SII-SWORD/CoKE huggingface dataset:
Myelin P2 protein (Myelin_P2)
Type: Family

Myelin protein P2 is a constituent of peripheral nervous system (PNS) myelin , also present in small amounts in central nervous system (CNS) myelin . As a structural protein, P2 is thought to stabilise the myelin membranes . Structurally, P2 belongs to the family of cytoplasmic fatty acid binding proteins (FABPs) .
Intracellular lipid binding protein (ILBP)
Type: Family

Fatty acid binding proteins (FABPs) and cellular retinoic-acid-binding proteins (CRBPs) are part of the intracellular-lipid-binding proteins (iLBPs) family .

The primary role of all the FABP members is regulation of fatty acid uptake and intracellular transport . To date, nine FABPs have been identified in mammals, each showing specific tissue distribution patterns and ligand preference. All FABP members have a similar β-barrel structure; fatty acid ligands are accommodated in the central cavity of the β-barrel, which dramatically increases their solubility in the aqueous cytoplasm, facilitating their movement to target sites .

Retinoic-acid-binding proteins (CRBPs) are specific for vitamin A derivatives and can be classified into the cellular retinoic acid-binding proteins (CRABP-I and II) and the cellular retinol-binding proteins (CRBP-I, II, III, and IV) .
Retinol-binding protein 1 (CRBP1)
Type: Family

The lipid-binding protein (LBP) family can be divided divided in four subfamiles. Subfamily I comprises proteins specific for vitamin A derivatives, and can be subdivided into the cellular retinoic acid-binding proteins (CRABP-I and II) and the cellular retinol-binding proteins (CRBP-I, II, III, and IV) .

Cellular retinol binding protein 1 (CRBP-I) is thought to be essential for vitamin A metabolism and synthesis of retinoic acid .
Fatty acid-binding protein, intestinal (FABP2)
Type: Family

Fatty acid-binding proteins (FABPs) have been designated according to the first tissue they were isolated from: intestinal (I-FABP), liver (L-FABP), adipocyte(A-FABP), heart (H-FABP), ileal, myelin, brain, epidermal, and sperm. However, each of these FABPs may be expressed in more than one tissue.

Intestinal fatty acid binding protein FABP2 (also known as IFABP) is expressed in intestinal enterocytes of mammals . IFABP may be involved with uptake of fatty acid from the lumen of the intestine, and with trafficking within the intestinal enterocyte to organelles . It may function as a lipid-sensing component of energy homeostasis that alters body weight gain in a gender-specific fashion .
Protein mono-ADP-ribosyltransferase PARP4 (PARP4)
Type: Family

PARP4, also known as vPARP, is the largest member of the poly-ADP-ribose polymerase (PARP) family. PARP4 exhibits PARP activity and can PARylate major vault protein (MVP) and, to a lesser extent, itself. Vaults are the largest ribonucleoprotein particles found in eukaryotic cells .

Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins . PARP family members are PAR polymerases that initiate the reaction by converting the substrate nicotinamide adenine dinucleotide (NAD+) to ADP-ribose, and then catalyse ADP-ribose polymerisation on nuclear acceptor proteins .
Amphoterin-induced protein (AMIGO)
Type: Family

The Amphoterin-induced protein (AMIGO) family consists of three cell surface leucine-rich repeat (LRR) proteins. AMIGO-1 is expressed on fibre tracts of neuronal tissues and participates in their formation . It has two other homologues, AMIGO-2, also known as DEGA (differentially expressed in human gastric adenocarcinoma) or as Alivin-1, due to its role in promoting survival of neurons, , and AMIGO-3, the function of which is not clear. All are thought to be cell adhesion molecules. They all have the same domain structure with an extracellular, N-terminal leucine-rich repeat (LRR) domain with six LRRs, an Ig domain, and a single transmembrane helix followed by a cytoplasmic tail.
ADP-dependent glucose/glucosamine kinase, archaeal (GlkA)
Type: Family

This entry comprises ADP-dependent glucokinases from hyperthermophilic archaea. The enzyme catalyses the phosphorylation of D-glucose to D-glucose 6-phosphate and glucosamine to glucosamine 6-phosphate using ADP as the phosphate donor .
DNA methylase, C-5 cytosine-specific, conserved site (C5_meth_CS)
Type: Conserved_site

C-5 cytosine-specific DNA methylases (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA . Such enzymes are found in the proteins described below.

