SII-SWORD/CoKE huggingface dataset:
Cargo protein 1, compact domain (crAss_CARG1)
Type: Domain

This entry represents the compact domain of cargo protein 1 (C1) found in crassviruses. This protein is unique in that different portions of it are found in both the capsid and the tail of the virion. This domain is bound to the portal protein wing domain inside the capsid, with 12 such segments interdigitating with wing loops (SH3-like domains) of the portal. Additionally, 12 copies of an α-helical segment of the same protein are located at the inner surface of the first and second rings of the tail barrel. A transmembrane helix is predicted in the N-terminal region, which may insert into the host cell membrane. The presence of cargo protein 1 in both the capsid and tail suggests a mechanism for protein ejection prior to complete ejection of genomic DNA, likely involving partial unfolding of the protein as it is extruded through the tail. Cargo protein 1 is believed to be ejected in the N to C direction, with the N-terminal part located in the tail exiting first, followed by the C-terminal domain located in the capsid. This protein likely contributes to the formation of a transmembrane channel for DNA ejection. The protein is broadly conserved among crassviruses, although members of the epsilon group lack a detectable homologue .
Cargo protein 2 (CARGO2)
Type: Family

This entry represents cargo protein 2, a protein stored in high quantity within bacteriophage capsids. This protein likely plays an important role during the phage infection process, particularly during genome ejection. Cargo proteins are packaged inside the viral capsid and are delivered to the host cell during infection, where they may assist in forming transmembrane channels for DNA ejection or perform other functions necessary for successful infection. Cargo protein 2 is present in 12 copies in the virion and has been detected in the capsid of Bacteroides phage crAss001, one of the most abundant bacteriophages in the human gut microbiome. The precise molecular function of this protein remains to be fully elucidated, but its conservation and abundance suggest it plays a critical role in the phage life cycle .
Synoviolin-like, RING finger (Znf_RING_synoviolin)
Type: Domain

This entry represents the C3H2C2-type RING-H2 finger in Synoviolin proteins and Hrd1p, its orthologue in fungi and plants.

Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets the tumour suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER-associated degradation (ERAD) and p53-mediated apoptotic pathways under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis by negatively regulating the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in Endoplasmic Reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis .
ERCC6L2-like, DEXH-box helicase domain (DEXHc_ERCC6L2)
Type: Domain

This domain contains the ATP-binding region in human ERCC6L2 and similar proteins from eukaryotes, including Switch 2 from Arabidopsis thaliana, which is thought to be a chromatin remodelling factor .

ERCC excision repair 6 like 2 (ERCC6L2, also known as RAD26L) is a member of the DEAD-like helicase superfamily, a diverse group of proteins involved in ATP-dependent RNA or DNA unwinding. ERCC6L2 may contribute to both DNA repair and mitochondrial function, and in humans, mutations in the ERCC6L2 gene are linked to bone marrow failure syndrome 2. This protein plays a role in DNA double-strand break (DSB) repair by restricting DNA end resection, thereby contributing to the maintenance of genomic stability .
RamC, C-terminal domain (RamC_C)
Type: Domain

This domain is found at the C-terminal end of RamC and similar proteins mainly found in actinomycetes.

Probable SapB synthase from Streptomyces coelicolor (RamC) is required for aerial hyphae formation . It is probably involved in processing the precursor of SapB to its mature form. It shows an α-β configuration. This protein is part of the LanC-like protein superfamily represented by

.
PHD finger protein MALE STERILITY 1-like, Zinc finger (Znf_MS1-like)
Type: Domain

This entry represents the PHD (homeodomain) zinc finger domain in MS1, PTC1 and similar proteins found in plants.

PHD finger protein MALE STERILITY 1 (MS1) is a nuclear transcriptional activator essential for anther and post-meiotic pollen development and maturation. It plays a key role in tapetal development, pollen wall biosynthesis, and may also influence inflorescence branching and floral development . MS1 contains both a leucine zipper-like domain and a plant homeodomain (PHD) finger motif, which are critical for its function. MMD1, encoded by the DUET gene, is another PHD finger protein expressed specifically in male meiocytes. It is required for proper male meiotic chromosome organisation and progression, and is thought to regulate gene expression during meiosis. Loss-of-function mutations in MMD1 lead to cell death in male meiocytes, highlighting its essential role in male gametophyte development.

