SII-SWORD/CoKE huggingface dataset:
Bacteriochlorophyll A protein (BChl_A)
Type: Family

Bacteriochlorophyll A (or FMO) protein is involved in the energy transfer system of photosynthetic bacteria, such as Green Sulphur Bacteria. Bacteriochlorophyll A acts as a light-harvesting complex that directs light energy from the chlorosomes attached to the cell membrane to the reaction centre . The protein forms a homotrimer, with each monomer unit containing seven molecules of bacteriochlorophyll A.
Histidine decarboxylase proenzyme (His_de-COase_proenz)
Type: Family

Histidine decarboxylase (

) catalyses the formation of histamine from histidine . It requires a pyruvoyl group for its activity. Cleavage of the proenzyme PI chain yields two subunits, alpha and beta, which arrange as a hexamer (alpha beta) 6 by nonhydrolytic self-catalysis.

In Lactobacillus cells, pyruvoyl-dependent histidine decarboxylase functions to counter the effects of acidic fermentation products, thus modifying extracellular pH. Cells take up histidine and decarboxylate it using histidine decarboxylase to consume a proton and produce histamine, which the cells excrete. These proteins are all dependent on the pyruvoyl cofactor, which is part of the active site and is located at the amino terminus of the alpha-chain (corresponding to residue 82 of the proenzyme in Lactobacillus sp. 30a), at the break between the beta and alpha chains. This pyruvoyl cofactor facilitates decarboxylation via a Schiff base mechanism resembling that of the more common PLP-dependent decarboxylases. This covalent intermediate allows for resonance stabilisation, facillitaing the decarboxylation step. The mechanism for this enzyme can be found in MACiE entry M0049 .
Mitochondrial glycoprotein (MAM33)
Type: Family

This mitochondrial matrix protein family contains members of the MAM33 family (also known as Complement component 1 Q subcomponent-binding protein in human) which bind to the globular 'heads' of C1Q.b . In vertebrates, these proteins are involved in inflammation and infection processes, ribosome biogenesis, protein synthesis in mitochondria, regulation of apoptosis, transcriptional regulation and pre-mRNA splicing . It is thought to be involved in mitochondrial oxidative phosphorylation and in nucleus-mitochondrion interactions .
Baculovirus p35, apoptosis preventing protein (Baculovirus_p35)
Type: Family

The anti-apoptotic protein p35 from baculovirus is thought to prevent the suicidal response of infected insect cells by inhibiting caspases. Ectopic expression of p35 in a number of transgenic animals or cell lines is also anti-apoptotic, giving rise to the hypothesis that the protein is a general inhibitor of caspases.
Propane/methane/phenol/toluene hydroxylase (Phenol_Hydrox)
Type: Family

This entry includes several components of multicomponent enzyme systems predominantly found in Proteobacteria and Actinobacteria.

Propane 2-monooxygenase multicomponent enzyme system is involved in the degradation of propane via the O2-dependent hydroxylation of propane . Propane 2-monooxygenase, hydroxylase component large and small subunit are also included in this entry.

Phenol hydroxylase is a multicomponent enzyme that catabolises phenol and some of its methylated derivatives . This family includes Phenol 2-monooxygenase, oxygenase component DmpL/DmpN, part of the oxygenase component of the complex in Pseudomonas sp. .

Methane monooxygenase component A is responsible for the initial oxygenation of methane to methanol in methanotrophs. It also catalyses the monohydroxylation of a variety of unactivated alkenes, alicyclic, aromatic and heterocyclic compounds. This family contains the alpha and beta chain of Methane monooxygenase component A.

Toluene-4-monooxygenase system, hydroxylase component subunits alpha and beta are also included in this family. These proteins hydroxylate toluene to form P-cresol in Pseudomonas mendocina .

