SII-SWORD/CoKE huggingface dataset:
Invertase/pectin methylesterase inhibitor domain superfamily (Invertase/methylesterase_inhib)
Type: Homologous_superfamily

This superfamily represents pectin methylesterases (PMEs) and invertases complex, and the uncharacterised protein Os08g from Oryza sativa subsp. japonica (Rice).

This domain inhibits pectin methylesterases (PMEs) and invertases through formation of a non-covalent 1:1 complex . It has been implicated in the regulation of fruit development, carbohydrate metabolism and cell wall extension . It may also be involved in inhibiting microbial pathogen PMEs. It has been observed that it is often expressed as a large inactive preprotein . It is also found at the N-termini of PMEs, suggesting that both PMEs and their inhibitor are expressed as a single polyprotein and subsequently processed. It has two disulphide bridges and is mainly α-helical .
SPIN90, SH3 domain (SPIN90_SH3)
Type: Domain

SPIN90, also known as NCK interacting protein with SH3 domain (NCKIPSD), is an F-actin binding protein that regulates actin polymerization and endocytosis . It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia . SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth . It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions . SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain .

This entry represents the SH3 domain of SPIN90.
DNA gyrase/topoisomerase IV, subunit A, C-terminal (Gyrase/topoIV_suA_C)
Type: Homologous_superfamily

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .

This entry represents the β-pinwheel continuous domain found at the C-terminal end of subunit A of topoisomerase IV (ParC) and subunit A of DNA gyrase (GyrA) . DNA gyrase is the topoisomerase II found primarily in bacteria and archaea that consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. This is distinct from the topoisomerase II found in most eukaryotes, which consists of a single polypeptide, with the N- and C-terminal regions corresponding to gyrB and gyrA, respectively, and which is not represented in this entry.

The ability of DNA gyrase to introduce negative supercoils into DNA is mediated in part by the C-terminal domain of subunit A, which forms a β-pinwheel fold that is similar to a β-propeller but with a different blade topology, and which forms a superhelical spiral domain . This β-pinwheel is capable of bending DNA by over 180 degrees over a 40 bp region, possibly by wrapping the DNA around the GyrA C-terminal β-pinwheel domain.

In topoisomerase IV, although the C-terminal domain forms a similar superhelical spiral to that of DNA gyrase A, it assembles as a broken form of a β-pinwheel as distinct from that of gyrA, due to the absence of a DNA gyrase-specific GyrA box motif . This difference may account for parC being less efficient than gyrA in mediating DNA-bending, leading to their divergence in terms of activity, where topoisomerase IV acts to relax positive supercoils, and DNA gyrase acts to introduce negative supercoils .
Dolichyl-phosphate beta-glucosyltransferase (DPG_synthase)
Type: Domain

UDP-glucose:dolichyl-phosphate glucosyltransferase (DolP-glucosyltransferase, DPG synthase) is a transmembrane-bound enzyme of the endoplasmic reticulum involved in protein N-linked glycosylation. This enzyme catalyzes the transfer of glucose from UDP-glucose to dolichyl phosphate .
High-affinity zinc uptake system protein ZnuA (ZnuA)
Type: Family

Zinc binding proteins ZnuA have been shown to function as initial receptors in the ABC uptake of Zn2+. They belong to the TroA superfamily of periplasmic metal binding proteins that share a distinct fold and ligand binding mechanism. They are comprised of two globular subdomains connected by a single helix and bind their specific ligands in the cleft between these domains. A typical TroA protein is comprised of two globular subdomains connected by a single helix and can bind the metal ion in the cleft between these domains. In addition, these proteins sometimes have a low complexity region containing a metal-binding histidine-rich motif (repetitive HDH sequence) .
Fus1, SH3 domain (Fus1_SH3)
Type: Domain

Fus1 is required at the cell surface for cell fusion during the mating response in yeast. It requires Bch1 and Bud7, which are Chs5-Arf1 binding proteins, for localization to the plasma membrane . It acts as a scaffold protein to assemble a cell surface complex which is involved in septum degradation and inhibition of the NOG pathway to promote cell fusion .
Sho1, SH3 domain (Sho1_SH3)
Type: Domain

Sho1 is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway . High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKKK Ste11 and in turn, activates the MAPK Hog1 . Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1 .
Collagen alpha-1(XVIII) chain, frizzled domain (Collagen_XVIII_Fz)
Type: Domain

