SII-SWORD/CoKE huggingface dataset:
GatD, N-terminal superfamily (GatD_N_sf)
Type: Homologous_superfamily

GatD (Glutamyl-tRNA(Gln) amidotransferase subunit D) is found only in the Archaea. It is part of a heterodimer, with GatE (

), that acts as an amidotransferase on misacylated Glu-tRNA(Gln) to produce Gln-tRNA(Gln). This function is carried out in bacteria by the GatABC system, which acts both on Asp-tRNA(Asn) and Glu-tRNA(Gln). GatABC orthologues also exist in some archaea, where it coexist with GatDE; while other archaea only posses GatED and use an asparaginyl-tRNA synthetase to produce Asn-tRNA by direct acylation of the tRNA .

This entry represents the N-terminal domain of GatD.
Protein 9b, SARS-CoV (Protein_9b_SARS)
Type: Homologous_superfamily

This is a superfamily of proteins found in severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-like viruses. Protein 9b is also known as ORF-9b and accessory protein 9b. The protein has a novel fold which forms a dimeric tent-like β structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules . This cavity is likely to be involved in membrane attachment . SARS-CoV ORF-9b targets mitochondrial antiviral signalling proteins (MAVS), suppressing innate immunity .
PapC, N-terminal domain superfamily (PapC_N_sf)
Type: Homologous_superfamily

Bacteiral pili are assembled using the chaperone usher system. In E. coli this is composed of the chaperone PapD and the usher PapC. This domain represents the N-terminal domain from PapC and its homologues. This domain is involved in substrate binding .
NADH-ubiquinone oxidoreductase 51kDa subunit, FMN-binding domain superfamily (Nuo51_FMN-bd_sf)
Type: Homologous_superfamily

This superfamily represents the FMN-binding domain for NADH-ubiquinone oxidoreductase 51kDa subunit from NADH:ubiquinone oxidoreductase. Its structure is composed of three layers (α/β/α) with a parallel β-sheet of four strands.

Among the many polypeptide subunits that make up complex I, there is one with a molecular weight of 51kDa (in mammals), which is the second largest subunit of complex I . The 51kDa subunit, as the corresponding bacterial subunit (Nqo1 in Thermus and NuoF in E. coli) , contains the NADH-binding site, the primary electron acceptor FMN-binding site, and a 4Fe-4S cluster .
CAC2185-like superfamily (CAC2185-like_sf)
Type: Homologous_superfamily

This protein has no known function. It is found in various hypothetical and putative bacterial proteins.

Structurally, it consists of two non-similar domains, each one composed of three layers (α/β/α). The first domain has parallel sheet of four strands, while the second domain has parallel sheet of five strands and antiparallel meander sheet of three strands.
Endoribonuclease EndoU-like (EndoU-like)
Type: Homologous_superfamily

This entry represents the EndoU-like endoribonucleases from a variety of organisms that range from viruses to humans. The founding member XendoU is a uridylate-specific, divalent cation-dependent enzyme that produces molecules with 2',3'-cyclic phosphate ends . The human EndoU, known as PP11, is a endoribonuclease with placental tissue specificity .

In human SARS coronavirus, EndoU (also known as NSP15) is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription. NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA , either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends . PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP) .
PhtA domain superfamily (PhtA_dom_sf)
Type: Homologous_superfamily

This entry represents the Pneumococcal histidine triad protein A (PhtA), which contains a repeated sequence region that includes a His-X-X-His-X-His (histidine triad) motif. Members of the superfamily are suggested to cleave human complement component 3, and family member PhpA has been shown in vaccine studies to be a protective antigen in mice .
Large ribosomal subunit protein bL35 superfamily (Ribosomal_bL35_sf)
Type: Homologous_superfamily

This entry represents the large ribosomal subunit protein bL35, previously known as L35, a basic protein of 60 to 70 amino-acid residues . Like many basic polypeptides, it completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes . This family of ribosomal proteins includes proteins from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants .

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 .

The core structure of L35 has an α-β(3)-α fold arranged in two layers (α/β).
Non-structural protein NSP8 superfamily, coronavirus (NSP8_sf_CoV)
Type: Homologous_superfamily

Viral non-structural protein NSP8 is part of the RNA-dependent RNA polymerase (RdRp) complex and forms a heterotetramer consisting of one molecule of NSP7, two copies of NSP8 and one of NSP12 . NSP8 and NSP7 adopts a hollow cylinder-like structure in which the dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RdRp . NSP7 and NSP8 are co-factors for the catalytic NSP12 that play a role in the stabilisation of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex . It has been demonstrated that NSP8 from human coronavirus 229E acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities . NSP8 has N-terminal and C-terminal D/ExD/E conserved motifs. The N-terminal motif is critical for RNA polymerase activity as these residues are part of the Mg2-binding active site .
NSP8 has a 'golf club'-like structure composed of a long α-helix N-terminal 'shaft' subdomain and an α/β C-terminal 'head' subdomain consisting of three α-helices and seven β-strands (

). The seven β-strands form an open-barrel with two antiparallel β-sheets packed orthogonally. More than half the residues in the C-terminal domain are hydrophobic, and the whole domain forms a tight hydrophobic core .

