SII-SWORD/CoKE huggingface dataset:
VQ (VQ)
Type: Domain

This short motif is found in a variety of plant proteins. These proteins vary greatly in length and are mostly composed of low complexity regions. They all conserve a short motif FXhVQChTG, where X is any amino acid and h is a hydrophobic amino acid. The function of this motif is uncertain, however one protein in this family has been found to bind the SigA sigma factor

. It would seem plausible that this motif is needed for this activity and that this whole family might be involved in modulating plastid sigma factors.
Vibrio cholerae RfbT (V_cholerae_RfbT)
Type: Family

This family consists of several RfbT proteins from Vibrio cholerae. It has been found that genetic alteration of the rfbT gene is responsible for serotype conversion of V. cholerae O1 and determines the difference between the Ogawa and Inaba serotypes, in that the presence of rfbT is sufficient for Inaba-to-Ogawa serotype conversion .
Viral nucleic acid binding (Viral_NABP)
Type: Family

This family is common to ssRNA positive-strand viruses and are commonly described as nucleic acid binding proteins (NABP).
Cold-regulated 413 protein (COR413)
Type: Family

This entry represents a group of plant multispanning transmembrane proteins that are regulated by cold. This family can be classified into two groups: the cold-regulated (COR)413-plasma membrane and COR413-thylakoid membrane groups. Proteins in this family have a highly conserved phosphorylation site and a glycosylphosphatidylinositol-anchoring site at the C-terminal end .
WGR domain (WGR_domain)
Type: Domain

This domain is named after the most conserved central motif of the domain. It is found in a variety of polyA polymerases as well as the Escherichia coli molybdate metabolism regulator

and other proteins of unknown function. The domain is found in isolation in proteins such as

and is between 70 and 90 residues in length. This domain participates in binding DNA near the 5' terminus and mediates domain-domain contacts essential for DNA-dependent activity .
Sugar 3,4-ketoisomerase QdtA, cupin domain (QdtA_cupin_dom)
Type: Domain

This entry represents cupin domain found in several bacterial proteins homologous to sugar 3,4-ketoisomerases.
Thermoanaerobacterium thermosaccharolyticum QdtA catalyzes a key step in the biosynthesis of these sugars, the conversion of thymidine diphosphate (dTDP)-4-keto-6-deoxyglucose to dTDP-3-keto-6-deoxyglucose . In Aneurinibacillus thermoaerophilus, TDP-4-oxo-6-deoxy-alpha-D-glucose-3,4-oxoisomerase (also known as FdtA (

)) is involved in the biosynthesis of dTDP-Fucp3NAc (3-acetamido-3,6-dideoxy-alpha-d-galactose), which is part of the repeating units of the glycan chain in the S-layer . Shewanella denitrificans bifunctional ketoisomerase/N-acetyltransferase (also known as FdtD) is involved in the third and fifth steps in the production of 3-acetamido-3,6-dideoxy-alpha-d-galactose or Fuc3NAc; the C-terminal cupin domain harbours the active site responsible for the isomerization reaction . Proteins containing this domain also includes WxcM (

) from Xanthomonas campestris pv campestris) .

Proteins in this entry belong to the cupin superfamily with a conserved "jelly roll-like" β-barrel fold capable of homodimerization .
Protein TIC214 (TIC214)
Type: Family

The chloroplast genomes of most higher plants contain two giant open reading frames designated ycf1 and ycf2. TIC214 is encoded by ycf1. In chloroplasts, Tic214, Tic100, Tic56, and Tic20-I form stable 1-MD TIC complexes, which were shown to associate with preproteins. TIC214 is involved in protein precursor import into chloroplasts . This entry also includes some uncharacterised mitochondrial genome proteins, such as AtMg00370.
Yeast trans-acting factor (Rep_fungi)
Type: Family

The majority of laboratory strains of S. cerevisiae contain 2-micron circle plasmids. 2-micron circle plasmids encode four open reading frames (FLP1, RAF1, REP1, and REP2) and three well known cis-acting sequences, ORI, FRT, and STB. Rep proteins, including Rep1 and Rep12, are part of the plasmid partitioning system that ensures the equal distribution of replicated plasmid molecules to daughter cells .
YopD-like (YopD-like)
Type: Family

