SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF3860 (DUF3860)
Type: Family

This protein family includes hypothetical protein (JCVI_PEP_1096688149193) whose crystal structure has been solved PDB:2OD5. The hypothetical protein is from an environmental metagenome (unidentified marine microbe).
Domain of unknown function DUF3869 (DUF3869)
Type: Domain

This domain of unknown fuction is found at the N-terminal of putative pore-forming toxin YP_001301288.1 from Bacteroides vulgatus ATCC 8482 (

,

), which shows weak but consistent remote homology with adhesive families such as immunoglobulins and cadherins, suggesting it might form an attachment module.
Inner membrane mitoribosome receptor Mba1, mitochondrial (Mba1)
Type: Family

This entry represents Mba1 from budding yeasts and its homologues.
Uncharacterised protein family YtxH (YtxH)
Type: Family

This family of uncharacterised proteins is found in bacteria. Proteins in this family are typically between 100 and 143 amino acids in length. The N-terminal region is the most conserved.
Pyridoxamine 5'-phosphate oxidase, Alr4036 family, FMN-binding domain (Pyridox_Oxase_Alr4036_FMN-bd)
Type: Domain

Pyridoxamine 5'-phosphate oxidase catalyses the oxidation of pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P (PLP), the terminal step in the de novo biosynthesis of PLP in Escherichia coli and part of the salvage pathway of this coenzyme in both E. coli and mammalian cells.
Kri1-like, C-terminal (Kri1-like_C)
Type: Domain

The yeast member of the Kri1-like family (Kri1p) is found to be required for 40S ribosome biogenesis in the nucleolus . This entry represents the C-terminal domain of this protein family.
V(D)J recombination-activating protein 1 (RAG1)
Type: Family

The development of B and T cells depends on the rearrangement of variable (V), diversity (D), and joining (J) gene segments to produce mature Ig and T cell receptor coding regions. This rearrangement process, known as V(D)J recombination is initiated by a complex consisting of multi-domain proteins RAG1 and RAG2. The RAG proteins catalyse DNA cleavage in the first phase of the reaction using a recombination signal sequence (RSS) that flanks V, D and J segments .

Recombination activating protein 1 (RAG1) is the catalytic component of the RAG complex . RAG1 contains a RING finger domain that can act as a ubiquitin ligase (E3), and can promote its own ubiquitylation and targets both karyopherin alpha 1 (KPNA1) and histone 3 (H3) .

Many of the proteins recognised by this entry are fragments.
Sulphotransferase Stf0, domain (Sulfotransferase_Stf0_dom)
Type: Domain

Members of this family are essential for the biosynthesis of sulpholipid-1 in prokaryotes. They adopt a structure that belongs to the sulphotransferase superfamily, consisting of a single domain with a core four-stranded parallel β-sheet flanked by α-helices .
Large ribosomal subunit protein mL67 (Ribosomal_mL67)
Type: Family

Saccharomyces cerevisiae Mhr1 (also known as Large ribosomal subunit protein mL67) promotes homologous DNA pairing and functions as a mitochondrial recombinase that mediates the predominant form of mtDNA replication and acts in mtDNA segregation and the repair of mtDNA double-stranded breaks (DSBs) . This entry also includes the Mhr1 homologue, ML67, from Neurospora crassa. Both Mhr1 and ML67 have been shown to be localised on the mitoribosomal large subunit .
Stc1 domain (Stc1)
Type: Domain

The domain contains 8 conserved cysteines that may bind to zinc. In S. pombe, proteins containing the domain act as protein linkers, which link the chromatin modifying CLRC complex to RNAi by tethering it to the RITS complex. This domain has a slightly different arrangement of its CxxC pairs from the LIM domain, hence it is not part of that family . The tandem zinc-finger structure could mediate protein-protein interactions.
Transcription factor p53, C-terminal, Drosophila (p53_C_Drosophila)
Type: Domain

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.

