SII-SWORD/CoKE huggingface dataset:
Integral membrane protein TerC (Integral_membrane_TerC)
Type: Family

A family containing a number of integral membrane proteins is named after TerC protein. TerC has been implicated in resistance to tellurium, and may be involved in efflux of tellurium ions. The tellurite-resistant Escherichia coli strain KL53 was found during testing of a group of clinical isolates for antibiotic and heavy metal ion resistance . The determinant of the strain's tellurite resistance was located on a large conjugative plasmid, and analyses showed the genes terB, terC, terD and terE were essential for conservation of this resistance. Members of this family contain a number of conserved aspartates which may be involved in metal ion binding.

A TerC homologue is known from the chloroplast thylakoid membrane from
Arabidopsis
which is important for thylakoid membrane biogenesis in the developing chloroplast ; it is required for insertion of proteins into the thylakoid membrane .
Cytochrome b6-f complex, subunit 8 (Cytochrome_b6-f_cplx_su8)
Type: Family

PetN is a small hydrophobic protein, crucial for cytochrome b6-f complex assembly and/or stability. It is found in bacteria and plants. Cytochrome b6-f complex is composed of 4 large subunits: cytochrome b6, subunit IV (17kDa polypeptide, petD), cytochrome f and the Rieske protein, as well as 4 small subunits: petG, petL, petM and petN. The complex functions as a dimer. The cytochrome b6-f complex mediates electron transfer between photosystem II (PSII) and photosystem I (PSI) .
Type IV secretion system, VirB10/TraB/TrbI (T4SS_VirB10/TraB/TrbI)
Type: Family

This entry represents type IV secretion system proteins VirB10, TraB and TrbI. Type IV secretion systems are found in plant and animal pathogens, as well as in symbiotic bacteria.

The tumour-inducing (Ti) plasmid of Rhizobium radiobacter (Agrobacterium tumefaciens) encodes various DNA transfer systems: VirB, Tra and Trb, where the virB operon is required for the transfer DNA to the plant host and the tra/trb systems are required for the conjugal transfer of the Ti plasmid between cells of Agrobacterium . Of the two unlinked regions of octopine-type Ti plasmids that contain genes required for conjugal transfer, the tra gene cluster is probably required for conjugal DNA processing, whilst the other gene cluster, trb, probably directs the synthesis of a conjugal pilus and mating pore . It has been suggested that TraB extends into the periplasmic space and is anchored in the inner membrane via a single transmembrane segment near the N terminus. It is also thought that TraB may interact with TraP, in order to stabilise the proposed transmembrane complex formed by the tra operon products .

The trbI gene encodes a 128-amino-acid polypeptide that is an intrinsic inner-membrane protein. TrbI may influence the kinetics of pilus outgrowth and/or retraction . Although not essential for conjugation, the TrbI protein greatly increases conjugational efficiency . In Plasmid pTiC58, all of the trb genes except trbI and trbK are essential for conjugal transfer .
6-carboxyhexanoate--CoA ligase (BioW)
Type: Family

This family contains the enzyme 6-carboxyhexanoate-CoA ligase

. This enzyme is involved in the first step of biotin synthesis, where it converts pimelate into pimeloyl-CoA . The enzyme requires magnesium as a cofactor and forms a homodimer .

This enzyme sometimes can be found as part of a bifunctional protein with 8-amino-7-oxononanoate synthase.
Protein of unknown function DUF309 (DUF309)
Type: Family

This family consists of eubacterial and archaebacterial proteins of unknown function. The proteins contain a motif HXXXEXX(W/Y) where X can be any amino acid. This motif is likely to be functionally important and may be involved in metal binding.
LamB/YcsF/PxpA-like (LamB/YcsF/PxpA-like)
Type: Family

This entry includes LamB/YcsF/PxpA and related proteins.

The lam locus of Emericella nidulans (Aspergillus nidulans) consists of two divergently transcribed genes, lamA and lamB, involved in the utilization of lactams such as 2-pyrrolidinone. Both genes are under the control of the positive regulatory gene amdR and are subject to carbon and nitrogen metabolite repression .

