SII-SWORD/CoKE huggingface dataset:
Glycoside hydrolase family 63 (Glycoside_hydrolase_63)
Type: Family

This family of enzymes belongs to glycosyl hydrolase family 63 (

). They catalyse the specific cleavage of the non-reducing terminal glucose residue from Glc(3)Man(9)GlcNAc(2). Mannosyl oligosaccharide glucosidase

is the first enzyme in the N-linked oligosaccharide processing pathway.

This family also includes glucosylglycerate hydrolase which catalyses the hydrolysis of glucosylglycerate to glycerate and glucose, during the mycobacterial recovery from nitrogen starvation. This process promotes the rapid mobilisation of the glucosylglycerate that accumulates under these conditions. This enzyme can also hydrolyse mannosylglycerate with lower efficiency .

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.
H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase, C-terminal (HMD_C)
Type: Domain

This entry represents the C-terminal domain of H2-forming N5,N10-methylene-tetrahydromethanopterin dehydrogenases. The N(5),N(10)-methylenetetrahydromethanopterin dehydrogenase system of methanogenic archaea is composed of H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd, represented by this entry) and F420-dependent methylenetetrahydromethanopterin dehydrogenase (

) . Hmd is an iron-sulphur-cluster-free enzyme that contains an intrinsic CO ligand bound to iron . This domain is found at the C terminus of two distinct subgroups: one has been experimentally characterised as H2-forming N(5),N(10)-methenyltetrahydromethanopterin dehydrogenase (Hmd or HmdI), and the other one contains isozymes that have not been experimentally characterised (HmdII and HmdIII). Because all three isozyme forms are present in each of the corresponding sequenced genomes, it has been suggested that HmdII and HmdIII may not exhibit Hmd activity and may have a different biological function . Based on on its ability to bind to aminoacyl-tRNA synthetases and tRNA, a role for HmdII has been proposed as a regulator of protein synthesis that senses intracellular methylene-H4 MPT concentration .
Mycoplasma lipoprotein, C-terminal (Lipoprotein_10_C)
Type: Domain

This domain is found along with a central domain (

) in a group of Mycoplasma lipoproteins of unknown function.
Mercury transport protein MerC (Mercury-R_MerC)
Type: Family

The mercury resistance protein, MerC, is an inner membrane protein that mediates Hg
2+
transport into the cytoplasm . MerA then converts the inorganic form of mercury Hg2+ to the less toxic form Hg0, thereby conferring mercury resistance .
Nitrogen fixation protein NifW (NifW)
Type: Family

Nitrogenase is a complex metalloenzyme composed of two proteins designated the Fe-protein and the MoFe-protein. Apart from these two proteins, a number of accessory proteins are essential for the maturation and assembly of nitrogenase. Even though experimental evidence suggests that these accessory proteins are required for nitrogenase activity, the exact roles played by many of these proteins in the functions of nitrogenase are unclear . Using yeast two-hybrid screening it has been shown that NifW can interact with itself as well as NifZ.
Borrelia outer surface protein D OspD (OspD)
Type: Family

This is a family of outer surface proteins from Borrelia. The function of these proteins is unknown.
Prenylated rab acceptor PRA1 (Prenylated_rab_accept_PRA1)
Type: Family

Prenylated Rab acceptor protein 1 (PRA1) family includes PRAF1/2/3 from mammals, Yip3 from budding yeasts and several PRA proteins from plants.

In budding yeast, Yip3 interacts with members of the Rab GTPase family and may be involved in transport between the ER and Golgi complex .

