SII-SWORD/CoKE huggingface dataset:
Beta-lactamase 2, metallo-hydrolase domain (BcII-like_MBL-B1)
Type: Domain

This entry represents the MBL-fold metallo-hydrolase domain of Beta-lactamase 2 from Bacillus cereus (also known as BcII) and similar sequences. MBLs (class B of the Ambler beta-lactamase classification) have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. BcII is a chromosome-encoded B1 MBL. B1 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile .
GtgE (GtgE)
Type: Family

This entry represents the effector protein GtgE from Salmonella enterica (

) and similar sequences specific to Salmonella species. GtgE contributes to the virulence of this pathogen by modulating trafficking of the Salmonella-containing vacuole. This protein, which exclusively targets inactive Rab GTPases, has been identified as a cysteine protease with the typical Cys-Hip-Asp catalytic triad. It functions by cleaving the Rab-family GTPases Rab29, Rab32 and Rab38, thereby preventing the delivery of antimicrobial factors to the bacteria-containing vacuole. It has been shown to solely process the inactive GDP-bound GTPase Rab32. However, weak binding of GtgE to the peptide encompassing the Rab29 cleavage site suggests that the function of GtgE may be dependent on other factors, such as a protein partner or interactions with the Salmonella-containing vacuole (SCV) membrane .
SCO3374-like (SCO3374-like)
Type: Family

This family includes proteins related to SCO3374 protein from Streptomyces coelicolor (

). Members of this family are found primarily in Streptomyces.
Zur-induced GTPase-like (ZigA-like)
Type: Family

This entry represents a group of uncharacterised proteins, predominantly found in proteobacteria, including Zinc metallochaperone GTPase ZigA from Acinetobacter sp. ZigA (Zur-induced GTPase A) is a zinc metallochaperone thought to be important for histidine utilization (HUT), supplying Zn to the histidine ammonia-lyase HutH when required under low-Zn conditions . Members of this family contain a C-terminal domain that is related to CobW-like, C-terminal domain superfamily

.
LACTB2-like, MBL-fold metallo hydrolase domain (LACTB2-like_MBL-fold)
Type: Domain

Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry .

This entry represents the MBL-fold hydrolase domain from metazoan and fungal proteins, including human endoribonuclease LACTB2 , the orthologue from Drosophila Beta-lactamase-like protein 2 homologue, fungal atrochrysone carboxyl ACP thioesterases , among others.
F-box/LRR-repeat protein 6, F-box domain (FBXL6_F-box)
Type: Domain

FBXL6, also called F-box and leucine-rich repeat protein 6, or F-box protein FBL6 (FBL6A), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression .
A-factor receptor protein-like (ArpA-like)
Type: Family

This entry represents a group of proteins from actinomycetes, including A-factor receptor protein from Streptomyces griseus (ArpA)

. ArpA represses the adpA expression by binding to its promoter region in the absence of A-factor, causing repression of streptomycin production and of sporulation . Members of this protein family have a TetR-type DNA-binding HTH domain (

) at its N-terminal end and at the C terminus, a domain typical for the TetR transcription regulators superfamily (

). These proteins are involved in the regulation of antibiotic production and other physiological responses .
Fyn/Yrk, SH2 domain (Fyn/Yrk_SH2)
Type: Domain

This entry represents the SH2 domain of Fyn and Yrk, which is involved in signal transduction. SH2 domains typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localise to tyrosine phosphorylated sites .

Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn is involved in the control of cell growth and is required in diverse pathways, including T and B cell receptor signalling, integrin-mediated signalling, growth factor and cytokine receptor signalling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilisation, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells . In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases . Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury .
Nickel-dependent lactate racemase LarA (Ni_dep_LarA)
Type: Family

This entry represents Lactate racemase from Lactiplantibacillus plantarum (LarA) and similar prokaryotic proteins.
LarA is a nickel-dependent lactate racemase that catalyses the interconversion between the D- and L-isomers of lactate . It may act as a rescue enzyme to ensure D-lactate production in physiological conditions where its production by the D-lactate dehydrogenase LdhD is not sufficient. D-Lactate essential for growth of L.plantarum .
Ferredoxin YfhL-like (YfhL-like)
Type: Family

