SII-SWORD/CoKE huggingface dataset:
Synaptobrevin/Vesicle-associated membrane protein (Synaptobrevin/VAMP)
Type: Family

This entry includes vesicle-associated membrane proteins VAMP1/synaptobrevin-1, VAMP2/synaptobrevin-2, VAMP3/synaptobrevin-3 and VAMP8/endobrevin.

VAMPs are a group of small, integral membrane proteins of synaptic vesicles that is mostly involved in vesicle fusion. The heterotrimeric SNARE complex is formed by syntaxin 1, synaptosomal-associated protein 25kDa (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin . VAMP1 plays an essential, non-redundant role in Ca2+-triggered vesicle exocytosis at the mouse neuromuscular junction . VAMP2 is extensively expressed in the central nervous system . Neurotransmitter release involves the assembly of a heterotrimeric SNARE complex composed of SNAP25, VAMP2 and syntaxin 1 . VAMP8 may be involved in regulated exocytosis of the exocrine system .
Lipase Rog1 (Rog1_fam)
Type: Family

This entry represents a group of lipases, including budding yeast Rog1. Rog1 is a monoacylglycerol (MAG) lipase that regulates lipid homeostasis . This entry also includes Rog1 paralogue YDL109C and the uncharacterised proteins YDR444W and C4A8.10.
Flavin oxidoreductase Frp family (Flavin_OxRdtase_Frp)
Type: Family

Reduced flavins participate in numerous biochemical processes. NAD(P)H-flavin oxiodoreductases (flavin reductases) catalyses the reduction of flavin by NAD(P)H. The representative member of this family, Frp (flavin reductase P), is a supplier of reduced flavin mononucleotide (FMNH2) to the bioluminescence reaction in Vibrio harveyi .

Oxygen-insensitive NADPH nitroreductase also belongs to this family. It catalyses the reduction of nitroaromatic compounds using NADH. It is a major component of the oxygen-insensitive nitroreductase activity of some bacteria, such as E.coli .

Both the reductase and nitroreductase are homodimeric flavoproteins that contain one FMN per monomer as a cofactor .
Translocation associated membrane protein (Translocation_assoc_membrane)
Type: Family

This group represents a translocation associated membrane protein.
Uncharacterised conserved protein UCP005522 (UCP005522)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Intermediate filament, ifa/ifb (Intermed_filament_ifa/ifb)
Type: Family

Intermediate filaments (IF) are proteins which are primordial components of the cytoskeleton and the nuclear envelope. All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled-coiled α-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins. While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain.

This entry represents a family of cytoplasmic intermediate filament proteins of invertebrates, and includes both A and B types .
Fatty acid synthase beta subunit AflB /Fas1-like, fungi (Fas1/AflB-like)
Type: Family

This entry represents a fatty acid synthase beta subunit found in fungi, including Fas1 from yeasts and aflB from Aspergillus parasiticus. The beta subunit contains domains for: [acyl-carrier-protein] acetyltransferase and malonyltransferase, S-acyl fatty acid synthase thioesterase, enoyl-[acyl-carrier-protein] reductase, and 3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase.

Fas1 is a fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH .
Coatomer beta' subunit (COPB2) (COPB2)
Type: Family

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .

This group represents the coatomer beta' subunit (COPB2), which is part of the outer-coat subcomplex together with alpha and epsilon subunits, of which the alpha and beta' subunits interact with dilysine K(X)KXX cargo motifs . This subunit consists of two WD40 β-propeller domains followed by an α-solenoid, a structural feature shared by other coat proteins such as clathrin and sec13/31 from COPII. COPB2 and COPI are essential regulators of skeletal homeostasis, as mutations of COPB2 lead to early onset osteoporosis and variable developmental delay .
Cysteine desulfurase (Cysteine_dSase)
Type: Family

This group represents a cysteine desulfurase, NifS type. NifS-like proteins are homodimeric and belong to the alpha-family of pyridoxal-5'-phoshate dependent enzymes which catalyse the reaction:
L-cysteine + (enzyme)-cysteine = L-alanine + (enzyme)-S-sulphanylcysteine

