SII-SWORD/CoKE huggingface dataset:
Tyrosine-protein kinase Frk, SH2 domain (SH2_Frk)
Type: Domain

Frk (RAK) is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth . Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes . FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2 . Frk has been demonstrated to interact with retinoblastoma protein . Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation . Frk also plays a role in regulation of embryonal pancreatic beta cell formation .

The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs .
Beta-1,3-glucan recognition protein, C-terminal (GH16_GRP_C)
Type: Domain

Beta 1,3-glucan recognition proteins (GRP, also called Gram-negative bacteria binding proteins or GNBPs) have specific affinity for beta 1,3-glucan, a component on the surface of fungi and bacteria. Beta-GRP (beta-1,3-glucan recognition protein) is one of several pattern recognition receptors (PRRs), also referred to as biosensor proteins, that complexes with pathogen-associated beta-1,3-glucans and then transduces signals necessary for activation of an appropriate innate immune response. They are present in insects and lack all catalytic residues .
Pyruvate dehydrogenase E1 component, N-terminal (PDC_E1_N)
Type: Domain

Pyruvate dehydrogenase multienzyme complex (PDC) catalyzes the oxidative decarboxylation of pyruvate and the subsequent acetylation of coenzyme A to acetyl-CoA. The E1 component of PDC catalyzes the first step of the multistep process, using thiamine pyrophosphate (TPP) and a divalent cation as cofactors. E. coli PDC is a homodimeric enzyme .
Large ribosomal subunit protein uL30, eukaryotic/archaeal (Ribosomal_uL30_euk_arc)
Type: Domain

This entry represents a structural domain of the large ribosomal subunit protein uL30 from eukaryotes and archaea (which are also known as L7 subunit) and the ribosome biogenesis protein RLP7 (ribosomal protein L7-like) from yeasts. RLP7 is required for the biogenesis of the 60S ribosomal subunit .

Ribosomal protein uL30 is one of the proteins from the large ribosomal subunit. uL30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila melanogaster, Dictyostelium discoideum (Slime mold), fungal and mammalian uL7 ribosomal proteins. uL30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic L7 are proteins of about 250 to 270 residues.
Nicotinate phosphoribosyltransferase, archaeal-type (NAPRTase_arc-type)
Type: Family

Nicotinate phosphoribosyltransferase catalyses the formation of nicotinate mononucleotide (NAMN) and PPi from 5-phosphoribosy -1-pyrophosphate (PRPP) and nicotinic acid, this is the first, and also rate limiting, reaction in the NAD salvage synthesis . This salvage pathway serves to recycle NAD degradation products.
Phosphatidylethanolamine-binding protein, eukaryotic (PEBP_euk)
Type: Family

Phosphatidylethanolamine-binding proteins (PEBPs) are present in all three major phylogenetic divisions (eukaryotes, bacteria, archaea). The members in this subgroup are present in eukaryotes. Members here include those in plants such as Arabidopsis thaliana FLOWERING LOCUS (FT) (

) and TERMINAL FLOWER1 (TFL1) (

), which function as a promoter and a repressor of the floral transitions respectively , as well as the mammalian Raf kinase inhibitory protein (RKIP), also known as phosphatidylethanolamine-binding protein 1 (PEBP-1) (

), which inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NFkappaB signalling cascades . Also, a member of this family is the large ribosomal subunit protein mL38 (MRPL38, known as MRPL35 in yeast) (

), which is located in the central protuberance of the mitochondrial large ribosomal subunit . Although their overall structures are similar, the members of the PEBP family have very different substrates and oligomerisation states (monomer/dimer/tetramer).
Netrin-4, NTR domain (Netrin-4_NTR)
Type: Domain

This is the C-terminal netrin (NTR) domain of netrin-4 (beta-netrin) . Netrins are secreted proteins that function as tropic cues in the direction of axon growth and cell migration during neural development. Netrin-4 is a basement membrane component that is important in neural, kidney and vascular development . It may also be involved in regulating the outgrowth and shape of epithelial cells during lung branching morphogenesis .
Methylenetetrahydrofolate dehydrogenase, NAD-binding domain (m-THF_DH_NAD-bd)
Type: Domain

Methylene-tetrahydrofolate (m-THF) is a versatile carrier of activated one-carbon units. The oxidation of metabolic intermediate methylene-THF to methenyl-THF requires the enzyme methylene-tetrahydrofolate dehydrogenase (m-THF DH). In eukaryotes, m-THF DH is typically found as part of a multifunctional protein. NADP-dependent m-THF DHs in mammals, birds and yeast are components of a trifunctional enzyme with DH, cyclohydrolase, and synthetase activities. Certain eukaryotic cells also contain homodimeric bifunctional DH/cyclodrolase form. In bacteria, monofunctional DH, as well as bifunctional DH/cyclodrolase are found. In addition, yeast (S. cerevisiae) also express an monofunctional DH. This family contains only the monofunctional DHs from yeast .
Secreted frizzled-related protein 3, NTR domain (NTR_Sfrp3)
Type: Domain

Secreted frizzled-related proteins (Sfrps) are soluble proteins containing an Netrin (NTR) domain C-terminal to a cysteine-rich Frizzled domain . They show diverse functions and are thought to work in Wnt signaling indirectly, as modulators or antagonists by binding Wnt ligands, and directly, via the Wnt receptor, Frizzled .