This entry represents Ferredoxin YfhL (also known as EcFd) from Escherichia coli and similar bacterial small soluble proteins bearing two low-potential [4Fe-4S] clusters .
Permease prefix domain 1 (Perm_prefix_1)
Type: Domain

The permease prefix domain 1 is found as the N-terminal domain of bacterial putative permeases resembling ABC transporter permeases, and also of bacterial hypothetical proteins of unknown function, including YwdD from Bacillus subtilis. In some permease families, this prefix domain is variably present, and may be replaced by a different, seemingly unrelated prefix domain.
Cell division protein FtsX, actinomycetes (FtsX_actino)
Type: Family

This entry represents the family of cell division protein FtsX found exclusively in Actinomycetes.

FtsX is an integral membrane protein encoded in the same operon as signal recognition particle docking protein FtsY and FtsE. FtsE is a hydrophilic nucleotide-binding protein that associates with the inner membrane by means of association with FtsX; FtsE mutants are viable only in high salt, supporting possible roles in cell division or in transport . FtsX belongs to a family of predicted permeases and may play a role in the insertion of proteins required for potassium transport, cell division, and other activities . FtsX is involved in sporulation in the Gram-positive bacterium Bacillus subtilis .
IS6 family transposase (Transpos_IS6)
Type: Family

This entry represents a group of proteins, from prokaryotes, belonging to the IS6 family of transposases. Most members of this protein family contain the DDE endonuclease domain (

).
KBTBD6/KBTBD7, BACK domain (KBTBD6_7_BACK)
Type: Domain

This entry represents the BACK domain of KBTBD6 and KBTBD7.

KBTBD6 and KBTBD7 are substrate adaptors of a cullin-3 RING ubiquitin ligase complex that mediates ubiquitylation and proteasomal degradation of T-lymphoma and metastasis gene 1 (TIAM1), a RAC1-specific guanine exchange factor (GEF), by cooperating with gamma-aminobutyric acid receptor-associated proteins (GABARAP), which regulates RAC1 signal transduction and downstream biological processes including the organisation of the cytoskeleton, cell migration and cell proliferation . KBTBD7 may also act as a new transcriptional activator in mitogen-activated protein kinase (MAPK) signalling .
F-box/LRR-repeat protein 14, F-box domain (FBXL14_F-box)
Type: Domain

This entry represents the F-box domain of human F-box/LRR-repeat protein 14 (FBXL14, also called F-box and leucine-rich repeat protein 14) and similar animal sequences. FBXL14 is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin-protein ligase complex, which acts by mediating ubiquitination and subsequent degradation of SNAIL1. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression .
KBTBD6/KBTBD7, BTB/POZ domain (KBTBD6_7_BTB_POZ)
Type: Domain

This entry represents the BTB/POZ domain found at the N-terminal of KBTBD6 and KBTBD7.

KBTBD6 and KBTBD7 are substrate adaptors of a cullin-3 RING ubiquitin ligase complex that mediates ubiquitylation and proteasomal degradation of T-lymphoma and metastasis gene 1 (TIAM1), a RAC1-specific guanine exchange factor (GEF), by cooperating with gamma-aminobutyric acid receptor-associated proteins (GABARAP), which regulates RAC1 signal transduction and downstream biological processes including the organisation of the cytoskeleton, cell migration and cell proliferation . KBTBD7 may also act as a new transcriptional activator in mitogen-activated protein kinase (MAPK) signalling .
BTBD7, first BTB/POZ domain (BTBD7_BTB_POZ_first)
Type: Domain

This entry represents the first BTB/POZ domain.

BTB/POZ domain-containing protein 7 (BTBD7) is a crucial regulator that is essential for region-specific epithelial cell dynamics and branching morphogenesis, especially for branching of embryonic mammalian salivary glands and lungs . It has been implicated in various cancers . BTBD7 contains two BTB domains and a BACK domain.
BTBD7, second BTB/POZ domain (BTBD7_BTB_POZ_second)
Type: Domain

This entry represents the second BTB/POZ domain of BTBD7.

