SII-SWORD/CoKE huggingface dataset:
NlpE, C-terminal OB domain (NlpE_C)
Type: Domain

NlpE is a bacterial outer membrane lipoprotein that is necessary for signalling by the Cpx pathway . This pathway responds to cell envelope disturbances and increases the expression of periplasmic protein folding and degradation factors. While the molecular function of the NlpE protein is unknown, it may be involved in detecting bacterial adhesion to abiotic surfaces. In Escherichia coli and Salmonella typhi, NlpE is also known to confer copper tolerance in copper-sensitive strains of Escherichia coli, and may be involved in copper efflux and delivery of copper to copper-dependent enzymes . This domain is found at the C terminus of the NlpE protein .
Glycosyl hydrolase family 30, beta sandwich domain (GH30_C)
Type: Domain

This β-sandwich domain is found in proteins from the glycosyl hydrolase family 30.

Glycoside hydrolase family 30

comprises enzymes with only one known activity; glucosylceramidase (

).

Family 30 encompasses the mammalian glucosylceramidases. Human acid beta-glucosidase (D-glucosyl-N-acylsphingosine glucohydrolase),
cleaves the glucosidic bonds of glucosylceramide and synthetic beta-glucosides . Any one of over 50 different mutations in the gene of glucocerebrosidase have been found to affect activity of this hydrolase, producing variants of Gaucher disease, the most prevalent lysosomal storage disease .
Glycosyl hydrolase family 30, TIM-barrel domain (Glyco_hydro_30_TIM-barrel)
Type: Domain

This entry represents a TIM-barrel domain found in the glycosyl hydrolase family 30 members.

Glycoside hydrolase family 30

comprises enzymes with only one known activity; glucosylceramidase (

).

Family 30 encompasses the mammalian glucosylceramidases. Human acid beta-glucosidase (D-glucosyl-N-acylsphingosine glucohydrolase),
cleaves the glucosidic bonds of glucosylceramide and synthetic beta-glucosides . Any one of over 50 different mutations in the gene of glucocerebrosidase have been found to affect activity of this hydrolase, producing variants of Gaucher disease, the most prevalent lysosomal storage disease .
RecG, wedge domain (RecG_wedge)
Type: Domain

RecG is involved in the processing of stalled replication forks. This domain is found N-terminal in RecG. It is a DNA-binding domain that has an OB-fold with large elaborations .
Transcriptional regulator AbiEi antitoxin, N-terminal domain (AbiEi_3_N)
Type: Domain

AbiEi is the cognate antitoxin of the type IV toxin-antitoxin 'innate immunity' bacterial abortive infection (Abi) system that protects bacteria from the spread of a phage infection. The Abi system is activated upon infection with phage to abort the cell, thus preventing the spread of phage through viral replication. There are some 20 or more Abis, and they are predominantly plasmid-encoded lactococcal systems. TA (toxin-antitoxin) systems on plasmids function by killing cells that lose the plasmid upon division. AbiE phage resistance systems function as novel Type IV TAs and are widespread in bacteria and archaea .

AbiEi, a member of a widespread family of putative transcriptional regulators, has an N-terminal winged-helix-turn-helix domain that is required for repression of abiE transcription and an uncharacterised bi-functional C-terminal domain, which is necessary for transcriptional repression and sufficient for toxin neutralisation . This entry represents the N-terminal domain.
Protein of unknown function DUF5132 (DUF5132)
Type: Family

Proteins in this family are uncharacterised. A members of this family,

, has been identified as part of a gene cluster for the synthesis of Ansamitocin .
Protein of unknown function DUF5133 (DUF5133)
Type: Family

This is a family of uncharacterised proteins from Streptomyces.

from S. parvulus has been identified as part of a borrelidin synthesis genomic cluster. Borrelidin is a polyketide antibiotic .
Protein of unknown function DUF5134 (DUF5134)
Type: Family

Proteins in this family are uncharacterised, but have been identified as members of a gene cluster for the synthesis of the tetramic-acid antibiotic streptolydigin, which inhibits bacterial RNA polymerase (RNAP) .
Spirocyclase AveC-like (AveC-like)
Type: Family

