SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF977 (DUF977)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Glycosyl hydrolase 94, supersandwich domain (Glyco_hydrolase_94_b-supersand)
Type: Domain

This entry represents a β-supersandwich domain found in the superfamily of enzymes referred to as GH94, formerly known as glycosyltransferase family GT36 .

Family 94 of glycoside hydrolases exclusively contains phosphorylases that cleave beta-glycosidic bonds. The substrate specificities found in this family are: cellobiose phosphorylase (

), cellodextrin phosphorylase (

), and N,N'-diacetyl chitobiose phosphorylase. Many members of this family contain two copies of the domain represented in this entry.
MtfA family (MtfA_fam)
Type: Family

Mlc titration factor A (MtfA, previously known as YeeI) is a transcription factor A that binds Mlc (make large colonies), itself a repressor of glucose and hence a protein important in regulation of the phosphoenolpyruvate:glucose-phosphotransferase (ptsG) system, the major glucose transporter in E. coli. Mlc is a repressor of ptsG, and MtfA is found to bind and inactivate Mlc with high affinity . The membrane-bound protein EIICBGlc encoded by the ptsG gene is the major glucose transporter in Escherichia coli. MtfA is found to be a glucose-regulated peptidase , whose activity is regulated by binding to Mlc available in the cytoplasm, which in turn has been released from EIICBGlc during times when no glucose is taken up. A physiologically relevant target for this peptidase is not yet known.
Protein of unknown function DUF982 (DUF982)
Type: Family

This family consists of several hypothetical proteins from Proteobacterial species. The function of this family is unknown.
tRNA-hydroxylase MiaE (tRNA-Hydrxlase_MiaE)
Type: Family

tRNA 2-(methylsulfanyl)-N(6)-isopentenyladenosine(37) hydroxylase (MiaE) is a nonheme diiron monooxygenase that catalyses the posttranscriptional allylic hydroxylation of a modified nucleoside in tRNA called 2-methylthio-N-6-isopentenyl adenosine (ms2i6A). ms2i6A is found at position 37, next to the anticodon at the 3' position in almost all eukaryotic and bacterial tRNA's that read codons beginning with uridine. The miaE gene is absent in Escherichia coli, a finding consistent with the absence of the hydroxylated derivative of ms2i6A in this species .
Queuosine precursor transporter QueT (QueT)
Type: Family

This family includes the queT gene encoding a hypothetical integral membrane protein with 5 predicted transmembrane regions. The queT genes in Firmicutes are often preceded by the PreQ1 (7-aminomethyl-7-deazaguanine) riboswitches of two distinct classes , suggesting involvement of the QueT transporters in uptake of a queuosine biosynthetic intermediate.
Anaerobic cobalt chelatase (Anaerobic_Co-chelatase)
Type: Family

This group, typified by Salmonella typhimurium CbiK, contains anaerobic cobalt chelatases that act in the anaerobic cobalamin biosynthesis pathway .

Cobalamin (vitamin B12) can be complexed with metal via ATP-dependent reactions (aerobic pathway) (e.g., in Pseudomonas denitrificans) or via ATP-independent reactions (anaerobic pathway) (e.g., in S. typhimurium) . The corresponding cobalt chelatases are not homologous. This group belongs to the class of ATP-independent, single-subunit chelatases that also includes distantly related protoporphyrin IX (PPIX) ferrochelatase (HemH) (Class II chelatases) . The structure of S. typhimurium CbiK shows that it has a remarkably similar topology to Bacillus subtilis ferrochelatase despite only weak sequence conservation . Both enzymes contain a histidine residue identified as the metal ion ligand, but CbiK contains a second histidine in place of the glutamic acid residue identified as a general base in PPIX ferrochelatase . Site-directed mutagenesis has confirmed a role for this histidine and a nearby glutamic acid in cobalt binding, modulating metal ion specificity as well as catalytic efficiency .

It should be noted that CysG and Met8p, which are multifunctional proteins associated with siroheme biosynthesis, include chelatase activity and can therefore be considered as the third class of chelatases . As with the class II chelatases, they do not require ATP for activity. However, they are not structurally similar to HemH or CbiK, and it is likely that they have arisen by the acquisition of a chelatase function within a dehydrogenase catalytic framework .
Urate oxidase N-terminal (Urate_ox_N)
Type: Domain

Cytochrome c urate oxidase (Uox) PuuD is involved in purine degradation. In contrast with soluble Uox it is a membrane protein with an 8-helix transmembrane N-terminal domain and a C-terminal cytochrome c .
ABC-2 transporter-like (ABC-2_transporter-like)
Type: Family

