SII-SWORD/CoKE huggingface dataset:
UDP-N-acetylglucosamine 2-epimerase WecB (WecB)
Type: Family

This entry represents UDP-N-acetylglucosamine 2-epimerase WecB (also known as RffE) from Enterobacteriaceae. WecB is involved in the Enterobacterial common antigen (ECA) biosynthesis, which is part of bacterial outer membrane biogenesis. ECA is a specific surface antigen (polysaccharide) shared by all members of the Enterobacteriaceae and is restricted to this family . It catalyses the reversible epimerization at C-2 of UDP-N-acetylglucosamine (UDP-GlcNAc) and thereby provides bacteria with UDP-N-acetylmannosamine (UDP-ManNAc), the activated donor of ManNAc residues .
Galactarate dehydratase (L-threo-forming) GarD, Enterobacteriaceae (GarD_Enterobacteriaceae)
Type: Family

This entry represents GarD, a galactarate dehydratase (L-threo-forming), from Enterobacteriaceae. It is involved in step 1 of the subpathway that synthesises D-glycerate from galactarate. It catalyses the dehydration of galactarate to form 5-dehydro-4-deoxy-D-glucarate .
dTDP-4-amino-4,6-dideoxygalactose transaminase WecE (WecE)
Type: Family

This entry represents dTDP-4-amino-4,6-dideoxygalactose transaminase WecE (also known as RffA) from Enterobacteriaceae. WecE is involved in the Enterobacterial common antigen (ECA) biosynthesis, which is part of bacterial outer membrane biogenesis. ECA is a specific surface antigen (polysaccharide) shared by all members of the Enterobacteriaceae and is restricted to this family . It catalyses the synthesis of dTDP-4-amino-4,6-dideoxy-D-galactose (dTDP-Fuc4N) from dTDP-4-keto-6-deoxy-D-glucose (dTDP-D-Glc4O) and L-glutamate .
ECA polysaccharide chain length modulation protein WzzE (WzzE)
Type: Family

This entry represents ECA polysaccharide chain length modulation protein WzzE from Enterobacteriaceae. WzzE is involved in the Enterobacterial common antigen (ECA) biosynthesis, which is part of bacterial outer membrane biogenesis. ECA is a specific surface antigen (polysaccharide) shared by all members of the Enterobacteriaceae and is restricted to this family . WzzE modulates the polysaccharide chain length of enterobacterial common antigen . It is required for the assembly of the phosphoglyceride-linked form of ECA (ECA(PG)) and the water-soluble cyclic form of ECA (ECA(CYC)) .
Lipid III flippase WzxE, Proteobacteria (WzxE_Proteobacteria)
Type: Family

This entry represents lipid III flippase WzxE from Proteobacteria. WzxE is involved in the Enterobacterial common antigen (ECA) biosynthesis, which is part of bacterial outer membrane biogenesis. ECA is a specific surface antigen (polysaccharide) shared by all members of the Enterobacteriaceae and is restricted to this family . WzxE mediates the transbilayer movement of Und-PP-GlcNAc-ManNAcA-Fuc4NAc (lipid III) from the inner to the outer leaflet of the cytoplasmic membrane during the assembly of ECA . It is required for the assembly of the phosphoglyceride-linked form of ECA (ECA(PG)) and the water-soluble cyclic form of ECA (ECA(CYC)) .
Dissimilatory sulfite reductase (Sulfite_reductase)
Type: Family

This entry include a group of dissimilatory sulfite reductases from Proteobacteria, including SirA from Shewanella oneidensis and MccA from Wolinella succinogenes . They are respiratory sulfite reductases that catalyse the reduction of sulfite to sulfide in a single step, consuming six electrons in the process . MccA is an unconventional octahaem cytochrome c containing a special haem c group that is bound via two cysteine residues arranged in a unique CX(15)CH haem c binding motif .
Cell division protein DedD (DedD)
Type: Family

This entry represents the cell division protein DedD from Enterobacteriaceae. DedD is an inner membrane protein that contributes to the cell constriction process during bacterial cytokinesis. It contains a C-terminal SPOR domain that may act as autonomous septal targeting determinant .
Cell division protein DamX (DamX)
Type: Family

This entry represents the cell division protein DamX from Enterobacteriaceae. DamX is an inner membrane protein that contributes to the cell constriction process during bacterial cytokinesis. It contains a C-terminal SPOR domain that may act as autonomous septal targeting determinant . DamX localises to the septal ring, but it is non-essential for cell division, and it inhibits cell division when overproduced . It has been suggested that it may contribute to cell envelope biogenesis or integrity in other ways distinct from its role in cell division .
PanD regulatory factor PanZ (PanZ)
Type: Family

