SII-SWORD/CoKE huggingface dataset:
Putative quorum-sensing-regulated virulence factor, QSregVF (QSregVF)
Type: Family

This entry represents a family of short 14kDa proteins from Psuedomonas. The structure of

a secreted protein has been solved and deposited as PDB:3npd. It comprises one structural domain with five β-strands and five α-helices. Various comparative structural prediction methods plus its genomic location point to the protein forming a functional dimer with its adjacent genomic partner,

. Together these might be regulated by the other product from the PotABCD operon, namely the putrescine-binding periplasmic protein

. which has been implicated in quorum-sensing. QSregVF is certainly up-regulated in quorum-sensing, and is predicted to be a virulence factor .
Centromere subunit L (CENP-L)
Type: Family

CENP-L is one of the components that assembles onto the CENP-A-nucleosome distal (CAD) centromere. It interacts with CENP-N and forms a deep channel through which a DNA duplex threads . Fta1 is the equivalent component of the fission yeast Sim4 complex .

The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. All active centromeres are characterised by the presence of long arrays of nucleosomes in which CENP-A replaces histone H3. CENP-A assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENP-A-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC .
PilX/PilW C-terminal domain (PilX/PilW_C)
Type: Domain

This domain is found at the C terminus of the type IV pilus assembly proteins PilX and PilW.
Protein of unknown function DUF4152 (DUF4152)
Type: Family

This family of archaeal proteins is functionally uncharacterised. The structure of the family member from Pyrococcus furiosus has been solved. It shows an RNaseH like fold that conserves critical catalytic residues . This suggests that these proteins may cleave nucleic acid.
Kinetochore Sim4 complex subunit Fta4 (Sim4_Fta4)
Type: Family

Fission yeast has three kinetochore protein complexes. Two complexes, Sim4 and Ndc80-MIND-Spc7 (NMS), are constitutive components, whereas the third complex, DASH, is transiently associated with kinetochores only in mitosis and is required for precise chromosome segregation. The Sim4 complex functions as a loading dock for the DASH complex. Sim4 consists of a number of different proteins including Ftas 1-7 and Dad1 .

This entry represents Fta4.
NFkB-p65-degrading zinc protease (Peptidase_M85)
Type: Family

This family of bacterial metallo-peptidases is thought to compromise the inflammatory response by degrading p65, thereby down-regulating the NF-kappaB signalling pathway . NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52; and the heterodimeric p65-p50 complex appears to be most abundant one.
Domain of unknown function DUF4209 (DUF4209)
Type: Domain

This short domain is functionally uncharacterised. It carries a highly conserved RNxxxHG sequence motif.
ATP25 mRNA stabilisation domain (ATP25_mRNA_stabil_dom)
Type: Domain

This domain is found in ATPase synthesis protein 25. It acts as an mRNA stabilisation factor .
Toxin TisB, type I toxin-antitoxin system (TisB_toxin)
Type: Family

TisB (toxicity-induced by SOS B) is an SOS-induced toxic peptide and is part of the type I toxin-antitoxin system, in which the antitoxin is a non-coding RNA. It is a hydrophobic membrane-spanning protein that inhibits cell growth . Its expression is inhibited by the antisense RNA IstR-1 . TisB appears to induce a persister state by dissipating transmembrane potential, thus depleting ATP. Persister cells, unable to grow until the persister state changes, survive a number of challenges, including exposure to most antibiotics .
Centromere protein Q (CAD_CENP-Q)
Type: Family

This entry includes CENP-Q and Fta7 proteins. CENP-Q is one of the components that assembles onto the CENP-A-nucleosome distal (CAD) centromere. Fta7 is the equivalent component of the fission yeast Sim4 complex .
Kinetochore Sim4 complex subunit Fta2 (Sim4_Fta2)
Type: Family

Fission yeast has three kinetochore protein complexes. Two complexes, Sim4 and Ndc80-MIND-Spc7 (NMS), are constitutive components, whereas the third complex, DASH, is transiently associated with kinetochores only in mitosis and is required for precise chromosome segregation. The Sim4 complex functions as a loading dock for the DASH complex. Sim4 consists of a number of different proteins including Ftas 1-7 and Dad1 .