Alkene monooxygenase system from Xanthobacter autotrophicus catalyses the O2 and NADH-dependent epoxidation of short chain (C2 to C6) alkenes to their corresponding epoxides . Oxygenase component subunits alpha and beta also belong to this group of proteins.
3 pythase, beta-propeller (B-propeller_Phytase)
Type: Domain

Phytase (

) (phytate 3-phosphatase) is a secreted enzyme which hydrolyses phytate to release inorganic phosphate. According to their three-dimensional structures and catalytic mechanisms, phytases are classified into different groups, one of them the β-propeller phytases . The β-propeller phytase domain is made of six blades. Each blade is a highly curved sheet composed of four to five antiparallel β-strands that are connected in a topologically identical manner. The fourth strand of each blade is connected across the top of the molecule to the first strand of the next blade. The six blades are aligned along the shaft of the propeller, which is a distinct central channel filled with many well-bound water molecules. Between the blades, extensive hydrophobic interactions are observed .
Replication terminator protein (RTP)
Type: Family

The bacterial replication terminator protein (RTP) plays a role in the termination of DNA replication by impeding replication fork movement. Two RTP dimers bind to the two inverted repeat regions at the termination site.
Capsid protein VP4 (Capsid_VP4_densovirus)
Type: Family

The virus capsid is composed of 60 icosahedral units of a combination of VP4, VP3, VP2 and VP1. Four different translation initiation sites of the Densovirus capsid protein mRNA give rise to these four viral proteins, VP1 to VP4. This family represents VP4.
Arterivirus GP2a envelope protein (Arteri_GP2a)
Type: Family

This family consists of a envelope glycoprotein GP2a or ORF2 in Porcine reproductive and respiratory syndrome virus (PRRSV) . Also in the family is a minor structural protein from lactate dehydrogenase-elevating virus.
Chaperonin-like RbcX (Chaperonin_RcbX)
Type: Family

The RbcX protein has been identified as having a chaperonin-like function as it assists in the correct assembly of RbcL and RbcS subunits during RuBisCO biogenesis and it is also required to reach its maximal activity . The rbcX gene is juxtaposed to and cotranscribed with rbcL and rbcS encoding RubisCO in Anabaena sp. (strain CA / ATCC 33047) . Crystal structure studies revealed that RbcX is composed almost exclusively of α-helices, which form an unusual four-helix bundle. Additionally, all known RbcX proteins exist as homodimers (RbcX2). The central cleft of this homodimer binds the C-terminal of a RbcL monomer, stabilizing it, and the peripheral region of RbcX2 binds a second RbcL monomer, which allows the RbcL homodimers to be in the correct orientation .
Chordopoxvirus fusion protein/multifunctional envelope protein A27 (Chordopox_Fusion/A27)
Type: Family

This is a family of viral fusion proteins from the Chordopoxvirinae. A 14kDa Vaccinia virus protein has been demonstrated to function as a viral fusion protein mediating cell fusion at endosmomal (low) pH . The protein, found in the envelope fraction of the virions, is required for fusing the outermost of the two golgi-derived membranes enveloping the virus with the plasma membrane, and its subsequent release extracellularly. The N-terminal proximal region is essential for its fusion ability.
Glycine dehydrogenase (decarboxylating) (GcvP)
Type: Family

The P protein, also known as Glycine dehydrogenase (decarboxylating), is part of the glycine decarboxylase multienzyme complex (GDC), also annotated as glycine cleavage system or glycine synthase. GDC consists of four proteins P, H, L and T . The P protein (

) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor, carbon dioxide is released and the remaining methylamin moiety is then transferred to the lipoamide cofactor of the H protein. The reaction catalysed by this protein is:

Glycine + lipoylprotein = S-aminomethyldihydrolipoylprotein + CO2

The subunit composition of glycine cleavage system P proteins have been classified into two types. Those from eukaryotes and some of the P proteins from prokaryotes (e.g. Escherichia coli) are in the homodimeric form. The rest of those from prokaryotes are heterotetrameric, with two different subunits which, based on sequence similarities, correspond respectively to the N and C-terminal halves of the eukaryotic subunit .

This entry represents the P protein homodimeric subfamily, which is found in eukaryotes and some prokaryotes, such as E. coli.
Glial cell line-derived neurotrophic factor receptor (GDNF_rcpt)
Type: Family

Glial cell line-derived neurotrophic factor (GDNF) and its related factors neurturin (NTN), artemin (ART) and persephin (PSP), are members of the GDNF family of neurotrophic factors. They form a sub-group in the transforming growth factor-beta (TGF-beta) superfamily. These factors are involved in the promotion of neurone survival, exerting their effects through specific receptors.