Cysteine desulfurase proteins play a central role in the delivery of sulphur to a variety of metabolic pathways . It is involved in the biosynthesis of iron-sulphur clusters, thio-nucleosides in tRNA, thiamine, biotin, lipoate and pyranopterin (molybdopterin) . They are present in all organisms (except viruses). In eukaryotes these enzymes occur in mitochondria since this is the primary site for Fe-S cluster assembly .
Xyloglucan endotransglucosylase/hydrolase (XTH)
Type: Family

This entry includes a group of xyloglucan endotransglucosylase/hydrolases (XTHs) from plants . Xyloglucan is a soluble hemicellulose with a backbone of beta-1,4-linked glucose units, partially substituted with alpha-1,6-linked xylopyranose branches. It binds noncovalently to cellulose, cross-linking the adjacent cellulose microfibrils, giving it a key structural role as a matrix polymer. XTHs catalyses xyloglucan endohydrolysis (XEH) and/or endotransglycosylation (XET) and are involved in the modification of cell wall structure by cleaving and, often, also re-joining xyloglucan molecules in primary plant cell walls .
Predicted cobalamin-independent methionine synthase, catalytic subunit (Met_Synthase_cat)
Type: Family

This group represents a predicted cobalamin-independent methionine synthase, catalytic subunit.
Formylmethanofuran dehydrogenase, subunit B (Formylmethanofuran_DH_bsu)
Type: Family

Formylmethanofuran dehydrogenase (

) is found in methanogenic and sulphate-reducing archaea. The enzyme contains molybdenum or tungsten, a molybdopterin guanine dinuceotide cofactor (MGD) and iron-sulphur clusters . It catalyses the reversible reduction of CO
2
and methanofuran via N-carboxymethanofuran (carbamate) to N-formylmethanofuran, the first and second steps in methanogenesis from CO
2
. This reaction is important for the reduction of CO
2
to methane, in autotrophic CO
2
fixation, and in CO
2
formation from reduced C
1
units . The synthesis of formylmethanofuran is crucial for the energy metabolism of archaea. Methanogenic archaea derives the energy for autrophic growth from the reduction of CO
2
with molecular hydrogen as the electron donor . The process of methanogenesis consists of a series of reduction reactions at which the one-carbon unit derived from CO
2
is bound to C
1
carriers.

There are two isoenzymes of formylmethanofuran dehydrogenase: a tungsten-containing isoenzyme (Fwd) and a molybdenum-containing isoenzyme (Fmd). The tungsten isoenzyme is constitutively transcribed, whereas transcription of the molybdenum operon is induced by molybdate . The archaean Methanobacterium thermoautotrophicum contains a 4-subunit (FwdA, FwdB, FwdC, FwdD) tungsten formylmethanofuran dehydrogenase and a 3-subunit (FmdA, FmdB, FmdC) molybdenum formylmethanofuran dehydrogenase .

This entry represents subunit B (FmdB and FwdB) of formylmethanofuran dehydrogenase. The other subunits are subunit A (

), subunit C (

), subunit D (

), subunit E (

) and subunit F. Some organisms also encode a fusion of the C and D subunits (

). Formylmethanofuran dehydrogenase catalyzes the first step in methane formation from CO2 in methanogenic archaea and some eubacteria. Members in this entry belong to the molybdopterin_binding (MopB) superfamily of proteins .
Uncharacterised conserved protein UCP005648, calcium-binding (UCP005648_Ca-bd)
Type: Family

The structure of the Methanobacterium thermoautotrophicum protein encoded by MTH1880 demonstrates the typical α + β fold found in many proteins with different functions . The molecular surface of the protein reveals a small, highly acidic pocket. MTH1880 protein contains a novel motif for calcium-specific binding, but does not show a calcium-induced conformational change typical of calcium sensor proteins. It may function as a calcium buffering protein .
Coatomer beta subunit (COPB1) (COPB1)
Type: Family

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .

This entry represents the coatomer beta subunit, which forms the adaptor subcomplex together with delta, gamma and zeta subunits, homologous to the clathrin adaptor AP complexes. It has an α-solenoid 'trunk' domain with interacts with an Arf1 molecule to anchor the coat to the membrane .
O-methyltransferase-like (COMT-like)
Type: Family

This entry represents proteins belonging to the Class I SAM-dependent methyltransferases superfamily, including caffeic acid O-methyltransferase (COMT), isoflavone-7-O-methyltransferase, inositol 4-methyltransferase and acetylserotonin O-methyltransferase .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.

The vast majority of methyltransferases belong to the Rossmann-like fold (Class I) which consists in a seven-stranded β-sheet adjoined by α-helices. Even within the structurally conserved family of Class I methyltransferases, a wide variety of mechanisms have evolved to activate the catalytic nucleophile, dependent on the polarizability of the target atom .
Molybdate-dependent transcriptional regulator ModE (ModE)
Type: Family

The ModE-Mo complex acts as a repressor of the modABC operon, which is involved in the transport of molybdate. Upon binding molybdate, the conformation of the protein changes, promoting dimerization of ModE-Mo. The protein dimer is then competent to bind a DNA region, upstream of the modABC operon, which contains an 8-base inverted repeat 5'-TAACGTTA-3' flanked by two CAT boxes. ModE also interacts with tungstate .
Electron transport complex, RnfB/RsxB, Proteobacteria (RnfB/RsxB_Proteobac)
Type: Family

This family of proteins is made up of electron transport complex subunit RnfB and RsxB, mainly from Proteobacteria.

The six subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes an apparent NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidised . This family of putative NADH oxidoreductase complexes exists in many of the same species as the related NQR, a Na(+)-translocating NADH-quinone reductase, but is distinct. This entry describes the B subunit.
NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex, subunit 2 (NADH_Ub_cplx-1_asu_su-2)
Type: Family

This group represents a NADH dehydrogenase [ubiquinone (complex I), alpha subcomplex, subunit 2.
Methanogenesis marker 3 protein (Methan_mark_3)
Type: Family

Members of this protein family are only found in archaeal methanogens. The functions of proteins in this family are unknown, but their role is likely one essential to methanogenesis .
DNA recombination and repair protein, RecA-like (DNA_recomb/repair_RecA-like)
Type: Family

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response . In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs . RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage .

RecA is a protein of about 350 amino acid residues. Its sequence is very well conserved among eubacterial species. It is also found in the chloroplast of plants . RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament visualised by X-ray crystallography, β-strand 3, the loop C-terminal to β-strand 2, and α-helix D of the core domain form one surface that packs against αa-helix A and β-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation . The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between β-strand 1 and α-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another nucleotide binding motif, the Walker B box is found at β-strand 4 in the RecA structure. The Walker B box is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP-binding interactions are contributed by the amino acid residues at β-strand 2 and the loop C-terminal to that strand, all of which are greater than 90% conserved among bacterial RecA proteins.

This entry represents a subset of the RecA-like proteins.
CCAAT/enhancer-binding protein, chordates (C/EBP_chordates)
Type: Family

This group represents a CCAAT/enhancer-binding protein.CCAAT/enhancer-binding proteins (C/EBPs) are basic region leucine zipper (bZIP) transcription factors. They regulate cell differentiation, growth, survival, and inflammation . They function in a variety of tissues. The prototypic C/EBP is a modular protein, consisting of an activation domain, a dimerization bZIP region, and a DNA-binding domain. All family members share the highly conserved dimerization domain, required for DNA binding, by which they form homo- and heterodimers with other family members. The least conserved parts of C/EBPs are the activation domains which vary from strong activators to dominant negative repressors .

C/EBPs have been found to promote the terminal differentiation of adipocytes. During the normal course of adipogenesis, C/EBP expression is restricted to a terminal phase when growth is paused and specialised cell phenotypes emerge. Since C/EBP is expressed in a variety of tissues, it may have a fundamental role in regulating the balance between cell growth and differentiation in higher animals .
Carbohydrate sulfotransferase (Carbohydrate_sulfotransferase)
Type: Family

This entry represents carbohydrate sulphotransferase, which catalyses the transfer of a sulphate to position 6 of the galactose (Gal) residues in keratan. It may function in the sulphation of sialyl N-acetyllactosamine oligosaccharide chains attached to glycoproteins and participate in the biosynthesis of selectin ligands. Selectin ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. Carbohydrate sulphotransferase CHST1, CHST2, CHST3, and CHST4 are all involved in producing functional L-selectin ligands .

