SII-SWORD/CoKE huggingface dataset:
Talin, central (Talin_cent)
Type: Domain

This domain adopts a structure consisting of five α-helices that fold into a bundle. It contains a vinculin binding site (VBS) composed of a hydrophobic surface spanning five turns of helix four. Activation of the VBS causes subsequent recruitment of vinculin, which enables maturation of small integrin/talin complexes into more stable adhesions. Formation of the complex between VBS and vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin .
tRNA pseudouridine synthase II, TruB, subfamily 2, C-terminal (tRNA_psdUridine_synth_fam2_C)
Type: Domain

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.

TruB is responsible for the pseudouridine residue present in the T loops of virtually all tRNAs. TruB recognises the preformed 3-D structure of the T loop primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA . The C-terminal domain adopts a secondary structure consisting of a four-stranded β sheet and one α helix, similar to that found in PUA domains. It is predominantly involved in RNA-binding, being mostly found in tRNA pseudouridine synthase B (TruB) .
Type III effector HopF2 (T3_effector_HopF2)
Type: Family

Many Gram-negative pathogenic bacteria directly translocate effector proteins into eukaryotic host cells via a type III secretion system. Type III effector proteins are determinants of virulence on susceptible plant hosts; they are also the proteins that trigger specific disease resistance in resistant plant hosts. Evolution of type III effectors is dominated by competing forces: the likely requirement for conservation of virulence function, the avoidance of host defenses, and possible adaptation to new hosts.

Members of this family of plant pathogenic proteins adopt an elongated structure somewhat reminiscent of a mushroom that can be divided into 'stalk' and 'head' subdomains. The stalk subdomain is composed of the N-terminal helix (alpha1) and β strands beta3-beta4. An antiparallel β sheet (beta5, beta7-beta8) forms the base of the head subdomain that interacts with the stalk. A pair of twisted antiparallel β sheets (beta1 and beta6; beta2 and beta9/9') supported by alpha2 form the dome of the head. The head subdomain possesses weak structural similarity with the catalytic portion of a number of ADP-ribosylt ransferase toxins .
Mitogen, Yersinia pseudotuberculosis (Mitogen_YERPS)
Type: Family

Members of this family of Yersinia pseudotuberculosis mitogens adopt a sandwich structure consisting of nine strands in two β sheets, in a jelly-roll topology. As with other superantigens, they are able to excessively activate T cells by binding to the T cell receptor .
SWA2-like, ubiquitin-associated domain (SWA2_UBA)
Type: Domain

Ubiquitin-associated (UBA) domains contain approximately 40 residues and bind ubiquitin non-covalently. They adopt a secondary structure consisting of three α-helices, and have been identified in various modular proteins involved in protein trafficking, clathrin assembly/disassembly, DNA repair, proteasomal degradation, and cell cycle regulation.
Carbapenam-3-carboxylate synthase, N-terminal (CarA_N)
Type: Domain

This domain is found in the N-terminal of carbapenam-3-carboxylate synthase (carA), and is composed of two antiparallel six-stranded β-sheets that form a sandwich, flanked on each side by two α-helices .
Protein of unknown function DUF1934 (DUF1934)
Type: Family

This entry represents a family of hypothetical bacterial proteins. Their precise function has not, as yet, been defined.
Domain of unknown function DUF1935 (DUF1935)
Type: Domain

This entry represents a conserved region found in various eukaryotic hypothetical proteins, as well as in homologues of the cysteine protease calpain. Its function has not, as yet, been defined.
Orange carotenoid-binding protein, N-terminal (Orange_carotenoid-bd_N)
Type: Domain

Carotenoids such as beta-carotene, lycopene, lutein and beta-cryptoxanthine are produced in plants and certain bacteria, algae and fungi, where they function as accessory photosynthetic pigments and as scavengers of oxygen radicals for photoprotection. They are also essential dietary nutrients in animals. Orange carotenoid-binding proteins (OCP) were first identified in cyanobacterial species, where they occur associated with phycobilisome in the cellular thylakoid membrane. These proteins function in photoprotection, and are essential for inhibiting white and blue-green light non-photochemical quenching (NPQ) . Carotenoids improve the photoprotectant activity by broadening OCP's absorption spectrum and facilitating the dissipation of absorbed energy. OCP acts as a homodimer, and binds one molecule of carotenoid (3'-hydroxyechinenone) and one chloride ion per subunit, where the carotenoid binding site is lined with a striking number of methionine residues. The carotenoid 3'-hydroxyechinenone is not found in higher plants. OCP has two domains: an N-terminal helical domain and a C-terminal domain that resembles a NTF2 (nuclear transport factor 2) domain. OCP can be proteolytically cleaved into a red form (RCP), which lacks 15 residues from the N terminus and approximately 150 residues from the C terminus .