This entry represents the C-terminal domain of Drosophila transcription factor p53. While the rest of the protein is quite conserved between the different transcription factors such as p53 and p73, the C-terminal domain is highly divergent. The Drosophila p53 structure is characterised by an additional N-terminal β-strand and a C-terminal helix .
Phospholipase D, C-terminal (PLipase_D_C)
Type: Domain

Phospholipase D (PLD) catalyses the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free head group. Phospholipase D activities have been detected in simple to complex organisms from viruses and bacteria to yeast, plants, and mammals . In higher organisms, PLD specifically catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA) and choline and is activated in response to stimulators of vesicle transport, endocytosis, exocytosis, cell migration, and mitosis.

This entry represents the C-terminal domain of eukaryotic phospholipase D. The domain is approximately 70 amino acids in length and contains a conserved FPD sequence motif.
DnaA N-terminal domain (DnaA_N_dom)
Type: Domain

This entry represents the N-terminal domain of bacterial DnaA proteins , which play an important role in initiating and regulating chromosomal replication. DnaA is an ATP- and DNA-binding protein. It binds specifically to 9 bp nucleotide repeats known as dnaA boxes which are found in the chromosome origin of replication (oriC). The structure of this domain is known . Its exact function is uncertain, but it has been suggested that the domain may play a role in oligomerisation.
Internalin, N-terminal (Internalin_N)
Type: Domain

This entry represents the N-terminal domain of internalin, the cap domain of the protein. This domain is found in bacteria, and is approximately 60 amino acids in length. There are two completely conserved residues (I and F) that may be functionally important. Internalin mediates bacterial adhesion and invasion of epithelial cells in the human intestine through specific interaction with its host cell receptor E-cadherin. The cap domain is conserved between different internalin types and does not interact with E cadherin; therefore its function is presumably structural: capping the hydrophobic core .
Gonadotropin hormone receptor, transmembrane domain (GnHR_TM)
Type: Domain

This domain represents the transmembrane region of follicular stimulating hormone and luteinizing hormone receptors- the two major gonadotropin hormone receptors. This domain is found in eukaryotes, and is approximately 70 amino acids in length. There are two completely conserved C residues that may be functionally important. The transmembrane region is conserved between the two different receptors, while the extracellular ligand binding domains are less well conserved . The follicular stimulating hormone and luteinizing hormone receptors are G protein-coupled receptors involved in development and maturation of germ cells in both fecund genders.
Histone lysine methyltransferase SET associated (SET_assoc)
Type: Domain

The SET domain is a protein-protein interaction domain found in protein lysine methyltransferase enzymes. This entry represents a domain of unknown function which is associated with the SET domain and found in histone lysine methyltransferases .
CTD kinase subunit gamma Ctk3, C-terminal (Ctk3_C)
Type: Domain

The C-terminal domain kinase (CTDK-1), is a three-subunit complex comprised of Ctk1, Ctk2, and Ctk3, that plays a key role in regulation of transcription and translation and in coordinating these two processes. Both Ctk2 and Ctk3 are regulated at the level of protein turnover, and are unstable proteins processed through a ubiquitin-proteasome pathway. Their physical interaction is required to protect both subunits from degradation, and both Ctk2 and Ctk3 are required for Ctk1 CTD kinase activation .

This entry represents the C-terminal domain of Ctk3.
CTD kinase subunit gamma Ctk3, N-terminal (Ctk3_N)
Type: Domain

The C-terminal domain kinase (CTDK-1), is a three-subunit complex comprised of Ctk1, Ctk2, and Ctk3, that plays a key role in regulation of transcription and translation and in coordinating these two processes. Both Ctk2 and Ctk3 are regulated at the level of protein turnover, and are unstable proteins processed through a ubiquitin-proteasome pathway. Their physical interaction is required to protect both subunits from degradation, and both Ctk2 and Ctk3 are required for Ctk1 CTD kinase activation . The mammalian P-TEFb is mirrored by the combined complexes in yeast of the CTDK1 and the Bur1/2 .
DNA polymerase epsilon subunit B, N-terminal (DNA_pol_e_bsu_N)
Type: Domain

This domain is found in the N-terminal of DNA polymerase epsilon subunit B proteins. It contains a single completely conserved phenylalanine residue that may be functionally important. It forms a primarily α helical structure in which four helices are arranged in two hairpins with connecting loops containing β strands which form a short parallel sheet.

