SII-SWORD/CoKE huggingface dataset:
Lipid transport protein, beta-sheet shell (Lipid_transp_b-sht_shell)
Type: Homologous_superfamily

This superfamily represents β-sheet shell domains found in lipid transport proteins such as vitellinogen. 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) . Domains with a β-sheet shell topology can be found within both lipovitellin-1 and lipoviteliin-2 peptide products.
Ty transposon capsid protein (TYA)
Type: Family

Ty are yeast transposons. A 5.7kb transcript codes for p3 a fusion protein of TYA and TYB. The TYA protein is analogous to the gag protein of retroviruses. TYA a is cleaved to form 46kd protein which can form mature virion like particles . This entry corresponds to the capsid protein from Ty1 and Ty2 transposons.

Yeast retrotransposon Ty1 produces its proteins as precursors that are subsequently cleaved by an aspartic protease encoded by the element. Cleavage of the gag and gag-Pol polyprotein precursors is a critical step in proliferation of retroviruses and retroelements. These cleavage events are essential for transposition as they release the active reverse transcriptase and integrase and they modify the structure of the virus-like particles in a way that is analogous to the morphological changes that occur during retrovirus core maturation .
Methyl-coenzyme M reductase, alpha subunit, N-terminal subdomain 2 (Me_CoM_Rdtase_asu_N_sub2)
Type: Homologous_superfamily

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This entry represents a subdomain of the N-terminal region of the alpha subunit. The N-terminal domain has a ferredoxin-like α/β-sandwich fold with a duplicated β-α-β topology. This subdomain has an α-β-sandwich topology.
Phosphoglycerate kinase, N-terminal (Phosphoglycerate_kinase_N)
Type: Homologous_superfamily

Phosphoglycerate kinase (

) (PGK) is an enzyme that catalyses the formation of ATP to ADP and vice versa. In the second step of the second phase in glycolysis, 1,3-diphosphoglycerate is converted to 3-phosphoglycerate, forming one molecule of ATP. If the reverse were to occur, one molecule of ADP would be formed. This reaction is essential in most cells for the generation of ATP in aerobes, for fermentation in anaerobes and for carbon fixation in plants.

PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a monomer containing two nearly equal-sized domains that correspond to the N-and C-termini of the protein (the last 15 C-terminal residues loop back into the N-terminal domain). 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase . At the core of each domain is a 6-stranded parallel β-sheet surrounded by α helices. Domain 1 has a parallel β-sheet of six strands with an order of 342156, while domain 2 has a parallel β-sheet of six strands with an order of 321456. Analysis of the reversible unfolding of yeast phosphoglycerate kinase leads to the conclusion that the two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded .

This superfamily represents the N-terminal domain of PGK.
Alpha-(1,6)-fucosyltransferase (Fut8)
Type: Family

Alpha-(1,6)-fucosyltransferase Fut8 catalyses the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype . Fut8 is also implicated to play roles in ageing and cancer metastasis . It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear .
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial (NDUFA10)
Type: Family

This entry represents the subunit 10 (also known as CI-42kD) of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). It is an accessory subunit that is believed not to be involved in catalysis .
Uncharacterised conserved protein UCP006363, ACT-type (UCP006363_ACT)
Type: Family

This group represents a predicted ligand-binding protein with an N-terminal ACT domain, AF1403 type. The ACT domain generally has a regulatory role that is linked to a wide range of metabolic enzymes that are regulated by amino acid concentration.
DNA-directed DNA polymerase, family B, mitochondrial linear plasmid (DNA-dir_DNA_pol_B_mt_lin_plsmd)
Type: Family

This group represents a family B type DNA-directed DNA polymerase which is encoded on mitochondrial linear plasmids .
Uncharacterised conserved protein UCP016642 (UCP016642)
Type: Family

The function of this family of uncharacterised proteins is not known.
Hydroxymethyl pyrimidine (HMP)/thiamine binding protein (HMP/thiamine-bd)
Type: Family

This group represents putative hydroxymethyl pyrimidine (HMP)/thiamine binding protein YkoF. It is part of the ABC transporter complex YkoCDEF that could transport HMP and/or thiamine. YkoF binds thiamine via its HMP moiety .
Uncharacterised conserved protein UCP026622, CAAX protease-type (UCP026622_CAAX_protease)
Type: Family

This group represents a predicted uncharacterised protein with CAAX amino terminal protease domain.
Uncharacterised conserved protein UCP027923, rubrerythrin-type (UCP027923_rubrerythrin)
Type: Family

This group represents an uncharacterised protein with rubrerythrin domain.
Bifunctional chloromethane dehalogenation methyltransferase corrinoid-binding protein CmuA (CmuA)
Type: Family

The pathway of chloromethane utilization, which allows the microorganisms that possess it to grow with chloromethane as the sole carbon and energy source, is believed to be initiated by a corrinoid-dependent methyltransferase system involving methyltransferase I (CmuA) and methyltransferase II (CmuB), which transfer the methyl group of chloromethane onto tetrahydrofolate (H4folate) . The methyl group of chloromethane is first transferred by the protein CmuA to a corrinoid protein, from where it is transferred to H4folate by CmuB, yielding methyl-H4folate . Both CmuA and CmuB display sequence similarity to methyltransferases of methanogenic archaea.