In humans, PRAF1 is a general Rab protein regulator required for vesicle formation from the Golgi complex. It may control vesicle docking and fusion by mediating the action of Rab GTPases to the SNARE complexes . It inhibits the removal of Rab GTPases from the membrane by GDI . PRAF2 plays a pro-apoptotic role in cerulenin-induced neuroblastoma apoptosis . PRAF3 negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate .
PucC-related (PucC-rel)
Type: Family

The PucC protein is required for high-level transcription of the PUC operon. It is an integral membrane protein. The entry includes PucC and other proteins from the Major Facilitator Superfamily.
P/V phosphoprotein, paramyxoviral (P/V_Pprotein_paramyxoviral)
Type: Family

Paramyxoviral P genes are able to generate more than one product, using alternative reading frames and RNA editing. The P gene encodes the structural phosphoprotein P. In addition, it encodes several non-structural proteins present in the infected cell but not in the virus particle. This family includes phosphoprotein P and the non-structural phosphoprotein V from different paramyxoviruses. Phosphoprotein P is a modular protein organised into two moieties that are both functionally and structurally distinct: a well-conserved C-terminal moiety that contains all the regions required for transcription, and a poorly conserved, intrinsically unstructured N-terminal moiety that provides several additional functions required for replication. The N-terminal moiety is responsible for binding to newly synthesized free N(0) (nucleoprotein that has not yet bound RNA), in order to prevent the binding of N(0) to cellular RNA. The C-terminal moiety consists of an oligomerisation domain, an N-RNA (nucleoprotein-RNA)-binding domain and an L polymerase-binding domain . Phosphoprotein P is essential for the activity of the RNA polymerase complex which it forms with the L subunit. Although all the catalytic activities of the polymerase are associated with the L subunit, its function requires specific interactions with phosphoprotein P . The P and V phosphoproteins are amino co-terminal, but diverge at their C-termini. This difference is generated by an RNA-editing mechanism in which one or two non-templated G residues are inserted into P-gene-derived mRNA. In Measles virus and Sendai virus, one G residue is inserted and the edited transcript encodes the V protein. In Mumps virus, Simian virus 5 and Newcastle disease virus, two G residues are inserted, and the edited transcript codes for the P protein . Being phosphoproteins, both P and V are rich in serine and threonine residues over their whole lengths. In addition, the V proteins are rich in cysteine residues at the C-termini .
Pectate lyase PlyH/PlyE-like (Pectate_lyase_PlyH/PlyE-like)
Type: Family

Pectate lyase is responsible for the maceration and soft-rotting of plant tissue. It catalyses the eliminative cleavage of pectate to produce oligosaccharides with 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends. Pectate lyase is an extracellular enzyme and is induced by pectin. It is subject to self-catabolite repression, and has been implicated in plant disease.

This entry represents a group of pectate lyases, including PlyE and PlyH from Aspergillus nidulans .
Pertactin, central region (Pertactin_central)
Type: Domain

Bordetella pertussis is a Gram-negative, aerobic coccobacillus that causes pertussis (whooping cough), especially in young children . Once present in the lungs, the bacterium attaches to ciliated pulmonary epithelial cells via a collection of outer membrane proteins, all of which are virulence factors.

Pertactin, or P69 protein, is one of these virulence factors. Pertactin and filamentous haemagglutinin have been identified as Bordetella adhesins . Both proteins contain an arg-gly-asp (RGD) motif that promotes binding to integrins, known to be important in cell mobility and development. The production of most Bordetella virulence factors (including pertactin) is controlled by a two-component signal transduction system, comprising the BvgA regulator and the BvgS sensor . Pertactin shares a high level of similarity with other Bordetella adhesins, such as BrkA. The protein is first produced as a 93kDa precursor. Upon secretion into the extracellular environment, a 30kDa domain at the C terminus remains in the outer membrane, while the mature 60.4kDa pertactin molecule is released .

The crystal structure of mature pertactin has been determined to 2.5A resolution by means of X-ray diffraction. The fold is characterised by a 16-stranded parallel β-helix, with a V-shaped cross-section. Several between-strand amino-acid repeats form internal and external ladders. The helical structure is interrupted by several protruding loops that contain motifs associated with the activity of the protein. One such sequence -[GGXXP]5 -appears directly after the RGD motif, and may mediate interaction with epithelial cells. The C-terminal region of P.69 pertactin contains a [PQP]5 motif loop, which contains the major immunoprotective epitope .

