SII-SWORD/CoKE huggingface dataset:
Alpha-2-macroglobulin receptor-associated protein, domain 1 (MG_RAP_rcpt_1)
Type: Domain

The alpha-2-macroglobulin receptor-associated protein (RAP) is a glycoprotein that binds to the alpha-2-macroglobulin receptor, as well as to other members of the low density lipoprotein receptor family (

). RAP acts to inhibit the binding of all know ligands for these receptors, and may prevent receptor aggregation and degradation in the endoplasmic reticulum, thereby acting as a molecular chaperone . RAP may be under the regulatory control of calmodulin, since it is able to bind calmodulin and be phosphorylated by calmodulin-dependent kinase II (

).

RAP is comprised of three domains. Both domains 1 and 3 are involved in binding to the alpha-2-macroglobulin receptor, while domain 1 is also involved in inhibiting the binding of activated alpha-2-macroglobulin (

). Structural studies have revealed the RAP domain 1 to be comprised of a partly opened bundle of three helices, the first one being shorter than the other two.
TAFII-230 TBP-binding (TAF_II_230-bd)
Type: Domain

In eukaryotes, the general transcription factor TFIID helps to regulate transcription by RNA polymerase II from class II promoters. TFIID consists of TATA-box-binding proteins (TBP) and TBP-associated factors (TAFIIs), which together mediate both activation and inhibition of transcription. In Drosophila, the N-terminal region of TAFII-230 (the TFIID 230kDa subunit) binds directly to TBP, thereby inhibiting the binding of TBP to the TATA box. The N-terminal domain is comprised of three α helices and a β hairpin, which forms the core that occupies the DNA-binding surface of TBP .
uS15/NS1, RNA-binding domain superfamily (uS15_NS1_RNA-bd_sf)
Type: Homologous_superfamily

The RNA-binding domains of the small ribosomal subunit protein uS15, also known as ribosomal protein S15, and the influenza virus non-structural protein NS1 share the same structural fold, consisting of three helices in an irregular array. uS15 is one of 21 proteins in the small, bacterial 30S ribosomal subunit, and is required for assembly of the subunit through its binding to 16S rRNA . The multifunctional glutamyl-prolyl-tRNA synthase (EPRS) contains three tandem repeats linking two catalytic domains, all three of which contribute to RNA-binding; the second repeated element bears structural resemblance to the uS15/NS1 RNA-binding domain .
Cysteine alpha-hairpin motif superfamily (Cys_alpha_HP_mot_SF)
Type: Homologous_superfamily

This entry represents the cysteine α-hairpin motif. Proteins with this structure include mature T-cell proliferation 1 neighbour protein and cytochrome c oxidase-assembly factors COX23 and COX19.
High mobility group box domain (HMG_box_dom)
Type: Domain

High mobility group (HMG) box domains are involved in binding DNA, and may be involved in protein-protein interactions as well. The structure of the HMG-box domain consists of three helices in an irregular array. HMG-box domains are found in one or more copies in HMG-box proteins, which form a large, diverse family involved in the regulation of DNA-dependent processes such as transcription, replication, and strand repair, all of which require the bending and unwinding of chromatin. Many of these proteins are regulators of gene expression. HMG-box proteins are found in a variety of eukaryotic organisms, and can be broadly divided into two groups, based on sequence-dependent and sequence-independent DNA recognition; the former usually contain one HMG-box motif, while the latter can contain multiple HMG-box motifs.

HMG-box domains can be found in single or multiple copies in the following protein classes: HMG1 and HMG2 non-histone components of chromatin; SRY (sex determining region Y protein) involved in differential gonadogenesis; the SOX family of transcription factors ; sequence-specific LEF1 (lymphoid enhancer binding factor 1) and TCF-1 (T-cell factor 1) involved in regulation of organogenesis and thymocyte differentiation ; structure-specific recognition protein SSRP involved in transcription and replication; MTF1 mitochondrial transcription factor; nucleolar transcription factors UBF 1/2 (upstream binding factor) involved in transcription by RNA polymerase I; Abf2 yeast ARS-binding factor ; yeast transcription factors lxr1, Rox1, Nhp6b and Spp41; mating type proteins (MAT) involved in the sexual reproduction of fungi ; and the YABBY plant-specific transcription factors.
Histone-fold (Histone-fold)
Type: Homologous_superfamily