DNA polymerase epsilon is required in DNA replication for synthesis of the leading strand. The N-terminal domain has close structural relation to AAA+ protein C-terminal domains .
Toxin-antitoxin type 1 system, toxin component (Toxin-antitoxin_type_1_toxin)
Type: Family

This family is the toxin of a type 1 toxin-antitoxin system which is found in a relatively widespread range of bacterial species. The species distribution suggests frequent horizontal gene transfer. In a type 1 system, as characterised for the plasmid-encoded E coli hok/sok system, the toxin-encoding stable mRNA encodes a protein which rapidly leads to cell death unless the translation is suppressed by a short-lived small RNA. The plasmid-encoded module prevents the growth of plasmid-free offspring, thus ensuring the persistence of the plasmid in the population. Plasmid-free cells arising after cell-division will be killed because the stable mRNA toxin is present while the comparably unstable anti-toxin is rapidly degraded. Where the system is transcribed chromosomally, the mechanism is poorly understood .
Hepatocyte growth factor-regulated tyrosine kinase substrate, helical domain (HRS_helical)
Type: Domain

This domain comprises the helical region of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS). It is approximately 100 amino acids in length.

Hrs, together with signal transducing adaptor molecule (STAM), forms the ESCRT-0 complex, which sorts ubiquitinated cell surface receptors to lysosomes for degradation .
SUZ-C domain (SUZ-C)
Type: Domain

The SUZ-C domain is a conserved motif found in one or more copies in several RNA-binding proteins . It is always found at the C terminus of the protein and appears to be required for localization of the protein to specific subcellular structures. The domain was first characterised in the C.elegans protein SZY-20, a centrosome-associated RNA-binding protein that negatively regulates centrosome assembly. SZY-20 and its animal orthologs share three prominent blocks of conservation. The N-terminal block is a short element, which is found exclusively in orthologs of SZY-2. The third block, the SUZ-C domain, is at the extreme C terminus and is defined by a characteristic pattern of two highly conserved glycines and one absolutely conserved proline. The SUZ and SUZ-C domains occur independently in proteins outside of the SZY-20 family. Many of these proteins contain known RNA-binding domains. The SUZ-C domain is a putative RNA-binding domain .
Histone deacetylase, glutamine rich N-terminal domain (Hist_deacetylase_Gln_rich_N)
Type: Domain

This domain is found in eukaryotic histone deacetylases, and is approximately 90 amino acids in length. The domain forms an α helix, which complexes to form a tetramer. The glutamine rich domains have many intra- and inter-helical interactions that are thought to be involved in reversible assembly and disassembly of proteins .
Mitochondrial export protein Som1 (Mitochondr_Som1)
Type: Family

Som1 is a component of the mitochondrial protein export system. Som1 proteins exhibit a highly conserved region and a pattern of cysteine residues . Stabilisation of Som1 occurs through an interaction between Som1 and Imp1, a peptidase required for proteolytic processing of certain proteins during their transport across the mitochondrial membrane . This suggests that Som1 represents a third subunit of the Imp1 peptidase complex .
Angiomotin, C-terminal (Angiomotin_C)
Type: Domain

This domain represents the C-terminal region of angiomotin. Angiomotin regulates the action of angiogenesis-inhibitor angiostatin . The C-terminal region of angiomotin appears to be involved in directing the protein chemotactically .
DNA polymerase alpha catalytic subunit, N-terminal domain (DNA_pol_a_cat_su_N)
Type: Domain

This entry represents the N-terminal domain of DNA polymerase alpha catalytic subunit (the DNA polymerase alpha complex is composed of four subunits). This domain is approximately 70 amino acids in length and it contains a specific labile site .
Transposon Tf2-1-like domain (Tf2-1-like_dom)
Type: Domain

This entry represents a domain found in Transposon Tf2-1 polyprotein from Schizosaccharomyces pombe (Tf2-1), a retrotransposon that belong to the gypsy-like elements. It shows high similarity to an aspartic peptidase domain. Members of this group are specific to Schizosaccharomyces.
Peptidase A2B, Ty3 transposon peptidase (Peptidase_A2B)
Type: Domain

