SII-SWORD/CoKE huggingface dataset:
RasGAP, SH3 domain (RasGAP_SH3)
Type: Domain

Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway . Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound . Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration .

Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras .

This entry represents the SH3 domain of RasGAP . The SH3 domain of RasGAP is unable to bind proline-rich sequences but have been shown to interact with protein partners such as the G3BP protein, Aurora kinases, and the Calpain small subunit 1. The RasGAP SH3 domain is necessary for the downstream signaling of Ras and it also influences Rho-mediated cytoskeletal reorganization .
Alpha-(1,6)-fucosyltransferase, SH3 domain (Fut8_SH3)
Type: Domain

Alpha-(1,6)-fucosyltransferase Fut8 catalyses the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype . Fut8 is also implicated to play roles in ageing and cancer metastasis . It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear .

This entry represents the SH3 domain of Fut8.
Elongation factor 4, domain IV (LepA_IV)
Type: Domain

Elongation factor 4, also known as ribosomal back-translocase LepA, is required for accurate and efficient protein synthesis under certain stress conditions. Its function is not clear. However, it may act as a fidelity factor of the translation reaction, by catalysing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Back-translocation proceeds from a post-translocation (POST) complex to a pre-translocation (PRE) complex, thus giving elongation factor G a second chance to translocate the tRNAs correctly . Elongation factor 4 binds to ribosomes in a GTP-dependent manner. The eukaryotic homologue is known as GUF1 and promotes protein synthesis in chloroplasts and mitochondria .

EF4 has six domains, of which four (I, II, III, and V) are homologous to corresponding domains in EF-G . This entry represents domain IV of EF4, homologous to domain V of EF-G.
116kDa U5 small nuclear ribonucleoprotein component, C-terminal (U5-116kDa_C)
Type: Domain

This domain is found in the C-terminal portion of the spliceosomal human 116kDa U5 small nuclear ribonucleoprotein (snRNP) protein (U5-116kDa), and its yeast counterpart Snu114p. This domain is homologous to the C-terminal domain of the eukaryotic translational elongation factor EF-2 . Yeast Snu114p is a GTPase component of U5 snRNP essential for pre-mRNA splicing .
Nostrin, SH3 domain (Nostrin_SH3)
Type: Domain

Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS) . It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP) . Increased expression of nostrin may be correlated to pre-eclampsia . Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. This entry represents the SH3 domain.
STAM1, SH3 domain (STAM1_SH3)
Type: Domain

This entry represents the SH3 domain of STAM1.

Signal transducing adapter molecule 1 (STAM1) is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome . It may also be involved in the regulation of IL2 and GM-CSF mediated signalling, and has been implicated in neural cell survival . STAM1, together with another GAT domain-containing protein Hrs, forms a Hrs/STAM1 core complex that consists of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The two GAT domains are connected by a two-stranded coiled-coil. The Hrs/STAM1 complex, an intertwined GAT heterodimer, is a scaffold for binding of ubiquitinated cargo proteins and coordinating ubiquitination and deubiquitination reactions that regulate sorting . It plays an important role in Dengue virus entry .

STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation . They function in cytokine signalling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases , Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS, ubiquitin interacting (UIM), and SH3 domains .
Conjugal transfer protein TrbF (TrbF)
Type: Domain

TrbF is known to be involved in conjugal transfer. It is thought to compose part of the pilus required for transfer . This domain is similar to the type IV secretion system (T4ASS) component VirB8 and possibly has a similar fold to the nuclear transport factor-2 (NTF-2)-like superfamily .
Sucrose-phosphate synthase, C-terminal (SPS_C)
Type: Domain

Sucrose phosphate synthase (SPS;

), also known as UDP-glucose-fructose-phosphate glucosyltransferase, catalyzes the transfer of a hexosyl group from UDP-glucose to D-fructose 6-phosphate to form UDP and D-sucrose-6-phosphate, this is the rate limiting step of sucrose synthesis . Several different isozymes of SPS exist in plants .

