SII-SWORD/CoKE huggingface dataset:
THO complex subunit 7/Mft1 (THOC7/Mft1)
Type: Family

The THO complex (THOC) is involved in transcription elongation and mRNA export from the nucleus . This entry represents the subunit THOC7, which is found in higher eukaryotes, and the non-homologous subunit Mft1 found in yeast.

Mft1 is a component the THO subcomplex of the TREX complex, which operates in coupling transcription elongation to mRNA export . The THO complex is recruited to transcribed genes and moves along the gene with the elongating polymerase during transcription . THO is important for stabilising nascent RNA in the RNA polymerase II elongation complex by preventing formation of DNA:RNA hybrids behind the elongating polymerase . It functions in cotranscriptional formation of an export-competent messenger ribonucleoprotein particle (mRNP) by facilitating the loading of ATP-dependent RNA helicase Sub2 and the mRNA export factor Yra1 along the nascent mRNA .
Prolamin-like domain (Prolamin-like)
Type: Domain

Proteins with this domain are found to be expressed in the plant embryo sac and are regulated by the Myb98 transcription factor. Computational analysis has revealed that they are homologous to the plant prolamin superfamily (Protease inhibitor-seed storage-LTP family,

) . In contrast to the typical prolamin members that have eight conserved Cys residues forming four pairs of disulphide bonds, proteins with this domain only contain six conserved Cys residues that may form three pairs of disulphide bonds. They may have potential functions in lipid transfer or protection during plant embryo sac development and reproduction . This domain includes both previous DUF784 and DUF1278 domains.
Putative ATP-dependent zinc protease (Put_Zn_protease)
Type: Domain

Some proteins with this domain are annotated as being ATP-dependent zinc proteases.
ER membrane protein complex subunit 6 (Emc6)
Type: Family

This entry represents ER membrane protein complex subunit 6 (Emc6). Emc6 is a component of the ER membrane protein complex (EMC), which is composed of Emc1, Emc2, Emc3, Emc4, Emc5 and Emc6 in budding yeast . The EMC complex is required for efficient folding of proteins in the ER and enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins .
Protein of unknown function DUF787 (DUF787)
Type: Family

This entry consists of several hypothetical proteins of unknown function from Borrelia species. They may be proteinases, as the majority contain a propeptide proteinase inhibitor domain which is associated with both serine and metallopeptidases.
SRP-independent targeting protein 2/TMEM208 (SND2/TMEM208)
Type: Family

This family includes SRP-independent targeting protein 2 (SND2) from yeast and transmembrane protein 208 (TMEM208) from mammals. Both are localized to the endoplasmic reticulum (ER) . SND2 works together with SND1 and SND3 in an alternative targeting route to the ER . TMEM208 regulates both ER stress and autophagy .

SND2 was previously known as Env10 in Saccharomyces cerevisiae, and its homologue as Mug69 in Schizosaccharomyces pombe. They were identified as proteins involved in vacuolar processing and morphology and meiosis , respectively.
Protein of unknown function DUF789 (DUF789)
Type: Family

This family consists of several plant proteins of unknown function.
Endonuclease Bax1 (Bax1)
Type: Family

This entry consists of several bacterial and archaeal endonuclease proteins that may be involved in either restriction-modification and/or DNA excision repair . Among its members is endonuclease Bax1 from archaea, a dual DNA endonuclease probably involved in nucleotide excision repair (NER) . The N-terminal nuclease domain (NTD) of the XPB-Bax1 complex cleaves on one side of a DNA bubble (which presumably mimics DNA damage), while the NUS nuclease domain cleaves the other side, respectively called 5' and 3' nuclease activities . In the absence of its XPB partner, Bax1 has weak 5' nuclease activity . Bax1 binds to and represses the ATPase activity (and probably also helicase activity) of XPB2 . The two helicase and the ThM domains of XPB2 with the NTD and CRD domains of Bax1 encircle the DNA, forming a tunnel where the 12 bp dsDNA and the ds-ssDNA junction are located .
Molybdate-anion transporter (MOT2/MFSD5)
Type: Family

This entry represents a group of molybdate-anion transporters, including MFSD5 (also known as hsMOT2) from humans and molybdate transporter (CrMOT2,

