SII-SWORD/CoKE huggingface dataset:
Expansin/Lol pI (Expan_Lol_pI)
Type: Family

Expansins are unusual proteins that mediate cell wall extension in plants . They are believed to act as a sort of chemical grease, allowing polymers to slide past one another by disrupting non-covalent hydrogen bonds that hold many wall polymers to one another. This process is not degradative and hence does not weaken the wall, which could otherwise rupture under internal pressure during growth.

Sequence comparisons indicate at least four distinct expansin cDNAs in rice and at least six in Arabidopsis. The proteins are highly conserved in size and sequence (75-95% amino acid sequence similarity between any pairwise comparison), and phylogenetic trees indicate that this multigene family formed before the evolutionary divergence of monocotyledons and dicotyledons . Sequence and motif analyses show no similarities to known functional domains that might account for expansin action on wall extension. It is thought that several highly-conserved tryptophans may function in expansin binding to cellulose, or other glycans. The high conservation of the family indicates that the mechanism by which expansins promote wall extensin tolerates little variation in protein structure.
Phage tail spike protein, N-terminal domain (Phage_tail_spike_N)
Type: Domain

This entry represents the conserved N-terminal domain found in Tail spike protein from Bacillus phage SPP1 (Gp21) and similar sequences from tailed bacteriophages and bacterial prophages. Gp21 binds to the host entry receptor YueB and triggers viral DNA ejection. This interaction initiates a cascade of conformational changes at the C terminus of the protein, causing disassembly of the tail spike organisation and opening of the cap region formed by the N-terminal .
DNA-directed RNA polymerase, subunit 2, hybrid-binding domain (DNA-dir_RNAP_su2_dom)
Type: Domain

RNA polymerases (

) catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This domain represents the hybrid-binding domain and the wall domain . The hybrid-binding domain binds the nascent RNA strand/template DNA strand in the Pol II transcription elongation complex. This domain contains the important structural motifs, switch 3 and the flap loop and binds an active site metal ion . This domain is also involved in binding to Rpb1 and Rpb3 . Many of the bacterial members contain large insertions within this domain, which are known as dispensable region 2 (DRII).
RNA polymerase, beta subunit, conserved site (RNA_pol_bsu_CS)
Type: Conserved_site

RNA polymerases (

) catalyse the DNA dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial. and chloroplast polymerases). This domain represents the hybrid binding domain and the wall domain . The hybrid-binding domain binds the nascent RNA strand / template DNA strand in the Pol II transcription elongation complex. This domain contains the important structural motifs, switch 3 and the flap loop and binds an active site metal ion . This domain is also involved in binding to Rpb1 and Rpb3 . Many of the bacterial members contain large insertions within this domain, which is known as dispensable region 2 (DRII).
Villin/Gelsolin (Villin/Gelsolin)
Type: Family

Gelsolin is an actin-modulating protein that severs F-actin, caps the barbed ends of actin filaments preventing monomer exchange, and promotes the nucleation step of actin polymerisation . It can be regulated by Ca2+ and phosphoinositides . The interaction between gelsolin and tropomyosin modulates actin dynamics . Gelsolin also plays a role in ciliogenesis . The structure of gelsolin has been solved .
Gelsolin-like domain (Gelsolin-like_dom)
Type: Domain

Gelsolin is a cytoplasmic, calcium-regulated, actin-modulating protein that binds to the barbed ends of actin filaments, preventing monomer exchange (end-blocking or capping) . It can promote nucleation (the assembly of monomers into filaments), as well as sever existing filaments. In addition, this protein binds with high affinity to fibronectin. Plasma gelsolin and cytoplasmic gelsolin are derived from a single gene by alternate initiation sites and differential splicing.

Sequence comparisons indicate an evolutionary relationship between gelsolin,
villin, fragmin and severin . Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. While the multiple repeats have yet to be related to any known function of the actin-severing proteins, the superfamily appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues .

This gelsolin-like domain can also be found in the C-terminal of the members of Sec23/Sec24 family. They are components of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
Histone H2A/H2B/H3 (Histone_H2A/H2B/H3)
Type: Domain

Five major families of histones exist: H1/H5, H2A, H2B, H3, and H4 . Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones. The core histones together with some other DNA binding proteins form a superfamily defined by a common fold and distant sequence similarities . Some proteins contain local homology domains related to the histone fold .

This entry represents a domain found in histones H2A, H2B and H3. This domain can also be found in transcription factors, such as OsNF-YC2 from rice .
Borrelia REV (Borrelia_REV)
Type: Family

This family consists of several REV proteins from Borrelia burgdorferi (Lyme disease spirochete) and Borrelia garinii. The function of REV is unknown although it has been shown that the gene is induced during the ingesting of host blood suggesting a role in the metabolic activation of borreliae to adapt to physiological stimuli .
RNA polymerase sigma factor 70, region 1.1 (RNA_pol_sigma_70_r1_1)
Type: Domain

The bacterial core RNA polymerase complex, which consists of five subunits, 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 . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .

This entry represents Region 1.1 which modulates DNA binding by region 2 and 4 when sigma is unbound by the core RNA polymerase . Region 1.1 is also involved in promoter binding, it contains a basic patch on its surface which suggests to play an important role in DNA interaction to facilitate open promoter complex formation .
Nuclear MIS12/MIND complex subunit PMF1/Nnf1 (PMF1/Nnf1)
Type: Family

This entry includes polyamine-modulated factor 1 (PMF1) from animals and Nnf1 from yeasts. PMF1 is part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis . Nnf1 is an essential component of the MIND kinetochore complex required for accurate chromosome segregation .
Ubiquinol-cytochrome c chaperone, CBP3 (Ubiqinol_cyt_c_chaperone_CPB3)
Type: Family

Saccharomyces cerevisiae ubiquinol-cytochrome C chaperone (known as CBP3) is required for assembly of coenzyme QF-2-cytochrome C reductase. The crystal structure of this protein has been resolved in the homologue from the bacteria Brucella abortus, showing an all-helical fold . Homologues are found in a number of different organisms including Homo sapiens (Ubiquinol-cytochrome-c reductase complex assembly factor 1, UQCC1) .
Diacylglycerol acyltransferase (DAGAT)
Type: Family

This family includes diacylglycerol acyltransferases which catalyse the terminal and only committed step in triacylglycerol (TAG) synthesis using diacylglycerol (DAG) and fatty acyl-CoA as substrates. It is required for synthesis and storage of intracellular triglycerides . In yeast, it is involved in lipid particle synthesis from the endoplasmic reticulum, promoting localized TAG production at discrete ER subdomains, and in ergosterol biosynthesis .

This family also includes Acyl-CoA wax alcohol acyltransferase 1 and 2 (AWAT1/2), which catalyse the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters . AWAT2 (also known as MFAT) also possesses acyl-CoA retinol acyltransferase (ARAT) activity that catalyses 11-cis-specific retinyl ester synthesis and shows higher catalytic efficiency toward 11-cis-retinol versus 9-cis-retinol, 13-cis-retinol, and all-trans-retinol substrates .

Phytyl ester synthase 1/2, chloroplastic, an acyltransferase involved in fatty acid phytyl ester synthesis in chloroplasts, also belongs to this family. This process is required for the maintenance of the photosynthetic membrane integrity during abiotic stress and senescence .
SLA1 homology domain 1, SHD1 (SHD1)
Type: Domain

The SLA1 homology domain (SHD1) is found in the cytoskeleton assembly control protein SLA1, which is responsible for the correct formation of the actin cytoskeleton. SHD1 is responsible for recognition of the NPFxD internalisation signal found in the cytoplasmic domains of transmembrane proteins .
Protein of unknown function DUF346 (DUF346)
Type: Repeat

This repeat is found as seven tandem copies in carbohydrate-binding proteins, including Fucose-binding Lectin from Photorhabdus laumondii (

)and similar fungal and bacterial proteins. It is composed of β-strands and forms a seven-bladed β-propeller structure . It is found in association with BNR repeats, which also form a β-propeller.
RNA polymerase II associated factor Paf1 (RNA_pol_II-assoc_Paf1)
Type: Family

