SII-SWORD/CoKE huggingface dataset:
Type III secretion system chaperone, YscY (T3SS_YscY)
Type: Family

This group represents a type III secretion machinery chaperone protein, YscY type. YscY from Yersinia pestis is required for Yop virulence proteins secretion. It probably functions as a chaperone which stabilises YscX within the cell, before its secretion . AscY is the homologue in Aeromonas salmonicida .
RNA-induced silencing complex, nuclease component Tudor-SN (Silence_cplx_Nase-comp_TudorSN)
Type: Family

This entry represents the Tudor staphylococcal nuclease (Tudor-SN) subunit of the RNA-induced silencing complex (RISC) . RISC is central to the mechanism of RNA interference (RNAi), which is triggered by the presence of dsRNA, resulting in silencing of the cognate gene. In RNAi, dsRNA is processed by RNase III ribonucleases (from Dicer family) to yield small interfering RNAs (siRNAs), which are unwound and incorporated into the RISC ribonucleoprotein complex that ultimately targets the cognate mRNA. Various components of the RISC have been identified that are highly conserved between species. In Drosophila melanogaster (Fruit fly) these subunits include the proteins Argonaute2, VIG, FXR and Tudor-SN. Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage.
Ribosome biogenesis factor, NIP7 (Ribosomal_synth_fac_NIP7)
Type: Family

This entry represents 60S ribosome subunit biogenesis protein Nip7, which is required for proper 27S pre-rRNA processing and 60S ribosome subunit assembly . In yeast, Nip7 interacts with nucleolar proteins such as Nol8 , and with the exosome subunit Rrp43p. Nip7 contains a PUA domain.
Mechanosensitive ion channel MscS-like, plants/fungi (MscS-like_plants/fungi)
Type: Family

This entry represents a group of MscS-like (mechanosensitive channels of small conductance-like) proteins found in fungi and plants. Ten MscS-Like (MSL) proteins have been found in the genome of Arabidopsis thaliana . In the fission yeast
Schizosaccharomyces pombe
the mechanosensitive ion channel proteins are known as Msy1 and Msy2 .

Mechanosensitive (MS) channels provide protection against hypo-osmotic shock, responding both to stretching of the cell membrane and to membrane depolarisation. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya . There are two families of MS channels: large-conductance MS channels (MscL) and small-conductance MS channels (MscS or YGGB). The pressure threshold for MscS opening is 50% that of MscL . The MscS family is much larger and more variable in size and sequence than the MscL family. Much of the diversity in MscS proteins occurs in the size of the transmembrane regions, which ranges from three to eleven transmembrane helices, although the three C-terminal helices are conserved.

In the fission yeast
Schizosaccharomyces pombe
the mechanosensitive ion channel proteins are known as Msy1 and Msy2 .
ESCRT-2 complex, Snf8 (ESCRT-2_cplx_Snf8)
Type: Family

Snf8 (also known as Vps22p/Eap30) is a subunit of ESCRT-II, a protein complex involved in driving protein sorting from endosomes to lysosomes.

The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. ESCRT (endosomal sorting complex required for transport)-I, -II and -III complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles .
tRNA-splicing endonuclease, SEN34 subunit (tRNA_splic_SEN34)
Type: Family

SEN34 constitutes one of the two catalytic subunits of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA .
tRNA (guanine(10)-N(2))-methyltransferase, TRM11 (tRNA_mtfrase_TRM11)
Type: Family

This entry represents tRNA (guanine(10)-N(2))-methyltransferase, TRM11 type. This protein is a catalytic subunit of an S-adenosyl-L-methionine-dependent tRNA methyltransferase complex that mediates the methylation of the guanosine nucleotide at position 10 (m2G10) in tRNAs .

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.
Sulfiredoxin (Sulfiredoxin)
Type: Family

Sulfiredoxins

belong to the oxidoreductase family, which are involved in cellular responses to oxidative stress . They catalyse the reaction
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH = peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R

It is a member of a conserved family of eukaryotic antioxidants and contains a conserved C-terminal cysteine which is essential for its antioxidant function.

Sulfiredoxin (Srx) plays a role in signalling through the catalytic reduction of oxidative modifications. It is responsible for the regulation of peroxiredoxin (Prx) by catalysing reduction of the conserved cysteine from sulfinic to sulfenic acid. This reduction prevents further reduction to sulfonic acid, which ultimately results in degradation.

Srx also has a role in glutathionylation.
Protein of unknown function UCP017292, zinc finger, CHY-type (UCP017292)
Type: Family

Proteins in this family contain a CHY-type zinc finger (

). However, unlike other CHY domain-containing proteins, these do not also contain a RING-type zinc finger (

).