The B. subtilis homologue of LamB (known as YcsF) has been reported to be a previously unidentified prokaryotic 5-oxoprolinase (named PxpA), and has been suggested to function, along with PxPB and PxpC, in the disposal of 5-oxoproline .
ADP-ribosylation/Crystallin J1 (Ribosyl_crysJ1)
Type: Family

This entry represents enzymes that perform ADP-ribosylations, including ADP-ribosylhydrolase ARH1/3 from animals, which preferentially hydrolyses the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose .

The family also includes ADP-ribosylarginine hydrolase Tri1 from Serratia proteamaculans. This protein neutralises Tre1-Sp both by occluding its active site via its N-terminal extension and by hydrolysing the ADP-ribosyl moiety from FtsZ. It functions as an immunity component of a contact-dependent interbacterial competition system (also called effector-immunity systems) .

ADP-ribosyl-[dinitrogen reductase] glycohydrolase is involved in the regulation of nitrogen fixation activity by the reversible ADP-ribosylation of one subunit of the homodimeric dinitrogenase reductase component of the nitrogenase enzyme complex in Rhodospirillum rubrum .

Jellyfish Crystallin proteins are also included in this group, although these proteins appear to have lost the presumed active site residues.
Flagellar basal body-associated protein FliL (FliL)
Type: Family

This FliL protein controls the rotational direction of the flagella during chemotaxis . FliL is a cytoplasmic membrane protein associated with the basal body .
Protein of unknown function DUF312, ALF (DUF312_ALF)
Type: Repeat

This entry represents a set of repeats named ALF (Alanine-rich, AL - conserved Phenylalanine, F), which are found in a small family of secreted proteins of no known function. They may be involved in signal transduction .
Human herpesvirus 6 immediate early protein (HHV6-IE)
Type: Family

The proteins in this family are poorly characterised, but an investigation has indicated that the immediate early protein is required for the down-regulation of MHC class I expression in dendritic cells. Human herpesvirus 6 immediate early protein is also referred to as U90.
B3 domain-containing protein At2g31720-like (At2g31720-like)
Type: Family

This entry represents a group of uncharacterised plant proteins, including B3 domain-containing protein At2g31720 (also known as Protein AUXIN RESPONSE FACTOR 70) from Arabidopsis. These are DNA-binding proteins likely to be involved in stress response .
A-factor biosynthesis hotdog domain (AfsA_hotdog_dom)
Type: Domain

The AfsA family are key enzymes in A-factor biosynthesis, which is essential for streptomycin production and resistance. This domain is distantly related to the thioester dehydratase FabZ family and therefore has a Hotdog domain .
CRISPR type III-associated RAMP protein Csm4 (Csm4)
Type: Family

CRISPR is a term for Clustered Regularly Interspaced Short Palidromic Repeats. A number of protein families appear only in association with these repeats and are designated Cas (CRISPR associated) proteins. Members of this cas gene family are found in the mtube subtype of CRISPR/cas locus and designated Csm4, for CRISPR/cas Subtype Mtube, protein 4 .

This entry represents the CRISPR system Cms protein Csm4. Csm4 is a component of the binary Csm complex. The backbone of the Csm complex is composed of a 5xCsm3 protein filament that is capped by the Cas10-Csm4 subcomplex at one end and by the Csm5 subunit at the opposite end . The 5'-handle of crRNA is bound by the Csm4 protein .
Senescence marker protein-30 (SMP-30) (SMP-30)
Type: Family

This entry represents members of the SMP-30/CGR1 family which act as lactonases such as regucalcin. Regucalcin (RGN) is a gluconolactonase (

), converting D-glucono-1,5-lactone to D-gluconate, but also hydrolyses other carbohydrate lactones. This enzyme is required for the penultimate step in vitamin C biosynthesis. From its crystal structure, regucalcin has a six-bladed β-propeller fold, and binds a single metal ion (either Ca
2+
or Zn
2+
)) . Homologues with similar catalytic activity have been isolated and characterised from bacteria . There are other bacterial homologues. L-arabinolactonase (

), from
Azospirillum brasilense
, converts L-arabino-gamma-lactone to L-arabonate, allowing the bacterium utilise L-arabinose as a sole carbon source ; lactonase drp35 from
Staphylococcus
species acts as a lactonase on dihydrocoumarin or 2-coumaranone .

A homologue from the squid
Loligo vulgari
can act as a diisopropyl-fluorophosphatase (

), but its physiological substrate is unknown .

