SII-SWORD/CoKE huggingface dataset:
Ribosomal RNA small subunit methyltransferase B-like, N-terminal domain (RsmB-like_N)
Type: Domain

This entry represents the N-terminal RNA binding domain of the rRNA-specific 5-methylcytidine transferase Sun, also known as RrmB or Fmu, shares the RNA-binding non-catalytic domain with the transcription termination factor NusB. The precise biological role of this domain in Sun is unknown, although it is likely to be involved in sequence-specific RNA binding. The C-terminal methyltransferase domain (represented in

) of Sun has been shown to catalyze formation of m5C at position 967 of 16S rRNA in Escherichia coli .
IS3 transposase (Transpos_IS3)
Type: Family

This entry represents a group of proteins mainly found in bacteria belonging to the IS3 family of transposases. Mmbers of this protein family contain the domain (

).
UlaG-like, metallo-hydrolase domain (UlaG-like_MBL-fold)
Type: Domain

UlaG is essential for L-ascorbate utilization under anaerobic conditions; it is a manganese-dependent l-ascorbate-6-P lactonase that catalyses the hydrolysis of L-ascorbate-6-phosphate to 3-keto-L-gulonate-6-phosphate. This entry represents the metallo-hydrolase domain which belongs to the MBL-fold metallo-hydrolase superfamily .
Chorismate lyase, cyanobacteria (Ch_lyase_cyan)
Type: Family

This entry includes a variant form of chorismate lyase that is widespread in the cyanobacteria, with founding member sll1797 (

) from Synechocystis sp. PCC6803. This protein plays an important role in the initiation of plastoquinone (PQ) biosynthesis in cyanobacteria . It catalyses the conversion of chorismate to 4-hydroxybenzoate by removing the enolpyruvyl group, initial and essential step in PQ biosynthesis in Synechocystis sp..
Endoplasmic reticulum metallopeptidase 1-like, M28 peptidase domain (Fxna-like_M28_dom)
Type: Domain

Endoplasmic reticulum metallopeptidase 1 (ERMP1, also known as Felix-ina, FXNA or Fxna peptidase) is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, Fxna may play a crucial role in processing proteins required for the organisation of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolysed has not yet been determined . This entry also includes vacuolar membrane proteases from fungi, such as PFF1 from yeast which are homologues of human ERMP1 . PFF1 may be involved in vacuolar sorting and osmoregulation .
RING finger protein 24, RING finger, H2 subclass (RNF24_RING-H2)
Type: Domain

This entry represents a RING finger domain present in the RNF24, an intrinsic membrane protein localised in the Golgi apparatus. RNF24 specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger .
G2/mitotic-specific cyclin-B1, first cyclin box (CCNB1_first_cyclin-box)
Type: Domain

CCNB1 (G2/mitotic-specific cyclin-B1) is essential for the control of the cell cycle at the G2/M (mitosis) transition, required for embryo development . Over-expression of human CCNB1 has been found in numerous cancers and has been associated with tumor aggressiveness . CCNB1 contains two cyclin boxes, the first one is represented in this entry. The cyclin box is a protein binding domain.
Cyclopropane fatty acid synthase CfaB-like (CfaB-like)
Type: Family

This entry represents homologues of CfaB from Pseudomonas putida KT2440 (

), a C17:cyclopropane fatty acid synthase . The members of this family are found exclusively in gammaproteobacteria.
Photosystem II assembly protein Psb34-like (Psb34-like)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Psb34 from Synechocystis sp. PCC 6803 (

). Members of this family are small, usually about 56 amino acids, with an N-terminal half related to HliA/B proteins belonging to a family of high-light-inducible proteins (Hlips), and a highly hydrophobic C-terminal half embedded in the thylakoid membrane . It has been proposed that the Psb34 protein regulates the binding of high-light-inducible proteins to assembly intermediates of photosystem II that contain CP47 .
PdtaR, receiver domain (PdtaR_REC)
Type: Domain