Most of the proteins in this entry are from bacteria, however, some eukaryotic proteins in this entry have been characterised, such as Hot13 (helper of Tim protein) from budding yeasts. Hot13 is required for the assembly or recycling of the small Tim proteins in the mitochondrial intermembrane, thereby participating in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane .
Purine 5'-nucleotidase (Pur_nucleotidase)
Type: Family

This entry includes cytosolic purine 5'-nucleotidases and 5'-nucleotidase domain-containing proteins.

Cytosolic purine 5'-nucleotidases, also known as cytosolic 5'-nucleotidase II (cN-II), is an IMP/GMP preferring 5'-nucleotidase that can function as a phosphatase and a phosphotransferase, and these activities might contribute to the maintenance of the qualitative and quantitative balance of intracellular purine compounds .
TRAPP I complex, subunit 5 (TRAPP-I_su5)
Type: Family

TRS31 (also known as TRAPPC5) is a subunit of the trafficking protein particle complex (TRAPP). It is one of the six core subunits of TRAPP complexes which play a key role in the regulation of ER-to-Golgi and intra-Golgi transport by tethering the vesicle membrane to the target membrane .
Aquaporin 11/12 (Aquaporin_11/12)
Type: Family

Aquaporins 11 and 12 are classified as members of a new AQP subfamily: the subcellular AQPs . AQP 11 and 12 appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily . In members of the subcellular AQPs, one of the two asparagine-proline-alanine (NPA) motifs are not completely conserved. They play a crucial role in selective water conduction and function as water channels . This group represents an aquaporin types 11 and 12.

The aquaporins (AQPs) are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes . AQP1 in pleural mesothelial cells participate in the formation of pleural fluid , renal AQP2 is involved in levels of solutes and changes in AQP9 in the hippocampus are related to delayed neuronal death . Aquaporins contain two tandem repeats, each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
Numb/numb-like (Numb/numb-like)
Type: Family

This group represents Protein numb and similar proteins from animals. This protein plays key roles in cell fate determination . Members of this protein family contain a PID domain, a type of PTB domain .

NUMB from Drosophila is required in determination of cell fate during sensory organ formation in embryos . It recruits alpha-Adaptin, and this physical interaction plays a role in downregulating Notch, presumably by stimulating endocytosis of Notch .

Numb-related protein 1 (NUMB1) from Caenorhabditis elegans is involved in the tethering and targeting of pkc-3 to modulate the intracellular distribution of the kinase .
Acid ceramidase-like (Acid_ceramidase-like)
Type: Family

This group represents acid ceramidases and some related proteins of currently unknown function. Ceramide is hydrolyzed by both acid and alkaline ceramidase . Acid ceramidase requires saposin D, a sphingolipid activator protein, for the lysosomal breakdown of ceramide to a fatty acid and sphingosine . Ceramide is found in plasma membranes and plays a pivotal role in the metabolism of sphingolipids. In addition, ceramide and sphingosine may have important roles as second messengers for cell function and survival .
3-hydroxyanthranilate 3, 4-dioxygenase, metazoan (3hydroanth_dOase_met)
Type: Family

This group represents a 3-hydroxyanthranilate 3,4-dioxygenase found in metazoan species, especially animals. 3-Hydroxyanthranilic acid 3,4-dioxygenase (3HAO) is a non-heme ferrous extradiol dioxygenase in the kynurenine pathway from tryptophan. It catalyzes the conversion of 3-hydroxyanthranilate (HAA) to quinolinic acid (QUIN), an endogenous neurotoxin, via the activation of N-methyl-D-aspartate (NMDA) receptors and the precursor of NAD+ biosynthesis . Kynurenine pathway metabolism has been implicated in neurological disease .
ATP synthase, F0 complex, gamma subunit, metazoa (ATP5MG_metazoa)
Type: Family

This entry represents the mitochondrial ATP synthase subunit g (ATP5MG) from animals.

Mitochondrial membrane ATP synthase (F1F0 ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and F0 - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. ATP5MG is part of the complex F0 domain .

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.
Conjugal transfer, TraD, beta/gamma-type (Conjugal_tfr_TraD_b/g-type)
Type: Family

This group represents a group of conjugal transfer TraD proteins found almost exclusively in the beta and gamma proteobacteria.
Conjugal transfer, TrbD (Conjugal_tfr_TrbD)
Type: Family

This group represents the plasmid conjugal transfer protein TrbD.
Photosynthesis system II assembly factor Ycf48/Hcf136 (Ycf48/Hcf136)
Type: Family

This entry represents a family of proteins predominantly found in the thylakoid membrane of plant chloroplasts and cyanobacteria, including Photosystem II assembly lipoprotein Ycf48 from Synechocystis sp. and Photosystem II stability/assembly factor HCF136, chloroplastic from Arabidopsis thaliana .