The superfamily also includes immunoglobulin A1 protease and adhesion penetration protein HAP.
Poxvirus P35 (Poxvirus_P35)
Type: Family

The Poxvirus P35 protein is an immunodominant envelope protein also known as Envelope protein OPG108. It binds to heparan sulphate on the cell surface to provide virion attachment to target cell .
Reversibly glycosylated polypeptide (RGP)
Type: Family

This family consists of previously named Reversibly Glycosylated Proteins (RGPs), which are plant-specific cytosolic proteins that tend to associate with the Golgi membranes and have been implicated in polysaccharide biosynthesis . In Arabidopsis thaliana the RGP protein family consists of five closely related members, three of which have been identified as UDP-arabinopyranose mutases that catalyze the formation of UDP-L-arabinofuranose (UDP-Araf) from UDP-Larabinopyranose (UDP-Arap). This interconversion is essential for cell wall establishment and plant development .

.
Rhabdovirus nucleoprotein (Rhabdo_ncap_2)
Type: Family

This is a family of Rhabdovirus nucleocapsid proteins. These proteins undergo phosphorylation.
Lactobacillus surface layer protein (S-layer_prot)
Type: Family

The bacterial S-layer forms a regular structure, composed of a monolayer of one glycolprotein on the surfaces of many prokaryotic species. S-layers fulfil different functions, such as serving as attachment structures for extracellular enzymes and acting as major virulence determinants for pathogenic species.

This entry represents a family of S-layer proteins from Lactobacillus .
Tombusvirus p19 core protein (Tombusvirus_p19)
Type: Family

This family represents the Tombusvirus P19 core protein.
ATPase, V1 complex, subunit C (ATPase_V1-cplx_csu)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents the C subunit that is part of the V1 complex, and is localised to the interface between the V1 and V0 complexes . This subunit does not show any homology with F-ATPase subunits. The C subunit plays an essential role in controlling the assembly of V-ATPase, acting as a flexible stator that holds together the catalytic (V1) and membrane (V0) sectors of the enzyme . The release of subunit C from the ATPase complex results in the dissociation of the V1 and V0 subcomplexes, which is an important mechanism in controlling V-ATPase activity in cells.
ATPase, V1 complex, subunit H (ATPase_V1-cplx_hsu)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents subunit H (also known as Vma13p) found in the V1 complex of V-ATPases. This subunit has a regulatory function, being responsible for activating ATPase activity and coupling ATPase activity to proton flow . The yeast enzyme contains five motifs similar to the HEAT or Armadillo repeats seen in the importins, and can be divided into two distinct domains: a large N-terminal domain consisting of stacked α helices, and a smaller C-terminal α-helical domain with a similar superhelical topology to an armadillo repeat .
Viral heat shock protein Hsp90 homologue (Vir_Hsp90)
Type: Family

This family includes the Beet yellows virus heat shock protein 90 homologue and other hypothetical proteins.
Yippee/Mis18/Cereblon (Yippee/Mis18/Cereblon)
Type: Domain

This domain is found in both Yippee-type proteins and Mis18 kinetochore proteins. Yippee are putative zinc-binding/DNA-binding proteins . Mis18 are proteins involved in the priming of centromeres for recruiting CENP-A . Mis18-alpha and beta form part of a small complex with Mis18-binding protein. Mis18-alpha is found to interact with DNA de-methylases through a Leu-rich region located at its carboxyl terminus . This domain includes the CULT domain from proteins such as Cereblon .
Gamma interferon inducible lysosomal thiol reductase GILT (Interferon-induced_GILT)
Type: Family

In humans, GILT (gamma-interferon-inducible lysosomal thiol reductase) functions in MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation by reducing disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation . Several other functions of GILT have also been found, for instance, GILT can act as a host factor for Listeria monocytogenes infection and is involved in the maintenance of cellular glutathione (GSH) levels .

