SII-SWORD/CoKE huggingface dataset:
N-acetylglutamate synthase, kinase-like domain (NAGS_kin)
Type: Domain

This is the N-acetylglutamate (NAG) kinase-like domain of the NAG Synthase (NAGS) of the arginine-biosynthesis pathway (ABP) found in gamma- and beta-proteobacteria and higher plant chloroplasts. The domain architecture of these NAGS consists of an N-terminal NAG kinase-like (ArgB) domain and a C-terminal NAG synthase, acetyltransferase (ArgA) domain. Both bacterial and plant sequences have a conserved N-terminal extension; a similar sequence in the NAG kinases of the cyclic arginine-biosynthesis pathway has been implicated in feedback inhibition sensing. Plant sequences also have an N-terminal chloroplast transit peptide and an insert (approx. 70 residues) in the C-terminal region of ArgB .
Elongation factor Tu, domain 2 (EFTU_2)
Type: Domain

Elongation factors Tu (EF-Tu) are three-domain GTPases with an essential function in the elongation phase of mRNA translation. The GTPase centre of EF-Tu is in the N-terminal domain (domain I), also known as the catalytic or G-domain. The G-domain is composed of about 200 amino acid residues, arranged into a predominantly parallel six-stranded β-sheet core surrounded by seven a-helices. Non-catalytic domains II and III are β-barrels of seven and six, respectively, antiparallel β-strands that share an extended interface. Either non-catalytic domain is composed of about 100 amino acid residues. EF-Tu proteins exist in two principal conformations: in a compact one, EF-Tu*GTP, with tight interfaces between all three domains and a high affinity for aminoacyl-tRNA, and in an open one, EF-Tu*GDP, with essentially no G-domain-domain II interactions and a low affinity for aminoacyl-tRNA. EF-Tu has approximately a 100-fold higher affinity for GDP than for GTP .

This entry represents domain II.
Prolyl-tRNA synthetase, catalytic domain (ProRS_core_arch_euk)
Type: Domain

This entry consists of the the Prolyl-tRNA synthetase (ProRS) class II core catalytic domain. ProRS is a homodimer. It is responsible for the attachment of proline to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent formation of the enzyme bound aminoacyl-adenylate. Class II assignment is based upon its structure and the presence of three characteristic sequence motifs in the core domain. This entry contains the core domain of ProRS from archaea, the cytoplasm of eukaryotes and some bacteria .
PET prickle (PET_prickle)
Type: Domain

Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway , which requires the conserved Frizzled/Dishevelled (Dsh). Prickle interacts with Dishevelled , thereby modulating the activity of Frizzled/Dishevelled and the PCP signalling. Two forms of prickle have been identified, namely prickle 1 and prickle 2. These are differentially expressed; prickle 1 is found in fetal heart and haematological malignancies, while prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of tumorous cells .

Prickle contains an N-terminal PET domain and three C-terminal LIM domains. This entry represents the PET domain of prickle. The PET domain is a protein-protein interaction domain, usually found in conjunction with the LIM domain, which is also involved in protein-protein interactions. The PET containing proteins serve as adaptors or scaffolds to support the assembly of multimeric protein complexes.
PET testin (PET_testin)
Type: Domain

Testin contains a PET domain at the N terminus and three C-terminal LIM domains . It is a cytoskeleton associated focal adhesion protein that localizes along actin stress fibres, at cell-cell contact areas, and at focal adhesion plaques . Testin interacts with a variety of cytoskeletal proteins, including zyxin, mena, VASP, talin, and actin and is involved in cell motility and adhesion events. Knockout mice experiments have revealed a tumour repressor function. .

The entry represents the testin PET domain. It is a protein-protein interaction domain and PET containing proteins serve as adaptors or scaffolds to support the assembly of multimeric protein complexes.
LIM1 prickle (LIM1_prickle)
Type: Domain

Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway , which requires the conserved Frizzled/Dishevelled (Dsh). Prickle interacts with Dishevelled , thereby modulating the activity of Frizzled/Dishevelled and the PCP signalling. Two forms of prickle have been identified, namely prickle 1 and prickle 2. These are differentially expressed; prickle 1 is found in fetal heart and haematological malignancies, while prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of tumorous cells .