This entry represents the N-terminal domain found predominantly in prokaryotic orange carotenoid proteins and related carotenoid-binding proteins. It adopts an α-helical structure consisting of two four-helix bundles .
Domain of unknown function DUF1936 (DUF1936)
Type: Domain

This domain is predominantly found in various hypothetical archaeal proteins. Its exact function has not been defined yet. It possesses a zinc ribbon fold .
Domain of unknown function DUF1937 (DUF1937)
Type: Domain

This entry represents a domain whose exact function has not, as yet, been described.
Methylated DNA-protein cysteine methyltransferase, ribonuclease H-like domain (MGMT_N)
Type: Domain

This domain, found in the archaeal protein O6-alkylguanine-DNA alkyltransferase (also known as Methylated-DNA--protein-cysteine methyltransferase, MGMT), adopts a secondary structure consisting of a three stranded antiparallel β-sheet and three α helices. This entry represents the N-terminal ribonuclease H-like domain of MGMT, whose exact function has not, as yet, been defined, though it has been postulated that it may confer thermostability to the protein .
Alpha-amylase C-terminal, prokaryotic (Alpha-amylase_C_pro)
Type: Domain

This entry represents a C-terminal domain associated with prokaryotic alpha-amylases. It adopts a secondary structure consisting of an eight-stranded antiparallel β-sheet containing a Greek key motif . The function of this domain was studied in the Alpha-amylase from Geobacillus thermoleovorans (

), showing this region plays an essential role raw starch binding .
Protein of unknown function DUF1940 (DUF1940)
Type: Family

This family adopts a secondary structure consisting of six α helices, with four long helices (alpha1, alpha2, alpha5, alpha6) forming a left-handed, antiparallel α helical bundle. The function of this family of archaeal hypothetical proteins has not, as yet, been defined .
Anthrax toxin lethal factor, central domain (Anthrax_LF_cen)
Type: Domain

Anthrax toxin is a plasmid-encoded toxin complex produced by the Gram-positive, spore-forming bacteria, Bacillus anthracis. The toxin consists of three non-toxic proteins: the protective antigen (PA), the lethal factor (LF) and the edema factor (EF) . These component proteins self-assemble at the surface of host cell receptors, yielding a series of toxic complexes that can produce shock-like symptoms and death. Anthrax toxin is one of a large group of Bacillus and Clostridium exotoxins referred to as binary toxins, forming independent enzymatic (A moiety) and binding (B moiety) components. The LF and EF proteins are the enzymes (A moiety) that act on cytosolic substrates, while PA is a multi-functional protein (B moiety) that binds to cell surface receptors, mediates the assembly and internalisation of the complexes, and delivers them to the host cell endosome . Once PA is attached to the host receptor , it must then be cleaved by a host cell surface (furin family) protease before it is able to bind EF and LF. The cleavage of the N terminus of PA enables the C-terminal fragment to self-associate into a ring-shaped heptameric complex (prepore) that can bind LF or EF competitively. The PA-LF/EF complex is then internalised by endocytosis, and delivered to the endosome, where PA forms a pore in the endosomal membrane in order to translocate LF and EF to the cytosol. LF is a Zn-dependent metalloprotease that cleaves and inactivates mitogen-activated protein (MAP) kinases, kills macrophages, and causes death of the host by inhibiting cell proliferation . EF is a calcium-and calmodulin-dependent adenylyl cyclase that can cause edema (fluid-filled swelling) when associated with PA. EF is not toxic by itself, and is required for the survival of germinated Bacillus spores within macrophages at the early stages of infection. EF dramatically elevates the level of host intracellular cAMP, a ubiquitous messenger that integrates many processes of the cell; increases in cAMP can interfere with host intracellular signalling .

This entry represents the central domain found in the lethal factor protein of anthrax toxin.
tRNA pseudouridine synthase II, TruB, subfamily 1, C-terminal (tRNA_sdUridine_synth_fam1_C)
Type: Domain

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.

