SII-SWORD/CoKE huggingface dataset:
Survival protein SurE-like phosphatase/nucleotidase (SurE-like_Pase/nucleotidase)
Type: Domain

This entry represents a SurE-like structural domain with a 3-layer α/β/α topology that bears some topological similarity to the N-terminal domain of the glutaminase/asparaginase family. This domain is found in the stationary phase survival protein SurE, a metal ion-dependent phosphatase found in eubacteria, archaea and eukaryotes. In Escherichia coli,
SurE also has activity as a nucleotidase and exopolyphosphatase, and may be involved in the stress response . E. coli cells with mutations in the surE gene survive poorly in stationary phase . The structure of SurE homologues have been determined from Thermotoga maritima and the archaea Pyrobaculum aerophilum . The T. maritima SurE homologue has phosphatase activity that is inhibited by vanadate or tungstate, both of which bind adjacent to the divalent metal ion.
Protein of unknown function DUF116 (DUF116)
Type: Family

These archaeal and bacterial proteins have no known function. Members of this family contain seven conserved cysteines and may also be an integral membrane protein .
UbiD decarboxylyase family (UbiD)
Type: Family

This family of proteins is found in prokaryotes, archaea and fungi, with two members in Archaeoglobus fulgidus. They are related to UbiD, a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase (also known as polyprenyl p-hydroxybenzoate decarboxylase) from Escherichia coli that is involved in ubiquinone biosynthesis . The member from Helicobacter pylori has a C-terminal extension of just over 100 residues that is shared, in part, by the Aquifex aeolicus homologue.

Proteins in this entry includes:

Bacterial UbiD that catalyses the decarboxylation of 3-octaprenyl-4-hydroxy benzoate to 2-octaprenylphenol. It is involved in ubiquinone biosynthesis .

Budding yeast Fdc1 that catalyses the reversible decarboxylation of aromatic carboxylic acids like ferulic acid, p-coumaric acid or cinnamic acid, producing the corresponding vinyl derivatives 4-vinylphenol, 4-vinylguaiacol, and styrene, respectively, which play the role of aroma metabolites . Fdc1 is not essential for ubiquinone synthesis .

4-hydroxybenzoate decarboxylase subunit C (also known as HBDC) that catalyses the reversible decarboxylation of 4-hydroxybenzoate .

Phenolic acid decarboxylase subunit C (YclC) that can catalyse the reversible decarboxylation of 4-hydroxybenzoate and vanillate and can also decarboxylate 3,4-dihydroxybenzoate .

Anhydromevalonate phosphate decarboxylase which is involved in Involved in the archaeal mevalonate pathway and catalyses the conversion of trans-anhydromevalonate 5-phosphate (tAHMP) into isopentenyl phosphate .
Transcription regulator TrmB, N-terminal (Tscrpt_reg_TrmB_N)
Type: Domain

This entry represents the N-terminal DNA-binding domain found in HTH-type sugar sensing transcriptional regulator TrmB from the hyperthermophilic archaea Pyrococcus furiosus and similar prokaryotic sequences. This domain contains a winged-helix-turn-helix (wHTH) .

TrmB, is a protein of 38,800 apparent molecular weight, that is involved in the maltose-specific regulation of the trehalose/maltose ABC transport operon in Thermococcus litoralis. TrmB has been shown to be a maltose-specific repressor, and this inhibition is counteracted by maltose and trehalose. TrmB binds maltose and trehalose half-maximally at 20 uM and 0.5 mM sugar concentration, respectively . Other members of this family are annotated as either transcriptional regulators or hypothetical proteins .
Peptidyl-tRNA hydrolase, PTH2 (PTH2)
Type: Family

Peptidyl-tRNA hydrolases are enzymes that release tRNAs from peptidyl-tRNA during translation .
Phosphoenolpyruvate guanylyltransferase CofC (CofC)
Type: Family

Coenzyme F420 is a hydride carrier cofactor that plays important roles in primary and secondary metabolism in a range of bacteria and archaea . This entry represents CofC family, guanylyltransferases involved in coenzyme F420 biosynthesis. CofC has been shown to catalyse the activation of phosphoenolpyruvate (PEP) as enolpyruvoyl-2-diphospho-5'-guanosine, via the condensation of PEP with GTP . This family also includes 3-phospho-D-glycerate guanylyltransferase which catalyses the activation of 3-phosphoglycerate (3PG) as 3-[glyceryl]-diphospho-5'-guanosine, via the condensation of 3PG with GTP.
PDCD5-like (PDCD5-like)
Type: Family

This protein family is found in archaea and eukaryota. Proteins in this family contain a predicted DNA-binding domain and may function as DNA-binding proteins. Methanobacterium thermoautotrophicum MTH1615 was predicted to bind DNA based on structural proteomics data, and this was confirmed by the demonstration that it can interact non-specifically with a randomly chosen 20-mer of double stranded DNA . This suggests that the human protein may be involved in nucleic acid binding or metabolism.

