SII-SWORD/CoKE huggingface dataset:
rRNA biogenesis protein RRP5, S1 domain, first repeat (Rrp5_S1_rpt_hs1_sc1)
Type: Domain

This entry represents the first S1 from both Homo sapiens Rrp5 (hs1) and S. cerevisiae (sc1).

Rrp5 has two distinct regions, an N-terminal region containing tandemly repeated S1 RNA-binding domains (12 S1 repeats in Saccharomyces cerevisiae Rrp5 and 14 S1 repeats in Homo sapiens Rrp5) and a C-terminal region containing tetratricopeptide repeat (TPR) motifs thought to be involved in protein-protein interactions. Mutational studies have shown that each region represents a specific functional domain. Deletions within the S1-containing region inhibit pre-rRNA processing at either site A3 or A2, whereas deletions within the TPR region confer an inability to support cleavage of A0-A2.

Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts . In humans, it is also known as NFBP, which is essential for the generation of 18S rRNA . In Arabidopsis, it is essential for normal development of female gametophytes .
Zinc finger and BTB domain-containing protein 11, BTB/POZ domain (ZBTB11_BTB_POZ)
Type: Domain

This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in zinc finger and BTB domain-containing protein 11 (ZBTB11), a transcriptional repressor of TP53 . ZBTB11 is critical for basal and emergency granulopoiesis and regulates neutrophil development through its integrase-like zinc finger domain . Its variants have been associated to neuropsychiatric phenotypes in humans .
GmtX-like (GmtX-like)
Type: Family

This family is named GmtX, for Gammaproteobacterial Mobile Trio system protein of unknown (X) function. The proteins included in this family are found regularly in the context of a XerC/XerD-related recombinase and a putative integrase

. Members of this family include VPA1268 (

) found in a pathogenicity island of Vibrio parahaemolyticus .
SE1832-like (SE1832-like)
Type: Family

This entry represents a family of small uncharacterised proteins found mainly in order Bacillales . Their function is unknown.
Ankyrin repeat and BTB/POZ domain-containing protein 2, BTB/POZ domain (ABTB2_BTB_POZ)
Type: Domain

This entry represents the BTB/POZ domain present in Ankyrin repeat and BTB/POZ domain-containing protein 2 (ABTB2), also called bood POZ containing gene type 2 (BPOZ-2), a scaffold protein that controls the degradation of many biological proteins with various functions ranging from embryonic development to tumour progression. It may be involved in the initiation of hepatocyte growth. It inhibits the aggregation of alpha-synuclein, with implications for Parkinson's disease [

,

. ABTB2 functions as an adaptor protein for the E3 ubiquitin ligase scaffold protein Cullin-3. It directly binds to eukaryotic elongation factor 1A1 (eEF1A1) to promote eEF1A1 ubiquitylation and degradation, and prevent translation. It is also involved in the growth suppressive effect of the phosphatase and tensin homolog (PTEN). It also contains an ankyrin repeat, BTB/POZ, and BACK domains. The BTB/POZ domain is a common protein-protein interaction motif of about 100 amino acids .
Upstream transcription factor 3, basic helix-loop-helix domain (USF3_bHLH)
Type: Domain

This entry represents the basic helix-loop-helix (bHLH) domain found in USF3, also known as Basic helix-loop-helix domain-containing protein USF3, which is involved in the negative regulation of epithelial-mesenchymal transition, the process by which epithelial cells lose their polarity and adhesion properties to become mesenchymal cells with enhanced migration and invasive properties .
Autophagy-related protein 26, PH-GRAM domain 2 (ATG26_PH_GRAM2)
Type: Domain

This entry represents the second PH-GRAM domain present in Sterol 3-beta-glucosyltransferase from Saccharomyces cerevisiae (also known as Autophagy-related protein 26, ATG26) and similar fungal proteins.

ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, is responsible for the biosynthesis of sterol glucoside . It is necessary for the degradation of medium peroxisomes. ATG26 contains 2 GRAM domains. They share little sequence conservation, but all have a common fold. GRAM domains are similar to Pleckstrin homology (PH) domains. GRAM and PH domains are often involved in targeting proteins to the plasma membrane, some of them display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain. GRAM and PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
Autophagy-related protein 26, PH-GRAM domain 1 (ATG26_PH_GRAM1)
Type: Domain

This entry represents the first PH-GRAM domain present in Sterol 3-beta-glucosyltransferase from Saccharomyces cerevisiae (also known as Autophagy-related protein 26, ATG26) and similar fungal proteins.

ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, is responsible for the biosynthesis of sterol glucoside . It is necessary for the degradation of medium peroxisomes. ATG26 contains 2 GRAM domains. They share little sequence conservation, but all have a common fold. GRAM domains are similar to Pleckstrin homology (PH) domains. GRAM and PH domains are often involved in targeting proteins to the plasma membrane, some of them display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain. GRAM and PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
BREX-3 system BrxF (BREX_3_BrxF)
Type: Family

This family includes BrxF from type 3 BREX (bacteriophage exclusion) systems. Most members contain a P-loop Gly-rich motif (GxxGxGKT), but in a considerable fraction of proteins, this region is relatively poorly conserved.

Bacteriophage exclusion (BREX) systems are multiprotein complexes encoded by a variety of bacteria and archaea that restrict phage infection. Discovered in Bacillus cereus, BREX was shown to allow phage adsorption but blocking phage DNA replication. BREX systems are encoded by single operons within genetic defense islands, and are currently categorised into six subtypes based on the number of genes in each system (typically between four and eight) and sequence-based functional annotation of proteins encoded by those genes . All known BREX systems have two genes in common. The first contains an alkaline phosphatase domain and the second contains an ATPase domain .
LarA-like (LarA-like)
Type: Family

This entry represents lactate racemase LarA and similar proteins mainly found in prokaryotes. LarA catalyses the interconversion between the D- and L-isomers of lactate . It may act as a rescue enzyme to ensure D-lactate production in physiological conditions where its production by the D-lactate dehydrogenase LdhD is not sufficient .

LarA is a nickel-dependent lactate racemase from the larA-E operon of Lactobacillus plantarum, whereas LarB, LarC and LarE are accessory proteins required for the incorporation of Ni in the lactate racemase apoprotein .

LarA contains 18 β-strands and 16 α-helices arranged in a novel fold composed of two domains of similar size.
Thylakoid membrane accumulation factor slr1796 (Thylak_slr1796)
Type: Family

Members of this family are found mainly in cyanobacteria and show significant similarity to proteins belonging to Thioredoxin-like superfamily (

). However, the core region of the protein family alignment shows either one Cys residue or none, suggesting that these proteins may share the thioredoxin-like fold but lack redox capability. The founding member of the family, slr1796 (

), proteomics analysis demonstrated that it localises to the thylakoid membrane, consistent with taxonomic restriction to cyanobacteria. Targeted mutagenesis of slr1796 suggested a role at post transcriptional level and in the insertion of photosystem I proteins into the thylakoid membrane .
Calicin, BTB/POZ (Calicin_BTB_POZ)
Type: Domain

Calicin is a basic cytoskeletal protein involved in the formation and maintenance of the highly regular organization of the postacrosomal perinuclear theca, the calyx of mammalian spermatozoa. It contains BTB and BACK domains at the N-terminal region and kelch repeats at the C-terminal region. This entry represents the BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids .
Transcriptional regulator CrgA-like, substrate binding domain (CrgA-like_PBP2)
Type: Domain

This entry represents the substrate binding domain of the LysR-type transcriptional regulator CrgA and similar proteins from proteobacteria.

This entry includes the LysR-type transcriptional regulator (LTTR) CrgA (

,

) from Neisseria meningitidis and similar proteins, such as the uncharacterised HTH-type transcriptional regulator YafC from E.coli. In contrast to the tetrameric form of other LTTRs, CrgA from Neisseria meningitidis assembles into an octameric ring, which can bind up to four 63-bp DNA oligonucleotides . Phylogenetic cluster analysis further showed that the CrgA-like regulators form a subclass of the LTTRs that function as octamers . The CrgA is an auto-repressor of its own gene and activates the expression of the mdaB gene, which coding for an NADPH-quinone reductase, and its action is increased by MBL (alpha-methylene-gamma-butyrolactone), an inducer of NADPH-quinone oxidoreductase.