TruB is responsible for the pseudouridine residue present in the T loops of virtually all tRNAs. TruB recognises the preformed 3-D structure of the T loop primarily through shape complementarity. It accesses its substrate uridyl residue by flipping out the nucleotide and disrupts the tertiary structure of tRNA . The C-terminal domain adopts a secondary structure consisting of a four-stranded β sheet and one α helix, similar to that found in PUA domains. It is predominantly involved in RNA-binding, being mostly found in tRNA pseudouridine synthase B (TruB) .
Transcription regulator MotA, C-terminal (MotA_Tscrpt_reg_C)
Type: Domain

Transcription factor MotA is required for the activation of middle promoters in Bacteriophage T4, in addition to phage T4 co-activator AsiA, and sigma-70-containing Escherichia coli RNA polymerase. Phage T4 middle promoters have the sigma70 -10 DNA element, but not the -35 element; instead, they have a MotA box at -30 to which the transcription factor MotA binds . MotA and AsiA interact with the C-terminal of sigma70 (region 4), which normally binds the -35 element and the β-flap, thereby diverting sigma70 away from host promoters that require -35 element-binding to phage T4 middle promoters.
Mitochondrial resolvase Ydc2, catalytic (Ydc2_cat)
Type: Domain

This domain forms a ribonuclease H fold consisting of two β sheets and one α helix, arranged as a β-α-β motif. Each β sheet has five strands, arranged in a 32145 order, with the second strand being antiparallel to the rest. They are capable of resolving Holliday junctions and cleave DNA after 5'-CT-3, and 5'-TT-3, sequences . This entry also includes a domain found in the mitochondrial RNA-splicing protein MRS1 which is involved in the excision of group I introns .
FimH, mannose-binding domain (FimH_man-bd)
Type: Domain

This domain adopts a secondary structure consisting of a β-sandwich, with nine strands arranged in two sheets in a Greek key topology. It is found in FimH, a mannose-specific adhesin of uropathogenic Escherichia coli strains. The domain appears to bind specifically to D-mannose and mediates cellular adhesion to mannosylated proteins, a prerequisite to colonization and subsequent invasion of epithelial tissues .
Nuclear RNA export factor Tap, RNA-binding domain (Tap_RNA-bd)
Type: Domain

This domain adopts a structure consisting of an α+β sandwich with an antiparallel β-sheet, arranged in a 2(β-α-β) motif. It is mainly found in mRNA export factors, which mediate the sequence nonspecific nuclear export of cellular mRNAs as well as the sequence-specific export of retroviral mRNAs bearing the constitutive transport element .
Formate dehydrogenase, transmembrane (Formate_DH_TM)
Type: Domain

The transmembrane domain of the beta subunit of formate dehydrogenase consists of a single transmembrane helix. This domain acts as a transmembrane anchor, allowing the conduction of electrons within the protein .
Vitamin D binding protein, domain III (VitD-bind_III)
Type: Domain

This domain is predominantly found in Vitamin D binding proteins, and adopts a multihelical structure. It is required for formation of an actin 'clamp', allowing the protein to bind to actin .
Ubiquinol-cytochrome c reductase iron-sulphur subunit, N-terminal (UQCRFS1_N)
Type: Domain

This entry represents the N-terminal domain of human Cytochrome b-c1 complex subunit Rieske, mitochondrial, also known as Ubiquinol-cytochrome c reductase iron-sulphur subunit (UQCRFS1), and similar sequences mainly from chordates and arthropods. UQCRFS1 adopts a structure consisting of many antiparallel β-sheets, with few α-helices, in a non-globular arrangement. They are required for proper functioning of the respiratory chain .
Biliverdin reductase, catalytic (Biliverdin_Rdtase_cat)
Type: Domain

This entry represents the biliverdin reductase, catalytic domain, which adopts a structure ccontaining a six-stranded β-sheet that is flanked on one face by several α-helices. This domain contains the catalytic active site which reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor .
MPT63-like (MPT63-like)
Type: Domain

MPT63 is a secreted protein of unknown function that is specific to Mycobacterium tuberculosis. MPT63 assumes a β-sandwich structure consisting of two antiparallel β-sheets (similar to an immunoglobulin-like fold), and an additional small, antiparallel β-sheet. The longer-stranded β-sheet is made up of four antiparallel β-strands. The shorter-stranded β-sheet consists of five β-strands, four of which form an antiparallel β-sheet. The exact function of this domain is unknown, though a putative role includes involvement in host-bacterial interactions involved in endocytosis or phagocytosis, possibly during bacterial internalisation .
X-Prolyl dipeptidyl aminopeptidase PepX, N-terminal domain (PepX_N_dom)
Type: Domain

This N-terminal domain adopts a secondary structure consisting of a helical bundle of eight α helices and three β strands, with the last α helix connecting to the first strand of the catalytic domain. The first strand of the N terminus also forms a small parallel β sheet with strand five of the catalytic domain. This domain mediates dimerisation of the protein, with two proline residues present in the domain being critical for interaction .
Breast cancer type 2 susceptibility protein, helical domain (BRCA2_hlx)
Type: Domain

This entry represents a domain found in BRCA2 proteins. This domain adopts a helical structure, consisting of a four-helix cluster core (α1, α8, α9, α10) and two successive β-hairpins (β1 to β4). An approximately 50-amino acid segment that contains four short helices (α2 to α4), meanders around the surface of the core structure. In BRCA2, the α9 and α10 helices pack with BRCA-2_OB1 (

) through van der Waals contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes that map to a 1.5-Mb locus deleted in an inherited developmental malformation syndrome .
Stn1, C-terminal (CST_STN1_C)
Type: Domain

Stn1 is a component of the CST complex, a complex that binds to single-stranded DNA and is required to protect telomeres from DNA degradation. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. In addition to telomere protection, the CST complex has probably a more general role in DNA metabolism at non-telomeric sites .

