SII-SWORD/CoKE huggingface dataset:
CASK, SH3 domain (CASK_SH3)
Type: Domain

CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations . Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation . Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling .
KpsF-like, SIS domain (SIS_Kpsf)
Type: Domain

KpsF is an arabinose-5-phosphate isomerase which contains a SIS (Sugar ISomerase) domain. SIS domains are found in many phosphosugar isomerases and phosphosugar binding proteins. KpsF catalyzes the reversible reaction of ribulose 5-phosphate to arabinose 5-phosphate. This is the second step in the CMP-Kdo biosynthesis pathway .
MPP1, SH3 domain (MPP1_SH3)
Type: Domain

This entry represents the SH3 domain of MPP1, which is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina . It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C . MPP1 belongs to the membrane-associated guanylate kinase (MAGUK) p55 subfamily.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
Phosphoglucose isomerase, SIS domain 1 (SIS_PGI_1)
Type: Domain

Phosphoglucose isomerase (PGI) is a multifunctional enzyme which as an intracellular dimer catalyses the reversible isomerization of glucose 6-phosphate to fructose 6-phosphate . As an extracellular protein, PGI also has functions equivalent to neuroleukin (NLK), autocrine motility factor (AMF), and maturation factor (MF) . Evidence suggests that PGI, NLK, AMF, and MF are closely related or identical. NLK is a neurotrophic growth factor that promotes regeneration and survival of neurons. The dimeric form of NLK has isomerase function, whereas its monomeric form carries out neurotrophic activity. AMF is a cytokine that stimulates cell migration and metastasis. MF mediates the differentiation of human myeloid leukemic HL-60 cells to terminal monocytic cells.

PGI is comprised of two domains; each domain is an α-β-α sandwich , which correspond to a SIS (Sugar ISomerase) domain fold.
SH3PXD2B, SH3 domain 1 (SH3PXD2B_SH3_1)
Type: Domain

This entry represents the first SH3 domain of SH3PXD2B.

SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Fad49 or Tks4) is an adaptor protein required for functional podosome formation . It binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides . It regulates epidermal growth factor-dependent cell migration and has been linked to cancer . Mutations in the SH3PXD2B gene cause Frank-ter Haar syndrome, a rare disease characterised by abnormalities that affect bone, heart, and eye development . It contains an N-terminal Phox homology (PX) domain and four SH3 domains.
SH3PXD2B, SH3 domain 2 (SH3PXD2B_SH3_2)
Type: Domain

This entry represents the second SH3 domain of SH3PXD2B.

SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Fad49 or Tks4) is an adaptor protein required for functional podosome formation . It binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides . It regulates epidermal growth factor-dependent cell migration and has been linked to cancer . Mutations in the SH3PXD2B gene cause Frank-ter Haar syndrome, a rare disease characterised by abnormalities that affect bone, heart, and eye development . It contains an N-terminal Phox homology (PX) domain and four SH3 domains.
SH3PXD2B, SH3 domain 3 (SH3PXD2B_SH3_3)
Type: Domain

This entry represents the third SH3 domain of SH3PXD2B.

SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Fad49 or Tks4) is an adaptor protein required for functional podosome formation . It binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides . It regulates epidermal growth factor-dependent cell migration and has been linked to cancer . Mutations in the SH3PXD2B gene cause Frank-ter Haar syndrome, a rare disease characterised by abnormalities that affect bone, heart, and eye development . It contains an N-terminal Phox homology (PX) domain and four SH3 domains.
SH3PXD2B, SH3 domain 4 (SH3PXD2B_SH3_4)
Type: Domain

This entry represents the fourth SH3 domain of SH3PXD2B.

SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Fad49 or Tks4) is an adaptor protein required for functional podosome formation . It binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides . It regulates epidermal growth factor-dependent cell migration and has been linked to cancer . Mutations in the SH3PXD2B gene cause Frank-ter Haar syndrome, a rare disease characterised by abnormalities that affect bone, heart, and eye development . It contains an N-terminal Phox homology (PX) domain and four SH3 domains.
GRAF, SH3 domain (GRAF_SH3)
Type: Domain

This entry represents the SH3 domain of GRAF.

