SII-SWORD/CoKE huggingface dataset:
Tropomyosin (Tropomyosin)
Type: Family

Tropomyosins , are a family of closely related proteins present in muscle and non-muscle cells. In striated muscle, tropomyosin mediate the interactions between the troponin complex and actin so as to regulate muscle contraction . The role of tropomyosin in smooth muscle and non-muscle tissues is not clear. Tropomyosin is an α-helical protein that forms a coiled-coil structure of 2 parallel helices containing 2 sets of 7 alternating actin binding sites . There are multiple cell-specific isoforms, created by differential splicing of the messenger RNA from one gene, but the proportions of the isoforms vary between different cell types. Muscle isoforms of tropomyosin are characterised by having 284 amino acid residues and a highly conserved N-terminal region, whereas non-muscle forms are generally smaller and are heterogeneous in their N-terminal region.

This entry represents tropomyosin (Tmp) 1, 2 and 3. Within the yeast Tmp1 and Tmp2, biochemical and sequence analyses indicate that Tpm2 spans four actin monomers along a filament, whereas Tpm1 spans five. Despite its shorter length, Tpm2 can compete with Tpm1 for binding to F-actin. Over-expression of Tpm2 in vivo alters the axial budding of haploids to a bipolar pattern, and this can be partially suppressed by co-over-expression of Tpm1. This suggests distinct functions for the two tropomyosins, and indicates that the ratio between them is important for correct morphogenesis .
Semialdehyde dehydrogenase, NAD-binding (Semialdehyde_DH_NAD-bd)
Type: Domain

The semialdehyde dehydrogenase family is found in N-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in arginine biosynthesis, and aspartate-semialdehyde dehydrogenase , an enzyme involved in the biosynthesis of various amino acids from aspartate. This family is also found in yeast and fungal Arg5,6 protein, which is cleaved into the enzymes N-acety-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in arginine biosynthesis. All proteins in this entry contain a NAD binding region of semialdehyde dehydrogenase.
Major sperm protein (MSP) domain (MSP_dom)
Type: Domain

Nematode sperm are unusual amoeboid cells in which motility is not based on actin, but instead on the major sperm protein (MSP). MSP is a dimeric molecule that polymerises to form non-polar filaments constructed from two helical subfilaments that wind round one another. The filaments then assemble into larger macromolecular assemblies called fibre complexes. MSP is a small (~14kDa) basic protein typically encoded by a multigene family of up to 28 members . An about 120-amino acid domain similar to MSP has been found in other proteins, including:

Animal Vesicle-Associated Membrane Protein-associated (VAMP-associated) protein family of 33kDa (VAP33). VAP33 is required for neurotransmitter release. It binds to the v-SNARE synaptobrevin/VAMP which is associated with vesicle fusion. VAP33 has a two-domain structure with its N terminus being highly homologous to MSP, whereas its C terminus is based on a putative α-helical coiled-coil combined with an extremely hydrophobic membrane-attachment region .

Nicotiana plumbaginifolia VAP27, a VAP33 homologue. It interacts with the resistance protein Cf9 .

Yeast inositol regulator SCS2, a VAP33 homologue. It is C-terminally anchored to the endoplasmic reticulum .

The MSP polypeptide chain has an immunoglobulin-like fold based on a seven-stranded β sandwich measuring approximately 15 A x 20 A x 45 A and having opposing three-stranded and four-stranded β sheets .

This entry represents the MSP domain.
Nuclear hormone receptor, ligand-binding domain (Nucl_hrmn_rcpt_lig-bd)
Type: Domain

Nuclear receptors (NRs), such as the receptors for steroids and thyroid hormones, retinoids and vitamin D3, are one of the most abundant classes of transcriptional regulators in animals (metazoans). They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. The most prominent feature differentiating them from other transcription factors is their capacity to bind small hydrophobic molecules specifically. These ligands constitute regulatory signals, which modify the NR transcriptional activity through conformational changes. Prototypical NRs share a common structural organisation with a variable N-terminal domain that contains a constitutively active activation function (AF)-1, a conserved DNA- binding domain (DBD) consisting of two zinc fingers, a linker region, and a C-terminal ligand-binding domain (LBD), also called HOLI domain .