This entry includes Mycobacterium tuberculosis PdtaR, also called Rv1626, and similar proteins containing a REC domain, represented in this entry, and an ANTAR (

) (AmiR and NasR transcription antitermination regulators) RNA-binding output domain. PdtaR is a response regulator that acts at the level of transcriptional antitermination and is a member of the PdtaR/PdtaS two-component regulatory system . REC domains function as phosphorylation-mediated switches within response regulators, but some also transfer phosphoryl groups in multistep phosphorelay.
ScyD/ScyE-like (ScyD/ScyE-like)
Type: Family

This bacterial family includes ScyE, a protein involved in scytomenin biosynthesis and export , and its paralogue ScyD. Some members of the family contain a C-terminal PEP-CTERM domain that predicts anchoring to the outer membrane.
ESAT6-like (ESAT6-like)
Type: Family

This entry represents a family of uncharacterised proteins that are found in Actinomycetes and related to ESAT-6 proteins.
HetZ-related protein 2 (HetZ-rel_2)
Type: Family

Members of this family are cyanobacterial proteins distantly related to heterocyst differentiation protein HetZ. Their function is unknown.
CopL-like (CopL-like)
Type: Family

This entry includes CopL and its homologues, a protein that is required for copper-inducible expression of multicopper oxidase CopA in X. axonopodis . The regulatory function of this protein is likely to involve a copper binding, whereas a DNA-binding transcriptional regulator activity was not demonstrated. Members of this family contain a number of conserved cysteine and histidine residues, that may be part of potential metal-binding sites.
Dual specificity protein phosphatase 8, dual specificity phosphatase domain (DUSP8_DSP)
Type: Domain

This entry represents the dual specificity phosphatase domain of Dual specificity protein phosphatase 8 (DUSP8), also called DUSP hVH-5 or M3/6, which functions as a protein-serine/threonine phosphatase (

) and a protein-tyrosine-phosphatase (

). Like other mitogen-activated protein kinase (MAPK) phosphatases (MKPs), it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP8 controls basal and acute stress-induced ERK1/2 signalling in adult cardiac myocytes, which impacts contractility, ventricular remodelling, and disease susceptibility. It also plays a role in decreasing ureteric branching morphogenesis by inhibiting p38MAPK. DUSP8 contains an N-terminal Cdc25/rhodanese-like domain (

), which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain .
Tlg1p-like, N-terminal domain (Tlg1p-like_N)
Type: Domain

Tlg1p (t-SNARE affecting a late Golgi compartment protein 1) from yeast, also called syntaxin TLG1, is a soluble NSF attachment protein receptor (SNARE) protein (of Qc type) involved in membrane fusion, probably in retrograde traffic of cytosolic double-membrane vesicles derived from both, early and possibly late endosomes/PVC (prevacuolar compartment) back to the trans-Golgi network (TGN or late Golgi) . It has been reported to function both as a (target membrane) t-SNARE and as a (vesicle) v-SNARE . This entry represents the N-terminal domain of Tlg1p, which consists of a three α-helical bundle (

) .
Dimethylamine monooxygenase subunit DmmA-like, C-terminal domain (DmmA-like_C)
Type: Domain

This entry represents the C-terminal domain of the dimethylamine monooxygenase subunit DmmA from Methylocella silvestris (Msil_3607,

), Heme-dependent oxidative N-demethylase delta subunit from Ectopseudomonas mendocina , and similar sequences mainly found in proteobacteria and actinomycetes. Dimethylamine (DMA) monooxygenase is required for metabolism of trimethylamine N-oxide (TMAO) .
HBPHA/CBPHA (HBPHA/CBPHA)
Type: Family

