SII-SWORD/CoKE huggingface dataset:
Photosystem II Psb28, class 1 (PSII_Psb28_class-1)
Type: Family

This family represents the low molecular weight transmembrane protein Psb28 (PsbW), one of the assembly factors of photosystem II (PSII). Psb28 is involved in guiding PSII biogenesis and assembly, stabilising dimeric PSII , and facilitating PSII repair after photo-inhibition . When Psb28 binds the membrane-intrinsic antenna protein CP47, it induces large conformational changes at the PSII acceptor side, which distort the binding pocket of the mobile quinone (QB) and replace the bicarbonate ligand of non-haem iron with glutamate, a structural motif found in reaction centres of non-oxygenic photosynthetic bacteria .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .
Amb V Allergen (Amb_V_allergen)
Type: Family

Amb V is an Ambrosia sp (ragweed) pollen allergen. Amb t V has been shown to contain a C-terminal helix as the major T cell epitope. Free sulphydryl groups also play a major role in the T cell recognition of cross-reactivity T cell epitopes within these related allergens .
CCAAT-binding factor (CCAAT-binding_factor)
Type: Domain

This domain is present in the CAATT-binding protein which is essential for growth and necessary for 60S ribosomal subunit biogenesis. Other proteins containing this domain stimulate transcription from the HSP70 promoter.
Actin interacting protein 3, C-terminal (AIP3_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 .
NrfD-like (NrfD-like)
Type: Family

This entry includes a group of integral membrane proteins that transfer of electrons from the quinone pool to the type-c cytochromes, found in bacteria and archaea. NrfD is an integral transmembrane protein with loops in both the periplasm and the cytoplasm. NrfD is thought to participate in the transfer of electrons, from the quinone pool into the terminal components of the Nrf pathway . This entry represents NrfD and related proteins, including an NrfD-related subunit of polysulphide reductase and a selenate reductase complex subunit .
Glutathione synthase (Glutathione_synthase)
Type: Family

This entry represents glutathione synthetase (

) (GSH-S), a homodimeric enzyme that catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to phosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis, the first step being catalysed by gamma-glutamylcysteine synthetase . In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, and increased rate of haemolysis and defective function of the central nervous system .
CcmH/CycL/Ccl2/NrfF, N-terminal (CcmH/CycL/Ccl2/NrfF_N)
Type: Domain

Cytochrome c-type biogenesis protein CcmH is a membrane-anchored thiol-oxidoreductase that is essential in the maturation of c-type cytochromes. CcmH consists of an N-terminal catalytic domain with the active site CXXC motif, exposed to the periplasm, and a C-terminal domain of unknown function which is predicted to contain TPR-like repeats. The CXXC motif is believed to be active in the reduction of the cysteines of the CXXCH motif on apocytochromes c . In Arabidopsis, AtCCMH (At1g15220) is a mitochondrial protein that plays a central role in mitochondrial cytochrome c maturation . It forms a complex with CcmF and performs the assembly of heme with c-type apocytochromes in plant mitochondria . NrfF is not required for the biogenesis of c-type cytochromes .

This domain is found in NrfF, CcmH, CycL, Ccl2; in some members it corresponds to the N-terminal domain while in others this is the only domain found.
Groucho/TLE, N-terminal Q-rich domain (Groucho/TLE_N)
Type: Domain

The N-terminal domain of the Grouch/TLE co-repressor proteins are involved in oligomerisation.
Outer membrane protein, OmpW (OMPW)
Type: Family

This family includes outer membrane protein W (OmpW) proteins from a variety of bacterial species. This protein may form the receptor for S4 colicins in Escherichia coli .

OmpW may confer salt tolerance in different bacteria such as Vibrio parahaemolyticus, Vibrio alginolyticus and Photobacterium damselae. In Vibrio cholerae contributes to its elevated salt tolerance and osmoadaptation as it is up-regulated under high NaCl concentrations which is mediated through the transport of carnitine .
Uncharacterised protein family, YajG (Uncharacterised_YajG)
Type: Family

The function of this presumed lipoprotein is unknown. The family includes Escherichia coli YajG