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked, cell surface receptors . Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. GFRalpha-1 and 2 are activated by GDNF and NTN respectively, although some degree of ligand promiscuity is thought to occur . Homologues for these receptor subtypes have been cloned from mammalian and avian tissue. The principal ligand for GFRalpha-3 is artemin. This receptor subtype is currently described only in mammals . GFRalpha-4 is activated by persephin and has so far only been found in chicken . This entry is general for types 1 to 3.

Activation of GFR family members triggers their interaction with the membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation, triggering a cascade of intracellular signalling events such as the activation of the Ras-mitogen-activated protein kinase (MAPK), phosphoinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and phospholipase C gamma (PLC gamma) dependent pathways .
Glycosyl transferase 48 domain (Glyco_trans_48_dom)
Type: Domain

This entry represents a domain found in glycosyltransferase 48 enzymes

, including various 1,3-beta-glucan synthase components such as Gls1, Gls2 and Gls3 from yeast. 1,3-beta-glucan synthase (

) also known as callose synthase catalyses the formation of a beta-1,3-glucan polymer that is a major component of the fungal cell wall . The reaction catalysed is:-

UDP-glucose + {1,3-beta-D-glucosyl}(N)
= UDP + {1,3-beta-D-glucosyl}(N+1).

This domain is often found in combination with

.

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

The NAC domain (for Petunia hybrida (Petunia) NAM and for Arabidopsis ATAF1, ATAF2, and CUC2) is an N-terminal module of ~160 amino acids, which is found in proteins of the NAC family of plant-specific transcriptional regulators (no apical meristem (NAM) proteins) . NAC proteins are involved in developmental processes, including formation of the shoot apical meristem, floral organs and lateral shoots, as well as in plant hormonal control and defence. The NAC domain is accompanied by diverse C-terminal transcriptional activation domains. The NAC domain has been shown to be a DNA-binding domain (DBD) and a dimerization domain .

The NAC domain can be subdivided into five subdomains (A-E). Each subdomain is distinguishable by blocks of heterogeneous amino acids or gaps. While the NAC domains were rich in basic amino acids (R, K and H) as a whole, the distribution of positive and negative amino acids in each subdomain were unequal. Subdomains C and D are rich in basic amino acids but poor in acidic amino acids, while subdomain B contains a high proportion of acidic amino acids. Putative nuclear localization signals (NLS) have been detected in subdomains C and D . The DBD is contained within a 60 amino acid region located within subdomains D and E . The overall structure of the NAC domain monomer consists of a very twisted antiparallel β-sheet, which packs against an N-terminal α-helix on one side and one shorter helix on the other side surrounded by a few helical elements. The structure suggests that the NAC domain mediates dimerization through conserved interactions including a salt bridge, and DNA binding through the NAC dimer face rich in positive charges .
tRNA threonylcarbamoyl adenosine modification protein TsaE (T6A_TsaE)
Type: Family

Members of this family have a conserved nucleotide-binding motif GXXGXGKT and a nucleotide-binding fold. Member protein YjeE of Haemophilus influenzae (HI0065) was shown to have ATPase activity . The protein has a nucleotide-binding fold with a four-stranded parallel β-sheet flanked by antiparallel β-strands on each side. The topology of the β-sheet is unique among P-loop proteins and has features of different families of enzymes. ADP has been shown to bind to the P-loop in the presence of Mg2+.

Recently YjeE has been renamed as TsaE . It is responsible for tRNA threonylcarbamoyl adenosine modification together with proteins TsaB, TsaC, and TsaD, and probably forms a complex with them .
Interleukin-15/Interleukin-21 family (IL-15/IL-21_fam)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

Interleukin-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses . It is required for division of CD8+ T cells of memory phenotype, a process that is increased by inhibition of IL-2 . The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2.