In budding yeasts, Paf1 is part of the Paf1 complex, an RNA polymerase II-associated protein complex containing Paf1, Cdc73, Ctr9, Rtf1 and Leo1 . Paf1 complex is involved in histone modifications, transcription elongation and other gene expression processes that include transcript site selection .
Ubiquitin-like-conjugating enzyme Atg3/Atg10 (Atg3/Atg10)
Type: Family

This entry represents a group of ubiquitin-like-conjugating enzymes, including Atg3 and Atg10.

Atg3 is the E2 enzyme for the LC3 lipidation process . It is essential for autophagocytosis. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place .

Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an α/β-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long α-helical structure that protrudes from the core region as far as 30 A . It interacts with Atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of Atg8. It also interacts with the C-terminal region of the E1-like Atg7 enzyme .

Atg10 acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5 .
Protein of unknown function DUF347 (DUF347)
Type: Repeat

This repeat is found as four tandem repeats in a family of bacterial membrane proteins. Each repeat contains two transmembrane regions and a conserved tryptophan.
Resuscitation-promoting factor, domain of unknown function DUF348 (DUF348)
Type: Domain

This domain normally occurs as tandem repeats. It is found in resuscitation-promoting factors RpfB from Mycobacterium tuberculosis and Rpf2 from Corynebacterium glutamicum. These are factors that stimulate resuscitation of dormant cells .
Antibiotic biosynthesis monooxygenase domain (ABM_dom)
Type: Domain

The antibiotic biosynthesis monooxygenase (ABM) domain is found in proteins involved in a diverse range of biological processes, including metabolism, transcription, translation and biosynthesis of secondary metabolites:

Streptomyces coelicolor ActVA-Orf6 monooxygenase, plays a role in the biosynthesis of aromatic polyketides, specifically the antibiotic actinorhodin, by oxidizing phenolic groups to quinones .

Escherichia coli probable quinol monooxygenase YgiN, can oxidize menadiol to menadione .

Staphylococcus aureus heme-degrading enzymes IsdG and IsdI .

Staphylococci signal transduction protein TRAP (target of RNAIII- activating protein) .

Mycobacterium tuberculosis heme-degrading monooxygenase MhuD (or Rv3592) .

Mycobacterium tuberculosis putative monooxygenase Rv0793, might be involved in antibiotic biosynthesis, or may act as reactive oxygen species scavenger that could help in evading host defenses .

Thermus thermophilus hypothetical protein TT1380 .

The ABM domain has only moderate sequence homology while sharing a high degree of structural similarity. The ABM domain crystallises as a homodimer. Each monomer is composed of three α-helices (H1-3) and four β-strands (S1-4) and has a ferredoxin-like split β-α-β-fold with an antiparallel β-sheet . The β-sheets of two monomers form a 10-strand, anti- parallel β-barrel. The barrel is built of two smaller sheets that are connected by long C-terminal strands crossing over from one monomer to the other providing important interactions within the dimer. The core of the barrel is mainly hydrophobic .
Protein of unknown function DUF349 (DUF349)
Type: Repeat

This motif is found singly or as up to five tandem repeats in a small set of bacterial proteins. There are two or three α-helices, and possibly a β-strand.
Protein of unknown function DUF350 (DUF350)
Type: Repeat

This motif occurs in a small set of bacterial proteins. It has two transmembrane regions, and often occurs as tandem repeats. The are no conserved catalytic residues.
Haemagglutinin-esterase glycoprotein, core (Hemagglutn-estrase_core)
Type: Domain

Haemagglutinin-esterase fusion glycoprotein (HEF) is a multi-functional protein embedded in the viral envelope of several viruses, including influenza C virus, coronaviruses and toroviruses . HEF is required for infectivity, and functions to recognise the host cell surface receptor, to fuse the viral and host cell membranes, and to destroy the receptor upon host cell infection. The haemagglutinin region of HEF is responsible for receptor recognition and membrane fusion, and bears a strong resemblance to the sialic acid-binding haemagglutinin found in influenza A and B viruses, except that it binds 9-O-acetylsialic acid. The esterase region of HEF is responsible for the destruction of the receptor, an action that is carried out by neuraminidase in influenza A and B viruses. The esterase domain is similar in structure to Streptomyces scabies esterase, and to acetylhydrolase, thioesterase I and rhamnogalacturonan acetylesterase.

