SII-SWORD/CoKE huggingface dataset:
SH3RF3, SH3 domain 3 (SH3RF3_SH3_3)
Type: Domain

This entry represents the third SH3 domain, located in the middle, of SH3RF3.

SH3RF3 (also known as POSH2) is a scaffold protein with E3 ubiquitin-protein ligase activity . It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions . It also interacts with GTP-loaded Rac1 . SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains.
FiwA/Osa (FiwA/Osa)
Type: Family

Osa and FiwA are fertility inhibition factors (FIN), which are employed by plasmids to block import of rival plasmids . Osa (oncogenic suppressive activity) of IncW group plasmid pSa gene inhibits the oncogenic properties of Agrobacterium tumefaciens. Osa is structurally similar to the ParB N-terminal domain/Srx superfamily of proteins: ParB acts in the bacterial and plasmid parABS partitioning systems . Osa has been shown to have ATPase and DNAse activities, and can block T-DNA transfer into plants . FiwA is encoded by plasmid RP1 and blocks the transfer of plasmid R388 . The gene product of Haemophilus influenzae p1056.10c also blocks T-DNA transfer .
MvaT, DNA-binding domain (MvaT_DBD)
Type: Domain

MvaT is a xenogeneic silencer conserved in Pseudomonas which assists in distinguishing foreign from self DNA. It prefers binding to flexible DNA segments with multiple TpA steps, and forms nucleoprotein filaments through cooperative polymerization .
RBM6, OCRE domain (RBM6_OCRE)
Type: Domain

RNA-binding protein 6 (RBM6) contains two RNA-binding motifs and shares protein sequence similarity with RBM5 . RBM6 is targeted to the splicing speckles and nascent transcripts . It may act mainly as a splicing activator . The elevated expression of RBM6 has been linked to certain tumours . A RBM6-CSF1R fusion has been found in acute megakaryoblastic leukemia .

RBM6 contains two RNA recognition motifs (RRMs), an OCtamer REpeat (OCRE) domain, two C2H2-type zinc fingers, a nuclear localization signal, and a G-patch/D111 domain. In contrast to RBM5, RBM6 has an additional unique domain, the POZ (poxvirus and zinc finger) domain, which may be involved in protein-protein interactions and inhibit binding of target sequences by zinc fingers. This entry represents the OCRE domain.

The OCRE (OCtamer REpeat) domain contains five repeats of an 8-residue motif, which were shown to form β-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed .
RBM10, OCRE domain (RBM10_OCRE)
Type: Domain

RBM10 contains two N-terminal RNA recognition motifs (RRMs) and an OCtamer REpeat (OCRE) domain, two C2H2-type zinc fingers, and a G-patch/D111 domain. This entry represents the OCRE domain.

RBM10, also known as S1-1, is a nuclear RNA-binding protein with domains characteristic of RNA processing proteins. Similar to RBM5, it promotes exon skipping of Fas pre-mRNA as well as selection of an internal 5'-splice site in Bcl-x pre-mRNA . It preferentially binds to G- and U-rich RNA sequences .

The OCRE (OCtamer REpeat) domain contains five repeats of an 8-residue motif, which were shown to form β-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed .
ZOP1, OCRE domain (ZOP1_OCRE)
Type: Domain

ZOP1 is a novel plant-specific nucleic acid-binding protein required for both RNA-directed DNA methylation (RdDM) and pre-mRNA splicing. It promotes RNA polymerase IV (Pol IV)-dependent siRNA accumulation, DNA methylation, and transcriptional silencing. As a pre-mRNA splicing factor, ZOP1 associates with several typical splicing proteins as well as with RNA polymerase II (RNAP II and Pol II). It also shows both RdDM-dependent and -independent roles in transcriptional silencing. ZOP1 contains an N-terminal C2H2-type Znf domain and an OCtamer REpeat (OCRE) domain that is usually related to RNA processing .

The OCRE (OCtamer REpeat) domain contains five repeats of an 8-residue motif, which were shown to form β-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed .
SUA-like, OCRE domain (SUA-like_OCRE)
Type: Domain

SUA is an RNA-binding protein located in the nucleus and expressed in all plant tissues. It functions as a splicing factor that influences seed maturation by controlling alternative splicing of ABI3. The suppression of the cryptic ABI3 intron indicates a role of SUA in mRNA processing. SUA also interacts with the prespliceosomal component U2AF65, the larger subunit of the conserved pre-mRNA splicing factor U2AF. SUA contains two RNA recognition motifs surrounding a zinc finger domain, an OCtamer REpeat (OCRE) domain, and a Gly-rich domain close to the C terminus .