This entry includes trans-o-hydroxybenzylidenepyruvate hydratase-aldolase (HBPHA) and trans-2'-carboxybenzalpyruvate hydratase-aldolase (CBPHA). HBPHA catalyses HBP to salicyaldehyde and pyruvate. This reaction is part of the degradative pathways for naphthalene and naphthalenesulfonates by bacteria. CBPHA is homologous to HBPHA and catalyses the cleavage of CBP to 2-carboxylbenzaldehyde and pyruvate during the degradation of phenanthrene. They are member of the DHDPS family of Schiff-base-dependent class I aldolases .
TraQ-like (TraQ-like)
Type: Family

This family includes uncharacterised proteins found in gammaproteobacteria and homologues of TraQ.
Rab GTPase 19/43 (Rab19/43)
Type: Family

Rab GTPases are the main regulators of vesicle-mediated membrane trafficking. This family includes Rab19 and the closely related Rab43 (also known as Rab41) protein .

Rab19 proteins are associated with Golgi stacks. It is negatively correlated with the tumor purity of oral squamous cell carcinoma and positively correlated with the immune infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. It has been reported that down-regulation of Rab19 antagonized the aggressive behaviors of gastric cancer .

Rab43 plays a neuron-specific role in targeting and sorting of GPCRs. It differentially regulates the overall surface expression of endogenous alpha2-adrenergic receptor and muscarinic acetylcholine receptor and their signaling, in primary neurons. Moreover, Rab43 exerts distinct effects on the dendritic and postsynaptic transport of specific receptors subtypes .
VpsF-like (VpsF-like)
Type: Family

Vps genes contribute to biofilm formation by directing biosynthesis of the exopolysaccharide VPS (Vibrio polysaccharide), a major component of the biofilm matrix. These genes are divided into different classes with different predicted functions, of which class VI genes encode the proteins VpsF, VpsJ, VpsM, VpsP and VpsQ. Deletion of VpsF, VpsJ or VpsM results in the complete loss of colony corrugation, an inability to form pellicles, and a reduction in biofilm and VPS production, which implies that these proteins have an important role in biofilm formation . This entry represents VpsF and related proteins.
TipC immunity protein-like (TipC-like)
Type: Family

Gram-positive bacteria transport macromolecules across the membrane through a multi-subunit membrane protein complex known as the type VII secretion system (T7SS). This family is represents homologues of TipC (also known as TipC1), an immunity protein for the toxin TelC, which is a type VII secretion system (T7SS) effector lipid II phosphatase . It was shown that TipC localises to the plasma membrane via an N-terminal transmembrane domain and that the upstream soluble region of TipC is sufficient to inhibit the toxic lipid II phosphatase activity of TelC .
Valine-tRNA ligase, actinomycetes (Valyl-tRNA_ligase_actino)
Type: Family

This entry represents a group of type 2 valine-tRNA ligases from actinomycetes.

Valine-tRNA ligase (also known as Valyl-tRNA synthetase) (

) is an alpha monomer that belongs to class Ia aminoacyl-tRNA ligase.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
DNA topoisomerase I, DNA-binding domain (Topoisomer_I_DNA-bd)
Type: Domain

This entry represents the N-terminal DNA-binding domain found in DNA topoisomerase (topo) I from animals and fungi. Topo I relaxes superhelical tension in duplex DNA by creating a single-strand nick, the broken strand can then rotate around the unbroken strand to remove DNA supercoils and, the nick is relegated, liberating topo I . These enzymes regulate the topological changes that accompany DNA replication, transcription and other nuclear processes. Human topo I is the target of a diverse set of anticancer drugs including camptothecins (CPTs) . CPTs bind to the topo I-DNA complex and inhibit religation of the single-strand nick, resulting in the accumulation of topo I-DNA adducts .
IS607 transposase (Transpos_IS607)
Type: Family

This entry represents a group of proteins from prokaryotes belonging to the IS607 family of transposases. Most members of this protein family contain the domain (

).
Chromatin structure-remodeling complex subunit RSC1/2, bromodomain (RSC1/2_bromodom)
Type: Domain