GILT is characterised by a CXXC motif in the active site and an enzymatic mechanism in which the pair of active site cysteine residues cooperate to reduce substrate disulfide bonds . The GIL homologues from Drosophila melanogaster may play a role in the innate immune response upon bacterial challenge .
Adenoviral core protein VII (Adeno_VII)
Type: Family

Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones. Protein VII forms complexes with nucleosomes, limiting DNA accessibility, and sequesters protein HMGB1 in the chromatin. HMGB1 is normally released in response to inflammatory stimuli and mediates activation of immune responses. This is thought to be part of a viral strategy to control extracellular immune signaling . Protein VII also plays a role in packaging the viral DNA .
Herpesvirus glycoprotein J (Herpes_gJ)
Type: Family

The exact function of the herpesvirus glycoprotein J is unknown, but it appears to play a role in the inhibition of apotosis of the host cell .
Antirestriction protein (Antirestrict)
Type: Family

This family includes various protein that are involved in antirestriction. The ArdB protein efficiently inhibits restriction by members of the three known families of type I systems of Escherichia coli .
Nonstructural protein NS-S, bunyaviral (NS-S_bunyaviral)
Type: Family

Bunyavirus has three genomic segments: small (S), middle-sized (M), and large (L). The S segment encodes the nucleocapsid and a non-structural protein (NS-S). The M segment codes for two glycoproteins, G1 and G2, and another non-structural protein (NSm). The L segment codes for an RNA polymerase.

This entry represents the segment S non-structural protein NS-S. This protein, present in infected cells, but absent from purified virus particles , is not essential for virus replication, but contributes substantially to pathogenesis . It has been shown to inhibit the production of alpha/beta interferons, and to inhibit interferon regulatory factor-mediated cell death . It is a viral suppressor of host RNAi and viral inducer of host attractiveness to insect vectors. NS-S acts as a suppressor of RNA-mediated gene silencing, also known as post-transcriptional gene silencing, a mechanism of plant viral defence that limits the accumulation of viral RNAs .
Aphid transmission protein (Caulimo_AT)
Type: Family

This protein is found in various caulimoviruses. It codes for an 18kDa protein (PII), which is dispensable for infection but which is required for aphid transmission of the virus . This protein interacts with the PIII protein .
Cdc37 (Cdc37)
Type: Family

In the budding yeast Saccharomyces cerevisiae (Baker's yeast), cell division control protein Cdc37 is required for the productive formation of Cdc28-cyclin complexes. Cdc37 may be a kinase targeting subunit of Hsp90 .
GmrSD restriction endonucleases, N-terminal domain (GmrSD_N)
Type: Domain

This entry (previously known as DUF262) represents a domain found N-terminal in the GmrSD family of modification-dependent restriction endonucleases including BrxU and SspE proteins . BrxU is a type IV DNA modification-dependent restriction enzyme, which is promiscuous and uses a range of nucleotide and metal co-factors to recognise and cleave DNA that contains any of at least three different modifications, and this activity is dependent on the initial nucleotide-driven dissociation of BrxU dimers, and subsequent nucleotide hydrolysis . SspE is a dual-function protein that exerts both N-terminal NTPase and C-terminal DNA nicking nuclease activities to defend against phage infection . BrxU targets and cleaves DNA containing one of at least three DNA modifications, 5mC, 5hmC or glc-5hmC whereas SspE has a phosphorothioate (PT) modification-binding preference and utilises epigenetic PT modification to accomplish self-nonself discrimination and to coordinate its NTPase and DNA nicking activities to fight against phages. The domain represented in this entry is involved in nucleotide binding, recognition and hydrolysis.
ESAG protein (ESAG)
Type: Family

