SII-SWORD/CoKE huggingface dataset:
BAR/IMD domain-containing adapter protein 2, I-BAR domain (BAIP2_I-BAR_dom)
Type: Domain

IRSp53, also known as IRS-58 or BAR/IMD domain-containing adapter protein 2 (BAIP2 or BAIAP2 for brain-specific angiogenesis inhibitor 1-associated protein 2), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature .

IRSp53 is an adaptor protein that acts at the membrane-actin interface, coupling membrane deformation with F-actin polymerisation . It is involved in the formation of filopodia and lamellipodia in cultured mesenchymal cells and contributes to assembly/maintenance of tight junctions in cultured epithelial cells . IRSp53 contains an N-terminal I-BAR domain, followed by a partial CRIB domain and a SH3 domain. It binds to small GTPase Cdc42, Rac1 and WAVE1 . IRSp53 binds Rac through its I-BAR domain and to WAVE through its SH3 domain, and thus contributes to membrane ruffling . Its SH3 domain also interacts with other regulators of actin dynamics, such as WAVE2, Mena, mDia1, Dynamin1, Eps8 and N-WASP .

This protein has been associated with human breast cancer and Gilles de la Tourette syndrome .

This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), which binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac .
Autoinducer 2 ABC transporter, substrate-binding protein LsrB (LsrB)
Type: Family

Autoinducers are signalling molecules secreted by bacteria to communicate with one another in a process called quorum sensing. Autoinducer 2-binding protein LsrB is part of the ABC transporter complex LsrABCD involved in autoinducer 2 (AI-2) import. It binds AI-2 and delivers it to the LsrC and LsrD permeases .

Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins .
Purine permease, plant (PUP_plant)
Type: Family

This entry represent a group of purine permeases (PUPs) from plants, including AtPUP1-22 from Arabidopsis. AtPUP1 and 2 mediate energy-dependent high-affinity adenine uptake and cytokinin transport . However, the transporter function of other family members is not clear - they may act as transporters for nucleosides, nucleotides, and their derivatives .
S-type anion channel (SLAC/SLAH)
Type: Family

This entry represents a family of S-type (slow current) anion channels that in Arabidopsis consists of SLAC1 (SLOW ANION CHANNEL-ASSOCIATED 1, At1g12480) and SLAC1-homologue proteins 1-4 (SLAH1-4). They have in common their plasma membrane localisation, but show distinct tissue-specific expression patterns. They are distant homologues of bacterial and fungal C4-dicarboxylate transporters .

SLAC1 is localised specifically to the plasma membrane of guard cells . It mediates CO2 sensitivity and is essential for stomatal closure in response to various endogenous and environmental stimuli , such as abscisic acid, ozone, light/dark transitions, humidity change, calcium ions, hydrogen peroxide and nitric oxide . It also functions as an essential negative regulator of inward potassium channels in guard cells.
WAT1-related protein (WAT1-related)
Type: Family

The plant drug/metabolite exporter (DME) family consists of a group of plant WAT1 (walls are thin1)-related proteins. They contain the EamA domains that can be found in some drug/metabolite exporters in bacteria. Arabidopsis WAT1 is required for secondary cell-wall deposition , and conferred broad-spectrum resistance to vascular pathogens . Auxin-induced protein 5NG4, another member of the family, is a putative transmembrane protein that is differentially expressed in mature and juvenile-phase shoots .
Malic acid transport protein (Mae1)
Type: Family

This entry represents a group of malic acid transport proteins from fungi. In fission yeast it serves as a permease for malate and other C4 dicarboxylic acids .
Ureide permease, plant (UPS_plant)
Type: Family

This entry represents ureide permeases (UPSs) from plants, including Arabodopsis AtUPS1-5. They are transporters for allantoin and other oxo derivatives of nitrogen heterocyclic compounds. In Arabidopsis, the UPS family members have distinct and partially overlapping expression patterns with regard to developmental stages or tissue specific localisation . AtUPS1 may be involved in the uptake of allantoin and other purine degradation products when primary sources are limiting . AtUPS1 and AtUPS2 mediate high affinity transport of uracil and 5-fluorouracil . AtUPS5 has two isoforms, long and short. The short isoform of ATUPS5 lacks two transmembrane domains and may be defective in transporting cyclic purine degradation products and pyrimidines .
Macrolide export protein MacA, alpha-hairpin domain superfamily (MacA_alpha-hairpin_sf)
Type: Homologous_superfamily

MacA is part of the MacAB-TolC complex (composed of an inner membrane transporter, MacB, a periplasmic membrane fusion protein, MacA, and an outer membrane component, TolC), which is a tripartite macrolide efflux transporter driven by hydrolysis of ATP . MacA interacts with MacB and TolC . MacA can bind rough-core lipopolysaccharide (R-LPS) specifically and with high affinity, suggesting that the complex could also transport R-LPS or a similar glycolipid . Its protein structure has been solved .

This entry represents the α-hairpin of MacA, which is implicated to bind to TolC.
Cytosine permease (CodB)
Type: Family

The CodB gene is part of the Escherichia coli codBA operon. CodB is a transmembrane protein required for cytosine transport into the cell .
Miniconductance mechanosensitive channel YbdG (YbdG)
Type: Family

YbdG is a low-abundance MscM-type mechanosensitive (MS) channel, which sense elevated membrane tension that arises from rapid water influx occurring when cells move from high to low osmolarity environments (hypoosmotic shock). YbdG plays minor roles in maintaining cell integrity, obviating the need to activate the major MS channels, MscS and MscL .
Nuclear RNA export factor (NXF_fam)
Type: Family

Mex67 is involved in the export of mRNA from the nucleus to the cytoplasm in Saccharomyces cerevisiae . Vertebrate TAP (also called NXF1 for nuclear RNA export factor 1) is the orthologue of Mex67 . TAP belongs to a multigene family with conserved modular architecture . Other members of the family in humans are NXF2, NXF3, and NFX5. Both TAP(NXF1) and NXF2 bind mRNA and display RNA nuclear export activity . NXF3 also has the ability to export mRNA from the nucleus to the cytoplasm but it uses a different mechanism . NXF1 and NXF2 are predominantly nuclear, whereas the cytoplasmic presence of NXF3 and NXF5 suggests that they have a different cellular function .

Three functional domains of TAP have been characterised: the RNA-binding domain, the Nuclear Transport Factor 2 (NTF2)-like domain, and the ubiquitin-associated (UBA) domain. The RNA-binding domain (RBD) of TAP is located at its amino terminus and is composed of two RNA recognition motifs (RRMs) and one leucine-rich region . Once bound to mRNA, TAP escorts the messenger ribonucleoprotein (mRNP) to the nuclear pore, where TAP interacts with nucleoporins via the NTF2-like (NTF2L) and UBA domains .
Activated CDC42 kinase 1, UBA domain (Ack1_UBA_dom)
Type: Domain

Activated CDC42 kinase 1 (Ack1) is a non-receptor tyrosine kinase (NRTK) that is implicated in metastatic behaviour, cell spreading and migration, and epidermal growth factor receptor (EGFR) signalling . It interacts with a number of transmembrane receptor tyrosine kinases and is involved in several cell signalling pathways. Its activation has been linked to cancer progression .

This entry represents the C-terminal ubiquitin-association (UBA) domain of ACK1.
Sla2 family (Sla2_fam)
Type: Family

The Sla2 family, also known as Sla2p/HIP1/HIP1R family, includes Sla2 from budding yeasts , End4 from fission yeasts , and Huntingtin-interacting protein 1 (HIP1) and HIP1-related (HIP1R) from humans and mice . They are adaptor proteins that link actin to clathrin and endocytosis in the clathrin-mediated endocytosis (CME) pathway. They contain the ENTH and ANTH (E/ANTH) domain that binds both inositol phospholipids and proteins and contributes to the nucleation and formation of clathrin coats on membranes . They may bind to actin through their I/LWEQ (talin-like) domain .
Sterol regulatory element-binding protein cleavage-activating protein (SCAP)
Type: Family

Sterol regulatory element-binding protein cleavage-activating protein (SCAP) is a escort protein required for cholesterol and lipid homeostasis . It is an endoplasmic reticulum protein with eight transmembrane helices that serves as a cholesterol sensor . In cholesterol-depleted cells, SCAP transports sterol regulatory element-binding proteins (SREBPs) to the Golgi, where the active fragment of SREBP is liberated by proteases so that it can activate genes for cholesterol synthesis .

A homologue of SCAP exists in Schizosaccharomyces pombe, named Scp1, which together with Sre1 (homologue to SREBP), may mediate a hypoxic response by monitoring oxygen-dependent sterol synthesis .
GPN-loop GTPase 3 (Gpn3)
Type: Family

GPN-loop GTPase 3 (Gpn3) belongs to the GPN-loop GTPase family . Budding yeast Gpn3 plays a role in biogenesis of RNA pol II and polIII and is involved in sister chromatid cohesion . Its human homologue, Parcs (pro-apoptotic protein is required for cell survival), is a dual regulator of cell proliferation and Apaf-1 function . Parcs is also required for the nuclear accumulation of RNA polymerase II .
GPN-loop GTPase 1 (Gpn1/Npa3/XAB1)
Type: Family

GPN-loop GTPase 1 (Gpn1) belongs to the GPN-loop GTPase family . It is also known as Npa3 in budding yeasts, QQT2 in plants and XAB1 in humans.

Npa3 has GTPase activity that is essential for its binding to RNA polymerase II (RNAPII) and the nuclear localisation of RNAPII .

The small GTPase QQT2 is essential for the correct formation of the tangential divisions in early embryos. This protein associates with microtubules during mitosis and may play a role in the positioning of the division plane .

XAB1 is a cytoplasmic GTPase involved in nuclear localisation of DNA repair protein XPA .

This entry also includes archaeal GPN-loop GTPases, such as PYRAB14380 from Pyrococcus abyssi .
GPN-loop GTPase 2 (Gpn2)
Type: Family

GPN-loop GTPase 2 (Gpn2) belongs to the GPN-loop GTPase family . It is also known as ATPBD1B in humans.

In budding yeasts, Gpn2 is a putative GTPase that has a role in biogenesis of RNA polymerase II and III . It is involved in sister chromatid cohesion .

In Arabidopsis thaliana, Gpn2 is also known as GPN-loop GTPase QQT1. It associates with microtubule during mitosis and may function in the positioning of the division plane. QQT1 is crucial for normal development of the plant .
Harmonin, N-terminal (Harmonin_N)
Type: Domain

This entry represents the N-terminal protein-binding module of Harmonin. It binds specifically to a short internal peptide fragment of the Cadherin 23 cytoplasmic domain, a component of the Usher protein network .

Harmonin is a F-actin binding protein that can be found in hair cell stereocilia and sensory cell microvilli . In the hair cells of the inner ear, harmonin is an upper tip-link density (UTLD) component that is necessary for normal hearing .
ATP-binding cassette sub-family C member 4, six-transmembrane helical domain 1 (ABCC4_TMD1)
Type: Domain

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .

This group of proteins includes ATP-binding cassette sub-family C member 4 (ABCC4, also known as Multidrug resistance-associated protein 4, MRP4) from animals. It belongs to the MRP (multidrug resistance protein) subfamily of the ATP-binding cassette (ABC) transporter family . MRP4 is a broad specificity organic anion exporter that seems to be able to mediate the transport of conjugated steroids, prostaglandins, and glutathione . It can localise to both basolateral and apical membranes in polarised cells, depending on the tissue where it is found . Together with CFTR, MRP4 functions in the regulation of cAMP and beta-adrenergic contraction in cardiac myocytes .

This entry represents the six-transmembrane helical domain 1 (TMD1) of ABCC4.
Chloride intracellular channel protein 2, C-terminal domain (GST_C_CLIC-2)
Type: Domain

Chloride intracellular channel (CLIC) proteins are multifunctional and participate in a wide variety of signaling activities. CLIC proteins are able to convert from a water-soluble state to a membrane channel state . Chloride intracellular channel protein 2 (CLIC-2) is found in in most tissues except the brain, and is highly expressed in the lung, spleen, skeletal muscle and myocardium. It inhibits cardiac ryanodine receptor Ca2+ release channels . It contains an intramolecular disulfide bond and exists as a monomer regardless of redox conditions .

This is the C-terminal helical domain.
ATP-binding cassette subfamily B member 9, six-transmembrane helical domain (ABCB9_6-TMD)
Type: Domain

ATP-binding cassette subfamily B member 9 (ABCB9, also known as ABC-type oligopeptide transporter ABCB9, TAP-like and TAPL) is a eukaryotic half transporter that belongs to the ABC_6TM exporter family. It translocates peptides from the cytosol into the lumen of lysosomes . It forms a homodimer and functions as a low affinity transporter that displays a broad peptide length specificity for 6-mer up to at least 59-mer peptides, with an optimum of 23-mers . Positively charged, aromatic, or hydrophobic residues are more efficiently transported than negatively charged ones .

The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein .

This entry represents the six-transmembrane helical domain (6-TMD) of ABCB9, which shows 6 TM helices.
Chloride intracellular channel protein 1, C-terminal domain (CLIC-1_C)
Type: Domain

This entry represents the C-terminal, α-helical domain of CLIC1 .

Intracellular chloride ion channel proteins (CLICs) has been shown to exist in both soluble and integral membrane forms. Chloride intracellular channel protein 1 (CLIC1) can insert into membranes and form chloride ion channels . Membrane insertion seems to be redox-regulated and may occur only under oxydising conditions . Channel activity has been shown to have a strong pH dependence . The soluble form of CLIC1 is monomeric and structurally homologous to the glutathione S-transferase superfamily, with a redox-active site resembling glutaredoxin .

CLIC1 (also known as NCC27) is involved in regulation of the cell cycle .
Nesprin-4 (SYNE4)
Type: Family

Nesprins (nuclear envelope spectrin-repeat proteins) are a family of giant spectrin-repeat containing proteins that act as versatile intracellular protein scaffolds . They are characterised by a central extended spectrin-repeat (SR) and a C-terminal Klarsicht/ANC-1/Syne homology (KASH) domain that can associate with Sad1p/UNC-84 (SUN)-domain proteins of the inner nuclear membrane within the periplasmic space of the nuclear envelope (NE) .

This entry represents Nesprin-4 predominantly from mammals. Nesprin-4 links the nucleus to microtubules through its binding to kinesin-1 . It is a component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, which plays critical roles in nuclear positioning, cell polarisation and cellular stiffness .
Signal recognition particle 43kDa protein, chromodomain 3 (CPSRP43_chromodomain_3)
Type: Domain

This group of proteins includes chloroplast signal-recognition particle 43kDa protein (CpSRP43) and similar plant proteins. In Arabidopsis, CpSRP43 (AT2G47450, CAO) is a component of the chloroplast signal recognition particle pathway that is involved in LHCP (light-harvesting chlorophyll a/b-binding protein) targeting. LHCPs are synthesised in the cytoplasm, and after import into the chloroplast, they are targeted and inserted into the thylakoid membrane. In addition, CpSRP43 functions as a chaperone preventing aggregation of LHCP following import into the chloroplast .

This entry represents the chromodomain 3 of SRP43, which appear to play a role in the functional organization of the eukaryotic nucleus. This domain is involved in the binding activity of these proteins to methylated histone tails and maybe RNA .
Interleukin-1 receptor-associated kinase 1-binding protein 1 (IRAK1BP1)
Type: Family

Interleukin-1 receptor-associated kinase 1-binding protein 1 (IRAK1BP1, also known as SIMPL) was originally identified in a yeast two-hybrid screen system . In mice, IRAK1BP1 inhibits inflammation by promoting nuclear translocation of NF-kappaB p50 . In Haliotis diversicolor, IRAK1BP1 plays an important role in the adult abalone immune system and might be essential in embryo and larval development in abalone .
Polyamine biosynthesis domain, conserved site (PABS_CS)
Type: Conserved_site

The nearly ubiquitous polyamines (putrescine, spermidine and spermine) are polycationic mediators of cell proliferation and differentiation whose functions likely provide both stability and neutralisation for nucleic acids. The following polyamine biosynthetic enzymes are evolutionary related and contain a polyamine biosynthesis (PABS) domain :

Spermidine synthase (

) (putrescine aminopropyltransferase). It catalyses the last step in the biosynthesis of spermidine from arginine and methionine; the conversion of putrescine to spermidine using decarboxylated S-adenosylmethionine as the cofactor.

Spermine synthase (

) (spermidine aminopropyltransferase). It converts spermidine into spermine using decarboxylated S-adenosylmethionine as the cofactor.

Putrescine N-methyltransferase (

). It catalyses a step in the biosynthesis of nicotine in plants; the methylation of putrescine to N-methylputrescine using S-adenosylmethionine as the cofactor.

This conserved site consists of a glycine-rich conserved region in the PABS domain.
Polyamine biosynthesis domain (PABS)
Type: Domain

The nearly ubiquitous polyamines (putrescine, spermidine and spermine) are polycationic mediators of cell proliferation and differentiation whose functions likely provide both stability and neutralisation for nucleic acids. The following polyamine biosynthetic enzymes are evolutionary related and contain a polyamine biosynthesis (PABS) domain :

Spermidine synthase (

) (putrescine aminopropyltransferase). It catalyses the last step in the biosynthesis of spermidine from arginine and methionine; the conversion of putrescine to spermidine using decarboxylated S-adenosylmethionine as the cofactor.

Spermine synthase (

) (spermidine aminopropyltransferase). It converts spermidine into spermine using decarboxylated S-adenosylmethionine as the cofactor.

Putrescine N-methyltransferase (

). It catalyses a step in the biosynthesis of nicotine in plants; the methylation of putrescine to N-methylputrescine using S-adenosylmethionine as the cofactor.

The PABS domain consists of two subdomains: an N-terminal subdomain composed of six β-strands, and a Rossmann-like C-terminal subdomain. The larger C-terminal catalytic core subdomain consists of a seven-stranded β-sheet flanked by nine α-helices. This subdomain resembles a topology observed in a number of nucleotide and dinucleotide-binding enzymes, and in S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases (MTases) .

This entry represents the PABS domain that includes the two subdomains.
Poxvirus cap-specific nucleoside 2-O-methyltransferase (Poxvir_cap_MeTfrase)
Type: Family

Members of this family are mRNA (nucleoside-2'-O-)-methyltransferases (

) from Poxviridae virus (also known as VP39). These enzymes are required for the formation of the 5' cap structure of mRNA . They also function as a poly(A) polymerase stimulatory factor to modify the 3' end of mRNA . Furthermore, they have a transcription elongation factor activity which is independent from their functions in mRNA modification .
Circularly permuted (CP)-type guanine nucleotide-binding (G) domain (G_CP_dom)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The TRAFAC (named after translation factors) class includes an atypical family characterised by a circularly permuted (CP) order of the GTPase motifs within the G domain: the normal G1-G2-G3-G4-G5 orientation of the G domain has been rearranged to G4(N/T-K-x-D)-G5(T/G-C/S-A)-G1(Walker A, P-loop)-G2(T)-G3(Walker B). Despite such a variation (in motif order) observed at the primary sequence level, which should lead to different topological connections between the secondary structure elements, the three dimensional fold is well preserved. In addition, the GTP-binding site too is well conserved. It has been proposed that the CP-type G domain has evolved due to the duplication of a classical GTPase domain followed by deletion of both N- and C-terminal regions. The CP- type G domain is unlikely to exist as a single domain and is accompanied by at least one additional domain .

The CP-type G domain has a typical G domain fold with a central seven-stranded β-sheet (six parallel strands, one antiparallel strand) surrounded by six α-helices .

This entry reprsents the entire CP-type G domain. Some proteins known to contain a CP-type G domain are listed below:

Bacterial YjeQ (RsgA), composed of a N-terminal oligonucleotide/ oligosaccharide binding (OB-fold) RNA-binding domain, a central G domain, and a C-terminal cysteine cluster forming a zinc-finger motif. YjeQ GTPases assist in ribosome biogenesis and bind to the 30S subunit of mature ribosomes .

MTG1/YlqF from eukaryotes, archaea, and bacteria. It is involved in ribosome biogenesis .

NOA1/MTG3/YqeH from eukaryotes and bacteria, binds ribosomes and consequently plays a role in their proper assembly and/or stability .

Nug2/YawG subfamily GTPases from eukaryotes and bacteria, implicated in biogenesis of the 60S ribosomal subunit .