The human programmed cell death protein 5 (PDCD5, also known as TFAR19) encodes a protein which shares significant homology to the corresponding proteins of species ranging from yeast to mice. PDCD5 exhibits a ubiquitous expression pattern and its expression is up-regulated in the tumour cells undergoing apoptosis. PDCD5 may play a general role in the apoptotic process .
Protein of unknown function DUF123 (DUF123)
Type: Family

This family includes a group of functionally uncharacterised hypothetical proteins from archaea and their bacterial homologs. These proteins contain a putative GIY-YIG domain that shows sequence homology with bacterial UvrC DNA repair proteins. Meanwhile, all of them share a C-terminal extension with semi-conserved Cys and His residues, which suggests that the extended region may be a zinc-binding nucleic acid interaction domain. Although the majority of family members have a standalone GIY-YIG domain composition, some of them do have an additional endonuclease III domain or sugar fermentation stimulation protein domain, both of which are N-terminally fused to the GIY-YIG domain. As a result, those proteins could perform some other role by cooperating with different domains, which remains to be determined in the future .

In Methanocaldococcus jannaschii (Methanococcus jannaschii) it occurs with an endonuclease domain

.
Mitochondrial biogenesis protein AIM24 (AIM24)
Type: Family

In eukaryotes, proteins in this family are involved in mitochondrial biogenesis . Its function in prokaryotes in unknown.
Phosphomevalonate dehydratase small subunit-like domain (PMDh-S-like_dom)
Type: Domain

This entry represents a domain centrally found in Phosphomevalonate dehydratase small subunit from Aeropyrum pernix (PMDh-S) and similar prokaryotic proteins previously annotated as aconitase X subunit 2, the swiveling domain subunit . PMDh-S is a component of a hydro-lyase that catalyses the dehydration of mevalonate 5-phosphate (MVA5P) to form trans-anhydromevalonate 5-phosphate (tAHMP) . It is involved in the archaeal mevalonate (MVA) pathway, which provides fundamental precursors for isoprenoid biosynthesis, such as isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) .

This domain is also found at the N-terminal end of Cis-3-hydroxy-L-proline dehydratase from Agrobacterium fabrum (LhpI), which catalyses the dehydration of cis-3-hydroxy-L-proline (c3LHyp) to Delta1-pyrroline-2-carboxylate (Pyr2C) .
V-type ATPase subunit E (ATPase_V1_Esu)
Type: Family

This entry represents subunit E from V-ATPases and A-ATPase/synthases. Subunit E appears to form a tight interaction with subunit G, which together may act as stators to prevent certain subunits from rotating with the central rotary element, much in the same way as the F0 complex subunit B does in F-ATPases . In addition to its key role in stator structure, subunit E appears to have a role in mediating interactions with putative regulatory subunits .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

The V-ATPases (or V1V0-ATPase) and A-ATPases (or A1A0-ATPase) are each composed of two linked complexes: the V1 or A1 complex contains the catalytic core that hydrolyses/synthesizes ATP, and the V0 or A0 complex that forms the membrane-spanning pore. The V-ATPase folding, localisation, and stability is made possible through the formation of a luminal glycan coat by the glycolipids and the glycosylated V0 subunits . The V- and A-ATPases both contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis . The V- and A-ATPases more closely resemble one another in subunit structure than they do the F-ATPases, although the function of A-ATPases is closer to that of F-ATPases.

A-type ATPases (archaeal-type ATPases) and V-ATPases, all included in this entry, are thought to have evolved from common ancestral genes .
ATPase, V0 complex, C/D subunit (ATPase_V0-cplx_csu/dsu)
Type: Family

This entry represents subunits C and D from the V0 complex of V-ATPases. There is more than one type of D subunit in V-ATPases, where the D1 subunit is ubiquitous, while the D2 subunit has limited tissue expressivity, possibly to account for differential functions, targeting or regulation of V-ATPase activity .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

The V-ATPases (or V1V0-ATPase) and A-ATPases (or A1A0-ATPase) are each composed of two linked complexes: the V1 or A1 complex contains the catalytic core that hydrolyses/synthesizes ATP, and the V0 or A0 complex that forms the membrane-spanning pore. The V-ATPase folding, localisation, and stability is made possible through the formation of a luminal glycan coat by the glycolipids and the glycosylated V0 subunits . The V- and A-ATPases both contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis . The V- and A-ATPases more closely resemble one another in subunit structure than they do the F-ATPases, although the function of A-ATPases is closer to that of F-ATPases.
F420-dependent methylenetetrahydromethanopterin dehydrogenase (MTD)
Type: Family

This archaeal enzyme family is involved in formation of methane from carbon dioxide

. The enzyme requires coenzyme F420 .
tRNA ribose 2'-O-methyltransferase, aTrm56 (tRNA_mtfrase_aTrm56)
Type: Family

This entry represents tRNA ribose 2'-O-methyltransferase aTrm56, which specifically catalyses the AdoMet-dependent 2'-O-ribose methylation of cytidine at position 56 in tRNAs.