The NR LBD plays a crucial role in ligand-mediated NR activity. In addition to its role is ligand recognition, the LBD also contains
a ligand-dependent AF-2. Conformational changes in AF-2 induced by various ligands can modulate interactions with conserved motifs of coregulatory
proteins. Specifically, the binding of ligands to the LBD determines the recruiting of transcriptional coregulators which triggers induction or repression of target genes. The coregulators include coactivators like the p160 factors also referred to as the steroid receptor coactivators (SRC) family, and corepressors such as SMART (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear corepressor) .

The overall structure of NR LBD is composed of about 11-13 α-helices that are arranged into a three-layer antiparallel α-helical sandwich with the three long helices (helices 3, 7, and 10) forming the two outer layers. The middle layer of helices (helices 4, 5, 8 and 9) is present only in the top half of the domain but is missing from the bottom half, thereby creating a cavity, so called ligand-binding pocket, for ligand binding in most receptors. The bound ligands stabilize the NR conformation through direct contacts with multiple structural elements including helices H3, H5, H6, H7, H10, and the loop proceeding the AF-2 helix. The C-terminal activation region also forms an α-helix (AF-2), which can adopt multiple conformation
depending on the nature of the bound ligand. Helices 3,4 and 12 enclose a shallow hydrophobic groove which is the site for coregulator binding. Despite the conserved fold of NR LBDs, the ligand-binding pocket is the least conserved region among different NR LBDs .
UbiA prenyltransferase (UbiA_prenyltransferase)
Type: Family

The UbiA family of prenyltransferases includes bacterial 4-hydroxybenzoate octaprenyltransferase (gene ubiA); yeast mitochondrial para-hydroxybenzoate--polyprenyltransferase (gene COQ2); protohaem IX farnesyltransferase (haem O synthase) from yeast and mammals (gene COX10), and from bacteria (genes cyoE or ctaB) ; and 2-acylphloroglucinol 4-prenyltransferase and 2-acyl-4-prenylphloroglucinol 6-prenyltransferase from plant chloroplasts which catalyse prenylation steps in the beta-bitter acid pathway . These are integral membrane proteins, which probably contain seven transmembrane segments.

Archaeal family members include lycopene elongase/hydratase - this type of enzyme has been shown to be involved in bacterioruberin synthesis in Halobacterium salinarum and Haloferax volcanii .
Link domain (Link_dom)
Type: Domain

The link domain is a hyaluronan(HA)-binding region found in proteins of vertebrates that are involved in the assembly of extracellular matrix, cell adhesion, and migration. The structure has been shown to consist of two α helices and two antiparallel β sheets arranged around a large hydrophobic core similar to that of C-type lectin. This domain contains four conserved cysteines involved in two disulphide bonds. The link domain has also been termed HABM (HA binding module) and PTR (proteoglycan tandem repeat). Proteins with such a domain include the proteoglycans aggrecan, brevican, neurocan and versican, which are expressed in the CNS; the cartilage link protein (LP), a proteoglycan that together with HA and aggrecan forms multimolecular aggregates; Tumour necrosis factor-inducible protein TSG-6, which may be involved in cell-cell and cell-matrix interactions during inflammation and tumourgenesis; and CD44 antigen, the main cell surface receptor for HA.
Frizzled/Smoothened, 7TM (Frizzled/Smoothened_7TM)
Type: Domain

This domain is the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane α-helices. Proteins related to Drosophila frizzled (

) are receptors for Wnt (mediating the beta-catenin signalling pathway) , but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly α-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding . The smoothened receptor mediates hedgehog signalling .
Flagellar motor protein MotA, conserved site (Flag_MotA_CS)
Type: Conserved_site

The bacterial protein motA is required for the rotation of the flagellar motor. This protein probably forms a transmembrane proton channel used to energize the flagellar rotary motor. The motA protein is an integral membrane protein that contains four transmembrane domains.
Cytoplasmic tRNA 2-thiolation protein 1 (Ncs6/Tuc1/Ctu1)
Type: Family