This family consists of several bacterial YopD like proteins. Virulent Yersinia species harbour a common plasmid that encodes essential virulence determinants (Yersinia outer proteins [Yops]), which are regulated by the extracellular stimuli Ca
2+
and temperature. YopD, also known as Type 3 secretion system translocon protein SctB, is inserted into the host membrane where it contributes to the formation of a pore and allows the translocation of effector proteins into the cytosol of target cells . It contains an amphipathic α-helix in its C terminus .
Zinc finger, piccolo-type (Znf_piccolo)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This (predicted) zinc finger is found in the bassoon and piccolo proteins, both of which are components of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release, where Piccolo plays a role in the trafficking of synaptic vesicles (SVs) . The Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. There are eight conserved cysteines in Piccolo-type zinc fingers, suggesting that they coordinates two zinc ligands.
Zona occludens toxin, N-terminal (Zot_N)
Type: Domain

This domain is found in bacterial and viral proteins which are very similar to the Zonular occludens toxin (Zot). Zot is elaborated by bacteriophage present in toxigenic strains of Vibrio cholerae. Zot is a single polypeptide chain of 44.8kDa, with the ability to reversibly alter intestinal epithelial tight junctions, allowing the passage of macromolecules through mucosal barriers. The Zot biologically active domain was localized towards the C terminus of the protein . This entry represents the N-terminal domain of Zot.
Alkaline ceramidase (ACER)
Type: Family

This entry consists of several ceramidases. Ceramidases are enzymes involved in regulating cellular levels of ceramides, sphingoid bases, and their phosphates .
Alpha-L-rhamnosidase, concanavalin-like domain (Rhamnosid_concanavalin)
Type: Domain

This concanavalin-like domain is found in rhamnosidase A and B enzymes. L-Rhamnose is abundant in biomass as a common constituent of glycolipids and glycosides, such as plant pigments, pectic polysaccharides, gums or biosurfactants. Some rhamnosides are important bioactive compounds. For example, terpenyl glycosides, the glycosidic precursor of aromatic terpenoids, act as important flavouring substances in grapes. Other rhamnosides act as cytotoxic rhamnosylated terpenoids, as signal substances in plants or play a role in the antigenicity of pathogenic bacteria .
Hemagglutinin component HA-17 (HA-17_C_botulinum)
Type: Family

This family consists of Clostridium botulinum haemagglutinin (HA) subcomponent HA-17. C. botulinum type D strain 4947 produces two different sizes of progenitor toxins (M and L) as intact forms without proteolytic processing. The M toxin is composed of neurotoxin (NT) and nontoxic-nonhaemagglutinin (NTNHA), whereas the L toxin is composed of the M toxin and haemagglutinin (HA) subcomponents (HA-70, HA-17, and HA-33) .
Eukaryotic translation initiation factor 3 subunit C, N-terminal domain (EIF3C_N_dom)
Type: Domain

The largest of the mammalian translation initiation factors, eIF3, consists of at least eight subunits ranging in mass from 35 to 170kDa. eIF3 binds to the 40 S ribosome in an early step of translation initiation and promotes the binding of methionyl-tRNAi and mRNA . The N-terminal domain of eukaryotic translation initiation factor 3 subunit C mediates eIF3 binding to eIF1 and eIF5 .
HAT, C-terminal dimerisation domain (HATC_C_dom)
Type: Domain

This dimerisation domain is found at the C terminus of the transposases of elements belonging to the Activator superfamily (hAT element superfamily). The isolated dimerisation domain forms extremely stable dimers
in vitro
.
Tubulin polymerization-promoting protein (TPP/p25)
Type: Family

This family includes Tubulin polymerization-promoting proteins, formerly known as 25kDa proteins (TPPP/p25) that are phosphorylated by a Ser/Thr-Pro kinase . Proteins in this family, including TPP and TPP3 from human, are regulators of microtubule dynamics . TPP plays a key role in myelination by promoting elongation of the myelin sheath and acts as a microtubule nucleation factor in oligodendrocytes; it specifically localizes to the postsynaptic Golgi apparatus region, and promotes microtubule nucleation . TPP3 is required for embryo implantation .
Sarcoglycan alpha/epsilon (Sarcoglycan_alpha/epsilon)
Type: Family

This entry contains alpha and epsilon sarcoglycans.