) from Chlamydomonas . They mediate high-affinity intracellular uptake of the rare oligo-element molybdenum.
Protein of unknown function DUF792, Borrelia species (DUF792_BOR_spp)
Type: Family

This entry consists of several hypothetical proteins found in Borrelia species.
Protein ROH1-like (ROH1-like)
Type: Family

This entry includes a family of proteins such as protein BYPASS1-LIKE , protein ROH1 and related proteins that are involved in the regulation of plant growth and development. ROH1 is an interactor of the exocyst subunit Exo70A1, and has been shown to be required for seed coat mucilage deposition . BYPASS1-LIKE prevents plant growth and development and regulates positively cold tolerance . It also regulates lateral root initiation via exocytic vesicular trafficking-mediated PIN recycling .
tRNA(Met) cytidine acetate ligase (tRNA(Met)_cyd_acetate_ligase)
Type: Family

This entry represents the tRNA(Met) cytidine acetate ligase family of predominantly bacterial proteins.
Type VI secretion system effector Hcp (T6SS_Hcp)
Type: Family

This entry consists of Hcp-like proteins. Hcp is part of the type VI secretion system of Gram-negative bacteria. Hcp is not only a secreted effector protein, but also might act as machine component .

Several bacterial pathogens mediate interactions with their hosts through protein secretion, often involving Hcp-like virulence loci, which are widely distributed among pathogenic bacteria. Homologues of Hcp are found in various bacteria of which most, but not all, are known pathogens. Many bacteria have two copies of hcp genes . In Pseudomonas syringae, Hcp1 is a virulence protein, while Hcp2 seems to be required for survival in competition with enterobacteria and yeasts, and its function is associated with the suppression of the growth of these competitors .

Hcp1 monomers form a hexameric ring with a large internal diameter. Assembly of this particle is likely to occur following secretion, and could have a role in building a channel for the transport of other macromolecules .

The type VI secretion system (T6SS), also known as CIS contractile injection system , is a supra-molecular bacterial complex that resembles phage tails. It is a toxin delivery systems which fires toxins into target cells upon contraction of its TssBC sheath . Thirteen essential core proteins are conserved in all T6SSs: the membrane associated complex TssJ-TssL-TssM, the baseplate proteins TssE, TssF, TssG, and TssK, the bacteriophage-related puncturing complex composed of the tube (Hcp), the tip/puncturing device VgrG, and the contractile sheath structure (TssB and TssC). Finally, the starfish-shaped dodecameric protein, TssA, limits contractile sheath polymerization at its distal part when TagA captures TssA .
Prokaryotic ubiquitin-like protein Pup (Ubiquitin-like_Pup)
Type: Family

This entry represents Prokaryotic ubiquitin-like protein Pup from Mycobacterium tuberculosis and similar short proteins, of 50-90 residues in length, predominantly found in Actinobacteria. Pup is covalently conjugated to the e-NH2 groups of lysines on several target proteins (pupylation) such as the malonyl CoA acyl carrier protein (FabD) . Pupylation of FabD was shown to result in its recruitment to the mycobacterial proteasome and subsequent degradation analogous to eukaryotic ubiquitin-conjugated proteins. Searches recovered Pup orthologous in all major actinobacteria lineages including the basal bifidobacteria and also sporadically in certain other bacterial lineages .

Members of this protein family, formerly known as DUF797, have a conserved motif with a G [EQ] signature at the C terminus and are suitable for conjugation via the terminal glutamate or the deamidated glutamine (as shown in the case of the Mycobacterium Pup ). Pup is structurally unrelated to the ubiquitin fold and has convergently evolved the function of protein modifier. It has a binding-induced folding recognition mechanism that is different from substrate recognition in the ubiquitin-proteasome system . This protein, intrinsically disordered, links to target proteins via the ligase PafA, acquiring an ordered assembly to form two helices connected by a linker, positioning the C-terminal glutamate in the active site of this ligase .
Na,K-Atpase Interacting protein (Na/K-Atpase_Interacting)
Type: Family