This entry represents a family that acts as the transmembrane domain (TMD) of ABC transporters . The family includes proteins responsible for the transport of herbicides .
DNA damage-inducible protein DinI-like (DNA_damage-inducible_DinI-like)
Type: Family

This family of short proteins includes DNA-damage-inducible protein I (DinI) and related proteins. The SOS response, a set of cellular phenomena exhibited by eubacteria, is initiated by various causes that include DNA damage-induced replication arrest, and is positively regulated by the co- protease activity of RecA. Escherichia coli DinI, a LexA-regulated SOS gene product, shuts off the initiation of the SOS response when overexpressed
in vivo
. Biochemical and genetic studies indicated that DinI physically interacts with RecA to inhibit its co-protease activity . The structure of DinI is known .
Satellite virus coat (Satellite_virus_coat)
Type: Family

This entry represents coat proteins found in several satellite viruses, including satellite panicum mosaic virus , satellite tobacco necrosis virus, and satellite St. Augustine decline virus. The coat proteins of satellite viruses consist of a β-sandwich jelly-roll fold, with usually eight strands making up the two sheets, although some members can have an extra 1-2 strands. The characteristic interaction between the domains of this fold allows the formation of five-fold and pseudo six-fold assemblies. Although the satellite virus coat proteins share the same jelly-roll fold, they differ in the arrangement of their secondary structural elements and in the interactions of adjacent subunits .
Protein of unknown function DUF991, YecM-like (DUF991_YecM-like)
Type: Family

This family incudes Protein YecM from Escherichia coli and similar proteins predominantly found in gammaproteobacteria. YecM shows a pseudo-twofold axis with eight β-strands forming a curved sheet that wraps around C-terminal α-helix and a presumed active site, forming a deep groove, and two α-helices on each side of the sheet. It may be a metal-binding protein and function as an enzyme, but its specific function is still unknown . Many members of this entry are predicted to belong to the vicinal oxygen chelate (VOC) superfamily .
5-nucleotidase (5-nucleotidase)
Type: Family

This family consists of both eukaryotic and prokaryotic 5'-nucleotidase sequences (

), including cytosolic 5'-nucleotidase 1A and 1B (NT5C1A/NT5C1B) from mammals. NT5C1A/NT5C1B dephosphorylate the 5' and 2'(3')-phosphates of deoxyribonucleotides and help to regulate adenosine levels .
Poxvirus A4L (Poxvirus_A4L)
Type: Family

This entry represents A4L from Vaccinia virus, also called 39kDa core protein OPG130 (p39), and similar proteins predominantly found in orthopoxvirus. A4L is a component of the virion core that participates in virion assembly .
Protein of unknown function DUF996 (DUF996)
Type: Family

This is a family of uncharacterised bacterial and archaeal proteins.
Protein of unknown function DUF997 (DUF997)
Type: Family

This is a family of predicted bacterial membrane protein with unknown function. This entry includes YhdT, an uncharacterised membrane protein from E. coli .
Tify domain (Tify_dom)
Type: Domain

The tify domain is a 36-amino acid domain only found among Embryophyta (land plants). It has been named after the most conserved amino acid pattern (TIF[F/Y]XG) it contains, but was previously known as the Zim domain. As the use of uppercase characters (TIFY) might imply that the domain is fully conserved across proteins, a lowercase lettering has been chosen in an attempt to highlight the reality of its natural variability.
PITH domain (PITH_dom)
Type: Domain

This entry represents the PITH domain (derived from Proteasome-Interacting THioredoxin). The protein Txnl1, which is a probable component of the 32kDa 26S proteasome, uses its C-terminal PITH domain to associate specifically with the 26S proteasome .

The PITH domain is dominated by a jelly roll β-sandwich structure. The β-sandwich is formed by face-to-face packing of two anti-parallel β-sheets. Another two-stranded β-sheet seals off one end of the β-barrel .
Glycogen debranching enzyme (AGL/Gdb1)
Type: Family

This family includes human glycogen branching enzyme AGL and yeast Gdb1 . This enzyme contains a number of distinct catalytic activities.
In Saccharomyces cerevisiae, Gdb1 is a multifunctional enzyme that acts as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation .
CCT domain (CCT_domain)
Type: Domain

The CCT (CONSTANS, CO-like, and TOC1) domain is a highly conserved basic module of ~43 amino acids, which is found near the C terminus of plant proteins often involved in light signal transduction. The CCT domain is found in association with other domains, such as the B-box zinc finger, the GATA-type zinc finger, the ZIM motif or the response regulatory domain. The CCT domain contains a putative nuclear localisation signal within the second half of the CCT motif and has been shown to be involved in nuclear localization and probably also has a role in protein-protein interaction .
Chromophore lyase CpcT/CpeT (CpcT/CpeT)
Type: Family

This entry represents the CpcT/CpeT biliprotein lyase, which has been shown to covalently attach chromophores to cystiene residue(s) of phycobiliproteins . These proteins contain a conserved motif PYR in the amino terminal half of the protein that may be functionally important. In the chromatically adapting cyanobacterium Fremyella diplosiphon, the proteins have been shown to be induced by green light, as part of the cpeCDESTR operon .
Cofactor of BRCA1 (COBRA1)
Type: Family

This family consists of several cofactor of BRCA1 (COBRA1) proteins (also known as negative elongation factor B). It is thought that COBRA1 along with BRCA1 is involved in chromatin unfolding. COBRA1 is recruited to the chromosome site by the first BRCT repeat of BRCA1, and is itself sufficient to induce chromatin unfolding. BRCA1 mutations that enhance chromatin unfolding also increase its affinity for, and recruitment of, COBRA1. It is thought that that reorganisation of higher levels of chromatin structure is an important regulated step in BRCA1-mediated nuclear functions .
Protein of unknown function DUF1003 (DUF1003)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Signaling lymphocytic activation molecule, N-terminal (Sig_lymph_act_molc_N)
Type: Domain

This entry is found in several mammalian signalling lymphocytic activation molecule (SLAM) proteins. Optimal T cell activation and expansion require engagement of the TCR plus co-stimulatory signals delivered through accessory molecules. SLAM, a 70kDa co-stimulatory molecule belonging to the Ig superfamily, is defined as a human cell surface molecule that mediates CD28-independent proliferation of human T cells and IFN-gamma production by human Th1 and Th2 clones . SLAM has also been recognised as a receptor for Measles virus .
Haemagglutinin-esterase glycoprotein, infectious salmon anaemia virus-type (Hemagglutn-estrase_ISAV-type)
Type: Family

This entry represents the haemagglutinin-esterase fusion glycoprotein (HEF) found specifically in infectious anaemia virus (ISAV), an orthomyxovirus-type virus that is an important fish pathogen in marine aquaculture . Other viruses, such as influenza C virus, coronaviruses and toroviruses, also contain surface HEF proteins, but whereas they usually bind 9-O-acetylsialic acid receptors, ISAV HEF appears to bind 4-O- acetylsialic acid receptors .
GAGA-binding transcriptional activator (GAGA-bd_tscrpt_act)
Type: Family

This family includes GAGA-binding protein protein (gbp) from Soybean that binds to GAGA element dinucleotide repeat DNA . It seems likely that the region which defines this family mediates DNA binding. This putative domain contains several conserved cysteines and a histidine suggesting this may be a zinc-binding DNA interaction domain.
Protein of unknown function DUF1005 (DUF1005)
Type: Family

This is a family of plant proteins with undetermined function.
Phage tail assembly chaperone Gp13-like (TAC_Gp13-like)
Type: Family

Tail assembly chaperones (TACs) are required for the morphogenesis of all long-tailed phages. Gp13, a TAC from bacteriophage HK97, is required for tail tube assembly and is thought to be a TAC. The gp13 monomer comprises a single domain consisting of a small three-stranded twisted β-sheet connected to a helical bundle. Gp13 adopts a spiral quaternary structure, similar to other TACs . This family includes gp13 and putative TACs from other Siphovirus.
Protein of unknown function DUF1007 (DUF1007)
Type: Family

This is a family of conserved bacterial proteins with unknown function.
Intracellular heme transport protein HutX-like (HutX-like)
Type: Family

This entry represents the homologues of intracellular heme transport protein HutX.

HutX is a member of the conserved heme utilization operon from pathogenic E. coli, and includes ChuS, HutX, HuvX, HugX, and ShuX in proteobacteria, among others. It forms a dimer which displays a very similar fold and organization to the monomeric structure of other heme utilization proteins such as HemS, ChuS, HmuS, PhuS; these latter occurring as duplicated domains. They all bind heme via a key conserved histidine. The genes encoded within these heme utilization operons enable the effective uptake and utilization of heme as an iron source in pathogenic microorganisms to enable multiplication and survival within hosts they invade .