The sarcoglycan family proteins are single pass transmembrane proteins that are part of the dystrophin-associated glycoprotein complex (DGC), a multiprotein complex that links the actin cytoskeleton to the extracellular matrix in cardiac and skeletal muscle . The DGC can be classified biochemically into three subcomplexes: the cytoplasmic subcomplex (contains dystrophin, the dystrobrevins and the syntrophins), the dystroglycan subcomplex and the sarcoglycan subcomplex. The function of the sarcoglycan subcomplex is not clear. However, mutations in alpha-, beta-, gamma- and delta-sarcoglycan cause different forms of autosomal recessive limb girdle muscular dystrophies (LGMD) demonstrating its importance for normal muscle function .
DALR anticodon binding (DALR_anticod-bd)
Type: Domain

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 all α helical domain is the anticodon binding domain (ABD) of arginyl tRNA synthetase, and also matches the ABD of some glycine tRNA synthetases. This domain is known as the DALR domain after characteristic conserved amino acids .
Mechanosensitive ion channel, conserved TM helix (MSC_TM_helix)
Type: Repeat

This entry represents a conserved transmembrane helix, often found in small conductance mechanosensitive channels (MscS) in association with

, such as

and

MscS assembles to a homoheptameric complex; each monomer consists of a N-terminal transmembrane region and a large cytoplasmic segment composed of a five-stranded antiparallel β-sheet (middle/second) domain (

) and a C-terminal α/β-domain (

). The N-terminal region consists of three membrane spanning helices (TM1, TM2 and TM3), TM1 is represented in this entry. In the heptamer, the permeation pathway is formed by the packing of TM3s, flanked by TM1-TM2 helical hairpins .
Short scorpion toxin, potassium channel inhibitor alpha-KTx 8/9 (Toxin_alpha-KTx_8/9)
Type: Family

Scorpion toxins that target K+ channels (KTx) have been classified into four large families: alpha, beta, gamma and kappa-KTx . This family consists of toxin-like peptides from the alpha-KTx 8 and alpha-KTx 9 subfamilies. The precursor of these toxins consists of 60 amino acid residues, with a putative signal peptide of 28 residues and an extra residue, and a mature peptide of 31 residues with an amidated C-terminal. The peptides share close homology with other scorpion K+ channel toxins and should present a common three-dimensional fold - the Cysteine -Stabilised alphabeta (CSalphabeta) motif . This family acts by blocking small conductance calcium activated potassium ion channels in their victim .
Uncharacterised protein family CoxE-like (Uncharacterised_CoxE)
Type: Family

This group of proteins contains a VWA type domain and the function of this family is unknown. It is found as part of a CO oxidising (Cox) system operon in several bacteria .
Zinc finger, CHY-type (Znf_CHY)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

Pirh2 is an eukaryotic ubiquitin protein ligase, which has been shown to promote p53 degradation in mammals. Pirh2 physically interacts with p53 and promotes ubiquitination of p53 independently of MDM2. Like MDM2, Pirh2 is thought to participate in an autoregulatory feedback loop that controls p53 function. Pirh2 proteins contain three distinct zinc fingers, the CHY-type, the CTCHY-type which is C-terminal to the CHY-type zinc finger and a RING finger. The CHY-type zinc finger has no currently known function .

As well as Pirh2, the CHY-type zinc finger is also found in the following proteins:

Yeast helper of Tim protein 13. Hot13 may have a role in the assembly and recycling of the small Tims, a complex of the mitochondrial intermembrane space that participates in the TIM22 import pathway for assembly of the inner membrane

Several plant hypothetical proteins that also contain haemerythrin cation binding domains

Several protozoan hypothetical proteins that also contain a Myb domain

The solution structure of this zinc finger has been solved and binds three zinc atoms as shown in the following schematic representation:

++---------+-----+
|| | |
CXHYxxxxxxxxxCCxxxxxCxxCHxxxxxHxxxxxxxxxxxCxxCxxxxxxxxxCxxC
| | | | | | | |
+-+-----------------+--+ +--+---------+--+

'C': conserved cysteine involved in the binding of one zinc atom.
'H': conserved histidine involved in the binding of one zinc atom.
Phosphatidylethanolamine-binding protein (PEBP)
Type: Family

The PEBP (PhosphatidylEthanolamine-Binding Protein) family is a highly conserved group of proteins that have been identified in numerous tissues in a wide variety of organisms, including bacteria, yeast, nematodes, plants, drosophila and mammals. The various functions described for members of this family include lipid binding, neuronal development , serine protease inhibition , the control of the morphological switch between shoot growth and flower structures , and the regulation of several signalling pathways such as the MAP kinase pathway , and the NF-kappaB pathway . The control of the latter two pathways involves the PEBP protein RKIP, which interacts with MEK and Raf-1 to inhibit the MAP kinase pathway , and with TAK1, NIK, IKKalpha and IKKbeta to inhibit the NF-kappaB pathway. Other PEBP-like proteins that show strong structural homology to PEBP include Escherichia coli YBHB and YBCL , the Rattus norvegicus (Rat) neuropeptide HCNP, and Antirrhinum majus (Garden snapdragon) protein centroradialis (CEN). Although their overall structures are similar, the members of the PEBP family bind very different substrates including phospholipids, opioids, and hydrophobic odorant molecules as well as having different oligomerization states (monomer/dimer/tetramer).
Peptidase M50 (Peptidase_M50)
Type: Domain