PHD finger protein PERSISTENT TAPETAL CELL 1 from Oryza sativa (PTC1) also belongs to this group. PTC1 is thought to be a transcriptional activator required for tapetal programmed cell death and degeneration, and pollen development in anthers .
PA-PLA1 (PA-PLA1)
Type: Family

This entry includes PA-PLA1 proteins, including SEC23-interacting protein (Sec23ip), Triacylglycerol hydrolase DDHD2 (DDHD2) and Phospholipase DDHD1, which are PA-PLA1 proteins in mammals. This entry also includes the homologue in Saccharomyces cerevisiae and putative homologues in Schizosaccharomyces pombe, Caenorhabditis elegans and Arabidopsis thaliana.

Phospholipase SGR2 from Arabidopsis thaliana has been identified as a member of the PA-PLA1 family, but their functions are not limited to phospholipase activity. It is involved in vacuolar formation or function (e.g. formation of vacuolar membrane 'bulbs'). It is also required for amyloplast sedimentation in the endodermis during shoot gravitropism, which are thus acting as statoliths. It is particularly important for the negative gravitropism leading to leaf movement observed in darkness .

Sec23ip plays a role in the organisation of endoplasmic reticulum exit sites. Specifically binds to phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-phosphate (PI5P). However, current evidence indicates that it does not exhibit actual phospholipase activity .

DDHD2 functions as a diacylglycerol (DAG) and triacylglycerol (TAG) lipase, playing a critical role in maintaining lipid homeostasis in the central nervous system . It acts in concert with PNPLA2/ATGL in neuronal TAG catabolism by hydrolysing sn-1,3 DAG downstream of PNPLA2/ATGL. In vitro studies show that DDH2 also exhibits phospholipase activity, preferentially hydrolysing phosphatidic acids such as 1,2-dioleoyl-sn-phosphatidic acid, as well as phosphatidylcholine and phosphatidylethanolamine. Additionally, it specifically binds to phosphoinositides, including phosphatidylinositol 3-phosphate (PI3P), PI4P, PI5P, and possibly PI(4,5)P2. This lipid-binding activity suggests a role in the maintenance of endoplasmic reticulum and Golgi structures, potentially influencing vesicular transport between the Golgi apparatus and the plasma membrane.

PA-PLA1 proteins are involved in various cellular processes related to membrane lipid metabolism and organelle structure maintenance. These proteins exhibit phospholipase activity, preferentially hydrolysing phosphatidic acid and phosphatidylethanolamine. They also have specific lipid-binding capabilities, interacting with phosphatidylinositol phosphates such as PI(3)P, PI(4)P, and PI(5)P. This binding is crucial for their role in organising endoplasmic reticulum exit sites and may influence transport between the Golgi apparatus and plasma membrane. The function of these proteins is essential for maintaining the integrity of the endoplasmic reticulum and Golgi structures, which are critical for proper cellular function .
TANC1/2-like, winged helix-turn-helix domain (HTH_TANC1/2)
Type: Domain

This presumed winged helix-turn-helix domain is found in Protein TANC1, TANC2 and similar proteins mainly found in animals. This domain is often found associated to a long region of ankyrin repeats (

).

TANC proteins function as scaffolding components in the postsynaptic density and dendritic spines. These proteins are involved in the organisation and stabilisation of synaptic structures. TANC1 proteins are likely involved in the postsynaptic density, interacting with various synaptic proteins such as DLG1, DLG4, and HOMER1, and may play a role in synaptic signalling and plasticity. TANC2 proteins act as immobile postsynaptic posts in dendritic spines, recruiting KIF1A-driven dense core vesicles, which are crucial for synaptic function and vesicle trafficking. The interaction of TANC2 with KIF1A is modulated by calcium levels, indicating a role in calcium-dependent synaptic processes .
Lipoprotein BBH37-like (BBH37-like)
Type: Family

This entry represents BBH37 from Borrelia burgdorferi (

) and related proteins from Spirochaetales. Many members posses a lipid attachment site. Proteins in this entry have a domain (

) that folds into a helical bundle (

).
CBU_0592-like (CBU_0592-like)
Type: Domain

This entry represents an uncharacterised domain in CBU_0592 protein from Coxiella burnetii RSA 493. These proteins are about 90 amino acids in length and rich in hydrophobic residues, suggesting a location largely in the membrane. A minority have an additional C-terminal domain related to cyclic nucleotide-binding domains. Some proteins have two copies of this domain.
PA3496-like (PA3496-like)
Type: Family