In E. coli O157:H7, HutX forms a dimer with a very similar fold to the monomer structure of two other heme utilization proteins, ChuS and HemS, despite low sequence homology. ChuX has been shown to bind heme in a 1:1 manner, inferring that the ChuX homodimer could coordinate two heme molecules in contrast to only one heme molecule bound in ChuS and HemS .
Protein FRG1 (FRG1)
Type: Family

This entry represents Frg1 (FSHD region gene 1), a protein that is considered to be a candidate for facioscapulohumeral muscular dystrophy (FSHD). FSHD is a dominant neuromuscular disorder caused by deletions in a number of tandem repeat units (called D4Z4) located on chromosome 4q35. D4Z4 contains a transcriptional silencer whose deletion causes the over-expression in skeletal muscle of 4q35 genes, including Frg1 . Frg1 is localised to nucleoli and appears to be a component of the human spliceosome . When overexpressed, it binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila, inhibiting myogenesis as a result .
LpxI, C-terminal (LpxI_C)
Type: Domain

This entry represents the catalytic C-terminal domain of the LpxI enzyme that is involved in biosynthesis of lipid A. LpxI hydrolyzes the pyrophosphate bond of UDP-2,3-diacylglucosamine to form 2,3-diacylglucosamine 1-phosphate (lipid X) and UMP by catalyzing the attack of water at the beta-P atom .
Protein of unknown function DUF1010 (DUF1010)
Type: Family

This is a family of plasmid encoded proteins with unknown function.
Embryo-specific ATS3 (Embryo-specific_ATS3)
Type: Family

This is a family of plant seed-specific proteins identified in Arabidopsis thaliana (Mouse-ear cress). ATS3 (Arabidopsis thaliana seed gene 3) is expressed in a pattern similar to the Arabidopsis seed storage protein genes .
ECSIT (ECSIT)
Type: Family

Activation of NF-kappaB as a consequence of signalling through the Toll and IL-1 receptors is a major element of innate immune responses. ECSIT (Evolutionarily conserved signaling intermediate in Toll pathway) plays an important role in signalling to NF-kappaB, functioning as an adapter protein of the Toll-like and IL-1 receptor signalling pathway and an intermediary in the signalling pathways between TRAF-6 and MEKK-1 . It is part of the MCIA (mitochondrial complex I intermediate assembly) complex, involved in the assembly of mitochondrial complex I .
Carbon monoxide dehydrogenase subunit G (CO_DH_gsu)
Type: Family

The CO dehydrogenase structural genes coxMSL are flanked by nine accessory genes arranged as the cox gene cluster. The cox genes are specifically and coordinately transcribed under chemolithoautotrophic conditions in the presence of CO as carbon and energy source .
CASTOR/POLLUX/SYM8 ion channel, conserved domain (CASTOR/POLLUX/SYM8_dom)
Type: Domain

This entry represents a short region in the middle of proteins that belong to the CASTOR/POLLUX/SYM8 family of ion channels, which are found in plants. They have been implicated in modulating the nuclear membrane envelope potential . Proteins containing this domain also include uncharacterised bacterial proteins.
Transcriptional cell cycle regulator TrcR (TrcR)
Type: Family

This family represents a transcriptional cell cycle regulator (TrcR) found in Proteobacteria, mainly Alphaproteobacteria. TrcR associates with promoters and coding sequences in vivo in a rifampicin-dependent manner and interacts physically and genetically with RNA polymerase, resulting in the integration of cell cycle and antibiotic stress control with the general transcriptional machinery .
Coiled-coil domain-containing protein 124/Oxs1 (Ccdc124/Oxs1)
Type: Family

This entry includes coiled-coil domain-containing protein 124 (Ccdc124) from animals and Oxs1 from fission yeasts. Ccdc124 is a centrosome and midbody protein involved in cytokinesis . Oxs1 (SPBC29A10.12) is part of the Pap1-Oxs1 complex that regulates transcription when cells are exposed to diamide or Cd that causes disulfide stress .
Ookinete surface antigen, EGF domain (Pvs25/Psv28_EGF)
Type: Domain

Pvs25 and Pvs28 are expressed on the surface of ookinetes from several species of Plasmodium. These proteins are potential candidates for vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunised animals . The structure of these protein shows they are composed of four EGF domains .
Acetate kinase EutQ (EutQ)
Type: Family

The eut operon of Salmonella typhimurium encodes proteins involved in ethanolamine degradation and is essential during anoxic growth on ethanolamine and tetrathionate . EutQ is an acetate kinase necessary to drive flux through the pathway under physiological conditions, preventing a buildup of acetaldehyde. The ATP generated by EutQ may be used as a substrate for EutT, the ATP-dependent corrinoid adenosyltransferase, and for the EutA ethanolamine ammonia-lyase reactivase . Proteins in this family belong to the cupin superfamily with a conserved jelly roll-like β-barrel fold capable of homodimerization. In contrast to the metal-binding catalytic cupins, the EutQ family does not possess the histidine residues that are responsible for metal coordination in the oxidoreductase and epimerase classes of cupins .
Capsule biosynthesis GfcC-like, C-terminal (Caps_synth_GfcC-like_C)
Type: Domain