This entry represents Fta2.
Centromere protein U (CENP-U)
Type: Family

CENP-U is one of the components that assembles onto the CENP-A-nucleosome associated complex (NAC).

The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. All active centromeres are characterised by the presence of long arrays of nucleosomes in which CENP-A replaces histone H3. CENP-A assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENP-A-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC .
Domain of unknown function DUF4427 (DUF4427)
Type: Domain

This presumed domain is functionally uncharacterised.
Domain of unknown function DUF3944 (DUF3944)
Type: Domain

This domain of unknown function is found in uncharacterised proteins from bacteria.
Domain of unknown function DUF4426 (DUF4426)
Type: Domain

This presumed domain is functionally uncharacterised.
PLAT/LH2 and C2-like Ca2+-binding lipoprotein (PLCC)
Type: Family

A small family of bacterial proteins, found in several species from bacteroidetes. Structure determination (NMR and Xray) shows an immunoglobulin β-barrel fold. Multiple homologues have been found in human gut metagenomics data sets. Structural experimentation shows it to share features with two well-established protein architectures in the SCOP database, ie, C2 (calcium/lipid-binding domain) of the C2 domain (

)
and the PLAT/LH2 domain (

). The C2 and PLAT/LH2 domains bind Ca2+ in their functions of targeting proteins to cell-membranes; this domain is also shown to bind Ca2+ as well as to be a novel fold .
Nuclear factor related to kappa-B-binding protein, winged helix-like domain (NFRKB_WH_1)
Type: Domain

This winged helix-like domain is found in nuclear factor related to kappa-B-binding (NFRKB) protein. This winged helix-like domain is however not involved in DNA binding but is instead thought to be involved in protein-protein interactions .

NFRKB is a putative regulatory component of the chromatin remodelling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair .
E1 N-terminal domain (E1-N_dom)
Type: Domain

This entry represents an uncharacterised α/β domain fused to E1 proteins. This protein is usually present in gene neighbourhoods with genes encoding a JAB protein and a predicted metal-binding protein. In related E1 proteins, the E1-N domain is replaced by an E2/UBC superfamily domain .
Domain of unknown function DUF3945 (DUF3945)
Type: Domain

This entry represents a C-terminal repeated domain found in a family of uncharacterised proteins identified by clustering human gut metagenomic sequences .
S1-like RNA binding domain (S1-like_RNA-bd_dom)
Type: Domain

This entry represents the S1-like RNA binding domain found in deleted in breast cancer 1 (DBC1) and its paralogue cell division cycle and apoptosis regulator protein 1 (CARP1) .
Cell cycle and apoptosis regulator protein (CCAR1/CCAR2)
Type: Family

Cell division cycle and apoptosis regulator protein 1 (CCAR1) associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery. CCAR1 also functions as a p53 coactivator and regulates expression of key proliferation-inducing genes .

Cell cycle and apoptosis regulator protein 2 (CCAR2, also known as DBC-1) regulates biological processes such as transcription, heterochromatin formation, metabolism, mRNA splicing, apoptosis, and cell proliferation . It is a core component of the DBIRD complex, which affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions . It binds to SIRT1 and is a negative regulator of SIRT1 . DBC-1 has been implicated in tumorigenesis .

This entry also includes protein SHORT ROOT IN SALT MEDIUM 1 (RSA1, also known as EMB1579) from Arabidopsis. It regulates the transcription of several genes involved in the detoxification of reactive oxygen species generated by salt stress and the SOS1 gene that encodes a plasma membrane Na(+)/H(+) antiporter essential for salt tolerance . RSA1 is localised to the nucleus and the loss of function of RSA1 affects global transcription and mRNA splicing .
Protein of unknown function DUF3956 (DUF3956)
Type: Family

This is a family of uncharacterised bacterial proteins.
Protein of unknown function DUF4170 (DUF4170)
Type: Family

The function of these proteins is not known.
Protein of unknown function DUF4169 (DUF4169)
Type: Family

The function of these proteins is not known.
Domain of unknown function DUF4171 (DUF4171)
Type: Domain

The function of this domain is not known. It is often found at the N terminus of proteins that contain an HMG-box domain.
YniB-like protein (YniB-like)
Type: Family

