SII-SWORD/CoKE huggingface dataset:
DNA polymerase III, psi subunit, subgroup (DNA_pol_III_psi_subgr)
Type: Family

DNA-directed DNA polymerase (

) catalyzes DNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. The enzyme also has 3' to 5' exonuclease activity. It has a core composed of alpha, epsilon and theta chains, that associate with a tau subunit which allows the core dimerization to form the PolIII' complex. PolIII' associates with the gamma complex (gamma, delta, delta', psi and chi chains) and with the beta chain. This family is the psi subunit, the small subunit of the DNA polymerase III holoenzyme in Escherichia coli and related species, whose exact function is not known. It appears to have a narrow taxonomic distribution, being restricted to the gammaproteobacteria.
Uncharacterised protein family UPF0324, prokaryote (UPF0324_pro)
Type: Family

This entry represents a family of uncharacterised multi-pass membrane proteins.
DNA-binding protein Tfx, euryarchaeota (Tfx_DNA-bd_euryarc)
Type: Family

This entry represents a family of Tfx DNA-binding proteins, which is restricted to euryarchaeota. TfX has a 2-layer α/β topology. Homology among the members is strongest in the helix-turn-helix-containing N-terminal region. Tfx from Methanothermobacter thermautotrophicus is associated with the operon for molybdenum formyl-methanofuran dehydrogenase and binds a DNA sequence near its promoter .
C4-dicarboxylate anaerobic carrier-like (C4_dicarb_anaerob_car-like)
Type: Family

Escherichia coli contains four different secondary carriers (DcuA, DcuB, DcuC, and DctA) for C4-dicarboxylates DcuA is used for aerobic growth on C4-dicarboxylates , whereas the Dcu carriers (encoded by the dcuA, dcuB, and dcuC genes) are used under anaerobic conditions and form a distinct family of carriers . Each of the Dcu carriers is able to catalyze the uptake, antiport, and possibly also efflux of C4-dicarboxylates. DcuB is the major C4-dicarboxylate carrier for fumarate respiration with high fumarate-succinate exchange activity. It is synthesized only in the absence of oxygen and nitrate and in the presence of C4-dicarboxylates . DcuA is expressed constitutively in aerobic and anaerobic growth and can substitute for DcuB .

These proteins are members of the C4-dicarboxylate Uptake C (DcuC) family. DcuC has 12 GES predicted transmembrane regions, is induced only under anaerobic conditions, and is not repressed by glucose. DcuC may therefore function as a succinate efflux system during anaerobic glucose fermentation. However, when overexpressed, it can replace either DcuA or DcuB in catalyzing fumarate-succinate exchange and fumarate uptake . DcuC shows the same transport modes as DcuA and DcuB (exchange, uptake, and presumably efflux of C4-dicarboxylates) .
TRAP transporter solute receptor DctP (DctP_fam)
Type: Family

The tripartite ATP-independent periplasmic (TRAP) transporters are substrate-binding protein (SBP)-dependent secondary transporters found in prokaryotes. They consist of a substrate-binding protein (SBP) of the DctP or TAXI families and two integral membrane proteins that form the DctQ and DctM protein families .

This entry represents the DctP family of the substrate-binding proteins. They are part of the DctP-TRAP (tripartite ATP-independent periplasmic) transporter involved in binding extracellular solutes for transport across the bacterial cytoplasmic membrane. Proteins in this family include DctP from R. capsulatus, SiaP from Haemophilus influenzae , DctB from Bacillus subtilis , and TeaA from Halomonas elongata . The structure of the SiaP receptor has revealed an overall topology similar to ATP binding cassette ESR (extracytoplasmic solute receptors) proteins . Upon binding of sialic acid, SiaP undergoes domain closure about a hinge region and kinking of an α-helix hinge component .
Pyrrolo-quinoline quinone beta-propeller repeat (PQQ_b-propeller_rpt)
Type: Repeat

Pyrrolo-quinoline quinone (PQQ) is a redox coenzyme, which serves as a cofactor for a number of enzymes (quinoproteins) and particularly for some bacterial dehydrogenases . A number of bacterial quinoproteins belong to this family.