Histones mediate DNA organisation and play a dominant role in regulating eukaryotic transcription. The histone-fold consists of a core of three helices, where the long middle helix is flanked at each end by shorter ones. The histone fold is a structural element that facilitates heterodimerisation . Proteins displaying this structure include the nucleosome core histones, which form octomers composed of two copies of each of the four histones, H2A, H2B, H3 and H4; archaeal histone, which possesses only the core domain part of eukaryotic histone; and the TATA-box binding protein (TBP)-associated factors (TAF), where the histone fold is a common motif for mediating TAF-TAF interactions. TAF proteins include TAF(II)18 and TAF(II)28, which form a heterodimer, TAF(II)42 and TAF(II)62, which form a heterotetramer similar to (H3-H4)2, and the negative cofactor 2 (NC2) alpha and beta chains, which form a heterodimer. The TAF proteins are a component of transcription factor IID (TFIID), along with the TBP protein. TFIID forms part of the pre-initiation complex on core promoter elements required for RNA polymerase II-dependent transcription. The TAF subunits of TFIID mediate transcriptional activation of subsets of eukaryotic genes. The NC2 complex mediates the inhibition of TATA-dependent transcription through interactions with TBP.
Co-chaperone HscB, C-terminal oligomerisation domain (HscB_oligo_C)
Type: Domain

This entry represents the C-terminal oligomerisation domain found in HscB (heat shock cognate protein B), which is also known as HSC20 (20K heat shock cognate protein) and J-protein Jac1 in yeast mitochondria . HscB acts as a co-chaperone to regulate the ATPase activity and peptide-binding specificity of the molecular chaperone HscA, also known as HSC66 (HSP70 class). HscB proteins contain two domains, an N-terminal J-domain, which is involved in interactions with HscA, connected by a short loop to the C-terminal oligomerisation domain; the two domains make contact through a hydrophobic interface. The core of the oligomerisation domain is thought to bind and target proteins to HscA and consists of an open, three-helical bundle . HscB, along with HscA, has been shown to play a role in the biogenesis of iron-sulphur proteins.
Acyl-CoA dehydrogenase/oxidase, C-terminal (AcylCo_DH/oxidase_C)
Type: Domain

Acyl-CoA dehydrogenases (

) are a family of flavoproteins that catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with the concomitant reduction of enzyme-bound FAD. Different family members share a high sequence identity, catalytic mechanisms, and structural properties, but differ in the position of their catalytic bases and in their substrate binding specificity. Butyryl-CoA dehydrogenase prefers short chain substrates, medium chain-and long-chain acyl-CoA dehydrogenases prefer medium and long chain substrates, respectively, and Isovaleryl-CoA dehydrogenase prefers branched-chain substrates.

The monomeric enzyme is folded into three domains of approximately equal size, where the N-terminal domain is all-α, the middle domain is an open barrel, and the C-terminal domain is a four-helical bundle. This entry represents the C-terminal domain found in medium chain acyl-CoA dehydrogenases, as well as in the related peroxisomal acyl-CoA oxidase-II enzymes, where this domain occurs as a tandem duplication. Acyl-CoA oxidase (ACO;

) catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids .
FKBP12-rapamycin binding domain (FRB_dom)
Type: Domain

The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the Tor proteins.

In budding yeast, the Tor2 protein exists in two distinct multi-component complexes, TORC1 and TORC2. TORC1 regulates cell growth by regulating many growth-related processes and is rapamycin sensitive, while TORC2 regulates the cell cytoskeleton and is rapamycin insensitive. Budding yeast TORC1 consists of either Tor1 or Tor2 in complex with Kog1, Lst8 and Tco89, while TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 . In both yeast and mammals, FKBP12-rapamycin binds to Tor (Tor1, Tor2, or mTOR) in TORC1, but not to Tor (Tor2 or mTOR) in TORC2. It has been suggested that the architecture of TORC2 or its unique composition might be responsible for the observed rapamycin resistance .
Proteasome activator PA28 (Proteasome_activ_PA28)
Type: Family

The 20S proteasome is a multicatalytic complex that is responsible for the non-lysosomal degradation of intracellular proteins. The proteasome is composed of a catalytic core that is regulated by protein complexes, which bind to the ends of the cylindrical core structure. One of these regulatory complexes is the PA28 activator complex (also known as the 11S regulator, or REG), a ring-shaped hexameric structure that enhances the peptidase activity of the core enzyme. Three REG subunits have been isolated, REGalpha, REGbeta and REGgamma. REGalpha and REGbeta preferentially form a heteromeric complex with alternating alpha and beta subunits. The structure of the human REGalpha subunit reveals a heptameric barrel-shaped assembly containing a central channel . The binding of REG is thought to create a pore through with substrates and products can pass.
Ferritin-like superfamily (Ferritin-like_SF)
Type: Homologous_superfamily

Ferritin is one of the major non-haem iron storage proteins in animals, plants, and microorganisms. It is a multisubunit protein with a hollow interior, which contains a mineral core of hydrated ferric oxide, thereby ensuring its solubility in an aqueous environment . Each subunit consists of a closed, four-helical bundle with a left-handed twist and one crossover connection.