AveC catalyzes the stereospecific spiroketalization of a dihydroxy-ketone polyketide intermediate in the biosynthetic pathway of Avermectin, a potent antiparasitic agent. Additionally, it has a unique dehydration activity that serves to determine the regiospecific saturation pattern for spiroketal diversity . MeiC, the counterpart in the biosynthesis of AVE-like meilingmycin, also has spirocyclase activity, but lacks the dehydratase activity.
Putative WW-binding domain and destruction box (WRNPLPNID)
Type: Domain

This short conserved region is a putative destruction-box, with its RxxLxxI sequence motif, though the homology is not absolute . The domain occurs on a number of tumourigenic proteins, on some RNA-binding proteins and serine-threonine regulatory proteins . The second less well-conserved motif, WITPS, is a potential WW domain ligand-binding motif for recruiting proteins to their substrates. WW domains bind tightly to short proline-containing peptides that are typically in regions of native disordered polypeptide, as this domain is as it lies between a PIN domain and a zinc-binding domain .
Cache 3/Cache 2 fusion domain (Cache_3-Cache_2)
Type: Domain

Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.

This entry represents a type of Cache domain that likely originated as a fusion of sCache_3 and sCache_2 domains .
Single cache domain 3 (sCache_3)
Type: Domain

Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.

This entry represents the single cache domain 3 (sCache_3) .
CSN8/PSMD8/EIF3K (CSN8_PSD8_EIF3K)
Type: Domain

This domain is conserved from fungi, plants to humans. It is a signature protein motif found in components of CSN (COP9 signalosome) where it functions as a structural scaffold for subunit-subunit interactions within the complex and is a key regulator of photomorphogenic development . It is found in Eukaryotic translation initiation factor 3 subunit K, a component of the eukaryotic translation initiation factor 3 (eIF-3) complex required for the initiation of protein synthesis . It is also found in 26S proteasome non-ATPase regulatory subunit 8 (PSMD8), a regulatory subunit of the 26S proteasome .
Cornichon, conserved site (Cornichon_conserved)
Type: Conserved_site

The drosophila cornichon protein (gene: cni), the founding member of this family, is an integral component of the COPII-coated vesicles that mediate cargo export from the yeast endoplasmic reticulum (ER) . It is required in the germline for dorsal-ventral signalling. The dorsal-ventral pattern formation involves a reorganisation of the microtubule network correlated with the movement of the oocyte nucleus, and depending on the initial correct establishment of the anterior-posterior axis via a signal from the oocyte produced by cornichon and gurken and received by torpedo protein in the follicle cells .
Tesmin/TSO1-like CXC domain (Tesmin/TSO1-like_CXC)
Type: Domain

This entry represents a CXC domain found in proteins such as Tesmin

and TSO1

. These proteins have two copies of a cysteine rich motif as follows: C-X-C-X4-C-X3-YC-X-C-X6-C-X3-C-X-C-X2-C.
Metaxin, glutathione S-transferase domain (Metaxin_GST)
Type: Domain

This entry represents a conserved glutathione S-transferase (GST) domain present in metaxins and failed axon connections (FAX). Metaxin is a mitochondrial outer membrane protein, which is involved in transport of proteins into the mitochondrion . FAX may play a role in axonal development .
CYTH-like domain superfamily (CYTH-like_dom_sf)
Type: Homologous_superfamily

The bacterial CyaB like adenylyl cyclase and the mammalian thiamine triphosphatases (ThTPases) define a superfamily of catalytic domains called the CYTH (CyaB, thiamine triphosphatase) domain that is present in all three superkingdoms of life . Proteins containing this domain act on triphosphorylated substrates and require at least one divalent metal cation for catalysis .

The catalytic core of the CYTH domain is predicted to contain an α/β scaffold with 6 conserved β-strands and 6 conserved α-helices. The CYTH domains contains several nearly universally conserved charged residues that are likely to form the active site. The most prominent of these are an EXEXK motif associated with strand-1 of the domain, two basic residues in helix-2, a K at the end of strand 3, an E in strand 4, a basic residue in helix-4, a D at the end of strand 5 and two acidic residues (typically glutamates) in strand 6. The presence of around 6 conserved acidic positions in the majority of the CYTH domains suggests that it coordinates two divalent metal ions. Both CyaB and ThTPase have been shown to require Mg(2) ions for their nucleotide cyclase and phosphatase activities. The four conserved basic residues in the CYTH domain are most probably involved in the binding of acidic phosphate moieties of their substrates. The conservation of these two sets of residues in the majority of CYTH domains suggests that most members of this group are likely to possess an activity dependent on two metal ions, with a preference
for nucleotides or related phosphate-moiety -bearing substrates. The proposed biochemical activity, and the arrangement of predicted strands in the primary structure of the CYTH domain imply that they may adopt a barrel or sandwich-like configuration, with metal ions and the substrates bound in the central cavity .

Protein containing a CYTH-like domain include the yeast RNA triphosphatase Cet1, whose active site is located within a topologically closed hydrophilic β-barrel (composed of 8 antiparallel β strands) known as the "triphosphate tunnel" . The superfamily including Cet-1-like RNA triphosphatases and all other CYTH proteins has been named Triphosphate Tunnel Metalloenzyme (TTM) .
Fatty acid kinase subunit A-like, C-terminal (FakA-like_C)
Type: Domain

This domain is found at the C-terminal of FakA (fatty acid subunit A) protein, which is part of the fatty acid kinase machinery . In the human pathogens Staphylococcus and Streptococcus, this system is used to scavenge host fatty acids. FakA is an ATP-binding subunit which interacts with varied FakB (fatty acid-binding protein) isoforms and synthesises acyl-phosphate from extracellular fatty acids [1]. FakA comprises three domains (FakA_N, FakA_M and FakA_C,

) and resembles an evolutionary mimic of the DhaK-DhaL kinase system. This entry represents FakA_C, which acts as a recipient of fatty acids transferred from FakB in the context of Fak activity .
DIRP domain (DIRP)
Type: Domain

DIRP (Domain in Rb-related Pathway) is postulated to be involved in the Rb-related pathway, which is encoded by multiple eukaryotic genomes and is present in proteins including lin-9 of Caenorhabditis elegans, aly of fruit fly and mustard weed. Studies of lin-9 and aly of fruit fly proteins containing DIRP suggest that this domain might be involved in development. Aly, lin-9, act in parallel to, or downstream of, activation of MAPK by the RTK-Ras signalling pathway .
Atos-like, C-terminal (Atos-like_C)
Type: Domain

This domain can be found in the C-terminal of Drosophila Atos and its homologues from mammals, Atos homologue protein A/B (ATOSA/B, formerly known as FAM241) and is referred to as the chromosome segregation domain . Atos is a transcriptional regulator that synchronizes transcriptional and translational programs to promote macrophage invasion of tissues. It induces transcriptional expression of metabolic enzymes as well as of the translational regulator pths/DDX47. With pths/DDX47, adjusts transcription and translation of a subset of OXPHOS genes to increase mitochondrial bioenergetics and allow macrophage tissue invasion .
Double Cache domain 1 (dCache_1)
Type: Domain

This entry represents double cache domain 1, which covers the last three strands from the membrane distal PAS-like domain, the first two strands of the membrane proximal domain, and the connecting elements between the two domains .

Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.
Single Cache domain 2 (sCache_2)
Type: Domain

Cache is an extracellular domain that is predicted to have a role in small-molecule recognition in a wide range of proteins, including the animal dihydropyridine-sensitive voltage-gated Ca2 channel alpha-2delta subunit, and various bacterial chemotaxis receptors. The name Cache comes from CAlcium channels and CHEmotaxis receptors.

This entry represents the single Cache domain 2 (sCache_2), which contains the long N-terminal helix domain .
Cell fusion protein Dni1/Fig1 (Dni1/Fig1)
Type: Family

This entry includes cell fusion protein Dni1 from fission yeasts and Fig1 from budding yeasts. Dni1 is a cell membrane protein which plays a relevant role in coordinating membrane organization and cell wall remodeling during mating . Fig1 is a integral membrane protein that facilitates Ca2+ influx and cell fusion during mating of Saccharomyces cerevisiae .
BRCA2-interacting transcriptional repressor EMSY (EMSY)
Type: Family

EMSY was originally reported as a transcriptional repressor and breast cancer-associated protein that interacts with the BRCA2 protein . It contains an N-terminal ENT domain which can bind BRCA2. It is involved in DNA damage repair, genomic instability, and chromatin remodeling . EMSY can function as an integral component of an NIF-1 complex and play an important role in the regulation of nuclear receptor-mediated transcription . It is also part of the EMSY/KDM5A/SIN3B complex that may function as a transcriptional repressor .
Protein EMSY-LIKE, plant (EMSY-LIKE_plant)
Type: Family