Enzymes in this group contain repeats composing a β propeller.
LysM domain (LysM)
Type: Domain

The LysM (lysin motif) domain is a small globular domain, approximately 40 amino acids long. It is a widespread protein module involved in binding peptidoglycan in bacteria and chitin in eukaryotes. The domain was originally identified in enzymes that degrade bacterial cell walls , but proteins involved in many other biological functions also contain this domain. It has been reported that the LysM domain functions as a signal for specific plant-bacteria recognition in bacterial pathogenesis . Many of these enzymes are modular and are composed of catalytic units linked to one or several repeats of LysM domains. LysM domains are found in bacteria and eukaryotes .
NADH-plastoquinone oxidoreductase, chain 5 subgroup (NADHpl_OxRdtase_5_subgr)
Type: Family

NADH-plastoquinone oxidoreductase chain 5 is part of the NADH-ubiquinone oxidoreductase (complex I), which catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane :

NADH + ubiquinone = NAD(+) + ubiquinol
Cryptochrome/DNA photolyase class 1, conserved site, C-terminal (DNA_photolyase_1_CS_C)
Type: Conserved_site

The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals . On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes . The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.

This entry represents a number of conserved sequence regions found in the C-terminal region of the class 1 cryptochrome/DNA photolyase.
2-keto-3-deoxygluconate permease, subgroup (2keto-3dGluconate_permease_sub)
Type: Family

This family includes the characterised 2-Keto-3-Deoxygluconate transporters from Bacillus subtilis and Erwinia chrysanthemi. There are homologues of this protein found in both Gram-positive and Gram-negative bacteria.

In E. chrysanthemi, a phytopathogenic bacterium, degraded pectin products from plant cell walls are transported by 2-keto-3-deoxygluconate permease into the bacterial cell to provide a carbon and energy source . 2-keto-3-deoxygluconate permease can mediate the uptake of glucuronate with a low affinity .
Lysosomal-associated transmembrane protein, 4A/5 (LAPTM_4A/5)
Type: Family

The lysosome associated protein transmembrane (LAPTM) family is comprised of three members: LAPTM5, LAPTM4a and LAPTM4b; they are lysosome-associated transmembrane proteins, found in mammals, insects and nematodes.

This entry represents LAPTM4 alpha (LAPTM4A) and LAPTM45. LAPTM4A regulates the intracellular compartmentalisation of amphipathic solutes and possibly the sensitivity of cells toward anthracyclines, antibiotics, ionophores, nucleobases and organic cations . LAPTM5 may have functional role during embryogenesis and in adult hematopoietic cells .
Malonate/sodium symporter MadM subunit, N-terminal (Mal/Na_symporter_MadM_N)
Type: Domain

This entry represent the N-terminal domain of the malonate/sodium symporter MadM subunit

The MSS family includes the monobasic malonate:Na+ symporter of Malonomonas rubra. It consists of two integral membrane proteins, MadL and MadM .The transporter is believed to catalyze the electroneutral reversible uptake of H+-malonate with one Na+, and both subunits have been shown to be essential for activity.
Silicon transporter, Cylindrotheca fusiformis (Silicon_transpt_CYLFU)
Type: Family

Marine diatoms such as Cylindrotheca fusiformis encode at least six silicon transport protein homologues which exhibit similar size and topology. One characterised member of the family (Sit1) functions in the energy-dependent uptake of either silicic acid [Si(OH)4] or silicate [Si(OH)3O-] by a Na
+
symport mechanism . The system is found in marine diatoms, which make their "glass houses" out of silicon.
Na+/H+ exchanger, isoforms 3/5 (Na/H_exchanger_3/5)
Type: Family

Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers . These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia . Human NHE is also involved in heart disease, cell growth and in cell differentiation . The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) . These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport .

This entry represents a conserved region found in Na+/H+ exchanger protein isoforms 3 and 5.
Cation/H+ exchanger, CPA1 family (Cation/H_exchanger_CPA1)
Type: Family

This entry represents the cation:proton antiporter family 1 (CPA1), which includes Na+/H+ exchangers and Na+(K+,Li+,Rb+)/H+ exchangers.

Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers . These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia . Human NHE is also involved in heart disease, cell growth and in cell differentiation . The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) . These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport .
Putative phosphate transport regulator (Put_Phosphate_transp_reg)
Type: Family

This family includes prokaryotic proteins of unknown function, as well as a protein annotated as the pit accessory protein from Rhizobium meliloti (Sinorhizobium meliloti) (

). However, while it has been hypothesised that this protein may play a role in orthophosphate transport (Pit stands for phosphate transport), its exact function is unknown .
Corticotropin-releasing factor conserved site (Corticotropin-releasing_fac_CS)
Type: Conserved_site

Corticotropin-releasing factor (CRF) (corticoliberin) is a hormone from the hypothalamus that regulates the release of corticotropin (ACTH) from the pituitary gland. CRF is evolutionary related to a number of other active peptides which are listed below.