This entry represents the interleukin-15 and interleukin-21 family.
Transcriptional regulator MraZ (MraZ)
Type: Family

This entry represents the MraZ protein from bacteria. This protein often is found with other genes of the dcw (division cell wall) gene cluster, including mraW, ftsI, murE, murF, ftsW, murG, etc. In E. coli, MraZ is a DNA-binding transcription factor . It acts as a repressor of Pmra, which is a promoter for mraZ and mraW. It also regulates the expression of genes outside the dcw cluster. Overproduction of Escherichia coli MraZ inhibits cell division .
Cation transporter (Cat_transpt)
Type: Family

This family consists of various potassium transport proteins (Trk) and V-type sodium ATP synthase subunit J or translocating ATPase J (

). These proteins are involved in active sodium uptake utilizing ATP in the process. TrkH from Escherichia coli is a hydrophobic membrane protein and determines the specificity and kinetics of cation transport by the TrK system in this organism . This protein interacts with TrkA and requires TrkE for transport activity .
Plasmid replication initiation, RepA (Plasmid_replication_init_RepA)
Type: Family

These proteins are plasmid encoded and essential for plasmid replication, they are also involved in copy control functions .
FemABX peptidyl transferase (FEMABX)
Type: Family

The entry represents the FemABX peptidyl transferase family.

FemABX peptidyl transferases catalyse the incorporation of amino acid(s) into the interchain peptide bridge of peptidoglycan using aminoacyl-tRNA as the amino acid donor, a reaction involved in the synthesis of the bacterial cell wall. The femABX enzymes catalyse the addition of amino acids to a peptidoglycan precursor, which in most cases is a lipid-linked sugar pentapeptide or, alternatively, a soluble nucleotide precursor for W. viridescens femX. The resulting branched peptide chain consists of one to five amino acids and is cross-linked to a pentapeptide of a neighbouring disaccharide chain by a transpeptidase in the final step of peptidoglycan synthesis. The interchain peptide and the femABX enzymes for their synthesis are found in several Gram-positive bacteria and in some Gram-negative, mainly pathogenic species. The femABX transferases differ by type, position and number of amino acids that are incoporated into the interchain. Some femABX proteins function as immunity factors that protect producers of interpeptide-specific endopeptidases against their own products. In addition, the interpeptide plays an important role in cell separation and virulence .

Some proteins known to belong to the femABX peptidyl transferase family:

Staphylococcal femA and femB, factors essential for expression of methicillin resistance. FemA adds glycines 2 and 3 of the pentaglycine interpeptide, while femB adds glycines 4 and 5.

Staphylococcal fmhB (for fem homologue) or femX, which incorporates the first glycine of the pentaglycine interchain peptide in peptidoglycan.

Weissella viridescens femX, which catalyses the transfer of an L-alanine from Ala-tRNA to the ε-amino group of L-lysine of UDP-MurNAc pentapeptide .

Streptococcus pneumoniae fibA/murM and fibB/murN, which synthesize branched structured cell wall muropeptides that are strain-specific.

Staphylococcus capitis epr (endopeptidase resistance), which renders the cells resistant to glycylglycine endopeptidase by increasing the serine content and decreasing the glycine content of the interpeptide chains.
Molybdopterin biosynthesis MoaE (Mopterin_biosynth_MoaE)
Type: Family

Members of the MoaE family are involved in biosynthesis of the molybdenum cofactor (Moco), an essential cofactor for a diverse group of redox enzymes. Moco biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes. Moco contains a tricyclic pyranopterin, termed molybdopterin (MPT), which carries the cis-dithiolene group responsible for molybdenum ligation. This dithiolene group is generated by MPT synthase in the second major step in Moco biosynthesis. MPT synthase is a heterotetramer consisting of two large (MoaE) and two small (MoaD) subunits .
Coronavirus protein 7 (Corona_7)
Type: Family

This is a family of proteins from Coronavirus, which may function in the formation of membrane-bound replication complexes or in viral assembly.
Replication origin-binding protein (Replication_origin-bd)
Type: Domain

This entry represents replication origin binding protein. It functions as a docking protein to recruit essential components of the viral replication machinery to viral DNA origins. In the presence of the major DNA-binding protein, it opens dsDNA which leads to a conformational change in the origin that facilitates DNA unwinding and subsequent replication .
4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH)
Type: Family

Terpenes are among the largest groups of natural products and include compounds such as vitamins, cholesterol and carotenoids. The biosynthesis of all terpenoids begins with one or both of the two C5 precursors of the pathway: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In animals, fungi, and certain bacteria, the synthesis of IPP and DMAPP occurs via the well-known mevalonate pathway, however, a second, nonmevalonate terpenoid pathway has been identified in many eubacteria, algae, malaria parasite and the chloroplasts of higher plants .