CrgA consists of an N-terminal HTH-domain (

) and a C-terminal substrate binding domain whose structural topology is most similar to that of the type 2 periplasmic binding proteins (PBP2), which are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains . This interaction triggers the ligand translocation across the cytoplasmic membrane energised by ATP hydrolysis.
Latrophilin-like receptor, 7TM (7tmB2_latrophilin-like)
Type: Domain

This entry represents the 7 transmembrane (7tm) domain of latrophilin-like proteins from invertebrates.

This entry includes latrophilin-like proteins found in invertebrates such as insects and worms, including Lat-1/2 from C. elegans , which are homologues from vertebrate latrophilins. Lat-1 plays a role in the establishment of anterior-posterior polarity in tissues during embryogenesis . It is required for the alignment of the mitotic spindles and division planes. It may also have a role in cell death events. It is required for normal defection and oocyte fertilization, being involved in sperm function.

Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are members of the adhesion family (subclass B2) that belongs to the class B GPCRs . Three subtypes of vertebrate latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif.
Regulator of G-protein signaling 22, third RGS domain (RGS22_RGS_third)
Type: Domain

This entry represents the third RGS domain from RGS22, which contains at least 3 copies of this domain in vertebrates and exists in multiple splicing variants.

Rgs22 is a testis-specific regulator of G-protein signaling involved in human and mouse spermiogenesis. It interacts with guanine nucleotide binding protein GNA12/13 . It has been shown to inhibit pancreatic adenocarcinoma cell migration through the G12/13 alpha subunit/F-actin pathway .
Regulator of G protein signaling domain 22, fourth RGS domain (RGS22_RGS_fourth)
Type: Domain

This entry represents the fourth RGS domain from RGS22, which contains at least 3 copies of this domain in vertebrates and exists in multiple splicing variants.

Rgs22 is a testis-specific regulator of G-protein signaling involved in human and mouse spermiogenesis. It interacts with guanine nucleotide binding protein GNA12/13 . It has been shown to inhibit pancreatic adenocarcinoma cell migration through the G12/13 alpha subunit/F-actin pathway .
Regulator of G protein signaling domain 22, second RGS domain (RGS22_RGS_second)
Type: Domain

This entry represents the second RGS domain from RGS22, which contains at least 3 copies of this domain in vertebrates and exists in multiple splicing variants.

Rgs22 is a testis-specific regulator of G-protein signaling involved in human and mouse spermiogenesis. It interacts with guanine nucleotide binding protein GNA12/13 . It has been shown to inhibit pancreatic adenocarcinoma cell migration through the G12/13 alpha subunit/F-actin pathway .
Chloroplastic group IIB intron splicing facilitator CRS2-like (CRS2-like)
Type: Family

Chloroplast RNA splicing 2 (CRS2) are nuclear-encoded proteins required for the splicing of group II introns in chloroplasts. CRS2 forms stable complexes with two CRS2-associated factors, CAF1 and CAF2, which are required for the splicing of distinct subsets of CRS2-dependent introns. CRS2 is closely related to bacterial peptidyl-tRNA hydrolases (PTH) . This entry also includes chloroplastic and mitochondrial PTHs, closely related to CRS2.
G-protein-coupled receptor 171 (GPR171)
Type: Family

GPR171 is phylogenetically related to the P2Y family of purinergic G protein-coupled receptors. The P2Y receptor family is composed of eight subtypes, which are activated by naturally occurring extracellular nucleotides such as ATP, ADP, UTP, UDP, and UDP-glucose .

It has been reported that the peptide LENSSPQAPARRLLPP (BigLEN) activates GPR171 to regulate body weight in mice . GPR171 is expressed in T-cells and it has been reported that BigLEN interacts with GPR171 to suppress T cell receptor-mediated signalling pathways and to inhibit T cell proliferation .

GPR171 is a member of the class A G protein-coupled receptor superfamily, which all have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. A common feature of GPCR signalling is agonist-induced conformational changes in the receptors, which then activate the heterotrimeric G proteins. G-proteins regulate a variety of cellular functions including metabolic enzymes, ion channels, and transporters, among many others .
Small membrane protein PA2485-like (PA2485-like)
Type: Family

Members of this family are small, uncharacterised, N-terminally hydrophobic proteins, 37 to 39 amino acids in length, regularly found encoded next the small regulatory protein PtrC (

) in species of Pseudomonas. The family is named for Pseudomonas aeruginosa PAO1 protein PA2485 (