Cytoplasmic tRNA 2-thiolation protein 1 (also known as Ncs6/Tuc1 in budding yeasts) is responsible for 2-thiolation of mcm5S2U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln) . It directly binds tRNAs and probably acts by catalysing adenylation of tRNAs, an intermediate required for 2-thiolation. Its fission yeast homologue, Ctu1 forms a complex with Ctu2 (Ncs2/Tuc2 homologue) and serves as a putative enzyme for the formation of 2-thiouridine . This family also includes tRNA-5-methyluridine(54) 2-sulfurtransferase, which catalyses the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine .
Acyltransferase ChoActase/COT/CPT (Carn_acyl_trans)
Type: Family

A number of eukaryotic acetyltransferases can, on the basis of sequence similarities, be grouped together into a family. These enzymes include:

Choline o-acetyltransferase

, an enzyme that catalyses the biosynthesis of the neurotransmitter acetylcholine .

Carnitine o-acetyltransferase

.

Peroxisomal carnitine octanoyltransferase

, a fatty acid beta-oxidation pathway enzyme which is involved in the transport of medium-chain acyl-coenzyme A's from peroxisome to mitochondria .

Mitochondrial carnitine palmitoyltransferases I and II

(CPT), enzymes involved in fatty acid metabolism and transport .

Mycoplasma pneumoniae putative acetyltransferase C09_orf600.
Octanoyltransferase (Octanoyltransferase)
Type: Family

Lipoate-protein ligase B (gene lipB), alternatively known as octanoyltransferase (

) is an enzyme that creates an amide linkage that joins the free carboxyl group of lipoic acid to the ε-amino group of a specific lysine residue in lipoate-dependent enzymes.
Lactalbumin (Lactalbumin)
Type: Family

Alpha-lactalbumin comprises 15 percent of the total human milk protein and is essential for lactose production . It is a globular calcium-binding metalloprotein secreted in the lactating mammary gland , the calcium being bound in a novel binding loop that is superficially similar to the classic EF-hand motif. Lactalbumin attaches to beta-galactosyltransferase on the luminal surface of the Golgi apparatus, creating the lactose synthetase complex , which catalyses the addition of galactose to glucose, forming lactose. It has been claimed that calcium controls the release of lactalbumin from the golgi membrane and that the pattern of ion binding may also affect the catalytic properties of the lactose synthetase complex. The lactalbumin gene also contains a novel upstream regulatory sequence called the `milk box' , which is also found in genes of other milk proteins, and may be involved in either hormone regulation or tissue-specific expression in the lactating mammary gland.
Alpha-lactalbumin is similar to C-type lysozyme in terms of primary sequence and structure , and has probably evolved from a common ancestral protein. There is, however, no similarity in function.
Clathrin, heavy chain/VPS, 7-fold repeat (Clathrin_H-chain/VPS_repeat)
Type: Repeat

Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin functions as a trimer, and these trimers, or triskelions, are comprised of three legs joined by a central vertex. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies . The clathrin heavy-chain repeat (CHCR) is also found in nonclathrin proteins such as Pep3, Pep5, Vam6, Vps41, Vps8 from Saccharomyces cerevisiae and their orthologues from other eukaryotes such as Vps11 in zebra fish . These proteins, like clathrins, are involved in vacuolar maintenance and protein sorting. The CHCR repeats in these proteins could mediate protein-protein interactions, or possibly represent clathrin-binding domains, or perform clathrin-like functions. CHCR repeats in the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human Vamp6 have been implicated in homooligomerization, suggesting that this may be the primary function of this repeat.