Together with NSP9, NSP8 suppresses protein integration into the cell membrane, thus, disrupting host immune defenses .

The core structure of NSP8 has an α-β(2)-α-β(4)-α-β fold with bifurcated barrel-like β-sheet.
NAP-like superfamily (NAP-like_sf)
Type: Homologous_superfamily

It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation .

The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organising centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes . During interphase, C-Nap1 localises to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles, and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis .

The structure of NAP-1 has a long α-helix, responsible for homodimerisation via a previously uncharacterised antiparallel non-coiled-coil, and an α/β domain composed of a four-stranded antiparallel β-sheet, implicated in protein-protein interaction .
NADH:ubiquinone oxidoreductase, 30kDa subunit superfamily (NADH_quin_OxRdtase_su_C/D-like)
Type: Homologous_superfamily

Respiratory-chain NADH dehydrogenase (

) (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase). Among the 25 to 30 polypeptide subunits of this bioenergetic enzyme complex there is one with a molecular weight of 30 Kd (in mammals) which has been found to be :

Nuclear encoded, as a precursor form with a transit peptide in mammals, and in Neurospora crassa.

Mitochondrial encoded in Paramecium (protein P1), and in the slime mold Dictyostelium discoideum (ORF 209).

Chloroplast encoded in various higher plants (ORF 159).

It is also present in bacteria:

In the cyanobacteria Synechocystis strain PCC 6803 (gene ndhJ).

Subunit C of Escherichia coli NADH-ubiquinone oxidoreductase (gene nuoC).

Subunit Nqo5 of Paracoccus denitrificans NADH-ubiquinone oxidoreductase. Nqo5 composes the hydrogenase-like module together with the Nqo4, Nqo6, and Nqo9 subunits. Homologous proteins of the Nqo5 subunit are also contained in membrane-bound multisubunit hydrogenases, while soluble-type hydrogenases are not. This subunit is essential in complex I assembly .
CcmK-like superfamily (CcmK-like_sf)
Type: Homologous_superfamily

Bacterial microcompartments (BMCs) are large proteinaceous structures comprised of a roughly icosahedral shell and a series of encapsulated enzymes. The shells of BMCs are made primarily of a family of proteins whose structural core is the BMC domain, and variations upon this core provide functional diversity. This domain is found in a variety of polyhedral organelle shell proteins (CcmK), including CsoS1A, CsoS1B and CsoS1C of Thiobacillus neapolitanus (Halothiobacillus neapolitanus) and their orthologues from other bacteria .

Some autotrophic and non-autotrophic organisms form polyhedral organelles, carboxysomes/enterosomes . The best studied is the carboxysome of Halothiobacillus neapolitanus, which is composed of at least 9 proteins: six shell proteins, CsoS1A, CsoS1B, CsoS1C, Cso2A, Cso2B and CsoS3 (carbonic anhydrase) , one protein of unknown function and the large and small subunits of RuBisCo (CbbL and Cbbs). Carboxysomes appear to be approximately 120 nm in diameter, most often observed as regular hexagons, with a solid interior bounded by a unilamellar protein shell. The interior is filled with type I RuBisCo, which is composed of 8 large subunits and 8 small subunits; it accounts for 60% of the carboxysomal protein, which amounts to approximately 300 molecules of enzyme per carboxysome. Carboxysomes are required for autotrophic growth at low CO
2
concentrations and are thought to function as part of a CO
2
-concentrating mechanism .

Polyhedral organelles, enterosomes, from non-autotrophic organisms are involved in coenzyme B
12
-dependent 1,2-propanediol utilisation (e.g., in Salmonella enterica ) and ethanolamine utilisation (e.g., in Salmonella typhimurium ). Genes needed for enterosome formation are located in the 1,2-propanediol utilisation
pdu
or ethanolamine utilisation
eut
operons, respectively. Although enterosomes of non-autotrophic organisms are apparently related to carboxysomes structurally, a functional relationship is uncertain. A role in CO
2
concentration, similar to that of the carboxysome, is unlikely since there is no known association between CO
2
and coenzyme B12-dependent 1,2-propanediol or ethanolamine utilisation . It seems probable that enterosomes help protect the cells from reactive aldehyde species in the degradation pathways of 1,2-propanediol and ethanolamine .