This entry represents the second bromodomain of RSC1/2 specific to fungi. RSC1 and RSC2 are components of the RSC complex (remodeling the structure of chromatin), are essential for transcriptional control, and have a specific domain architecture including two bromodomains . The RSC complex has also been linked to homologous recombination and nonhomologous end-joining repair of DNA double strand breaks. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.
Transcriptional regulator BldC-like (BldC-like)
Type: Family

This entry represents a group of proteins from actinomycetes, incuding BldC from Streptomyces, a helix-turn-helix transcription factor with homology to the mercury resistance transcriptional regulator MerR. This group of regulators show an asymmetric head-to-tail oligomerization for cooperative DNA binding, rather than classic dimerisation .
Amuc_1100 pilus-like (Amuc_1100-like)
Type: Family

This entry includes the functionally uncharacterised protein Amuc_1100 (

) from Akkermansia muciniphila, a probiotic bacterium known to influence glucose homeostasis and to contribute to gut health. The crystal structure of Amuc_1100 was determined (

) and revealed a structural similarity to three proteins related to pilus formation, PilO, PilN and EpsL, indicating potential similarity in function . Amuc_1100 folds into an α/β structure consisting of a four-stranded antiparallel curved β-sheet with α-helices packed on the concave side of the sheet.

Amuc_1100 was shown to interact with Toll-like receptor 2 and to improve the gut barrier via activation of this receptor .
AP180-like N-terminal domain, plants (ANTH_N_plant)
Type: Domain

This entry represents the N-terminal region of ANTH domains of plant clathrin coat assembly protein AP180 and similar proteins.

Arabidopsis thaliana AP180 (At-AP180, also known as PICALM6) is a binding partner of plant alphaC-adaptin; it functions as a clathrin assembly protein that promotes the formation of cages with an almost uniform size distribution . In addition to At-AP180, Arabidopsis thaliana contains many ANTH domain containing proteins labelled as putative clathrin assembly proteins included in this entry such as At4g02650 (also known as PICALM5B), At1g03050 (also known as PICALM5A), At5g10410, At2g25430, and At1g33340, among others , that may play an important role in clathrin-mediated endocytosis, proper cell wall assembly and morphogenesis . PICALM5A/B are required for the pollen tube plasma membrane integrity via recycling ANXUR kinases .

ANTH domains bind both inositol phospholipids and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. The ANTH domain is a unique module whose N-terminal half is structurally similar to the Epsin N-Terminal Homology (ENTH) and Vps27/Hrs/STAM (VHS) domains, containing a superhelix of eight α-helices. In addition, it contains a coiled-coil C-terminal half with structural similarity to spectrin repeats. It binds phosphoinositide PtdIns(4,5)P2 at a short conserved motif K[X]9[K/R][H/Y] between helices 1 and 2 .
Biofilm-associated protein BapA-like, prefix-like domain (BapA-like_prefix-like)
Type: Domain

This entry represents the N-terminal domain of two largely unrelated repetitive proteins, both named Biofilm-associated protein BapA (from Salmonella enterica and from Paracoccus denitrificans), which share homology domains at the two ends. Both lack a typical signal peptide for translocation by Sec, and instead depend on type I secretion for export and for contribution to biofilm formation. The conserved prefix (N-terminal) domain is shared by a number of other large, repetitive proteins of proteobacteria thought to be associated with adhesion or biofilm formation .
Fimbrial subunit type 1-like (FM1-like)
Type: Family

This entry represents a group of proteins from actinomycetes and firmicutes, including Fimbrial subunit type 1 (FMI1) from Actinomyces viscosus and FMI2 from Actinomyces naeslundii. Members of this family are pilin major subunits whose structure includes an LPXTG motif-containing signal near the C terminus, for processing by sortases. Most contain a recognisable D2-type fimbrial isopeptide formation domain (

