxin to the cell membrane. Furthermore, the C1 domain was found to structurally resemble the phospholipid-binding domain of C. difficile toxin B . Functional studies in Vibrio cholerae indicate that the subdomain at the N terminus of RID (Rho-inactivation domain), homologous to the membrane targeting C1 domain of Pasteurella multocida toxin, is a conserved membrane localization domain essential for proper localization . The Rho-inactivation domain (RID) of MARTX (Multifunctional Autoprocessing RTX toxin) is responsible for inactivating the Rho-family of small GTPases in Vibrio cholerae. It is a bacterial toxin that self-process by a cysteine peptidase mechanism .
Packaging enzyme P4 (Packaging_enz_P4)
Type: Family

This entry represents P4, a packaging motor which is involved in the packaging of Pseudomonas bacteriophage genomes into preformed capsids using ATP. The P4 protein is located at the vertices of the icosahedral capsid. ATP drives RNA translocation through cooperative conformational changes .
CGT/MARTX, cysteine protease (CPD) domain (CPD_dom)
Type: Domain

Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms of post-translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is regulated by a unique allosteric activation mechanism. Binding of the eukaryotic-specific small molecule inositol hexakisphosphate (InsP(6)) to a basic cleft within the CPD induces a structural rearrangement that exposes the protease active site to its substrates. Proteins containing this domain belong to the peptidase family C80 of clan CD .

The CGT/MARTX CPD domain consists of a central β-sheet that is surrounded by α-helices. Additional β-strands at the C terminus form a subdomain known as the β-flap, that is loosely attached to the core protease. The CGT/MARTX CPD catalytic dyad is composed of one His and one Cys residue. The distance between the catalytic residues indicates that the Cys is not activated by protonation from His, but rather suggests that the Cys is substrate-activated by close alignment of the scissile bond, while the His functions solely to protonate the leaving group .
UvsW.1 domain (UvsW.1_dom)
Type: Domain

This entry represents the UvsW.1 domain, a small α-helical domain that is typically encoded by the gene adjacent (UvsW.1) to that of phage UvsW-like SF2 helicases. UvsW.1 domain features a trihelical bundle fold that is related to other nucleic acid binding domains such as the HRDC domain of the RecQ helicases .
LCI fold (Antimicrobial_lci)
Type: Domain

This entry represents the LCI fold found in bacteria, functionally related to antimicrobial activity. It is approximately 40 amino acids in length and consists of three antiparallel β-strands in a β1-β3-β2 topology. This domain has been reported linked to CHAP, PGBD and SH3 domains in a putative cysteine protease .
Beta-casein-like (Beta-casein-like)
Type: Family

This entry represents eukaryotic proteins that are typically between 216 to 240 amino acids in length which have two conserved sequence motifs: VLR and TRIY. Beta-casein-like protein is associated with cell morphology and a regulation of growth pattern of tumours. It is found in adenocarcinomas of uterine cervical tissues.
Cryptochrome C-terminal (Cryptochrome_C)
Type: Domain

Cryptochromes are blue/ultraviolet-A light sensing photoreceptors involved in regulating various growth and developmental responses in plants . Cryptochromes are inactive monomers in the dark but change its conformation to homooligomers upon photon absoption . This entry represents the C-terminal end of Cryptochrome proteins from plants, which is typically between 113 and 125 amino acids in length. The domain is found in association with

and

.

In Arabidopsis, a conformational change in the C-terminal domain is required for activity . The domain is know to interact with the protein COP1 .
Uncharacterised protein family A0KLC6 (Uncharacterised_A0KLC6)
Type: Family

This family of proteins is found in bacteria and are typically between 114 and 143 amino acids in length. There is a conserved KNLFD sequence motif. The annotation with this family suggests that it may be the B subunit of bacterial type IIA DNA topoisomerase but there is no evidence to support this annotation.
Menbrane protein HflK, N-terminal (Membrane_HflK_N)
Type: Domain