CmuA is a two-domain methyltransferase/corrinoid-binding protein involved in methyl transfer from chloromethane to a corrin moiety. CmuA shows similarity to known methyltransferases as well as to their cognate corrinoid protein-binding proteins in the N-terminal and C-terminal parts of its sequence, respectively . Mutation analysis shows that CmuA acts as methyltransferase I . Mutation analysis shows that CmuA acts as methyltransferase I . By analogy to similar methyltransferase systems, it is thought that CmuA acts as both the methyltransferase I and the corrinoid-binding protein in the dehalogenation of chloromethane . Therefore, CmuA catalyses the first step of the chloromethane-degradation pathway, comprising the dehalogenation of chloromethane and the methylation of an associated cobalt corrin moiety.
DNA methyase, ParB domain-containing (DNA_MeTrfase_ParB)
Type: Family

This group represents an adenine methyltransferase with ParB-like nuclease domain.
RNA-directed RNA polymerase, tospovirus (RNA-dir_pol_tospovirus)
Type: Family

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This group represents a RNA-directed RNA polymerase, Tospovirus type.
RNA-directed RNA polymerase, tenuivirus (RNA-dir_pol_tenuivirus)
Type: Family

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This entry represents a protein family specific to Tenuivirus, including RNA-directed RNA polymerase L from Rice stripe virus (Pc1), which degrade ssRNA with preference for unstructured ssRNA, but not DNA .
RNA-directed RNA polymerase, nairovirus (RNA-dir_pol_nairovirus)
Type: Family

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This group represents a RNA-directed RNA polymerase, Nairovirus type.
Pantothenate kinase, acetyl-CoA regulated, two-domain type (PanK_long)
Type: Family

Pantothenate kinase (PanK,

) catalyses the conversion of CAATP and pantothenate to ADP and D-4'-phosphopantothenate, the key regulatory step in the biosynthesis of coenzyme A (CoA) . Members in this entry represents a two-domain form with an additional C-terminal domain of unknown function. This type of pantothenate kinase is typical for eukaryotes. It is not related by sequence to bacterial PanK (

) and differs in a number of biochemical properties (such as inhibition by acetyl-CoA) . However, this group also includes proteins from several Gram-positive bacteria (

) that are suggested to have originated from the eukaryotic form by lateral transfer .

Hallervorden-Spatz syndrome is caused by a defect in a pantothenate kinase gene .

For additional information please see .
Agropine synthesis reductase (Mas1)
Type: Family

Several agrobacteria cause neoplastic diseases in plants, including crown gall disease (Agrobacterium tumefaciens) and hairy root disease (Agrobacterium rhizogenes). The mechanism involves transfer via infective plasmids and subsequent expression of both oncogenes and genes for the synthesis of opines, which can be specifically used as nutrients by the invading bacteria . Opines are low molecular weight amino acid and sugar phosphate derivatives, e.g., octopine, agropine, and mannopine. The proteins in this group are products of the
mas1
genes (and homologues) encoding the reductase that produces mannopine from deoxyfructosylglutamine. Subsequently, mannopine can be lactonized to form agropine. The C-terminal short chain dehydrogenase domain is coupled with an N-terminal phosphoglycerate mutase family domain (

), the role of which is unknown . Sequences reported from Ti plasmid pTiC58 are missing half or all of the N-terminal domain.
Exoribonuclease, phosphorolytic domain 2 (ExoRNase_PH_dom2)
Type: Domain

This entry represents the phosphorolytic (PH) domain 2, which has a core 3-layer α/β/α structure. This domain is found in bacterial/organelle PNPases and in archaeal/eukaryotic exosomes .

The PH (phosphorolytic) domain is responsible for 3'-5' exoribonuclease activity, although in some proteins this domain has lost its catalytic function. An active PH domain uses inorganic phosphate as a nucleophile, adding it across the phosphodiester bond between the end two nucleotides in order to release ribonucleoside 5'-diphosphate (rNDP) from the 3' end of the RNA substrate.

PH domains can be found in bacterial/organelle RNases and PNPases (polynucleotide phosphorylases) , as well as in archaeal and eukaryotic RNA exosomes , the later acting as nano-compartments for the degradation or processing of RNA (including mRNA, rRNA, snRNA and snoRNA). Bacterial/organelle PNPases share a common barrel structure with RNA exosomes, consisting of a hexameric ring of PH domains that act as a degradation chamber, and an S1-domain/KH-domain containing cap that binds the RNA substrate (and sometimes accessory proteins) in order to regulate and restrict entry into the degradation chamber . Unstructured RNA substrates feed in through the pore made by the S1 domains, are degraded by the PH domain ring, and exit as nucleotides via the PH pore at the opposite end of the barrel .
Polyribonucleotide nucleotidyltransferase, RNA-binding domain (PNPase_PH_RNA-bd_bac/org-type)
Type: Domain

The PH (phosphorolytic) domain is responsible for 3'-5' exoribonuclease activity, although in some proteins this domain has lost its catalytic function. An active PH domain uses inorganic phosphate as a nucleophile, adding it across the phosphodiester bond between the end two nucleotides in order to release ribonucleoside 5'-diphosphate (rNDP) from the 3' end of the RNA substrate.

PH domains can be found in bacterial/organelle RNases and PNPases (polynucleotide phosphorylases) , as well as in archaeal and eukaryotic RNA exosomes , the later acting as nano-compartments for the degradation or processing of RNA (including mRNA, rRNA, snRNA and snoRNA). Bacterial/organelle PNPases share a common barrel structure with RNA exosomes, consisting of a hexameric ring of PH domains that act as a degradation chamber, and an S1-domain/KH-domain containing cap that binds the RNA substrate (and sometimes accessory proteins) in order to regulate and restrict entry into the degradation chamber . Unstructured RNA substrates feed in through the pore made by the S1 domains, are degraded by the PH domain ring, and exit as nucleotides via the PH pore at the opposite end of the barrel .

This entry represents an RNA-binding domain found in bacterial and organelle PNPases, but not in exosomes. It usually occurs in combination with PH domain 1 (

) and PH domain 2 (

), both of which are found in PNPases and exosomes. The core structure of the RNA-binding domain consists of a DNA/RNA-binding 3-helical bundle.
Amyloidogenic glycoprotein, heparin-binding (Amyloid_glyco_heparin-bd)
Type: Domain

Amyloid-beta precursor protein (APP, or A4) is associated with Alzheimer's disease (AD), because one of its breakdown products, amyloid-beta (A-beta), aggregates to form amyloid or senile plaques . Mutations in APP or in proteins that process APP have been linked with early-onset, familial AD. Individuals with Down's syndrome carry an extra copy of chromosome 21, which contains the APP gene, and almost invariably develop amyloid plaques and Alzheimer's symptoms.

APP is important for the neurogenesis and neuronal regeneration, either through the intact protein, or through its many breakdown products . APP consists of a large N-terminal extracellular region containing heparin-binding and copper-binding sites, Kunitz domain, E2 domain, a short hydrophobic transmembrane domain, and a short C-terminal intracellular domain. The N-terminal region is similar in structure to cysteine-rich growth factors and appears to function as a cell surface receptor, contributing to neurite growth, neuronal adhesion, axonogenesis and cell mobility . APP acts as a kinesin I membrane receptor to mediate the axonal transport of beta-secretase and presenilin 1. The N-terminal domain can regulate neurite outgrowth through its binding to heparin and collagen I and IV, which are components of the extracellular matrix. APP is also coupled to apoptosis-inducing pathways, and is involved in copper homeostasis/oxidative stress through copper ion reduction, where copper-metallated APP induces neuronal death . The C-terminal intracellular domain appears to be involved in transcription regulation through protein-protein interactions. APP can promote transcription activation through binding to APBB1/Tip60, and may bind to the adaptor protein FE65 to transactivate a wide variety of different promoters.

APP can be processed by different sets of enzymes:

In the non-amyloidogenic (non-plaque-forming) pathway, APP is cleaved by alpha-secretase to yield a soluble N-terminal sAPP-alpha (neuroprotective) and a membrane-bound CTF-alpha. CTF-alpha is broken-down by presenilin-containing gamma-secretase to yield soluble p3 and membrane-bound AICD (nuclear signalling).

In the amyloidogenic pathway (plaque-forming), APP is broken down by beta-secretase to yield soluble sAPP-beta and membrane-bound CTF-beta. CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact.

This entry represents a heparin-binding domain found at the N-terminal of the extracellular domain, which is itself found at the N-terminal of amyloidogenic glycoproteins such as amyloid-beta precursor protein (APP, or A4). The core of the heparin-binding domain has an unusual disulphide-rich fold, consisting of a β-x-α-β-loop-β topology .
ABC transporter, CbiO/EcfA subunit (ABC_transpr_CbiO/EcfA_su)
Type: Domain

This entry represents a domain found in the energy-coupling factor transporter ATP-binding proteins CbiO (from the CbiMNOQ complex, involved in cobalt import) and EcfA (from the common ECF ABC-transporter complex) .
FAD synthetase (FAD_synthase)
Type: Domain

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (

), which converts it into FMN, and FAD synthetase (

), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme , the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family . The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases .

This entry represents prokaryotic-type FAD synthetase, which occurs primarily as part of a bifunctional enzyme.
Riboflavin kinase domain, bacterial/eukaryotic (Riboflavin_kinase_bac/euk)
Type: Domain

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (

), which converts it into FMN, and FAD synthetase (

), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme , the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family . The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases .

This entry represents the riboflavin kinase domains from bacteria and eukaryotes.
Serine-tRNA synthetase, type1, N-terminal (Ser-tRNA-synth_1_N)
Type: Domain

This entry represents the N-terminal domain of Serine-tRNA synthetase, which consists of two helices in a long α-hairpin and corresponds to the tRNA binding domain. Serine-tRNA synthetase (

) exists as monomer and belongs to class IIa aminoacyl-tRNA synthetase .

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .