SII-SWORD/CoKE huggingface dataset:
MIA2, SH3 domain (MIA2_SH3)
Type: Domain

MIA2 is expressed specifically in hepatocytes and its expression is controlled by hepatocyte nuclear factor 1 binding sites in the MIA2 promoter . It inhibits the growth and invasion of hepatocellular carcinomas (HCC) and may act as a tumour suppressor . A mutation in MIA2 in mice resulted in reduced cholesterol and triglycerides. Since MIA2 localizes to ER exit sites, it may function as an ER-to-Golgi trafficking protein that regulates lipid metabolism . MIA2 contains an N-terminal SH3-like domain, similar to MIA.

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 .
FCHSD2, SH3 domain 2 (FCHSD2_SH3_2)
Type: Domain

F-BAR and double SH3 domains protein 2 (FCHSD2), also known as carom, contains an N-terminal F-BAR domain and two SH3 domains at the C terminus . It may mediate receptor endocytosis and transport . This entry represents the second SH3 domain of FCHSD2.
Sorting nexin-18, SH3 domain (SNX18_SH3)
Type: Domain

Sorting nexin-18 (SNX18) is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1 . It binds FIP5 and is required for apical lumen formation . It may also play a role in axonal elongation . SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system . SNX18 also contains BAR and SH3 domains.

This entry represent the SH3 domain of SNX18.
SNX9, SH3 domain (SNX9_SH3)
Type: Domain

Sorting nexin 9 (SNX9) has been suggested to be involved in the endocytic process as an accessory factor . SNX9 has binding sites for both clathrin and adaptor protein AP-2 in a low complexity region, and binds dynamin-2 (Dyn2) by its SH3 domain. SNX9 has its own membrane-binding activity, mediated by a carboxyl-terminal region containing the PX domain and the BAR domain . Endogenous SNX9 partially co-localizes with AP-2 and Dyn2 at the plasma membrane, and over expression in K562 and HeLa cells of truncated versions of SNX9 inhibits the uptake of transferrin . Moreover, SNX9 is required for efficient clathrin-mediated endocytosis, which suggests that it functions to regulate dynamin activity .

SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains a BAR and a SH3 domain. This entry represents the SH3 domain of SNX9.
Nck2, SH3 domain 1 (Nck2_SH3_1)
Type: Domain

This entry represent the first SH3 domain of Nck2. It binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression .

Nck2 (also known as Grb4) is a member of the Nck family. It plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds neuronal signaling proteins such as ephrinB .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Nck2, SH3 domain 2 (Nck2_SH3_2)
Type: Domain

This entry represent the second SH3 domain of Nck2. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif .

Nck2 (also known as Grb4) is a member of the Nck family. It plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds neuronal signaling proteins such as ephrinB .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Nck2, SH3 domain 3 (Nck2_SH3_3)
Type: Domain

This entry represent the third SH3 domain of Nck2. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif .

Nck2 (also known as Grb4) is a member of the Nck family. It plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds neuronal signaling proteins such as ephrinB .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Nck1, SH3 domain 1 (Nck1_SH3_1)
Type: Domain

This entry represent the first SH3 domain of Nck1. The first SH3 domain of Nck binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression .

Nck1 (also called Nck-alpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds and activates RasGAP, resulting in the downregulation of Ras . It is also involved in the signaling of endothilin-mediated inhibition of cell migration .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Splicing factor 3A subunit 1, ubiquitin domain (SF3As1_ubi)
Type: Domain

Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form . The 120kDa subunit (SF3a120) has a carboxy-terminal ubiquitin-like domain and two SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, at its amino-terminus .

This entry represents the C-terminal ubiquitin domain.
Nck1, SH3 domain 2 (Nck1_SH3_2)
Type: Domain

This entry represent the second SH3 domain of Nck1. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif .

Nck1 (also called Nck-alpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds and activates RasGAP, resulting in the downregulation of Ras . It is also involved in the signaling of endothilin-mediated inhibition of cell migration .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Nck1, SH3 domain 3 (Nck1_SH3_3)
Type: Domain

This entry represent the third SH3 domain of Nck1. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif .

Nck1 (also called Nck-alpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling . It binds and activates RasGAP, resulting in the downregulation of Ras . It is also involved in the signaling of endothilin-mediated inhibition of cell migration .

Cytoplasmic proteins Nck are non-enzymatic adaptor proteins composed of three SH3 (Src homology 3) domains and a C-terminal SH2 domain . They regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates . They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics . They associate with tyrosine-phosphorylated growth factor receptors or their cellular substrates . There are two vertebrate Nck proteins, Nck1 and Nck2.
Ribosomal protein bL20, C-terminal (Ribosomal_protein_bL20_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the ribosomal protein bL20. The C-terminal domain of this protein is an α-helical domain. It specifically recognizes RNA .