NKAIN (Na,K-Atpase INteracting) proteins are a family of evolutionary conserved transmembrane proteins that localise to neurons, that are critical for neuronal function, and that interact with the beta subunits, beta1 in vertebrates and beta in Drosophila, of Na,K-ATPase. NKAINs have highly conserved trans-membrane domains but otherwise no other characterised domains. NKAINs may function as subunits of pore or channel structures in neurons or they may affect the function of other membrane proteins. They are likely to function within the membrane bilayer .
Putative lipoprotein GNA1162-like (GNA1162-like)
Type: Family

This entry represents a family of putative lipoproteins predominantly found in Proteobacteria, including GNA1162 from Neisseria meningitidis (

). This protein shows five α-helices and four β-strands, three of them forming a β-sheet .
Mff/Tango-11 (Mff/Tango-11)
Type: Family

This family includes Golgi organisation protein 11 (tango-11), and mitochondrial fission factor (Mff). The latter protein has a role in mitochondrial and peroxisomal fission .
Tandem-repeating region of mucin, epiglycanin-like (Tandem-repeating_mucin)
Type: Domain

The unusual mucin, epiglycanin, is membrane-bound at the C terminus but has a long region of this tandem-repeat at the N terminus . It was the first mucin identified to be associated with the malignant behaviour of carcinoma cells . Mouse Muc21/epiglycanin is thought to be a highly glycosylated molecule, which makes it likely that its function is dependent on its glycoforms. Cells expressing Muc21 are significantly less adherent to each other and to extracellular matrix components than control cells, and this loss of adhesion is mediated by the tandem-repeat portion of Muc21 .
Domain of unknown function DUF802 (DUF802)
Type: Domain

This region is found as two or more repeats in a small number of hypothetical proteins.
Magnesium transporter NIPA (Mg_trans_NIPA)
Type: Family

NIPA (nonimprinted in Prader-Willi/Angelman syndrome) is a family of integral membrane proteins which function as magnesium transporters . This entry also includes a group of uncharacterised bacterial proteins, such as Cgl0250 (UniProt:P42459) from Corynebacterium glutamicum.
Protein of unknown function DUF805 (DUF805)
Type: Family

This family consists of several bacterial proteins of unknown function.
Protein of unknown function DUF806 (DUF806)
Type: Family

This family consists of several Siphovirus and Lactococcus proteins of unknown function. The viral sequences are thought to be tail component proteins.
Protein of unknown function DUF807, Coxiella burnetii (DUF807_COXBU)
Type: Family

This family consists of several proteins of unknown function from Coxiella burnetii (the causative agent of a zoonotic disease called Q fever).
Inner membrane protein YedI (YedI)
Type: Family

This family of proteins includes inner membrane protein YedI.
Protein of unknown function DUF809 (DUF809)
Type: Family

This family consists of several proteins of unknown function from Raphanus sativus (Radish) and Brassica napus (Rape).
Protein unc-13 homologue (unc-13_homologue)
Type: Family

This family consists mainly of uncharacterised proteins from plants. The unc-13 homologue from
Arabidopsis thaliana
has been shown to control tethering of the proton ATPase AHA1 to the plasma membrane, and to be essential for the opening of stomata in repsonse to low levels of carbon dioxide and light. The unc13-like protein contains two Munc13 homology domains, which are known to mediate synaptic priming in neuronal exocytosis in animals, and may act similarly for plant stomata .
Coiled-coil domain-containing protein 22 (CCDC22)
Type: Family

Human coiled-coil domain-containing protein 22 (CCDC22) is involved in regulation of NF-kappa-B signalling; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex . It is part of the OMMD/CCDC22/CCDC93 (CCC) complex, which interacts with the multisubunit WASH complex required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer .

This entry also includes CCDC22 homologues from animals and plants.
NFACT, RNA-binding domain (NFACT_RNA-bd)
Type: Domain

This domain occurs in proteins that have been annotated as fibronectin/fibrinogen binding protein by similarity. This annotation comes from

where the N-terminal region is involved in this activity . This entry represents an RNA binding domain in the NFACT (NEMF, FbpA, Caliban, and Tae2) proteins. This domain is found in two eukaryotic gene contexts: fused to the NFACT-N and NFACT-C domains in the NFACT protein involved in the ribosomal quality control pathway which contributes to CAT-tailing, and as a standalone domain . Additionally this domain contains a conserved motif D/E-X-W/Y-X-H that may be functionally important.
Protein of unknown function DUF815 (DUF815)
Type: Family

This entry represents a family of bacterial proteins of unknown function. Many members contain an AAA+ ATPase domain (

).
Baculovirus protein of unknown function DUF816 (DUF816)
Type: Family

This family includes proteins that are about 200 amino acids in length. The proteins are all from baculoviruses. This family includes ORF107 from Orgyia pseudotsugata multicapsid polyhedrosis virus (OpMNPV) and a variety of other numbered ORF proteins, such as ORF52

, ORF140

from other baculoviruses. The function of these proteins is unknown.
Protein of unknown function DUF817 (DUF817)
Type: Family

This family consists of several bacterial proteins of unknown function.
Protein of unknown function DUF818 (DUF818)
Type: Family

This is a family of functionally uncharacterised proteins.
Protein of unknown function DUF819 (DUF819)
Type: Family

This family contains proteins of unknown function from archaeal, bacterial and plant species.
Putative restriction endonuclease (Uma2)
Type: Domain

This entry includes a group of putative nuclease, including hypothetical protein TT1808 (also known as Uma2 or TTHA1514), an AT-rich DNA-binding protein from Thermus thermophilus. This domain has a 3-layer α/β/α topology similar to that found in restriction endonucleases . The nuclease domain is ubiquitously found in enzymes involved in metabolism of nucleic acids, mostly in nucleases with diverse biological functions .
BES1/BZR1 plant transcription factor, N-terminal (BES1_N)
Type: Domain

This entry represents the N-terminal regions of several plant transcription factors. It is classified as BES1/BZR1, a plant-specific transcription factor that cooperates with transcription factors such as BIM1 to regulate brassinosteroid-induced genes .

Proteins containing this domain are transcriptional repressors involved in controlling the response to Brassinosteroids (BRs). BRs are plant hormones that play essential roles in growth and development. BZR1 binds directly to DNA repressing the synthesis of genes involved in BR synthesis. Phosphorylation of BZR1 by BIN1 targets BZR1 to the 20S proteosome, while dephosphorylation leads to nuclear accumulation of BZR1 .
InvasinE, Adhesion domain (InvE_AD)
Type: Domain

This entry represents the Adhesion domain found in InvasinE (InvE) from Yersinia pseudotuberculosis (

). Invasins are members of the inverse autotransporter (IAT) family also referred to as type Ve secretion system. In general, they consist of an N-terminal β-barrel-like domain, which is responsible for attachment of invasin to the outer membrane region of bacteria, repetitive Immunoglobulin-like (Ig) domains, which vary significantly in number among all the invasins, and the C-terminal domain/adhesion domain (AD), which provides invasins with the specificity to bind to its host target molecules. This domain adopts a C-type lectin-like domain (CTLD) fold with unique modifications. Its core structure is made up of a globular α/β fold and can be divided into three sub-sections: a lasso-shaped loop structure termed the "adaptor ring" since it forms a ring-shaped platform that connects BIg21 (

) with the two other sub-sections in the domain; the "C-type lectin-like domain" and the "wedge module". AD lacks the ability to coordinate Ca2+, and motifs such as EPN, QPD, and WND that are responsible for the specificity of carbohydrate recognition are also absent, giving rise to the notion that the it is not a carbohydrate binding domain .

This domain is also found repeated in sequences from Enterobacterales such as Salmonella typhimurium and Escherichia coli. These repeats are almost always found with

and are associated with RatA and RatB, the coding sequences of which are found in the pathogeneicity island of Salmonella. The sequences may be determinants of pathogenicity .
Bacterial Immunoglobulin-like 21 (BIg21)
Type: Domain

This entry represents the Bacterial Immunoglobulin-like 21 (BIg21) domain found in InvasinE (InvE). Invasins are members of the inverse autotransporter (IAT) family also referred to as type Ve secretion system. In general, they consist of an N-terminal β-barrel-like domain, which is responsible for attachment of invasin to the outer membrane region of bacteria, repetitive Immunoglobulin-like (Ig) domains, which vary significantly in number among all the invasins, and the C-terminal domain/adhesion domain (AD)