HflK is a bacterial membrane protein which is thought, together with the HflC protein, to form a membrane protease complex whose activity is modulated by the GTPase HflX . This entry represents the N-terminal, membrane-spanning, region of of HflK responsible for anchoring the protein in the bacterial membrane. It is often found in association with

.
Monopolin complex subunit Csm1/Pcs1, C-terminal (-Csm1/Pcs1_C)
Type: Domain

Saccharomyces cerevisiae Csm1 is part of the monopolin complex. Csm1 forms a complex with Mde4 and promotes monoorientation during meiosis . It plays a mitotic role in DNA replication and is required for condensin recruitment to the replication fork barrier site and rDNA repeat segregation . This entry also contains the Schizosaccharomyces pombe homologue to Csm1, Pcs1. Pcs1 forms a complex with Mde4 and acts in the central kinetochore domain to clamp microtubule binding sites together. The two complexes (Csm1/Lrs4 and Pcs1/Mde4) contribute to the prevention of merotelic attachment .
Bacteriophage T4, GpT, holin (Phage_T4_GpT_holin)
Type: Family

One mechanism by which bacteriophages effect host lysis begins with the accumulation of a holin in the host membrane and an endolysin in the host cytoplasm during late gene expression. At an allele-specific time, the holin disrupts the membrane, thus allowing the endolysin to enter the periplasm and degrade the cell wall peptidoglycan. This entry represents a specific holin, known as T, which has an unusual C-terminal periplasmic domain thought to be involved in the transduction of environmental information for the real-time control of lysis timing .
Basic leucine-zipper, C-terminal (Basic_leucine-zipper_C)
Type: Domain

Basic leucine-zipper (bZIP) proteins are found in eukaryotes. They are typically between 174 and 411 amino acids in length. Various bZIP proteins have been found and shown to play a role in seed-specific gene expression. bZIP binds to the alpha-globulin gene promoter, but not to promoters of other major storage genes such as glutelin, prolamin and albumin .
Speedy (Speedy)
Type: Family

This entry represents Speedy proteins found in animals.

Speedy (Spy1, also known as RINGO A) is a cell cycle regulatory protein which binds and activates CDK1 and CDK2 , protein kinases that allows progression through G1/S phase and further replication events. Spy1 activates CDK2 inducing a conformational change of the CDK2 T-loop that avoids its phosphorylation . Spy1 expression overcomes a p27-induced cell cycle arrest to allow for DNA synthesis, so cell cycle progression occurs due to an interaction between Spy1 and p27 .
Cell surface protein Shp, haem-binding domain (Cell_surface_Shp_haem-bd)
Type: Domain

Shp is a cell-surface protein which forms part of a complex responsible for haem uptake in Streptococcus pyogenes. During haem uptake Shp transfers a bound haem to HtsA, the lipoprotein component of an ABC transporter. This entry represents the haem-binding domain of Shp. It contains an immunoglobulin-like β-sandwich fold and has a unique haem-iron coordination, with the axial ligands being two methionine residues from the same Shp molecule . Surrounding the haem pocket, there is a negative surface which may serve as a docking interface for haem transfer.
Chemotaxis inhibitory protein (CHIPS)
Type: Family

Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a . CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound .

CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation . By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown .

The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy . This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism . The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation . The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) .
Centromere protein Cenp-M (Centromere_Cenp-M)
Type: Family

The prime candidate for specifying centromere identity is the array of nucleosomes assembles associated with CENP-A . CENP-A recruits a nucleosome associated complex (CENP-A-NAC complex) comprised of CENP-M which this entry represents, along with two other proteins . Assembly of the CENP-A NAC at centromeres is partly dependent on CENP-M. The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival .
Peptidase U32, collagenase (Pept_U32_collagenase)
Type: Domain

The peptidases families associated with clan U-have an unknown catalytic mechanism as the protein fold of the active site domain and the active site residues have not been reported.

This domain is found in a number of proteins belonging to the MEROPS peptidase family U32. Peptidase family U32 contains endopeptidases, including collagenase, from bacteria.