The YniB-like protein family includes the Escherichia coli YniB protein

, which is functionally uncharacterised. It also includes protein YfeE from Yersinia, a putative regulator of the ABC transporter locus yfeABCD, involved in inorganic iron transport. The proteins in this family are integral membrane proteins and are found in bacteria.
Domain of unknown function DUF4172 (DUF4172)
Type: Domain

The function of this domain is not known. It is often associated with a Fido domain .
Domain of unknown function DUF4174 (DUF4174)
Type: Domain

This domain of unknown function is found in a putative tumour suppressor gene and in a ligand for the the urokinase-type plasminogen activator receptor, which plays a role in cellular migration and adhesion .
Protein of unknown function DUF4176 (DUF4176)
Type: Family

The function of these proteins is not known.
YjzH-like (YjzH-like)
Type: Family

This entry represents a group of prokaryotic proteins, including the uncharacterised protein YjzH from Bacillus subtilis. YjzH is a member of the sigma W regulon, which is induced in response to cell envelope stress caused by antibiotics, alkaline shock and salt shock . This family was previously known as DUF4177.
Domain of unknown function DUF4178 (DUF4178)
Type: Domain

This is a domain of unknown function, mainly found in bacterial proteins.
SR1 protein (SR1P)
Type: Family

This family of proteins is encoded by the dual function SR1 RNA. SR1 is a sRNA which regulates arginine metabolism , it also encodes a short protein that binds to glyceraldehyde-3-phosphate dehydrogenase (GapA) and stabilises the gapA operon mRNAs .
Domain of unknown function DUF4183 (DUF4183)
Type: Domain

This domain of unknown function from bacterial proteins contains a highly conserved ING motif.
Protein of unknown function DUF4184 (DUF4184)
Type: Family

These proteins of unknown function contain several highly conserved histidines.
Domain of unknown function DUF4187 (DUF4187)
Type: Domain

This short, cysteine-rich domain is often found C-terminal to a G-patch domain.
Domain of unknown function DUF4189 (DUF4189)
Type: Domain

This domain of unknown function contains six well-conserved cysteine residues.
Domain of unknown function DUF4190 (DUF4190)
Type: Domain

This presumed domain is functionally uncharacterised.
Protein of unknown function DUF4193 (DUF4193)
Type: Family

These functionally uncharacterised proteins contains four conserved cysteines and a conserved histidine, including a CXXXXH motif.
Domain of unknown function DUF4195 (DUF4195)
Type: Domain

This domain is found at the N terminus of a number of proteins that carry PHD-like zinc-finger domains.
Coiled-coil domain-containing protein 82 (CCDC82)
Type: Domain

This short domain is found in Ccdc82 and homologous sequences. Its function is not known.
Protein of unknown function DUF4197 (DUF4197)
Type: Family

The function of these proteins is not known.
Transposase IS30-like HTH domain (IS30-like_HTH)
Type: Domain

This helix-turn-helix domain is found in some transposases and is likely to be DNA-binding.
Type II methyltransferase M.EcoRI-like (EcoRI-like_methylase)
Type: Family

Type II methyltransferase M.EcoRI recognises the double-stranded sequence GAATTC, causes specific methylation on A-3 on both strands, and protects the DNA from cleavage by the EcoRI endonuclease . This entry also includes Type II methyltransferases M.MgeORF184P and M.MpnI from the human pathogens Mycoplasma genitalium and Mycoplasma pneumoniae, respectively .
Domain of unknown function DUF4007 (DUF4007)
Type: Domain

This presumed domain is functionally uncharacterised.
KH domain, NusA-like (KH_dom_NusA-like)
Type: Domain

This entry represents K homology (KH) domains of the type found in NusA transcription termination factors. KH domains bind RNA, and can function in RNA recognition . NusA binds to RNA polymerase alpha subunit and promotes termination at certain RNA hairpin structures .
Protein of unknown function DUF4199 (DUF4199)
Type: Family

The function of these proteins is not known.
Domain of unknown function DUF4213 (DUF4213)
Type: Domain

This domain of unknown function has an enolase N-terminal domain-like fold. Its genomic context suggests that it may have a role in anaerobic vitamin B12 biosynthesis. This domain is often found at the N terminus of proteins containing