Many bacteria are covered in a layer of surface-associated polysaccharide called the capsule. These capsules can be divided into four groups depending upon the organisation of genes responsible for capsule assembly, the assembly pathway and regulation . This family plays a role in group 4 capsule biosynthesis . These proteins have a β-grasp fold . Two β-grasp domains, D2 and D3, are arranged in tandem. There is a C-terminal amphipathic helix which packs against D3. A helical hairpin insert in D2 binds to D3 and constrains its position, a conserved arginine residue at the end of this hairpin is essential for structural integrity . This is the C-terminal domain which covers D3 and D4 domains .
Trimethylamine methyltransferase (MTTB_MeTrfase)
Type: Family

This family consists of several trimethylamine methyltransferase (MTTB) proteins. This enzyme, which catalyses the transfer of a methyl group from trimethylamine to a trimethylamine-specific corrinoid protein (MttC), is involved in methanogenesis from trimethylamine .

This family also includes MtgB, a glycine betaine methyltransferase ; MtcB, which is involved in the degradation of the quaternary amine L-carnitine ; and MtpB, which is involved in the degradation of the quaternary amine L-proline betaine .
Domain of unknown function DUF1023 (DUF1023)
Type: Domain

This entry represents a domain found in uncharacterised proteins mainly from Actinobacteria. It covers the full length of the protein in some sequences such as MT0992 and is found associated with

in others like MT2140 from Mycobacterium tuberculosis. Computational analysis suggests that they may belong to the α-β hydrolase family of enzymes, as they are predicted to form the core secondary structures and catalytic machinery common to these proteins . Genomic context suggests that they may function as lipases, controlling the concentration of their putative phospholipid substrates.
Zincin-like metallopeptidase (Zincin_1)
Type: Family

This family of proteins has a conserved HEXXH motif, suggesting they are putative peptidases of zincin fold . The structure of this family is a minimal version of the metalloprotease fold (

).
Protein of unknown function DUF1028 (DUF1028)
Type: Family

This is a family of bacterial and archaeal proteins with unknown function.
Fascin (Fascin)
Type: Family

This entry represents fascin (FSCN) and its homologues, including FSCN1/2/3 from mammals and protein singed from fruit flies. Fascin is a globular actin cross-linking protein, which functions in forming parallel actin bundles in cell protrusions that are key specialisations of the plasma membrane for environmental guidance and cell migration . Human FSCN1 organises filamentous actin into bundles with a minimum of 4.1:1 actin/fascin ratio. Overexpression of fascin has been linked to a more aggressive clinical course of cancer .
RDD (RDD)
Type: Domain

This domain contains three highly conserved amino acids: one arginine and two aspartates, hence the name of RDD domain. This region contains two predicted transmembrane regions. The arginine occurs at the N terminus of the first helix and the first aspartate occurs in the middle of this helix. In Halobacillus andaensis, RDD has been shown to function as a Na+(Li+, K+)/H+ antiporter .
Plant specific eukaryotic initiation factor 4B (EIF-4B_pln)
Type: Family

This family consists of several plant specific eukaryotic initiation factor 4B proteins .
Protein of unknown function DUF1033 (DUF1033)
Type: Family

This family consists of several hypothetical bacterial proteins.
C5a peptidase/Subtilisin-like protease SBT2-like, Fn3-like domain (C5a/SBT2-like_Fn3)
Type: Domain

This is a Fn3-like domain found as the first of three on streptococcal C5a peptidase (SCP), a subtilisin-like, highly specific protease and adhesin/invasin that acts as an essential GAS virulence factor for the rapid dissemination of bacteria in soft tissues . This domain is also found at the C-terminal of subtilisin-like protease SBT2 from Arabidopsis and in PI-II-type proteinase.
Herpesvirus UL84 (Herpes_UL84)
Type: Family

This family consists of several Cytomegalovirus UL84 proteins. The open reading frame UL84 of human cytomegalovirus encodes a multifunctional regulatory protein which is required for viral DNA replication and binds with high affinity to the immediate-early transactivator IE2-p86 . This protein interacts with DNA sequences in oriLyt containing several CCAAT/enhancer binding protein (C/EBPα) transcription factor binding sites, which is essential for its amplification .