SII-SWORD/CoKE huggingface dataset:
PilZ domain (PilZ_domain)
Type: Domain

The ubiquitous bacterial second messenger cyclic-di-GMP (c-di-GMP) is associated with the regulation of biofilm formation, the control of exopolysaccharide synthesis, flagellar- and pili-based motility, gene expression, interactions of bacteria with eukaryotic hosts and multicellular behaviour in diverse bacteria. This second messenger binds to PliZ domains from cytoplasmic receptors through its RXXXR and [D/N]hSXXG motifs . However, some PilZ-related domains lack these motifs and do not bind c-di-GMP. The crystal structure, at 1.7 A, of a PilZ domain::c-di-GMP complex from Vibrio cholerae shows c-di-GMP contacting seven of nine strongly conserved residues. Binding of c-di-GMP causes a conformational switch whereby the C- and N-terminal domains are brought into close opposition forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface . Structural and sequence analysis of PilZ-related domains allow the description of three types of domains, the canonical PilZ domain (represented in this entry), whose structure includes a six-stranded β-barrel and a C-terminal α helix, an atypical PilZ domain containing two additional α helices and forms tetramers, and divergent PilZ-related domains, which include the PilZ protein and the YcgR N-terminal domains (PilZN and PilZNR). PilZN-type domains are evolutionarily related to PliZ domains and are found fused to the canonical PilZ domains in specific taxa, such as spirochetes, actinobacteria, aquificae, cellulose-degrading clostridia, and deltaproteobacteria .

Some examples of proteins containing this domain are BcsA subunits of bacterial cellulose synthases and flagellar brake protein YcgR (see

) . c-di-GMP binding to PilZ brings about conformational changes in the protein that stabilise the bound ligand and probability initiates the downstream signal transduction cascade. In the case of YcgR, c-di-GMP binding regulates flagellum-based motility in a c-di-GMP-dependent manner (see

) . The association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.
Outer membrane adhesin OpcA (OM_adhesin_OpcA)
Type: Family

This entry represents OpcA-type outer membrane adhesion proteins. OpcA (formerly called 5C) was isolated from Neisseria meningitidis, causative agent of meningococcal meningitis and septicemia. An outer membrane protein embedded in the lipid bilayer, OpcA was shown to play an important role in meningococcal adhesion and invasion of both epithelial and endothelial cells, mediating attachment to host cells by binding proteoglycan cell-surface receptors . OpcA forms a 10-stranded β-barrel with five highly mobile extracellular loops that protrude above the surface of the membrane . These extracellular loops combine to form a crevice in the external surface that is lined by positively charged residues, which is predicted to be a binding site for proteoglycan polysaccharides involved in pathogenesis. Conformational changes in the extracellular loops modulate the surface of OpcA, which could affect the proteoglycan binding site . These conformational changes could also lead to pore opening.
Phlebovirus glycoprotein G2, fusion domain (Phlebovirus_G2_fusion)
Type: Domain

HRTV is an insect-borne virus found in America that can infect humans. It belongs to the newly defined family Phenuiviridae, order Bunyavirales. HRTV contains three single-stranded RNA segments (L, M, and S). The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc. Gc is a fusion protein facilitating virus entry into host cells . G2 (also known as Gc) is necessary for optimal glycoprotein G1 (also found as Gn) expression and efficient production or viral-like particles and possibly for the cell infection, as G2 is determinant for cell fusion . Phleboviral G2 fusion glycoprotein is both functionally and structurally analogous to the fusion glycoproteins of alphaviruses and flaviviruses, all of them recognize DC-SIGN receptor to enable viral attachment .

This domain consists of the N-terminal and middle domains, known as fusion domain, of several Phlebovirus glycoprotein G2 sequences.
Phlebovirus nonstructural NS-M (Phlebovirus_NSM)
Type: Domain

This entry consists of several Phlebovirus nonstructural NS-M proteins, which represent the N-terminal region of the M polyprotein precursor. The function of this family is unknown.
Glyoxal oxidase, N-terminal (Glyoxal_oxidase_N)
Type: Domain

This entry represents the N terminus (approximately 300 residues) of a number of plant and fungal glyoxal oxidase enzymes. Glyoxal oxidase catalyses the oxidation of aldehydes to carboxylic acids, coupled with reduction of dioxygen to hydrogen peroxide. It is an essential component of the extracellular lignin degradation pathways of the wood-rot fungus Phanerochaete chrysosporium .
Protein of unknown function DUF1433 (DUF1433)
Type: Family