. The structure of

,

, suggests that the whole protein has this enolase N-terminal-like fold and an Rossmann-like C-terminal domain. Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The protein may be playing a role in heavy-metal chelation .
Domain of unknown function DUF4200 (DUF4200)
Type: Domain

This entry represents a coiled-coil domain. Its function is unknown.
Type I toxin-antitoxin system, toxin Ldr (Toxin_Ldr)
Type: Family

This family includes the Ldr (long direct repeat) toxins. In Escherichia coli there are four Ldr toxins, LdrA, LdrB, LdrC and LdrD. These toxins inhibit cell growth, decrease cell viability and cause nucleoid condensation. They are part of the type I toxin antitoxin (TA) system, where expression of the proteinaceous toxin is controlled by an antisense sRNA. For example, LdrD expression is inhibited by the antisense RNA RdlD, which functions as an antitoxin .
CCDC113/CCDC96, coiled-coil (CCDC113/CCDC96_CC)
Type: Domain

This entry represents the coiled-coil region of coiled-coil domain-containing protein 113 (CCDC113, also known as cilia- and flagella-associated protein 263, CFAP263) and coiled-coil domain-containing protein 96 (CCDC96, also known as cilia- and flagella-associated protein 184, CFAP184). These proteins form a complex and regulate ciliary beating that connects radial spoke 3 (RS3) to the inner dynein arm (IDA) and the nexin-dynein regulatory complex (N-DRC). The complex is positioned parallel to N-DRC and forms a connection between the arch at the base of RS3, the IDA tail and N-DRC .
Protein of unknown function DUF4202 (DUF4202)
Type: Family

The function of these proteins is unknown, although some are incorrectly annotated as glutamyl tRNA synthetases. There are two conserved sequence motifs: LED and KMS.
TM7S3/TM198-like domain (TM7S3/TM198-like_dom)
Type: Domain

This domain is found at the C-terminal end of human Transmembrane 7 superfamily member 3 (TM7SF3), towards the N terminus of human Transmembrane protein 198 (TM198), and in similar proteins mainly found in animal, fungi and bacteria.

TM7SF3 is involved in the inhibition of cytokine-induced death of pancreatic beta cells . The protein acts as a pro-survival homeostatic factor that attenuates the development of cellular stress .

TM198 promotes LRP6 phosphorylation by casein kinases and thereby plays a role in Wnt signalling .
Deubiquitinating enzyme MINDY-3/4, conserved domain (MINDY-3/4_CD)
Type: Domain

This is a conserved domain found in deubiquitinating enzymes, MINDY-3 and MINDY-4.

Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the functional outcome of ubiquitylation. This entry includes MINDY-3/4. They belong to the MINDY (motif interacting with Ub-containing novel DUB) family (peptidase family C121), whose members are deubiquitinating enzymes releasing Lys48-linked ubiquitin .
Rubicon Homology Domain (RH_dom)
Type: Domain

This is the Rubicon homology domain (RH) characterised at the C-terminal of Rubicon, PLEKHM1 and Pacer, proteins that modulate late steps in autophagy . Rubicon (RUBCN) negatively regulates autophagy and endolysosomal trafficking by inhibiting PI3K complex II (PI3KC3-C2), which impairs autophagosome maturation process. Decrease in autophagy is associated to aging, then suppression of this process by Rubicon has been linked to decreased clearance of alpha-synuclein aggregates in neural tissues, impairment of liver cell homeostasis, and interstitial fibrosis in the kidney. PLEKHM1 is an adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways , being involved in the suppression of endocytic transport rather than autophagosome maturation. Mutations in PLEKHM1 causes osteopetrosis . On the other hand, Pacer (Protein associated with UVRAG as autophagy enhancer or Rubicon-like) positively regulates autophagy, promoting autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns3P) in late steps of autophagy . It antagonizes RUBCN, thereby stimulating phosphatidylinositol 3-kinase activity of the PI3K/PI3KC3 complex . Pacer is involved in neuronal autophagy, whose deficiency leads to impaired autophagy and accumulation of protein aggregates in ALS which correlates with cell death and vulnerability of motoneurons during ALS pathogenesis .