SFRP3 (also known as FRZB) regulates chondrocyte maturation and long bone development . It is an antagonist of Wnt8 signalling .
Procollagen C-endopeptidase enhancer, NTR domain (NTR_PCOLCE)
Type: Domain

Procollagen C-endopeptidase enhancers (PCOLCEs) are extracellular matrix proteins that enhance the activity of procollagen C-proteases, by binding to the procollagen I C-peptide. They contain a C-terminal NTR domain, which has been suggested to possess inhibitory functions towards specific serine proteases but not towards metzincins, which are inhibited by the related TIMPs .
Complement C3-like, NTR domain (NTR_complement_C3)
Type: Domain

The NTR domain found in complement C3 is also known as the C345C domain because it occurs at the C terminus of complement C3, C4 and C5. Complement C3 plays a pivotal role in the activation of the complement systems, as all pathways (classical, alternative, and lectin) result in the processing of C3 by C3 convertase. The larger fragment, activated C3b, contains the NTR/C345C domain and binds covalently, via a reactive thioester, to cell surface carbohydrates including components of bacterial cell walls and immune aggregates. The smaller cleavage product, C3a, acts independently as a diffusible signal to mediate local inflammatory processes. The structure of C3 shows that the NTR/C345C domain is located in an exposed position relative to the rest of the molecule. The function of the domain in complement C3 is poorly understood .

This domain is also found in cobra venom factor, a functional analogue of human complement component C3b .
SH3RF1/SH3RF3, fourth SH3 domain (SH3RF1/SH3RF3_SH3_4)
Type: Domain

SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains . This entry represents the fourth SH3 domain, located at the C terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp . It may also have a role in regulating death receptor mediated and JNK mediated apoptosis . SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1 .
Dynamin-binding protein, first N-terminal SH3 domain (DNMBP_SH3_N1)
Type: Domain

Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain . It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation .

The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles . This entry represents the first N-terminal SH3 domain.
Dynamin-binding protein, second N-terminal SH3 domain (DNMBP_SH3_N2)
Type: Domain

Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain . It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation .

The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles . This entry represents the second N-terminal SH3 domain.
Dynamin-binding protein, third N-terminal SH3 domain (DNMBP_SH3_N3)
Type: Domain

Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain . It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation .

The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles . This entry represents the third N-terminal SH3 domain.
Dynamin-binding protein, first C-terminal SH3 domain (DNMBP_SH3_C1)
Type: Domain

Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain . It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation .

The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton . This entry represents the first C-terminal SH3 domain.
Sla1, third SH3 domain (Sla1_SH3_3)
Type: Domain

Sla1 is a fungal protein involved in coupling the actin cytoskeleton to the endocytic machinery during endocytosis. It binds to Sla2 (yeast Huntingtin interacting protein-1 HIP1), which plays a role in regulating actin dynamics and endocytosis . It serves as the targeting signal recognition factor for NPFX(1,2)D-mediated endocytosis .

Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1). This entry represents the third SH3 domain of Sla1.
SH3RF2, third SH3 domain (SH3RF2_SH3_3)
Type: Domain

Plenty of SH3 domains protein 2 (POSH2 also known as SH3 domain-containing RING finger protein 3 or putative E3 ubiquitin-protein ligase SH3RF2) contains the Src homology 3 (SH3) domains and a RING finger domain which confers E3 ligase activity to the protein. It belongs to the POSH family, which includes POSH1, POSH2 and POSH3 . POSH2 interacts with GTP-loaded Rac1, which is a small signaling G protein .

This entry represents the third SH3 domain of SH3RF2.
ARHGEF37, first C-terminal SH3 domain (ARHGEF37_SH3_C1)
Type: Domain

ARHGEF37 contains a RhoGEF (or Dbl homology, DH) domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP .

This entry represents the firs C-terminal SH3 domain of ARHGEF37.
Endophilin-A, SH3 domain (Endophilin_A_SH3)
Type: Domain

Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting . They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery . They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes . Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain .

This entry icludes the SH3 domain of endophilin.
Alpha Spectrin, SH3 domain (Alpha_Spectrin_SH3)
Type: Domain

Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability . Defects in alpha spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay . Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats.

This entry includes the SH3 domain of spectrin.
TRIM34, PRY/SPRY domain (TRIM34_PRY/SPRY)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of E3 ubiquitin-protein ligase TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and also known as RBCC proteins . The TRIM34 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain . It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary . TRIM34 functions as an antiviral protein and contributes to the defense against retroviral infections . The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection .
TRIM22, PRY/SPRY domain (PRY/SPRY_TRIM22)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM22, also known as RING finger protein 94 (RNF94) or STAF50 (Stimulated trans-acting factor of 50kDa). TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and also known as RBCC proteins . TRIM22 is an interferon-induced protein, predominantly expressed in peripheral blood leukocytes, in lymphoid tissue such as spleen and thymus, and in the ovary . TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 inhibits influenza A virus (IAV) infection by targeting the viral nucleoprotein for degradation; it represents a novel restriction factor up-regulated upon IAV infection that curtails its replicative capacity in epithelial cells . Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. A large number of high-risk non-synonymous (ns)SNPs have been identified in the highly polymorphic TRIM22 gene, most of which are located in the SPRY domain and could possibly alter critical regions of the SPRY structural and functional residues, including several sites that undergo post-translational modification . TRIM22 is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells . Its expression in Wilms tumors is negatively associated with disease relapse. It is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines; p53 dysfunction may be one of the mechanisms for its down-regulation .
TRIM6, PRY/SPRY domain (PRY/SPRY_TRIM6)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM6, also known as RING finger protein 89 (RNF89). TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and also known as RBCC proteins . It is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells . TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response .
TRIM4, PRY/SPRY domain (PRY/SPRY_TRIM4)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM4 which is also known as RING finger protein 87 (RNF87). TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and also known as RBCC proteins . TRIM4 is a positive regulator of RIG-I-mediated interferon (IFN) induction. It regulates virus-induced IFN induction and cellular antiviral innate immunity by targeting RIG-I for K63-linked poly-ubiquitination . Over-expression of TRIM4 enhances virus-triggered activation of transcription factors IRF3 and NF-kappaB, as well as IFN-beta induction . Expression of TRIM4 differs significantly in Huntington's Disease (HD) neural cells when compared with wild-type controls, possibly impacting down-regulation of the Huntingtin (HTT) gene, which is involved in the regulation of diverse cellular activities that are impaired in Huntington's Disease (HD) cells .
TRIM62, PRY/SPRY domain (PRY/SPRY_TRIM62)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM62. TRIM62 is a RING finger E3 ubiquitin ligase, also called DEAR1 (ductal epithelium associated RING chromosome 1) . It is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer and thus, making TRIM62 a predictive biomarker . Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer . Decreased levels of TRIM62 also represent an independent adverse prognostic factor in acute myeloid leukemia .
TRIM21, PRY/SPRY domain (PRY/SPRY_TRIM21)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kDa Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and are are also known as RBCC proteins . As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs) . It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue-destructive inflammatory process . It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterised by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins . It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity .
Jouberin, SH3 domain (AHI1_SH3)
Type: Domain

Jouberin, also called AHI-1, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates its distribution and function, affecting cilium formation and vesicle transport . Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterised by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy . AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression . AHI-1 contains WD40 and SH3 domains.
SGSM3, SH3 domain (SGSM3_SH3)
Type: Domain

SGSM3 (also known as MAP, RUSC3, or RabGAP5) is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signalling . It is involved in modulating NGF-mediated neurite outgrowth and differentiation . It also interacts with the tumour suppressor merlin and may play a role in the merlin-associated suppression of cell growth . SGSM3 contains TBC, SH3, and RUN domains.

This entry includes the SH3 domain of SGSM3.
SH3 domain-containing protein 19, SH3 domain 1 (Eve1_SH3_1)
Type: Domain

SH3 domain-containing protein 19 (also known as Eve-1 or EBP) exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. Eve-1 interacts with ADAMs (A disintegrin and metalloprotease) and is required for ectodomain shedding of epidermal growth factor receptor ligands . It inhibits Ras signaling .

This entry represents the first SH3 domain of Eve1.
SH3 domain-containing protein 19, SH3 domain 3 (Eve1_SH3_3)
Type: Domain

SH3 domain-containing protein 19 (also known as Eve-1 or EBP) exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. Eve-1 interacts with ADAMs (A disintegrin and metalloprotease) and is required for ectodomain shedding of epidermal growth factor receptor ligands . It inhibits Ras signaling .

This entry represents the third SH3 domain of Eve1.