SII-SWORD/CoKE huggingface dataset:
Zf-FLZ domain (Zf-FLZ_dom)
Type: Domain

Zinc fingers are a ubiquitous class of protein domain with considerable variation in structure and function. The FCS-type zinc finger is a highly diverged group of C2-C2 zinc finger, named after the conserved phenylalanine and serine residues associated with the third cysteine. The FCS-type zinc finger is a structurally diverse family which accommodate both nucleic-protein and protein-protein interaction zinc fingers. The FCS-Like Zinc finger (FLZ) domain is a plant specific domain. FLZ domain containing proteins are bryophytic in origin and this protein family is expanded in higher plants. Although the molecular functions of the FLZ protein family members in general are not well understood, many of the members are attributed to plant growth and development, stress mitigation, sugar signaling and senescence. The FLZ-type zinc finger is likely to be involved in protein-protein interaction .

The FLZ-type zinc finger is predicted to form an α-β-α secondary structure composed of an N-terminal short α-helix, a β-hairpin followed by a longer C-terminal α-helix. Four highly conserved cysteine residues in the FLZ-type zinc finger are believed to bind zinc in a tetrahedral coordination .

Some proteins known to contain a FLZ-type zinc finger are listed below :

Arabidopsis thaliana MEDIATOR OF ABA-REGULATED DORMANCY 1 (MARD1) or FLZ9, involved in abcissic acid (ABA)-mediated seed dormancy and induced during senescence.

Arabidopsis thaliana INCREASED RESISTANCE TO MYZUS PERSICAE (IRM1) or FLZ4, constitutive over expression of IRM1 results in mechanical barriers that make it difficult for M. persicae to reach the phloem and subsequently reduces its population size.

Wheat salt related hypothetical protein (TaSRHP), over expression of TaSHRP results in enhanced resistance to salt and drought stress.
Lipin, N-terminal (Lipin_N)
Type: Domain

Mutations in the lipin gene lead to fatty liver dystrophy in mice. The protein has been shown to be phosphorylated by the TOR Ser/Thr protein kinases in response to insulin stimulation. This entry represents a conserved domain found at the N terminus of the member proteins .
Alpha 1,4-glycosyltransferase domain (A1-4-GlycosylTfrase_dom)
Type: Domain

The glycosphingolipids (GSL) form part of eukaryotic cell membranes. They consist of a hydrophilic carbohydrate moiety linked to a hydrophobic ceramide tail embedded within the lipid bilayer of the membrane. Lactosylceramide, Gal1,4Glc1Cer (LacCer), is the common synthetic precursor to the majority of GSL found in vertebrates. Alpha 1.4-glycosyltransferases utilise UDP donors and transfer the sugar to a beta-linked acceptor .

No function has been yet assigned to this domai
Signal peptidase complex subunit 3 (SPC3)
Type: Family

This entry includes signal peptidase complex subunit 3 (Spc3, also known as SPC22) and its homologues from fungi, plants and animals.

Translocation of polypeptide chains across the endoplasmic reticulum membrane is triggered by signal sequences. During translocation of the nascent chain through the membrane, the signal sequence of most secretory and membrane proteins is cleaved off. Cleavage occurs by the signal peptidase complex (SPC) which consists of four subunits in yeast and five in mammals .
NAD-dependent histone deacetylase Sir2, N-terminal (NAD-dep_histone_deAcase_SIR2_N)
Type: Domain

This N-terminal region is found in SIR2 proteins (

) and its homologues. Its function is uncharacterised.
Surface lipoprotein assembly modifier, C-terminal domain (Slam_C)
Type: Domain

Slam, also known as NTHI1171 in Haemophilus influenzae, is a surface lipoprotein that may have a role in virulence . In Neisseria, it is required for the surface display of lipidated virulence factors . This entry represents the C-terminal eight-stranded β-barrel domain .
GTD-binding domain (GTD-bd)
Type: Domain