The haemagglutinin-esterase glycoprotein HEF must be cleaved by the host's trypsin-like proteases to produce two peptides (HEF1 and HEF2) in order for the virus to be infectious. Once HEF is cleaved, the newly exposed N-terminal of the HEF2 peptide then acts to fuse the viral envelope to the cellular membrane of the host cell, which allows the virus to infect the host cell.

The haemagglutinin-esterase glycoprotein is a trimer, where each monomer is composed of three domains: an elongated stem active in membrane fusion, an esterase domain, and a receptor-binding domain, where the stem and receptor-binding domains together resemble influenza A virus haemagglutinin. Two of these domains are composed of non-contiguous sequence: the receptor-binding haemagglutinin domain is inserted into a surface loop of the esterase domain, and the esterase domain is inserted into a surface loop of the haemagglutinin stem.
Vacuolar protein sorting-associated Vps28 (Vps28)
Type: Family

The Endosomal Sorting Complex Required for Transport (ESCRT) complexes form the machinery driving protein sorting from endosomes to lysosomes. ESCRT complexes are central to receptor down-regulation, lysosome biogenesis, and budding of HIV. Yeast ESCRT-I consists of three protein subunits, Vps23, Vps28, and Vps37. In humans, ESCRT-I comprises TSG101, VPS28, and one of four potential human VPS37 homologues. The main role of ESCRT-I is to recognise ubiquitinated cargo via the UEV domain of the VPS23/TSG101 subunit. The assembly of the ESCRT-I complex is directed by the C-terminal steadiness box (SB) of VPS23, the N-terminal half of VPS28, and the C-terminal half of VPS37. The structure is primarily composed of three long, parallel helical hairpins, each corresponding to a different subunit. The additional domains and motifs extending beyond the core serve as gripping tools for ESCRT-I critical functions .
Small-subunit processome, Utp11 (SSU_processome_Utp11)
Type: Family

A large ribonuclear protein complex is required for the processing of the small-ribosomal-subunit rRNA -the small-subunit (SSU) processome . This preribosomal complex contains the U3 snoRNA and at least 40 proteins, which have the following properties:

They are nucleolar.

They are able to coimmunoprecipitate with the U3 snoRNA and Mpp10 (a protein specific to the SSU processome).

They are required for 18S rRNA biogenesis.

There appears to be a linkage between polymerase I transcription and the formation of the SSU processome; as some, but not all, of the SSU processome components are required for pre-rRNA transcription initiation. These SSU processome components have been termed t-Utps. They form a pre-complex with pre-18S rRNA in the absence of snoRNA U3 and other SSU processome components. It has been proposed that the t-Utp complex proteins are both rDNA and rRNA binding proteins that are involved in the initiation of pre18S rRNA transcription. Initially binding to rDNA then associating with the 5' end of the nascent pre18S rRNA. The t-Utpcomplex forms the nucleus around which the rest of the SSU processome components, including snoRNA U3, assemble . From electron microscopy the SSU processome may correspond to the terminal knobs visualised at the 5' ends of nascent 18S rRNA.

This entry contains Utp11, a large ribonuclear protein that associates with snoRNA U3 .
Microtubule-associated protein, MAP65/Ase1/PRC1 (MAP65_Ase1_PRC1)
Type: Family

This is a family of microtubule associated proteins, including MAP65 (MAP65-1/2/3/4/5/6/7/8/9) from Arabidopsis, Ase1 from yeast, and PRC1 from mammals.