), which originally was predicted to be longer.
Transcriptional regulator SutA (SutA)
Type: Family

This entry represents the transcriptional regulator SutA from Pseudomonas aeruginosa and similar proteins found in gammaproteobacteria. SutA causes widespread changes in gene expression, and plays a direct role in the regulation of genes encoding ribosomal components. It associates with chromosomal DNA through interaction with RNA polymerase. This protein contributes to biofilm formation and secondary metabolite production, and it is important during transitions to and from the survival state . SutA shows a central α-helix with unstructured N- and C-terminal tails .
Type III secretion system co-regulatory protein PtrC-like (T3SS_coreg_PtrC-like)
Type: Family

PtrC (Pseudomonas type III repressor gene C), represented by locus PA2486 (

) in Pseudomonas aeruginosa PAO1, is a small protein, typically around 64 amino acids, rich in charged residues. Overexpression represses T3SS expression, although the mechanism is not described and may depend on protein-protein interaction rather than direct interaction with DNA .
ParC-like (ParC-like)
Type: Family

This entry represents ParC and similar proteins found in proteobacteria. ParC is encoded by the parABC cluster, in which parA gene encodes an ATPase, whereas parB and parC encode auxiliary partition proteins .
GrdB-related (GrdB-like)
Type: Family

Members of this family are homologues of the N-terminal domain of GrdB, a selenoprotein subunit in the glycine reductase complex. These proteins, however, are not selenoproteins. These proteins are mainly found in Firmicutes and in a different context, not in vicinity of other glycine reductase subunits.
YniD-like (YniD-like)
Type: Family

This entry represents a group of proteins from gammaproteobacteria, including YniD, an uncharacterised membrane protein from Escherichia coli K-12 . It has been associated with bacterial stress response but its specific function is unknown.
Cytochrome c oxidase subunit CcoM-like (Cyt_ox_CcoM-like)
Type: Family

This entry represents homologs of the cytochrome c oxidase subunit CcoM from the Cbb3 cytochrome c oxidase that was identified in Pseudomonas stutzeri (also known as Stutzerimonas stutzeri) strain ZoBell . Biochemical studies suggest that CcoM may be involved in CcO complex assembly or stabilization. It may also play a role in anaerobic respiration, as the knockout strain displayed altered growth rates under anaerobic denitrifying conditions.
Lipoprotein PA5502-like (PA5502-like_lipo)
Type: Family

This family represents a group of uncharacterised sequences from Pseudomonas, including

, which are predicted lipoproteins.
Four-cysteine protein VF_A0006-like (VF_A0006-like)
Type: Family

Members of this family, including VF_A0006 (

) of Vibrio fischeri, PSPA7_2531 (

) of Pseudomonas aeruginosa, and BPSL3341 (

) from Burkholderia pseudomallei, have an N-terminal signal peptide and four invariant Cys residues suggesting the formation of two disulfide bonds. The function of these proteins is unknown.
Cys-rich small protein PSPA7_2676-like (Cys_rich_PSPA7_2676-like)
Type: Family

Members of this family are small proteins, averaging 47 amino acids in length with four invariant Cys residues (two in a CxxC motif) and typically six overall. The richness in Cys residues, as in the motif CxCCxxC motif found in many members, suggests metal-binding activity.
Maintenance of carboxysome distribution protein A (McdA)
Type: Family

This entry includes Maintenance of carboxysome distribution protein A (McdA), a ParA family member , and related proteins that are found mainly in proteobacteria. McdA is an ATPase that forms dynamic gradients on the nucleoid in response to adapter protein McdB, which associates with carboxysomes. The interplay between McdA gradients on the nucleoid and McdB-bound carboxysomes result in the equal spacing of Cbs along the cell length .