Deficiency of CHST3 (also known as chondroitin-6-sulphotransferase) has been associated with severe chondrodysplasia with progressive spinal involvement . Macular corneal dystrophy (MCD) has also been shown to be caused by mutations in the carbohydrate sulphotransferase 6 gene (CHST6) .
Phycobilisome linker protein (Phycobilisome)
Type: Family

This group represents a phycobilisome rod linker polypeptide, phycocyanin-associated. They are linker polypeptides that determine the state of aggregation and the location of the disk-shaped phycobiliprotein units within the phycobilisome and modulate their spectroscopic properties in order to mediate a directed and optimal energy transfer .
Nicotinamide phosphoribosyl transferase (Nicotinamide_PRibTrfase)
Type: Family

This entry represents the family of nicotinamide phosphoribosyl transferases (NAMPT). NAMPT consists of two intertwined α/β domains one of which is a rudiment of the classical TIM-barrel . It forms dimers that exist in a head to tail configuration.

Nicotinamide phosphoribosyl transferase (NAMPT) catalyses the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD . NAMPT is also known as pre-B cell colony-enhancing factor (PBEF) or visfatin.
Transcription regulator, MJ0621, predicted (Tscrpt_reg_MJ0621_prd)
Type: Family

This group is represented by predicted transcriptional regulator MJ0621 from Methanocaldococcus jannaschii.
Deoxycytidylate deaminase (dCMP_deaminase)
Type: Family

Deoxycytidylate deaminase (

) (dCMP deaminase) hydrolyzes deoxycytidylate mono phosphate (dCMP) into deoxyuridine mono phosphate (dUMP), thus providing the nucleotide substrate for thymidylate synthase. The enzyme requires zinc for catalytic activity which is regulated by the ratio of dCTP to dTTP, both the end products of the pyrimidine salvage pathway . It contains a cytidine and deoxycytidylate deaminase domain.
Phosphate acetyltransferase, bacteria (P-Actrans_bac)
Type: Family

E. coli is able to metabolise excess acetate and even use it as sole carbon source. The enzymes involved are acetyl-CoA synthetase (Acs, non-reversible dissimilation) and the phosphotransacetylase-acetate kinase pathway (Pta-Ack), which is characterised by its reversibility . This entry represents phosphate acetyltransferase Pta from bacteria.
SH3 domain protein (SH3_dom_pro)
Type: Family

Members of this protein family have a signal peptide, a strongly conserved SH3 domain, a variable region, and then a C-terminal hydrophobic transmembrane α helix region.
Fructosamine/Ketosamine-3-kinase (Fructo-/Ketosamine-3-kinase)
Type: Family

Ketosamines derive from a non-enzymatic reaction between a sugar and a protein . Ketosamine-3-kinases (KT3K), of which fructosamine-3-kinase (FN3K) is the best-known example, catalyse the phosphorylation of the ketosamine moiety of glycated proteins. The instability of a phosphorylated ketosamine leads to its degradation, and KT3K is thus thought to be involved in protein repair .

The function of the prokaryotic members of this group has not been established. However, several lines of evidence indicate that they may function as fructosamine-3-kinases (FN3K). First, they are similar to characterised FN3K from mouse and human. Second, the Escherichia coli members are found in close proximity on the genome to fructose-6-phosphate kinase (PfkB). Last, FN3K activity has been found in a Anacystis montana (Gloeocapsa montana Kutzing 1843) , indicating such activity-directly demonstrated in eukaryotes-is nonetheless not confined to eukaryotes.

This family includes eukaryotic fructosamine-3-kinase enzymes which may initiate a process leading to the deglycation of fructoselysine and of glycated proteins and in the phosphorylation of 1-deoxy-1-morpholinofructose, fructoselysine, fructoseglycine, fructose and glycated lysozyme. The family also includes bacterial members that have not been characterised but probably have a similar or identical function.