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This entry contains metallopeptidases belonging to MEROPS peptidase family M50 (S2P protease family, clan MM).
Retrovirus capsid, C-terminal (Retrov_capsid_C)
Type: Homologous_superfamily

The Gag polyprotein from retroviruses is processed by viral protease to produce the major structural proteins, including the capsid protein. The newly formed capsid protein rearranges to form the capsid core particle that surrounds the viral genome of the mature virus. The capsid is composed of two domains, the N-terminal domain (NTD), which contributes to viral core formation, and the C-terminal domain (CTD), which is required for capsid dimerisation, Gag oligomerization and viral formation. The CTD contains the major homology region (MHR), a stretch of 20 amino acids that is conserved across retroviruses and is essential for viral assembly, maturation and infectivity. The CTD is composed of a bundle of four helices in an up and down arrangement, where helix 3 is shorter than the others .
Transcription factor, Skn-1-like, DNA-binding domain superfamily (TF_DNA-bd_sf)
Type: Homologous_superfamily

The DNA-binding domain of certain eukaryotic transcription factors displays a distinctive helix-turn-helix (HTH) motif. The MafG basic region-leucine zipper (bZIP) protein and the Caenorhabditis elegans Skn-1 transcription factor share this HTH motif.

MafG is a member of the Maf family of proteins, which are a subgroup of bZIP proteins that function as transcriptional regulators of cellular differentiation. Mafs can form either homodimers, or heterodimers with other bZIP proteins through their leucine zipper domains. MafG proteins are small Mafs that lack a putative transactivation domain. The DNA-binding domain of MafG contains the conserved Maf extended homology region (EHR), which is not present in other bZIP proteins. The EHR together with the basic region are responsible for the DNA-binding specificity of Mafs.

Skn-1 is a transcription factor that specifies mesodermal development in C. elegans. Skn-1 and MafG share a conserved DNA-binding motif, however Skn-1 lacks the leucine zipper dimerisation domain that is found in all bZIP proteins. Skn-1 acts as a monomer.
Helix-hairpin-helix motif, class 2 (HhH2)
Type: Conserved_site

The helix-hairpin-helix (HhH) motif is an around 20 amino acids domain present in prokaryotic and eukaryotic non-sequence-specific DNA binding proteins. The HhH motif is similar to, but distinct from, the helix-turn-helix (HtH) and the helix-loop-helix (HLH) motifs. All three motifs have two helices (H1 and H2) connected by a short turn. DNA-binding proteins with a HhH structural motif are involved in non-sequence-specific DNA binding that occurs via the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups. These HhH motifs are observed in DNA repair enzymes and in DNA polymerases. By contrast, proteins with a HtH motif bind DNA in a sequence-specific manner through the binding of H2 with the major groove; these proteins are primarily gene regulatory proteins. DNA-binding proteins with the HLH structural motif are transcriptional regulatory proteins and are principally related to a wide array of developmental processes .

Examples of proteins that contain a HhH motif include the eukaryotic/prokaryotic RAD2 family of 5'-3' exonucleases such as T4 RNase H and T5 , eukaryotic 5' endonucleases such as FEN-1 (Flap) , and some viral exonucleases.
Retrovirus capsid, N-terminal (Retrov_capsid_N)
Type: Homologous_superfamily

The Gag polyprotein from retroviruses is processed by viral protease to produce the major structural proteins, including the capsid protein. The newly formed capsid protein rearranges to form the capsid core particle that surrounds the viral genome of the mature virus. The capsid is composed of two domains, the N-terminal domain (NTD), which contributes to viral core formation, and the C-terminal domain (CTD), which is required for capsid dimerisation, Gag oligomerization and viral formation. The NTD is composed of a five-helix bundle .
Transcription regulator FadR/GntR, C-terminal (TF_FadR/GntR_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal ligand binding domain of many members of the Gluconate operon transcriptional repressor (GntR) family. This domain probably binds to a range of effector molecules that regulate the transcription of genes through the action of the N-terminal DNA-binding domain. It is a α helical domain that is also found in the known structure of Fatty acid metabolism regulator (FadR) where it binds to acyl-coA .