SII-SWORD/CoKE huggingface dataset:
Mechanosensitive ion channel MscS (MscS_channel_2nd)
Type: Domain

This entry includes small conductance mechanosensitive channels (MscS), which assembles to a homoheptameric complex . Each monomer consists of a N-terminal transmembrane region and a large cytoplasmic segment composed of a five-stranded antiparallel β-sheet (middle/second) domain and a C-terminal α/β-domain .

This entry represents the all-β domain which adopts a SH3-like barrel structure.

Mechanosensitive (MS) channels provide protection against hypo-osmotic shock, responding both to stretching of the cell membrane and to membrane depolarisation. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya . There are two families of MS channels: large-conductance MS channels (MscL) and small-conductance MS channels (MscS or YGGB). The pressure threshold for MscS opening is 50% that of MscL . The MscS family is much larger and more variable in size and sequence than the MscL family. Much of the diversity in MscS proteins occurs in the size of the transmembrane regions, which ranges from three to eleven transmembrane helices, although the three C-terminal helices are conserved.

MscS folds as a homo-heptamer with a cylindrical shape, and can be divided into transmembrane and extramembrane regions: an N-terminal periplasmic region, a transmembrane region, and a C-terminal cytoplasmic region (middle and C-terminal domains). The transmembrane region forms a channel through the membrane that opens into a chamber enclosed by the extramembrane portion, the latter connecting to the cytoplasm through distinct portals .

In the fission yeast Schizosaccharomyces pombe the mechanosensitive ion channel proteins are known as msy1 and msy2 .
Mechanosensitive ion channel MscS, conserved site (MscS_channel_CS)
Type: Conserved_site

MscS is a mechanosensitive channel present in the membrane of bacteria, archaea and eukarya that responds both to stretching of the cell membrane and to membrane depolarisation . MscS folds as a homo-heptamer with a cylindrical shape, and can be divided into transmembrane and extramembrane regions: an N-terminal periplasmic region, a transmembrane region, and a C-terminal cytoplasmic region. The C-terminal cytoplasmic region can be further divided into middle and C-terminal domains, which together create a framework that connects to the cytoplasm through distinct openings. The middle domain exhibits a Sm-like structure, consisting of five β-strands that pack together with those of other subunits to form a barrel-like sheet extending around the entire protein.
Outer membrane protein, OmpA-like, conserved site (OMPA-like_CS)
Type: Conserved_site

Most of the bacterial outer membrane proteins in this group are porin-like integral membrane proteins (such as ompA) , but some are small lipid-anchored proteins (such as pal) . It is also found in MotB and related proteins. They are present in the outer membrane of many Gram-negative organisms . This domain is found at the C-terminal half of these proteins and is well conserved. The N-terminal half is variable although some of the proteins in this group have the OmpA-like transmembrane domain

at the N terminus.
DNA gyrase/topoisomerase IV, subunit A, C-terminal repeat (GyrA/parC_rep)
Type: Repeat

This repeat is found as 6 tandem copies at the C-termini of GyrA and ParC DNA gyrases. It is predicted to form 4 β strands and to probably form a β-propeller structure . This region has been shown to bind DNA non-specifically and may stabilise the DNA-topoisomerase complex .
COPA/B, second beta-propeller domain (Beta-prop_COPA/B_2nd)
Type: Domain

This entry represents the second β-propeller found in Coatomer subunits alpha and beta (COPA1-3, COPB2 and COB21-3), from eukaryotes. Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles .Coat protein I (COPI)-coated vesicles mediate retrograde transport from the Golgi to the endoplasmic reticulum (ER), as well as transport within the Golgi . The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex. COPB2 is a vital oncogene in many cancer types that regulates multiple biological behaviours of tumor cells, including proliferation, survival, tumourigenesis, invasion, and metastasis . COPA constitutes part of COPI, playing a role in the retrograde transport of cargo proteins between the Golgi and the ER and the movement of vesicles within the Golgi .