Regucalcin, also known as senesence marker protein-30 (SMP30), was discovered in 1978 as a Ca
2+
binding protein that does not contain EF-hand motifs, suggesting a novel class of Ca
2+
binding protein. It is primarily localised to the liver and kidney cortex of animals. Expression of its mRNA in the liver and renal cortex of rats is stimulated by an increase in cellular Ca
2+
levels .

Regucalin, as a regulatory protein of Ca
2+
, has a pivotal role in the control of many cell functions. The protein has a reversible effect on Ca
2+
-induced activation and inhibition of many enzymes in both the liver and renal cortex cells . It has also been shown to inhibit various protein kinases (including Ca
2+
/calmodulin-dependent protein kinase , protein kinase C and tyrosine kinase) and protein phosphatases, indicating a regulatory role in signal transduction within the cell. In addition, regucalcin regulates intracellular Ca
2+
homeostasis by enhancing Ca
2+
-pumping activity in the plasma membrane through activation of the pump enzymes . Moreover, it can inhibit RNA synthesis in the nuclei of normal and regenerating rat livers in vitro .

Hydropathy profiles indicate hydrophobic domains in both N-and C-terminal regions of the regucalcin molecule; the protein also exhibits hydrophilic characteristics. Human and rodent regucalcins share 89% sequence identity, the high degree of conservation between species suggesting that the complete structure is required for physiological function.
PRONE domain (PRONE_dom)
Type: Domain

In plants, the small GTP-binding proteins called Rops work as signalling switches that control growth, development and plant responses to various environmental stimuli. Rop proteins (Rho of plants, Rac-like and atRac in Arabidopsis thaliana belong to the Rho family of Ras-related GTP-binding proteins that turn on signalling pathways by switching from a GDP-bound inactive to a GTP-bound active conformation. Activation depends on guanine nucleotide exchange factors (GEFs) that catalyse the otherwise slow GDP dissociation for subsequent GTP binding. The plant-specific RopGEFs represent a unique family of exchange factor that display no homology to any known RhoGEFs from animals and fungi. They comprise a highly conserved catalytic domain termed PRONE (plant-specific Rop nucleotide exchanger) with exclusive substrate specificity for members of the Rop family. The PRONE domain has been shown to be necessary and sufficient to promote nucleotide release from Rop .

The PRONE domain can be divided into three highly conserved subdomains separated by two short stretches of variable amino acid residues . It is approximately 370 residues in length and displays an almost all α-helical structure except for a β-turn that protrudes from the main body of the molecule. The overall structure of the PRONE domain can be divided into two subdomains, the first one including helices alpha1-5 and alpha13, the second alpha6-12 .
Late embryogenesis abundant protein, LEA_1 subgroup (LEA_1)
Type: Family

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .

This entry represents Pfam LEA_1, or D-113 from Dure, or group 4 from Bray. Proteins in this entry include LEA6, LEA18 and LEA46 from Arabidopsis. They may play roles in the adaptive process to water deficit in higher plants .
Chymotrypsin family Peptidase-S1 (DUF316)
Type: Family

This is a family of trypsin-6 part of the chymotrypsin family S21, ie a serine peptidase. The C. elegans sequence (

) is trypsin-6: all the active site residues are present (His90, Asp168, Ser267).
Vitelline membrane outer layer protein I (VOMI) (VOMI)
Type: Family

Vitelline membrane outer layer protein I (VMO-I) is one of the proteins found in the outer layer of the vitelline membrane of eggs. VMO-I, lysozyme, and VMO-II are bound tightly to ovomucin fibrils of the egg yolk membrane. The structure of VMO-I consists of three β-sheets forming Greek key motifs, which are related by an internal pseudo three-fold symmetry. It is a member of the β-prism-fold family and the structure of VOM-I has strong similarity to the structure of the delta-endotoxin, as well as a carbohydrate-binding site in the top region of the common fold . VMO-I has been shown to synthesize N-acetylchito-oligosaccharides from N-acetylglucosamine.
Remorin, C-terminal (Remorin_C)
Type: Domain