Collagen XVIII (C18) regulates major cellular functions such as the differential epithelial morphogenesis of early lung and kidney development. It exists as three amino terminal end variants with specific amino terminal polypeptide modules. Variant 3 (V3C18) contains a frizzled module which carries structural identity with the extracellular cysteine-rich domain of the frizzled receptors . V3C18 can be proteolytically processed into a cell surface frizzled module-containing 50kDa glycoprotein precursor capable of inhibiting Wnt/beta-catenin signaling, whereas full-length V3C18 is unable to inhibit Wnt signaling .
NDPK7, first NDPk domain (NDPk7A)
Type: Domain

The nm23-H7 nucleoside diphosphate kinase (also known as NDPk7 or NME7) consists of an N-terminal DM10 domain and two functional catalytic NDPk modules, NDPk7A and NDPk7B. The function of the DM10 domain, which also occurs in multiple copies in other proteins, is unknown. NDPk7 is predominantly expressed in testes, although appreciable amounts are also found in liver, heart, brain, ovary, small intestine and spleen . The nm23-H7 gene is located in or near the hereditary prostrate cancer susceptibility locus. Nm23-H7 may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner .

This entry represents the first NDPk domain (NDPk7A) of NDPk7.
Obscurin, SH3 domain (Obscurin_SH3)
Type: Domain

Obscurin is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines . It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane . It is associated with the contractile apparatus through binding with titin and sarcomeric myosin . It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in skeletal muscle, approximately 800kDa in size, is composed of many adhesion modules and signaling domains .

Obscurin harbors 49 Ig and 2 FNIII repeats at the N terminus, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800kDa form of the protein, but is part of smaller spliced products present in heart muscle.
Protein of unknown function DUF5388 (DUF5388)
Type: Family

This is a family of unknown function found mostly in Lactobacillales.
Phage-like element PBSX protein XtrA (PBSX_XtrA)
Type: Family

This is a family of unknown function mostly found in Bacilli.
GTP binding protein 1-like, GTP-binding domain (GTPBP1-like)
Type: Domain

This GTP-binding domain is found in mammalian GTP binding protein 1 (GTPBP1), GTPBP2, and nematode homologues AGP-1 and CGP-1 .

Even though GTPBP1 has a GTP-binding domain, it has not been reported to have GTPase activity. GTPBP1 is thought to modulate mRNA decay by destabilizing the interactions between the RBPs and the cytoplasmic exosome using a GTP-binding-dependent mechanism .
DBS, SH3 domain (DBS_SH3)
Type: Domain

This entry represents the SH3 domain of DBS.

DBS, also called MCF2L or OST, functions as a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42 . Depending on cell type, DBS can also activate RhoA and RhoG . DBS contains a Sec14-like domain , spectrin-like repeats, a RhoGEF or Dbl homology (DH) domain, a Pleckstrin homology (PH) domain , and an SH3 domain.
Interleukin-1 receptor-associated kinase 1, death domain (Death_IRAK1)
Type: Domain

Interleukin-1 receptor-associated kinases (IRAKs) are essential components of innate immunity and inflammation in mammals and other vertebrates. They are involved in signal transduction pathways involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB (NF-kB), and mitogen-activated protein kinases (MAPKs). IRAKs contain an N-terminal death domain (DD) and a C-terminal kinase domain .

IRAK1 is an active kinase and also plays adaptor functions. It binds to the MyD88-IRAK4 complex via its DD, which facilitates its phosphorylation by IRAK4, activating it for further auto-phosphorylation . Hyper-phosphorylated IRAK1 forms a cytosolic complex with TRAF6, leading to the activation of NF-kB and MAPK pathways. IRAK1 is involved in autoimmunity and may be associated with lupus pathogenesis .

Death domains (DDs) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
DBS, PH domain (DBS_PH)
Type: Domain

This entry represents the PH domain of guanine nucleotide exchange factor DBS. The DBS PH domain participates in binding to both the Cdc42 and RhoA GTPases . PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner .

DBS, also called MCF2L or OST, functions as a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42 . Depending on cell type, DBS can also activate RhoA and RhoG . DBS contains a Sec14-like domain , spectrin-like repeats, a RhoGEF or Dbl homology (DH) domain, a Pleckstrin homology (PH) domain , and an SH3 domain.
Fungal myosin-I, SH3 domain (Fungal_myosin-I_SH3)
Type: Domain

Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing .

Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton . Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization .
Disks large homologue 5, SH3 domain (DLG5_SH3)
Type: Domain

DLG5 is a multifunctional scaffold protein that is located at sites of cell-cell contact and is involved in the maintenance of cell shape and polarity . Mutations in the DLG5 gene are associated with Crohn's disease (CD) and inflammatory bowel disease (IBD) . DLG5 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterised by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK) . The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain . DLG5 contains 4 PDZ domains as well as an N-terminal domain of unknown function.
PPIL4-like, cyclophilin domain (Cyclophilin_PPIL4)
Type: Domain

This is a cyclophilin-type peptidylprolyl cis-trans isomerase domain occuring with a C-terminal RNA recognition motif domain (RRM). It is found in a number of eukaryotic cyclophilins having the RRM domain, including the nuclear proteins: human cyclophilin-like protein PPIL4 , Arabidopsis thaliana AtCYP59 , Caenorhabditis elegans sig-7 and Paramecium tetrurelia Kin241. The Kin241 protein has been shown to have a role in cell morphogenesis .
Protein of unknown function DUF5387 (DUF5387)
Type: Family

This is a family of unknown function mostly found in Rhabditida.
FYB, helically extended SH3 domain (FYB_hSH3)
Type: Domain

FYN-binding protein 1 (FYB1), also known as ADAP or SLAP, is an adapter protein in beta 1 integrin signalling and T lymphocyte migration . It has been found to co-localise with F-actin in membrane ruffles, adhesion plaques/podosomes and phagocytic cups . In activated T cells, Fyb/SLAP associates with Ena/VASP family proteins and may link T cell signalling to the actin cytoskeleton remodelling . FYB1 also interacts with mammalian actin binding protein 1 (mAbp1) that affects F-actin dynamics .

The SH3 domain of FYB adopts an altered fold referred to as a helically extended SH3 (hSH3) domain characterised by clusters of positive charges. The hSH3 domain can no longer bind conventional proline-rich peptides; instead, it functions as a novel lipid interaction domain and can bind acidic lipids such as phosphatidylserine, phosphatidylinositol, phosphatidic acid, and polyphosphoinositides .
Neutrophil cytosol factor P40, SH3 domain (p40phox_SH3)
Type: Domain

p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection . NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner . It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox . The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C terminus of p47phox .

This entry represents the SH3 domain of p40phox.
Cyclophilin-RNA interacting protein (CRIP)
Type: Family

The name CRIP, for cyclophilin-RNA interacting protein, has been proposed for this family of proteins that comprise a cyclophilin-type peptidyl-prolyl isomerase domain, an RNA recognition motif, followed by a region rich in glutamate and lysine (EK domain) and a C-terminal string of serines . The family includes among others Paramecium tetraurelia KIN241 , human cyclophilin-like protein PPIL4 , Arabidopsis thaliana AtCYP59 , and Caenorhabditis elegans sig-7 .
Translation initiation factor eIF-2B subunit epsilon, N-terminal (eIF-2B_epsilon_N)
Type: Domain

This is the N-terminal domain of epsilon subunit of the eukaryotic translation initiation factor 2B (eIF-2B). eIF-2B is a guanine nucleotide-exchange factor which mediates the exchange of GDP (bound to initiation factor eIF2) for GTP, generating active eIF2-GTP complex. EIF2B is a complex multimeric protein consisting of five subunits named alpha, beta, gamma, delta and epsilon. Subunit epsilon shares sequence similarity with gamma subunit, and with a family of bifunctional nucleotide-binding enzymes such as ADP-glucose pyrophosphorylase, suggesting that epsilon subunit may play roles in nucleotide binding activity. In yeast, eIF2B gamma enhances the activity of eIF2B-epsilon leading to the idea that these subunits form the catalytic subcomplex .
Outer membrane lipoprotein virB7 (VirB7)
Type: Family

The type IV secretion systems (T4SSs) are ancestrally related to bacterial conjugation machines and are able to translocate proteins and/or protein-DNA complexes to the extracellular milieu or the host interior, in many cases contributing to the ability of the bacterial pathogen to colonize the host and evade its immune system . In the pathogenic plant pathogen Agrobacterium tumefaciens T4SS allows the bacterium to transfer a segment of its tumor inducing (Ti-) plasmid DNA into plant cells causing crown gall tumor disease. Proteins in the virB and virD operons catalyze processing of the T-DNA and its transfer to plants. The VirB proteins assemble a secretion apparatus spanning both bacterial membranes to allow transfer of DNA and protein substrates into plant cells. VirB7 and VirB8, along with VirB6, VirB9 and VirB10, are the core components of the Agrobacterium DNA translocation apparatus. Structural studies with the Escherichia coli plasmid pKM101 VirB homologues showed that three proteins, TraN (VirB7 homologue), TraO (VirB9) and TraF (VirB10), form a hetero-tetradecameric structure with 14-fold symmetry forming an outer membrane channel through which the substrates pass. VirB7 stabilizes VirB9 and in its absence bacteria do not accumulate VirB9 preventing assembly of the secretion machine . Members of the VirB7 family are typically 45-65 residues long, becoming 15-20 residues shorter after removal of the N-terminal signal sequence and covalent attachment to lipid molecules .
Neutrophil cytosol factor 2, SH3 domain 1 (p67phox_SH3_1)
Type: Domain

NADPH oxidase is a multisubunit complex that assembles during phagocytosis to generate reactive oxygen species. Neutrophil cytosol factor 2 (NCF2/p67-phox) and 1 (NCF1/p47-phox) are required for activation of the phagocyte NADPH oxidase. The activators p67phox and p47phox form a ternary complex together with adaptor protein p40phox. P40phox is involved in activation of the phagocyte oxidase by regulating membrane recruitment of p67phox and p47phox . p40phox associates with p67phox via binding of the p40phox PC motif to the p67phox PB1 domain .

p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. This entry represents the first SH3 domain found in p67phox. The N-terminal SH3 domain increases the affinity of p67phox for the oxidase complex .
Phospholipase B (Phospholipase_B)
Type: Domain

Membrane-associated phospholipase B/lipase (PLB/LIP) consists of four tandem homologous domains (repeats 1 to 4), and repeat 2 is the catalytic domain that catalyzes phospholipase A2, lysophospholipase, and lipase activities .
Bem1/Scd2, SH3 domain 1 (Bem1/Scd2_SH3_1)
Type: Domain

This entry represents the first SH3 domain found in budding yeast Bem1 and fission yeast Scd2.

Bem1 (Bud emergence protein 1) is involved in establishing cell polarity and morphogenesis . It interacts with Axl2 (required for axial budding in haploid cells) and forms a complex with Cdc42, Cdc24, and Cla4 . Scd2 forms complexes with both scd1 and cdc42sp and is required for normal morphology and mating .
Bem1/Scd2, SH3 domain 2 (Bem1/Scd2_SH3_2)
Type: Domain

This entry represents the second SH3 domain found in budding yeast Bem1 and fission yeast Scd2.

Bem1 (Bud emergence protein 1) is involved in establishing cell polarity and morphogenesis . It interacts with Axl2 (required for axial budding in haploid cells) and forms a complex with Cdc42, Cdc24, and Cla4 . Scd2 forms complexes with both scd1 and cdc42sp and is required for normal morphology and mating .
Bem1/Scd2, PX domain (Bem1/Scd2_PX)
Type: Domain

This entry represents the phox homology (PX) domain found in budding yeast Bem1 and fission yeast Scd2. The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification. The PX domain of Bem1 specifically binds phosphatidylinositol-4-phosphate (PI4P) .

Bem1 (Bud emergence protein 1) is involved in establishing cell polarity and morphogenesis . It interacts with Axl2 (required for axial budding in haploid cells) and forms a complex with Cdc42, Cdc24, and Cla4 . Scd2 forms complexes with both scd1 and cdc42sp and is required for normal morphology and mating .
Boi1/2, SH3 domain (Boi1/2_SH3)
Type: Domain

This entry represents the N-terminal SH3 domain found in the Saccharomyces cerevisiae proteins Boi1 and Boi2 (BEM1-interacting protein 1/2) and similar fungal proteins. Besides the N-terminal SH3 domain, they contain a Sterile alpha motif (SAM,

), and a Pleckstrin homology (PH) domain at the C terminus. Boi1 and Boi2 interact with the SH3 domain of Bem1, a protein involved in bud formation . They promote polarized cell growth and participates in the NoCut signalling pathway, which is involved in the control of cytokinesis , and promote the fusion of secretory vesicles with the plasma membrane at sites of polarized growth .
Mti1, SH3 domain (Mti1_SH3)
Type: Domain

This entry represents the N-terminal SH3 domain found in the Saccharomyces cerevisiae protein Mti1 (Myosin tail region-interacting protein, also known as bbc1) and similar proteins. Mti1 interacts with and regulates type I myosins in yeast, Myo3 and Myo5, which are involved in actin cytoskeletal reorganization . It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex .
Cytokinesis protein 3, SH3 domain (Cyk3_SH3)
Type: Domain

Cytokinesis protein 3 (Cyk3) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis . Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain.
Otoraplin, SH3 domain (Otoraplin_SH3)
Type: Domain

Otoraplin, also known as MIAL (MIA-like), is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans . It is a member of the MIA family.

MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel β sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands .