SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF1195 (DUF1195)
Type: Family

This family consists of several plant specific hypothetical proteins of around 160 residues in length. The function of this family is unknown.
Gp5, C-terminal (Gp5_C)
Type: Repeat

This repeat composes the C-terminal part of the Bacteriophage T4 baseplate protein Gp5. This region of the protein forms a needle like projection from the baseplate that is presumed to puncture the bacterial cell membrane. Structurally three copies of the repeated region trimerise to form a β solenoid type structure . This entry also includes repeats from some bacterial Vgr proteins.
Erythromycin biosynthesis protein CIII-like, C-terminal domain (EryCIII-like_C)
Type: Domain

This entry represents the conserved C-terminal domain found in Erythromycin biosynthesis protein CIII (EryCIII) from Saccharopolyspora erythraea, also known as 3-alpha-mycarosylerythronolide B desosaminyl transferase, and similar bacterial proteins. EryCIII is organised into two domains, both of them with a Rossmann-like α/β fold. This domain contains the nucleotide disphospho-sugar (NDP-sugar) binding site .
3D domain (3D_dom)
Type: Domain

This short presumed domain contains three conserved aspartate residues, hence the name 3D. This conservation is suggestive of a cation binding function. The central aspartate is found in a DTG motif that is suggestive of a peptidase like active site.
Pescadillo (PES)
Type: Family

Pescadillo (PES) protein was first identified as an essential protein for zebrafish embryonic development . It is conserved from yeasts to humans. Pescadillo homologues are involved in embryonic development and ribosome biogenesis . It has been linked to chromosomal instability and cancer .
RAD3-like helicase, DEAD (RAD3-like_helicase_DEAD)
Type: Domain

This domain is found in the RAD3-like DNA-binding helicase Regulator of telomere elongation helicase 1 homolog from Drosophila melanogaster (Rtel1), General transcription and DNA repair factor IIH helicase subunit XPD from Saccharomyces cerevisiae (RAD3) and similar proteins that are seemingly ubiquitous, including members of eukaryotic, bacterial and archaeal origin.

Regulator of telomere elongation helicase 1 (Rtel1) is the animal functional analogue of yeast Srs2, which is a DNA helicase and DNA-dependent ATPase involved in DNA repair and checkpoint recovery . Rtel1 is an essential DNA helicase that disassembles a variety of DNA secondary structures to facilitate DNA replication, repair, and recombination processes, and to maintain both telomeric and genomic stability . It is recruited by Trf2 to telomeres in S phase to promote T-Loop unwinding . It is also required for the export and the correct cytoplasmic trafficking of the small nuclear (sn) RNA pre-U2, a component of the major spliceosome complex . Human Rtel1 is implicated in the etiology of Dyskeratosis congenital (DC, is an inherited bone marrow failure and cancer predisposition syndrome) . Point mutations in its helicase domains, and truncations which result in loss of its C terminus have been discovered in DC families. It acts as anti-recombinase and antagonises homologous recombination by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis . Rtel1 is also a candidate gene influencing glioma susceptibility .

RAD3 is involved in nucleotide excision repair, and forms part of the transcription factor TFIIH in yeast .
Herpesvirus UL97 (Herpes_UL97)
Type: Domain

The gene product form the gene UL97 is a serine/threonine kinase. Although it can phosphorylates the antiviral drug ganciclovir , its biological function is the phosphorylation of its natural viral and cellular protein substrates which affect viral replication at many levels.
Endosomal/lysosomal proton channel TMEM175-like (TMEM175-like)
Type: Family

In animals, TMEM175 is an organelle-specific proton channel that catalyses proton efflux from endosomes and lysosomes to maintain a steady-state pH . It may also act as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes , however, this activity in unclear in vivo.

This entry also includes TMEM175 homologues from bacteria and archaea.
Resuscitation-promoting factor, core lysozyme-like domain (RPF)
Type: Domain

Resuscitation-promoting factor (RPF) proteins, found in various (G+C)-rich Gram-positive bacteria, act to reactivate cultures from stationary phase. This protein shares elements of the structural core of lysozyme and related proteins. Furthermore, it shares a conserved active site glutamate which is required for activity, and has a polysaccharide binding cleft that corresponds to the peptidoglycan binding cleft of lysozyme. Muralytic activity of Rpf in Micrococcus luteus correlates with resuscitation, supporting a mechanism dependent on cleavage of peptidoglycan by RPF .
Threonine/serine exporter-like, N-terminal domain (ThrE-like_N)
Type: Domain