The GTD-binding domain is a plant-specific protein-protein interaction domain. It emerged in primitive land plants and founded a multigene family that is conserved in all flowering plants. Proteins with GTD-binding domains fall into four groups, where group 1-3 contain the GTD-binding domain at the C-terminal half of the protein and one (group 2) or more (group1) predicted transmembrane domains, or an endoplasmic reticulum signal peptide (group 3) at the N- terminus, whereas group 4 contains the GTD-binding domain near the N terminus. GTD-binding domain proteins may constitute a family of myosin receptors, which are associated with the surface of specific plant organelles, bind to the globular tail domain (GTD) of myosin motor proteins, and thereby promote actin-dependent organelle motility. It seems likely that myosin binding is a common property of the GTD-binding domain, whereas the ability of FLOURY1 to bind maize-specific zeins is a specific feature of this endoplasmic reticulum (ER)-associated protein.

The GTD-binding domain is predicted to adopt a coiled-coil structure.

Some proteins known to contain a GTD-binding domain are listed below:

Maize FLOURY1 (FL1), which belongs to group 1. Its GTD-binding domain facilitates the localization of 22kDa alpha-zein .

Arabidopsis myosin binding (MyoB) proteins 1-6 and 7, which belong respectively to group 3 and 4. They bind to myosin XI .

Tobacco RAC5 interacting subapical pollen tube protein (RISAP), which belongs to group 3. It binds via its GTD-binding domain to the GTD domain of a pollen tube myosin XI .

Lily LLP13, which belongs to group 3. It is likely a cytoskeleton-binding protein that binds with intermediate filaments (IFs) that potentially exist in pollen tubes .
Glycosyltransferase 61 (Glycosyltransferase_61)
Type: Family

Glycosyltransferase 61 family members are further processed into a mature form. Proteins in this family includes O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 (POMGnT2, also known as EOGTL) and EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) .

This entry also includes plant beta-(1,2)-xylosyltransferase .
Protein of unknown function DUF594 (DUF594)
Type: Family

This is a family of uncharacterised proteins.
Keratin, high-sulphur matrix protein (Keratin_matx)
Type: Family

This is a family of keratins, high-sulphur matrix proteins. The keratin products of mammalian epidermal derivatives such as wool and hair consist of microfibrils embedded in a rigid matrix of other proteins. The matrix proteins include the high-sulphur and high-tyrosine keratins, having molecular weights of 6-20kDa, whereas microfibrils contain the larger, low-sulphur keratins (40-56kDa) .
Poxvirus D3 (Poxvirus_D3)
Type: Family

This entry represents Protein D3 from Vaccinia virus, also known as Core protein OPG115, and similar sequences from poxvirus. D3 is a late protein which is part of a large complex required for early virion morphogenesis. This complex participates in the formation of virosomes and the incorporation of virosomal contents into nascent immature virions . The conserved region occupies the entire length of D3 protein.
Reovirus sigma C capsid protein, C-terminal (SigmaC_C)
Type: Domain

Protein sigmaC in its native state was shown to be a homotrimer. It was demonstrated that the sigmaC subunits are not covalently bound via disulphide linkages and the formation of an intrachain disulphide bond between the two cysteine residues of the sigmaC polypeptide may have a negative effect on oligomer stability. The susceptibility of the trimer to pH, temperature, ionic strength, chemical denaturants and detergents indicates that hydrophobic interactions contribute much more to oligomer stability than do ionic interactions and hydrogen bonding .
Baculoviridae p74 (Baculo_p74)
Type: Family

Baculoviruses are distinct from other virus families in that there are two viral phenotypes: budded virus (BV) and occlusion-derived virus (ODV). BVs disseminate viral infection throughout the tissues of the host and ODVs transmit baculovirus between insect hosts. In the Autographa californica nuclear polyhedrosis virus, p74 (also known as per os infectivity factor 0) is important for attachment to the host caterpillar midgut and fusion by binding to a specific host receptor . P74 is anchored in the ODV envelope by a C-terminal transmembrane anchor domain and is N-terminally exposed on the ODV surface .
Poxvirus A28 (Poxvirus_A28)
Type: Family