The OCRE (OCtamer REpeat) domain contains five repeats of an 8-residue motif, which were shown to form β-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed .
AGGF1, OCRE domain (AGGF1_OCRE)
Type: Domain

Angiogenic factor with G patch and FHA domains 1 (AGGF1, also known as VG5Q) functions as a potent angiogenic factor in promoting angiogenesis through interacting with TWEAK (also known as TNFSF12), which is a member of the tumour necrosis factor (TNF) superfamily that induces angiogenesis in vivo. VG5Q can bind to the surface of endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. The chromosomal translocation t(5;11) and the E133K variant in VG5Q are associated with Klippel-Trenaunay syndrome (KTS), a disorder characterised by diverse effects in the vascular system. In addition to a forkhead-associated (FHA) domain and a G-patch motif, VG5Q contains an N-terminal OCtamer REpeat (OCRE) domain that is characterised by a 5-fold, imperfectly repeated octameric sequence .

The OCRE (OCtamer REpeat) domain contains five repeats of an 8-residue motif, which were shown to form β-strands. Based on the architectures of proteins containing OCRE domains, a role in RNA metabolism and/or signalling has been proposed .
Tfc3-like, extended winged-helix domain (Tfc3-like_eWH)
Type: Domain

Tfc3 (also known as Tau138) is one of three subunits of the tauB subcomplex of yeast transcription factor IIIC. This extended winged-helix domain of tau138 appears to interact with the TPR (tetratricopeptide repeat) array of tauA subunit tau131, and may therefore play a role in linking tauA, tauB, and TFIIIB to regulate the formation of the RNA polymerase III pre-initiation complex .

Proteins containing this domain also include mammalian general transcription factor 3C polypeptide 1 (Gtf3c1), which is a transcription factor IIIC box B binding subunit .
N-acetylgalactosamine-6-sulfatase (GALNS)
Type: Family

Lysosomal galactosamine-6-sulfatase (GALNS) removes sulfate groups from a terminal N-acetylgalactosamine-6-sulfate (or galactose-6-sulfate) in mucopolysaccharides such as keratan sulfate and chondroitin-6-sulfate. Defects in GALNS lead to accumulation of substrates, resulting in the development of the lysosomal storage disease mucopolysaccharidosis IV A .
TcpC, C-terminal (TcpC_C)
Type: Domain

This entry represents the C-terminal domain of TcpC.

TcpC is required for efficient conjugative transfer, localizing to the cell membrane independently of other conjugation proteins, where membrane localization is important for its function, oligomerization and interaction with the conjugation proteins TcpA, TcpH, and TcpG . Its C-terminal domain is critical for interactions with these other conjugation proteins . TcpC has low level sequence identity to proteins encoded by the conjugative transposon Tn916, which is responsible for a large proportion of the tetracycline resistance in different pathogens .
Nebulin, SH3 domain (Nebulin_SH3)
Type: Domain

Nebulin is a giant filamentous protein (600-900 kD) that plays a role in numerous cellular processes including regulation of muscle contraction, Z-disc formation, and myofibril organization and assembly in skeletal muscle. It contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. The N terminus of nebulin is located near the pointed end of the thin filament and contains a binding site for the actin filament capping protein tropomodulin (Tmod). The super repeat region of nebulin has been shown to interact with kelch-like family member 40 (KLHL40). The C terminus of nebulin is located within the highly specialized boundary of the sarcomere (Z-disc), and plays an important role in myofibril assembly, mechanosensing, signaling, force generation and transmission, and sarcolemmal resilience. The SH3 domain of nebulin interacts with multiple proteins, such as alpha-actinin, XIRP2 and titin . Mutations in nebulin can cause nemaline myopathy, characterised by muscle weakness which can be severe and can lead to neonatal lethality .
Lasp1, SH3 domain (Lasp1_SH3)
Type: Domain

Lasp1 (LIM and SH3 domain protein 1) is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation . It is overexpressed in several cancer cells, including breast, ovarian, bladder, and liver . In some cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumour size and poor prognosis . Lasp1 is a 36kDa protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain .
Nebulette, SH3 domain (Nebulette_SH3)
Type: Domain

Nebulette is a cardiac-specific protein that localizes to the Z-disc . It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles . Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure . Nebulette is a 107kDa protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain . It can crosslink actin filaments and it affects cell spreading . Lasp2 is a 34kDa protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain.
UBASH3B, SH3 domain (UBASH3B_SH3)
Type: Domain

This entry represents the SH3 domain of UBASH3B.

