SII-SWORD/CoKE huggingface dataset:
TraG, N-terminal, Proteobacteria (TraG_N_Proteobacteria)
Type: Domain

This domain is found in the N-terminal region of the TraG protein (

) from Escherichia coli. This is a membrane-spanning protein, with three predicted transmembrane segments and two periplasmic regions . The TraG protein is known to be essential for DNA transfer in the process of conjugation, with the N-terminal portion being required for F pilus assembly . The protein is thought to interact with the periplasmic domain of TraN (

) to stabilise mating-cell interactions .
Vitamin K epoxide reductase (VKOR)
Type: Domain

Vitamin K epoxide reductase (VKOR) recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a co-factor that is essential for the posttranslational γ-carboxylation of several blood coagulation factors . VKORC1, the catalytic subunit of the VKOR complex, is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea . Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner . In fact, in some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases . VKOR is part of a disulphide bond formation pathway that uses electrons from cysteines of newly synthesized proteins to reduce a quinone .
HicA mRNA interferase family (HicA_mRNA_interferase)
Type: Family

This entry represents the HicA mRNA interferase family, which form the toxic component of a toxin-antitoxin (TA) module . Family members contain a double-stranded RNA-binding domain and probably act as translation-independent mRNA interferases. They may form a complex with the antitoxin HicB which inhibits their mRNA interferase activity .
Zinc finger, AD-type (Znf_AD)
Type: Domain

The zinc finger-associated domain (Znf-AD domain, also known as ZAD), is found at the N terminus of the C2H2 proteins of many arthropods . In vertebrates, only one protein containing an N-terminal structure similar to the ZAD has been found, Zinc finger protein 276. This domain forms an atypical treble-cleft-like zinc co-ordinating fold. The Znf-AD domain is a protein-protein interaction module with the capability to form homodimers, but does not bind to DNA .

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.
Endoplasmic reticulum vesicle transporter, C-terminal (Erv_C)
Type: Domain

This entry represents the C-terminal domain of the endoplasmic reticulum vesicle transporter proteins.

Proteins included in this entry are conserved from plants and fungi to humans. Erv46 (ERGIC3) works in close conjunction with Erv41 (ERGIC2) and together they form a complex which cycles between the endoplasmic reticulum and Golgi complex. Erv46-41 interacts strongly with the endoplasmic reticulum glucosidase II. Mammalian glucosidase II comprises a catalytic alpha-subunit and a 58kDa beta subunit, which is required for ER localisation. All proteins identified biochemically as Erv41p-Erv46p interactors are localised to the early secretory pathway and are involved in protein maturation and processing in the ER and/or sorting into COPII vesicles for transport to the Golgi .

Proteins containing this domain also include disulfide isomerase (PDI)-C subfamily members from Arabidopsis. They are chimeric proteins containing the thioredoxin (Trx) domain of PDIs, and the conserved N- and C-terminal domains of Erv cargo receptors .
Terminal nucleotidyltransferase (TET5)
Type: Family

This entry includes terminal nucleotidyltransferase 5A/B/C/D (TENT5A/B/C/D). In general, they contain a NTase (nucleotidyltransferase) domain, some members possess additional C-terminal PAP/OAS1 substrate binding domain . They are active non-canonical poly(A) polymerases, which modify cytosolic and/or nuclear RNA 3' ends . They have different functions in many tissues at various stages of development.

Human TENT5A is a SMAD signalling pathway related protein, where SMADs are intercellular effectors of transforming growth factor-beta (TGF-beta) . The TENT5C gene is one of the most frequently mutated genes in multiple myeloma. TENT5C acts as an onco-suppressor in multiple myeloma . TENT5C also seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon .
Glucose/Sorbosone dehydrogenase (Glc/Sorbosone_DH)
Type: Domain

Proteins containing this domain are thought to be glucose/sorbosone dehydrogenases. The best characterised of these proteins is soluble glucose dehydrogenase (

) from Acinetobacter calcoaceticus, which oxidises glucose to gluconolactone. The enzyme is a calcium-dependent homodimer which uses PQQ as a cofactor .
Glycosyl hydrolase family 92 (Glyco_hydro_92)
Type: Domain