Proteins synthesised 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 . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .
Partial AB-hydrolase lipase domain (AB_hydrolase_lipase)
Type: Domain

The alpha/beta hydrolase fold is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an α/β sheet, not barrel, of eight β-sheets connected by α-helices . This entry represents the N-terminal part of an alpha/beta hydrolase domain found in a number of lipases.
Fatty acid hydroxylase (Fatty_acid_hydroxylase)
Type: Domain

This entry includes fatty acid and carotene hydroxylases and sterol desaturases. Beta-carotene hydroxylase is involved in zeaxanthin synthesis by hydroxylating beta-carotene, but the enzyme may be involved in other pathways . This family includes C-5 sterol desaturase and C-4 sterol methyl oxidase (SMO) . Members of this family are involved in cholesterol biosynthesis and biosynthesis a plant cuticular wax. These enzymes contain two copies of a HXHH motif, involved in coordination of two iron atoms in the catalytic centre. Members of this family are ER integral membrane proteins with a mushroom-like structure consisting of four transmembrane helices (TM1-TM4) that anchor them to the membrane, capped by a cytosolic domain containing the unique histidine-coordinating di metal centre .

The plant SMO amino acid sequences possess three histidine-rich motifs (HX3H, HX2HH and HX2HH), characteristic of the small family of membrane-bound non-haem iron oxygenases that are involved in lipid oxidation .
Protein of unknown function DUF423 (DUF423)
Type: Family

This is a potential integral membrane protein with no known function.
RecBCD enzyme subunit RecC (RecC)
Type: Family

The exodeoxyribonuclease V enzyme or RecBCD enzyme is a multisubunit enzyme comprised of the proteins RecB (

), RecC (this family) and RecD (

). This enzyme plays an important role in homologous genetic recombination, repair of double strand DNA breaks resistance to UV irradiation and chemical DNA-damage. The enzyme (

) catalyzes hydrolysis of single-stranded (ss) DNA or double-stranded (ds) DNA and unwinding of the ends of dsDNA . Its nuclease activity is controlled by Chi sites (5' G-C-T-G-G-T-G-G 3') in such a way that the enzyme produces a potent single-stranded DNA substrate for homologous pairing by RecA and single-stranded DNA binding proteins.
Uncharacterised protein family UPF0229 (UPF0229)
Type: Family

This family consists of bacterial proteins of unknown function.
Glycerol uptake operon antiterminator (GlpP)
Type: Family

Glycerol enters bacterial cells via facilitated diffusion, an energy-independent transport process catalysed by the glycerol transport facilitator GlpF, an integral membrane protein of the aquaporin family. Intracellular glycerol is usually converted to glycerol-3-P in an ATP-requiring phosphorylation reaction catalysed by glycerol kinase (GlpK). Glycerol-3-P, the inducer of the glpFK operon, is not a substrate for GlpF and hence remains entrapped in the cell where it is metabolized further. In some bacterial species, for example Bacillus firmus, glycerol-3-P activates the antiterminator GlpP . In B. subtilis, glpF and glpK are organised in an operon followed by the glycerol-3-P dehydrogenase-encoding glpD gene and preceded by glpP coding for an antiterminator regulating the expression of glpFK, glpD and glpTQ. Their induction requires the inducer glycerol-3-P, which activates the antiterminator GlpP by allowing it to bind to the leader region of glpD and presumably also of glpFK and glpTQ mRNAs.
Ribosomal RNA small subunit methyltransferase E (RsmE)
Type: Family

Methyltransferases (Mtases) are responsible for the transfer of methyl groups between two molecules. The transfer of the methyl group from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms. The reaction is catalysed by Mtases and modifies DNA, RNA, proteins or small molecules, such as catechol, for regulatory purposes. Proteins in this entry belong to the RsmE family of Mtases, this is supported by crystal structural studies, which show a close structural homology to other known methyltransferases .

