SII-SWORD/CoKE huggingface dataset:
Thermostable direct haemolysin, vibrio (Thermostable_hemolysn_vibrio)
Type: Family

Thermostable direct haemolysin (TDH) is considered an important virulence factor in Vibrio parahaemolyticus gastroenteritis and is a dimer composed of two identical subunit molecules of approximately 21kDa. The tetrameric form contains a central pore permitting entry and exit of water molecules. A number of biological properties have been attributed to TDH including haemolytic activity, enterotoxicity, cytotoxicity and cardiotoxicity .
Serine incorporator/TMS membrane protein (TDE1/TMS)
Type: Family

The serine incorporator/TMS membrane protein (TDE1/TMS) family include SERINC1-5 from mammals and its homologues membrane protein Tms1 from yeasts. Members in this family contain eleven transmembrane helices.

SERINC1-5 function in incorporating serine into membranes and facilitating the synthesis of two serine-derived lipids, phosphatidylserine and sphingolipids . SERINC3 (also known as TDE1) and SERINC5 are restriction factors required to restrict infectivity of lentiviruses, such as HIV-1; they act by inhibiting an early step of viral infection and they impair the penetration of the viral particle into the cytoplasm . SERINC3/5 are non-ATP-dependent, non-specific lipid transporters for phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine that functions as a scramblase that flips lipids in both directions across the membrane. Phospholipid scrambling results in HIV-1 surface exposure of phosphatidylserine and loss of membrane asymmetry, which leads to changes in HIV-1 Env conformation and loss of infectivity . SERINC3 is overexpressed in tumours .
Outer membrane protein transport protein (OMPP1/FadL/TodX) (OMPP1/FadL/TodX)
Type: Family

This family includes TodX from Pseudomonas putida (strain F1/ATCC 700007)

and TbuX from Burkholderia pickettii (Ralstonia pickettii) (Pseudomonas pickettii) PKO1

. These are membrane proteins of uncertain function that are involved in toluene catabolism. Related proteins involved in the degradation of similar aromatic hydrocarbons are also in this family, such as CymD

. This family also includes FadL involved in translocation of long-chain fatty acids across the outer membrane. It is also a receptor for the bacteriophage T2.
DOMON domain (DOMON_domain)
Type: Domain

The DOMON domain is an 110-125 residue long domain which has been identified in the physiologically important enzyme dopamine beta-monooxygenase and in several other secreted and transmembrane proteins from both plants and animals. It has been named after DOpamine beta-MOnooxygenase N-terminal domain. The DOMON domain can be found in one to four copies and in association with other domains, such as the Cu-ascorbate dependent monooxygenase domain, the epidermal growth factor domain, the trypsin inhibitor-like domain (TIL), the SEA domain and the Reelin domain . The DOMON domain may be involved in heme and sugar recognition .

The sequence conservation is predominantly centred around patches of hydrophobic residues. The secondary structure prediction of the DOMON domain points to an all-β-strand fold with seven or eight core strands supported by a buried core of conserved hydrophobic residues. There is a chraracteristic motif with two small positions (Gly or Ser) corresponding to a conserved turn immediately C-terminal to strand three. It has been proposed that the DOMON domain might form a β-sandwich structure, with the strands distributed into two β-sheets as is seen in many extracellular adhesion domains such as the immunoglobulin, fibronectin type III, cadherin and PKD domains .
Methyladenine glycosylase (Adenine_glyco)
Type: Family

This family of methyladenine glycosylases includes DNA-3-methyladenine glycosylase I (

) which acts as a base excision repair enzyme by severing the glycosylic bond of numerous damaged bases. The enzyme is constitutively expressed and is specific for the alkylated 3-methyladenine DNA .
Protein LIN-8 (LIN-8)
Type: Family

This entry represents a family of proteins found in Caenorhabditis called LIN-8, previously known as DUF278.

LIN-8 is a nuclear protein, present at the sites of transcriptional repressor complexes, which interacts with LIN-35 Rb. Lin35 Rb is a product of the class B synMuv gene lin-35 which silences genes required for vulval specification through chromatin modification and remodelling . The biological role of the interaction has not yet been determined however predictions have been made. The interaction shows that class A synMuv genes control vulval induction through the transcriptional regulation of gene expression. LIN-8 normally functions as part of a protein complex however when the complex is absent, other family members can partially replace LIN-8 activity.
Terminase large subunit-like (Terminase_largesu-like)
Type: Family

Terminase large subunit (TerL) from bacteriophages and evolutionarily related viruses, is an important component of the DNA packing machinery and comprises an ATPase domain, which powers DNA translocation and a nuclease domain that cuts concatemeric DNA . TerL forms pentamers in which the ATPase domains form a ring distal to the capsid. The ATPase domain contains a C-terminal subdomain that sits above the ATPase active site, called the "Lid subdomain" with reference to analogous lid subdomains found in other ATPases . It contains a hydrophobic patch (Trp and Tyr residues) that mediates critical interactions in the interface between adjacent ATPase subunits and assists the positioning of the arginine finger residue that catalyses ATP hydrolysis . The endonuclease cuts concatemeric DNA first in the initiation phase in a sequence specific site and later in the completion stage of the DNA packaging process when the capsid is full . Cryo-EM studies indicate that TerL forms a pentamer that binds to a dodecameric assembly called portal and attaches to the capsid. It has been proposed that nuclease domains form a radially arranged ring that is proximal to portal, playing a key role in pentamer assembly . The nuclease domain has a RNAse H-like fold and it has been proposed to utilise a two-metal catalysis mechanism like in other RNAse H-like endonucleases such as RNase H, transposases, retroviral integrases and RuvC Holliday junction resolvases . This entry also includes uncharacterised bacterial sequences.
Viral trans-activator protein (Pox_TAP)
Type: Family

This family of proteins function as a trans-activator of viral late genes.
Viral late protein H2 (Pox_LP_H2)
Type: Family

This entry represents the late protein H2 found in Vaccinia and other poxviruses. This protein is a highly conserved viral membrane protein found in all sequenced poxviruses, containing an N-terminal transmembrane domain and four conserved cysteines thought to be involved in the formation of intramolecular disulphide bonds . H2 has been shown to be necessary for entry into the host cell and virus-induced cell-cell fusion, but is not required for virus morphogenesis or the attachment of virus particles to cells. It is part of an entry-fusion complex composed of eight viral membrane proteins .
Snf7 family (Snf7_fam)
Type: Family

Snf7 family members are small coil-coiled proteins that share protein sequence similarity with budding yeast Snf7, which is part of the ESCRT-III complex that is required for endosome-mediated trafficking via multivesicular body (MVB) formation and sorting .

Proteins in this entry also includes human CHMPs (charged multivesicular body proteins), budding yeast Did4/Did2,
Arabidopsis
vacuolar protein sorting-associated proteins and the archaean
Sulfolobus acidocaldarius
cell division protein B which is a component required for cell division, forming polymers with segregating nucleoids .
NADPH-dependent FMN reductase-like domain (FMN_Rdtase-like_dom)
Type: Domain

This domain in found in several flavoproteins such as FMN-dependent NADPH-azoreductase, which catalyses the reductive cleavage of azo bond in aromatic azo compounds to the corresponding amines , and NAD(P)H:quinone oxidoreductase, which reduces quinones to the hydroquinone state to prevent interaction of the semiquinone with O2 and production of superoxide . In Arabidopsis NADPH:quinone oxidoreductase is involved in detoxification pathways . NAD(P)H:quinone oxidoreductase prefers NADH over NADPH, while FMN-dependent NADPH-azoreductase requires NADPH, but not NADH, as an electron donor for its activity.
SAPAP family (SAPAP)
Type: Family

This entry represents the SAPAP family, whose members include mars from fruit flies and disks large-associated proteins from vertebrates.

Mars binds to microtubules and protein phosphatase 1. It is involved in cell signalling, mitotic spindle organisation and regulation of mitotic cell cycle . It is essential for the early development of Drosophila embryos .
Glycosyl transferase, family 43 (Glyco_trans_43)
Type: Family

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Glycosyltransferase family 43

comprises enzymes with only one known activity: beta-glucuronyltransferase(GlcAT-I;

) .

GlcAT-I is a key enzyme involved in the initial steps of proteoglycan synthesis . GlcAT-I catalyzes the transfer of a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region of trisaccharide Gal-beta-(1-3)-Gal-beta-(1-4)-Xyl of proteoglycans. The enzyme has two subdomains that bind the donor and acceptor substrate separately . The active site is located at the cleft between both subdomains in which the trisaccharide molecule is oriented perpendicular to the UDP .
Herpesvirus intermediate/early protein 2/3 (Herpes_IE2_3)
Type: Domain

This domain of unknown function is found in the intermediate/early proteins of the Herpes virus. Many of these proteins play a role in transcriptional regulation.
Herpesvirus UL47 (Herpes_UL47)
Type: Family

The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred to collectively as VP13/14, which are believed to be differentially modified forms of the same protein. These proteins have been show to target to the nucleus. The function of this family is unknown but it contains a number of Herpesviridae proteins.
Herpesvirus leader protein (Herpes_LP)
Type: Domain

This entry contains Epstein-Barr virus EBNA-LP protein. It is a protein involved in latency whose function is not fully understood. The protein contains three domains, each of which contains conserved serine residues within conserved regions (CR1 to CR3). These regions are essential for the EBNA2 cooperativity function. The domains have a bipartite nuclear localisation signal and nuclear localisation of EBNA-LP is essential for EBNA2 cooperativity function. .
Coenzyme Q-binding protein COQ10, START domain (COQ10_START)
Type: Domain

This entry represents the START domain found in polyketide cylcases/dehydrases such as TcmN and in coenzyme Q-binding protein COQ10 . COQ10 is required for the function of coenzyme Q in the respiratory chain and has a steroidogenic acute regulatory protein-related lipid transfer (START) domain, known to bind specific lipids in other START domain family members .
YEATS (YEATS)
Type: Family

This family is named after YEATS (Yaf9, ENL, AF9, Taf14, and Sas5), an evolutionarily conserved module present in 4 proteins (ENL, AF9, GAS41, and YEATS2) in humans and 3 proteins (Sas5, Taf14, and Yaf9) in yeast. These proteins are found in major chromatin-remodeling and histone acetyl-transferase (HAT) complexes and implicated in regulation of chromatin structure, histone acetylation and deposition, gene transcription and DNA damage response. The YEATS domain, which as previously shown is found in a number of chromatin-associated proteins, has recently been shown to have the capacity to bind histone lysine acetylation . The ability of the YEATS domains of human AF9 and yeast Taf14 to recognise the histone mark H3K9ac, have shown that these proteins are members of the family of acetyllysine readers .
Dicer, dimerisation domain (Dicer_dimerisation)
Type: Domain

This entry represents the dimerisation domain in Dicer. It is essential for the activity of Dicer . It is a divergent double-stranded RNA-binding domain . The N-terminal α helix of this domain is in a different orientation to that found in canonical dsRNA-binding domains. This results in a change of charge distribution at the potential dsRNA-binding surface and in the N- and C-terminal of the domain being nearby . This domain has weak dsRNA-binding activity. It mediates heterodimerisation of Dicer proteins with their respective protein partners .

Dicer endoribonuclease plays a central role in short dsRNA-mediated post-transcriptional gene silencing. It cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs . Dicer shows two N-terminal helicase domains (

), a dimerisation domain (

), a platform domain (

), a PAZ domain (

), two RNase III a/b domains (

) and a dsRNA-binding domain in its C-terminal region (

).
Herpesvirus UL3 (Herpes_UL3)
Type: Family

Herpes simplex viruses are large DNA viruses, the genome of which encode approximately 80 genes. The UL3 gene of Human herpesvirus 2 (HHV-2) is predicted to encode a 233 amino acid protein with a molecular mass of 26kDa. Homologues of the UL3 protein are encoded only among alphaherpesviruses. The function of the UL3 protein of Herpes simplex viruses remains unknown but it is known to localize to the nucleus and is a phosphoprotein .
CBM21 (carbohydrate binding type-21) domain (CBM21_dom)
Type: Domain

The carbohydrate binding type-21 or CBM21 domain is a 90-130 amino acid carbohydrate binding domain. The domain is named after proteins classified in carbohydrate-binding module (CBM) family 21 and is sometimes called starch-binding domain (SBD) . The CBM21 domain occurs in several eukaryotic proteins implicated in glycogen metabolism. A glucoamylase active site region or alpha amylase catalytic domain can occur C-terminal to the CBM21 domain. The CBM21 domain of Rhizopus oryzae glucoamylase can bind to raw starch. Most conserved residues are located in a region with a length of 35 in the N-terminal part and in a 15-25 residue motif II at the C terminus of the domain .
Pre-mRNA-splicing factor 38 (PRP38)
Type: Family

Members of this family are related to the pre mRNA splicing factor PRP38 from yeast , therefore all the members of this family could be involved in splicing. This conserved region could be involved in RNA binding. The putative domain is about 180 amino acids in length. PRP38 is a unique component of the U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) particle and is necessary for an essential step late in spliceosome maturation .
Octapeptide repeat (Octapeptide)
Type: Repeat

This octapeptide repeat is found in several bacterial proteins, including immunoglobulin G-binding protein A from Staphylococcus. The function of this repeat is unknown.
Antirepressor protein, C-terminal (Ant_C)
Type: Domain

This entry represents the C-terminal domain of the antirepressor protein (Ant) from Enterobacteria phage P1. Prophages P1 and P7 exist as unit copy DNA plasmids in the bacterial cell. Maintenance of the prophage state requires the continuous expression of two repressors: (i) C1 is a protein which negatively regulates the expression of lytic genes including the C1 inactivator gene coi, and (ii) C4 is an antisense RNA which specifically inhibits the synthesis of an anti-repressor Ant.