This domain occurs within alpha-1,2-mannosidases, which remove alpha-1,2-linked mannose residues from Man(9)(GlcNAc)(2) by hydrolysis. They are critical for the maturation of N-linked oligosaccharides and ER-associated degradation .
Nucleic acid binding NABP (NABP)
Type: Domain

This domain occurs in some putative nucleic acid binding proteins. One of these proteins has been partially characterised and contains two putative phosphorylation sites and a possible dimerisation / leucine zipper domain.
Phenol hydroxylase-like, C-terminal dimerisation domain (Phe_hydrox_C_dim_dom)
Type: Domain

Phenol hydroxylase is a homodimer which hydroxylates phenol to catechol, or similar products. The enzyme is comprised of three domains. The first two domains form the active site. The third domain, this domain, is involved in forming the dimerisation interface. The domain adopts a thioredoxin-like fold . Protein containing this domain also include 3-hydroxybenzoate 4-monooxygenase from Comamonas testosteroni .

This domain is also found in a number of FAD-dependent monooxygenases such as ankC, ucdD, terD and other related proteins .
SRR1-like domain (SRR1-like)
Type: Domain

This domain is found in SRR1-like proteins.

SRR1 are signalling proteins thought to be involved in regulating the circadian clock input pathway, which is required for normal oscillator function. In Arabidopsis thaliana it regulates the expression of clock-regulated genes such as CCA1 and TOC1. It is also involved in both the phytochrome B (PHYB) and PHYB-independent signaling pathways . The mouse homologue of the plant circadian-regulating protein SRR1 plays roles in heme-regulated circadian rhythms and cell proliferation .

The yeast SRR1-like protein Ber1 is involved in microtubule stability .
Centrosomin, N-terminal motif 1 (Cnn_1N)
Type: Domain

This domain (Cnn_1N) is a short conserved motif found in the N-terminal of a group of centrosome or spindle pole body (SPB) associated proteins, including Mto1 and Pcp1 from S. pombe , centrosomin from flies and myomegalin/CDK5RAP2 from mammals .
RagB/SusD domain (SusD_RagB_dom)
Type: Domain

This domain is found in bacterial cell surface proteins such as SusD

and SusD-like proteins

as as well RagB, an outer membrane surface receptor antigen.
Tubulin binding cofactor C-like domain (Tubulin-bd_cofactor_C_dom)
Type: Domain

This domain is found in tubulin-binding cofactor C (or tubulin-specific chaperone C) (TBCC) and in protein XRP2. TBCC is a folding cofactor that participates in tubulin biogenesis along with the other tubulin folding cofactors A (TBCA), B (TBCB), E (TBCE) and D (TBCD), as well as the GTP-binding protein Arl2 . XRP2 is a GTPase-activating protein (GAP) involved in intracellular trafficking .
X8 domain (X8)
Type: Domain

The X8 domain contains 6 conserved cysteine residues that presumably form three disulphide bridges. The domain is found in an Olive pollen allergen as well as at the C terminus of family 17 glycosyl hydrolases . This domain may be involved in carbohydrate binding.
Threonyl/alanyl tRNA synthetase, SAD (tRNA_SAD)
Type: Domain

The catalytically active form of threonyl/alanyl tRNA synthetase is a dimer. Within the tRNA synthetase class II dimer, the bound tRNA interacts with both monomers making specific interactions with the catalytic domain, the C-terminal domain, and this SAD domain (the second additional domain). The second additional domain is comprised of a pair of perpendicularly orientated antiparallel β sheets, of four and three strands, respectively, that surround a central α helix that forms the core of the domain .
AARP2CN (AARP2CN)
Type: Domain

This domain is the central domain of AARP2 (asparagine and aspartate rich protein 2). It is weakly similar to the GTP-binding domain of elongation factor TU . PfAARP2 is an antigen from Plasmodium falciparum of 150kDa, which is encoded by a unique gene on chromosome 1 . The central region of Pfaarp2 contains blocks of repetitions encoding asparagine and aspartate residues.
Alpha enterocin/lactococcin (Alpha_enterocin/lactococcin)
Type: Family