LytB(IspH) is the last enzyme in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the 1-deoxy-d-xylulose-5-phosphate (DOXP, the nonmevalonate pathway, also known as MEP) pathway . This enzyme contains a [4Fe-4S] cluster and forms a stable complex with ferredoxin, which suggests that ferredoxin/ferredoxin-NADP+ reductase redox system serves as the physiological electron donor for LytB . Escherichia coli LytB protein had been found to regulate the activity of RelA (guanosine 3',5'-bispyrophosphate synthetase I), which in turn controls the level of a regulatory metabolite. It is involved in penicillin tolerance and the stringent response .
Stem cell factor (SCF)
Type: Family

Stem cell factor (SCF) is a homodimer involved in hematopoiesis. SCF binds to and activates KIT, a receptor tyrosine kinase . SCF stimulates the proliferation of mast cells and is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow culture. It also mediates cell-cell adhesion and acts synergistically with other cytokines. SCF is a type I membrane protein, but is also found in a secretable, soluble form. The crystal structure of human SCF has been resolved and a potential receptor-binding site identified .
ABC transport permease subunit MlaE, proteobacteria (ABC_MlaE_roteobac)
Type: Family

This entry represents a subfamily of ABC transporter permease subunits. In

it is involved in L-glutamate import into the cell . In

it is involved in lipid transfer within the cell . In

(MlaE) it is involved in phospholipid transport as part of the Mla system, whose role is preserving outer membrane lipid asymmetry . Many bacterial species have one or two members from this family. The Mycobacteria have large paralogous families included in

, but excluded from this subfamily .
Monooxygenase component MmoB/DmpM (MOase_MmoB_DmpM)
Type: Family

This entry represents a family of monooxygenase components that include Methane monooxygenase regulatory protein B (MmoB), and Phenol 2-monooxygenase, stimulatory component DmpM. When MmoB is present at low concentration it converts methane monooxygenase from an oxidase to a hydroxylase and stabilises intermediates required for the activation of dioxygen . DmpM lacks redox co-factors and is required for optimal turnover of Phenol hydroxylase . This protein catabolises phenol and some of its methylated derivatives in the first step of phenol biodegradation, and is required for growth on phenol.

This family also includes Propane 2-monooxygenase, effector component (MimD) which has been shown to function as a coupling protein in the multicomponent propane 2-monooxygenase enzyme system in the degradation of propane as well as the conversion of phenol to hydroquinone .

Toluene-4-monooxygenase system, effector component (TmoD) from Pseudomonas mendocina also belongs to this group. It catalyses the O2 and NADH-dependent hydroxylation of toluene to form p-cresol , and the Alkene monooxygenase system, effector subunit from Xanthobacter autotrophicus, which catalyses the O2 and NADH-dependent epoxidation of short chain (C2 to C6) alkenes to their corresponding epoxides .
Mercuric transport protein MerT (Transprt_MerT)
Type: Family

MerT is an mercuric transport integral membrane protein and is responsible for transport of the Hg2+ iron from periplasmic MerP (also part of the transport system) to mercuric reductase (MerA) .
Bacteriophage T4, Gp38, tail fibre assembly (Phage_T4_Gp38_tail_assem)
Type: Family

This family contains Bacteriophage T4 gp38 and related bacterial prophage and phage proteins. Gene 38 of phage T4 codes for a protein containing 183 amino acid residues with molecular weight of 22.3kDa. Together with genes 36 and 37, whose products are structural proteins of the fibre distal part, gene 38 forms one transcription unit. Gp38, is a chaperone, which is required for assembly of the distal part of the long fibres and which is absent from the mature phage particle. In the absence of gp38 gp37, which is a component of the distal part of the long tail fibre, fails to oligomerise. The carboxy-terminal region of gp37 forms the tip of the distal fibre that interacts with the cell receptors. Functionally the role of gp38 can be replaced by pTfa of Bacteriophage lambda .

The function of many of the other members of this family remain to be elucidated.