This entry represents the EMSY-like proteins from plants. They contain an EMSY N-terminal (ENT) domain, a central Agenet domain, and a putative C-terminal coiled-coil structure. Arabidopsis EMSY-like proteins contribute to RPP7-mediated and basal immunity, especially against Hyaloperonospora arabidopsidis isolate Hiks1 .
E3 ubiquitin-protein ligase RBBP6 family (RBBP6)
Type: Family

RBBP6 interacts with both p53 and pRb and has been implicated in mRNA processing . It also acts as a E3 ubiquitin-protein ligase that interacts with YB-1 and ZBTB38, leading to ubiquitination of both proteins . It is involved in regulating DNA replication and common fragile site stability .

This family also includes the homologues from yeast Mpe1 and PARAQUAT TOLERANCE3 from Arabidopsis .
Leucine-rich PPR motif-containing protein (LRP130)
Type: Family

LRP130 is a pentatricopeptide motif protein that binds to mitochondrial and nuclear RNAs . It associates with mRNA/mRNP complexes at the outside of NE and ER, and plays a role in control of mRNA metabolism . It may be involved in mitochondrial RNA transcript stability, transcription termination, and RNA processing .
Probable E3 ubiquitin-protein ligase MID2, RING finger, HC subclass (MID2_HC-RING)
Type: Domain

MID2 shares high structural and functional similarities with MID1, an ubiquitin E3 ligase that regulates the turnover of microtubular protein phosphatase 2Ac. MID2 interacts with Astrin (a microtubule-organizing protein) and regulates Astrin levels to promote cell division . MID1 and MID2 may play roles in regulating tissue remodelling in early development .

Mutations in the MID2 gene lead to human X-linked intellectual disability (XLID) .

This entry represents the HC-RING finger found at the N-terminal of MID2.
Tripartite motif-containing protein 54, B-box-type 2 zinc finger (Trim54_Bbox2_Zfn)
Type: Domain

This entry represents the B-box-type 2 zinc finger of Trim54, which is characterised by a CHC3H2 zinc-binding consensus motif.

Tripartite motif-containing protein 54 (Trim54, also known as MuRF-3) is involved in the muscle growth and development . It serves as a regulator of the microtubule network of striated muscle cells . It can function as a E3 ubiquitin ligase in ubiquitin-mediated muscle protein turnover .
NUDE family (NUDE)
Type: Family

This entry includes nuclear distribution element 1 (NDE1) and NDE-like 1 (NDEL1). Human NDE1 and NDEL1 are believed to be evolved from a common ancestral gene, such as the NudE gene of Aspergillus nidulans. They share protein sequence and structure similarities and have overlapping functions in the cell and developing brain. They are essential for mitosis and neurodevelopment . They both interact with LIS1 through their N-terminal domain, and this interaction stimulates the movement of dynein. However, their expression and post-translational modification within the cell are different . This entry also includes Emericella nidulans NUDE, which is required for nuclear migration within hyphae during vegetative growth .
Mitochondrial ribonuclease P catalytic subunit, PIN domain (MRPP3_PIN_dom)
Type: Domain

MRPP3 is part of mitochondrial ribonuclease P (mt-RNase P) that cleaves tRNA molecules in their 5'-ends . In humans, mt-RNase P is composed of three protein subunits (MRPP1-3) and is only active as a tripartite complex. MRPP1 and MRPP2 deliver the pre-tRNA substrate and activate MRPP3 .

This entry represents the PIN (PilT N terminus) domain of MRPP3, which belongs to a large nuclease superfamily. Its active centre consists of three highly conserved catalytic residues which coordinate metal ions .
Gawky, RNA recognition motif (GW182_RRM)
Type: Domain

Protein Gawky (also known as GW182) plays a role in RNA-mediated gene silencing by micro-RNAs (miRNAs) . It is a component of cytoplasmic mRNA processing bodies required for early Drosophila development . GW182 interacts with AGO1, and this interaction is essential for silencing by miRNAs . It recruits the CCR4-NOT deadenylase complex through the interaction with PABPC1 .