Remorins are plant-specific plasma membrane-associated proteins. In tobacco remorin co-purifies with lipid rafts. Most remorins have a variable, proline-rich N-half and a more conserved C-half that is predicted to form coiled coils. Consistent with this, circular dichroism studies have demonstrated that much of the protein is α-helical. Remorins exist in plasma membrane preparations as oligomeric structures and form filaments in vitro. The proteins can bind polyanions including the extracellular matrix component oligogalacturonic acid (OGA). In vitro, remorin in plasma membrane preparations is phosphorylated (principally on threonine residues) in the presence of OGA and thus co-purifies with a protein kinases(s). The biological functions of remorins are unknown but roles as components of the membrane/cytoskeleton are possible .
Translation elongation factor EFG/EF2, domain IV (Transl_elong_EFG/EF2_IV)
Type: Domain

Included in this entry is a domain of mitochondrial Elongation factor G1 (mtEFG1) proteins that is homologous to domain IV of EF-G. Eukaryotic cells harbor 2 protein synthesis systems: one localized in the cytoplasm, the other in the mitochondria. Most factors regulating mitochondrial protein synthesis are encoded by nuclear genes, translated in the cytoplasm, and then transported to the mitochondria. The eukaryotic system of elongation factor (EF) components is more complex than that in prokaryotes, with both cytoplasmic and mitochondrial elongation factors and multiple isoforms being expressed in certain species. During the process of peptide synthesis and tRNA site changes, the ribosome is moved along the mRNA a distance equal to one codon with the addition of each amino acid. In bacteria this translocation step is catalyzed by EF-G_GTP, which is hydrolyzed to provide the required energy. Thus, this action releases the uncharged tRNA from the P site and transfers the newly formed peptidyl-tRNA from the A site to the P site. Eukaryotic mtEFG1 proteins show significant homology to bacterial EF-Gs. Mutants in yeast mtEFG1 have impaired mitochondrial protein synthesis, respiratory defects and a tendency to lose mitochondrial DNA .

EF2 has five domains. This entry represents domain IV found in EF2 (or EF-G) of both prokaryotes and eukaryotes. The EF2-GTP-ribosome complex undergoes extensive structural rearrangement for tRNA-mRNA movement to occur. Domain IV, which extends from the 'body' of the EF2 molecule much like a lever arm, facilitates the movement of peptidyl-tRNA from the A to the P site, being critical for the structural transition to take place .

Elongation factor EF2 (EF-G) is a G-protein. It brings about the translocation of peptidyl-tRNA and mRNA through a ratchet-like mechanism: the binding of GTP-EF2 to the ribosome causes a counter-clockwise rotation in the small ribosomal subunit; the hydrolysis of GTP to GDP by EF2 and the subsequent release of EF2 causes a clockwise rotation of the small subunit back to the starting position . This twisting action destabilises tRNA-ribosome interactions, freeing the tRNA to translocate along the ribosome upon GTP-hydrolysis by EF2. EF2 binding also affects the entry and exit channel openings for the mRNA, widening it when bound to enable the mRNA to translocate along the ribosome.

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.
Remorin, N-terminal (Remorin_N)
Type: Domain

Remorin binds both simple and complex galaturonides. The N-terminal region of remorin is proline rich, while the C-terminal region has been predicted to form a coiled-coil, that is expected to interact with other macromolecules, most likely DNA. Functional similarities between the behavior of the proteins and viral proteins involved in intercellular communication have been noted .
Acid phosphatase, class B-like (Acid_phosphat_B-like)
Type: Family

This family of class B acid phosphatases also contains a number of vegetative storage proteins (VPS25) . The acid phosphatase activity of VPS has been experimentally demonstrated .
Attacin, N-terminal (Attacin_N)
Type: Domain

This domain is found in attacin and sarcotoxin, but not diptericin (which shares similarity to the C-terminal region of attacin). All these proteins are insect antibacterial proteins which are induced by the fat body and subsequently secreted into the hemolymph where they act synergistically to kill the invading microorganism .
Attacin, C-terminal (Attacin_C)
Type: Domain

This domain is found in attacin, sarcotoxin and diptericin. All members of these proteins are insect antibacterial proteins which are induced by the fat body and subsequently secreted into the hemolymph where they act synergistically to kill the invading microorganism .
Inositol polyphosphate kinase (IPK)
Type: Family

Inositol phosphates (IPs) act as signalling messengers to regulate various cellular processes such as growth. This entry includes a group of inositol polyphosphate kinase, including inositol polyphosphate multikinase Arg82 and Inositol hexakisphosphate/inositol heptakisphosphate kinase Kcs1 from budding yeast. They play important roles in vacuole biogenesis and the cell's response to certain environmental stresses. The kinase activity of Arg82 and Kcs1 is required for the production of soluble inositol phosphates . Independently of its catalytic activity, Arg82 is crucial for assembling the Arg80-Mcm1 protein complex at the promoter region of genes involved in arginine metabolism .