.
Negative modulator of initiation of replication SeqA (SeqA)
Type: Family

The binding of the negative modulator of initiation of replication (SeqA) protein to hemimethylated GATC sequences is important in the negative modulation of chromosomal initiation at oriC, and in the formation of SeqA foci necessary for Escherichia coli chromosome segregation . SeqA tetramers are able to aggregate or multimerize in a reversible, concentration-dependent manner . Apart from its function in the control of DNA replication, SeqA may also be a specific transcription factor .
Chaperone NapD, nitrate reductase assembly (Chaperone_NapD_NO3_reduct)
Type: Family

Periplasmic nitrate reductase (NapABC enzyme) is responsible for nitrate dissimilation . This entry represents NapD, the twin-arginine signal-peptide-binding chaperone for NapA, functioning as an assembly protein for NapABC which is essential for its activity. It may have a role in the insertion of the NapA molybdenum cofactor . The periplasmic NapABC enzyme likely functions during growth in nitrate-limited environments .
Corrinoid adenosyltransferase PduO/GlcC-like (PduO/GlcC-like)
Type: Family

This entry includes Protein GlcG from Escherichia coli, Corrinoid adenosyltransferase PduO from Salmonella typhimurium and many uncharacterised proteins from bacteria and fungi. GlcG controls the expression of the genes of the glycolate pathway . The structure of GlcG is composed of an α-β(2)-α(3)-β(2)-α fold, similar to the Roadblock/LC7 domain. PduO converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), the cofactor for propanediol dehydratase .

Extracellular haem-binding protein from Streptomyces reticuli (HbpS,

) is also included in this entry. This protein interacts with the SenS/SenR two-component signal transduction system. Iron binds to surface-exposed lysine residues of an octomeric assembly of the protein .

This entry also includes the formaldehyde-sensing protein EfgA that directly binds formaldehyde and causes rapid growth arrest and cessation of translation in response to elevated levels of formaldehyde .
PepSY-associated TM protein (PepSY-ass_TM)
Type: Family

This family contains proteins of up to five transmembranes helices found in bacterial species, some of which carry a nested PepSY domain. Coil residues are significantly more conserved than other residues and are frequently found within channels and transporters, where they introduce the flexibility and polarity required for transport across the membrane .

PepSY (peptidase (M4) and YpeB of subtilis) is a repeated region first identified in Thermoanaerobacter tengcongensis. The PepSY domain functions in the control of M4 peptidases through their propeptide and in the germination of spores. It may also play a part in regulating protease activity .
Recombinase Flp protein, C-terminal (Recombinase_Flp_C)
Type: Domain

Yeast Flp-like recombinases mediate the amplification of the 2 micron circular plasmid copy number by catalyzing the intra-molecular recombination between two inverted repeats during replication. They belong to the DNA breaking-rejoining enzyme superfamily, which also includes prokaryotic tyrosine recombinases and type IB topoisomerases. These enzymes share the same fold in their catalytic domain containing six conserved active site residues and the overall reaction mechanism. Flp-like recombinases are almost exclusively found in yeast and are highly diverged in sequence from the prokaryotic tyrosine recombinases. They cleave their target DNA in trans with a composite active site in which the catalytic tyrosine is provided by a promoter bound to a site other than the one being cleaved. Thus each active site within Flp complexes is assembled by domain swapping and contains catalytic residues from two different monomers. Two DNA segments are synapsed by the tetrameric enzyme, carrying the nucleophilic tyrosine in each active site with only two of the four monomers active at a given time. The catalytic domain is linked through a flexible loop to the N-terminal domain, which is largely responsible for non-specific DNA binding and isomerization. Its overall fold is similar to the SAM domain fold also found in the N-terminal domains of lambda integrase and XerD recombinase .
CutC-like (CutC-like)
Type: Family

CutC was originally thought to be involved in copper tolerance in Escherichia coli, as mutation in the corresponding gene lead to an increased copper sensitivity . However, this phenotype has been later reported to depend on the levels of the mRNA-interfering complementary RNA regulator MicL, which is transcribed from a promoter located within the coding sequence of the cutC gene in the enterobacteria . In the plant pathogen Xylella fastidiosa, this protein has been reported as specific for copper efflux . The structure of this protein in the bacteria Shigella flexneri showed a monomer structure that adopts a common TIM β/α barrel with 8 β-strands surrounded by 8 α-helices .