This entry represents the C-terminal RNA recognition motif (RRM) of GW182.
Agglutinin-like protein (ALS)
Type: Family

This entry includes a group of cell surface adhesion proteins mostly from fungi, including ALS1-9 from Candida albicans and Sga1 from Saccharomyces cerevisiae. ALS1-7 plays an important role in the pathogenesis of C.albicans infections . Sga1 promotes cellular aggregation during mating .
USPL1 peptidase (USPL1)
Type: Family

The USPL1 peptidase (MEROPS identifier C98.001) is an isopeptidase that releases the SUMO protein from tagged proteins . USPL1 does not release ubiquitin from conjugates . USPL1 colocalizes with coilin in Cajal body . RNAi knockdown of USPL1 leads to disruption of Cajal bodies, relocalization of coilin to the nucleolus and impaired cell proliferation . These effects do not require USPL1 to be catalytically active, and further studies have shown that USPL1 plays a role in snRNA transcription by RNA polymerase II .

Cajal bodies are spherical sub-organelles of 0.3-1.0 micrometers in diameter found in the nucleus of proliferative cells such as embryonic and tumour cells, or metabolically active cells such as neurons, involved in small nuclear ribonucleoprotein (RNP) and spliceosomal small nuclear RNP biogenesis, maintenance of telomeres and processing of histone RNA.
E3 ubiquitin-protein ligase RNF146 (RNF146)
Type: Family

RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling . It contains an N-terminal RING domain followed by a WWE domain that binds iso-ADPr. RNF146 is a RING E3 ligase whose activities are regulated by non-covalent ligand binding .
Rho guanine nucleotide exchange factor Cdc24/Scd1, PH domain (Cdc24/Scd1_PH_dom)
Type: Domain

This entry represents the PH domain found in Cdc24 from budding yeasts and Scd1 from fission yeasts. Cdc24 and Scd1 are guanine nucleotide exchange factors (GEFs) for Cdc42 .
Protein TFG (TFG)
Type: Family

TFG (TRK-fused gene) is localised at endoplasmic reticulum (ER) exit sites and modulates ER export . It may function at the ER/ERGIC interface to locally concentrate COPII-coated transport carriers and link exit sites on the ER to ERGIC membranes . It is also an inhibitory regulator of the ubiquitin-proteasome system . Mutations in the TFG gene cause Okinawa hereditary motor and sensory neuropathy (HMSNO) and spastic paraplegia 57, autosomal recessive (SPG57) .
CARD8/ASC/NALP1, CARD domain (CARD8/ASC/NALP1_CARD)
Type: Domain

This entry represents the caspase activation and recruitment domain (CARD) found in a group of proteins, including ASC (apoptosis-associated speck-like protein containing a CARD), caspase recruitment domain-containing protein 8 (CARD8) and NALP1 (CARD7, NLRP1). CARD domain containing proteins are known to be important in the signalling pathways for apoptosis, inflammation and host-defense mechanisms .
DDX54/DBP10 family, DEAD-box helicase domain (DDX54/DBP10_DEAD-box_helicase)
Type: Domain

This group of DEAD-box RNA helicases includes Dbp10 from fungi and DDX54 (also known as DP97) from mammals. DDX54 interacts in a hormone-dependent manner with nuclear receptors . It plays an important role in central nervous system myelination . Dbp10 has a role in ribosome biogenesis .

This entry represents the DEAD-box helicase domain of DDX54 and similar eukaryotic proteins. This domain contains the ATP-binding region.
Receptor-type tyrosine-protein phosphatase-like N/N2 (IA-2/IA-2_beta)
Type: Family

This entry includes mammalian receptor-type tyrosine-protein phosphatase-like N and N2, also known as islet antigen 2/2 beta (IA-2 and IA-2 beta). They are dense core vesicle (DCV) transmembrane proteins that play a role in vesicle-mediated secretory processes. They are major autoantigens in type 1 diabetes and are required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation . This entry also includes Ida-1 from Caenorhabditis elegans .
Leu/Phe/Val dehydrogenases active site (Glu/Leu/Phe/Val_DH_AS)
Type: Active_site

Glutamate dehydrogenases (

,

, and

) (GluDH) are enzymes that catalyse the NAD- or NADP-dependent reversible deamination of glutamate into alpha-ketoglutarate . GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism.

Leucine dehydrogenase (

) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues .

Phenylalanine dehydrogenase (

) (PheDH) is a NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl- pyruvate .

Valine dehydrogenase (

) (ValDH) is a NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate .

These dehydrogenases are structurally and functionally related. A conserved lysine residue located in a glycine-rich region has been implicated in the catalytic mechanism. This entry represents the conserved region around this residue.