This entry represents the C-terminal domain of Stn1, which has two winged helix-turn-helix (wHTH) motifs, wHTH1 and wHTH2 . wHTH1 is structurally similar to that in RPA32 with an additional large insertion between helices alpha2 and alpha3, unique to Stn1, and it may allow interaction with a different set of proteins that function at telomeres such as Ctc1 . wHTH2 is most similar to the DNA-binding wHTH motifs of the pur operon repressor and RepE replication initiator, but it does not bind double-stranded DNA .
N-glycosylase/DNA lyase-like (AGOG-like)
Type: Family

This entry represents a set of known and suspected archaeal N-glycosylase/DNA lyases. These DNA repair enzymes are part of the base excision repair (BER) pathway; they protect from oxidative damage by removing the major product of DNA oxidation, 8-oxoguanine (GO), from single- and double-stranded DNA substrates .Cleavage of the N-glycosidic bond between the aberrant base and the sugar-phosphate backbone generates an apurinic (AP) site. Subsequently, the phosphodiester bond 3' from the AP site is cleaved by an elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. The protein contains two α-helical subdomains, with the 8-oxoguanine binding site located in a cleft at their interface. A helix-hairpin-helix (HhH) structural motif and a Gly/Pro-rich sequence followed by a conserved Asp (HhH-GPD motif) are present .
Vitellinogen, open beta-sheet (Vitellinogen_open_b-sht)
Type: Domain

This entry represents the open β-sheet domain found in vitellinogen, which generally corresponds to a domain within the lipovitellin-1 peptide product. This domain adopts a structure consisting of several large open β-sheets .

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved .

In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: lipovitellin-1, phosvitin, lipovitellin-2, and a von Willebrand factor type D domain (YGP40). Vitellinogens are post-translationally glycosylated and phosphorylated in the endoplasmic reticulum and Golgi complex of hepatocytes, before being secreted into the circulatory system to be taken up by oocytes. In the ovary, vitellinogens bind to specific Vtgr receptors on oocyte membranes to become internalised by endocytosis, where they are cleaved into yolk proteins by cathepsin D. YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.

The different yolk proteins have distinct roles. Phosvitins are important in sequestering calcium, iron and other cations for the developing embryo. Phosvitins are one of the most phosphorylated (10%) proteins in nature, the high concentration of phosphate groups providing efficient metal-binding sites in clusters . Lipovitellins are involved in lipid and metal storage, and contain a heterogeneous mixture of about 16% (w/w) noncovalently bound lipid, most being phospholipid. Lipovitellin-1 contains two chains, LV1N and LV1C .
Initiation factor eIF2 gamma, C-terminal (eIF2g_C)
Type: Domain

In eukaryotes and archaea, the e/aIF2 factor is involved in the initiation of protein biosynthesis. In its GTP bound form, e/aIF2 delivers methionylated initiator tRNA to the small subunit of the ribosome. After the pairing between the AUG initiation codon on mRNA and the CAU anticodon of the initiator tRNA, GTP is hydrolysed and e/aIF2:GDP is released from the ribosome. In eukaryotes, eIF2B acts as the guanine nucleotide exchange factor for eIF2. Archaea have no equivalent of eIF2B, and the exchange between GDP and GTP is thought to be spontaneous . eIF2 is composed of three subunits, alpha, beta and gamma. The gamma subunit forms the core of the heterotrimer and confers both tRNA binding and GTP/GDP binding .

This entry represents the C-terminal domain of the gamma subunit of eukaryotic translation initiation factor 2 (eIF2-gamma) found in Eukaryota and Archaea. This domain has a β barrel structure with Greek key topology. It is required for formation of the ternary complex with GTP and initiator tRNA .
Repressor of RNA polymerase III transcription Maf1 (Maf1)
Type: Family

Maf1 is a negative regulator of RNA polymerase III . It inhibits the de novo assembly of TFIIIB onto DNA . Maf1 represses Pol III in response to DNA damage, oxidative stress, growth to stationary phase, treatment with rapamycin or chlorpromazine, and blocking of the secretory pathway . It targets the initiation factor TFIIIB . Its structure has been solved .