This entry represents the ferritin-like superfamily. Proteins with this structure include ferritin and other ferritin-like proteins such as bacterioferritin (cytochrome b1) that binds haem between two subunits, non-haem ferritin, dodecameric ferritin homologue (DPS) that binds to and protects DNA, and the N-terminal domain of rubrerythrin that is found in many air-sensitive bacteria and archaea . In addition, ribonucleotide reductase-like proteins show a similar structure to the ferritin-like fold; these di-iron carboxylate proteins constitute a diverse class of non-haem iron enzymes performing a multitude of redox reactions . The superfamily also includes the alpha and beta subunits of methane monooxygenase hydrolase, delta 9-stearoyl-acyl carrier protein desaturase and manganese catalase.
Four-helical cytokine-like, core (4_helix_cytokine-like_core)
Type: Homologous_superfamily

This superfamily contains a domain with a core structure consisting of a closed bundle of four helices in a left-handed twist, with two crossover connections. Proteins containing this domain include long-chain cytokines, such as leukaemia inhibitory factor (LIF) , the growth hormone somatotropin , interleukin-6 and leptin ; short-chain cytokines, such as erythropoietin , stem cell factor (SCF) , macrophage colony-stimulating factor (M-CSF) and interleukin-2, -3, -4, -5, -13, -15 and -21; and interferons/interleukin-10.
Aminoacyl-tRNA synthetase, class Ia, anticodon-binding (tRNAsynth_Ia_anticodon-bd)
Type: Homologous_superfamily

Aminoacyl-tRNA synthetase (aaRS) is a key enzyme during protein biosynthesis. Each aaRS contains a catalytic central domain (CCD), responsible for activating amino acid, and an anticodon-binding domain (ABD), necessary for binding the anticodon in cognate tRNA. aaRSs are classified into class I and II (aaRS-I and aaRS-II) based on the topologies of CCDs. Whereas the structure of the CCDs is similar among the members of each of the two different aaRS classes, the ABDs are diverse in structure .

The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan and valine belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases. Both classes of tRNA synthetases have been subdivided into three subclasses, designated Ia, Ib, Ic and IIa, IIb, IIc.

This superfamily represents the anticodon binding domain (ABD) of class Ia aminoacyl-tRNA synthetases, and also matches the ABD of glycine tRNA synthetases.
Phosphopantetheine binding ACP domain (PP-bd_ACP)
Type: Domain

This entry represents the phosphopantetheine binding ACP domain. This domain forms a small negatively charged four helical bundle.

Acyl carrier protein (ACP) is an essential cofactor in the synthesis of fatty acids by the fatty acid synthetases systems in bacteria and plants. In addition to fatty acid synthesis, ACP is also involved in many other reactions that require acyl transfer steps, such as the synthesis of polyketide antibiotics, biotin precursor, membrane-derived oligosaccharides, and activation of toxins, and functions as an essential cofactor in lipoylation of pyruvate and alpha-ketoglutarate dehydrogenase complexes . Phosphopantetheine (or pantetheine 4' phosphate) is the prosthetic group of acyl carrier proteins (ACP) in some multienzyme complexes where it serves as a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups . Phosphopantetheine is attached to a serine residue in these proteins. The core structure of ACP consists of a four-helical bundle, where helix three is shorter than the others.

Several other proteins share structural homology with ACP, such as the bacterial apo-D-alanyl carrier protein, which facilitates the incorporation of D-alanine into lipoteichoic acid by a ligase, necessary for the growth and development of Gram-positive organisms ; and the thioester domain of the bacterial peptide carrier protein (PCP) found within large modular non-ribosomal peptide synthetases, which are responsible for the synthesis of a variety of microbial bioactive peptides .
Transcription factor IIA, alpha-helical domain (TFIIA_a-hlx)
Type: Homologous_superfamily

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .

This superfamily represents the α-helical domain found at the N-terminal of the gamma subunit of transcription factor TFIIA.
B transposition protein, C-terminal (B_transpositn_C)
Type: Domain

Bacteriophage Mu can integrate into the host bacterial genome and replicate via transposition. Mu requires the activity of four proteins for DNA transposition. Two of these proteins are the phage-encoded A and B transposition proteins, while the other two are host-specified accessory factors HU and IHF. These four proteins can form nucleoprotein complexes (transposomes), which enable strand transfer. The stable protein-DNA intermediate is subsequently disassembled prior to DNA replication by host proteins.

The Mu B transposition protein is an ATP-dependent, DNA-binding protein required for target capture and immunity, as well as for activating transpososome function . The C-terminal domain of the B transposition protein is believed to be involved in both DNA-binding and protein-protein contacts with the Mu A transposition protein. The structure of the C-terminal domain consists of four helices in an irregular array .
Bacteriocin AS-48 (Bacteriocin_AS48)
Type: Homologous_superfamily

Bacteriocin AS-48 is a cyclic peptide antibiotic produced by the eubacteria Enterococcus faecalis (Streptococcus faecalis) that shows a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Bacteriocin AS-48 is encoded by the pheromone-responsive plasmid pMB2, and acts on the plasma membrane in which it opens pores leading to ion leakage and cell death . The globular structure of bacteriocin AS-48 is comprised of five α helices enclosing a hydrophobic core. The mammalian NK-lysin effector protein of T and natural killer cells has a similar structure, though it lacks sequence homology with bacteriocins AS-48.