This domain contains nine conserved cysteines and one conserved histidine, which have been predicted to bind divalent zinc cations, being required for Rubicon and PLEKHM1 to interact with Rab7 .
Coiled-coil domain-containing protein 34/181 (CCDC34/181)
Type: Domain

This domain can be found in animal CCDC34 and CCDC181 proteins. CCDC34 promotes cell proliferation and invasive properties in human cancer . CCDC181 is a microtubule-binding protein that may play a role in mediating ciliary motility .
Chromodomain-helicase-DNA-binding protein 1-like, C-terminal domain (CHD1-like_C)
Type: Domain

This entry represents a domain found at the C terminus of chromodomain-helicase-DNA-binding proteins, including Chromodomain-helicase-DNA-binding protein 1 from human (CHD1), an ATP-dependent chromatin-remodeling factor which acts as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. This protein functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 . This helical domain, which is also found in CHD1 helical C-terminal domain-containing protein 1 (also known as C17orf64) from mammals , consists of five α-helices organised in a variant helical bundle topology. Its surface is positively charged and can bind dsDNA and nucleosomes, but its specific function remains unknown .
Atos-like, conserved domain (Atos-like_cons_dom)
Type: Domain

This domain is found in the central region of Drosophila Atos, its homologues from mammals, Atos homologue protein A/B (ATOSA/B, formerly known as FAM241) and S.pombe C3H8.04 (SPACC3H8.04), the orthologue of human ATOSA which, from a high-throughput knockout screening, was identified as a protein required for meiotic chromosome segregation . Atos is a transcriptional regulator that synchronizes transcriptional and translational programs to promote macrophage invasion of tissues. It induces transcriptional expression of metabolic enzymes as well as of the translational regulator pths/DDX47. With pths/DDX47, adjusts transcription and translation of a subset of OXPHOS genes to increase mitochondrial bioenergetics and allow macrophage tissue invasion .
Quorum-sensing regulator protein G (QseG)
Type: Family

Quorum-sensing regulator protein G (QseG, also known as YfhG) is involved in the regulation of virulence and metabolism in enterohemorrhagic Escherichia coli (EHEC) . It is required for pedestal formation in host epithelial cells during infection and for translocation of effector molecules into host epithelial cells .
YhdP, central domain (YhdP_central)
Type: Domain

This entry describes the central domain in YhdP and related bacterial proteins. This domain is predicted to span the periplasm. It contains an elongated β-strand groove. This domain represents a region of sequence homology that is collectively conserved amongst all bacterial AsmA-like proteins (

).

Intermembrane phospholipid transporter YhdP is involved in maintaining lipid homeostasis in the outer membrane of Gram-negative bacteria. It likely transports phospholipids between the inner and outer membranes, providing a bridge-like structure that shields the lipids as they traverse the periplasm. Phosphate-containing molecules are thought to be captured along a hydrophobic groove that extends throughout the protein, excluding the extreme N-terminal. YhdP also appears to influence the levels of cyclic enterobacterial common antigen, a soluble molecule located in the periplasm. Along with TamB and YdbH, YhdP performs an essential function in supporting bacterial growth and outer membrane stability, though these proteins are redundant but not functionally equivalent. The transport activity of YhdP is thought to be biased towards phospholipids with saturated fatty acids, whereas TamB may preferentially handle more unsaturated phospholipids. Despite their differences, any one of these three proteins is sufficient to sustain growth under normal conditions . This protein is predicted to be related to AsmA proteins .
Cag pathogenicity island protein Cag12 (Cag12)
Type: Family

This is a Proteobacterial family of Cag pathogenicity island proteins .
WPP domain (WPP_dom)
Type: Domain

The WPP domain is thought to be exclusively found in plants. The WPP stands for a tryptophan-proline-proline motif that is highly conserved in the domain . The WPP domain is known to direct RanGAP (Ran GTPase-activating protein) to the nuclear envelope . RanGAP is an accessory protein for the small signaling GTPase Ran, which is involved in nucleocytoplasmic transport. Non-RanGAP nuclear envelope proteins are also known to encode WPP domains, such as MFP1 attachment factor 1 (MAF1) , WPP1 and WPP2 .