Urocortin (Ucn) , a brain mammalian peptide with corticotropin-releasing factor activity.

Urotensin 1 from the urophysis of fish. Like CRF and Ucn, it acts in ACTH secretion.

Sauvagine from frog skin, a peptide with a potent hypotensive action that elicits a diuretic effect.

Diuretic hormone (DH) (or diuretic peptide (DP) from a variety of insects. DH is involved in the regulation of fluid secretion .

All these hormones are peptides of about 40 amino acid residues which are C-terminally amidated and processed from a larger precursor protein. This signature is a pattern of conserved residues, running from position 4 to 19 in these peptides.
Sec-independent protein translocase protein TatB (TatB)
Type: Family

Translocation of proteins across the two membranes of Gram-negative bacteria can be carried out via a number of routes. Most proteins marked for export carry a secretion signal at their N terminus, and are secreted by the general secretory pathway. The signal peptide is cleaved as they pass through the outer membrane. Other secretion systems include the type III system found in a select group of Gram-negative plant and animal pathogens, and the CagA system of Helicobacter pylori .

In some bacterial species, however, there exists a system that operates independently of the Sec pathway . It selectively translocates periplasmic-bound molecules that are synthesised with, or are in close association with, "partner" proteins bearing an (S/T)RRXFLK twin arginine motif at the N terminus. The pathway is therefore termed the Twin-Arginine Translocation or TAT system. Surprisingly, the four components that make up the TAT system are structurally and mechanistically related to a pH-dependent import system in plant chloroplast thylakoid membranes . The gene products responsible for the Sec-independent pathway are called TatA, TatB, TatC and TatE.

This entry represents Sec-independent protein translocase protein TatB (TatB) and similar proteins predominantly found in Proteobacteria. TatB is essential for the secretion of large folded proteins containing a characteristic twin-arginine motif in their signal peptide across membranes. It may form an oligomeric binding site that transiently accommodates folded Tat precursor proteins before their translocation . It may form a circular arrangement with TatC .
NIL domain (NIL_domain)
Type: Domain

This domain is found at the C terminus of ABC transporter proteins involved in D-methionine transport as well as a number of ferredoxin-like proteins. This domain is likely to act as a substrate binding domain. The domain has been named after a conserved sequence in some members of the family.
Romo1/Mgr2 (Romo1/Mgr2)
Type: Family

This entry includes a group of mitochondrial proteins, including reactive oxygen species modulator 1 (Romo1) from animals and Mgr2 from fungi.
NAF/FISL domain (NAF/FISL_domain)
Type: Domain

The NAF domain is a 24 amino acid domain that is found in a plant-specific subgroup of serine-threonine protein kinases (CIPKs), that interact with calcineurin B-like calcium sensor proteins (CBLs). Whereas the N-terminal part of CIPKs comprises a conserved catalytic domain typical of Ser-Thr kinases, the much less conserved C-terminal domain appears to be unique to this subgroup of kinases. The only exception is the NAF domain that forms an 'island of conservation' in this otherwise variable region. The NAF domain has been named after the prominent conserved amino acids Asn-Ala-Phe. It represents a minimum protein interaction module that is both necessary and sufficient to mediate the interaction with the CBL calcium sensor proteins .

The secondary structure of the NAF domain is currently not known, but secondary structure computation of the C-terminal region of Arabidopsis thaliana CBL-interacting protein kinase 1 revealed a long helical structure .

The NAF domain has also been named FISL motif for its conserved amino acid residues .
Phosphotransferase system, glucitol/sorbitol-specific IIA component, subgroup (PTS_IIA_glucitol/sorbitol_sub)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates and coupled with translocation across the cell membrane, makes the PTS a link between the uptake and metabolism of sugars.

The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred via a signal transduction pathway, to enzyme I (EI) which in turn transfers it to a phosphoryl carrier, the histidine protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease, a membrane-bound complex known as enzyme 2 (EII), which transports the sugar to the cell. EII consists of at least three structurally distinct domains IIA, IIB and IIC . These can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

This family consists only of glucitol-specific transporters, and occur both in Gram-negative and Gram-positive bacteria. The system in Escherichia coli consists of a IIA protein, and a IIBC protein. This family is specific for the IIA component.
Phosphotransferase system, sorbose subfamily IIB component, subgroup (PTS_IIB_sorbose-sp_subgr)
Type: Family

Bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) transporters transport and concomitantly phosphorylate their sugar substrates, and typically consist of multiple subunits or protein domains . The Man family is unique in several respects among PTS permease families:

It is the only PTS family in which members possess a IID protein.