Prickle contains an N-terminal PET domain and three C-terminal LIM domains. LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs . The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

This entry represents the first LIM domain of prickle.
LIM2 prickle (LIM2_prickle)
Type: Domain

Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway , which requires the conserved Frizzled/Dishevelled (Dsh). Prickle interacts with Dishevelled , thereby modulating the activity of Frizzled/Dishevelled and the PCP signalling. Two forms of prickle have been identified, namely prickle 1 and prickle 2. These are differentially expressed; prickle 1 is found in fetal heart and haematological malignancies, while prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of tumorous cells .

Prickle contains an N-terminal PET domain and three C-terminal LIM domains. LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs . The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

This entry represents the second LIM domain of prickle.
LIM3 prickle (LIM3_prickle)
Type: Domain

Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway , which requires the conserved Frizzled/Dishevelled (Dsh). Prickle interacts with Dishevelled , thereby modulating the activity of Frizzled/Dishevelled and the PCP signalling. Two forms of prickle have been identified, namely prickle 1 and prickle 2. These are differentially expressed; prickle 1 is found in fetal heart and haematological malignancies, while prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of tumorous cells .

Prickle contains an N-terminal PET domain and three C-terminal LIM domains. LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs . The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes.

This entry represents the third LIM domain of prickle.
Threonine-tRNA ligase catalytic core domain (ThrRS_core)
Type: Domain

Threonyl-tRNA synthetase (ThrRS) is responsible for the attachment of threonine to the 3' OH group of ribose of the appropriate tRNA. ThrRS is a homodimer. This core domain is primarily responsible for ATP-dependent formation of the enzyme bound aminoacyl-adenylate. ThrRS has been assigned to class II based upon its structure and the presence of three characteristic sequence motifs in the core domain .
Serine-tRNA ligase catalytic core domain (SerRS_core)
Type: Domain

Serine--tRNA ligase or seryl-tRNA synthetase (SerRS) is responsible for the attachment of serine to the 3' OH group of ribose of the appropriate tRNA. SerRS is a class II aminoacyl-tRNA synthetase, this assignment is based upon its structure and the presence of three characteristic sequence motifs in the core domain . This core domain is primarily responsible for ATP-dependent formation of the enzyme bound aminoacyl-adenylate. SerRS synthetase is a homodimer .
Prokaryote proline-tRNA ligase core domain (ProRS_core_prok)
Type: Domain

Prolyl-tRNA synthetase (ProRS) is responsible for the attachment of proline to the 3' OH group of ribose of the appropriate tRNA. ProRS is a homodimer. There are two structurally distinct classes of aminoacyl-tRNA synthetases; ProRS has been assigned to class II based upon its structure and the presence of three characteristic sequence motifs in the core domain . The core domain is primarily responsible for ATP-dependent formation of the enzyme bound aminoacyl-adenylate.

This entry contains the core domain of ProRS from prokaryotes and from the mitochondria of eukaryotes.
Glycyl-tRNA synthetase-like core domain (GlyRS-like_core)
Type: Domain

Glycyl-tRNA synthetase (GlyRS) functions as a homodimer in eukaryotes, archaea and some bacteria and as a heterotetramer in the remainder of prokaryotes. It is responsible for the attachment of glycine to the 3' OH group of ribose of the appropriate tRNA. The core catalytic domain is primarily responsible for ATP binding and hydrolysis. GlyRS has been assigned to class II aminoacyl-tRNA synthetases (aaRS) based upon its structure and the presence of three characteristic sequence motifs .

This glycyl-tRNA synthetase (GlyRS)-like domain includes the core catalytic domain of class II glycyl-tRNA synthetases (GlyRS) that form homodimers. The heterotetramer glyQ is in a different family of class II aaRS. This domain is also found at the N terminus of the accessory subunit of mitochondrial polymerase gamma (Pol gamma b). Pol gamma b stimulates processive DNA synthesis and is functional as a homodimer, which can associate with the catalytic subunit Pol gamma alpha to form a heterotrimer. Despite significant both structural and sequence similarity with GlyRS,Pol gamma b lacks conservation of several class II functional residues .
ATP synthase, F1 complex, alpha subunit nucleotide-binding domain (ATP_synth_F1_a_nt-bd_dom)
Type: Domain