The TULA family includes two members termed p70/STS-1/TULA-2 and UBASH3A/STS-2/TULA/Cbl-InteractingProtein 4 (CLIP4). TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl (a multidomain adaptor and an E3 ubiquitinligase) through the SH3 domain and to ubiquitin via UBA .
UBASH3A, SH3 domain (UBASH3A_SH3)
Type: Domain

UBASH3A (ubiquitin-associated and SH3 domain-containing protein A, also known as STS-2 or TULA) belongs to the TULA family. It is only found in lymphoid cells and exhibits weak phosphatase activity . UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF . It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase .

This entry represents the SH3 domain of UBASH3A.

The TULA family includes two members termed p70/STS-1/TULA-2 and UBASH3A/STS-2/TULA/Cbl-InteractingProtein 4 (CLIP4). TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl (a multidomain adaptor and an E3 ubiquitinligase) through the SH3 domain and to ubiquitin via UBA .
Ephexin-1, SH3 domain (Ephexin-1_SH3)
Type: Domain

Ephexin-1 is a RhoGEF (Rho-type guanine nucleotide exchange factor) that activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP . It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus plays a critical role in the maturation and neurotransmission of neuromuscular junctions . Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA . It is required for normal axon growth and EphA-induced growth cone collapse .
ARHGEF37, SH3 domain 2 (ARHGEF37_SH3_2)
Type: Domain

ARHGEF37 (Rho guanine nucleotide exchange factor 37) 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.

This entry represents the second SH3 domain of ARHGEF37.
JIP2, SH3 domain (JIP2_SH3)
Type: Domain

JNK-interacting protein 2 (JIP2, also known as MAPK8IP2, IB2 or C-Jun-amino-terminal kinase-interacting protein 2) is widely expressed in the brain, where it forms complexes with fibroblast growth factor homologous factors (FHFs) which facilitates activation of the p38delta MAPK . JIP2 is enriched in postsynaptic densities and may play a role in motor and cognitive function . In addition to a JNK binding domain, JIP2 also contains SH3 and phosphotyrosine-binding (PTB) domains. The SH3 domain of the related protein JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself .
JIP1, SH3 domain (JIP1_SH3)
Type: Domain

JNK-interacting protein 1 (JIP1, also known as IB1, MAPK8IP1 or C-Jun-amino-terminal kinase-interacting protein 1) is highly expressed in neurons where it functions as an adaptor linking motor to cargo during axonal transport . It also affects microtubule dynamics in neurons. JIP1 is also found in pancreatic beta-cells where it is involved in regulating insulin secretion . In addition to a JNK binding domain, JIP1 also contains SH3 and Phosphotyrosine-binding (PTB) domains. Its SH3 domain homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself .
CPSF2, metallo-hydrolase domain (CPSF2_MBL)
Type: Domain

Cleavage and polyadenylation specificity factor (CPSF) plays a key role in pre-mRNA 3'-end formation, recognising the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition .

This entry represents a metallo-hydrolase domain in subunit 2. In addition to this metallo-beta-lactamase (MBL)-fold metallo-hydrolase domain, subunit 2 contains a beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain .
Endophilin B2, SH3 domain (Endophilin_B2_SH3)
Type: Domain

Endophilin-B2 is a cytoplasmic protein that colocalizes to the cytoplasmic compartment of the cell together with Bax and is excluded from the nucleus . It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy . Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition and endosomal sorting. They 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain .
GRB2, N-terminal SH3 domain (GRB2_N_SH3)
Type: Domain

GRB2 (growth factor receptor-bound protein 2) is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis and angiogenesis . In lymphocytes, GRB2 is associated with antigen receptor signaling components . GRB2 contains an N-terminal SH3 domain, a central SH2 domain and a C-terminal SH3 domain.

This entry represents the SH3 domain found at the N terminus of GRB2. This SH3 domain has been found to bind to Sos and Sos-derived proline-rich peptides .
MraZ, N-terminal (MraZ_N)
Type: Domain

MraZ proteins are highly conserved in bacteria. In Escherichia coli, MraZ functions as a transcriptional regulator . The crystal structure of this protein reveals two subdomains related by a pseudo two-fold axis, with each subdomain containing a highly conserved DXXXR sequence motif in close proximity to each other, suggested to form the functional site .

This entry represents the N-terminal subdomain.
GRB2, C-terminal SH3 domain (GRB2_C_SH3)
Type: Domain

GRB2 (growth factor receptor-bound protein 2) is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis and angiogenesis . In lymphocytes, GRB2 is associated with antigen receptor signaling components . GRB2 contains an N-terminal SH3 domain, a central SH2 domain and a C-terminal SH3 domain.