This family contains a number of hypothetical bacterial proteins of unknown function approximately 100 residues in length.
Gypsy (Gypsy)
Type: Family

This family consists of several Gypsy/Env proteins from Drosophila and Ceratitis fruit fly species. Gypsy is an endogenous retrovirus of Drosophila melanogaster. Phylogenetic studies suggest that occasional horizontal transfer events of gypsy occur between Drosophila species. Gypsy possesses infective properties associated with the products of the envelope gene that might be at the origin of these interspecies transfers .
Inner membrane protein YgfX (YgfX)
Type: Family

This family includes bacterial proteins including the probable inner membrane protein YgfX from Escherichia coli (formerly known as CptA). This had been thought to be a toxin, but it has no effect on cell growth . It has been shown to interact with the cytoskeletal proteins FtsZ and MreB and to inhibit FtsZ GTP-dependent and MreB ATP-dependent polymerization . In Serratia strains deficient in sdhE-ygfX, YgfX restores production of the antibiotic prodigiosin .
Protein of unknown function DUF1435 (DUF1435)
Type: Family

This family consists of several hypothetical Enterobacterial proteins of around 80 residues in length. The function of this family is unknown.
Progressive ankylosis (ANKH)
Type: Family

This family consists of several progressive ankylosis protein (ANK or ANKH) sequences, also known as Mineralization regulator ANKH in mammals. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PP
i
), a major inhibitor of physiologic and pathologic calcification, bone mineralisation and bone resorption . Mutations in ANK are thought to give rise to Craniometaphyseal dysplasia (CMD) which is a rare skeletal disorder characterised by progressive thickening and increased mineral density of craniofacial bones and abnormally developed metaphyses in long bones .
Immunity protein CdiI, Proteobacteria type (CdiI_Proteobact)
Type: Family

Contact-dependent growth inhibition (CDI) toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighbouring bacteria. This entry includes the inhibitor (CdiI) of the CdiA effector protein from Escherichia coli EC869 (which is a DNAse). CdiA secretion is dependent on the outer membrane protein CdiB. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered. The inhibitors are intracellular proteins that inactivate the toxin/effector protein .
Dentin matrix 1 (DMP1)
Type: Family

This family consists of several mammalian dentin matrix protein 1 (DMP1) sequences. The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human chromosome 4q21 . DMP1 is a bone and teeth specific protein initially identified from mineralised dentin. DMP1 is primarily localised in the nuclear compartment of undifferentiated osteoblasts. In the nucleus, DMP1 acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the early phase of osteoblast maturation, Ca
2+
surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II. This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite. DMP1 is a unique molecule that initiates osteoblast differentiation by transcription in the nucleus and orchestrates mineralised matrix formation extracellularly, at later stages of osteoblast maturation . The DMP1 gene has been found to be ectopically expressed in lung cancer although the reason for this is unknown .
Tapetum specific TAP35/TAP44 (TAP35_44)
Type: Family

This family consists of several plant tapetum specific proteins. Members of this family are found in Arabidopsis thaliana, Brassica napus and Sinapis alba. Members of this family may be involved in sporopollenin formation and/or deposition .
Nucleopolyhedrovirus capsid P80/P87 (Nucleo_P80/P87)
Type: Family

This family consists of several nuclear polyhedrosis viruses capsid P80 and P87 protein sequences . P87 is expressed late in infection and concentrated in infected cell nuclei . P80 (VP80) is involved in the packaging of nucleocapsids and in the egress of progeny nucleocapsids from the virogenic stroma toward the nuclear periphery .
Exported (EppA_BapA)
Type: Family

This family consists of a number of exported protein precursor (EppA and BapA) sequences which seem to be specific to Borrelia burgdorferi (Lyme disease spirochete). bapA gene sequences are quite stable but the encoded proteins do not provoke a strong immune response in most individuals. Conversely, EppA proteins are much more antigenic but are more variable in sequence. It is thought that BapA and EppA play important roles during the B. burgdorferi infectious cycle .
Protein of unknown function DUF1438 (DUF1438)
Type: Family

This family consists of several hypothetical proteins of around 170 residues in length predominantly found in rodents. The function of this family is unknown.
Cytadhesin P30/P32 (Cytadhesin_P30/P32)
Type: Family

This family consists of several Mycoplasma species specific Cytadhesin P32 and P30 proteins. P30 has been found to be membrane associated and localised on the tip organelle. It is thought that it is important in cytadherence and virulence .
Orthoreovirus P17 (Orthoreo_P17)
Type: Family

This family consists of several Orthoreovirus P17 proteins. P17 is specified be ORF2 of the S1 gene and represents a nonstructural protein which associate with cell membranes .
Protein of unknown function DUF1440 (DUF1440)
Type: Family

This family contains a number of bacterial proteins of unknown function approximately 180 residues long. These are possibly integral membrane proteins .
Antirestriction (ArdA)
Type: Family

This family consists of several bacterial antirestriction (ArdA) proteins. ArdA functions in bacterial conjugation to allow an unmodified plasmid to evade restriction in the recipient bacterium and yet acquire cognate modification .
Apopolysialoglycoprotein (PSGP)
Type: Repeat

This entry represents a series of 13 residue repeats found in the apopolysialoglycoprotein of Oncorhynchus mykiss (Rainbow trout) and Oncorhynchus masou (Cherry salmon). Polysialoglycoprotein (PSGP) of unfertilised eggs of rainbow trout consists of tandem repeats of a glycotridecapeptide, Asp-Asp-Ala-Thr*-Ser*-Glu-Ala-Ala-Thr*-Gly-Pro-Ser- Gly (* denotes the attachment site of a polysialoglycan chain). In response to egg activation, PSGP is discharged by exocytosis into the space between the vitelline envelope and the plasma membrane, i.e. the perivitelline space, where the 200kDa PSGP molecules undergo rapid and dramatic depolymerisation by proteolysis into glycotridecapeptides .
Bacteriophage VT1-Sakai, H0025 (Phage_VT1-Sakai_H0025)
Type: Family

This entry is represented by Bacteriophage VT1-Sakai, H0025. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several hypothetical Enterobacterial proteins of around 160 residues in length. The function of this family is unknown.
Protein of unknown function DUF1442 (DUF1442)
Type: Family

This family consists of several hypothetical Arabidopsis thaliana proteins of around 225 residues in length. The function of this family is unknown.
Per os infectivity factor AC110 (AcMNPV_AC110)
Type: Family

This family of Baculovirus proteins includes Autographa californica nuclear polyhedrosis virus (AcMNPV) Per os infectivity factor AC110, which is required for oral infectivity. It may play a role after occlusion-derived virions pass through the host's peritrophic membrane .
2-vinyl bacteriochlorophyllide hydratase (BCHF)
Type: Family

This family contains the bacterial enzyme 2-vinyl bacteriochlorophyllide hydratase (approximately 150 residues long). This is involved in the light-independent bacteriochlorophyll biosynthesis pathway by adding water across the 2-vinyl group .This enzyme is apparently absent from cyanobacteria (which do not use bacteriochlorophyll).
D-glutamate cyclase (D-Glu_cyclase)
Type: Family

This family includes mitochondrial D-glutamate cyclase (

), which converts D-glutamate to 5-oxo-D-proline . The family also includes numerous uncharacterised proteins from bacteria.
RNA polymerase epsilon subunit (RpoY)
Type: Family

RNA polymerase in bacteria is a multisubunit protein complex that is essential for gene expression. This entry represents the epsilon subunit encoded by the rpoY gene. The structure of epsilon shows simple β-sheet with an α-helix running diagonally along the back of the structure forming a β-β-α-β fold .
Methylamine utilisation protein, MauE (Methylamine_util_MauE)
Type: Domain

This entry consists of several bacterial methylamine utilisation MauE proteins. Synthesis of enzymes involved in methylamine oxidation via methylamine dehydrogenase (MADH) is encoded by genes present in the mau cluster. MauE and MauD are specifically involved in the processing, transport, and/or maturation of the beta-subunit and that the absence of each of these proteins leads to production of a non-functional beta-subunit which becomes rapidly degraded .
Nmi/IFP 35 domain (Nmi/IFP35_dom)
Type: Domain

This entry represents a domain of approximately 90 residues that is tandemly repeated within interferon-induced 35kDa protein (IFP 35) and the homologous N-myc-interactor (Nmi). This domain mediates Nmi-Nmi protein interactions and subcellular localisation .

