SII-SWORD/CoKE huggingface dataset:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, catalytic domain (PLC-eta1_cat)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

The PLC-eta gene is transcribed to several splicing variants. This entry represents PLC-eta-1, which may have an important role in the brain .

This entry represents the catalytic domain of PLC-eta1, a TIM barrel with two highly conserved regions (X,

, and Y,

) split by a highly degenerate linker sequence .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, catalytic domain (PLC-eta2_cat)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-eta-2 may function downstream of G-protein-coupled receptors and may be important for formation and maintenance of the neuronal network in the postnatal brain .

This entry represents the catalytic domain of PLC-eta2, a TIM barrel with two highly conserved regions (X,

, and Y,

) split by a highly degenerate linker sequence .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, RA domain 2 (PLC-epsilon1_RA2)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-epsilon-1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organisation and T-cell activation .

This entry represents the Ras-associating (RA) domain 2, which show an ubiquitin-like fold and can bind Ras and activate it .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, EF hand motif (PLC-beta1_EF)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-beta-1 is the predominant PLC isoform in the brain. PLC-beta-1 knockout mice exhibit behavioral abnormalities as a result of disrupted cortical development and plasticity . PLC-beta-1 is involved in cell cycle control and in development and fertility . It has an important role in the control of mouse oocyte meiosis. PLC beta 1 is first exclusively localised to the nucleus and then migrates to the cytoplasm when the oocyte is fully grown; this chronology being crucial for the production of competent oocytes . It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia and epileptic encephalopathy .

PLC-beta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs (represented by this entry), a PLC catalytic core, and a single C2 domain.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, catalytic domain (PLC-beta2_cat)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-beta-2 may be involved in the transduction of bitter taste stimuli .

This entry represents the catalytic TIM barrel domain of this enzyme .
Suppressor of cytokine signalling 2, SOCS box domain (SOCS2_SOCS_box)
Type: Domain

Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers . All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 .

SOCS2 is necessary for normal growth regulation . It appears to be a negative regulator in the growth hormone/IGF1 signaling pathway .

This entry represents the SOCS (suppressors of cytokine signalling) box of SOCS2-like proteins .
Suppressor of cytokine signalling 3, SOCS box domain (SOCS3_SOCS_box)
Type: Domain

Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers . All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 .

SOCS3 interacts with gp130, a common cytokine receptor for interleukin (IL)-6, leukemia inhibitory factor (LIF) and other members of the IL-6 family of cytokines. SOCS3 has been reported also to interact with the leptin receptor, erythropoietin receptor, insulin receptor, IL-12beta receptor and granulocyte-colony stimulating factor receptor .

This entry represents the SOCS (suppressors of cytokine signalling) box of SOCS3-like proteins .
CAP, conserved site, C-terminal (CAP_CS_C)
Type: Conserved_site

This entry represents a conserved site in the C-terminal of the CAP protein. Structurally, CAP is a protein of 474 to 551 residues, which consist of two domains separated by a proline-rich hinge. In budding and fission yeasts the CAP protein is a bifunctional protein whose N-terminal domain binds to adenylyl cyclase, thereby enabling that enzyme to be activated by upstream regulatory signals, such as Ras. The N terminus also catalyses cofilin-mediated severing of actin filaments . The C-terminal domain plays a role in in recycling cofilin-bound, ADP-actin monomers .
GREB1 (GREB1)
Type: Family

GREB1 (gene regulated in breast cancer 1 protein) is a ESR1 (estrogen receptor 1)-upregulated protein that may regulate estrogen action and it is associated with estrogen-stimulated cell proliferation . It acts as a regulator of hormone-dependent cancer growth in breast, ovarian and prostate cancers . This protein may be a target to inhibit tumour-promoting pathways both downstream and independent of ESR1 as a possible treatment strategy.

This entry represents a protein family that includes Protein GREB1 and similar proteins from chordates.
Huntingtin family (Huntingtin_fam)
Type: Family

The huntingtin family consists of huntingtin proteins, including Dictyostelium HD protein homologue. Abnormalities in the huntingtin protein (Htt) are associated with Huntington's disease , but despite its importance the function of Htt is largely unknown. In Dictyostelium discoideum Htt is required for normal chemotaxis and cytokinesis .
Peptide methionine sulfoxide reductase MsrB (Met_Sox_Rdtase_MsrB)
Type: Family

The oxidation of methionine residues in proteins is considered to be one of the consequences of oxidative damage to cells, which in many cases leads to the loss of biological activity. Peptide methionine sulphoxide reductase (Msr) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulphoxide, (MetO), to methionine . Methionine (Met) can be oxidised to the R and S diastereomers of methionine sulfoxide (MetO). Methionine sulfoxide reductases A (MsrA) and B (MsrB) reduce MetO back to Met in a stereospecific manner, acting on the S and R forms, respectively. Msr is present in most living organisms .