This domain, also known as KilAC domain, may be a DNA-binding domain of the viral regulatory proteins .
Adenovirus E3B protein (Adeno_E3B)
Type: Family

Adenoviruses are medium-sized, non-enveloped viruses containing double-stranded DNA. They can cause a variety of diseases including pneumonia, cystitis, conjunctivitis and diarrhoea, all of which can be fatal to patients who are immunocompromised . These viruses have many mechanisms to evade the host immune response, including several proteins which are expressed as part of the early transcription unit 3 (E3) . One of the regions of E3, known as the E3B region, encodes three proteins known as 10.4K, 14.5K and 14.7K. Two of these proteins, 10.4K and 14.5K, form the RID complex (receptor internalisation and degradation) which protects the infected cell from host-induced lysis by clearing the the TNF and Fas receptors from the cell surface . Other receptors, such as the epidermal growth factor receptor, are also known to be cleared by RID .
TAL effector repeat (TAL_effector_rpt)
Type: Repeat

The proteins in this group bind to DNA. Each repeat binds to a base pair in a predictable way. The structure shows that each repeat is composed of two α helices .
Exportin-2, C-terminal (XPO2_C)
Type: Domain

Exportin-2, also known as CAS, is an export receptor for importin-alpha . It binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Exportin-2 mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm .

This entry represents the C-terminal domain of XPO2. Structural studies of its yeast homologue, Cse1, indicate that this domain binds to both the transport-orchestrating protein RanGTP and the cargo molecule that is being exported .
Protein of unknown function DUF282, Caenorhabditis species (DUF282_CAE_spp)
Type: Family

This family consists of proteins of unknown function found in Caenorhabditis species.
CDC50/LEM3 family (CDC50/LEM3_fam)
Type: Family

CDC50/LEM3 is a family of membrane proteins whose members include cell cycle control protein 50, alkylphosphocholine resistance protein LEM3, which is is required for phospholipid translocation across the plasma membrane in Saccharomyces cerevisiae , and several ALA-interacting subunits, which are plant proteins involved in lipid translocation and secretory vesicle formation . CDC50 (also known as P4-ATPase flippase complex beta subunit TMEM30A) is an accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. It is required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:CDC50A flippase complex, which may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). In complex with ATP8A1, may play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane .
Protein of unknown function DUF285 (DUF285)
Type: Family

This is a family proteins of unknown function which includes predicted surface proteins (often lipoproteins) from Listeria monocytogenes, Listeria innocua, Enterococcus faecalis (Streptococcus faecalis), Lactobacillus plantarum, Mycoplasma spp., Helicobacter hepaticus, and other species. Eukaryotic sequences are also included in this family. Many proteins contain a tandem peptide repeat sequence of 25 or 26 residues.
7TM GPCR, serpentine receptor class xa (Srxa) (7TM_GPCR_serpentine_rcpt_Srxa)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli . Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' . Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr . Many of these proteins have homologues in Caenorhabditis briggsae.

This entry represents serpentine receptor class xa (Srxa), from the Str superfamily .
Domain of unknown function DUF287 (DUF287)
Type: Domain

This is a domain is found predominantly in Arabidopsis proteins. Its function is unknown.
STELLO-like (STL-like)
Type: Family

Members of this family have been characterised in plants and named STELLO. STELLO1 and 2 from Arabidopsis are Golgi-localized proteins that can interact with cellulose synthase CesA and control cellulose quantity. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. STELLO1 and 2 are though to regulate CSC assembly in the plant Golgi apparatus. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen .

The role of the metazoan members of this family is not known.
Early nodulin 93 ENOD93 protein (Enod93)
Type: Family

The expression of early nodulin (ENOD) genes has been well characterised in several legume species. Based on their biochemical attributes and expression patterns, they are postulated to have roles in cell structure, in the control of nodule ontogeny by the degradation of Nod factor, and in carbon metabolism .
Herpesvirus UL46 (Herpes_UL46)
Type: Family

The UL46 protein (VP11/12) is produced in the late phase of Herpes virus infection in a manner highly dependent on viral DNA synthesis, and is mainly distributed at the edge of the nucleus in the cytoplasm. It is a tegument phosphoprotein reported to modulate the activity of UL48 (anti-TNF) protein.