This entry consists of the alpha enterocins and lactococcin G peptides. These peptides have some antimicrobial properties; they inhibit the growth of Enterococcus spp. and a few other Gram-positive bacteria. These peptides act as pore-forming toxins that create cell membrane channels through a barrel-stave mechanism and thus produce an ionic imbalance in the cell. This family of antimicrobial peptides belongs to the class II group of bacteriocin .
Berberine/berberine-like (BBE)
Type: Domain

This domain is found in the berberine bridge and berberine bridge-like enzymes, flavoproteins which have an unusual bicovalent attachment of the FAD cofactor that are involved in the biosynthesis of numerous isoquinoline alkaloids. They catalyse the transformation of the N-methyl group of (S)-reticuline into the C-8 berberine bridge carbon of (S)-scoulerine . This domain is found in many flavoproteins mainly from bacteria, fungi and plants.
BING4, C-terminal domain (BING4_C_dom)
Type: Domain

This C-terminal domain is found in the BING4 family of nucleolar WD40 repeat proteins .
BOP1, N-terminal domain (BOP1_N_dom)
Type: Domain

This domain is found in the N-terminal region of BOP1-like WD40 proteins. Bop1 is a nucleolar protein involved in rRNA processing, thereby controlling the cell cycle . It is required for the maturation of the 25S and 5.8S ribosomal RNAs. It may serve as an essential factor in ribosome formation that coordinates processing of the spacer regions in pre-rRNA.
BP28, C-terminal domain (BP28_C_dom)
Type: Domain

This domain is found in the C-terminal of BAP28 proteins (which are involved in nucleolar processing of pre-18S ribosomal RNA and ribosome biosynthesis ) and in other BAP28-like proteins.
CASP, C-terminal (CASP_C)
Type: Domain

This domain is the C-terminal region of the CASP family of proteins. These are Golgi membrane proteins which are thought to have a role in vesicle transport .
CARG-binding factor, N-terminal (CARG-binding_factor_N)
Type: Domain

This N-terminal domain is found in CARG-binding factor A-like proteins .
CHD, C-terminal 2 (CHD_C2)
Type: Domain

This entry represents the C-terminal domain of CHD (Chromodomain, Helicase, DNA-binding) proteins. CHD3 and CHD4 belong to the class II subfamily of CHD ATPases, and each is present as a core catalytic subunit in separate NuRD complexes, which regulate chromatin organisation and gene transcription . CHD5 forms a NuRD-type chromatin remodeling complex and acts as a tumour suppressor .

There are nine members of the Chromodomain, Helicase, DNA-binding (CHD) family. They are characterised by two chromodomains arranged in tandem, N-terminal to the ATPase/helicase domain. Chromodomains are comprised of a β-sheet folded against an α-helix that collectively mediates binding to methyl-lysine residues .
CHD, N-terminal (CHD_N)
Type: Domain

This entry represents the N-terminal domain of CHD (Chromodomain, Helicase, DNA-binding) proteins. CHD3 and CHD4 belong to the class II subfamily of CHD ATPases, and each is present as a core catalytic subunit in separate NuRD complexes, which regulate chromatin organisation and gene transcription . CHD5 forms a NuRD-type chromatin remodeling complex and acts as a tumour suppressor .

There are nine members of the Chromodomain, Helicase, DNA-binding (CHD) family. They are characterised by two chromodomains arranged in tandem, N-terminal to the ATPase/helicase domain. Chromodomains are comprised of a β-sheet folded against an α-helix that collectively mediates binding to methyl-lysine residues .
CPL domain (CPL_dom)
Type: Domain

This C-terminal domain is found in Penguin-like proteins (CPL) and is associated with Pumilio like repeats .
Dyskerin-like (Dyskerin-like)
Type: Domain

This is an N-terminal domain of dyskerin-like proteins, which is often associated with the TruB N-terminal (