It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue.

Its permease members exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars.

The mannose permease of Escherichia coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and other sugars. Other members of this can transport sorbose, fructose and N-acetylglucosamine. The active site histidine receives a phosphate group from the IIA subunit and transfers it to the substrate . This entry is specific for the IIB components of this family of PTS transporters .
PTR2 family proton/oligopeptide symporter, conserved site (PTR2_symporter_CS)
Type: Conserved_site

The transport of peptides into cells is a well-documented biological phenomenon which is accomplished by specific, energy-dependent transporters found in a number of organisms as diverse as bacteria and humans. The PTR family of proteins is distinct from the ABC-type peptide transporters and was uncovered by sequence analyses of a number of recently discovered peptide transport proteins . These proteins that seem to be mainly involved in the intake of small peptides with the concomitant uptake of a proton .

These integral membrane proteins are predicted to comprise twelve transmembrane regions.

This entry describes two conserved sites. The first conserved site is found within a region that includes the end of the second transmembrane region, a cytoplasmic loop as well as the third transmembrane region. The second conserved site corresponds to the core of the fifth transmembrane region.
LacY/RafB permease family, conserved site (LacY/RafB_perm_fam_CS)
Type: Conserved_site

This entry represents two conserved regions that correspond to cytoplasmic loops in the integral membrane proteins of the LacY family.

In bacteria there are a number of families of transport proteins, including symporters and antiporters, that mediate the intake of a variety of sugars with the concomitant uptake of hydrogen ions (proton symporters) . The LacY family of Escherichia coli and Klebsiella pneumoniae are proton/beta-galactoside symporters, which, like most sugar transporters, are integral membrane proteins with 12 predicted transmembrane (TM) regions. Also similar to the LacY family are the rafinose (RafB) and sucrose (CscB) permeases from E. coli and melibiose permease (MelY) from Enterobacter cloacae .
RII binding domain (RII-bd_1)
Type: Domain

This domain is found is a wide variety of AKAPs (A kinase anchoring proteins) .
Na+/H+ antiporter, NhaC-like, C-terminal (Na/H_Antiport_NhaC-like_C)
Type: Domain

This entry represents the C-terminal domain of a group of integral membrane proteins, some of which are Na/H antiporters .
Centromere protein Cenp-F, N-terminal (Centromere_CenpF_N)
Type: Domain

Mitosin or centromere-associated protein-F (Cenp-F) is a coiled-coil protein that dimerizes and localizes to diverse subcellular locations, including microtubule plus-ends, mitochondria, nuclear pores, and kinetochores . It localizes to kinetochores during mitosis and is then rapidly degraded after mitosis. It is required for kinetochore-microtubule interactions and spindle checkpoint function . Cenp-F contains two microtubule-binding domains, and physically associates with dynein motor regulators . Cenp-F has also been shown to couple mitochondria to dynamic microtubule tips .

This entry represents the N-terminal region of Cenp-F.
Centromere protein O (CENP-O)
Type: Family

This entry represents centromere protein O (CENP-O) and its homologues in yeasts, Mcm21 and Mal2.
Centromere protein Scm3/HJURP (Scm3/HJURP)
Type: Family

This entry includes human holliday junction recognition protein (HJURP) and its homologue, Scm3 from budding yeasts.
Yeast cell wall synthesis Kre9/Knh1-like, N-terminal (Kre9/Knh1-like_N)
Type: Domain

This domain is found at the N-terminal of a group of cell wall synthesis proteins, such as Knh1 and Kre9 from budding yeast, involved in cell wall beta 1,6-glucan synthesis. Kre9 is also involved in cell wall beta-glucan assembly . In Saccharomyces cerevisiae, a kre9 null mutation leads to severe growth defects, aberrant multi-budded morphology, and mating defects . Over-expression of Knh1 suppresses growth defects of a kre9 null mutant . Knh1 is required for propionic acid resistance . In Aspergillus fumigatus, proteins containing this domain play a role in fungal cell wall organisation . This entry includes proteins from Lentinula edodes, involved in fruiting body formation, and may have a more general role in signalling in other organisms as it interacts with MAPK . This entry also includes uncharacterised proteins from fission yeast, archaea and bacteria.