) which provides invasins with the specificity to bind to its host target molecules. The overall structure of InvE shows that it comprises of three domain architecture in which the domains BIg20 (Bacterial Immunoglobulin-like 20) and BIg21 adopt two layer β-sandwich fold resembling eukaryotic members of Immunoglobulin-superfamily (IgSF), while the AD is a globular, α/β-domain. The structure of BIg21 belongs to the I2 set of IgSF with a unique modification in the C-E interstrand loop, important for its interaction with AD. BIg21 and AD form a functional super-domain as well, necessary to target the host receptor .
Uncharacterised protein family Ycf2 (Uncharacterised_Ycf2)
Type: Family

This family consists of chloroplast encoded Ycf2, which is around 2000 residues in length. Ycf2 is a component of the Ycf2-FtsHi complex which has been identified as chloroplast import motor. The Ycf2-FtsHi complex is composed of six distinct components. This heterohexameric assembly is organized in a counterclockwise order with components arranged as Ycf2, FtsHi5, FtsHi1, FtsHi2, FtsHi4, and FtsH12 . A collaborative interplay between the Ycf2-FtsHi complex and the TIC (translocon at the inner chloroplast membrane) complex, contributes to the efficient translocation of preproteins into the chloroplasts .
Protein of unknown function DUF826 (DUF826)
Type: Family

This family consists of several enterobacterial and caudovirales sequences of unknown function. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
WEB family (Web)
Type: Family

Proteins in this family include WEB1 (At2g26570) and PMI15 (At5g38150) from Arabidopsis thaliana.

Both Web1 and PMI15 are required for the chloroplast avoidance response under high intensity blue light. This avoidance response consists in the relocation of chloroplasts on the anticlinal side of exposed cells. Web1 acts in association with PMI2 to maintain the velocity of chloroplast photorelocation movement via cp-actin filaments regulation .
VAN3-binding protein-like, auxin canalisation domain (VAN3-bd-like_auxin_canal)
Type: Domain

This domain can be found at the N-terminal end of several plant proteins, including VAN3-binding protein from Arabidopsis thaliana (also known as FORKED1), a component of the auto-regulatory loop which enables auxin canalisation by recruitment of the PIN1 auxin efflux protein to the cell membrane . This domain is frequently found on proteins containing

at the C terminus.
Protein of unknown function DUF829, TMEM53 (DUF829_TMEM53)
Type: Family

This signature identifies Transmembrane protein 53, that have no known function but are predicted to be integral membrane proteins.
Herpesvirus tegument protein BRRF2-like (Herpesvirus_BRRF2-like)
Type: Family

This entry contains BRRF2 from Epstein-Barr virus. This protein family is restricted to the herpesviruses; it's function is not known. The protein is phosphorylated and is associated with the viral tegument .
Transport and Golgi organisation protein 2 (TANGO2)
Type: Family

In eukaryotes this family is predicted to play a role in protein secretion and Golgi organisation . In plants this family includes

, which is involved in water permeability in the cuticles of fruit .

has been found to be expressed during early embryogenesis in mice . This protein contains a conserved NRDE motif. This gene has been characterised in Drosophila melanogaster and named as transport and Golgi organisation 2, hence the name Tango2.
Domain of unknown function DUF834 (DUF834)
Type: Domain

This short presumed domain is found in a large number of hypothetical plant proteins. The domain is quite rich in conserved glycine residues. It occurs in some putative transposons but currently has no known function.
Domain of unknown function DUF835 (DUF835)
Type: Domain

The members of this archaebacterial protein entry are around 250-300 amino acid residues in length. The function of these proteins is not known.
Glutaredoxin-like (Glutaredoxin-like)
Type: Family

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This family contains several viral glutaredoxins, and many related bacterial and eukaryotic proteins of unknown function. The best characterised member of this family is G4L (

) from Vaccinia virus (strain Western Reserve/WR) (VACV), which is necessary for virion morphogenesis and virus replication . This is a cytoplasmic protein which functions as a shuttle in a redox pathway between membrane-associated E10R and L1R or F9L .