Ty3 is a gypsy-type, retrovirus-like, element found in the budding yeast. The Ty3 aspartyl protease is required for processing of the viral polyprotein into its mature species . This domain is predicted to adopt structure similar to

.
FAD-containing D-sorbitol dehydrogenase small subunit (FAD-SLDH_ssu)
Type: Family

There are two types of membrane-bound D-sorbitol dehydrogenase: PQQ-SLDH (pyrroloquinoline quinone sorbitol dehydrogenase) and FAD-SLDH (FAD-containing sorbitol dehydrogenase). FAD-SLDH is involved in oxidation of D-sorbitol to L-sorbose and consists of a large, small and cytochrome c subunits .

This entry represents the small subunit of the FAD-containing D-sorbitol dehydrogenase. This family of proteins is found in bacteria and contains a conserved ALM sequence motif. The role of the small subunit is unknown.
Trichodiene synthase (Trichodiene_synth)
Type: Family

This family consists of several fungal trichodiene synthase proteins (

). TRI5 encodes the enzyme trichodiene synthase, which has been shown to catalyse the first step in the trichothecene pathways of Fusarium and Trichothecium species .

Proteins in this entry also includes COP6 from Coprinopsis cinerea and CLM1 from Gibberella zeae. COP6 is an alpha-cuprenene synthase involved in the biosynthesis of alpha-cuprenene and oxidized derivatives . CLM1 is a longiborneol synthase required for culmorin production .
Peptidase, metallopeptidase M10/M27/M57 (Peptidase_M10/M27/M57)
Type: Family

This entry represents the metallopeptidases M10, M27 and M57. The catalytic triad for proteases in this entry is HE-H-H, which in many members is in the sequence motif HEIGH .
Calcineurin-like phosphoesterase domain, lpxH-type (Calcineurin-like_PHP_lpxH)
Type: Domain

This calcineurin-like phosphoesterase domain can be found in some of the bacterial UDP-2,3-diacylglucosamine hydrolases (lpxH), archaeal DNA double-strand break repair protein Mre11 and the N-terminal of the nuclease SbcCD subunit D from bacteria. It can also be found in the eukaryotic vacuolar protein sorting-associated protein 29 (VPS29).
Asl1-like, glycosyl hydrolase catalytic domain (Asl1_glyco_hydro_catalytic)
Type: Domain

This entry represents the glycosyl hydrolase catalytic core of a group of poorly characterised proteins, mainly from bacteria and fungi, including the cell wall protein Asl1 from S. pombe.
Ammonia monooxygenase, subunit A, archaeal (AmoA_arc)
Type: Family

This entry represents a group of archaeal proteins that contains ammonia monooxygenase subunit A. Ammonia monooxygenase is an enzyme that oxidises ammonia to nitrite and nitrate, thus playing a significant role in the nitrogen cycle. Ammonia-oxidising archaea (AOA) are widespread in marine environments .
COMPASS complex Set1 subunit, N-SET domain (COMPASS_Set1_N-SET)
Type: Domain

The COMPASS complex (complex proteins associated with Set1p) is conserved in yeasts and in other eukaryotes up to humans. The COMPASS complex functions to methylate the fourth lysine of Histone 3 and for the silencing of genes close to the telomeres of chromosomes .
Major capsid protein Gp5 (Phage_coat_Gp5)
Type: Family

This family of proteins includes Gp5 from bacteriophage P22 and related proteins. Gp5 is involved in the formation of the pro-capsid shells in the bacteriophage. In total, there are 415 molecules of the coat protein which are arranged in an icosahedral shell .
UNC-45/Cro1/She4, central domain (UCS_central_dom)
Type: Domain

The UNC-45 protein contain an NH2-terminal domain with three tetratricopeptide repeat motifs, a unique central domain, and a COOH-terminal domain homologous to CRO1 and She4 . This entry represents the central domain of the UNC-45 protein.
DNA-directed RNA polymerase III, subunit Rpc31 (RNA_pol_III_Rpc31)
Type: Family

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

RNA polymerase III contains seventeen subunits in yeasts and in human cells. Twelve of these are akin to RNA polymerase I or II and the other five are RNA polymerase III-specific, and form the functionally distinct groups: (i) Rpc31-Rpc34-Rpc82, and (ii) Rpc37-Rpc53. Rpc31, Rpc34 and Rpc82 form a cluster of enzyme-specific subunits that contribute to transcription initiation in Saccharomyces cerevisiae and Homo sapiens. There is evidence that these subunits are anchored at or near the N-terminal Zn-fold of Rpc1, itself prolonged by a highly conserved but RNA polymerase III-specific domain .

This entry represents the Rpc31 subunit. It is also known as RPC7 or RPC32 .
Trafficking protein particle complex II-specific subunit 65 (Trs65)
Type: Family

Trs65 is a specific subunit of the TRAPP II complex, a highly conserved vesicle tethering complex that functions in the late Golgi as a guanine nucleotide exchanger (GEF) for the Golgi YPT1 GTPase .

TRAPP subunits are found in three forms-core TRAPP/TRAPPI, TRAPPII, and TRAPPIII and they function in various vesicle trafficking pathways. TRAPPI mediates transport from endoplasmic reticulum to cis-Golgi by tethering COPII (coat protein complex II)-coated vesicles; TRAPPII interacts with COPI-coated vesicles in mammalian cells and aids in endosome-to-Golgi transport and TRAPPIII plays a unique role in autophagy. A distinct feature of the TRAPP complexes is they act as GEFs and play an essential role in catalysing nucleotide exchange for Ypt/Rab GTPase. The three complexes share a core of six different proteins (Bet3, Bet5, Trs20, Trs23, Trs31, and Trs33) that make up core TRAPPI. TRAPPII contains four additional proteins (Trs120, Trs130, Trs65, and Tca17), and TRAPPIII has one additional Trs85 in yeast .
L-arabinose isomerase, C-terminal (Ara_Isoase_C)
Type: Domain

This entry represents a C-terminal non-catalytic domain in L-arabinose isomerase.

This entry includes L-arabinose isomerases, AraA, (

). These enzymes catalyse the reaction: L-arabinose => L-ribulose. This reaction is the first step in the pathway of L-arabinose utilisation as a carbon source after entering the cell L-arabinose is converted into L-ribulose by the L-arabinose isomerases enzyme .
Thrombospondin/cartilage oligomeric matrix protein, coiled-coil domain (TSP/COMP_CC)
Type: Domain

Thrombospondins (TSP) are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. Cartilage oligomeric matrix protein (TSP5/COMP) may play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as collagen and fibronectin .

TSP3/4 and TSP5/COMP contain a five-stranded coiled-coil domain represented by this entry. This domain has a binding site between two internal rings formed by Leu37 and Thr40 .
HnRNP M, nuclear localisation signal (HnRNP_M_PY-NLS)
Type: Domain

Heterogeneous nuclear ribonucleoproteins (hnRNPs) bind directly to nascent RNA polymerase II transcripts and play an important role in both transcript-specific packaging and alternative splicing of pre-mRNAs . hnRNP M proteins are an abundant group of hnRNPs that have been shown to bind avidly to poly(G) and poly(U) RNA homopolymers .
hnRNP M family members are able to induce exon skipping and promote exon inclusion, suggesting that the proteins may broadly contribute to the fidelity of splice site recognition and alternative splicing regulation .

This entry represents the N-terminal PY nuclear localisation signal of heterogeneous nuclear ribonucleoprotein M .
GA-binding protein alpha subunit, N-terminal (GABP_asu_N)
Type: Domain

GA-binding protein alpha is a transcription factor capable of interacting with purine rich repeats (GA repeats). This N-terminal domain found in the transcription factor GABP alpha consists of a five-stranded β-sheet crossed by a distorted helix and has been termed OST domain. The surface of the GABP alpha OST domain contains two clusters of negatively-charged residues suggesting there are positively-charged partner proteins. The OST domain binds to the CH1 and CH3 domains of the co-activator histone acetyltransferase CBP/p300 .