This group of proteins includes Ribosomal RNA small subunit methyltransferase E (RsmE) from Escherichia coli, which specifically methylates the uridine in position 1498 of 16S rRNA in the fully assembled 30S ribosomal subunit . This enzyme has two distinct but structurally related domains: the N-terminal PUA domain and the conserved MTase domain at the C-terminal end. This protein adopts a dimeric configuration that is functionally critical for substrate binding and catalysis .
Casparian strip membrane protein domain (CASP_dom)
Type: Domain

This domain is found mainly in plant proteins known as Casparian strip membrane proteins (CASPs). CASPs are four-membrane-span proteins that mediate the deposition of Casparian strips in the endodermis by recruiting the lignin polymerization machinery. Interestingly, the CASP first extracellular loop was found conserved in euphyllophytes but absent in plants lacking Casparian strips .
AIG1-type guanine nucleotide-binding (G) domain (G_AIG1)
Type: Domain

This entry represents the AIG1-type G domain.

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The TRAFAC (translation factor related) class AIG1/Toc34/Toc159-like paraseptin GTPase family contains the following subfamilies :

The GTPases of immunity-associated protein (GIMAP)/immune-associated nucleotide-binding protein (IAN) subfamily is conserved among vertebrates and angiosperm plants and has been postulated to regulate apoptosis, particularly in context with diseases such as cancer, diabetes, and infections. The function of GIMAP/IAN GTPases has been linked to self defense in plants and to the development of T cells in vertebrates .

Plant-specific Toc (translocon at the outer envelope membrane of chloroplasts) proteins. Toc proteins function as integral components of the chloroplast protein import machinery. The Toc translocon contains the two membrane-bound GTPases Toc33/34 and Toc 159, which expose their G domains to the cytosol and recognise and then deliver precursor proteins through the translocation pore Toc75 .

The GIMAP/IAN GTPases contain a avrRpt2 induced gene 1 (AIG1)-type G domain that exhibits the five motifs G1-G5 characteristic for GTP/GDP-binding proteins. In addition, the AIG-type G domain contains a unique, highly conserved, hydrophobic motif between G3 and G4. It has a divergent version of the guanine recognition motif (G4) at the end of the core strand 5 and an additional helix alpha6 at the C terminus. The AIG1-type G domain contains a central β-sheet sandwiched by two layers of α-helices.
Leukocyte surface antigen CD47 (CD47)
Type: Family

Leukocyte surface antigen CD47 (also known as integrin-associated protein, IAP) is a widely expressed membrane protein with multiple functions in immunological and neuronal processes. For example, CD47-induces caspase-independent cell death which may be mediated by cytoskeleton reorganisation . In red blood cells, CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha . The protein can also act as a thrombospondin receptor .

This entry also includes a group of CD-47-like proteins found in poxviruses (Poxviridae) such as protein A38, also known as Protein OPG166 .
Extensin domain (Extensin_dom)
Type: Domain

Extensins shares protein sequence similarity with hydroxyproline-rich glycoproteins (HRGPs) found in the plant extracellular matrix. They form a structural component which strengthens the primary cell wall; they can account for up to 20% of the dry weight of the cell wall. The key to the role of HRGPs in cell wall self-assembly and cell extension lies in their chemistry, which is dependent on extensive post-translational modifications (PTMs): hydroxylation, glycosylation, and cross-linking. Repetitive peptide motifs characterise HRGPs .
Type VII secretion system membrane protein EccD (T7SS_EccD)
Type: Family

This entry represents the EccD family of proteins, which includes EccD1-5. EccD1, also known as Snm4, has a ubiquitin-like fold and forms a dimer, with a negatively charged groove which indicates that it likely interacts with positive charged partners and may recruit other T7SS components or secretion substrates or it may form a gating element to close the channel during inactive periods. The residues forming the negatively charged groove are not conserved in EccD1 homologs from other ESX systems, suggesting that they have a system-specific role. It is responsible for multiple suppressive effects on macrophages and required for bacterial replication after phagocytosis .

