SII-SWORD/CoKE huggingface dataset:
Phospholipase A2 inhibitor, N-terminal domain (PLipase_A2_inh_N)
Type: Domain

This entry represents a domain located at the N-terminal end of a group of proteins predominantly found in vertebrates that inhibit basic phospholipase A2 isozymes in snake's venom .
Prefoldin alpha-like (Prefoldin_subunit_alpha)
Type: Family

This entry represents prefoldin subunit alpha-like proteins. Prefoldin (PFD) is a chaperone that interacts exclusively with type II chaperonins, hetero-oligomers lacking an obligate co-chaperonin that are found only in eukaryotes (chaperonin-containing T-complex polypeptide-1 (CCT)) and archaea. Eukaryotic PFD is a multi-subunit complex containing six polypeptides in the molecular mass range of 14-23kDa. In archaea, on the other hand, PFD is composed of two types of subunits, two alpha and four beta. The six subunits associate to form two back-to-back up-and-down eight-stranded barrels, from which hang six coiled coils. Each subunit contributes one (beta subunits) or two (alpha subunits) β hairpin turns to the barrels. The coiled coils are formed by the N and C termini of an individual subunit. Overall, this unique arrangement resembles a jellyfish. The eukaryotic PFD hexamer is composed of six different subunits; however, these can be grouped into two alpha-like (PFD3 and -5) and four beta-like (PFD1, -2, -4, and -6) subunits based on amino acid sequence similarity with their archaeal counterparts. Eukaryotic PFD has a six-legged structure similar to that seen in the archaeal homologue . This family contains the archaeal alpha subunit, eukaryotic prefoldin subunits 3 and 5 and the UXT (ubiquitously expressed transcript) family.

Eukaryotic PFD has been shown to bind both actin and tubulin co-translationally. The chaperone then delivers the target protein to CCT, interacting with the chaperonin through the tips of the coiled coils. No authentic target proteins of any archaeal PFD have been identified, to date.
GPN-loop GTPase (Gpn)
Type: Family

Proteins in this entry belong to the GPN-loop GTPase family , including Npa3 (also known as Gpn1) and Gpn2/3 from budding yeasts. In humans, Npa3 homologue is known as XAB1; Gpn2 is known as GPN2/ATPBD1B; Gpn3 is known as Parcs.
Pyrophosphate-energised proton pump (PPase-energised_H-pump)
Type: Family

Two types of proteins that hydrolyse inorganic pyrophosphate (PPi), very different in both amino acid sequence and structure, have been characterised to date: soluble and membrane-bound proton-pumping pyrophosphatases (sPPases and H+)-PPases, respectively). sPPases are ubiquitous proteins that hydrolyse PPi to release heat, whereas H+-PPases, so far unidentified in animal and fungal cells, couple the energy of PPi hydrolysis to proton movement across biological membranes . The latter type is represented by this group of proteins. H+-PPases (

) are also called vacuolar-type inorganic pyrophosphatases (V-PPase) or pyrophosphate-energised vacuolar membrane proton pumps . In plants, vacuoles contain two enzymes for acidifying the interior of the vacuole, the V-ATPase and the V-PPase (V is for vacuolar) . In Arabidopsis, AVP1 contributes to H+-electrochemical potential difference between the citosol and vacuole lumen and also facilitates auxin transport by modulating apoplastic pH and regulates auxin-mediated developmental processes .

Two distinct biochemical subclasses of H+-PPases have been characterised to date: K+-stimulated and K+-insensitive .
Kinetoplastid membrane protein 11 (KMP11)
Type: Family

Kinetoplastid membrane protein 11 is a major cell surface glycoprotein of the parasite Leishmania donovani. It stimulates T-cell proliferation and may play a role in the immunlogy of the dieases Leishmaniasis.
DAN (DAN_dom)
Type: Domain