The crystal structure of Pyrococcus horikoshii aTrm56 complexed with S-adenosyl-L-methionine has been determined to 2.48 A resolution. aTrm56 consists of the SPOUT domain, which contains the characteristic deep trefoil knot, and a unique C-terminal β-hairpin .

A conserved cytidine at position 56 of tRNA contributes to the maintenance of the L-shaped tertiary structure. aTrm56 catalyses the 2'-O-methylation of the cytidine residue in archaeal tRNA, using S-adenosyl-L-methionine. Biochemical assays showed that aTrm56 forms a dimer and prefers the L-shaped tRNA to the lambda form as its substrate .
NrpR regulatory domain (NRD)
Type: Domain

NrpR is an transcriptional repressor of nitrogen assimilation genes found primarily in Euryarchaeota . In the thermophilic archaeon Methanocaldococcus jannaschii it consists of a putative N-terminal winged helix-turn-helix (wHTH) domain used for DNA binding followed by two NrpR regulatory domains (NRD1 and NRD2) that sense and bind 2-oxoglutarate . In different organisms, NrpR proteins can vary on how many NrpR regulatory domains they contain and in their configuration. They can contain two NrpR domains, or one NrpR domain with or without the N-terminal HTH motif .
Coenzyme F420:L-glutamate ligase-like domain (F420-0_gamma-glut_ligase-dom)
Type: Domain

This entry represents a domain found in the coenzyme F420:L-glutamate ligase (also known as F420-0:gamma-glutamyl ligase) and related proteins. Coenzyme F420:L-glutamate ligase catalyses the GTP-dependent successive addition of multiple gamma-linked L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form polyglutamated F420 derivatives .
Translin family (Translin_fam)
Type: Family

Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-stranded DNA ends generated by staggered breaks occuring at recombination hot spots . Translin folds into an α-α superhelix, consisting of two curved layers of α/α topology .

This entry also includes translin-associated protein X (TRAX), which was found to interact with translin .
Protein of unknown function DUF131 (DUF131)
Type: Family

This archaebacterial protein family has no known function. The proteins are predicted to contain two transmembrane helices.
PIN family, putative toxin-antitoxin system toxin component (PIN_toxin-like)
Type: Family

This uncharacterised protein family, part of the PIN domain superfamily, is restricted to bacteria and archaea. A comprehensive in silico study of toxin-antitoxin systems finds evidence that this family represents the toxin-like component of one class of type 2 toxin-antitoxin systems.
Uncharacterised protein family UPF0251 (UPF0251)
Type: Family

The bacterial and archaeal proteins in this family have no known function. A study suggests that some archaeal members may be G-quadruplex binding proteins .
Transcription initiation factor IIE subunit alpha, N-terminal (TFIIE_asu)
Type: Domain

This entry represents the conserved N-terminal region of eukaryotic TFIIE-alpha and proteins from archaebacteria (TFE) that are also presumed to be TFIIE-alpha subunits .

Initiation of eukaryotic mRNA transcription requires melting of promoter DNA with the help of the general transcription factors TFIIE and TFIIH. In higher eukaryotes, the general transcription factor TFIIE consists of two subunits: the large alpha subunit (

) and the small beta (

). TFIIE beta has been found to bind to the region where the promoter starts to open to be single-stranded upon transcription initiation by RNA polymerase II. The approximately 120-residue central core domain of TFIIE beta plays a role in double-stranded DNA binding of TFIIE .

The TFIIE β-central core DNA-binding domain consists of three helices with a β-hairpin at the C terminus, resembling the winged helix proteins. It shows a novel double-stranded DNA-binding activity where the DNA-binding surface locates on the opposite side to the previously reported winged helix motif by forming a positively charged furrow .
Phosphopantoate/pantothenate synthetase (PPS/PS)
Type: Family

Proteins in this family include pantothenate synthetase (

) from Methanosarcina mazei and 4-phosphopantoate--beta-alanine ligase, also known as phosphopantothenate synthetase, (