This entry represents the large ribosomal subunit protein family bL20 that contains members from eubacteria, as well as their mitochondrial and plastid homologs. bL20 is an assembly protein, required for the first in vitro reconstitution step of the 50S ribosomal subunit, but does not seem to be essential for ribosome activity. bL20 has been shown to partially unfold in the absence of RNA, in regions corresponding to the RNA-binding sites. bL20 represses the translation of its own mRNA via specific binding to two distinct mRNA sites, in a manner similar to the bL20 interaction with 23S ribosomal RNA .
Antitoxin epsilon/PezA domain superfamily (Antitoxin_epsilon/PezA_dom_sf)
Type: Homologous_superfamily

The epsilon antitoxin, produced by various prokaryotes, forms part of a post-segregational killing system, which is involved in the initiation of programmed cell death of plasmid-free cells. The protein is folded into a three-helix bundle directly interacting with the zeta toxin, inactivating it .

PezA is the cognate antitoxin to the S. pneumoniae PezT toxin. PezA shares sequence similarity in the C-terminal region with the epsilon antitoxin. The PezA protein functions as a transcriptional repressor of the pezAT operon together with PezT, by binding a palindrome sequence that overlaps the promoter. This differs from the epsilon-zeta system in which epsilon functions solely as the antitoxin and transcriptional regulation is carried out by another protein designated omega .
UPF0234, N-terminal (UPF0234_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of UPF0234 uncharacterised proteins, which includes YajQ.

In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period . Earlier, YajQ was characterised as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains .

The polypeptide chain of YajQ is folded into two domains with identical folding topology. Each domain has a four-stranded antiparallel β-sheet flanked on one side by two α-helices. This structural motif is a characteristic feature of many RNA-binding proteins .
UPF0234-like, C-terminal (UPF0234-like_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of UPF0234 uncharacterised proteins, which includes YajQ. It also found also in UPF0381 uncharacterised proteins.

In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period . Earlier, YajQ was characterised as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains .

The polypeptide chain of YajQ is folded into two domains with identical folding topology. Each domain has a four-stranded antiparallel β-sheet flanked on one side by two α-helices. This structural motif is a characteristic feature of many RNA-binding proteins .
Tyrosine-protein kinase Tec, SH3 domain (Tec_SH3)
Type: Domain

This entry represents the SH3 domain of Tec .
Friend leukemia integration 1 transcription factor, pointed domain (SAM_PNT-FLI-1)
Type: Domain

This is the SAM pointed domain of FLI-1 (Friend Leukemia Integration) subfamily of ETS transcriptional regulators. It is a putative protein-protein interaction domain. The FLI-1 protein participates in regulation of cellular differentiation, proliferation, and survival . The Fli-1 gene was initially described in Friend virus-induced erythroleukemias as a site for virus integration. It is highly expressed in hematopoietic tissues and at lower level in lungs, heart, and ovaries. Fli-1 is a proto-oncogene implicated in Ewing's sarcoma and erythroleukemia . Members of this family are potential targets for cancer therapy .
Tyrosine-protein kinase BTK, SH3 domain (BTK_SH3)
Type: Domain

Btk (Bruton tyrosine kinase) is a member of the Tec family, which is a group of nonreceptor tyrosine kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Btk also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions .

Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells . It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation . Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis . Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans .
Type VI secretion system TssC (T6SS_TssC)
Type: Family

TssC (also known as VipB) is a family of Gram-negative type VI secretion system components of the tail sheath. They have been known as COG3517. These sheath-components, of which there are many copies in the sheath, are also variously referred to as TssC. On contact with another bacterial cell the sheath contracts and pushes the puncturing device and tube through the cell envelope and punches the target bacterial cell . VipA and VipB (TssB and TssC) proteins were shown to form a cog-wheel like tubular structure in V. cholerae that was noticed to resemble T4 phage gp18 polysheath. Two β-strands of VipA and four β-strands of VipB intertwine forming the middle layer of the sheath. The sheath assembles around an inner Hcp tube and is attached to a structure called a baseplate that spans the bacterial membranes. Importantly, VipA/VipB sheath was shown to form a long contractile organelle in V. cholerae and in E. coli, suggesting that sheath contraction powers the secretion .

This entry includes TssC mostly from Bacteroidetes.

The type VI secretion system (T6SS), also known as CIS contractile injection system , is a supra-molecular bacterial complex that resembles phage tails. It is a toxin delivery systems which fires toxins into target cells upon contraction of its TssBC sheath . Thirteen essential core proteins are conserved in all T6SSs: the membrane associated complex TssJ-TssL-TssM, the baseplate proteins TssE, TssF, TssG, and TssK, the bacteriophage-related puncturing complex composed of the tube (Hcp), the tip/puncturing device VgrG, and the contractile sheath structure (TssB and TssC). Finally, the starfish-shaped dodecameric protein, TssA, limits contractile sheath polymerization at its distal part when TagA captures TssA .
Styelin (Styelin)
Type: Family

This is a family of antimicrobial peptides found in Stela clava (Sea squirt). Family members are α-helical phenylalanine-rich antimicrobial peptides effective against a panel of Gram-negative and Gram-positive bacteria. Styelin contains unusual amino acids such as dihydroxyarginine, dihydroxylysine, 6-bromotryptophan, and 3,4-dihydroxyphenylalanine, which are important for the CC antimicrobial activity at high salt concentrations .
Tyrosine-protein kinase TXK, SH3 domain (TXK_SH3)
Type: Domain

TXK is a member of the Tec family, which is a group of nonreceptor tyrosine kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. TXK forms a complex with EF-1alpha and PARP1 that regulates interferon-gamma gene transcription in Th1 cells .

This entry represents the SH3 domain of TXK.
Domain of unknown function DUF5465 (DUF5465)
Type: Domain

This domain is found in Enterobacteria phage T7.
Protein of unknown function DUF5418 (DUF5418)
Type: Family

This is a family of unknown function found in Methanocaldococcus jannaschii. Family members have three predicted trans-membrane regions.
Tyrosine-protein kinase ITK, SH3 domain (ITK_SH3)
Type: Domain

ITK (also known as Tsk or Emt) is a member of the Tec family, which is a group of nonreceptor tyrosine kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation , and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions.

This entry represents the SH3 domain of ITK.
Amidophosphoribosyltransferase, N-terminal (PurF_N)
Type: Domain

This glutaminase domain is found at the N-terminal of glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase (GPATase), also known as amidophosphoribosyltransferase. The glutaminase domain catalyses amide nitrogen transfer from glutamine to the appropriate substrate. In this process, glutamine is hydrolysed to glutamic acid and ammonia.

Purine nucleotides are synthesised both via the de novo pathway and via the salvage pathway and are vital for cell functions and cell proliferation through DNA and RNA syntheses and ATP energy supply. Amidophosphoribosyltransferase (

) is the rate-limiting enzyme in the de novo pathway of purine ribonucleotide synthesis and is regulated by feedback inhibition by AMP and GMP .

5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = L-glutamine + 5-phospho-alpha-D-ribose 1-diphosphate + H2O

This enzyme crystallises as a homotetramer, but can also exist as a homodimer .
Phosphatidylinositol 3-kinase regulatory subunit beta, SH3 domain (PI3K_p85beta_SH3)
Type: Domain

This entry represents the SH3 domain of PI3K (phosphoinositide-3-kinase) subunit beta (also known as subunit p85-beta).
DUS-like, FMN-binding domain (DUS-like_FMN-bd)
Type: Domain

This entry represents a dihydrouridine synthase-like (DUS-like) FMN-binding domain . Proteins containing this domain catalyse the reduction of the 5,6-double bond of a uridine residue on tRNA. Dihydrouridine modification of tRNA is widely observed in prokaryotes and eukaryotes, and also in some archaea. Most dihydrouridines are found in the D loop of t-RNAs. The role of dihydrouridine in tRNA is currently unknown, but may increase conformational flexibility of the tRNA. It is likely that different family members have different substrate specificities, which may overlap . 1VHN, a putative flavin oxidoreductase, has high sequence similarity to DUS. The enzymatic mechanism of 1VHN is not known at the present .

Dihydrouridine synthases (Dus) is a large family of flavoenzymes comprising eight subfamilies. They catalyse the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Mainly, they contain two functional conserved domains, an N-terminal catalytic domain (TBD) adopting a TIM barrel fold and a unique C-terminal helical domain (HD) devoted to tRNA recognition. However, DUS2 is distinguished from its paralogues and its fungi orthologues by the acquisition of an additional domain, a double stranded RNA binding domain (dsRBD), which serves as the main tRNA binding module .
Janus kinase 2, pseudokinase domain (PTK_Jak2_rpt1)
Type: Domain

Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors . Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities . It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis .

Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain .

This entry represents the pseudokinase domain of Jak2.