This entry represents a domain found in ThrE family members, found in bacteria, fungi and some archaeal species. ThrE is a family of proteins that catalyse the export of L-threonine from the cell .

has been characterised as being necessary for this export. The domain exhibits 10 putative TMs and catalyses the proton-motive-force-dependent efflux of threonine and serine .
Beta-propeller repeat (SBBP_repeat)
Type: Repeat

This family is related to

and is likely to also form a β-propeller. SBBP stands for Seven Bladed Beta Propeller.
Domain of unknown function DUF1214 (DUF1214)
Type: Domain

This entry represents the domain of unknown function that is found in the C-terminal region of a number of uncharacterised bacterial proteins, as well as in other proteins.
FAST kinase leucine-rich (FAST_Leu-rich)
Type: Domain

This entry represents a conserved region of eukaryotic Fas-activated serine/threonine (FAST) kinases that contains several conserved leucine residues. This domain can be found in the FASTK family members, including FASTK, FASTKD1, FASTKD2 and FASTKD5. FAST kinase has been shown to be rapidly activated during Fas-mediated apoptosis, when it phosphorylates TIA-1, a nuclear RNA-binding protein that has been implicated as an effector of apoptosis . However, a critical active site residues are not conserved within the family and their kinase activity has been questioned .
Type VI secretion system IcmF, C-terminal (IcmF_C)
Type: Domain

This entry represents a conserved region situated towards the C-terminal end of IcmF-like proteins. IcmF was thought to be involved in Vibrio cholerae cell surface reorganisation that results in increased adherence to epithelial cells leading to an increased conjugation frequency . IcmF as a whole interacts with DotU whereby these bind tightly and form the docking area of the T6SS within the inner membrane. The exact function of this domain is not clear .
KaiC domain (KaiC_dom)
Type: Domain

This entry represents a domain found in bacterial proteins related to Circadian clock oscillator protein KaiC and archaeal uncharacterised sequences belonging to the UPF0273 family. More than one copy is sometimes found in each protein in this group. KaiC is one of the Kai proteins among which direct protein-protein association may be a critical process in the generation of circadian rhythms in cyanobacteria . The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal in
Cyanobacteria. KaiC performs autophosphorylation and acts as its own transcriptional repressor.
CHCH (CHCH)
Type: Domain

A conserved motif was identified in the LOC118487 protein was called the CHCH motif. Alignment of this protein with related members showed the presence of three subgroups of proteins, which are called the S (Small), N (N-terminal extended) and C (C-terminal extended) subgroups. All three sub-groups of proteins have in common that they contain a predicted conserved [coiled coil 1]-[helix 1]-[coiled coil 2]-[helix 2] domain (CHCH domain). Within each helix of the CHCH domain, there are two cysteines present in a C-X9-C motif. The N-group contains an additional double helix domain, and each helix contains the C-X9-C motif. This family contains a number of characterised proteins: Cox19 protein -a nuclear gene of Saccharomyces cerevisiae, codes for an 11kDa protein (Cox19p) required for expression of cytochrome oxidase. Because cox19 mutants are able to synthesise the mitochondrial and nuclear gene products of cytochrome oxidase, Cox19p probably functions post-translationally during assembly of the enzyme. Cox19p is present in the cytoplasm and mitochondria, where it exists as a soluble intermembrane protein. This dual location is similar to what was previously reported for Cox17p, a low molecular weight copper protein thought to be required for maturation of the CuA centre of subunit 2 of cytochrome oxidase. Cox19p have four conserved potential metal ligands, these are three cysteines and one histidine. Mrp10 -belongs to the class of yeast mitochondrial ribosomal proteins that are essential for translation . Eukaryotic NADH-ubiquinone oxidoreductase 19kDa (NDUFA8) subunit . The CHCH domain was previously called DUF657 .
Protein of unknown function DUF1217 (DUF1217)
Type: Family

This family represents a conserved region that is found within bacterial proteins, most of which are hypothetical. Some members contain multiple copies.
Prepilin peptidase A24, N-terminal (Prepilin_pept_A24_N)
Type: Domain

This domain is found at the N terminus of the prepilin peptidases. Members included in this entry have been characterised as bifunctional , and this domain may contain the N-methylation activity ([ec:2.1.1.-]). It consists of an intracellular region between a pair of transmembrane sections. This region contains an invariant proline and four almost fully conserved cysteine residues which bind Zn, as described
for PilD from Pseudomonas aeruginosa (

) . These cysteines have been shown to be essential to the overall function of the enzyme .
Ethanolamine ammonia-lyase heavy chain (EutB)
Type: Family

This family consists of several bacterial ethanolamine ammonia-lyase heavy chain (EutB) (also known as ethanolamine ammonia lyase large subunit and ethanolamine ammonia-lyase alpha subunit) proteins. Ethanolamine ammonia-lyase is a bacterial enzyme that catalyses the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia. The enzyme consists of EutB and C (beta-subunit) subunits which form a trimer composed of the (α-β)2 dimer . EutB is organised in a (β/α)8 barrel which contains the active site.
Insect allergen-related (Ins_allergen)
Type: Family

This family exemplifies a case of novel gene evolution. The case in point is the arms-race between plants and their infective insective herbivores in the area of the glucosinolate-myrosinase system. Brassicas have developed the glucosinolate-myrosinase system as chemical defence mechanism against the insects, and consequently the insects have adapted to produce a detoxifying molecule, nitrile-specifier protein (NSP). NSP is present in the Pieris rapae (Cabbage white butterfly). NSP is structurally different from and has no amino acid homology to any known detoxifying enzymes, and it appears to have arisen by a process of domain and gene duplication of a sequence of unknown function that is widespread in insect species and referred to as insect-allergen-repeat protein. Thus this family is found either as a single domain or as a multiple repeat-domain .
Olduvai domain (Olduvai_dom)
Type: Domain

Proteins of the neuroblastoma breakpoint family (NBPF) contain a highly conserved domain of unknown function, which is known as NBPF, also known as Olduvai or DUF1220 . The NBPF/DUF1220 domain is present in multiple copies in NBPF proteins and once, with lower homology, in mammalian myomegalin, a protein localised in the Golgi/centrosomal area which functions as an anchor to localise components of the cyclic adenosine monophosphate-dependent pathway to this region. The implications of the resemblance of NBPF proteins to myomegalin remain obscure.

NBPF domains are typically built of two exons . The number of NBPF repeat copies is highly expanded in humans, reduced in African great apes, further reduced in orangutan and Old World monkeys, single-copy in nonprimate mammals, and absent in nonmammalian species. The NBPF domain that is found as a singly copy in nonprimate mammals is the likely ancestral domain. Studies suggest an association between NBPF/DUF1220 copy number and brain size, and more specifically neocortex volume . An association has been established between DUF1220 subtype CON1 copy number and autism severity , and between subtype CON2 copy number and cognitive function .
Domain of unknown function DUF1221 (DUF1221)
Type: Domain

This is a group of plant proteins, most of which are hypothetical and of unknown function. All members contain the

domain, suggesting that they may possess kinase activity.
Bacteriophage lambda, GpZ, minor tail (Phage_lambda_GpZ)
Type: Family

This family is represented by bacteriopage lambda GpZ, the minor tail protein. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Protein of unknown function DUF1223 (DUF1223)
Type: Family

This family consists of several hypothetical proteins of around 250 residues in length, which are found in both plants and bacteria. The function of this family is unknown.
Heparan sulphate 6-sulfotransferase/Protein-tyrosine sulfotransferase (Heparan_SO4-6-sulfoTrfase)
Type: Family

This family consists of several heparan sulphate 6-sulphotransferase (HS6ST) proteins. Heparan sulphate 6-O-sulphotransferase (HS6ST) catalyses the transfer of sulphate from adenosine 3'-phosphate, 5'-phosphosulphate to the 6th position of the N-sulphoglucosamine residue in heparan sulphate . This entry also includes protein-tyrosine sulfotransferase, which catalyses the O-sulfation of tyrosine residues within acidic motifs of polypeptides .
Class II hydrophobin (Class_II_hydrophobin)
Type: Family

This entry represents Class II hydrophobins and related fungal proteins, particularly ascomycetes.

Hydrophobins are small, moderately hydrophobic extracellular proteins characterised by eight cysteine residues arranged in a strictly conserved motif. They are typically found on the outer surface of conidia and the hyphal wall, where they are thought to mediate contact and communication between the fungus and its environment . The hydrophobin family includes proteins such as cryparin, a cell surface-associated hydrophobin secreted by filamentous fungi ; cerato-ulmin, a secreted toxin implicated in Dutch elm disease ; and trihydrophobin from Claviceps fusiformis, which self-assembles at hydrophilic-hydrophobic interfaces on the hyphal surface . Hydrophobins are broadly categorised into two classes based on their solubility and assembly properties. Class I hydrophobins form rodlet bundles that coat aerial cell surfaces and contribute to cellular hydrophobicity, supporting fungal growth, development, and dispersal. In contrast, Class II hydrophobins form highly ordered films at water-air interfaces via intermolecular interactions but do not form rodlet structures. Hyd1 is a class II hydrophobin that not only fulfils structural roles but also functions as an elicitor of induced systemic resistance (ISR) in plants. During interaction with maize, Hyd1 binds the host target protein UBL and recruits additional UBL proteins in the roots, triggering defence responses such as cell death and activation of brassinosteroid, jasmonate (JA), and ethylene (ET) signalling pathways .
Sif (Sif)
Type: Family

This family consists of several SifA and SifB and SseJ proteins. They are effector proteins function to alter host cell physiology and promote bacterial survival in host tissues.
SifA, SifB and SseJ have been demonstrated to localise to the Salmonella-containing vacuole (SCV) and to Salmonella-induced filaments (Sifs). Trafficking of SseJ and SifB away from the SCV requires the SPI-2 effector SifA. SseJ trafficking away from the SCV along Sifs is unnecessary for its virulence function .
Actin-rearrangement-inducing factor (Actin-rearrang-inducing_fac)
Type: Family

This family consists of several Nucleopolyhedrovirus actin-rearrangement-inducing factor (Arif-1) proteins. In response to Autographa californica nuclear polyhedrosis virus (AcMNPV) infection, a sequential rearrangement of the actin cytoskeleton occurs this is induced by Arif-1 . Arif-1 is tyrosine phosphorylated and is located at the plasma membrane as a component of the actin rearrangement-inducing complex .
Low temperature requirement A (Low_temperature_requirement_A)
Type: Family

This entry consists of several bacteria specific low temperature requirement A (LtrA) protein sequences which have been found to be essential for growth at low temperatures in Listeria monocytogenes . It also contains a number of uncharacterised fungal proteins.
Invasion protein B (Invasion_prot_B)
Type: Family

This family consists of several invasion associated locus B (IalB) proteins and related sequences. IalB is known to be a major virulence factor in Bartonella bacilliformis where it was shown to have a direct role in human erythrocyte parasitism. IalB is up-regulated in response to environmental cues signalling vector-to-host transmission. Such environmental cues would include, but not be limited to, temperature, pH, oxidative stress, and haemin limitation. It is also thought that IalB would aide B. bacilliformis survival under stress-inducing environmental conditions .
Helical and beta-bridge domain (HBB)
Type: Domain

HBB is the domain on DEAD-box eukaryotic DNA repair helicases ([ec:3.6.1.-]) that appears to be a unique fold. It's conformation is of α-helices 12-16 plus a short β-bridge to the FeS-cluster domain at the N-terminal. The full-length XPD protein verifies the presence of damage to DNA and allows DNA repair to proceed. XPD is an assembly of several domains to form a doughnut-shaped molecule that is able to separate two DNA strands and scan the DNA for damage. HBB helps to form the overall DNA-clamping architecture . This family represents a conserved region within a number of eukaryotic and prokaryotic DNA repair helicases ([ec:3.6.1.-]).
Heme-dependent peroxidase ChdC/CLD (ChdC/CLD)
Type: Family

Proteins in this family are heme-dependent peroxidases, including coproheme decarboxylase (ChdC, also known as HemQ) and chlorite dismutase (CLD). Coproheme decarboxylases (ChdC) catalyze the hydrogen peroxide-mediated conversion of coproheme to heme b . Its structure has been revealed . Chlorite dismutase catalyses the disproportionation of chlorite into chloride and oxygen .
Putative MFS transporter YjiJ (MFS_4)
Type: Family

This entry represents a group of putative bacterial membrane proteins which may be sugar transporters. Members carry twelve transmembrane regions which are characteristic of members of the major facilitator sugar-transporter superfamily.
Uncharacterised protein family UPF0257 (UPF0257)
Type: Family

This is a group of proteins of unknown function.
Uncharacterised protein family UPF0270 (UPF0270)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Nitrate/trimethylamine N-oxide reductase NapE/TorE (NapE_TorE)
Type: Family

This family consists of several bacterial periplasmic nitrate reductase NapE proteins. Seven genes, napKEFDABC, encoding the periplasmic nitrate reductase system were cloned from the denitrifying phototrophic bacterium Rhodobacter sphaeroides. NapE is thought to be a transmembrane protein .
PrkA, C-terminal domain (PrkA_C)
Type: Domain

This entry represents the C-terminal domain in PrkA proteins.

ATP-dependent protease PrkA proteins are bacterial and archaeal serine kinases, approximately 630 residues in length. They possesses the A-motif of nucleotide-binding proteins and exhibit distant homology to eukaryotic protein kinases .
Sugar transport protein (Sugar_transport)
Type: Family

This is a family of bacterial sugar transporters approximately 300 residues long. Members include glucose uptake proteins , ribose transport proteins, and several putative and hypothetical membrane proteins probably involved in sugar transport across bacterial membranes.
Domain of unknown function DUF1232 (DUF1232)
Type: Domain

This domain can be found in RNF170 from eukaryotes and some uncharacterised proteins from bacteria and archaea. RNF170 is an E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway .
NlpB/DapX lipoprotein (NlpB/DapX)
Type: Family

This entry consists of a number of bacterial lipoproteins often known as NlpB or DapX. This lipoprotein is detected in outer membrane vesicles in Escherichia coli and appears to be non-essential .
Bacteriophage lambda tail assembly I (Phage_lambda_tail_I)
Type: Family

This family consists of several Bacteriophage lambda tail assembly protein I and related phage and bacterial sequences . Members of this family are typically around 200 residues in length.
Clp1, C-terminal (Clp1_C)
Type: Domain

This entry represents the C-terminal domain of Clp1.

Polyribonucleotide 5-hydroxyl-kinase Clp1 is a component of the cleavage factor IA (CF IA) complex, which is involved in the endonucleolytic cleavage during polyadenylation-dependent pre-mRNA 3'-end formation . It is involved in both the endonucleolyitc cleavage and polyadenylation steps of mRNA 3'-end maturation . Human Clp1 can also function as a tRNA splicing enzyme . In human, mutations in Clp1 affect tRNA biogenesis and lead to impairment of both peripheral and central nervous system function, causing severe motor-sensory defects, cortical dysgenesis and microcephaly . Clp1 contains three domains, a small N-terminal β sandwich domain involved in DNA binding , a C-terminal domain containing a novel α/β-fold and a central domain that binds ATP .
TRAP C4-dicarboxylate transport system permease DctM subunit (DctM)
Type: Domain

This entry represents the transmembrane segments from a diverse range of transporter proteins from the tripartite ATP-independent periplasmic (TRAP) transport system, in which the driving force for solute accumulation is an electrochemical ion gradient and not ATP hydrolysis . The first TRAP transporter to be characterised was the high-affinity C4-dicarboxylate transport (Dct) system from
Rhodobacter capsulatus which consists of ESR (DctP) and small (DctQ) and large (DctM) integral membrane proteins . In general, C4-dicarboxylate transport systems allow C4-dicarboxylates like succinate, fumarate, and malate to be taken up. TRAP C4-dicarboxylate carriers are secondary carriers that use an electrochemical H+ gradient as the driving force for transport. DctM is an integral membrane protein that is one of the constituents of TRAP carriers . This entry also includes SiaM and SiaT (involved in sialic acid uptake) and YiaN (involved in the uptake of 2,3-diketo-L-gulonate) .
ImpA, N-terminal (ImpA_N)
Type: Domain

This entry represents a conserved region located towards the N-terminal end of ImpA and related proteins. ImpA is an inner membrane protein, which has been suggested to be involved with proteins that are exported and associated with colony variations in Actinobacillus actinomycetemcomitans . Note that many members are hypothetical proteins.
Nodulin-like (Nodulin-like)
Type: Domain

This entry represents a conserved domain within plant nodulin-like proteins and a number of uncharacterised proteins.
Including this domain is the Arabidopsis thaliana protein NFD4 (Nuclear Fusion Defective 4) (

). NFD4 is required for karyogamy during female gametophyte development, when the two polar nuclei fuse to form the diploid central cell nucleus

.
Reverse transcriptase connection (RVT_connect)
Type: Domain

This domain is known as the connection domain. This domain lies between the thumb and palm domains .