The poxvirus A28 protein, also known as Envelope protein OPG155, is expressed at late times during the virus replication cycle and is a membrane component of the intracellular mature virion. Repression of A28 inhibits cell-to-cell spread, suggesting that all poxviruses use a common A28-dependent mechanism of cell penetration . An N-terminal hydrophobic sequence, present in all poxvirus A28 orthologues, anchors the protein in the virion surface membrane so that most of it is exposed to the cytoplasm .
ADP-specific phosphofructokinase/glucokinase (ADP_PFK/GK)
Type: Family

Although ATP is the most common phosphoryl group donor for kinases, certain hyperthermophilic archaea, such as Thermococcus litoralis and Pyrococcus furiosus, utilise unusual ADP-dependent glucokinases (ADPGKs) and phosphofructokinases (ADPPKKs) in their glycolytic pathways . ADPGKs and ADPPFKs exhibit significant similarity, and form an ADP-dependent kinase (ADPK) family, which was tentatively named the PFKC family . A ~460-residue ADPK domain is also found in a bifunctional ADP-dependent gluco/phosphofructo-kinase (ADP-GK/PFK) from Methanocaldococcus jannaschii (Methanococcus jannaschii) as well as in homologous proteins present in several eukaryotes . Structure determination for eukaryotic ADPGK revealed an overall similar fold to archaeal orthologues with some differences in secondary structural elements. In the nucleotide-binding loop of eukaryotic ADPGK there is a disulfide bond between conserved cysteines; one of the cysteines coordinating the AMP defines an apparently nucleotide-binding motif unique to eukaryotic ADPGKs. Mammalian enzymes are specific for glucose .

The whole structure of the ADPK domain can be divided into large and small α/β subdomains. The larger subdomain, which carries the ADP binding site, consists of a twisted 12-stranded β-sheet flanked on both faces by 13 α-helices and three 3(10) helices, forming an α/β 3-layer sandwich. The smaller subdomain, which covers the active site, forms an α/β two-layer structure containing 5 bβ-strands and four α-helices. The ADP molecule is buried in a shallow pocket in the large subdomain. The binding of substrate sugar induces a structural change, the small domain closing to form a complete substrate sugar binding site .
Hypoxia induced protein, domain (Hypoxia_induced_domain)
Type: Domain

This entry represents the transmembrane region found in the hypoxia induced gene 1 (HIG1), Respiratory supercomplex factor 1/2 (rcf1) and other proteins such as RING-H2 finger protein ATL48.

The hypoxia induced gene 1 (HIG1) or hypoglycemia/hypoxia inducible mitochondrial protein (HIMP1) is up-regulated by stresses of the microenvironment such as low oxygen or low glucose conditions. HIG1 is a mitochondrial inner membrane protein, which is ubiquitously expressed. It is predicted to be an integral membrane protein consisting of two hydrophobic helices, 21-23 residues in length that might tend to form a hairpin-like loop across the bilayer. HIG1 could be implied in apoptotic or cytoprotective signals. HIG1 is a member of a well conserved eukaryote protein family. The predicted transmembrane helice (TMH) and loop regions represent the most highly conserved regions in these proteins . The profile we developed covers the predicted TMH and loop regions.

This domain is found in proteins thought to be involved in the response to hypoxia . It is also found in altered inheritance of mitochondria proteins.
RFX1 transcription activation region (RFX1_trans_act)
Type: Domain

The RFX family is a family of winged-helix DNA-binding proteins. RFX1 is a regulatory factor essential for expression of MHC class II genes. This region is found N-terminal to the RFX DNA-binding region (

) in some mammalian RFX proteins, and is thought to activate transcription when associated with DNA. Deletion analysis has identified the region 233-351 in human RFX1 (

) as being required for maximal activation .
Carbohydrate sulfotransferase Chst-1-like (Chst-1-like)
Type: Family

A chondroitin sulfate (CS) sulfotransferase has been identified in the nematode Caenorhabditis elegans, and has been named as chst-1 (CarboHydrate SulfoTransferase) . This chondroitin 4-O-sulfotransferase plays an important role in protecting nematodes from oxidative stress .
Protein of unknown function DUF596 (DUF596)
Type: Family

This family contains several uncharacterised proteins.
Selenoprotein P, N-terminal (Selenoprotein-P_N)
Type: Domain

SelP is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec) residues, and accounts for more than 50% of the selenium content of rat and human plasma . It is thought to be glycosylated . SelP may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitrite toxicity . The high selenium content of SelP suggests that it may be involved in selenium intercellular transport or storage . The promoter structure of bovine SelP suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function .