ESX-1 to ESX-5 gene clusters encode proteins that are either secreted or building blocks of the actinobacterial Type 7 secretion system (T7SS) . In Mycobacterium tuberculosis ESX-1 is responsible for secretion of important virulence factors such as EsxA and EsxB as well as other virulence-associated proteins, ESX-3 is involved in metal acquisition being critical for mycobacterial survival. ESX-5 is also important for the secretion of members of the PE/PPE family of proteins that play a role in virulence and cell wall integrity. The function of ESX-2 and ESX-4 is still unknown although ESX-4 seems to be the ancestral system from which ESX systems have evolved. All ESX gene clusters contain three or four ESX conserved components (Ecc), named EccB, EccC, and EccD, with EccE being present in all ESX systems, except of ESX-4. EccC is a member of the FtsK/SpoIIIE-like ATPase family and provides the energy to transport proteins across the mycobacterial membrane; EccB and EccE have N-terminal transmembrane elements and large C-terminal regions predicted to be localised in the periplasm, but their function, molecular function or interacting partners remain unknown. EccD contains an N-terminal cytoplasmic domain followed by 11 predicted transmembrane helices, which is thought to form a cytoplasmic membrane channel through which the proteins are secreted .
Pex19 protein (Pex19)
Type: Family

Peroxisome(s) form an intracellular compartment, bounded by a typical lipid bilayer membrane. Peroxisome functions are often specialised by organism and cell type; two widely distributed and well-conserved functions are H2O2-based respiration and fatty acid beta-oxidation. Other functions include ether lipid (plasmalogen) synthesis and cholesterol synthesis in
animals, the glyoxylate cycle in germinating seeds ("glyoxysomes"), photorespiration in leaves, glycolysis in trypanosomes ("glycosomes"), and methanol and/or amine oxidation and assimilation in some yeasts.

PEX genes encode the machinery ("peroxins") required to assemble the peroxisome. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Matrix protein import follows a branched pathway of soluble recycling receptors, with one branch for each class of peroxisome targeting sequence (two are well characterised), and a common trunk for all. At least one of these receptors, Pex5p, enters and exits peroxisomes as it functions. Proliferation of the organelle is regulated by Pex11p. Peroxisome biogenesis is remarkably conserved among eukaryotes. A group of fatal, inherited neuropathologies are recognised as peroxisome biogenesis diseases. Pex19 is involved in membrane assembly and maintenance and functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs) .
Small-subunit processome, Utp14 (SSU_processome_Utp14)
Type: Family

A large ribonuclear protein complex is required for the processing of the small-ribosomal-subunit rRNA -the small-subunit (SSU) processome . This preribosomal complex contains the U3 snoRNA and at least 40 proteins, which have the following properties:

They are nucleolar.

They are able to coimmunoprecipitate with the U3 snoRNA and Mpp10 (a protein specific to the SSU processome).

They are required for 18S rRNA biogenesis.

There appears to be a linkage between polymerase I transcription and the formation of the SSU processome; as some, but not all, of the SSU processome components are required for pre-rRNA transcription initiation. These SSU processome components have been termed t-Utps. They form a pre-complex with pre-18S rRNA in the absence of snoRNA U3 and other SSU processome components. It has been proposed that the t-Utp complex proteins are both rDNA and rRNA binding proteins that are involved in the initiation of pre18S rRNA transcription. Initially binding to rDNA then associating with the 5' end of the nascent pre18S rRNA. The t-Utpcomplex forms the nucleus around which the rest of the SSU processome components, including snoRNA U3, assemble . From electron microscopy the SSU processome may correspond to the terminal knobs visualised at the 5' ends of nascent 18S rRNA.