As a component of type II restriction-modification systems in prokaryotes and some bacteriophages. Such enzymes recognise a specific DNA sequence where they methylate a cytosine. In doing so, they protect DNA from cleavage by type II restriction enzymes that recognise the same sequence. The sequences of a large number of type II C-5 Mtases are known.

In vertebrates, there are a number of C-5 Mtases that methylate CpG dinucleotides. The sequence of the mammalian enzyme is known.

C-5 Mtases share a number of short conserved regions. This conserved region is located at the C-terminal extremity in type-II enzymes.
Transglycosylase SLT domain 2 (SLT_2)
Type: Domain

This domain is found mainly in proteins from bacteria, such as membrane-bound lytic murein transglycosylase B (mltB, also known as Slt35) from E. coli. MltB is a murein-degrading enzyme that catalyses the cleavage of the glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine residues in peptidoglycan . This domain is related to the SLT domain 1 (

).

Bacterial lytic transglycosylases degrade murein via cleavage of the beta-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine, with the concomitant formation of a 1,6-anhydrobond in the muramic acid residue. There are both soluble (Slt enzymes) and membrane-bound (Mlt enzymes) lytic transglycosylases that differ in size, sequence, activity, specificity and location. The multi-domain structure of the 70 Kd soluble lytic transglycosylase Slt70 is known . Slt70 has 3 distinct domains, each rich in α helices: an N-terminal superhelical U-shaped domain, a superhelical linker domain (L-domain,

), and a C-terminal catalytic domain (

). Both the U-and L-domain share a similar superhelical structure. These two domains are connected, and together form a closed ring with a large central hole; the catalytic domain is packed on top of, and interacts with, this ring. The catalytic domain has a lysosome-like fold.
Casein alpha/beta, conserved site (Casein_CS)
Type: Conserved_site

Caseins are the major protein constituent of milk. Caseins can be classified into two families; the first consists of the kappa-caseins, and the second groups the alpha-s1, alpha-s2, and beta-caseins. The alpha/beta caseins are a rapidly diverging family of proteins. However two regions are conserved: a cluster of phosphorylated serine residues and the signal sequence. This conserved site is based on the last eight residues of the signal sequence.
CcdC protein (CcdC)
Type: Family

This entry includes protein CcdC from Bacillus subtilis. The function of Ccdc is not known.
Ninja family (Ninja_fam)
Type: Family

This entry represents the Ninja family of proteins, which play a role in stress-related and growth-related signalling cascades . In Arabidopsis thaliana, Ninja (also known as AFP homologue 2, At4g28910) is a negative regulator of jasmonate responses. Through protein Ninja, Jasmonate ZIM-domain (JAZ) repressor proteins recruit the Groucho/Tup1-type co-repressor TOPLESS (TPL) and TPL-related proteins (TPRs) . Ninja-family proteins AFP1 and AFP4 have been shown to act as negative regulators of the abscisic acid (ABA) response .
Uncharacterised conserved protein UCP028777 (UCP028777)
Type: Family

This group represents an uncharacterised conserved protein.
Large ribosomal subunit protein uL5, C-terminal (Ribosomal_uL5_C)
Type: Domain

This entry represents the C-terminal domain of ribosomal protein uL5.

Large ribosomal subunit protein uL5, previously known as Ribosomal protein L5, is ~180 amino acids in length. In Escherichia coli, uL5 is known to be involved in binding 5S RNA to the large ribosomal subunit .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Large ribosomal subunit protein uL5, N-terminal (Ribosomal_uL5_N)
Type: Domain

This entry represents the N-terminal domain of the ribosomal protein uL5.

Large ribosomal subunit protein uL5, previously known as Ribosomal protein L5, is ~180 amino acids in length. In Escherichia coli, uL5 is known to be involved in binding 5S RNA to the large ribosomal subunit .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Chitin-binding type R&R consensus (CHIT_BIND_RR_consensus)
Type: Conserved_site

This entry represents the 35-36 amino acid motif known as the R&R consensus. This is a conserved region found in insect cuticular proteins .
Sodium/sulphate symporter, conserved site (Na/sul_symport_CS)
Type: Conserved_site

Integral membrane proteins that mediate the intake of a wide variety of molecules with the concomitant uptake of sodium ions (sodium symporters) can be grouped, on the basis of sequence and functional similarities into a number of distinct families. The SLC13 family consists mainly of dicarboxylate and sulfate transporters , and includes of the following proteins:

Mammalian sodium/sulphate cotransporter .