This entry represents the N-terminal region of SelP, which can exist independently of the C-terminal region. The N terminus is larger, contains less Selenium and is thought to be heavily glycosylated. It appears to supply selenium to the kidney . Zebrafish selenoprotein Pb (

) lacks the C-terminal Sec-rich region, and a protein encoded by the rat SelP gene and lacking this region has also been reported . The N-terminal region contains a conserved SecxxCys motif, which is similar to the CysxxCys found in thioredoxins. It is speculated that the N-terminal region may adopt a thioredoxin fold and catalyse redox reactions . The N-terminal region also contains a His-rich region, which is thought to mediate heparin binding. Binding to heparan proteoglycans could account for the membrane binding properties of SelP .

The function of the bacterial members of this family is uncharacterised.
Selenoprotein P, C-terminal (SelP_C)
Type: Domain

SelP is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec) residues, and accounts for more than 50% of the selenium content of rat and human plasma . It is thought to be glycosylated . SelP may have antioxidant properties. It can attach to epithelial cells, and may protect vascular endothelial cells against peroxynitrite toxicity . The high selenium content of SelP suggests that it may be involved in selenium intercellular transport or storage . The promoter structure of bovine SelP suggests that it may be involved in countering heavy metal intoxication, and may also have a developmental function . The N-terminal region always contains one Sec residue, and this is separated from the C-terminal region (9-16 sec residues) by a histidine-rich sequence . The large number of Sec residues in the C-terminal portion of SelP suggests that it may be involved in selenium transport or storage. However, it is also possible that this region has a redox function .
Condensin subunit 1 (Condensin_cplx_su1)
Type: Family

This entry includes condensin subunit 1 (CND1). CND1 is a regulatory subunit of the condensin complex (contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG), a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes . The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases .

Condensin is a multi-subunit protein complex that acts as an essential regulator of chromosome condensation . It contains both SMC (structural maintenance of chromosomes) and non-SMC subunits. Condensin plays an important role during mitosis in the compaction and resolution of chromosomes to remove and prevent catenations that would otherwise inhibit segregation. This is thought to be achieved by the introduction of positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. During interphase condensin promotes clustering of dispersed loci into subnuclear domains and inhibits associations between homologues. In meiosis, condensin has been shown to influence the number of crossover events by regulating programmed double-strand breaks. Roles in gene regulation and lymphocyte development have also been defined.
Poxvirus F5/Telomere-binding protein I6 domain (Poxvirus_F5/I6_dom)
Type: Domain

This entry represents a domain found in 36 kDa major membrane protein F5 and Telomere-binding protein I6 from Vaccinia virus, and similar sequences from poxvirus. F5, also named Protein OPG049, plays a role in the spread of virus to neighbouring cells ex vivo . I6, also known as Telomere-binding protein OPG082, binds tightly and with great specificity to the hairpin form of the viral telomeric sequence. This telomere binding protein is thought to play a role in the initiation of vaccinia virus genome replication and/or genome encapsidation .
Poxvirus F15 (Poxvirus_F15)
Type: Family

This entry represents Protein F15 from Vaccinia virus, also known as Protein OPG060, and similar sequences from poxvirus. The function of this protein is still unknown.
Ribophorin I (Ribophorin_I)
Type: Family

Ribophorin I is an essential subunit of oligosaccharyltransferase (OST), which is also known as dolichyl-diphosphooligosaccharide--protein glycosyltransferase, (