This entry represents PanD maturation factor PanZ (also known as PanM or YhhK) from Enterobacteriaceae. PanD is a l-aspartate alpha-decarboxylase involved in pantothenate biosynthesis. It is synthesised as pro-PanD, which undergoes auto-proteolytic cleavage to generate active PanD. PanM binds to and activates PanD by stabilising pro-PanD in an autocleavage-prone conformation . PanM acts as an acetyl-CoA sensor that can trigger the maturation of pro-PanD, but lacks acetyltransferase activity . The regulation of PanD by PanZ allows enterobacterial species to closely regulate production of beta-alanine and hence pantothenate in response to metabolic demand .
Probable UbiX-like flavin prenyltransferase (UbiX_pad_YclB)
Type: Family

This entry represents a group of putative UbiX-like flavin prenyltransferase from bacteria, including YclB (BsdB) from Bacillus subtilis and EcdB (Pad1) from Escherichia coli. They are involved in the decarboxylation and detoxification of phenolic derivatives under both aerobic and anaerobic conditions .
Phenolic acid decarboxylase subunit C (BsdC)
Type: Family

This entry represents the phenolic acid decarboxylase subunit C from bacteria, including YclC (BsdC) from Bacillus subtilis . It is a involved in the decarboxylation and detoxification of phenolic derivatives under both aerobic and anaerobic conditions . It can catalyse the reversible decarboxylation of 4-hydroxybenzoate and vanillate and can also decarboxylate 3,4-dihydroxybenzoate .
Ferulic acid decarboxylase-like (FDC-like)
Type: Family

This entry includes ferulic acid decarboxylase 1 (Fdc1) from fungi and bacterial pyrrole-2-carboxylic acid decarboxylase HudA (also known as UbiD-like decarboxylase and ferulic acid decarboxylase-like protein) . HudA catalyses the prenyl-FMN-dependent decarboxylation of pyrrole-2-carboxylate (P2C) and it can also catalyse the carboxylation of pyrrole in the presence of elevated concentrations of CO2 or bicarbonate . It attenuates the virulence of P.aeruginosa in a Drosophila model when overexpressed . Budding yeast Fdc1 catalyses the reversible decarboxylation of aromatic carboxylic acids like ferulic acid, p-coumaric acid or cinnamic acid, producing the corresponding vinyl derivatives (4-vinylphenol, 4-vinylguaiacol, and styrene respectively) which play the role of aroma metabolites . Fdc1 is not essential for ubiquinone synthesis .
2-phytyl-1,4-naphtoquinone methyltransferase MenG (MenG)
Type: Family

Phylloquinone (vitamin K(1)) is synthesised in cyanobacteria and in chloroplasts of plants, where it serves as electron carrier of photosystem I. This entry represents 2-phytyl-1,4-naphtoquinone methyltransferase MenG, which is required for the last step of phylloquinone synthesis .
O-acetyltransferase WecH (WecH)
Type: Family

WecH (also known as yiaH) is responsible for the incorporation of O-acetyl groups into the enterobacterial common antigen (ECA) trisaccharide repeat units. It catalyses the acetylation of both cyclic ECA (ECA(CYC)) and phosphoglyceride-linked ECA (ECA(PG)) .
Lipopolysaccharide assembly protein A (LapA)
Type: Family

Lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) constitutes the major amphiphilic component of the envelope of most Gram-negative bacteria. This entry represents lipopolysaccharide assembly protein A (LapA) from Gammaproteobacteria. LabA and another heat shock protein, LapB, function together in the assembly of lipopolysaccharide (LPS) .
Tubulin-like protein CetZ (CetZ)
Type: Family

This entry represents tubulin-like protein CetZ mostly from Archaea. It co-exists with another tubulin-like protein, FtsZ, in many archaea. CetZ is required for differentiation of the irregular plate-shaped cells into a rod-shaped cell type that is essential for normal swimming motility .
Lipid A 1-diphosphate synthase (LpxT)
Type: Family