This entry represents the characteristic domain of bacteriocin AS-48.
Rab geranylgeranyltransferase, alpha subunit, insert-domain (RabGGT_asu_insert-domain)
Type: Domain

Rab geranylgeranyltransferase (RabGGT) catalyses the transfer of geranylgeranyl groups to the C-terminal cysteine residues of Rab proteins, Ras-related small GTPases that function in intracellular vesicular transport . RabGGT is only able to prenylate Rab when it is complexed to the Rab escort protein (REP), after which REP remains bound to the prenylated Rab and delivers it to its target membrane. RabGGT is a member of the protein prenyltransferase family, all of which are heterodimers consisting of alpha and beta subunits. RabGGT is distinct from other members of the prenyltransferase family because of the presence of an Ig-like insert domain in the alpha subunit that is folded into an eight-stranded sandwich between two helices in the helical domain.
Transcription factor IIA, beta-barrel (TFIIA_b-brl)
Type: Homologous_superfamily

This superfamily represents the β-barrel domain found at the C-terminal of both TOA1 (or α/β) and TOA2 (or gamma) subunits of TFIIA, and their homologues.

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .
XRCC4, N-terminal domain superfamily (XRCC4_N_sf)
Type: Homologous_superfamily

XRCC4 is essential for non-homologous DNA end joining (NHDJ) in eukaryotes, which is required for double-strand break repair, and V(D)J recombination in immunoglobulin and T-cell receptor genes. XRCC4 forms a complex with DNA ligase IV, and acts as a regulatory element required for the stability and activity of the ligase. XRCC4 forms an elongated dumb-bell-like tetramer consisting of a C-terminal stalk that interacts with DNA ligase IV and an N-terminal globular head. The N-terminal head domain consists of a β sandwich and a helix-turn-helix (HTH) motif, which may be involved in DNA binding .
Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II (RCC1/BLIP-II)
Type: Homologous_superfamily

The beta-lactamase-inhibitor protein II (BLIP-II) is a secreted protein produced by the soil bacteria Streptomyces exfoliates SMF19. BLIP-II acts as a potent inhibitor of beta-lactamases such as TEM-1, which is the most widespread resistance enzyme to penicillin antibiotics. BLIP-II binds competitively to TEM-1, but no direct contacts are made with TEM-1 active site residues. BLIP-II shows no sequence similarity with BLIP, even though both bind to and inhibit TEM-1. However, BLIP-II does share significant sequence identity with the regulator of chromosome condensation (RCC1) family of proteins. These two families are clearly related, both having a seven-bladed β-propeller structure, although they differ in the number of strands per blade, BLIP-II having three antiparallel β-strands per blade, while RCC1 has four-stranded blades . RCC1 is a eukaryotic nuclear protein that acts as a guanine nucleotide exchange factor for Ran, a member of the Ras GTPase family. RCC1 mediates a Ran-GTP gradient necessary for the regulation of spindle formation and nuclear assembly during mitosis, as well as for the transport of macromolecules across the nuclear membrane during interphase.
Telokin-like protein, Tlp20, baculovirus (Telokin-like_Tlp20_baculovir)
Type: Family

The baculovirus, Autographa californica nuclear polyhedrosis virus (AcMNPV), telokin-like protein (Tlp20) lies in a region of the baculoviral genome that is expressed late in the viral replication cycle, however its function is unknown. Tlp20 was discovered using anti-telokin antibodies, telokin being the C-terminal domain of smooth-muscle myosin light-chain kinase . Both Tlp20 and telokin display a seven-stranded antiparallel β-barrel structure, although the 3-dimensional structures of the β-barrels are different and there is no sequence homology between the two. Tlp20 is structurally similar to dUTPase in its fold and trimeric assembly .
Bacteriophage P22 tailspike, N-terminal (P22_tailspike_N)
Type: Domain

The tailspike protein of Salmonella bacteriophage P22 is a viral adhesion protein that mediates attachment of the viral protein to host cell-surface lipopolysaccharide. The tailspike protein displays both receptor binding and destroying properties, inactivating the receptor by endoglycosidase activity. The N-terminal, head-binding domain mediates the non-covalent attachment of the six homotrimeric tailspike molecules to the DNA injection apparatus . The N-terminal domain of the P22 tailspike protein shows significant sequence similarity to the N-terminal domain of the Shigella phage Sf6 tailspike protein .