BTB/POZ domain-containing protein 7 (BTBD7) is a crucial regulator that is essential for region-specific epithelial cell dynamics and branching morphogenesis, especially for branching of embryonic mammalian salivary glands and lungs . It has been implicated in various cancers . BTBD7 contains two BTB domains and a BACK domain.
BTBD7, BACK domain (BTBD7_BACK)
Type: Domain

This entry represents the BACK domain of BTBD7.

BTB/POZ domain-containing protein 7 (BTBD7) is a crucial regulator that is essential for region-specific epithelial cell dynamics and branching morphogenesis, especially for branching of embryonic mammalian salivary glands and lungs . It has been implicated in various cancers . BTBD7 contains two BTB domains and a BACK domain.
EexN-like lipoprotein (Eex_IncN-like)
Type: Family

This entry represents a bacterial family of lipoproteins that are typically associated with mobile elements such as phage, and related to the entry exclusion protein Eex of IncN-type plasmids . Members of this family tend to be small (around 90 amino acid residues in length) with three invariant Cys residues, one of which is part of the lipoprotein signal peptide. This family may be distantly related to

, which includes the entry exclusion lipoprotein TrbK of IncPalpha-type plasmids.
Orphan adhesion receptor GPR128, 7TM domain (GPR128_7tmB2)
Type: Domain

GPR128, also known as Adhesion G-protein coupled receptor G7 (AGRG7), is an orphan receptor of the adhesion family (subclass B2) that belongs to class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance, as its knockout mice showed a decrease in body weight gain and an increase in intestinal contraction frequency compared to wild-type controls .

The adhesion receptors are characterised by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain (7tmB). These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, or EMR3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions .

This entry represents the 7tmB domain of GPR128/AGRG7.
Adenine-specific DNA-methyltransferase PglX (BREX_1_PglX)
Type: Family

This entry represents the adenine-specific methyltransferase PglX, which specifically methylates the adenine in the fifth position of the 5'-TAGGAG-3' region in genomic DNA but not in phage DNA upon infection . It is associated with BREX (bacteriophage exclusion) type 1 systems , which provides immunity against bacteriophage. It allows phage adsorption but blocks phage DNA replication . The methylation on non-palindromic TAGGAG motifs in the bacterial genome guides self/non-self discrimination and is essential for the defensive function of the BREX system. Unlike restriction-modification systems, phage DNA does not appear to be cleaved or degraded by BREX.
Olfactory receptor 1330-like (OR1330-like_7tmA)
Type: Family

This entry includes a group of poorly characterised olfactory receptors, including the olfactory receptor 1330 from mouse (

, also known as olfactory receptor family 10 subfamily AK member 16, Or10ak16), Olr859 from rat, and related proteins in other mammals. Olfactory receptors (ORs) play a central role in olfaction, the sense of smell. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs. Binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf). The G protein (Golf and/or Gs) in turn stimulates adenylate cyclase to make cAMP, which opens cyclic nucleotide-gated ion channels, allowing the influx of calcium and sodium ions, that results in depolarization of the olfactory receptor neuron and triggering an action potential which transmits this information to the brain .
ArhGAP19, RhoGAP domain (ARHGAP19_RhoGAP)
Type: Domain

This entry represents the RhoGAP (Rho-like GTPase-activator) domain of Rho GTPase-activating protein 19 (ArhGAP19) and similar proteins mainly found in vertebrates. In mice, a possible role of ArhGAP19 has been described in the regulation of the uterine endometrial epithelium and implantation . Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude .
Ribonucleoprotein PTB-binding 2, RNA recognition motif 3 (RAVER2_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of RAVER2.

Raver-2 is member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family . It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localises to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localisation signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harbouring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs .
Ribonucleoprotein PTB-binding 2, RNA recognition motif 1 (RAVER2_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of RAVER2.