This entry contains Utp14, a large ribonuclear protein associated with snoRNA U3 .
Glycoside hydrolase, family 43 (Glyco_hydro_43)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 43

includes enzymes with the following activities, beta-xylosidase (

), alpha-L-arabinofuranosidase (

); arabinanase (

), and xylanase (

).
Hox9, N-terminal activation domain (Hox9_activation_N)
Type: Domain

This domain constitutes the N-terminal of the paralogous homeobox proteins HoxA9, HoxB9, HoxC9 and HoxD9. The N-terminal region is thought to act as a transcription activation region. Activation may be by interaction with proteins such as Btg proteins, which are thought to recruit a multi-protein Ccr4-like complex .
HD-ZIP protein, N-terminal (HD-ZIP_N)
Type: Domain

Homeodomain leucine zipper (HDZip) genes encode putative transcription factors that are unique to plants. This observation suggests that homeobox-leucine zipper genes evolved after the divergence of plants and animals, perhaps to mediate specific regulatory events .

This domain is the N-terminal of plant homeobox-leucine zipper proteins. Its function is unknown.
Adhesin, Dr-family (Adhesin_Dr)
Type: Family

The Afa/Dr family of adhesins bind to the Dr blood group antigen component of decay-accelerating factor. These proteins contain both fimbriated and afimbriated adherence structures and mediate adherence of uropathogenic Escherichia coli to the urinary tract, leading to urinary tract infections (UTIs) and pregnancy complications . They also confer the mannose-resistant hemagglutination (MHRA) phenotype, which can be inhibited by chloramphenicol. The N-terminal portion of the mature protein is thought to be responsible for chloramphenicol sensitivity . These proteins remain attached to host cells or collagen once bound even in the presence of elevated shear stress or of chloramphenicol, a competitive inhibitor of binding .
Flagellar filament outer layer protein FlaA (FlaA)
Type: Family

Periplasmic flagella are the organelles of spirochete mobility, and are structurally different from the flagella of other motile bacteria. They reside inside the cell within the periplasmic space, and confer mobility in viscous gel-like media such as connective tissue . The flagella are composed of an outer sheath of FlaA proteins and a core filament of FlaB proteins. Each species usually has several FlaA protein species .
PEA3-type ETS-domain transcription factor, N-terminal (ETS_PEA3_N)
Type: Domain

The N-terminal of the PEA3 transcription factors is implicated in transactivation and in inhibition of DNA binding . Transactivation is potentiated by activation of the Ras/MAP kinase and protein kinase A signalling cascades. The N-terminal region contains conserved MAP kinase phosphorylation sites .
ERG2/sigma1 receptor-like (ERG2_sigma1_rcpt-like)
Type: Family

This family consists of the fungal C-8 sterol isomerase and mammalian sigma1 receptor. C-8 sterol isomerase (delta-8--delta-7 sterol isomerase), catalyses a reaction in ergosterol biosynthesis, which results in unsaturation at C-7 in the B ring of sterols . Sigma 1 receptor is a low molecular mass mammalian protein located in the endoplasmic reticulum , which interacts with endogenous steroid hormones, such as progesterone and testosterone . It also binds the sigma ligands, which are a set of chemically unrelated drugs including haloperidol, pentazocine, and ditolylguanidine . Sigma1 effectors are not well understood, but sigma1 agonists have been observed to affect NMDA receptor function, the alpha-adrenergic system and opioid analgesia.
Adenovirus E1B protein, N-terminal (Adeno_E1B_55K_N)
Type: Domain

This domain constitutes the N-terminal of E1B 55kDa (

). E1B 55K binds p53 the tumour suppressor protein converting it from a transcriptional activator which responds to damaged DNA into an unregulated repressor of genes with a p53 binding site . This protects the virus against p53 induced host anitviral responses and prevents apoptosis as induced by the adenovirus E1A protein . The role of the N-terminal in the function of E1B is not known.