), in which Lys-to-Asn isopeptide bond formation provides additional structural integrity to support adhesion despite shear.
Cyclin-Q, second cyclin box (Cyclin-Q_second_cyclin_box)
Type: Domain

The CCNM family proteins, also called ancient conserved domain proteins (ACDPs), are evolutionarily conserved Mg2 transporters. CCNM, also called cyclin-Q (CCNQ), or CDK10-activating cyclin, or cyclin-related protein FAM58A, associates with CDK10 to promote its kinase activity . These proteins contain two cyclin boxes, the second one corresponds to this entry. The cyclin box is a protein binding domain.
PE cleavage protein A, C-terminal domain (PecA_C)
Type: Domain

This entry represents the C-terminal domain of PE cleavage protein A (PecA) and related proteins found in mycobacteria. PecA from Mycobacterium marinum (

), and related paralogues from Mycobacterium tuberculosis PE_PGRS35 (

), and PE_PGRS16 (

), are all PE domain-containing proteins secreted by a type VII secretion system (T7SS, also called ESX in Mycobacterium). These proteins share a common C-terminal aspartic protease-like domain. PecA is known to be a functional aspartic protease that cleaves within the PE domain of T7SS secretion substrates containing this domain, in addition to its autoproteolytic activity .

The structure of PE_PGRS16 (

) revealed fold and catalytic site architecture with a greater similarity to pepsins than to retroviral proteases. It was found that this protein is insensitive to common pepsin substrates, suggesting that PE_PGRS16 may have a narrow specificity .
Cyclin-Q, first cyclin box (Cyclin-Q_first_cyclin_box)
Type: Domain

The CCNM family proteins, also called ancient conserved domain proteins (ACDPs), are evolutionarily conserved Mg2 transporters. CCNM, also called cyclin-Q (CCNQ), or CDK10-activating cyclin, or cyclin-related protein FAM58A, associates with CDK10 to promote its kinase activity . These proteins contain two cyclin boxes, the first one corresponds to this entry. The cyclin box is a protein binding domain.
AUP1, CUE domain (AUP1_CUE)
Type: Domain

Lipid droplet-regulating VLDL assembly factor AUP1 is a component of the HRD1-SEL1L endoplasmic reticulum (ER) quality control complex, playing a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome.It is also essential for the US11-mediated dislocation of class I MHC heavy chains . It also binds to the membrane-proximal KVGFFKR motif of the cytoplasmic tail of the integrin alphaCTs that plays a crucial role in the inside-out signalling of αΙΙbβ3. AUP1 is found in both the ER and in lipid droplets, in which it plays a role in lipid droplet formation and induces lipid droplet clustering . It recruits the ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation .

AUP1 contains two conserved cytoplasmic domains, an acyltransferase domain, a CUE domain and a C-terminal E2 ubiquitin conjugase G2 (UBE2G2)-binding domain (G2BR), and it is uniquely required to maintain normal levels of UBE2G2 .

This entry corresponds to the CUE domain of AUP1 which mediates interaction with components in the HRD1 ERAD pathway and misfolded proteins. This domain may also be involved in lipid droplet clustering and in ubiquitination of AUP1 itself .
Probable G protein-coupled receptor 34, 7TM (GPR34_7tmA)
Type: Domain

This entry represents the seven-transmembrane segments of the probable G-protein coupled receptor 34 (GPR34), an orphan receptor primarily expressed in the immune system, particularly in microglia and macrophages, which suggests its involvement in immune regulation and inflammatory responses . GPR34 is a member of the rhodopsin-like, class A GPCRs, a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signalling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. .
rRNA biogenesis protein RRP5, S1 domain, eleventh repeat (Rrp5_S1_rpt_hs11_sc8)
Type: Domain

This entry represents the S1 repeat 11 from Homo sapiens Rrp5 (hs11) and S1 repeat 8 in S. cerevisiae (sc8).

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 .