). OST catalyses the transfer of an oligosaccharide from dolichol pyrophosphate to selected asparagine residues of nascent polypeptides as they are translocated into the lumen of the rough endoplasmic reticulum. In the past Ribophorin I and OST48 were thought to be responsible for OST catalytic activity , it is in reality the OST STTs subunits that are responsible for this activity . Both yeast and mammalian proteins are glycosylated but the sites are not conserved. Glycosylation may contribute towards general solubility but is unlikely to be involved in a specific biochemical function . Most family members are predicted to have a transmembrane helix at the C terminus of this region.
Gasdermin (Gasdermin)
Type: Family

The precise function of this protein is unknown. However, it is thought that this entry represents the gasdermin family which plays a role as a secretory or metabolic product involved in the secretory pathway and includes gasdermins A-E (GSDMA-E). A N-terminal fragment released by proteolysis of gasmerdin A binds to lipids and homo-oligomerizes in the membrane forming pores, which may have a bactericidal function .

GSDMB (GSDM) may play a role in achieving and maintaining the final differentiation state of epithelial cells . A deletion/insertion mutation in GSDMB (DFNA5) is associated with an autosomal dominant non-syndromic hearing impairment form .

Certain gasdermins are cleaved by inflammatory and apoptotic caspases . Gasmedin E is cleaved by caspase-3 and the N-terminal fragment released forms pores in the cell membrane, switching from cell death by apoptosis to pyroptosis .
Poxvirus G5 (Poxvirus_G5)
Type: Family

This entry represents Protein G5 from Vaccinia virus, also known as Putative nuclease OPG089, and similar sequences from poxvirus. G5 seems to be required for double-strand break repair, homologous recombination, and production of full-length viral genomic DNA .
Beta-trefoil domain of unknown function DUF569 (DUF569)
Type: Domain

This domain is found in a family of hypothetical proteins mainly from plants. Some family members contain two copies of the domain. It is predicted to adopt a β-trefoil fold.
Arabinofuranosyltransferase, central domain (Arabino_trans_central)
Type: Domain

Arabinosyltransferases EmbA, EmbB and EmbC are known to be involved in arabinogalactan (AG) and lipoarabinomannan (LAM) biosynthesis in mycobacteria. Synthesis of LAM, but not AG, ceases after inactivation of EmbC, while the arabinan of AG is affected by EmbA or EmbB disruption . The arabinans of the mycobacterial cell wall are key structural and immunological polymers. These enzymes could have important clinical applications as they are believed to be the target of the antimycobacterial drug Ethambutol .
Ran-interacting Mog1 protein (Mog1)
Type: Family

Segregation of nuclear and cytoplasmic processes facilitates regulation of many eukaryotic cellular functions such as gene expression and cell cycle progression. Trafficking through the nuclear pore requires a number of highly conserved soluble factors that escort macromolecular substrates into and out of the nucleus. The Mog1 protein has been shown to interact with RanGTP, which stimulates guanine nucleotide release, suggesting Mog1 regulates the nuclear transport functions of Ran . The human homologue of Mog1 is thought to be alternatively spliced.
Lantibiotic, type A, Lactobacillales-type (Lantibiotic_typ-A_Lactobact)
Type: Family

Lantibiotics are heavily-modified bacteriocin-like peptides from Gram-positive bacteria. They contain alpha,beta-unsaturated amino acids (dehydroalanine and dehydrobutyrine) and lanthionine or 3-methyllanthionine rings (collectively known as thioether rings). There are 2 types of lantibiotic:

Type A (which include nisin, subtilin, epidermin, gallidermin and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5 inhibit the growth of Gram-positive bacteria, probably by voltage-dependent pore formation in the cytoplasmic membrane, resulting in cellular efflux of electrolytes, amino acids and ATP;

Type B lantibiotics possess at most one positive charge and are not bactericidal.

This entry represents type A Lantibiotics that are mostly from Lactobacillales.
Zinc finger, Ogr/Delta-type (Znf_Ogr/Delta)
Type: Domain

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.

This entry represents a set of zinc fingers found in bacteriophage transcriptional activators and some bacterial proteins . These zinc fingers all contain the consensus sequence: C-X(2)-C-X(3)-A-(X)2-R-X(15)-C-X(4)-C-X(3)-F .