The BMC domain fold consists of three α-helices (designated A, B, and C) and four β-strands (

). Some instances of the BMC shell protein reveal a circular permutation in which a highly similar tertiary structure is built from secondary structure elements occurring in a different order. The secondary structure elements contributed by the C-terminal region of the typical BMC fold are instead contributed by the N-terminal region of the BMC circularly permuted domain (

) .

CcmK has a Ferredoxin-like fold with an extra C-terminal helix and forms a compact hexameric 'tiles' of hexagonal shape.
ImmE5 superfamily (ImmE5_sf)
Type: Homologous_superfamily

Colicins, which are produced by bacteria carrying the corresponding Col plasmids, kill sensitive Escherichia coli cells using different mechanisms. Colicin E5 is a tRNase toxin. The immunity protein ImmE5 is a specific inhibitor of colicin E5 that is expressed to protect the host cells. It binds to E5 C-terminal ribonuclease domain (CRD) to prevent cell death .

The structure of ImmE5 is composed of an α-β(2)-α-β fold arranged in two layers (α/β) with antiparallel β-sheet.
TRCF-like, C-terminal D7 domain (TRCF-like_C_D7)
Type: Homologous_superfamily

The transcription-repair coupling factor (TRCF, product of the mfd gene) couples transcription and DNA repair in bacteria. TRCF removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair (NER) machinery to the site. This protein, comprised of eight domains, including region of structurally similar to UvrB, shows to distinct activities: the relief of transcription-dependent inhibition of nucleotide excision repair (NER) by recognition and ATP-dependent removal of a stalled RNAP covering the damaged DNA; and the stimulation of DNA repair by recruitment of the Uvr(A)BC endonuclease. The C-terminal region of TRCF have been shown to be necessary for RNAP displacement .

Structural domains comprising this superfamily share the structure of the C-terminal D7 (handle) domain of TRCF, whose precise role is yet to be clarified although some insights have been revealed. Most residues conserved between TRCF and UvrB in the putative UvrA binding surface are buried in the D2/D7 interface and are thus not available for binding UvrA. It is believed that once TRCF engages with the stalled RNAP and displaces it, an RNAP-triggered conformational change in TRCF moves D7 relative to D2, unmasking the putative UvrA binding surface. This enables the recruitment of Uvr(AB) via UvrA binding to D2. Overall, D7 appears to block the otherwise deleiterious interaction between TRCF and UrvA until a conformational change in the former, during its functional cycle, unmasks the UvrA binding determinant .
STIV B116-like superfamily (STIV_B116-like_sf)
Type: Homologous_superfamily

The sulfolobus turreted icosahedral virus (STIV) infects Sulfolobus species found in the hot springs of Yellowstone National Park. It has 37 ORFs including B116, whose function is unknown. The structure of B116 reveals a fold consisting of a five-stranded β-sheet flanked on one side by three α helices. Two subunits come together to form a homodimer with a 10-stranded mixed β-sheet, where the topology of the central strands resembles an unclosed β-barrel .
IlvD/EDD, N-terminal domain (IlvD/EDD_N)
Type: Homologous_superfamily

Two dehydratases, dihydroxy-acid dehydratase (

) (gene ilvD or ILV3) and 6-phosphogluconate dehydratase (

) (gene edd) have been shown to be evolutionary related . Dihydroxy-acid dehydratase catalyses the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of 2,3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyses the first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is Escherichia coli YjhG, which has been identified as a D-xylonate dehydratase . The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a 2Fe-2S iron-sulphur cluster .

The structure of the N-terminal domain contains a large cluster of helices and a mixed β-sheet of four strands where strands 3 and 4 are parallel.
YbiA-like superfamily (YbiA-like_sf)
Type: Homologous_superfamily

This superfamily contains E. coli swarming motility protein YbiA. Mutations in YbiA cause defects in Escherichia coli swarming, but not necessarily in motility. This family was predicted to be involved in NAD-utilizing pathways, likely to act on ADP-ribose derivatives, and was been named NADAR (NAD and ADP-ribose) . More recently, YbiA has been shown to be involved in the disposal of riboflavin intermediates. It catalyzes the hydrolysis of the N-glycosidic bond in the first two intermediates of riboflavin biosynthesis, which are highly reactive metabolites, yielding relatively innocuous products .
Oxysterol-binding protein superfamily (OSBP_sf)
Type: Homologous_superfamily

A number of eukaryotic proteins that seem to be involved with sterol synthesis and/or its regulation have been found to be evolutionary related. These include mammalian oxysterol-binding protein (OSBP), a protein of about 800 amino-acid residues that binds a variety of oxysterols (oxygenated derivatives of cholesterol) ; yeast Osh1, a protein of 859 residues that also plays a role in ergosterol synthesis ; yeast proteins Hes1 and Kes1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis ; Probable transporter efuK from the fungi Hormonema carpetanum, which is involved in the biosynthesis of enfumafungin ; and OSBP-related proteins (ORP) from plants such as Arabidopsis thaliana .