This poorly understood protein family consists of small and highly divergent proteins, about 65 amino acids long. It is widely distributed in Gram-negative bacteria. One member, PA3496 from Pseudomonas aeruginosa, was shown to be upregulated in the presence of inulin or inulin-derived fructooligosaccharide. Moraxella catarrhalis strains in which another member of this family, MCR_0424, is knocked out by mutation have a severe defect in resistance to the complement present in serum. The latter result suggests a role as a cell envelope integrity protein. This family appears related to

.
HYC_CC_PP family protein (HYC_CC_PP)
Type: Family

This uncharacterised family of proteins, widespread in gram-negative bacteria, is named for three well-conserved motifs, HYC, CC (which may appear twice), and PP.
SCO4848-like (SCO4848-like)
Type: Family

This entry represents SCO4848 from Streptomyces coelicolor A3(2) , a 79 amino acid putative membrane protein. It is best known for having the integration site for Streptomyces phage phiBT1 lie within its gene. Homologs of SCO4848 are found broadly within Streptomyces, Saccharomonospora, Arthrobacter, and Nocardioides, and related genera.
SCO7613, C-terminal domain (SCO7613_C)
Type: Domain

This entry describes a conserved region found at the C-terminal of large but variable-length hydrophobic proteins found mostly in members of the Actinomycetes such as Streptomyces, Micromonospora, Actinoplanes, and Nocardioides. The founding member, SCO7613 from Streptomyces coelicolor, is among a limited set of proteins directly regulated by the response regulator transcription factor MacR (Morphogenesis and ACtinorhodin Regulator, SCO2120) .
FFLEELY motif contaning (FFLEE_fam)
Type: Family

This uncharacterised family is named for its highly conserved motif, FF[LVF][ED][ED]LY. Members of this family are found mostly in gammaproteobacterial genera such as Acinetobacter, Aeromonas, Alteromonas, and Psychrobacter, but also in betaproteobacteria and in the Leptospira genus of spirochetes.
STM2901-like (STM2901-like)
Type: Family

The founding member of this family of uncharacterised proteins is STM2901, a putative cytoplasmic protein from many but not all forms of SPI-1 (Salmonella Pathogenicity Island 1). members of this family are found in gamma- and betaproteobacteria.
LIC_10190-like (LIC_10190-like)
Type: Family

Members of this broadly distributed family average about 600 amino acids in length and are highly hydrophobic. Two of the very few invariant amino acids occur in a DxxxY motif. Some members of this family show sequence similarity to dolichyl-phosphate-mannose-protein mannosyltransferases (see

), suggesting they may be glycosyltranferases.
pXO2-14/BXB0013/GBAA_pXO2_0013, N-terminal domain (pXO2-14_N)
Type: Domain

This entry represents the N-terminal domain in large, membrane-embedded proteins of mobile elements such as the Bacillus subtilis natto plasmid pLS20. They show distant relationships to better-characterised VirB-like conjugal transfer proteins. These proteins also show homology to the family of Mbov_0396-like transmembrane proteins found in ICE elements of Mycoplasmopsis bovis and related species. The Transporter Classification Database (TCDB) assigns 3.A.7.13.2 to the plasmid pLS20-like conjugation system, whose member proteins include VirB1, VirB4, VirB11, VirD2, and VirD4 homologs .
CC_3452-like (CC_3452-like)
Type: Family

This entry represents a family of uncharacterised proteins found mainly in alphaproteobacteria.
LIC_13387-like (LIC_13387-like)
Type: Family

This entry represents a family of uncharacterised bacterial proteins. It is named for LIC_13387 from Leptospira interrogans, but members are found in wide variety of bacterial species. In Leptospira, LIMLP_17285 was observed to have lower expression in response to hydrogen peroxide stress.
Threonine/serine transporter ThrP (ThrP)
Type: Family

This entry represents Threonine/serine transporter ThrP, a member of the Amino Acid-Polyamine-Organocation (APC) family according to the transporter classification database (TDCB.org). Threonine and serine are substrates. In Escherichia coli K-12, the member protein was previously known as YifK.