Plant SPSs consist of three domains. The N-terminal region has no clear similarity with any other proteins. The central region contains a glycosyltransferase domain responsible for the catalytic function of SPS. The C-terminal region resembles sucrose phosphate phosphatase. This entry represents the C-terminal domain of SPS from plants .
EMP46/EMP47, N-terminal lectin domain (EMP46/EMP47_N)
Type: Domain

EMP46 and EMP47 are fungal type-I transmembrane proteins that cycle between the endoplasmic reticulum and the golgi apparatus and are thought to function as cargo receptors that transport newly synthesized glycoproteins . EMP47 is a receptor for EMP46 responsible for the selective transport of EMP46 by forming hetero-oligomerization between the two proteins. EMP46 and EMP47 are 45% sequence-identical to one another and have sequence homology to a class of intracellular lectins defined by ERGIC-53 and VIP36 .

EMP46 and EMP47 have an N-terminal lectin-like carbohydrate recognition domain as well as a C-terminal transmembrane domain. This entry represents the EMP46 and EMP47 N-terminal carbohydrate recognition domain.
VIP36, lectin domain (VIP36_lectin)
Type: Domain

The vesicular integral protein of 36kDa (VIP36) is a type 1 transmembrane protein of the mammalian early secretory pathway that acts as a cargo receptor transporting high mannose type glycoproteins between the Golgi and the endoplasmic reticulum (ER) . Lectins of the early secretory pathway are involved in the selective transport of newly synthesized glycoproteins from the ER to the ER-Golgi intermediate compartment (ERGIC) .
VcfQ, lectin domain (VcfQ_lectin)
Type: Domain

This domain is found in bacterial proteins homologous to the VcfQ (also known as MshQ) bacterial pilus biogenesis protein. VcfQ is encoded by the vcfQ gene of the type IV pilus gene cluster of Vibrio cholerae and is essential for type IV pilus assembly .
Fungal multicopper oxidase, cupredoxin domain 3 (MCO_CuRO_3)
Type: Domain

This domain is found in fungal proteins with similarity to ascorbate oxidase . Ascorbate oxidase catalyzes the oxidation of ascorbic acid to dehydroascorbic acid. It can detect levels of ascorbic acid and eliminate it. The biological function of ascorbate oxidase is still not clear.

Ascorbate oxidase belongs to multicopper oxidase (MCO) family which couple oxidation of substrates with reduction of dioxygen to water. MCOs are capable of oxidizing a vast range of substrates, varying from aromatic compounds to inorganic compounds such as metals. Although the members of this family have diverse functions, majority of them have three cupredoxin domain repeats. The copper ions are bound in several sites: Type 1, Type 2, and/or Type 3. The ensemble of types 2 and 3 copper is called a trinuclear cluster. MCOs oxidize their substrate by accepting electrons at a mononuclear copper centre and transferring them to the active site trinuclear copper centre. The cupredoxin domain 3 of 3-domain MCOs contains the Type 1 (T1) copper binding site and part the trinuclear copper binding site, which is located at the interface of domains 1 and 3 .
Plant RIN2/3, CUE domain (RIN3_plant_CUE)
Type: Domain

RIN2 and RIN3 are two closely related RPM1-interacting proteins conserved in higher eukaryotes. They are orthologs of the mammalian autocrine motility factor receptor (AMFR), a cytokine receptor localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). RIN2 and RIN3 have been identified as membrane-bound RING-finger type ubiquitin ligases with six apparent transmembrane domains, a RING-finger domain and a CUE domain. They act as positive regulators of RPM1- and RPS2-dependent hypersensitive response (HR) .

This entry represents the CUE domain found in plant RIN2 and RIN3.
Amicyanin (Amicyanin)
Type: Family

In Paracoccus denitrificans bacteria, amicyanin acts as an intermediary of a three-member redox complex along with methylamine dehydrogenase (MADH) and cytochrome c-551i. The electron is transferred from the active site of MADH via the amicyanin copper ion to the cytochrome heme iron. The electron transfer from MADH to cytochrome c-551i does not involve a ternary complex but occurs via a ping-pong mechanism in which amicyanin uses the same interface for the reactions with MADH and cytochrome c-551i .
GDSL lipase/esterase-like, plant (SGNH_plant_lipase-like)
Type: Family

This entry represents a plant specific subfamily of the SGNH-family of hydrolases, a diverse family of lipases and esterases. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely resembles the Ser-His-Asp(Glu) triad found in other serine hydrolases .

This entry also includes alpha-L-fucosidase 3 (

) which hydrolyses alpha-1,2-linked fucose and other fucosylated xyloglucan oligosaccharides .
Plant AGD1/2/3/4, BAR domain (AGD1/2/3/4_BAR_plant)
Type: Domain

The plant protein SCARFACE (SFC, also known as AGD) is an Arf GTPase Activating Protein (GAP) that plays a role in the trafficking of auxin efflux regulators from the plasma membrane to the endosome. It is required for the normal vein patterning in leaves . SCF contains an N-terminal BAR domain, followed by a Pleckstrin Homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. This entry represents the BAR domain found in plant AGD1/2/3/4 and homologues are also found in chlorophytes.

BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration .
DsbD gamma (DsbD_gamma)
Type: Domain

DsbD gamma is the C-terminal periplasmic domain of the bacterial protein DsbD. It contains a CXXC motif in a Thioredoxin (TRX) fold and shuttles the reducing potential from the membrane domain (DsbD beta) to the N-terminal periplasmic domain (DsbD alpha). DsbD beta, a transmembrane domain comprising of eight helices, acquires its reducing potential from the cytoplasmic thioredoxin. DsbD alpha transfers the acquired reducing potential from DsbD gamma to target proteins such as the periplasmic protein disulphide isomerases, DsbC and DsbG. This flow of reducing potential from the cytoplasm through DsbD allows DsbC and DsbG to act as isomerases in the oxidizing environment of the bacterial periplasm. DsbD also transfers reducing potential from the cytoplasm to specific reductases in the periplasm which are involved in the maturation of cytochromes .
ERdj5, first thioredoxin domain (ERdj5_TRX_N)
Type: Domain

ERdj5, also known as Dnajc10 (DnaJ homologue subfamily C member 10), JPDI or macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains . This entry comprises the first TRX domain of ERdj5 located after the DnaJ domain at the N-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress . It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation .
ERdj5, C-terminal thioredoxin domain (ERdj5_TRX_C)
Type: Domain

ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox-active TRX domains . This entry represents the three TRX domains located at the C-terminal half of the protein. ERdj5 is a ubiquitous protein localised in the endoplasmic reticulum (ER) and is abundant in secretory cells. Its transcription is induced during ER stress . It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation . Also included in this entry is the single complete TRX domain of an uncharacterised protein from Tetraodon nigroviridis.
STAM2, SH3 domain (STAM2_SH3)
Type: Domain

This entry represents the SH3 domain of STAM2.

Signal transducing adapter molecule 2 (STAM2), a subunit of the ESCRT-0 complex, is an endosomal protein acting as a regulator of receptor signaling and trafficking. It contains an N-terminal VHS domain, UIM (ubiquitin-interacting motif), SH3, coiled-coil (CC), SSM (STAM-specific motif) and C-terminal ITAM (immunoreceptor tyrosine-based activation motif) domains. It may play a regulatory role in the endosomal sorting of ubiquitinated membrane proteins. It is highly expressed in neurons, where it is localized in the nucleus .

STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation . They function in cytokine signalling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases , Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS, ubiquitin interacting (UIM), and SH3 domains .
SH2 adaptor protein C, SH2 domain (SHC_SH2)
Type: Domain

The SH2-containing Shc adapter proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to the Ras/mitogen-activated protein kinase (MAPK) pathway . Three Shc genes were originally identified in mammals that encode proteins characterised by an amino-terminal phosphotyrosine binding (PTB) domain and a carboxy-terminal Src homology 2 domain. Shc1 (ShcA) is ubiquitously expressed, whereas expression of Shc2 (ShcB) and Shc3 (ShcC) appears to be limited to neuronal cells .

SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation . In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
ASAP2, SH3 domain (ASAP2_SH3)
Type: Domain

This entry represents the SH3 domain of ASAP2 (Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2).

ArfGAPs are a protein family containing the ArfGAP domain. There are 31 genes encoding ArfGAPs in human . They catalyse the hydrolysis of GTP that is bound to Arf, thereby converting Arf-GTP to Arf-GDP .
srGAP4, SH3 domain (srGAP4_SH3)
Type: Domain

This entry represents the SH3 domain of srGAP4. srGAP4 is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation . It is able to stimulate the GTPase activity of three members of Rho GTPases, Rac1, Cdc42 and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth .

The SLIT-ROBO Rho GTPase-activating protein (srGAP) family consists of four members: srGAP1, -2, -3 and -4. They contain F-BAR, RhoGAP and SH3 domains. Their RhoGAP domain is involved in negative regulation of Rho GTPase activities important for cytoskeleton rearrangement . The srGAP family members have an "inverse F-BAR" or IF-BAR domain that is distinct from other F-BAR domains such as FBP17. They are multifunctional adaptor proteins involved in various aspects of neuronal development .
Magnesium-dependent phosphatase-1, eukaryotic-type (MDP-1_euk)
Type: Family

This family includes eukaryotic magnesium-dependent phosphatase-1 (MDP-1) which is most likely a phosphotyrosine phosphatase catalyzing the dephosphorylation of tyrosine-phosphorylated proteins , and some bacterial sequences annotated as FkbH-like proteins. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis.
Hydroxyacylglutathione hydrolase, MBL domain (Clx_II_MBL)
Type: Domain

Hydroxyacylglutathione hydrolase is also known as glyoxalase II, S-2-hydroxylacylglutathione hydrolase, hydroxyacylglutathione hydrolase, or acetoacetylglutathione hydrolase. In the second step of the glyoxalase system this enzyme hydrolyzes S-d-lactoylglutathione to d-lactate and regenerates glutathione in the process. It has broad substrate specificity for glutathione thiol esters, hydrolyzing a number of these species to their corresponding carboxylic acids and reduced glutathione .

Glyoxalase II belongs to the metallo-beta-lactamase (MBL)-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions . The enzyme consists of two domains. The first domain folds into a four-layered β sandwich, similar to that seen in the metallo-beta-lactamases. The second domain is predominantly α-helical. The active site contains a binuclear zinc-binding site and a substrate-binding site extending over the domain interface .
ComA-like, MBL domain (ComA-like_MBL)
Type: Domain

This domain is found in proteins required for natural transformation competence including Neisseria gonorrhoeae ComA , Pseudomonas stutzeri ComA , Bacillus subtilis ComEC (also known as ComE operon protein 3) and Haemophilus influenza ORF2 encoded by the rec-2 gene , as well as Escherichia coli YcaI which does not mediate spontaneous plasmid transformation on nutrient-containing agar plates . It also includes the phosphorylcholine esterase (Pce) domain of choline-binding protein e from streptococcus pneumonia . 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.
Phosphonate metabolism protein, MBL domain (PhnP_MBL)
Type: Domain

Escherichia coli PhnP catalyzes the hydrolysis of 5-phospho-D-ribose-1,2-cyclic phosphate to D-ribose-1,5-bisphosphate, a step in the C-P lyase pathway . PhnP belonsg to the metallo-beta-lactamase (MBL)-fold metallo-hydrolase superfamily .
Smoothened, 7TM (SMO_7TM)
Type: Domain

Smoothened (SMO) is a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway . SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc) . SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors .
Arginyl-tRNA synthetase, catalytic core domain (ArgRS_core)
Type: Domain

Arginyl tRNA synthetase (ArgRS), a class I aminoacyl tRNA synthetase, is a monomer which aminoacylates the 2'-OH of the nucleotide at the 3' of the appropriate tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. There are at least three subgroups of ArgRS. One type contains both characteristic class I HIGH and KMSKS motifs, which are involved in ATP binding. The second subtype lacks the KMSKS motif; however, it has a lysine N-terminal to the HIGH motif, which serves as the functional counterpart to the second lysine of the KMSKS motif. A third group, which is found primarily in archaea and a few bacteria, lacks both the KMSKS motif and the HIGH loop lysine .
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain (DRE_TIM_HOA)
Type: Domain

4-hydroxy 2-ketovalerate aldolase (also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. Acetaldehyde is then converted by acetaldehyde dehydrogenase (acylating) (DmpF;

) to acetyl-CoA. The two enzymes are tightly associated. This family includes the Escherichia coli MhpE aldolase , the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase . In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF) and is inactive without it . HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site . This family belongs to the DRE-TIM metallolyase superfamily.

DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core β(8)-α(8) motif with the eight parallel β strands forming an enclosed barrel surrounded by eight α helices. The domain has a catalytic centre containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name 'DRE-TIM' .

This entry represents the N-terminal catalytic TIM barrel domain.