The CHCR repeat folds into an elongated right-handed superhelix coil of short α-helices . Individual 'helix-turn-helix-loop' or helix hairpin units comprise the canonical repeat and stack along the superhelix axis to form a single extended domain. The canonical hairpin repeat of the clathrin superhelix resembles a tetratrico peptide repeat (TPR), but is shorter and lacks the characteristic spacing of the hydrophobic residues in TPRs.
Myelin basic protein (Myelin_BP)
Type: Family

The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction . Myelin basic protein (MBP) is a hydrophilic protein that may function to maintain the correct structure of myelin, interacting with the lipids in the myelin membrane by electrostatic and hydrophobic interactions. In mammals various forms of MBP exist which are produced by the alternative splicing of a single gene; these forms differ by the presence or the absence of short (10 to 20 residues) peptides in various internal locations in the sequence. The major form of MBP is generally a protein of about 18.5 Kd (170 residues). MBP is the target of many post-translational modifications: it is N-terminally acetylated, methylated on an arginine residue, phosphorylated by various serine/threonine protein-kinases, and deamidated on some glutamine residues.
Photosystem I reaction center subunit V/PsaK (PSI_PsaG/PsaK)
Type: Family

This entry represents Photosystem I reaction centre subunits V (PsaG) and PsaK from Cyanobacteria, Rhodophyta (red algae) and plants.

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. It is found in the chloroplasts of plants and cyanobacteria. PSI is composed of at least 14 different subunits, two of which are small hydrophobic proteins of about 7 to 9 Kd and evolutionary related, PsaG (also known as PSI-G) and PsaK (also known as PSI-K), both integral membrane proteins. Cyanobacteria contain only PsaK . While cyanobacterial PSI have phycobilisomes to harvest light, eukaryotic PSI have a membrane-imbedded peripheral antenna .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .
7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase, HPPK (Hppk)
Type: Domain

All organisms require reduced folate cofactors for the synthesis of a variety of metabolites. Most microorganisms must synthesise folate
de novo
because they lack the active transport system of higher vertebrate cells which allows these organisms to use dietary folates. Enzymes involved in folate biosynthesis are therefore targets for a variety of antimicrobial agents such as trimethoprim or sulphonamides. 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (

) (HPPK) catalyses the attachment of pyrophosphate to 6-hydroxymethyl-7,8-dihydropterin to form 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. This is the first step in a three-step pathway leading to 7,8 dihydrofolate. Bacterial HPPK (gene folK or sulD) is a protein of 160 to 270 amino acids. In the lower eukaryote Pneumocystis carinii, HPPK is the central domain of a multifunctional folate synthesis enzyme (gene fas) .
Large ribosomal subunit protein eL42 (Ribosomal_eL44)
Type: Family

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence similarities. One of these families consists of mammalian L44 (also known as L36A and eL42) , Trypanosoma brucei and fungal L44, Caenorhabditis elegans rpl-36.A, and Haloarcula marismortui LA .

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 .
Small ribosomal subunit protein eS7 (Ribosomal_eS7)
Type: Family

A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities .
This entry represents the small ribosomal subunit protein eS7 (also referred to as S7) . These proteins have about
200 amino acids.

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 .
JAB1/MPN/MOV34 metalloenzyme domain (JAMM/MPN+_dom)
Type: Domain

This domain is known as the MPN domain , PAD-1-like domain , JABP1 domain or JAMM domain . Proteins with this domain include proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. They are metalloenzymes that function as the ubiquitin isopeptidase/deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes . Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are predicted to have a similar role .

The archaeal (H. volcanii) JAMM domain containing protein, HvJAMM1, cleaves ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates . The bacterial JAMM domain containing protein QbsD from Pseudomonas fluorescens cleaves the C-terminal amino acid residues of the sulfur carrier protein QbsE prior to the formation of the carboxy-terminal thiocarboxylate .
Glycoside hydrolase, 48F (Glyco_hydro_48F)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 48

comprises enzymes with several known activities; endoglucanase (

); cellobiohydrolase (

).

The largest cellulase gene sequenced to date is one of the cellulases (celA) from the genome of the thermophilic anaerobic bacterium Caldocellum saccharolyticum. The celA gene product is a polypeptide of 1751 amino acids; this has a multidomain structure comprising two catalytic domains and two cellulose-binding domains, linked by Pro-Thr-rich regions. The N-terminal domain encodes an endoglucanase activity on carboxymethylcellulose, consistent with its similarity to several endo-1, 4-beta-D-glucanase sequences. The C-terminal domain shows similarity to a cellulase from Clostridium thermocellum (CelS), which acts synergistically with a second component to hydrolyse crystalline cellulose .