The photosynthesis system II (PSII) is a multi-subunit pigment-protein complex responsible for water oxidation during oxygenic photosynthesis . Its assembly is regulated by PSII assembly factors including Ycf48/Hcf136, Psb27 and Psb28. Ycf48/Hcf136 contains the BNR repeats and can be found predominantly in the thylakoid membrane. Ycf48/Hcf136 is required for assembly and repair of an early intermediate in PSII assembly that includes D2 (psbD) and cytochrome b559 . This entry also includes some Ycf48-like proteins that may not affect PSII activity.
Cleavage/polyadenylation specificity factor subunit 5 (Cleav_polyA_spec_factor_su5)
Type: Family

This entry represents cleavage and polyadenylation specificity factor subunit 5, also known as the cleavage and polyadenylation specificity factor 25kDa subunit. These proteins are a component of the cleavage factor Im (CFIm) complex involved in pre-mRNA 3' end processing . CFIm may also play a role in regulation of poly(A) site selection .
Conjugal transfer, TraB, rhizobiales (Conjugal_tfr_TraB_rhizob)
Type: Family

This family consists of several TraB proteins, which seem to be found exclusively in Agrobacterium species. TraB is known to be involved in conjugal transfer .
Aspartoacylase (Aspartoacylase)
Type: Family

Aspartoacylase (ASPA) is the N-acetylaspartate- (NAA)-hydrolysing enzyme. It catalyses the deacetylation of N-acetyl-L-aspartate to produce L-aspartate and acetate. N-phosphonomethyl-L-aspartate is a potent inhibitor of this enzyme . There is a high concentration of (NAA) in neurons of the central nervous system, which is used as an indicator of neuronal viability. The myelin-associated pathology; Canavan disease (also known as spongy degeneration of the brain), is an inherited childhood disorder that results from a mutation of ASPA. The dysmyelination that results from the inactivation of ASPA is characterised by selective decreases as well as some increases in specific lipids .
Dehydratase subunit HadA-like (HadA-like)
Type: Family

This protein family includes HadA from Mycobacterium tuberculosis (Rv0636,

), HadA from Mycolicibacterium smegmatis (MSMEG_1340,

) and other bacterial proteins from the UPF0336 family. HadA is a component of the beta-hydroxyacyl-ACP dehydratase HadAB complex. It adopts a hotdog fold with a central β-sheet, which is twisted to form a concave cavity at the centre where a long α-helix is embedded, and some additional α-helices .
Emp46/Emp47 (Emp46/Emp47)
Type: Family

This entry includes Emp46 and its paralogue, Emp47, from budding yeasts. They are integral membrane components of ER-derived COPII-coated vesicles. They are involved in the secretion of glycoproteins and functions in ER to Golgi transport .
Sds23 (Ssd23)
Type: Family

This entry represents the fungal Sds23 protein, also known as Moc1 or Psp1. The exact function of this protein is not known but it is thought to be required for proper DNA replication and mitosis . It has also been shown to induce sexual development and is involved in the response to nutrient deprivation stress . Phosphorylation seems to be important in regulating the activity of Sds23 - in actively growing cells the protein is predominatly dephosphorylated while in stationary phase the predominant form is phosphorylated. The Cdc2-Cdc13 complex has been shown to phosphorylate the protein in vitro .

S. cerevisiae has homologues (Sds23 and Sds24) of the S. pombe Sds23 protein .
Small ribosomal subunit protein bS1m-like (Rbsml_bS1m-like)
Type: Family

This entry represents the small ribosomal subunit protein bS1m from yeast and similar fungal sequences. bS1m, previously known as MRP51, is a component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain. The mitoribosomes are attached to the mitochondrial inner membrane and translation products are cotranslationally integrated into the membrane. bS1m functionally interacts with the 5'-UTR of mitochondrial mRNAs . This family also includes Small ribosomal subunit protein L51-b from Schizosaccharomyces pombe (also known as Mug178), which has a role in meiosis .
Poly(A) polymerase complex subunit Air1/2, budding yeast (Air1/2_Saccharomycetales)
Type: Family

This group represents a poly(A) polymerase complex Air1/2 subunits from budding yeasts . They are components of the TRAMP complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism limiting inappropriate expression of genetic information .
Mannan endo-1,4-beta-mannosidase B/E (MANB/E)
Type: Family

This group represents mannan endo-1,4-beta-mannosidase MANB from Bacillus subtilis and MANE from Emericella nidulans. It catalyses the endo hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans, galactomannans and glucomannans .
Platelet-activating factor acetylhydrolase-like, eukaryote (PAF_acetylhydro_eukaryote)
Type: Family

Platelet-activating factor acetylhydrolase (PAF-AH) is a subfamily of phospholipase A2, and is involved in regulation of inflammation through the inactivation of platelet-activating factor and polar phospholipids .