The human homologue of this protein, which structure showed a potential copper-binding site, has an important role in intracellular copper homeostasis .
General secretion pathway protein K (GspK)
Type: Family

Members of this family are involved in the general secretion pathway required for the energy-dependent secretion of extracellular factors such as proteases and toxins from the periplasm, such as GspK. GspK plays a role in pseudo pilus assembly and seems to control its length. It interacts with the pseudopilus tip complex that is critical for the recognition and binding of secretion substrates . The family includes proteins such as ExeK , PulK , OutK and XcpX .
Beta-glucan synthesis-associated protein Skn1/Kre6/Sbg1 (Skn1/Kre6/Sbg1)
Type: Family

This family consists of the beta-glucan synthesis-associated proteins SKN1, KRE6 and Sbg1. Beta1,6-Glucan is a key component of the yeast cell wall, interconnecting cell wall proteins, beta1,3-glucan, and chitin. SKN1 and KRE6 show similarities to glycoside hydrolase family 16 glycoside hydrolases, suggesting that they are glycosyl hydrolases or transglycosylases . Loss of KRE6 shows reduced levels of both beta-1,3-glucan and beta-1,6-glucan synthesis, while loss of SKN1 affects sphingolipid biosynthesis , being related with the synthesis and anchorage of cell wall proteins of glucan polymers of the yeast cell wall, although they play redundant roles . SKN1, KRE6 and Sbg1 share the SKN1 domain, which is conserved in SKN1 and KRE6 proteins of many fungal species. Sbg1 is an integral membrane protein essential for contractile-ring constriction and septum formation during cytokinesis, which interacts with the conserved beta-glucan synthase Bgs1 and regulates its protein levels and localisation .
Terpene synthase, metal-binding domain (Terpene_synthase_metal-bd)
Type: Domain

Sequences containing this domain belong to the terpene synthase family . It has been suggested that this gene family be designated tps (for terpene synthase). Sequence comparisons reveal similarities between the monoterpene (C
10
) synthases, sesquiterpene (C
15
) synthases and the diterpene (C
20
) synthases. It has been split into six subgroups on the basis of phylogeny, called Tpsa-Tpsf .

Tpsa includes vetispiradiene synthase

, 5-epi- aristolochene synthase,

and (+)-delta-cadinene synthase

.

Tpsb includes (-)-limonene synthase,

.

Tpsc includes copalyl diphosphate synthase (kaurene synthase A),

.

Tpsd includes taxadiene synthase,

, pinene synthase,

and myrcene synthase,

.

Tpse includes ent-kaurene synthase B

.

Tpsf includes linalool synthase

.

In the fungus Phaeosphaeria sp. (strain L487) the synthesis of ent-kaurene from geranylgeranyl diphosphate is promoted by a single bifunctional protein .

This domain is involved in the cyclization of linear terpenes .
Flavinator of succinate dehydrogenase (SDH)
Type: Family

This family includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE.

Both yeast and human Sdh5/SDHAF2 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Mutational inactivation of Sdh5 confers tumor susceptibility in humans .

This family was previously annotated in Pfam as being a divergent TPR repeat but structural evidence has indicated this is not true.
Chaperone protein Skp (Chaperone_Skp)
Type: Family

The 17kDa protein Skp (also known as OmpH) of Escherichia coli is a homotrimeric periplasmic chaperone for newly synthesised outer-membrane proteins, the X-ray structure of which has been reported at resolutions of 2.35 A and 2.30 A . Three hairpin-shaped α-helical extensions reach out by approximately 60 A from a trimerisation domain, which is composed of three intersubunit β-sheets that wind around a central axis. The α-helical extensions approach each other at their distal turns, resulting in a fold that resembles a 'three-pronged grasping forcep'. The overall shape of Skp is reminiscent of the cytosolic chaperone prefoldin, although it is based on a radically different topology. The peculiar architecture, with apparent plasticity of the prongs and distinct electrostatic and hydrophobic surface properties, supports the recently proposed biochemical mechanism of this chaperone: formation of a Skp(3)-Omp complex protects the outer membrane protein from aggregation during passage through the bacterial periplasm.

The ability of Skp to prevent the aggregation of model substrates in vitro is independent of ATP. Skp can interact directly with membrane lipids and lipopolysaccharide. These interactions are needed for efficient Skp-assisted folding of membrane proteins .