This entry also includes human inositol hexakisphosphate kinase 1/2/3 (IP6K1/2/3), inositol polyphosphate multikinase (IPMK) and inositol-trisphosphate 3-kinase A/B/C (IP3KA/B/C) . They are involved in inositol phosphate biosynthesis . Independently of its catalytic activity, IPMK mediates the activation of mammalian target of rapamycin (mTOR) in response to essential amino acids [

. Crystallographic analysis showed that the disordered domains of IPMK modulates its kinase activity .
Domain of unknown function DUF317, SPDY (DUF317_SPDY)
Type: Domain

This domain is currently found in streptomyces bacteria, in a set of bacterial proteins with no known function. Most proteins contain two copies of this domain .
Predicted permease DUF318 (DUF318)
Type: Family

This family of integral membrane proteins are predicted to be permeases of unknown specificity.
Septum formation inhibitor MinC, C-terminal (Septum_form_inhib_MinC_C)
Type: Domain

In Escherichia coli, three Min proteins (MinC, MinD and MinE) negatively regulate FtsZ assembly at the cell poles in order to ensure the Z-ring only assembles at cell midpoint. MinC inhibits formation of the Z-ring by preventing FtsZ assembly. MinD binds to MinC near the cell poles, sequestering MinC away from the cell midpoint so the Z-ring can form there. MinC is an oligomer, probably a dimer, that consists of two domains: the N-terminal domain is responsible for FtsZ inhibition, while the C-terminal domain is responsible for binding to MinD and to a component of the division septum .
Cell division topological specificity factor MinE (MinE)
Type: Family

Cytokinesis needs to be regulated spatially in order to ensure that it occurs between the daughter genomes. In prokaryotes such as Escherichia coli, cytokinesis is initiated by FtsZ, a tubulin-like protein that assembles into a ring structure at the cell centre called the Z ring. A fundamental problem in prokaryotic cell biology is to understand how the midcell division site is identified. Two major negative regulatory systems are known to be involved in preventing Z-ring assembly at all sites except the midcell. One of these systems, called nucleoid occlusion, blocks Z-ring assembly in the area occupied by an unsegregated nucleoid until a critical stage in chromosome replication or segregation is reached. The other system consists of three proteins, MinC, MinD and MinE, which prevent assembly of Z rings in regions of the cell not covered by the nucleoid, such as the cell poles. MinC is an inhibitor of FtsZ polymerisation, resulting in the inhibition of Z ring assembly in the cell; MinD greatly enhances the inhibitory effects of MinC in vivo; and MinE antagonizes the effects of MinC and MinD .

MinE is a small bifunctional protein. The amino terminus of MinE is required to interact with MinD, while the carboxyl terminus is required for 'topological specificity'- that is, the ability of MinE to antagonise MinCD inhibition of Z rings at the midcell position but not at the poles .

This entry also includes plant MinE1 located in chloroplasts. AtMinE1 acts as a topological specificity factor during plastid division and specify plastid constriction sites .
Chaplin domain (ChpA-H)
Type: Domain

Streptomycetes differentiate by forming specialized spore-bearing aerial hyphae that grow into the air. In order to break surface tension streptomycetes have to coat their aerial hyphae in an extremely hydrophobic sheath that is absent from the vegetative hyphae growing in the aqueous phase. The hydrophobic sheath, which permits the aerial hyphae to escape surface tension and likely also prevents their desiccation in air, is made up of two families of proteins, the chaplins, for coelicolor hydrophobic aerial proteins, and the rodins. The chaplins are surface-active proteins that can be divided into two classes: the short chaplins and the long chaplins. The chaplins share a highly conserved, hydrophobic domain of ~40 amino acids, termed the chaplin domain, and all have an N-terminal Sec secretion signal. The short chaplins have one chaplin domain, whereas the long chaplins have two chaplin domains and a C-terminal 'sorting signal' that targets them for covalent attachment to the cell wall by sortase enzymes. The chaplins self- assemble via their chaplin domains into amyloid-like filaments on the surface of the aerial hyphae and spores .