Members of this family contain a variant of the A motif (also known as the 'Walker Box' or P-loop (phosphate binding loop)), that is XXXKGGXXK[TS] where X is any amino acid and amino acids in brackets indicate alternatives.
Cold shock protein-like, N-terminal extension domain (CSP_N_ext_dom)
Type: Domain

This entry represents a hydrophobic N-terminal domain from a group of uncharacterised proteins, primarily found in Pseudomonas species, which have a C-terminal cold shock domain (

).
Glutamine synthetase GlnII (Gln_syn_GlnII)
Type: Family

This family includes glutamine synthetase GlnII (

also known as GlnB in Streptomyces hygroscopicus (

)), which catalyses the ATP-dependent biosynthesis of glutamine from glutamate and ammonia .
Diguanylate cyclase DgcA (Dguan_cyc_DgcA)
Type: Family

This family represents diguanylate cyclase A (DgcA,

) from Spirochetes, such as DgcA from Treponema denticola . It catalyses the conversion of GTP to cyclic-di-GMP (c-di-GMP) under aerobic and anaerobic reaction conditions. Treponema denticola is a pathogen associated to periodontal disease (PD), a progressive inflammatory condition characterised by degradation of the gingival epithelium, periodontal ligament, and alveolar bone ultimately resulting in tooth loss, which contributes to immune dysregulation and direct tissue destruction. All members of this family contain C-terminal GGDEF domain

.
MobT relaxase (MobT)
Type: Family

This entry represents a group of proteins mainly from firmicutes, that belong to the MobT family of relaxases . Members of this family contain the domains

,

and

.
YghX hydrolase-like (YghX_hydrolase-like)
Type: Family

YghX is a predicted hydrolase, homologous to dienelactone hydrolases, but its function is unknown. YghX is encoded intact in Escherichia coli O157:H7 str. Sakai, but is a frameshifted pseudogene in Escherichia coli K-12 MG1655, and consequently is used occasionally as a site for minimally disruptive genetic engineering .
Dimethylamine corrinoid protein MtbC (Dimeth_corrin_MtbC)
Type: Family

This family includes the dimethylamine corrinoid protein MtbC from archaea, which acts as a methyl group carrier between MtbB1 and MtbA. MtbC binds one corrinoid cofactor per protein, which is subsequently demethylated by MtbA (

) .
Methylcobamide:CoM methyltransferase MtbA (Methylcob_mtaseMtbA)
Type: Family

This family represents Methylcobamide:CoM methyltransferase MtbA (

) from archaea, a methyltransferase involved in methanogenesis from methylamines. It catalyses the transfer of the methyl group bound to the cobal cofactor from the methylated corrinoid protein MtmC (MtmC1 or MtmC2) or MtbC to coenzyme M, forming the substrate for coenzyme-B sulfoethylthiotransferase, the enzyme that catalyses the final step in methanogenesis .
Cps14G polysaccharide biosynthesis glycosyltransferase-like domain (Cps14G-like)
Type: Domain

This entry represents a glycosyltransferase-like domain found in a group of proteins that are homologous to Cps14G from Streptococcus pneumoniae. Gps14G is a beta-1,4-galactosyltransferase that is responsible for the second step in oligosaccharide subunit synthesis, the transfer of galactose to lipid-linked glucose .
MobB relaxase (MobB)
Type: Family

This entry represents a group of proteins mainly from flavobacteriales that belong to the MobB family of relaxases .
Esterase EstA/EstP (Esterase_EstP/EstA)
Type: Family

This family represents a group of proteins found in Pseudomonas, including esterases EstA and EstP. EstA is required for rhamnolipid production, all kinds of cell motility (swimming, swarming, and twitching), and biofilm formation, however, the exact role of EstA in these processes is unclear . EstA and EstP have esterase activity towards p-nitrophenyl esters of short acyl chain length (C4-C6) and Tween detergents. They also show relatively high activity towards beta-naphthyl butyrate, whereas its activities towards triacylglycerols and acyls-CoA are negligible . These protein consist of an N-terminal domain with catalytic activity and a C-terminal autotransporter domain .
Exo-alpha-(1->6)-L-arabinopyranosidase (Alph_arabinopyran)
Type: Family

This family includes exo-alpha-(1->6)-L-arabinopyranosidase (APY) from bifidobacteria, which catalyses the hydrolysis of a non-reducing terminal alpha-L-arabinopyranosidic linkage in ginsenoside Rb2 (alpha-L-arabinopyranosyl-(1->6)-alpha-D-glucopyranosyl) to release alpha-D-glucopyranosyl (Rd). It is not able to hydrolyze alpha-L-arabinofuranosyl-(1->6)-alpha-D-glucopyranosyl (Rc) .
MobP2 relaxase (MobP2)
Type: Family

This entry represents a group of proteins mainly from bacilli that belong to the MobP2 family of relaxases .