) and PUA (

) domains .
ATP-dependent RNA helicase Ski2/MTR4, C-terminal (Ski2/MTR4_C)
Type: Domain

This C-terminal domain is found in Ski2/MTR4/helY-like DEAD box helicases .
Peptidase M54, archaemetzincin (Pept_M54_archaemetzincn)
Type: Family

Peptidase family M54 (archaemetzincin or archaelysin) is a zinc-dependent aminopeptidase that contains the consensus zinc-binding sequence HEXXHXXGXXH/D and a conserved Met residue at the active site, and is thus classified as a metzincin. Archaemetzincins, first identified in archaea, are also found in bacteria and eukaryotes, including two human members, archaemetzincin-1 and -2 (AMZ1 and AMZ2). AMZ1 is mainly found in the liver and heart while AMZ2 is primarily expressed in testis and heart; both have been reported to be aminopeptidases, degrading synthetic substrates and peptides. The peptidase M54 family contains an extended metzincin concensus sequence of HEXXHXXGX3CX4CXMX17CXXC such that a second zinc ion is bound to four cysteines, thus resembling a zinc finger. Phylogenetic analysis of this family reveals a complex evolutionary process involving a series of lateral gene transfer, gene loss and genetic duplication events .

Archaemetzincin (from Mycococcus xanthus) seem to have evolved into a zinc-binding transcription factor fulfilling only a structural
role . The structure of archaemetzincin from Methanopyrus kandleri has been resolved .
HAAS transmembrane region (HAAS_TM)
Type: Domain

This entry represents the transmembrane region (TM) fused to HAAS (HTH-associated α-helical signaling) domain found in a number of hypothetical bacterial proteins.
Protein of unknown function DUF1702 (DUF1702)
Type: Family

This family of proteins contains many bacterial proteins that are encoded by the unbL gene. The function of these proteins is unknown.
Meiotically up-regulated protein Msb1/Mug8 domain (Msb1/Mug8_dom)
Type: Domain

This domain of unknown function is found in fungal proteins, including Mug8 from Schizosaccharomyces pombe which may have a role in meiosis and septation . Saccharomyces cerevisiae homologue MSB1(

) may be involved in positive regulation of 1,3-beta-glucan synthesis and the Pkc1p-MAPK pathway .
Anillin homology domain (AHD)
Type: Domain

Anillin is a protein involved in septin organisation during cell division. It is an actin binding protein that is localised to the cleavage furrow, and it maintains the localisation of active myosin, which ensures the spatial control of concerted contraction during cytokinesis .

This entry represents a conserved domain found in anillin and anillin-like proteins. This domain shares homology with the RhoA binding protein Rhotekin .
O-methyltransferase, dimerisation domain (COMT_dimerisation)
Type: Domain

This domain is found at the N-terminal in a variety of O-methyltransferases (COMT). It has been shown to mediate dimerisation of these proteins . It is also found in some N-methyltransferases such as Anthranilate N-methyltransferase and 3-aminomethylindole N-methyltransferase which are involved in the biosynthesis of indole and acridine alkaloids .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
FerIin domain (FerIin_dom)
Type: Domain

The ferlin gene family are characterised by multiple tandem C2 domains and a C-terminal transmembrane domain. They are found in a wide range of species and their function remains unknown, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease .

This domain is present in proteins of the Ferlin family, which includes Otoferlin, Myoferlin and Dysferlin. It is often located between two C2 domains .
Fibrinogen binding protein (Fibrinogen_BP)
Type: Family

Proteins in this family bind to fibrinogen. Fibrinogen is capable of binding to a wide number of endogenous proteins and cell receptors during haemostasis, including binding to platelets to promote their aggregation . Included in this family is receptor FbsA (

) from the pathogen Streptococcus agalactiae, which is responsible for causing endocarditis in humans. FbsA is considered an important virulence factor that is capable of binding fibrinogen, through which it elicits platelet aggregation and adherence to the extracellular matrix. This enables the bacteria to invade the pulmonary epithelium, which may be a prerequisite for infection .
Polysaccharide lyase 8, N-terminal alpha-helical (Lyase_8_alpha_N)
Type: Domain