The core structure of OSBP has a large meander β-sheet of 12 strands wrapped around the N-terminal (distorted) α-hairpin. It shares some similarity with transmembrane β-barrel proteins.
ORC1-binding domain (ORC1-binding_dom)
Type: Homologous_superfamily

This entry represents the ORC1-binding domain of Sir1. It has a complex fold, composed of an α-hairpin, meander β-sheet and a five-stranded barrel of unusual topology. Sir1 interacts with the BAH domain of the Orc1 subunit of the origin recognition complex (ORC) resulting in the establishment of silent chromatin at HMR and HML in S.cerevisiae . The amino acids from the ORC interaction region of Sir1 are presented on a conserved, convex surface that forms a complementary interface with the Orc1 BAH domain, critical for transcriptional silencing .
E2F-DP heterodimerization region (E2F-DP_heterodim)
Type: Homologous_superfamily

The E2F transcription factors associated with the corresponding domain of the DP transcription factor forming an heterodimer fold with the N-terminal long helices of both chains forming a parallel coiled coil and their C-terminal folded β-hairpins interlocking together in a β-sandwich. This complex binds the C terminus of retinoblastoma protein .
Vanadium-binding protein 2 superfamily (Vanabin-2_sf)
Type: Homologous_superfamily

The Vanadium binding protein, Vanabin2, contains four α-helices connected by nine disulphide bonds. Vanadium accumulates in Ascidians however the biological reason remains unclear .
Viral leader polypeptide zinc finger (Viral_lead_polypep_zc_finger)
Type: Homologous_superfamily

This is the N-terminal domain of a family of virion proteins which contains a zinc finger domain. Its structure consists of a small β-hairpin with CxH motif and a short helix with CxxC motif. This protein was recently shown to inhibit cellular nucleocytoplasmic transport .
Thylakoid soluble phosphoprotein TSP9 superfamily (TSP9_sf)
Type: Homologous_superfamily

The plant-specific protein, TSP9 is phosphorylated and released in response to changing light conditions from the photosynthetic membrane. The protein resembles the characteristics of transcription/translation regulatory factors. The structure of the protein is predicted to consist of a random coil .
FIP-RBD, C-terminal domain superfamily (FIP-RBD_C_sf)
Type: Homologous_superfamily

The Rab11 GTPase regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis. A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognise the active form of Rab11. FIPs are diverse in sequence length and composition toward their N-termini, presumably a feature that underpins their specific roles in Rab11-mediated vesicle trafficking. They have been divided into three subfamilies (classe I, II, and III)on the basis of domain architecture. Class I FIPs comprises a subfamily of three proteins (Rip11/pp75/FIP5, Rab-coupling protein (RCP), and FIP2) that possess an N-terminal C2 domain, localize to recycling endosomes, and regulate plasma membrane recycling. The class II subfamily consists of two proteins (FIP3/eferin/arfophilin and FIP4) with tandem EF hands and a proline-rich region. Class II FIPs localize to recycling endosomes, the trans-Golgi network, and have been implicated in the regulation of membrane trafficking during cytokinesis. The class III subfamily consists of a single protein, FIP1, which does not contain obvious homology domains or motifs other than the FIP-RBD .

The FIP-RBD domain is also found in Rab6-interacting protein Erc1/Elks. Erc1 is the regulatory subunit of the IKK complex and probably recruits IkappaBalpha/NFKBIA to the complex . It may be involved in the organisation of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. It may also be involved in vesicle trafficking at the CAZ, as well as in Rab-6 regulated endosomes to Golgi transport .

The FIB-RBD domain consists of an N-terminal long α-helix, followed by a 90 degrees bend at a conserved proline residue, a 3(10) helix and a C-terminal short β-strand, adopting an "L" shape. The long α-helix forms a parallel coiled-coil homodimer that symmetrically interacts with two Rab11 molecules on both sides, forming a quaternary Rab11-(FIP)2-Rab11 complex. The Rab11-interacting region of FIP-RBD is confined to the C-terminal 24 amino acids, which cover the C-terminal half of the long α-helix and the short β-strand .