Mammalian renal sodium/dicarboxylate cotransporter , which transports succinate and citrate.

Mammalian sodium/citrate cotransporter , which mediates the entry of citrate into cells, which is a critical participant of biochemical pathways .

Mammalian intestinal sodium/dicarboxylate cotransporter.

Chlamydomonas reinhardtii putative sulphur deprivation response regulator SAC1 .

These transporters are proteins of from 430 to 620 amino acids which are highly hydrophobic and which probably contain about 12 transmembrane regions.

This entry represents a conserved region located in or near the penultimate transmembrane region.
SAPK-interacting protein 1, Pleckstrin-homology domain (Sin1_PH_dom)
Type: Domain

This entry represents a pleckstrin-homology domain found at the C terminus of Stress-activated map kinase interacting 1 (Sin1) and its Saccharomyces cerevisiae orthologue Avo1. It is conserved from yeast to humans. PH-domains are involved in intracellular signalling or as constituents of the cytoskeleton. Sin1 plays an essential role in signal transduction, and the PH domain is involved in lipid and membrane binding .
Deoxynucleoside kinase domain (DNK_dom)
Type: Domain

This entry represents a domain found in various deoxynucleoside kinases including cytidine (

), guanosine (

), adenosine (

) and thymidine kinase (

), which also phosphorylates deoxyuridine and deoxycytosine. These enzymes catalyse the production of deoxynucleotide 5'-monophosphate from a deoxynucleoside, using ATP and yielding ADP in the process.

Proteins containing this domain also include 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 .
LNS2/PITP (LNS2/PITP)
Type: Domain

This domain is found in lipins, lipin homologues from Saccharomyces cerevisiae (Smp2, PAH1) and Schizosaccharomyces pombe (Ned1) , and in class II phosphatidylinositol transfer proteins (PITP) . Lipin proteins are phosphatidate phosphatases which catalyse the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in triacylglycerol synthesis .
Anti-sigma-28 factor FlgM, C-terminal (FlgM_C)
Type: Domain

FlgM binds and inhibits the activity of the transcription factor sigma 28. Inhibition of sigma 28 prevents the expression of genes from flagellar transcriptional class 3, which include genes for the filament and chemotaxis. Correctly assembled basal body-hook structures export FlgM, relieving inhibition of sigma 28 and allowing expression of class 3 genes. NMR studies show that free FlgM is mostly unfolded, which may facilitate its export. The C-terminal half of FlgM adopts a tertiary structure when it binds to sigma 28. All mutations in FlgM that prevent sigma 28 inhibition affect the C-terminal domain and is the region thought to constitute the binding domain. A minimal binding domain has been identified between Glu 64 and Arg 88 in Salmonella typhimurium (

).The N-terminal portion remains unstructured and may be necessary for recognition by the export machinery .

This entry represents the C-terminal domain of FlgM.
Tom37, C-terminal domain (Tom37_C)
Type: Domain

The TOM37 protein is one of the outer membrane proteins that make up the TOM complex for guiding cytosolic mitochondrial β-barrel proteins from the cytosol across the outer mitochondrial membrane into the intramembrane space. In conjunction with TOM70 it guides peptides without an MTS into TOM40, the protein that forms the passage through the outer membrane . It has homology with Metaxin-1, also part of the outer mitochondrial membrane β-barrel protein transport complex .
OPI10 family (OPI10)
Type: Family

OPI10 family members include protein Hikeshi from vertebrates and protein Opi10 from yeasts.
Alpha-amylase, C-terminal domain (A-amylase_C)
Type: Domain

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry represents the alpha-amylase C-terminal domain.
GAGE (GAGE)
Type: Domain

This domain is found in antigens belonging to the GAGE/PAGE family. These antigents been implicated in human cancers .
Uncharacterised conserved protein UCP012641, putative zinc-binding metallo-peptidase (UCP012641)
Type: Family

This family has a highly conserved HHExxH motif with a highly conserved ED pairing downstream. HExxH is indicative of a zinc-binding metallo-peptidase.
Shikimate kinase/gluconokinase (Shikimate/glucono_kinase)
Type: Family

Shikimate kinase (

) catalyses the fifth step in the biosynthesis of aromatic amino acids from chorismate (the so-called shikimate pathway) . The enzyme catalyses the following reaction:

ATP + shikimate = ADP + shikimate-3-phosphate

The protein is found in bacteria (gene aroK or aroL), plants and fungi (where it is part of a multifunctional enzyme that catalyses five consecutive steps in this pathway). In 1994, the 3D structure of shikimate kinase was predicted to be very close to that of adenylate kinase, suggesting a functional similarity as well as an evolutionary relationship . This prediction has since been confirmed experimentally. The protein is reported to possess an α/β fold, consisting of a central sheet of five parallel β-strands flanked by α-helices. Such a topology is very similar to that of adenylate kinase .