This α-helical domain is found in a group of secreted bacterial lyase enzymes (

) capable of acting on hyaluronan and chondroitin in the extracellular matrix of host tissues, contributing to the invasive capacity of the pathogen.
Nucleolar GTP-binding protein 2, N-terminal domain (NOG2_N_dom)
Type: Domain

This N-terminal domain is found in Nucleolar GTP-binding protein 2 .
NLE (NLE)
Type: Domain

This domain is located N-terminal to WD40 repeats(

). It is found in the microtubule-associated protein

.
NOG, C-terminal (NOG_C)
Type: Domain

This C-terminal domain is found in the NOG subfamily of nucleolar GTP-binding proteins .
Nucleolar protein 58/56, N-terminal (NOP58/56_N)
Type: Domain

This N-terminal domain is found in Nucleolar protein 58/56 from fungi and animals and the homologues form plants. These are RNA-binding proteins of the NOP5 family . Nop56 and Nop58 are components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles . This domain interacts with Nop1 and forms the box B/C side, in the case of Nop56, or box C'/D side in the case of Nop58, of U3 snoRNP .
NOPS (NOPS)
Type: Domain

This domain is found in the DBHS (Drosophila behavior human splicing) family members. It is C-terminal to the RNA recognition motifs (RRMs).

DBHS (Drosophila behavior human splicing) family are characterised by a core domain arrangement consisting of tandem RNA recognition motifs (RRMs), a conserved intervening sequence referred to as a NONA/ParaSpeckle (NOPS) domain, and a ~100 amino acid coiled-coil domain. Its members include p54nrb (also known as NONO), PTB-associated splicing factor/splicing factor proline-glutamine rich (PSF or SFPQ) and PSPC1 (paraspeckle protein component 1). They are found in the nucleoplasm and can be triggered by binding to local high concentrations of various nucleic acids to form microscopically visible nuclear bodies, paraspeckles or large complexes such as DNA repair foci. They may also function cytoplasmically and on the cell surface in defined cell types. All three DBHS proteins are conserved throughout vertebrate species, while flies, worms, and yeast express a single DBHS protein .
NOSIC (NOSIC)
Type: Domain

This entry represents a domain centrally located in a group of pre-RNA processing ribonucleoproteins (RNPs), including the eukaryotic proteins Prp31, Nop56 and Nop58 and the archaeal homologue Nop5. This domain was named after the central domain in Nop56/SIK1-like proteins . It is found associated with the Nop domain (

).

U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31) is involved in pre-mRNA splicing as component of the spliceosome . This protein is required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome . It is associated with a progressive pigmentary retinopathy characterised by night vision blindness and loss of midperipheral visual field .

Nucleolar protein 56 and 58 (NOP56/58) are required for 60S ribosomal subunit synthesis . They are core components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles . In humans, NOP56 is associated with a type of slowly progressive neurodegenerative disorder characterised by late-onset ataxia followed by variable involvement of the motor neuron system .
SDA1, N-terminal (SDA1_N)
Type: Domain

This entry represents the N-terminal domain of SDA1 (also referred to as NUC130/133) . It consists of HEAT repeats .

Sda1 is required for 60S pre-ribosomal subunits export to the cytoplasm and may also be required for 60S ribosomal subunit maturation and accumulation. It is involved in G1 events and passage through start, and possibly actin cytoskeleton organisation .
RRP12, HEAT domain (HEAT_RRP12)
Type: Domain

This entry represents a conserved domain found in RRP12 proteins, which consists of HEAT repeats.

Ribosomal RNA-processing protein 12 (RRP12) proteins are members of pre-ribosome-associated HEAT repeats-containing proteins . They are involved in the maturation and nuclear export of both pre-40S and pre-60S ribosomal subunits. They are required for the processing of RNA components within pre-ribosomes, which is a critical step in the assembly of functional ribosomes. They are associated with the late maturation of the 18S and 5.8S rRNA of the pre-40S ribosomes and for maturation of the 25S and 5.8S rRNA of the pre-60S ribosomes .