The Haemophilus influenzae member of the family, OMP26, is an outer membrane protein that shows significant potential as a vaccine candidate . It is not clear if this protein has undergone adaptive changes in H. influenzae so as to locate to the outer membrane, or if Skp proteins are to some extent peripherally associated with the outer membrane in all species.
Large ribosomal subunit protein uL23, N-terminal (Ribosomal_uL23_N)
Type: Domain

The N-terminal domain appears to be specific to the eukaryotic large ribosomal subunit protein uL23 (also known as L25, L23, and L23a).

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Male specific sperm protein (MSSP)
Type: Family

This is a family of Drosophila proteins, that are typified by the repetitive motif C-G-P.
Inner centromere protein, ARK-binding domain (Inner_centromere_prot_ARK-bd)
Type: Domain

This region of the inner centromere protein has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has been implicated in the coordination of chromosome segregation with cell division in yeast .
DTW (DTW)
Type: Domain

This presumed domain is found DTWD1/DTWD2 from humans and YfiP (also known as TapT) from Escherichia coli. The domain contains multiple conserved motifs including a DTXW motif that this domain has been named after. DTW domain containing protein may have a SAM-dependent acp transferase activity .
TAP C-terminal (TAP-C) domain (TAP_C_dom)
Type: Domain

The vertebrate Tap protein is a member of the NXF family of shuttling transport receptors for nuclear export of mRNA. Tap has a modular structure, and its most C-terminal domain is important for binding to FG repeat-containing nuclear pore proteins (FG-nucleoporins) and is sufficient to mediate nuclear shuttling . The structure of the C-terminal domain is composed of four helices . The structure is related to the UBA domain.

The NXF family of mRNA nuclear export factors includes vertebrate NXF1 (also called tip-associated protein or mRNA export factor TAP), NXF2 (also called cancer/testis antigen CT39 or TAP-like protein TAPL-2), Caenorhabditis elegans NXF1 (ceNXF1), Saccharomyces cerevisiae mRNA nuclear export factor Mex67p and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. An NXF protein is multi-domain with a nuclear localization sequence (NLS), a non-canonical mRNA-binding domain, and four leucine-rich repeats (LLR) at the N-terminal region. Its C-terminal part contains a NTF2-like domain and a ubiquitin-associated (UBA)-like domain, joined by flexible Pro-rich linker. Caenorhabditis elegans NXF1 are essential for the nuclear export of poly(A)+mRNA. In budding yeast, Mex67p binds mRNAs through its adaptor Yra1/REF. It also interacts directly with Nab2, an essential shuttling mRNA-binding protein required for export. Moreover, Mex67p associates with both nuclear pore protein (nucleoporin) FG repeats and Hpr1, a component of the TREX/THO complex linking transcription and export .
Pesticidal crystal protein, domain III (Pest_crys_dom-III)
Type: Domain

This entry represents the conserved third domain of the toxic core.

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production . When an insect ingests these proteins, they are activated by proteolytic cleavage. The N terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. The activated region (toxic core) of the toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (

) involved in membrane insertion and pore formation; a β-sheet central domain involved in receptor binding; and a C-terminal β-sandwich domain (

) that interacts with the N-terminal domain to form a channel .
Pesticidal crystal protein, domain I (Pest_crys_dom_I)
Type: Domain

This entry represents the conserved first domain of the toxic core.

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production . When an insect ingests these proteins, they are activated by proteolytic cleavage. The N terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. The activated region (toxic core) of the toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (

) involved in membrane insertion and pore formation; a β-sheet central domain involved in receptor binding; and a C-terminal β-sandwich domain (

) that interacts with the N-terminal domain to form a channel .
Hexon-associated protein IX (Hexon_assoc_IX)
Type: Family

Hexon is the major coat protein in type 2 adenoviruses. Hexon forms a homo-trimer, 240 copies of which are present in the capsid, organised so that 12 lie on each of the 20 facets of this structure. The central 9 hexons in a facet are cemented together by 12 copies of protein IX . Protein IX is not neccessarily required for viral replication, but has been shown to affect several processes including DNA-packaging capacity, thermostability, and the transcriptional activity of several promoters. For more information see .
Lysine exporter LysO (LysO)
Type: Family

Members of this family contain a conserved core of four predicted transmembrane segments. Some members have an additional pair of N-terminal transmembrane helices. This entry includes lysine exporter LysO (YbjE) from E. coli .