ThrP is a permease that mediates the proton-dependent uptake of threonine and serine . It shows higher specificity for threonine , and it cannot transport homoserine .
Morphogenic membrane protein MmpB (MmpB-like)
Type: Family

This entry represents the morphogenic membrane protein MmpB and related proteins from Streptomycetaceae. MmpB expression in S. coelicolor is regulated by a two-component system (TCS) MacRS . MmpB interacts with the membrane proteins MmpA and MmpC, which are also regulated by MacRS TCS . MmpA-C proteins are morphogenic factors that delay the formation of aerial mycelium.
WalR, receiver domain (WalR_REC)
Type: Domain

This entry represents the phosphoacceptor receiver (REC) domain of Transcriptional regulatory protein WalR from Bacillus subtilis (also known as YycF) and similar proteins predominantly found in firmicutes. REC domains function as phosphorylation-mediated switches within response regulators, but some also transfer phosphoryl groups in multistep phosphorelays .

WalR is a member of the two-component regulatory system WalK/WalR involved in the regulation of the ftsAZ operon, the yocH, ykvT, cwlO, lytE, ydjM, yjeA, yoeB genes and the tagAB and tagDEF operons. It is essential for cell wall metabolism . In Streptococcus pneumoniae, this protein inhibits transcription of fabT, probably acting in an unphosphorylated form, thereby playing a role in the regulation of fatty acid biosynthesis . WalR belongs to the OmpR family of response regulators, which are characterised by a REC domain and a winged helix-turn-helix effector domain involved in DNA binding .
LIC_12708-like (LIC12708-like)
Type: Family

This entry represents putative bacterial lipoproteins mainly found in spirochetes. They are named after LIC_12708 from Leptospira interrogans. Some of the members contain a lipoprotein lipid attachment site suggesting they may be associated with the membrane.
Silver-binding protein SilE (SilE)
Type: Family

This entry represents the silver-binding protein SilE, a component of the sil cation-efflux system that provides resistance to silver. SilE functions as a periplasmic molecular sponge for silver ions, capable of binding up to 38 Ag(+) ions. It shares approximately 48% sequence identity with the periplasmic copper-binding protein PcoE, which is known to bind both silver and copper .
Bacteriocin-like conserved region (Bacteriocin-like)
Type: Conserved_site

The sequence region that defines this family is found predominantly in the genus Chryseobacterium, consistently located at the N terminus. It terminates with a Gly-Gly (or occasionally Gly-Ala) motif, beyond which the sequences, while typically rich in cysteine, exhibit considerable diversity. This pattern is highly characteristic of bacteriocin leader peptides. Some members of this family are located near genes encoding C39 family Gly-Gly peptidase domain-containing transporters, lantibiotic dehydratases, and related proteins.
Chitoporin (Chitoporin)
Type: Family

This entry represents enterobacterial chitoporin and related proteins from gammaproteobacteria. Chitoporin is an outer membrane protein required to import chitin-derived oligosaccharides .
NADH oxidase (NOXase)
Type: Family

This protein family includes NADH oxidase from Streptococcus pneumoniae (NOXase) and similar sequences mainly found in firmicutes. NOXase catalyses the four-electron reduction of molecular oxygen to water and may be involved in mediating bacterial adhesion to host cells . It plays a role in redox balance maintenance .
Ag473-like (Ag473-like)
Type: Family

Members of this surface-exposed meningococcal lipoprotein family, called Ag473, have variable numbers of the sequence KEAVTEA. Most members contain a lipoprotein lipid attachment site suggesting may be associated with the membrane.
Cj0814 flagellar-dependent secreted protein (Cj0814-like)
Type: Family

Members of this family, restricted to the genus Campylobacter, appear not to be flagellar proteins, but depend on flagellar expression in order to be secreted and be found in culture supernatant.
LIC_12936-like (LIC_12936-like)
Type: Family

Members of this family are named after LIC_12936 from Leptospira interrogans, and found in all three clades of Leptospira (Pathogenic, Intermediate, and Saprophytic). Members have a conserved signal peptide region. The function is unknown.
LBF_1011-like (LBF_1011-like)
Type: Family

This family is named after protein LBF_1011 from Leptospira biflexa, a saprophytic (non-pathogenic) species of Leptospira.
LBF_2127 (LBF_2127)
Type: Family

Members of this family of putative lipoproteins occur in more than half the known species of Leptospira and Leptonema. The function is unknown. The founding member is LBF_2127.
LIC_11090-like (LIC_11090-like)
Type: Family

Members of this family average about 150 amino acids in length and share five invariant Cys residues, including two CxC motifs. The family is found in Leptospira, and named for LIC_11090 from the model strain Leptospira interrogans serovar Copenhageni str. Fiocruz L1-130. Some members contain a lipoprotein lipid attachment site suggesting they may be associated with a membrane.
Slr1658-like (Slr1658-like)
Type: Family

This entry represents Slr1658 protein and homologues. It has been reported that Slr1658 had extensive effects on the expression of genes encoding regulatory proteins, proteins involved in the remodelling and degradation of the photosynthetic apparatus and proteins modulating electron transport in Cyanobacteria. Slr1658 homologs have been identified in many species .
PP_RS20740-like (PP_RS20740-like)
Type: Family

This entry represents a subset of uncharacterised bacterial proteins related to PP_RS20740 from Pseudomonas putida. A missense mutation (V338F) in this protein improved tolerance to furfural, a metabolite of pentose degradation . The function is unknown.
Immunodominant staphylococcal antigen B (IsaB)
Type: Family

This entry represents IsaB (immunodominant staphylococcal antigen B, or immunodominant surface antigen B) from Staphylococcus aureus. IsaB is a virulence factor that impedes autophagy by host defence systems. It is unrelated to IsaA, an apparent soluble lytic transglycosylase . Additional members of this family are found in numerous species of Staphylococcus, Mammaliicoccus, Macrococcus, and Jeotgalicoccus.
XAC2610 domain (XAC2610_dom)
Type: Domain

This entry represents a central domain in Xanthomonas Type IV Secretion System related protein

and related proteins. This domain is formed by two β-sheets. The founding member of this family, XAC2610

is an apparent type IV secretion system effector protein.
Peptidoglycan hydrolase PcsB (PcsB)
Type: Family

This entry represents Peptidoglycan hydrolase PcsB from Streptococcus pneumoniae and similar proteins from lactobacillales.

PcsB is required for the maintenance of normal growth and cellular morphology and is involved in the splitting of the septum during cell division . This protein is organised into three regions: an α-helical coiled coil (CC) domain, an alanine-rich linker region and a globular catalytic CHAP domain (

) with an α+β papain-like amidase fold .
EgtUBC, C-terminal periplasmic solute-binding domain (EgtUBC_SBD)
Type: Domain

This entry represents the C-terminal periplasmic solute-binding domain (SBD) of Probable ergothioneine transporter EgtUBC from Staphylococcus aureus and similar proteins predominantly found in firmicutes. EgtUBC is part of an ABC transporter complex EgtU required for the uptake of ergothioneine (EGT), a natural low-molecular weight (LMW) thiol antioxidant. This domain binds to EGT with sub-micromolar affinity .
50S ribosomal protein bL37, Actinomycetota type (bL37_actino)
Type: Family

This entry represents the homologues of bL37 ribosomal protein. bL37 is a small, highly basic protein found in the ribosomes of certain bacteria, notably mycobacteria such as Mycolicibacterium smegmatis and Mycobacterium tuberculosis. It consists of 24 amino acids and has a theoretical molecular weight of about 2.84 kDa. bL37 is located near the peptidyltransferase center (PTC) of the large (50S) ribosomal subunit, which is a crucial site for protein synthesis and it may play a role in stabilising this region or modulating its function . PTC ia a common target for antibiotics and knockout studies in Mycolicibacterium smegmatis have shown that the absence of bL37 increases sensitivity to the antibiotic linezolid .
FcpA (FcpA)
Type: Family

FcpA (flagellar-coiling protein A) is unique to Leptospira, Leptonema and Turneriella. It is part of the filament sheath of the spirochete periplasmic flagellum .
WWWY-motif domain (WWWY)
Type: Domain

This extremely hydrophobic domain is found in Clostridia and related Gram-positive species, either as the C-terminal portion of a protein with an N-terminal predicted helix-turn-helix (HTH) DNA-binding domain or standalone. This domain includes a highly unusual motif within a strongly hydrophobic stretch, WxxxWxxWxxY, in which all four aromatic residues are invariant.
LA_2272-like repeat (LA_2272-like)
Type: Repeat

This entry represents a 15-amino acid repeat. Numbers of repeats in proteins vary. Notable surface-exposed proteins with this repeat domain include lipoproteins LA_2272 (Q8F3X7) and LA_2273 (Q8F3X6) from Leptospira interrogans and VC2662 (Q9KNR9) from Vibrio cholerae.