This entry represents the SH3 domain found at the C terminus of GRB2. This SH3 domain has been found to bind to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C terminus of FGRF2 .
MraZ, C-terminal (MraZ_C)
Type: Domain

MraZ proteins are highly conserved in bacteria. In Escherichia coli, MraZ functions as a transcriptional regulator . The crystal structure of this protein reveals two subdomains related by a pseudo two-fold axis, with each subdomain containing a highly conserved DXXXR sequence motif in close proximity to each other, suggested to form the functional site .

This entry represents the C-terminal subdomain.
GRAP, N-terminal SH3 domain (GRAP_N_SH3)
Type: Domain

GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway . It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease . GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain.
GRAP2, C-terminal SH3 domain (GRAP2_C_SH3)
Type: Domain

GRAP2 (also called GADS) is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway . It also has roles in antigen-receptor and tyrosine kinase mediated signaling . GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage .
EF-G domain III/V-like (EFG_III/V)
Type: Homologous_superfamily

EF2 (or EFG) participates in the elongation phase of protein synthesis by promoting the GTP-dependent translocation of the peptidyl tRNA of the nascent protein chain from the A-site (acceptor site) to the P-site (peptidyl tRNA site) of the ribosome. EF2 also has a role after the termination phase of translation, where, together with the ribosomal recycling factor, it facilitates the release of tRNA and mRNA from the ribosome, and the splitting of the ribosome into two subunits . EF2 is folded into five domains, with domains I and II forming the N-terminal block, domains IV and V forming the C-terminal block, and domain III providing the covalently-linked flexible connection between the two. Domains III and V have the same fold (although they are not completely superimposable and domain III lacks some of the superfamily characteristics), consisting of an α/β sandwich with an antiparallel β-sheet in a (β/α/β)x2 topology .

Elongation factor 4 (EF4/LepA) is a highly conserved guanosine triphosphatase translation factor. EF4 has six domains, of which four (I, II, III, and V) are homologous to corresponding domains in EF-G. It differs from EF-G by having a short domain IV, and possessing a conserved C-terminal domain .

This superfamily represents a domain found in EF2, EF4, as well as in some tetracycline resistance proteins, peptide chain release factors and in the C-terminal region of the bacterial hypothetical protein, YigZ.
srGAP1/2/3, SH3 domain (srGAP1/2/3_SH3)
Type: Domain

This entry represents the SH3 domain found in srGAP proteins 1, 2 and 3. srGAP1 (also called ARHGAP13) is a key GTPase activating protein (GAP) downstream of Slit-Robo pathway, and has been shown to inhibit neuronal migration and glioma cell invasion by reducing the activation of Cdc42 . srGAP2 (ARHGAP34) regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation . srGAP3 (ARHGAP14) interacts with lamellipodin at the cell membrane and regulates Rac-dependent cellular protrusions .

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 .
EFG, domain V (EFG_V)
Type: Domain

Elongation factor G (EFG) is folded into five domains, with domains I and II forming the N-terminal block, domains IV and V forming the C-terminal block, and domain III providing the covalently-linked flexible connection between the two .

This entry consists of domains similar to the C-terminal domain (domain V) of the bacterial translational elongation factor (EF) EF-G. Included in this group is the C terminus of mitochondrial elongation factor G1 (mtEFG1) and G2 (mtEFG2) proteins .
Tetracycline resistance protein, C-terminal (Tet_C)
Type: Domain

This domain is found in the C terminus of ribosomal protection proteins Tet(M) and Tet(O), and related proteins. This domain has homology to the C-terminal domains of the elongation factors EF-G and EF-2. Tet(M) and Tet(O) catalyze the release of tetracycline (Tc) from the ribosome in a GTP-dependent manner, thereby mediating Tc resistance . Tcs are broad-spectrum antibiotics. Typical Tcs bind to the ribosome and inhibit the elongation phase of protein synthesis, by inhibiting the occupation of site A by aminoacyl-tRNA .
BipA, domain V (BipA_V)
Type: Domain

This domain describes the C-terminal portion of BipA (or TypA) having homology to the domain V of the elongation factors EF-G . A member of the ribosome binding GTPase superfamily, BipA is widely distributed in bacteria and chloroplasts . It has been implicated in regulating a variety of cellular processes, including bacterial virulence and various stress responses .
BipA is phosphorylated on a tyrosine residue under some cellular conditions .

BipA contains domains that are homologous EF-G domain I, II, III, V. This entry represent the domain that is homologous to domain V.