Raver-2 is member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family . It is present in vertebrates and shows high sequence homology to raver-1, a ubiquitously expressed co-repressor of the nucleoplasmic splicing repressor polypyrimidine tract-binding protein (PTB)-directed splicing of select mRNAs. In contrast, raver-2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is mainly limited to differentiated neurons and glia cells. Although it displays nucleo-cytoplasmic shuttling in heterokaryons, raver2 localises to the nucleus in glia cells and neurons. Raver-2 can interact with PTB and may participate in PTB-mediated RNA-processing. However, there is no evidence indicating that raver-2 can bind to cytoplasmic proteins. Raver-2 contains three N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two putative nuclear localisation signals (NLS) at the N- and C-termini, a central leucine-rich region, and a C-terminal region harbouring two [SG][IL]LGxxP motifs. Raver-2 binds to PTB through the SLLGEPP motif only, and binds to RNA through its RRMs .
LIMS1/2-like, LIM domain 1 (LIMS1/2-like_LIM1)
Type: Domain

This is the first LIM (LIM1) domain from LIMS1/2 and its homologues. This domain in LIMS1 interacts with integrin-linked kinase (ILK), thereby mediating focal adhesions via a specific integrin/ILK signaling pathway .

This entry includes LIM and senescent cell antigen-like-containing domain protein 1/2 (LIMS1/2, also known as PINCH-1/2) and its homologues LIM domain-containing protein unc-97 and LIM domain-containing protein pin-2 from C.elegans. LIMS1/2 are LIM domain adapter proteins that functions in the integrin and growth factor signal transduction pathway, involved in the regulation of cell survival, cell proliferation and cell differentiation . Unc-97 is part of the integrin containing attachment complex, which is required for muscle development and maintenance ; it may also function in adherens junction . These proteins consist of five LIM domains, which function as adaptors or scaffolds to support the assembly of multimeric protein complexes.
2-methylisoborneol synthase (MIB_synthase)
Type: Family

This entry represents 2-methylisoborneol synthase (2-MIBS), mainly found in Actinomycetes. This enzyme catalyses the cyclization of 2-methylgeranyl diphosphate (2-MeGPP) to 2-methylisoborneol (2-MIB) . 2-MIB is one of the terpenoid compounds that are known as odorous and volatile microbial metabolites. It is produced by a wide variety of Actinomycete soil organisms, myxobacteria, and cyanobacteria. It has an unusually low odor threshold and, together with geosmin, is responsible for the characteristic smell of moist soil as well as unpleasant taste and odor associated with public water supplies and contamination of various foods, including fish, wine, and beer. In Streptomyces coelicolor, this enzyme (

) is also able to catalyse the cyclization of geranyl diphosphate (GPP), although with lower efficiency, leading to the formation of a complex mixture of cyclic monoterpenes .
LIM and senescent cell antigen-like-containing domain protein 1/2-like (PINCH-1/2-like)
Type: Family

This entry includes LIM and senescent cell antigen-like-containing domain protein 1/2 (LIMS1/2, also known as PINCH-1/2) and its homologues LIM domain-containing protein unc-97 and LIM domain-containing protein pin-2 from C.elegans. LIMS1/2 are LIM domain adapter proteins that functions in the integrin and growth factor signal transduction pathway, involved in the regulation of cell survival, cell proliferation and cell differentiation . Unc-97 is part of the integrin containing attachment complex, which is required for muscle development and maintenance ; it may also function in adherens junction . These proteins consist of five LIM domains, which function as adaptors or scaffolds to support the assembly of multimeric protein complexes.
Ovarian tumor domain-containing protein 4, OTU domain (OTU4_OTU)
Type: Domain

This entry represents the OTU (ovarian tumor) domain of Deubiquitinating enzyme OTU4 from Arabidopsis thaliana, also called OTU domain-containing protein 4 and similar sequences from streptophytes. OTU4 is a deubiquitinase (DUB) or ubiquitin thiolesterase (

) that catalyses the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins . Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signalling, autophagy, transcription, translation, and the DNA damage response. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. This protein belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad .
F-box/LRR-repeat protein 18, F-box domain (FBXL18_F-box)
Type: Domain

In general, F-box proteins share a F-box motif and also have either WD40 repeat domains, LRR domains or various other domains. F-box proteins recruit specific substrates for ubiquitination via different protein-protein interaction domains, such as WD40 repeats and leucine rich repeats (LRRs) .

This entry represents the F-box domain of F-box/LRR repeat protein 18 (FBXL18). This protein is a component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF-Fbxl18 complex has been shown to ubiquitinate FBXL7 and LRRK2 and promote their degradation through the proteasome pathway . By mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein FBXL7 that may impact cellular processes involved in cell cycle progression. It promotes glioma progression by promoting K63-linked ubiquitination of Akt .