This domain contains 9 conserved cysteines and is extracellular. Therefore the cysteines may form disulphide bridges. This family of proteins has been termed the DAN family after the first member to be reported. This family includes DAN, Bursicon, Neuroblastoma suppressor of tumorigenicity 1, Cerberus and Gremlin. Bursicon is the final heterodimeric neurohormone released at the end of the molting cycle, involved in the sclerotization (tanning) of the insect cuticle, melanization and wing spreading . The gremlin protein is an antagonist of bone morphogenetic protein signalling. It is postulated that all members of this family antagonize different TGF beta TGF-beta ligands .
Nitronate monooxygenase (NMO)
Type: Domain

Nitronate monooxygenase (NMO), formerly referred to as 2-nitropropane dioxygenase (NPD) (

), is an FMN-dependent enzyme that uses molecular oxygen to oxidise (anionic) alkyl nitronates and, in the case of the enzyme from Neurospora crassa, (neutral) nitroalkanes to the corresponding carbonyl compounds and nitrite. Previously classified as 2-nitropropane dioxygenase , but it is now recognised that this was the result of the slow ionisation of nitroalkanes to their nitronate (anionic) forms . The enzymes from the fungus Neurospora crassa and the yeast Williopsis saturnus var. mrakii (formerly classified as Hansenula mrakii) contain non-covalently bound FMN as the cofactor. Active towards linear alkyl nitronates of lengths between 2 and 6 carbon atoms and, with lower activity, towards propyl-2-nitronate. The enzyme from N. crassa can also utilise neutral nitroalkanes, but with lower activity. One atom of oxygen is incorporated into the carbonyl group of the aldehyde product. The reaction appears to involve the formation of an enzyme-bound nitronate radical and an a-peroxynitroethane species, which then decomposes, either in the active site of the enzyme or after release, to acetaldehyde and nitrite.
Hydroxylamine reductase/Ni-containing CO dehydrogenase (HCP/CODH)
Type: Family

This entry represent the hydroxylamine reductases (Hcp, also known as Prismane) and the Ni-containing CO dehydrogenases (CODH) (

).

Hydroxylamine reductases have been identified in bacteria, archaea and eukaryotic protozoa. They contain two Fe/S centres - a [4Fe-4S] cubane cluster, and a hybrid [4Fe-2S-2O] cluster. The physiological role of this protein is as yet unknown, although a role in nitrate/nitrite respiration has been suggested . The Hcp protein from Escherichia coli was shown to contain hydroxylamine reductase activity (NH2OH + 2e + 2 H+ ->NH3 + H2O). This activity is rather low .
HSV U79 / HCMV P34 (U79_P34)
Type: Family

This family represents herpes virus protein U79 and cytomegalovirus early phosphoprotein P34 (UL112).
Glycosyl transferase, family 13 (Glyco_trans_13)
Type: Family

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (GNT-I, GLCNAC-T I)

transfers N-acetyl-D-glucosamine from UDP to high-mannose glycoprotein N-oligosaccharide. This is an essential step in the synthesis of complex or hybrid-type N-linked oligosaccharides. The enzyme is an integral membrane protein localized to the Golgi apparatus, and is probably distributed in all tissues . Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNTI, GNT-I.2) participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins . These proteins are members of the glycosyl transferase family 13 (

)
Exocyst complex component Exo70 (Exo70)
Type: Family

The Exo70 protein forms one subunit of the exocyst complex (consist of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 in budding yeast). First discovered in Saccharomyces cerevisiae , it is evolutionarily conserved in eukaryotes. It mediates the tethering of post-Golgi secretory vesicles to the plasma membrane and promotes the assembly of the SNARE complex for membrane fusion. It also plays a role in cell polarisation, primary ciliogenesis, cytokinesis, pathogen invasion, tumourigenesis and metastasis . It is a member of the the Complex Associated with Tethering Containing Helical Rods (CATCHRs) family which also includes Conserved Oligomeric Golgi complex (COG) and Golgi-Associated Retrograde Protein complex (GARP) and DSL1 complexes, all evolutionarily related and share structural features consisting of α-helical bundles at the C terminus and coiled-coil region at the N terminus . Exo70 interacts with phospholipids the Rho3 GTPase . This interaction with Rho3 mediates one of the three known functions of Rho3 in cell polarity: vesicle docking and fusion with the plasma membrane (the other two functions are regulation of actin polarity and transport of exocytic vesicles from the mother cell to the bud) .
NDRG (NDRG)
Type: Family