This entry represents lipid A 1-diphosphate synthase LpxT (also known as YeiU) from Enterobacteriaceae. It is involved in the modification of the lipid A domain of lipopolysaccharide (LPS), which is part of Gram-negative bacteria outer membrane. Variation of the lipid A domain of LPS serves to promote bacterial resistance . LpxT transfers a phosphate group from undecaprenyl pyrophosphate (C55-PP) to lipid A to form lipid A 1-diphosphate and contributes to the recycling of undecaprenyl phosphate (C55-P) . It also has low undecaprenyl-diphosphate phosphatase activity
in vitro
.
Vam6/VPS39/TRAP1 family (Vam6/VPS39/TRAP1)
Type: Family

This entry includes fungal Vam6/Vps3 and animal Vps39/TRAP1. Vps39 is also known as Vam6 or TRAP1-Like-Protein (TLP) . Vam6/Vps39 acts as a component of the HOPS complex that functions during the docking stage of vacuole fusion. It is required for late endosomal-lysosomal fusion events and the delivery of endocytic cargo to lysosomes . In addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls the function of the central regulator of eukaryotic cell growth TORC1 by activating the Gtr1 subunit of the EGO complex .

TRAP1 plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway .
Protein SON (SON)
Type: Family

Protein SON is a RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. It facilitates splicing through the recruitment of SR proteins, such as SC35, to RNAP complexes. It regulates a large number of genes dedicated to cell cycle progression .
Lipid transferase CIDEA, N-terminal (CIDEA_N)
Type: Domain

CIDEA is a member of the CIDE (cell-death-inducing DFF45-like effector) family . CIDEA is associated with lipid droplets and insulin sensitivity in humans . It is a lipid transferase that promotes unilocular lipid droplet formation by mediating lipid droplet fusion . It has an important role in the development of obesity and diabetes in rodents . It can also act as a transcriptional coactivator of C/EBPbeta in mammary glands to control milk lipid secretion .

This entry represents the N-terminal domain of CIDE-A.
Calmodulin-regulated spectrin-associated protein (CAMSAP)
Type: Family

The calmodulin-regulated spectrin-associated (CAMSAP) proteins are defined by a CKK domain that binds microtubules . It includes CAMSAPs from vertebrates and Patronin from invertebrates . CAMSAP1 is the representative member. It contains a conserved region, CC1, that binds to both spectrin and Ca2+/calmodulin in vitro and links spectrin-binding to neurite outgrowth . Patronin binds to and protects the MT minus-end against depolymerization . CAMSAP2 is a key microtubule-organising protein that specifically binds the minus end of non-centrosomal microtubules and regulates their dynamics and organisation. CAMSAP proteins carry an N-terminal region that includes two CH domains represented by

and

, a central region including a predicted coiled-coil, and a C-terminal CKK domain

, which is involved in binding CAMSAP proteins to microtubules .
BPI/LBP/Plunc family (BPI/LBP/Plunc)
Type: Family

The BPI (bactericidal permeability-increasing proteins)/LBP (lipopolysaccharide-binding proteins)/PLUNC (palate, lung and nasal epithelium clone) family consists of proteins involved in host defence against bacteria, many acting in early recognition of bacteria in the upper respiratory tract . They share homology with cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), both of which are involved in lipid transport in blood plasma . This entry also matches UPF0522 proteins from Dictyostelium (slime mold), whose function is unknown.
BPI fold-containing family A member 3 (Bpifa3)
Type: Family

BPI fold-containing family A member 3, also known as short palate, lung and nasal epithelium carcinoma-associated protein 3 (Splunc3) belongs to the PLUNC family, whose members are involved in host defence against bacteria . The function of Splunc3 is not known.
Glutamate--cysteine ligase regulatory subunit (Gclm)
Type: Family

Glutamate--cysteine ligase or gamma-glutamylcysteine synthetase (gamma-GCS) catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine to form L-gamma-glutamyl-L-cysteine, the first and rate-limiting step in glutathione (GSH) biosynthesis . The enzyme is a heterodimer composed of a catalytic subunit and a regulatory subunit. The catalytic subunit exhibits all of the catalytic activity, but its association with the regulator subunit alters its kinetic properties to enhance activity . In addition to some conditions which specifically upregulate the catalytic subunit gene, expression of both genes is increased in response to oxidants, heavy metals, phenolic antioxidants, GSH-conjugating agents and lack of amino acids .
Polyprenol kinase family (Polypren_kinase)
Type: Family

Dolichol kinase catalyses the CTP-mediated phosphorylation of dolichol in eukaryotic cells, the terminal step in dolichyl monophosphate (Dol-P) biosynthesis de novo. Dol-P serves as a glycosyl carrier lipid in the assembly of N-linked glycoproteins, glycosylphosphatidylinositol anchors, and the C- and O-mannosylation of proteins in the endoplasmic reticulum (ER) of yeast and animal cells . Phytol kinase catalyses the CTP-dependent phosphorylation of phytol to phytylmonophosphate (PMP) and has a role in tocopherol biosynthesis in plants . Both of these enzymes belong to the polyprenol kinase family.
YjeF N-terminal domain-containing protein NAXE-like (YJEFN_prot_NAXE-like)
Type: Family

This entry represents a subgroup of the YjeF N-terminal domain-containing proteins from eukaryotes, bacteria and archaea, including NAXE and YJEFN3 from humans . NAXE is an NAD(P)H-hydrate epimerase that has been shown to regulate cholesterol efflux from endothelial cells . YJEFN3 may play a role in spermiogenesis and oogenesis .

In bacteria or archaea, YjeF N-terminal domains are often fused to a YjeF C-terminal domain . It is a bifunctional enzyme that catalyses the epimerisation of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP . However, this entry represents the subgroup that only contain the YjeF N-terminal domain.

The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. Eukaryotic NAD(P)H-hydrate epimerase catalyses the epimerisation of the S- and R-forms of NAD(P)HX, the damaged form of NAD(P)H. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX .
Zinc finger MYND domain-containing protein 19 (ZMYND19)
Type: Family

This zinc finger protein may be involved in MCH-R1 (melanin-concentrating hormone receptor 1) signaling .
Cytosolic endo-beta-N-acetylglucosaminidase (ENGase)
Type: Family

Endo-β-N-acetylglucosaminidase (ENGase) is a glycosyl hydrolase that cleaves the β-1,4-glycosidic bond within the di-N-acetylchitobiose core of N-glycosylated proteins, leaving one N-acetylglucosamine residue attached to the protein and releasing the remainder of the glycan. It plays a key role in the cytosolic degradation of free oligosaccharides derived from the endoplasmic reticulum, aiding in the recycling of sugars. ENGases possess an eight-stranded α/β barrel structure and belong to glycosyl hydrolase family 85 (GH85), sharing sequence similarity with

chitinases .

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.
Roundabout homologue 1, immunoglobulin-like domain 3 (Robo1_Ig-like3)
Type: Domain

The secreted Slit repellents and their Roundabout (Robo) receptors were originally identified as important axon guidance molecules. The SLIT-ROBO interaction has been found to be involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast . There are four Robo homologues in vertebrates (Robo1-4).

Robo1 is known to play a crucial role in axon guidance . They overlap to cooperate in guiding longitudinal axons, but each isoform has specialised functions in spinal commissural axon guidance . Robo1 prevents axonal stalling after crossing . Robo1 may also be involved in lung and heart development .

Deregulation of Robo is implicated in several neuropathological conditions and cancers .

This entry represents the third immunoglobulin-like domain of Robo1.
Contactin-4, Ig6 (CNTN4_Ig6)
Type: Domain

Contactins are cell adhesion molecules that belong to the immunoglobulin superfamily and are involved in neural development . They usually consist of six N-terminal Ig domains, four fibronectin type III domains, and a C-terminal glycophosphatidylinositol (GPI)-anchor to the extracellular part of the cell membrane .

Contactin-4 (CNTN4/BIG-2) mediates cell surface interactions during nervous system development . It functions as an axon guidance molecule in olfactory sensory neurons and in the accessory optic system . This protein plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. It is associated with developmental delay in 3p syndrome and cerebellar degeneration in spinocerebellar ataxia type 16 .

This entry represents the sixth immunoglobulin (Ig) domain of contactin-4.
WD repeat Cdc20/Fizzy (Cdc20/Fizzy)
Type: Family

The anaphase promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that targets mitotic regulators for degradation in exit from mitosis. At the end of mitosis, APC/C is activated by phosphorylation and association with the WD-40 protein Cdc20/Fizzy . The inhibitory phosphorylation of Cdc20/Fizzy may have a role as a safeguard to keep the cyclosome inactive in early mitosis and under conditions of mitotic checkpoint arrest . This entry includes Cdc20/Fizzy homologues from fungi, plants and animals.

Three characterised budding yeasts homologues are included in this entry: Cdc20, Cdh1 and Ama1. Cdc20 and Cdh1 have been shown to activate APC/C during mitosis, while Ama1 is a meiosis-specific activator of the APC/C . The APC/C-Cdh1 is also found involved in the cellular response to DNA damage .
Palladin, C-terminal immunoglobulin-like domain (Palladin_C)
Type: Domain

Palladin is a cytoskeletal actin scaffold protein that regulates actin dynamics. The immunoglobulin-like domain of palladin is directly responsible for both actin binding and bundling . Palladin also interacts with different actin binding proteins and signalling intermediaries required for regulation of cytoskeleton organisation, including profilin , VASP , Eps8 , ezrin , Lasp-1 , and Src . Palladin plays an important role in smooth and skeletal muscle differentiation , contraction and cell migration .

Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions . This entry represents the C-terminal immunoglobulin-like domain (Ig5).
Glutaredoxin domain-containing cysteine-rich protein 2 (GRXCR2)
Type: Family

Glutaredoxin domain-containing cysteine-rich protein 2 (GRXCR2) may be involved in the development of stereocilia bundles, specialised structures on the apical surface of sensory cells in the cochlea that are critical for sound detection .
Whirlin, harmonin_N-like domain 2 (Whirlin_HN-like_dom2)
Type: Domain

Whirlin (also known as DFNB31) is a PDZ-scaffold protein that plays an indispensable role in the cochlea and retina. It is involved in vestibular and auditory hair cell transduction, and is also expressed by proprioceptive sensory neurons (pSNs) in dorsal root ganglia in mice . It has been shown to act as a cytoskeletal linker to ensure proper paranodal compaction and stabilization of the axonal cytoskeleton in myelinated axons .

Mutations in the whirlin gene cause retinal degeneration and hearing loss in Usher syndrome type II (USH2) and non-syndromic deafness, DFNB31 .

This entry represents the second harmonin_N-like domain of the long isoform of Whirlin, also present in the short isoform. It is thought to have a protein-binding role.
Scc2/Nipped-B family (Scc2/Nipped-B)
Type: Family

This entry represents the Nipped-B protein and its homologues, including Mis4 from fission yeast, Scc2 from budding yeast and Nipbl from zebrafish and Nipped-B from Drosophila.

Budding yeast Scc2 is known to be part of the loader for the cohesion to be loaded onto the chromosome . It has also been shown to regulate gene expression independent of cohesin .

Drosophila melanogaster Nipped-B protein is a chromatin binding protein that is involved in sister chromatid cohesion. Nipped-B and its Mau-2 partner are required for cohesin to associate with chromosomes . The Drosophila Nipped-B has also been shown to regulate gene expression .

The zebrafish Nipbl has also been shown to regulate transcription. Nipbl has the ability to interact with other molecules such as histone deacetylases, HP-1gamma, and chromatin remodelling factors. It has been suggested that Nipbl is a cohesin-asociated scaffold protein that have functions other than loading cohesin .
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 (NDUFB9)
Type: Family

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 (NDUFB9, also known as LYRM3) is part of the mitochondrial respiratory chain complex I, which is an NAD-ubiquinone oxidoreductase .
Doublecortin domain-containing protein 2, doublecortin-like domain 2 (DCDC2_DCX_dom2)
Type: Domain

Doublecortin domain-containing protein 2 (DCDC2) interacts with the mediator of Wnt signalling dishevelled. The overexpression of DCDC2 inhibits beta-catenin-dependent Wnt signalling . It also plays an important role in hair cell kinocilia and supporting cell primary cilia length regulation, likely via its role in microtubule formation and stabilisation . It also affects length and signalling of primary cilia in neurons and has been associated with learning disabilities . Genetic variation in humans is associated with neonatal sclerosing cholangitis, a rare biliary disease leading to liver transplantation in childhood .

This entry represents the doublecortin-like domain 2 of DCDC2.
FAS-associated factor 1-like, UBX domain (FAF1-like_UBX)
Type: Domain

FAS-associated factor 1 (FAF1) is a multidomain protein involved in various biological processes, including regulation of apoptosis and NFkappaB activity, and ubiquitination and proteasomal degradation . It has been linked to cancer, asbestos-induced mesotheliomas, and Parkinson's disease . FAF1 contains multiple ubiquitin-related domains, including ubiquitin-associated (UBA), ubiquitin-like 1 and 2 (UBL1, UBL2), and ubiquitin regulatory X (UBX) domains. FAF1 interacts with polyubiquitinated proteins via its N-terminal UBA domain and with valosin containing protein (VCP) via its C-terminal UBX domain .

This entry represents the UBX domain as found in FAF1 and homologues. The UBX domain has a β-grasp fold similar to that of ubiquitin; however, UBX lacks the C-terminal double glycine motif and is thus unlikely to be conjugated to other proteins.