Trypanosoma brucei is the causative agent of sleeping sickness in humans and nagana in cattle. The parasite lives extracellularly in the blood and tissue fluids of the mammalian host, and is transmitted by the bite of infected tsetse. Each variant surface glycoprotein (Vsg) expression site (ES) in bloodstream-form T. brucei is a polycistronic transcription unit containing several distinct expression site-associated genes (esag), in addition to a single vsg gene. They are co-transcribed with the gene encoding the VSG protein, forming the surface coat of the parasite.
Iron permease FTR1/Fip1/EfeU (FTR1/Fip1/EfeU)
Type: Family

Fungi uptake extracellular ferrous iron (Fe2+) using a bipartite high-affinity transporter consisting of a multicopper ferroxidase associated with a membrane permease which translocates generated ferric iron (Fe3+) into the cytosol. The Saccharomyces cerevisiae (Baker's yeast) iron permease FTR1 is a plasma membrane permease for high-affinity iron uptake . FTR1, together with multicopper oxidase FET3, mediate high-affinity iron uptake. Schizosaccharomyces pombe Fio1 (ferrous iron oxidase) and Fip1 (ferriferous permease), share significant similarity to FET3 and FTR1 from S. cerevisiae . In Neosartorya fumigata, the high affinity iron permease is known as FtrA .

Many bacteria possess Fe2+ transporters with functional similarities to the FET3-FTR1 system. Escherichia coli encodes an EfeUOB transporter where EfeU is homologous to the high-affinity iron permease FTR1 of Saccharomyces cerevisiae . Bacillus subtilis encodes similar proteins, but not identical to the E. coli EfeUOB transporter components. B. subtilis EfeUOB uses a transport system that permits the high-affinity acquisition of both Fe2+ and Fe3+ .

This entry also includes the vacuolar iron transporter FTH1 .
HpaB/PvcC/4-BUDH (HpaB/PvcC/4-BUDH)
Type: Family

4-hydroxyphenylacetate (4HPA) 3-monooxygenase consists of two components, a large component, HpaB, which is an oxygenase, and a small component, HpaC, which is a reductase. 4-HPA 3-monooxygenase is NADH-dependent and uses FAD as the redox chromophore. HpaB utilises FADH2 supplied by HpaC to catalyse the hydroxylation of 4-hydroxyphenylacetic acid, leading to the production of 3,4-dihydroxyphenylacetic acid (DHPA) .

This entry represents the 4-hydroxyphenylacetate 3-monooxygenase oxygenase component, HpaB. It also represents the related prokaryotic enzymes Pyoverdin chromophore biosynthetic protein (PvcC), which may play a role in one of the proposed hydroxylation steps of pyoverdine chromophore biosynthesis , 4-nitrophenol 2-monooxygenase, oxygenase component (NphA1), which utilizes the flavins supplied by NphA2 to catalyse the degradation of 4-nitrophenol (4-NP) via 4-nitrocatechol (4-NC) for its use as the sole carbon, nitrogen, and energy source by Rhodococcus sp. , and 4-hydroxybutyryl-CoA dehydratase (4-BUDH), a key enzyme in the metabolism of gamma-aminobutyrate . (3S)-3-amino-3-(3-chloro-4-hydroxyphenyl) propanoyl-[peptidyl-carrier protein SgcC2] monooxygenase (SgcC), the oxygenase component of a two-component system involved in antibiotic biosynthesis is also included in this group.
Late embryogenesis abundant protein, LEA_3a subgroup (LEA_3a)
Type: Family

This entry represents Lea5(D73) by LEA-3. Proteins in this entry includes LEA5 from Citrus sinensis , whose expression is induced by salt, drought and heat stress . This entry also includes At4g02380 (SAG21), At1g02820 (LEA2), At3g53770 (LEA37) and At4g15910 (LEA41) from Arabidopsis .

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .