SII-SWORD/CoKE huggingface dataset:
Notch, NOD domain (Notch_NOD_dom)
Type: Domain

NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals . NOD (NOTCH protein domain) represents a region present in many NOTCH proteins and NOTCH homologues in multiple species such as 0, NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. Role of NOD domain remains to be elucidated.
Reverse transcriptase thumb (RVT_thumb)
Type: Domain

This domain is known as the thumb domain. It is composed of a four helix bundle . Reverse transcriptase converts the viral RNA genome into double-stranded viral DNA. Reverse transcriptase often occurs in a polyprotein; with integrase, ribonuclease H and/or protease, which is cleaved before the enzyme takes action. The impact of antiretroviral treatment on the first 400 amino acids of HIV reverse transcriptase is good. Little is known, however, of the antiretroviral drug impact on the C-terminal domains of Pol, which includes the thumb, connection and RNase H . Evidence suggests that these might be well conserved domains.
Serine hydrolase RBBP9/YdeN (RBBP9/YdeN)
Type: Family

This entry represents RBBP9 proteins. They contain a conserved serine hydrolase motif, GXSXG/A, where the serine is a putative nucleophile . They contain an α-β hydrolase fold . These proteins are implicated in the regulation of TGF-beta signalling, potentially acting as negative regulators by inhibiting the phosphorylation of SMAD2 and SMAD3. This action may contribute to the resistance against the growth-inhibitory effects of TGF-beta. They are also associated with the transformation process, where it can interact with RB1, leading to the displacement of E2F1 and thus affecting cell cycle progression. Additionally, the enzymatic activity of these proteins can be inhibited by emetine, a natural product from the ipecac root. Eukaryotic members of this family have a conserved LXCXE motif, which binds to retinoblastomas. This motif is absent from prokaryotic members of this family . This entry also includes Putative hydrolase YdeN.
Zinc finger, FPG/IleRS-type (Znf_FPG/IleRS)
Type: Domain

This entry represents a zinc finger domain found at the C-terminal in both DNA glycosylase/AP lyase enzymes and in isoleucyl tRNA synthetase. In these two types of enzymes, the C-terminal domain forms a zinc finger. Some related proteins may not bind zinc.

DNA glycosylase/AP lyase enzymes are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. These enzymes have both DNA glycosylase activity (

) and AP lyase activity (

) . Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity;

) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity;

). Fpg has a preference for oxidised purines, excising oxidised purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge . The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidised base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes . Fpg binds one ion of zinc at the C terminus, which contains four conserved and essential cysteines . Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidised pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine .
Lipopolysaccharide assembly, LptC-related (LipoPS_assembly_LptC-rel)
Type: Family

This family consists of several related groups of proteins, one of which is the LptC family. LptC is involved in lipopolysaccharide-assembly on the outer membrane of Gram-negative organisms . The lipopolysaccharide component of the outer bacterial membrane is transported form its source of origin to the outer membrane by a set of proteins constituting a transport machinery that is made up of LptA, LptB, LptC, LptD, LptE. LptC is located on the inner membrane side of the intermembrane space.
Protein of unknown function DUF1240 (DUF1240)
Type: Family

This family consists of a number of hypothetical putative membrane proteins which are mainly found in Photorhabdus and Yersinia species. The function of this family is unknown.
Zinc finger, GRF-type (Znf_GRF)
Type: Domain

This entry represents Glycine-arginine-phenylalanine (GRF)-type zinc fingers (GRF-ZFs), 45- to 50-residue domains with a conserved GRxF motif. GRF-ZFs are widely distributed throughout eukaryotes in proteins that are involved in DNA damage response (DDR), transcriptional regulation, and RNA metabolism. GRF-ZFs are nucleic acid interaction modules and in several cases these motifs have been shown to enhance enzymatic activity. Some members of this group of proteins are rRNA N6-adenosine-methyltransferase ZCCHC4, a 28S rRNA-specific N6-adenosine-methyltransferase; DNA-(apurinic or apyrimidinic site) endonuclease 2 (APE2, known as Apn2 in yeast); DNA topoisomerase 3 and Transcription termination factor 2 .

This domain comprises a three-stranded anti-parallel β-sheet that folds into a crescent-shaped claw-like structure (

). A single bound Zn(2+) ion plays a central structural role in this domain, and is coordinated with tetrahedral geometry by a "CHCC" sequence motif .