) from Pyrococcus kodakaraensis. Pantothenate synthetase catalyses the condensation of pantoate with beta-alanine in an ATP-dependent and ADP-producing reaction . 4-phosphopantoate--beta-alanine ligase catalyses the conversion of (R)-4-phosphopantoate and beta-alanine to 4'-phosphopantothenate in the CoA biosynthesis pathway. It cannot use (R)-pantoate as substrate and thus does not display pantothenate synthetase (PS) activity .
Zinc finger, CXXC-type (Znf_CXXC)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to non-methylated CpG dinucleotides. The domain is characterised by two CGXCXXC repeats. The RecQ helicase has a single repeat that also binds to zinc, but this has not been included in this family. The DNA binding interface has been identified by NMR .
PKD/REJ-like domain (PKD/REJ-like)
Type: Domain

The REJ (Receptor for Egg Jelly) domain is found in PKD1

and the sperm receptor for egg jelly

. The exact function of this domain is unknown. The domain is 600 amino acids long so is probably composed of multiple structural domains. There are six completely conserved cysteine residues that may form disulphide bridges. This region contains tandem PKD-like domains.

Sequence similarity between a region of the autosomal dominant polycystic kidney disease (ADPKD) protein, polycystin-1 and a sea urchin sperm glycoprotein involved in fertilization, the receptor for egg jelly (suREJ) has been known for some time. The suREJ protein binds the glycoprotein coat of the egg (egg jelly), triggering the acrosome reaction, which transforms the sperm into a fusogenic cell. The sequence similarity and expression pattern suggests that the predicted human PKDREJ protein is a mammalian equivalent of the suREJ protein and therefore may have a central role in human fertilization .
BNR repeat (BNR_rpt)
Type: Repeat

Members of this entry contain multiple BNR (bacterial neuraminidase repeat) repeats or Asp-boxes. The repeats are short, however the repeats are never found closer than 40 residues together suggesting that the repeat is structurally longer. These repeats are found in a variety of non-homologous proteins, including bacterial ribonucleases, sulphite oxidases, reelin, netrins, sialidases, neuraminidases, some lipoprotein receptors, and a variety of glycosyl hydrolases .
Reeler domain (Reeler_dom)
Type: Domain

The reeler or reelin domain is a ~170 amino acid module, which has been identified in the amino terminus of the extracellular matrix proteins reelin and F-spondin (renamed Spon1) . The reelin domain is found in association with other modules, such as the thrombospondin type I repeat (TSP1), the spondin domain, the fibronectin type III domain or the Kunitz trypsin protease inhibitor domain. Its function is not yet known .

Extracellular matrix (ECM) proteins play an important role in early cortical development, specifically in the formation of neural connections and in controlling the cyto-architecture of the central nervous system. The product of the reeler gene in mouse is reelin,a large extracellular protein secreted by pioneer neurons that coordinates cell positioning during neurodevelopment . F-spondin and mindin are a family of matrix-attached adhesion molecules that share structural similarities and overlapping domains of expression. Both F-spondin and mindin promote adhesion and outgrowth of hippocampal embryonic neurons and bind to a putative receptor(s) expressed on both hippocampal and sensory neurons .
Domain of unknown function DUF16 (DUF16)
Type: Domain

Proteins that contain this domain are of unknown function. It appears to be confined to proteins from Mycoplasma pneumoniae .
Acyl-ACP thioesterase, N-terminal hotdog domain (Acyl-ACP_thioesterase_NHD)
Type: Domain

This entry represents the N-terminal hotdog domain of various acyl-acyl carrier protein (ACP) thioesterases (TE) which terminate fatty acyl group extension via hydrolysing an acyl group on a fatty acid . These proteins usually contain of a pair of tandem HotDog domains. This entry represents the N-terminal one of the pair.
Maturase MatK (Maturase_MatK)
Type: Family

Group II introns are widespread in plant cell organelles . In vivo, most plant group II introns do not self-splice, but require the assistance of proteinaceous splicing factors, known as maturases. In higher plants, maturases are encoded for in the nuclear genes , but are otherwise encoded by organellar introns.

This entry represents maturase K, which is usually encoded in the trnK tRNA gene intron, and probably assists in splicing its own and other chloroplast group II introns.
IBR domain (IBR_dom)
Type: Domain

The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers. This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain . Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organisms. RBR family members play roles in protein quality control and can indirectly regulate transcription . Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease .

IBR domain is a cysteine-rich (C6HC) zinc finger domain that is present in Triad1, and which is conserved in other proteins encoded by various eukaryotes. The C6HC consensus pattern is:

C-x(4)-C-x(14-30)-C-x(1-4)-C-x(4)-C-x(2)-C-x(4)-H-x(4)-C

The C6HC zinc finger motif is the fourth family member of the zinc-binding RING, LIM, and LAP/PHD fingers. Strikingly, in most of the proteins the C6HC domain is flanked by two RING finger structures

. The novel C6HC motif has been called DRIL (double RING finger linked). The strong conservation of the larger tripartite TRIAD (twoRING fingers and DRIL) structure indicates that the three subdomains are functionally linked and identifies a novel class of proteins .