This entry represents the platelet-activating factor acetylhydrolases from eukaryotes. It also includes the orthologue from S. pombe, the putative phospholipase A2 Pgl7.
Regulator of ribonuclease activity B (RraB)
Type: Family

Regulator of ribonuclease activity B (RraB) globally modulates RNA abundance by binding to RNase E (Rne) and regulating its endonucleolytic activity. It can modulate Rne action in a substrate-dependent manner by altering the composition of the degradosome .
Gip2/Pig2 (Gip2/Pig2)
Type: Family

This entry includes budding yeast Gip2 (GLC7-interacting protein 2) and its paralogue, Pig2 (Protein Interacting with Gsy2). Pig2 is is a putative type-1 protein phosphatase (PP1) targeting subunit that tethers the Glc7p type-1 protein phosphatase to the Gsy2p glycogen synthase .
rRNA (guanine-N1-)-methyltransferase A, predicted (rRNA_m1G-MeTrfase_A_prd)
Type: Family

This entry represents proteins predicted to function as rRNA (guanine-N1-)-methyltransferases (

). These enzymes specifically methylate the guanosine residue m1G in 23S rRNA. The rrmA gene was predicted to encode 23S rRNA m1G745 methyltransferase in Saccharomyces cerevisiae (Baker's yeast), and maps to the same locus as gene yebH .
Guided entry of tail-anchored proteins factor CAMLG (CAMLG)
Type: Family

This entry represents the Guided entry of tail-anchored proteins factor CAMLG (also known as Calcium signal-modulating cyclophilin ligand CAML) which is required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum . Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol . It is required for the stability of GET1 . CAMLG also stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium , and it is essential for the survival of peripheral follicular B cells.
Phosphatidate cytidylyltransferase, eukaryota (PC_Trfase_euk)
Type: Family

Cytidinediphosphate diacylglycerol synthase (CDS) is a membrane-bound enzyme that catalyzes the transfer of a cytidyl group from cytidine triphosphate (CTP) to phosphatidic acid (PA), producing cytidine diphosphate diacylglycerol (CDP-DAG), the important branch point intermediate in the glycerolipid biosynthesis of prokaryotic and eukaryotic organisms. In eukaryotes, CDS is found in the inner mitochondrial membrane and the endoplasmic reticulum, while plants possess CDS activity in the inner envelope membrane of plastids as well . This entry represents CDS from eukaryotes.
Bet3 family (Bet3)
Type: Family

This entry includes Bet3 (also known as TRAPPC3) and Bet3-like (TRAPPC3L) proteins from eukaryotes. They seem to be involved in vesicle-mediated transport

.

Yeast Bet3 is a core component of transport protein particle (TRAPP) complexes I-III. The TRAPPI complex recognises the coat (COPII) on ER-derived vesicles, whereas the TRAPPII complex recognises the coat (COPI) on Golgi-derived vesicles . TRAPPIII is responsible for vesicular transport from early endosomes to Golgi, facilitating Atg9 cycling in autophagy .

Mammalian TRAPPs complexity is increased by the presence of multiple TRAPP homologues and novel subunits or binding proteins that are not part of the yeast
TRAPP complexes . Bet3 and its homologue Bet3-like are both components of the mammalian TRAPP complex .
DNA polymerase alpha, subunit B (DNA_pol_alpha_bsu)
Type: Family

This group represents a DNA polymerase alpha, subunit B, which is essential for DNA replication in higher eukaryotes as it initiates synthesis on both leading and lagging strand single-stranded DNA templates. It consists of a primase heterodimer that synthesises RNA primers, a DNA polymerase that extends them, and a fourth subunit, p68 (also termed B-subunit), which is believed to regulate the whole complex. This domain docks on the SV40 helicase and activates the viral primosome .
Transcription regulator, ArsR, predicted (Tscrpt_reg_ArsR_prd)
Type: Family

This group represents a predicted transcriptional regulator, ArsR type.
Insulin-related peptide, invertebrates (IRP_inv)
Type: Family

This entry represents a family of insulin-related peptides from insects and molluscs. This venomous insulin facilitates prey capture by rapidly inducing hypoglycemic shock. Intraperitoneal injection of this peptide into zebrafish lowers blood glucose with the same potency as human insulin. In vivo, when applied to water, this peptide reduces overall locomotor activity of zebrafish larvae, observed as a significant decrease in the percentage of time spent swimming and movement frequency. For example, Con-Ins G2 from Conus geographus. Con-Ins G2 is a specialized insulin used for fish-hunting by its venomous cone snail .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)
Ogawa serotype, WbeT (Ogawa_serotype_WbeT)
Type: Family

This group represents an Ogawa serotype protein WbeT.
Repressor protein C1 (Repressor_C1)
Type: Family

Repressor protein C1 is a sequence-specific DNA-binding protein required for the establishment and maintenance of lysogeny. The binding of C1 to operator DNA is sensitive to N-ethylmaleimide .