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.
Bacteriophage T4, Gp19, tail tube (Phage_T4_Gp19)
Type: Family

This family consists of several tail tube protein gp19 and gp3 from the T4-like viruses . The contractile tail of bacteriophage T4 consists of a contractile sheath, a tube and a baseplate. The central cylindrical segment of the tail consists of a rigid tube, composed of multiple copies of gp19, surrounded by the outer contractile sheath assembled from gp18 subunits . Gp3 plays an essential role in tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for the completion protein .
Disaggregatase-related domain (Disaggr-rel_dom)
Type: Domain

This entry describes a region often found in multiple copies in archaeal disaggregatase proteins . This region is also found in single copies in several hypothetical proteins from archaea and bacteria.
IMP biosynthesis enzyme PurP, N-terminal (IMP_biosynth_PurP_N)
Type: Domain

The last two steps of
de novo
purine biosynthesis are:

conversion of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-monophosphate (AICAR) to 5-formaminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-monophosphate (FAICAR)

conversion of FAICAR to inosine5'-monophopsphate (IMP)

In bacteria and eukaryotes, these steps are catalysed by the well-characterised bifunctional enzyme PurH . Archaea do not appear to posses PurH, however, and perform these reactions by a different mecahnism . In archaea, step i) is catalysed by the well-conserved PurP protein, while step ii) is catalysed by the PurO enzyme in some (though not all) species .

This entry represents the N-terminal domain of PurP. Its function is not known, though it is almost always found in association with

.
Protein of unknown function UPF0346 (UPF0346)
Type: Family

This family consists of several short hypothetical bacterial proteins of around 70 residues in length. The majority of the members of this family seem to all belong to the order Bacillales or Lactobacillales. The function of this family is unknown.
Nucleolar GTP-binding protein 1, Rossman-fold domain (NOG1_Rossman_fold_dom)
Type: Domain

This domain represents a conserved region of approximately 60 residues in length within nucleolar GTP-binding protein 1 (NOG1). The NOG1 family includes eukaryotic, bacterial and archaeal proteins. In Saccharomyces cerevisiae, the NOG1 gene has been shown to be essential for cell viability, suggesting that NOG1 may play an important role in nucleolar functions. In particular, NOG1 is believed to be functionally linked to ribosome biogenesis, which occurs in the nucleolus. In eukaryotes, NOG1 mutants were found to disrupt the biogenesis of the 60S ribosomal subunit .

The DRG and OBG proteins as well as the prokaryotic NOG-like proteins are homologous throughout their length to the amino half of eukaryotic NOG1, which contains the GTP binding motifs (

); the N-terminal GTP-binding motif is required for function.
RNA methyltransferase bin3, C-terminal (Bin3_C)
Type: Domain

This entry represents the C-terminal conserved region of the Drosophila probable RNA methyltransferase bin3 . Proteins containing this domain also include human pre-miRNA 5'-monophosphate methyltransferase BCDIN3D and 7SK snRNA methylphosphate capping enzyme MEPCE . This domain contains a conserved HLN motif.
Human herpes virus type 4, BALF1 (HHV-4_BALF1)
Type: Family

Epstein-Barr virus (strain GD1) (HHV-4), a human tumour DNA virus and a prominent member of gamma-herpesviruses, encodes homologues of cellular antiapoptotic viral Bcl-2 proteins BALF1 and BHRF1. They protect the virus from apoptosis in its host cell during virus synthesis . The virus infects B lymphocytes to establish a latent infection and yield proliferating, growth-transformed B cells in vitro. Bcl-2 genes are essential for the initial evasion of apoptosis which allows it to establish a latent infection or cause cellular transformation, or both .

Bcl-2 family proteins can inhibit or induce programmed cell death in part by counteracting the activity of other BCL-2 family members. BALF1, inhibits the antiapoptotic activity of EBV BHRF1 and of KSBcl-2 in several transfected cell lines. BALF1 fails, however, to inhibit the cellular BCL-2 family member, BCL-x(L). Thus, BALF1 acts as a negative regulator of the survival function of BHRF1, similar to the counterbalance observed between cellular BCL-2 family members .
U3 small nucleolar RNA-associated protein 25 (UTP25)
Type: Family

This family represents U3 small nucleolar RNA-associated protein 25 (UTP25), a DEAD-box RNA helicase-like protein component of the ribosomal small subunit processome for the biogenesis of ribosomes, which functions in pre-ribosomal RNA (pre-rRNA) processing. U3 small nucleolar RNA-associated protein 25 homologue (also known as Digestive organ expansion factor (DEF)) from animals is essential for embryonic development in part through the regulation of p53 pathway and controls the expansion growth of digestive organs and liver . It is though to be also involved in the sympathetic neuronal development. UTP25 mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 .

Protein NUCLEOLAR FACTOR 1 from Arabidopsis thaliana (Nof1) is also included in this group. This protein is involved in the control of rRNA expression, embryo development and female gametogenesis .
Domain of unknown function DUF1254 (DUF1254)
Type: Domain

This entry represents an immunoglobulin-like β-sandwich domain found in a group of hypothetical proteins of unknown function.
TraH-2 (TraH_2)
Type: Family

This family consists of several TraH proteins, which seem to be specific to Agrobacterium and Rhizobium species. This protein is thought to be involved in conjugal transfer but its function is unknown. This family does not appear to be related to

.
Plethodontid receptivity factor PRF/cardiotrophin-like (PRF/CT)
Type: Family

This family includes plethodontid receptivity factor (PRF) proteins which seem to be specific to Plethodon jordani (Jordan's salamander). PRF is a courtship pheromone produced by males increase female receptivity .

This family also includes cardiotrophin-2 (neuropoietin) and cardiotrophin-like cytokine factor 1 (CLCF1) from mammals, which share sequence similarity to PRF . They are four-helix bundle cytokines that signal through the gp130 receptor subunit .
Plant self-incompatibility response (SCRL)
Type: Family

This family consists of several plant self-incompatibility response (SCRL) proteins . The male component of the self-incompatibility response in Brassica has been shown to be encoded by the S locus cysteine-rich gene (SCR). SCR is related, at the sequence level, to the pollen coat protein (PCP) gene family whose members encode small, cysteine-rich proteins located in the proteo-lipidic surface layer (tryphine) of Brassica pollen grains .
Protein of unknown function DUF1262 (DUF1262)
Type: Family

This family represents a conserved region within a number of proteins of unknown function that seem to be specific to Arabidopsis thaliana. Note that some family members contain more than one copy of this region.
RNA polymerase II transcription factor SIII, subunit A (RNA_pol_II_trans_fac_SIII_A)
Type: Family

This family represents a conserved region within RNA polymerase II transcription factor SIII (Elongin) subunit A. In mammals, the Elongin complex activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin is a heterotrimer composed of A, B, and C subunits of 110, 18, and 15 kilodaltons, respectively. Subunit A has been shown to function as the transcriptionally active component of Elongin .
Domain of unknown function DUF1263 (DUF1263)
Type: Domain

This entry represents a conserved region located towards the C terminus of a number proteins of unknown function that seem to be specific to Oryza sativa.
Oil body-associated protein-like (OBAP-like)
Type: Family

This entry includes a group of oil body associated proteins (OBAPs) from plants and some uncharacterised proteins from fungi and bacteria. The plant obap proteins are predominantly expressed during embryo development and may be involved in the stability of oil bodies .
Putative stage IV sporulation YqfD (YqfD)
Type: Family

This family consists of several putative bacterial stage IV sporulation (SpoIV) proteins. YqfD of Bacillus subtilis (

) is known to be essential for efficient sporulation although its exact function is unknown .
Probable ECA polymerase WzyE (WzyE)
Type: Family

This family consists of several WzyE proteins, which may be involved in the polymerisation of enterobacterial common antigen (ECA) trisaccharide repeat units. It is required for the assembly of the phosphoglyceride-linked form of ECA (ECA(PG)) and the water-soluble cyclic form of ECA (ECA(CYC)) .
RTX iron-regulated FrpC (FrpC)
Type: Family

This family consists of several RTX iron-regulated FrpC proteins which appear to be found exclusively in Neisseria meningitidis. FrpC has been shown to be related to the RTX family of bacterial cytotoxins. FrpC is found in the meningococcal outer membrane. The function of this family is unknown although it is thought to be a virulence factor .
Divergent 4Fe-4S mono-cluster (Divergent_4Fe-4S_mono-cluster)
Type: Domain

Members of this family contain three highly conserved cysteine residues. This family includes proteins containing divergent domains which are most likely to bind to iron-sulfur clusters.
Uncharacterised protein family VirK (Uncharacterised_VirK)
Type: Family

This family consists of several bacterial VirK proteins of around 145 residues in length. The function of this family is unknown .
Fas apoptotic inhibitory molecule 1 (FAIM1)
Type: Family

FAIM1 (Fas apoptotic inhibitory molecule 1) plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells .
Protein of unknown function DUF1272 (DUF1272)
Type: Family

This family consists of several hypothetical bacterial proteins of around 80 residues in length. This family contains a number of conserved cysteine residues and its function is unknown.
YspA SLOG family (YspA)
Type: Family