The N terminus of threonine synthase-like 1 from metazoan shares protein sequence similarity with shikimate kinase and is included in this entry. However, their functions may be different.
RHS repeat (RHS_repeat)
Type: Repeat

RHS (rearrangement hotspot) proteins contain extended repeat regions. These repeats often appear to be involved in ligand binding . Note that the signature in this entry does not find all the repeats in a protein and that it covers two RHS repeats. The 3D structure of an RHS-repeat-containing protein (the B and C components of an ABC toxin complex) has been determined. The RHS repeats form an extended strip of β-sheet that spirals around to form a hollow shell, encapsulating the variable C-terminal domain .

The RHS repeat shares structural similarity with the eukaryotic tyrosine-aspartate (YD)-repeat .
Mini-chromosome maintenance protein (MCM)
Type: Family

MCM proteins are DNA-dependent ATPases required for the initiation of eukaryotic DNA replication . In eukaryotes there is a family of eight proteins, MCM2 to MCM9. They were first identified in yeast where most of them have a
direct role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called minichromosome maintenance proteins, MCM proteins . These proteins are evolutionarily related and belong to the AAA+ superfamily. They contain the Mcm family domain, which includes motifs that are required for ATP hydrolysis (such as the Walker A and B, and R-finger motifs). Mcm2-7 forms a hexameric complex in which individual subunits associate with different affinities, and there is a tightly associated core of Mcm4 (Cdc21), Mcm6 (Mis5) and Mcm7 . Mcm2-7 complex is the replicative helicase involved in replication initiation and elongation , whereas Mcm8 and Mcm9 from and separate one, conserved among many eukaryotes except yeast and C. elegans. Mcm8/9 complex play a role during replication elongation or recombination, being involved in the repair of double-stranded DNA breaks and DNA interstrand cross-links by homologous recombination. Drosophila is the only organism that has MCM8 without MCM9, involved in meiotic recombination .

This family is also present in the archebacteria in 1 to 4 copies. Methanocaldococcus jannaschii (Methanococcus jannaschii) has four members, MJ0363, MJ0961, MJ1489 and MJECL13.

Schizosaccharomyces pombe (Fission yeast) MCMs, like those in metazoans, are found in the nucleus throughout the cell cycle. This is in contrast to the Saccharomyces cerevisiae (Baker's yeast) in which MCM proteins move in and out of the nucleus during each cell cycle. The assembly of the MCM complex in S. pombe is required for MCM localisation, ensuring that only intact MCM complexes remain in the nucleus .
Ephrin (Ephrin)
Type: Family

Ephrins are a family of proteins that are ligands of class V (EPH-related) receptor protein-tyrosine kinases. These receptors and their ligands have been implicated in regulating neuronal axon guidance and in patterning of the developing nervous system and may also serve a patterning and compartmentalisation role outside of the nervous system as well.

Ephrins are membrane-attached proteins of 205 to 340 residues. Attachment appears to be crucial for their normal function. Type-A ephrins are linked to the membrane via a glycosylphosphatidylinositol (GPI)-linkage, while type-B ephrins are type-I membrane proteins.
Neutral/alkaline non-lysosomal ceramidase, N-terminal (NEUT/ALK_ceramidase_N)
Type: Domain

This entry represents the N-terminal domain of a group of neutral/alkaline ceramidases found in both bacteria and eukaryotes . The EC classification is (

). The enzyme hydrolyses ceramide to generate sphingosine and fatty acid. The enzyme plays a regulatory role in a variety of physiological events in eukaryotes and also functions as an exotoxin in particular bacteria. This N-terminal domain carries two metal-binding sites, the first for Zn2+ residing within the domain, and the second, for Mg2+/Ca2+ lying at the interface between the two domains .