Ase1 is required for spindle elongation and stabilisation. It is cell cycle-regulated by anaphase promoting complex . It is a potential Cdc28p substrate .
Sas10/Utp3/C1D (Sas10/Utp3/C1D)
Type: Family

This entry represents Something about silencing protein 10 (SAS10, also known as UTP3)
and U3 small nucleolar ribonucleoprotein protein LCP5 which are components of the U3 ribonucleoprotein complex . It also includes Nuclear nucleic acid-binding protein C1D from Mus musculus (Mouse), which plays a role in the recruitment of the RNA exosome complex to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA , Protein THALLO from Arabidopsis thaliana, essential during embryogenesis and the human protein Neuroguidin, an initiation factor 4E (eIF4E)-binding protein .
Transcription factor Vhr (TF_Vhr)
Type: Family

The Vhr1 family of budding yeast transcription factors consists of Vhr1 and Vhr2 . Vhr1 regulates the biotin-dependent expression of transporters VHT1 and BIO5 . Vhr2 regulates ERG9, but seems to have a more global function in transcription .
Small-subunit processome, Utp12 (SSU_processome_Utp12)
Type: Domain

A large ribonuclear protein complex is required for the processing of the small-ribosomal-subunit rRNA -the small-subunit (SSU) processome . This preribosomal complex contains the U3 snoRNA and at least 40 proteins, which have the following properties:

They are nucleolar.

They are able to coimmunoprecipitate with the U3 snoRNA and Mpp10 (a protein specific to the SSU processome).

They are required for 18S rRNA biogenesis.

There appears to be a linkage between polymerase I transcription and the formation of the SSU processome; as some, but not all, of the SSU processome components are required for pre-rRNA transcription initiation. These SSU processome components have been termed t-Utps. They form a pre-complex with pre-18S rRNA in the absence of snoRNA U3 and other SSU processome components. It has been proposed that the t-Utp complex proteins are both rDNA and rRNA binding proteins that are involved in the initiation of pre18S rRNA transcription. Initially binding to rDNA then associating with the 5' end of the nascent pre18S rRNA. The t-Utpcomplex forms the nucleus around which the rest of the SSU processome components, including snoRNA U3, assemble . From electron microscopy the SSU processome may correspond to the terminal knobs visualised at the 5' ends of nascent 18S rRNA.

This domain is found at the C terminus of proteins containing WD40 repeats. These proteins are part of the U3 ribonucleoprotein. In yeast, these proteins are called Utp5, Utp1 or Pwp2, Utp12 or DIP2

. They interact with snoRNA U3 and with MPP10 . Pwp2 is an essential Saccharomyces cerevisiae (Baker's yeast) protein involved in cell separation.
Leo1-like protein (Leo1)
Type: Family

In budding yeasts, Leo1 is part of the Paf1 complex, an RNA polymerase II-associated protein complex containing Paf1, Cdc73, Ctr9, Rtf1 and Leo1. Paf1 complex is involved in histone modifications, transcription elongation and other gene expression processes that include transcript site selection .
HUS1/Mec3 (HUS1/Mec3)
Type: Family

This entry consists of the human HUS1 protein and budding yeast Mec3. They are components of the checkpoint clamp complex involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes .
Protein of unknown function DUF354 (DUF354)
Type: Family

Members of this family are around 350 amino acids in length. They are found in archaea and some bacteria and have no known function.
Adenosine specific kinase (Adenosine_kinase)
Type: Family

The structure of a member of this family from the hyperthermophilic archaeon Pyrobaculum aerophilum contains a modified histidine residue which is interpreted as stable phosphorylation. In vitro binding studies confirmed that adenosine and AMP but not ADP or ATP bind to the protein .
Protein of unknown function DUF356 (DUF356)
Type: Family

Members of this family are around 120 amino acids in length and are found in some archaebacteria. The function of this family is unknown. However it contains a conserved motif IHPPAH that may be involved in its function.
MamQ/LemA (MamQ_LemA)
Type: Family

This family includes the magnetosome protein MamQ as well as a functionally uncharacterised protein called LemA which is predicted to be a transmembrane protein with an extracellular N terminus . MamQ has been shown to be essential for magnetosome formation .