Rho GTPase-activating protein 26 (ARHGAP26), also known as GTPase regulator associated with focal adhesion kinase (GRAF), is a GTPase-activating protein for the small GTPases of the Rho family RhoA and CDC42 . GRAF influences cytoskeletal changes mediated by Rho proteins . It is recognised as a tumor suppressor . GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho .
Phosphoglucose isomerase, SIS domain 2 (SIS_PGI_2)
Type: Domain

Phosphoglucose isomerase (PGI) is a multifunctional enzyme which as an intracellular dimer catalyses the reversible isomerization of glucose 6-phosphate to fructose 6-phosphate . As an extracellular protein, PGI also has functions equivalent to neuroleukin (NLK), autocrine motility factor (AMF), and maturation factor (MF) . Evidence suggests that PGI, NLK, AMF, and MF are closely related or identical. NLK is a neurotrophic growth factor that promotes regeneration and survival of neurons. The dimeric form of NLK has isomerase function, whereas its monomeric form carries out neurotrophic activity. AMF is a cytokine that stimulates cell migration and metastasis. MF mediates the differentiation of human myeloid leukemic HL-60 cells to terminal monocytic cells.

PGI is comprised of two domains; each domain is an α-β-α sandwich , which correspond to a SIS (Sugar ISomerase) domain fold.
GRAF, BAR domain (GRAF_BAR)
Type: Domain

This entry represents the BAR domain of GRAF. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously .

Rho GTPase-activating protein 26 (ARHGAP26), also known as GTPase regulator associated with focal adhesion kinase (GRAF), is a GTPase-activating protein for the small GTPases of the Rho family RhoA and CDC42 . GRAF influences cytoskeletal changes mediated by Rho proteins . It is recognised as a tumor suppressor . GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho .
Bifunctional phosphoglucose/phosphomannose isomerase, SIS domain 1 (SIS_PGI/PMI_1)
Type: Domain

Bifunctional phosphoglucose/phosphomannose isomerase has both the phosphoglucose isomerase (PGI) and the phosphomannose isomerase (PMI) functions. These functions catalyze the reversible reactions of glucose 6-phosphate to fructose 6-phosphate, and mannose 6-phosphate to fructose 6-phosphate, respectively, at an equal rate .

This protein contains two SIS (Sugar ISomerase) domains. This entry represents the first SIS domain.
GRAF2, SH3 domain (GRAF2_SH3)
Type: Domain

GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA . It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death . It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions .

This entry represents the SH3 domain of GRAF2.
Fructosamine deglycase FrlB, SIS domain 1 (FrlB_SIS)
Type: Domain

FrlB catalyses the conversion of a range of fructosamine 6-phosphates to glucose 6-phosphate and a free amino acid .

This entry represents the first SIS domain of FrlB. SIS (Sugar ISomerase) domains are found in many phosphosugar isomerases and phosphosugar binding proteins. SIS domains are also found in proteins that regulate the expression of genes involved in synthesis of phosphosugars .
MYO15B, SH3 domain (MYO15B_SH3)
Type: Domain

Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function .
GlmS/FrlB, SIS domain 2 (GlmS/FrlB_SIS)
Type: Domain

This entry represents the SIS (Sugar ISomerase) domain 2 found in glucosamine 6-phosphate synthase (GlmS) and fructosamine deglycase FrlB.

GlmS contains a N-terminal glutaminase domain and C-terminal isomerase domain (consisting of two SIS domains) and catalyzes the first step in hexosamine metabolism, converting fructose 6-phosphate into glucosamine 6-phosphate using glutamine as nitrogen source . The glutaminase domain hydrolyzes glutamine to glutamate and ammonia. Ammonia is transferred through a channel to the isomerase domain for glucosamine 6-phosphate synthesis. In the absence of glutamine, GlmS catalyzes the isomerization of fructose 6-phosphate into glucose 6- phosphate .

FrlB catalyses the conversion of a range of fructosamine 6-phosphates to glucose 6-phosphate and a free amino acid .
ARHGAP12, SH3 domain (ARHGAP12_SH3)
Type: Domain

Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating hepatocyte growth factor (HGF)-driven cell growth and invasiveness . It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains .

This entry represents the SH3 domain of ARHGAP12.
FNBP1, SH3 domain (FNBP1_SH3)
Type: Domain

This entry represents the SH3 domain of FNBP1.

Formin-binding protein 1 (FNBP1, also known as formin-binding protein 17) contains a N-terminal FER-CIP4 homology (FCH) domain and a C-terminal SH3 domain. It belongs to the CIP4 (Cdc42 interacting protein-4) subfamily of the F-BAR protein family. F-BAR proteins (F for FCH, Fer-CIP4 homology domain) are proteins with an extended CIP4-Fer domain. The F-BAR proteins have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis . FNBP1 was originally isolated as a molecule that binds to the proline-rich region of formin . It induces tubular membrane invaginations and participates in endocytosis . It interacts with sorting nexin, SNX2, and is linked to acute myelogeneous leukemia .
FNBP1L, SH3 domain (FNBP1L_SH3)
Type: Domain

This entry represents the SH3 domain of FNBP1L.

Formin-binding protein 1-like (FNBP1L, also known as Toca-1) is part of the Toca-1-N-WASP complex that induces the formation of filopodia and endocytic vesicles . CIP4 and FNBP1L contain an F-BAR domain (

), a HR1 domain (

) and an SH3 domain (

) . FNBP1L belongs to the CIP4 (Cdc42 interacting protein-4) subfamily of the F-BAR (F for FCH, Fer-CIP4 homology domain) protein family. The F-BAR proteins have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis . FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens.
FNBP1L, F-BAR domain (FNBP1L_F-BAR)
Type: Domain

This entry represents the F-BAR domain of FNBP1L.

Formin-binding protein 1-like (FNBP1L, also known as Toca-1) is part of the Toca-1-N-WASP complex that induces the formation of filopodia and endocytic vesicles . CIP4 and FNBP1L contain an F-BAR domain (

), a HR1 domain (

) and an SH3 domain (

) . FNBP1L belongs to the CIP4 (Cdc42 interacting protein-4) subfamily of the F-BAR (F for FCH, Fer-CIP4 homology domain) protein family. The F-BAR proteins have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis . FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens.
Caskin-1, SH3 domain (Caskin1_SH3)
Type: Domain

This entry represents the SH3 domain of Caskin-1 (CASK-interacting protein 1).

Caskin-1 and Caskin-2 are multidomain proteins containing six N-terminal ankyrin repeats, a single SH3 domain, and two sterile alpha motif (SAM) domains followed by a long proline-rich sequence and a short conserved C-terminal domain. Caskin-1 may link the scaffolding protein CASK to downstream intracellular effectors . Caskin-1 polymerises, via the tandem SAM domains, to form long, 8 nM wide fibres, upon which other proteins can assemble .
Caskin1/2, SAM repeat 1 (Caskin1/2_SAM_1)
Type: Domain

This is the SAM (sterile alpha motif) domain repeat 1 of caskin 1 and caskin 2 proteins; it is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression .
Caskin1/2, SAM repeat 2 (Caskin1/2_SAM_2)
Type: Domain

This is the SAM (sterile alpha motif) domain repeat 2 of caskin 1 and caskin 2 proteins; it is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression .
Caskin2, SH3 domain (Caskin2_SH3)
Type: Domain

Caskin2 is a multidomain adaptor protein that contains six ankyrin repeats, a single SH3 domain, tandem sterile alpha motif (SAM) domains, and a long disordered proline-rich region. It shares a domain architecture with Caskin1, but does not bind CASK . The CASKIN2 SH3 domain has two substitutions that prevent it from binding typical polyproline ligands, which indicates that it could be a nonfunctional remnant in this protein .
Nuclear hormone receptor-like domain superfamily (NHR-like_dom_sf)
Type: Homologous_superfamily

Steroid or nuclear hormone receptors constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. The receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. Nuclear hormone receptors consist of a highly conserved DNA-binding domain that recognises specific sequences (

), connected via a linker region to a C-terminal ligand-binding domain. In addition, certain nuclear hormone receptors have an N-terminal modulatory domain (

). The ligand-binding domain acts in response to ligand binding, which caused a conformational change in the receptor to induce a response, thereby acting as a molecular switch to turn on transcriptional activity . For example, after binding of the glucocorticoid receptor to the corticosteroid ligand, the receptor is induced to perform functions ranging from nuclear translocation, oligomerization, cofactor/kinase/transcription factor association, and DNA binding . The ligand-binding domain is a flexible unit, where the binding of a ligand stabilises its conformation, which in turn favours coactivator binding to modify receptor activity ; the coactivator can bind to the activator function 2 (AF2) site at the C-terminal end of the ligand-binding domain . The binding of different ligands can alter the conformation of the ligand-binding domain, which ultimately affects the DNA-binding specificity of the DNA-binding domain. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components.

This entry represents the all helical domain involved in ligand-binding.
Cytokine-like nuclear factor N-PAC, PWWP domain (GLYR1_PWWP)
Type: Domain

The PWWP domain is an essential part of the cytokine-like nuclear factor N-PAC protein, also known as NP60 or GLYR1, which enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha . NPAC/GLYR1 is a nucleosome-destabilizing factor that is recruited to genes during transcriptional activation and facilitates Pol II transcription through nucleosomes . It is a KDM1B demethylase cofactor that stimulates H3K4me1 and H3K4me2 demethylation . In addition to the PWWP domain, NP60 also contains an AT-hook and a C-terminal NAD-binding domain alpha .

The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids. The PWWP domain is found in numerous proteins that are involved in cell division, growth and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding proteins, that function as transcription factors regulating a variety of developmental processes .
IOC4-like, PWWP domain (IOC4-like_PWWP)
Type: Domain

This PWWP domain is found in Loc4 (ISWI one complex protein 4), a component of of the S. cerevisiae ISW1B complex, as well as in S. pombe PWWP domain-containing protein2 (SPBC215.07c). The ISWI (imitation switch) complex acts in chromatin remodelling . SPBC215.07c has also been proposed to bind chromatin .
MUM1-like, PWWP domain (MUM1-like_PWWP)
Type: Domain

This entry represents the PWWP domain. The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids. The PWWP domain is found in numerous proteins that are involved in cell division, growth and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding proteins, that function as transcription factors regulating a variety of developmental processes .

PWWP domain-containing DNA repair factor 3A (also known as EXPAND1 or MUM1) is a nucleosome-binding protein that contributes to the maintenance of chromatin state. Through its interaction with 53BP1, it serves as an accessory factor in the DNA damage response pathway to promote chromatin change in response to DNA damage . MUM1 promotes cell survival following DNA damage, suggesting that it may facilitate DNA repair by regulating the organization of chromatin structure .
Pollen allergen/Uncharacterized protein Os (Pollen_allergen/Os)
Type: Homologous_superfamily

This superfamily represents a domain found in different pollen allergen proteins and in uncharacterised proteins from Oryza sativa (rice) including OsI_031781 and OsI_030282.

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

Proteins in this family belong to the Poa p (Poa pratensis or Kentucky bluegrass) IX and Phl p (Phleum pratense) VI allergen family, and include allergens with the following designations: Lol p 5, Pha a 5, Phl p 6, and Poa p 9. Phl p 5b has been shown to possess ribonuclease activity . Grass pollen allergens are one of the major causes of type I allergies (including allergic rhinoconjunctivitis, allergic bronchial asthma and hayfever), afflicting 15-20% of a genetically predisposed population .
Unconventional myosin-Ie/If, SH3 domain (Ie/If_SH3)
Type: Domain

This entry represents the SH3 domain found in these unconventional myosins.

Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long-tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis . In the kidney, Myole is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe are associated with focal segmental glomerulosclerosis, a disease characterised by massive proteinuria and progression to end-stage kidney disease .
STAC1, SH3 domain (STAC1_SH3)
Type: Domain

Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C terminus. There are three mammalian members: Stac1, Stac2, and Stac3. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C terminus. They regulate voltage-gated calcium channel (CaV) trafficking and function .

This entry represents the first C-terminal Src homology 3 (SH3) domain of SH3 and cysteine-rich domain-containing protein (Stac or Stac1). Stac1 has been found to be expressed differently in mature dorsal root ganglia (DRG) neurons .
Stac2, SH3 domain (Stac2_SH3)
Type: Domain

Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons .

This entry represents the SH3 domain of Stac2.
SH3YL1, SH3 domain (SH3YL1_SH3)
Type: Domain

SH3YL1 (SH3 domain-containing YSC84-like protein 1) localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain . In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2 and SHIP2 .

This entry represents the SH3 domain of SH3YL1.