This domain is predicted to contain a region that is swapped between tandem of RRM domains in IFP 35, Nmi and closely related proteins containing the tandem. This entry corresponds to the sequence repeat in these proteins that in the structural models is swapped between the two RRM-like domains.
Protein of unknown function DUF1450 (DUF1450)
Type: Family

This entry consists of several hypothetical bacterial proteins of around 80 residues in length representing two families. Members contain four highly conserved cysteine residues and their function is unknown.
Fibroin P25 (Fibroin_P25)
Type: Family

This family consists of several insect fibroin P25 proteins. Silk fibroin produced by the silkworm Bombyx mori consists of a heavy chain, a light chain, and a glycoprotein, P25. The heavy and light chains are linked by a disulphide bond, and P25 associates with disulphide-linked heavy and light chains by noncovalent interactions. P25 is plays an important role in maintaining integrity of the complex .
Zinc-ribbon containing domain (DUF1451)
Type: Family

This family consists of several hypothetical bacterial proteins of around 160 residues in length. Members of this family contain four highly conserved cysteine resides toward the C-terminal region of the protein.
TraP (TraP)
Type: Family

This family consists of several bacterial conjugative transfer TraP proteins from Escherichia coli and Salmonella typhimurium. TraP appears to play a minor role in conjugation and may interact with TraB, which varies in sequence along with TraP, in order to stabilise the proposed transmembrane complex formed by the tra operon products .
Dolichol phosphate-mannose biosynthesis regulatory (DPM2)
Type: Family

This family consists of several eukaryotic dolichol phosphate-mannose biosynthesis regulatory (DPM2) proteins. Biosynthesis of glycosylphosphatidylinositol and N-glycan precursor is dependent upon a mannosyl donor, dolichol phosphate-mannose (DPM). DPM2, an 84 amino acid membrane protein expressed in the endoplasmic reticulum (ER), makes a complex with DPM1 that is essential for the ER localisation and stable expression of DPM1. Moreover, DPM2 enhances binding of dolichol phosphate, a substrate of DPM synthase. Biosynthesis of DPM in mammalian cells is regulated by DPM2 .
NnrU domain (NnrU_dom)
Type: Domain

This entry represents a domain found in bacterial NnrU proteins. It can also be found in plant 15-cis-zeta-carotene isomerase (Z-ISO). NnrU is thought to be involved in the reduction of nitric oxide. The exact function of NnrU is unclear. It is thought however that NnrU and perhaps NnrT are required for expression of both nirK and nor .

Plant Z-ISO is an isomerase involved in the biosynthesis of carotenoids. It catalyses the cis- to trans-conversion of the 15-cis-bond in 9,15,9'-tri-cis-ζ-carotene .
SRA1/Sec31 (SRA1/Sec31)
Type: Domain

This domain can be found in several hypothetical mammalian steroid receptor RNA activator proteins. The SRA-RNAs encode stable proteins that are widely expressed and upregulated in breast cancer cell lines. SRA-RNA is a steroid receptor co-activator which acts as a functional RNA .

This domain is also found at the C terminus of Sec31, a component of the coat protein complex II (COPII, which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). COPII has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules .
Protein of unknown function DUF1454 (DUF1454)
Type: Family

This family consists of several Enterobacterial sequences of around 200 residues in length, which are often known as YiiQ proteins. The function of this family is unknown.
Protein of unknown function DUF1455 (DUF1455)
Type: Family

This family consists of several hypothetical putative outer membrane proteins which appear to be specific to Anaplasma marginale and Anaplasma ovis.
Heptaprenyl diphosphate synthase subunit 1 (HEPPP_synth_su1)
Type: Family

This family contains subunit 1 of bacterial heptaprenyl diphosphate synthase (HEPPP synthase) (

) (approximately 230 residues long). The enzyme consists of two subunits, both of which are required for catalysis of heptaprenyl diphosphate synthesis, the precursor for the side chain of the isoprenoid quinone menaquinone-7 (MQ-7) .
YehS-like (YehS-like)
Type: Family

This entry represents a family of bacterial proteins that includes Uncharacterized protein YehS from Escherichia coli, which appears to be associated with growth in the presence of n-butanol or n-hexane . This protein is predicted to have an all-α structure.
Protein of unknown function DUF1457 (DUF1457)
Type: Family

This family contains a number of hypothetical bacterial proteins of unknown function approximately 200 residues long. Members of this group contain a domain that is distantly similar to other PAS domains.
Dodecin (Dodecin)
Type: Family

Dodecin flavoprotein is a small dodecameric flavin-binding protein from Halobacterium salinarium (Halobacterium halobium) that contains two flavins stacked in a single binding pocket between two tryptophan residues to form an aromatic tetrade . Dodecin binds riboflavin, although it appears to have a broad specificity for flavins. Dodecin protects the bound flavins against light-damage through a quick quenching the flavin excited state and the degradation of riboflavin to lumichrome . The subunit assembly and the probable biological unit is a dodecamer .
Protein of unknown function DUF1459 (DUF1459)
Type: Family

This family consists of several hypothetical Caenorhabditis elegans proteins of around 85 residues in length. The function of this family is unknown.
Protein of unknown function DUF1463 (DUF1463)
Type: Family

This entry represents a family of hypothetical proteins of around 140 residues in length found in Borrelia species. The function of this family is unknown.
Type III secretion system flagellar brake protein YcgR, PilZN domain (T3SS_YcgR_PilZN)
Type: Domain

This entry represents the N-terminal domain of YcgR proteins, located N-terminal to PilZ domains, thus named PilZN domain (also known as YcgR domain) . The function of this domain is not known, but it is known to interact with the C-terminal which has cyclic-di-GMP bound . YcgR is involved in the flagellar motor function and is a member of the flagellar regulon . This domain exhibits a similar structure as PilZ domains comprising a β-barrel fold but lack the C-terminal α-helix .
Protein of unknown function DUF1464 (DUF1464)
Type: Family

This family consists of several hypothetical archaeal proteins of around 350 residues in length. The function of this family is unknown.
Primosomal DnaI, N-terminal (DnaI_N)
Type: Domain

This entry represents the N terminus (approximately 120 residues) of bacterial primosomal DnaI proteins, although one family member appears to be of viral origin. DnaI is one of the components of the Bacillus subtilis replication restart primosome, and is required for the DnaB75-dependent loading of the DnaC helicase .
Type III secretion sytem,YscO (T3SS_YscO)
Type: Family

This family contains the bacterial type III secretion protein YscO, which is approximately 150 residues long. YscO has been shown to be required for high-level expression and secretion of the anti-host proteins V antigen and Yops in Yersinia pestis .
Structural protein Vp10, Seadornavirus (Seadorna_Vp10)
Type: Family

This entry represents Vp10 protein from Seadornavirus. It is around 240 residues in length. Vp10 forms the virion spike "foot" and helps anchor the Vp9 spike "head" protein in the virion .
Curtovirus V2 (Curto_V2)
Type: Family

This family consists of several Curtovirus V2 proteins. The exact function of V2 is unclear but it is known that the protein is required for a successful host infection process .
RCS1 (RCS1)
Type: Family

RCS1 (also known as FAM64A, CATS or PIMREG) is a substrate of APC/C. It may control the metaphase to anaphase transition . It is also a substrate of the Kinase Interacting Stathmin (KIS). RCS1 is highly expressed in cancer cell lines in a cell cycle dependent manner and is induced by mitogens .
T-DNA border endonuclease VirD1 (VirD1)
Type: Family

This family consists of several T-DNA border endonuclease VirD1 proteins, which appear to be found exclusively in Agrobacterium species. Agrobacterium, a plant pathogen, is capable to stably transform the plant cell with a segment of its own DNA called T-DNA (transferred DNA). This process depends, among others, on the specialised bacterial virulence proteins VirD1 and VirD2 that excise the T-DNA from its adjacent sequences. VirD1 is thought to interact with VirD2 in this process .
Protein of unknown function DUF1467 (DUF1467)
Type: Family

This family consists of several bacterial proteins of around 90 residues in length. The function of this family is unknown.
Domain of unknown function DUF1468 (DUF1468)
Type: Domain

This entry represents a domain found in a group of uncharacterised bacterial sequences, including 16.3 kDa protein in TAR-I ttuC' 3'region from the common pathogen of grapevine Agrobacterium vitis . In most members of this group, this domain covers the whole length of the protein, and many of them are annotated as the TctB subunit of the tripartite tricarboxylate transport (TTT) family. However there is no direct evidence to support this annotation as characterised members of this family are not associated with the entry.