This family consists of proteins from different gene families: Ndr1/RTP/Drg1, Ndr2, and Ndr3. Their similarity was previously noted . The precise molecular and cellular function of members of this family is still unknown, yet they are known to be involved in cellular differentiation events. The Ndr1 group was the first to be discovered. Their expression is repressed by the proto-oncogenes N-myc and c-myc, and in line with this observation, Ndr1 protein expression is down-regulated in neoplastic cells, and is reactivated when differentiation is induced by chemicals such as retinoic acid. Ndr2 and Ndr3 expression is not under the control of N-myc or c-myc. Ndr1 expression is also activated by several chemicals: tunicamycin and homocysteine induce Ndr1 in human umbilical endothelial cells; nickel induces Ndr1 in several cell types. Members of this family are found in wide variety of multicellular eukaryotes, including an Ndr1 type protein in Helianthus annuus (Common sunflower), known as Sf21. Interestingly, the highest scoring matches in the noise are all α/β hydrolases (

), suggesting that this family may have an enzymatic function.
Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL), catalytic domain (BPL_LPL_catalytic)
Type: Domain

This entry represents the catalytic domain of a group of lipoyl ligases/lipoyltransferases, such as Lipoate-protein ligase A/B (LipA/B) from E.coli and mammalian lipoyltransferases . These proteins catalyse the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes. Lipoic acid is an essential cofactor of the alpha-ketoacid dehydrogenase complexes and the glycine cleavage system.

Biotin and lipoic acid are the covalently bound cofactors of various
multicomponent enzyme complexes that catalyse key metabolic reactions. In
these enzymes complexes, biotin and lipoic acid are attached via amide linkage
through their carboxyl group and the ε-amino group of a specific lysine
residue of a protein module known respectively as the biotinyl and the lipoyl
domain. Covalent attachment of biotin and lipoic acid to
these enzyme complexes occurs post-translationally, and it is mediated by
biotinylating and lipoylating protein enzymes, which specifically recognise
the biotinyl and lipoyl domains, ensuring their correct post-translational
modification. Lipoylating and biotinylating enzymes are evolutionarily related
protein families containing a homologous catalytic module .

Amino acid sequence conservation between the catalytic modules of biotinyl
protein ligases (BPLs) and lipoyl protein ligases (LPLs) is very low, and
mainly affects residues that are important for the scaffold of the structure,
such as those contributing to the hydrophobic core. Despite the poor overall
sequence similarity, a single lysine residue is strictly conserved in all LPL
and BPL sequences. This lysine residue is likely to bind specifically to the
carbonyl oxygen of the carboxyl group of biotin or at the end of the hydrogen-
carbon tail of the lipoyl moiety . The BPL/LPL catalytic domain contains a
seven-stranded mixed β-sheet on one side and four α-helices on the
other side .
Domain of unknown function DUF243 (DUF243)
Type: Domain

This domain is only found in arthropod proteins. It is found associated with YLP motifs (

) in some proteins.
DC1 (DC1)
Type: Domain

This entry represents a domain found predominantly in plant proteins, including Probable nucleoredoxin 1 (NRX1) and Protein VACUOLELESS GAMETOPHYTES (VLG) from Arabidopsis thaliana. This region is found at the C- terminal end of NRX1, which is likely to be a thiol-disulfide oxidoreductase required for pollen tube growth and pollen function in the pistil [

,

. VLG is essential for development of both female (megagametogenesis) and male (microgametogenesis) gametophytes by promoting the formation of large vacuoles early in development, maybe via the regulation of vesicular fusion .