The F-ATPase is found in bacterial plasma membranes, mitochondrial inner membranes and in chloroplast thylakoid membranes. It has also been found in the archaea Methanosarcina barkeri . It uses a proton gradient to drive ATP synthesis and hydrolyzes ATP to build the proton gradient. The extrinsic membrane domain, F1, is composed of alpha, beta, gamma, delta and epsilon subunits with a stoichiometry of 3:3:1:1:1 . There is a substrate-binding site on each of the alpha and beta subunits, those on the beta subunits being catalytic, while those on the alpha subunits are regulatory. The alpha and beta subunits form a cylinder that is attached to the central stalk. The alpha/beta subunits undergo a sequence of conformational changes leading to the formation of ATP from ADP, which are induced by the rotation of the gamma subunit, itself driven by the movement of protons through the F0 complex C subunit .

This entry represents the nucleotide-binding central domain of the F1-ATPase alpha subunit.
Jacalin-like lectin domain, plant (Jacalin-like_lectin_dom_plant)
Type: Domain

This entry refers to jacalin-like lectin domains found in plants.

Jacalin-like lectins are sugar-binding protein domains mostly found in plants. They adopt a β-prism topology consistent with a circularly permuted three-fold repeat of a structural motif. Proteins containing this domain may bind mono- or oligosaccharides with high specificity. The domain can occur in tandem-repeat arrangements with up to six copies, and in architectures combined with a variety of other functional domains. While the family was initially named after an abundant protein found in the jackfruit seed, taxonomic distribution is not restricted to plants. The domain is also found in the salt-stress induced protein from rice and an animal prostatic spermine-binding protein. Proteins containing this domain include:

Jacalin, a tetrameric plant seed lectin and agglutinin from Artocarpus heterophyllus (jackfruit), which is specific for galactose .

Artocarpin, a tetrameric plant seed lectin from A. heterophyllus .

Lectin MPA, a tetrameric plant seed lectin and agglutinin from Maclura pomifera (Osage orange), .

Heltuba lectin, a plant seed lectin and agglutinin from Helianthus tuberosus (Jerusalem artichoke) .

Agglutinin from Calystegia sepium (Hedge bindweed) .

Griffithsin, an anti-viral lectin from red algae (Griffithsia species) .

Ipomoelin, a Jacalin-related lectin from sweet potato (Ipomoea batatas cv. Tainung 57) .
Asparagine synthase, N-terminal domain (AsnB_N)
Type: Domain

This entry includes the N-terminal domain of asparagine synthase.

Asparagine synthetase B catalyses the ATP-dependent conversion of aspartate to asparagine . This enzyme is a homodimer, with each monomer composed of a glutaminase domain and a synthetase domain. The N-terminal glutaminase domain hydrolyzes glutamine to glutamic acid and ammonia .
Peptidase M10A, catalytic domain (M10A_MMP)
Type: Domain

This entry represents the matrix metalloproteinase (MMP) sub-family M10A catalytic domain. MMPs are responsible for a great deal of pericellular proteolysis of extracellular matrix and cell surface molecules, playing crucial roles in morphogenesis, cell fate specification, cell migration, tissue repair, tumorigenesis, gain or loss of tissue-specific functions, and apoptosis . In many instances, they are anchored to cell membranes via trans-membrane domains, and their activity is controlled via TIMPs (tissue inhibitors of metalloproteinases) .

Sequences having this domain are extracellular metalloproteases, such as collagenase and stromelysin, which degrade the extracellular matrix, are known as matrixins. They are zinc-dependent, calcium-activated proteases synthesised as inactive precursors(zymogens), which are proteolytically cleaved to yield the active enzyme .

All MMPs possess an N-terminal domain and a zinc-binding catalytic domain. The N-terminal domain peptide, cleaved during the activation step, includes a conserved PRCGVPDV octapeptide, known as the cysteine switch, whose Cys residue chelates the active site zinc atom, rendering the enzyme inactive . The catalytic domain contains a zinc ion, which is responsible for the peptide hydrolysis reaction. Another zinc ion and one to three calcium ions are present in the catalytic domain with a structural role . All but two of the human MMPs (MMP-7 and MMP-26) also have a C-terminal hemopexin-like domain, and two MMPs (MMP-2 and MMP-9) contain fibronectin insertions into their catalytic domains .
Aminopeptidase P (Pept_M24B)
Type: Domain