Family in the SLOG superfamily showing fusions to NAD utilization and ADP-ribosylation domains including NUDIX, NADAR and MACRO. Members of this family are predicted to function as sensors of nucleotide, nucleotide-derived ligands, or nucleic acids, which are potentially processed/modified by the associating enzymes .
Protein of unknown function DUF1275 (DUF1275)
Type: Family

This family consists of several hypothetical bacterial proteins of around 200 residues in length. The function of this family is unknown although a few members are thought to be membrane proteins.
Periplasmic pectate lyase (Pectate_lyase_2)
Type: Family

This family consists of several Enterobacterial periplasmic pectate lyase proteins. A major virulence determinant of the plant-pathogenic enterobacterium Erwinia chrysanthemi is the production of pectate lyase enzymes that degrade plant cell walls .
Fatty acid cis-trans isomerase (Fatty_acid_cis-trans_isomerase)
Type: Family

This family consists of several fatty acid cis/trans isomerase proteins, which appear to be found exclusively in bacteria of the orders Vibrionales and Pseudomonadales. Cis/trans isomerase (CTI) catalyses the cis-trans isomerisation of esterified unsaturated fatty acids in phospholipids, mainly palmitoleic acid (C16:1) and cis-vaccenic acid (C18:1), in response to toxic organic solvents, heat and osmotic stress, and heavy metals
. The CTI protein is located in the periplasm and has been shown to be involved in solvent tolerance in Pseudomonas strains .
Protein of unknown function DUF1285 (DUF1285)
Type: Family

This family consists of several hypothetical bacterial proteins. The structure of some members has been solved but the function of this family is still unknown .
5'(3')-deoxyribonucleotidase (5'(3')-deoxyribonucleotidase)
Type: Family

This family consists of several 5' nucleotidase, deoxy (Pyrimidine), and cytosolic type C (NT5C) proteins. 5'(3')-deoxyribonucleotidase is a ubiquitous enzyme in mammalian cells whose physiological function is not known .
Protein of unknown function DUF1289 (DUF1289)
Type: Family

This family consists of a number of hypothetical bacterial proteins. The aligned region spans around 56 residues and contains 4 highly conserved cysteine residues towards the N terminus. The function of this family is unknown.
Group XII secretory phospholipase A2 precursor (PLA2G12)
Type: Family

This family consists of several group XII secretory phospholipase A2 precursor (PLA2G12) (

) proteins. Group XII and group V PLA(2)s are thought to participate in helper T cell immune response through release of immediate second signals and generation of downstream eicosanoids .
Arsenical-resistance operon trans-acting repressor ArsD (Arsenical-R_ArsD)
Type: Family

This family consists of several bacterial arsenical resistance operon trans-acting repressor ArsD proteins. ArsD is a trans-acting repressor of the arsRDABC operon that confers resistance to arsenicals and antimonials in Escherichia coli. It possesses two-pairs of vicinal cysteine residues, Cys(12)-Cys(13) and Cys(112)-Cys(113), that potentially form separate binding sites for the metalloids that trigger dissociation of ArsD from the operon. However, as a homodimer it has four vicinal cysteine pairs .
Xyloglucan endo-transglycosylase, C-terminal (XET_C)
Type: Domain

This entry represents the C terminus (approximately 60 residues) of plant xyloglucan endo-transglycosylases (XET). Xyloglucan is the predominant hemicellulose in the cell walls of most dicotyledons. With cellulose, it forms a network that strengthens the cell wall. XET catalyses the splitting of xyloglucan chains and the linking of the newly generated reducing end to the non-reducing end of another xyloglucan chain, thereby loosening the cell wall .
Coatomer, alpha subunit, C-terminal (Coatomer_asu_C)
Type: Domain

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .

This entry represents the C terminus (approximately 500 residues) of the eukaryotic coatomer alpha subunit . This domain is found along with the

domain.
RecQ helicase-like 5 (RECQ5)
Type: Domain

This entry represents a domain found in RECQ5. RecQ helicases is a group of highly conserved 3'-5' DNA helicases involved in maintaining genomic stability. RECQ5 plays an important role in DNA replication, transcription and repair . It interacts with RNA polymerase II to reduce transcription-associated replication impairment and recombination . As a helicase, it can disrupt RAD51 filaments assembled on ssDNA, thereby inhibiting homologous recombination . It also participates in psoralen-induced interstrand cross-link repair . It stimulates DNA decatenation mediated by TOP2A .
Protein of unknown function DUF1294 (DUF1294)
Type: Family

This family includes a number of hypothetical bacterial and archaeal proteins of unknown function.