This domain, which is rich in cysteines and histidines, is termed DC1 for divergent C1 domain as it has a pattern of conservation that is similar to that found in (

). It probably binds to two zinc ions and bind to molecules such as diacylglycerol.
ABC1 atypical kinase-like domain (ABC1_dom)
Type: Domain

This entry represents a domain found in Escherichia coli UbiB, known in Providencia stuartii as Aarf, which is required for ubiquinone (CoQ) biosynthesis . Some proteins with this domain are described as aarF domain-containing protein kinases (ADCKs). This domain is also found in yeast ABC1 proteins (

) required for function of the mitochondrial bc1 complex , in which CoQ functions as an essential cofactor.
BAR domain (BAR_dom)
Type: Domain

Endocytosis and intracellular transport involve several mechanistic steps:

For the internalisation of cargo molecules, the membrane needs to bend to form a vesicular structure, which requires membrane curvature and a rearrangement of the cytoskeleton;

Following its formation, the vesicle has to be pinched off the membrane;

The cargo has to be subsequently transported through the cell and the vesicle must fuse with the correct cellular compartment.

Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs)-domain, which is required for their
in vivo
function and their ability to tubulate membranes .

The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.
Zinc-finger, NAD-dependent DNA ligase C4-type (Znf_DNAligase_C4)
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 entry represents the zinc finger domain found in NAD-dependent DNA ligases. DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor . This domain is a small zinc binding motif that is presumably DNA binding. It is found only in NAD-dependent DNA ligases.
NAD-dependent DNA ligase, OB-fold (NAD_DNA_ligase_OB)
Type: Domain

DNA ligases catalyse the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor . This family is a small domain found after the adenylation domain DNA_ligase_N in NAD+-dependent ligases (

). OB-fold domains generally are involved in nucleic acid binding.
7TM GPCR, serpentine receptor class e (Sre) (7TM_GPCR_serpentine_rcpt_Sre)
Type: Family

This entry represents serpentine receptor class e (Sre) from the Sra superfamily .

The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli . Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' . Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr . Many of these proteins have homologues in Caenorhabditis briggsae.

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .
GAT domain (GAT_dom)
Type: Domain

The GAT domain is a region of homology of ~130 residues, which is found in eukaryotic GGAs (for Golgi-localized, gamma ear-containing ADP ribosylation factor (ARF)-binding proteins) and vertebrate TOMs (for target of myb). The GAT domain is found in its entirety only in GGAs, although, at the C terminus it shares partial sequence similarity with a short region of TOMs. The GAT domain is found in association with other domains, such as VHS and GAE. The GAT domain of GGAs serves as a molecular anchor of GGA to trans-Golgi network (TGN) membranes via its interaction with the GTP-bound form of a member of the ARF family of small GTPases and can bind specifically to the Rab GTPase effector rabaptin5 and to ubiquitin .

The GGA-GAT domain possesses an all α-helical structure, composed of four helices arranged in a somewhat unusual topology, which has been called the helical paper clip. The overall structure shows that the GAT domain has an elongated shape, in which the longest helix participates in two small independent subdomains: an N-terminal helix-loop-helix hook and a C-terminal three-helix bundle. The hook subdomain has been shown to be both necessary and sufficient for ARF-GTP binding and Golgi targeting of GGAs. The N-terminal hook subdomain contains a hydrophobic patch, which is found to interact directly with ARF . It has been proposed that this interaction might stabilise the hook subdomain . The C-terminal three-helix bundle is involved in the binding with Rabaptin5 and ubiquitin .
CXCXC repeat (CXCXC_repeat)
Type: Repeat

This repeat contains the conserved pattern CXCXC where X can be any amino acid. The repeat is found in up to five copies in Vascular endothelial growth factor C and D . In the salivary glands of the dipteran Chironomus tentans, a specific messenger ribonucleoprotein (mRNP) particle, the Balbiani ring (BR) granule, can be visualized during its assembly on the gene and during its nucleocytoplasmic transport. This repeat is found over 70 copies in the balbiani ring protein 3 (

). It is also found in some silk proteins .
Anticodon-binding (Anticodon-bd)
Type: Domain

tRNA synthetases, or tRNA ligases are involved in protein synthesis. This domain is found in histidyl, glycyl, threonyl and prolyl tRNA synthetases . It is probably the anticodon binding domain .