This entry represents the catalytic domain of aminopeptidases P, which are members of peptidase subfamily M24B, including aminopeptidases P1 (MEROPS identifier M24.005) and P2 (M24.009), both of which are assigned to E.C. 3.4.11.9. The enzymes are also known as X-Pro aminopeptidases, proline aminopeptidases and aminoacylproline aminopeptidases. They catalyse release of any N-terminal amino acid, including proline, that is linked with proline, even from a dipeptide or tripeptide .
Sequestosome-1, UBA domain (SQSTM_UBA)
Type: Domain

This UBA domain is found in sequestosome-1 (SQSTM) and similar proteins .

Sequestosome-1 (SQSTM), also known as ubiquitin-binding protein p62, is a widely expressed multifunctional cytoplasmic protein that is able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin-proteasome pathway. It functions as a scaffolding protein that regulates a diverse range of signaling pathways . It plays a critical role in cell's selective autophagy and oxidative stress response.
IQ motif and SEC7 domain-containing protein, PH domain (IQSEC_PH)
Type: Domain

The IQSEC (IQ motif and SEC7 domain-containing protein), also called BRAG (Brefeldin A-resistant Arf-gunanine nucleotide exchange factor) family are a subset of Arf GEFs that have been shown to activate Arf6, which acts in the endocytic pathway to control the trafficking of a subset of cargo proteins including integrins. IQSEC family also have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina . The family consists of 3 members: IQSEC1 (also called BRAG2/GEP100), IQSEC2 (also called BRAG1), and IQSEC3 (also called SynArfGEF, BRAG3, or KIAA1110). IQSEC1 interacts with clathrin and modulates cell adhesion by regulating integrin surface expression and in addition to Arf6, it also activates the class II Arfs, Arf4 and Arf5 . Mutations in IQSEC2 cause non-syndromic X-linked intellectual disability as well as reduced activation of Arf substrates (Arf1, Arf6) . IQSEC3 regulates Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM .

These IQSEC family members contain a IQ domain that may bind calmodulin, a PH domain that is thought to mediate membrane localization, and a SEC7 domain that can promote GEF activity on ARF . The PH domain of BRAG2 has been shown to potentiate nucleotide exchange by binding to polyanionic membranes without marked phosphoinositides preference .
Effector protein HopAB, Pto-binding domain (HopAB_PID)
Type: Domain

HopAB family members are type III effector proteins that are secreted by the plant pathogen Pseudomonas syringae into the host plant to inhibit its immune system and facilitate the spread of the pathogen . AvrPtoB, also called HopAB3, is the best studied member of the family. It suppresses host basal defenses by interfering with PAMP (pathogen-associated molecular signature)-triggered immunity (PTI) through binding and inhibiting BAK1, a kinase which serves to activate defense signaling . It also recognizes the kinase Pto to activate effector-triggered immunity (ETI) .

AvrPtoB contains an N-terminal region that contains two kinase-interacting domains (KID) and a C-terminal E3 ligase domain. The first KID recognizes the PTI-associated kinase Bti9 as well as Pto, and is referred to as the Pto-binding domain (PID). The second KID interacts with BAK1 and FLS2, which are leucine-rich repeat-containing receptor-like kinases, and is called the BAK1-interacting domain (BID)
. The family member HopPmaL is shorter and lacks the C-terminal E3 ligase domain .

This entry represents the Pto-binding domain.
RBM8, RNA recognition motif (RRM_RBM8)
Type: Domain

This entry corresponds to the RNA recognition motif of RBM8. RNA-binding protein RBM8, also termed binder of OVCA1-1 (BOV-1) or RNA-binding protein Y14, is one of the components of the exon-exon junction complex (EJC) . It has two isoforms, RBM8A and RBM8B, both of which are identical except that RBM8B is 16 amino acids shorter at its N terminus . RBM8, together with other EJC components (such as Magoh, Aly/REF, RNPS1, Srm160, and Upf3), plays critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. RBM8 binds to mRNA 20-24 nucleotides upstream of a spliced exon-exon junction. It is also involved in spliced mRNA nuclear export, and the process of nonsense-mediated decay of mRNAs with premature stop codons. RBM8 forms a specific heterodimer complex with the EJC protein Magoh which then associates with Aly/REF, RNPS1, DEK, and SRm160 on the spliced mRNA, and inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA .

RBM8 contains an N-terminal putative bipartite nuclear localization signal, one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), in the central region, and a C-terminal serine-arginine rich region (SR domain) and glycine-arginine rich region (RG domain) .
Mitochondria fission protein Fis1, cytosolic domain (Fis1_cytosol)
Type: Domain

Fis1, along with Dnm1 and Mdv1, is an essential protein in mediating mitochondrial fission. Dnm1 and Fis1 are highly conserved, with a common mechanism in disparate species. In mutants of these proteins, mitochondrial fission is impaired, resulting in networks of undivided mitochondria. Fis1 appears to act via the recruitment of division complexes to the mitochondrial outer membrane. Dnm1 is recruited to mitochondria via interactions with the adaptor proteins Caf4 and Mdv1, which bind directly to Fis1 .

The Fis1 N terminus is cytosolic and tethered to the mitochondrial outer membrane via a C-terminal transmembrane domain. The cytosolic domain of Fis1 forms a six-helix bundle, in which the central four helices consist of two tandem tetratricopeptide repeat (TPR)-like motifs, known to mediate protein-protein interactions .
Glucosylglycerate phosphorylase (GGa_phosphorylase)
Type: Family

Glucosylglycerate phosphorylase (part of subfamily 18 of glycoside hydrolase family 13 (GH13_18) in CAZy) was previously thought to function as a sucrose phosphorylase, and was previously known as putative sucrose phosphorylase YcjM. However, studies have since shown it to be a glucosylglycerate phosphorylase, and to have no activity on sucrose .
Class I PurE (PurE_ClassI)
Type: Domain

The novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N5-carboxy-AIR (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE) . Class I and class II PurEs are mechanistically related but bind different substrates. In yeast and plants PurE is found in PurK-class I PurE fusion proteins, known as ADE2 , while animal class II PurEs are found in PurC-PurE fusion proteins, also known as ADE2 or PAICS .

This domain represents the class I PurE which is a N5-carboxyaminoimidazole ribonucleotide mutase .
L-ribulose-5-phosphate 4-epimerase AraD (AraD_entero)
Type: Family

L-Ribulose-5-phosphate 4-epimerase AraD (

) catalyzes the interconversion of L-ribulose 5-phosphate (L-Ru5P) and D-xylulose 5-phosphate (D-Xu5P). It is one of three enzymes in the AraBAD operon that allow bacteria to utilize arabinose as an energy source by converting it into an intermediate in the pentose phosphate pathway (D-Xu5P) . AraD is present in Enterobacteriaceae.
Polyprenyl synthetase, conserved site (Polyprenyl_synt_CS)
Type: Conserved_site

A variety of isoprenoid compounds are synthesised by various organisms. For example in eukaryotes the isoprenoid biosynthetic pathway is responsible for the synthesis of a variety of end products including cholesterol, dolichol, ubiquinone or coenzyme Q. In bacteria this pathway leads to the synthesis of isopentenyl tRNA, isoprenoid quinones, and sugar carrier lipids. Among the enzymes that participate in that pathway, are a number of polyprenyl synthetase enzymes which catalyse a 1'4-condensation between 5 carbon isoprene units.

It has been shown that these enzymes share some regions of sequence similarity. Two of these regions, represented by this entry, are rich in aspartic-acid residues and could be involved in the catalytic mechanism and/or the binding of the substrates.
MetA family (MetA_family)
Type: Family

Homoserine O-succinyltransferase (HST) also known as homoserine O-transsuccinylase (HTS), catalyses the first step in the biosynthesis of methionine :

Succinyl-CoA + L-homoserine = CoA + O-succinyl-L-homoserine

The activation of homoserine through succinylation of homoserine in some bacteria, such as Escherichia coli and Bacillus cereus, is carried out by homoserine O-succinyltransferase (HTS;

), while other bacteria, such as Haemophilus influenzae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis, acetylate homoserine via homoserine O-acetyltransferase (HTA;

).

This family also includes serine acetyltransferase CysE (

) from Lactobacillus casei, which catalyses the formation of O-acetyl serine from L-serine and acetyl-CoA, and is involved in cysteine biosynthesis .