Many bacteria, particularly pathogens, possess methionine sulfoxide reductase MsrA and MsrB as a fusion form (MsrAB) . This entry includes MsrB and the fusion form of these enzymes.
NADP-reducing hydrogenase subunit HndA-like (NADP_DH_HndA-like)
Type: Family

The NADP-reducing hydrogenase complex from Desulfovibrio is a heterotetramer encoded by the hndABCD operon. It catalyses the reduction of NADP in the presence of molecular H2 to yield NADPH . This entry represents NADP-reducing hydrogenase subunit HndA from D.fructosivorans and similar prokaryotic sequences, such as HydC that acts as a bifurcating [FeFe] hydrogenase, which uses the exergonic oxidation of reduced ferredoxin to drive the unfavorable oxidation of NADH to produce H2 . Proteins in this entry belong to the [2Fe-2S] ferredoxin family and are organised into two independent structural domains .
Parvin (Parvin)
Type: Family

This entry include parvins from mammals and paralysed arrest at two-fold protein 6 (pat-6) from C. elegans. Parvins and pat-6 contain an actin-binding domain (ABD) that consists of two in tandem arranged calponin homology (CH) domains. The ABD domain enables parvins to recruit F-actin to focal adhesions and associate with stress fibres . Parvins bind to actin binding/regulatory proteins and co-localise with integrins . Therefore, they may be involved in integrin-mediated adhesion and actin-dependent processes such as cell shape regulation and cell migration .

In humans, there are three parvins. Alpha-parvin (also known as actopaxin/CH-ILKBP) is ubiquitously expressed and is required for normal development of the embryonic cardiovascular system . Beta-parvin (also known as affixin) is enriched in heart and skeletal muscle . The expression of gamma-parvin (gamma-pv) is restricted to haematopoietic cells and plays a subtle role for blood cell homeostasis .
Plakophilin/Delta catenin (Plakophilin/d_Catenin)
Type: Family

The p120 subfamily of armadillo-related proteins includes deta-catenin, Splicing regulator ARVCF, p0071/plakophilin-4, and plakophilins 1-3 . These proteins are involved in mediating cell-cell adhesion. Besides their junctional localisation, these proteins can be found in the cytoplasm and nucleus where they play additional roles .
Transcription factor TRPS1 (TRPS1)
Type: Family

The TRPS1 gene encodes a multi zinc-finger nuclear regulator of chondrocyte proliferation and differentiation . Mutations in the gene cause trichorhinophalangeal syndrome (TRPS), an autosomal dominant skeletal dysplasia . The Trps1 protein also acts as regulator of histone deacetylation, interacting with two histone deacetylases, Hdac1 and Hdac4, thereby increasing their activity .
ABI gene family member 3, SH3 domain (ABI3_SH3)
Type: Domain

ABI gene family member 3 (ABI3, also known as NESH) belongs to the ABI family and is a component of the Abi/WAVE complex . It contains a SH3 domain that interacts with p21-activated kinase (PAK), which is involved in regulation of cell motility .

This entry represents the SH3 domain found at the C-terminal end of ABI3 .
ABI family (ABI)
Type: Family

This entry represents the ABI family, which includes Abi1, Abi2 and Abi3. They are SH3 domain-containing proteins that are involved in regulation of actin organisation. Abi1, Abi2 and Abi3 all participate in the formation of the Abi/WAVE complex, which regulates Arp2/3-mediated actin filament nucleation and actin network assembly . This entry also include Abl interactor homologue (abiA) from Dictyostelium discoideum (Slime mold). abiA is part of a Scar/WAVE complex that is required for proper cytokinesis .
Twinfilin (Twinfilin)
Type: Family

This entry represents the twinfilin family. Its members include twinfilin from Drosophila and twinfilin-1/2 from mammals. They are actin-binding proteins involved in motile and morphological processes . They inhibit actin polymerisation, likely by sequestering G-actin .
Tyramine beta-hydroxylase/Dopamine beta-hydroxylase (Tbh/DBH)
Type: Family

This entry includes tyramine beta-hydroxylases from invertebrates and dopamine beta-hydroxylases from mammals.
Smc1, ATP-binding cassette domain (Smc1_ABC)
Type: Domain

This entry represents the ATP-binding cassette domain of eukaryotic Smc1 proteins.

Smc1 (Structural maintenance of chromosomes protein 1) is involved in chromosome cohesion during cell cycle and in DNA repair. In eukaryotes, the Smc1-Smc3 heterodimer is part of the cohesin complex, which is required for the cohesion of sister chromatids after DNA replication .
Protein phosphatase EYA (EYA)
Type: Family

Members of the eye absent (EYA) family were originally characterised in fly eye development. EYA proteins are both transcriptional activators and tyrosine phosphatases , and have been shown to dephosphorylate H2AX, promoting repair and cell survival in the response to DNA damage . EYA proteins (EYA1-4) are normally expressed early in development . Their phosphatase activity regulates Six1-Dach-Eya transcriptional effects in precursor cell proliferation and survival in mammalian organogenesis .
Protein S100-A10 (S100-A10)
Type: Family

S100A10 (also known as p11) belongs to the S100 calcium-binding family and is involved in intracellular trafficking and cell migration . S100A10 may be involved in the promotion of cancer cell invasion and migration . S100A10 is required for the activity of Rac1, which regulates actin dynamics and promotes cell spreading . S100A10 forms a heterotetrameric complex with ANX2 (membrane-binding protein annexin A2), which is involved in membrane transport events such as endocytosis and exocytosis . ANX2 can also bind and bundle actin filaments and is required for actin dynamics to promote cell migration and spreading .
Protein S100-B (S100-B)
Type: Family

S100-B belongs to the S100 calcium-binding family. It has been implicated in oligodendrocyte progenitor cell (OPC) regeneration in response to demyelinating insult . S100B is a marker of the glial cells and its expression defines a late developmental stage after which GFAP-expressing cells lose their neural stem cell potential . S100-B can be used as a marker for early assessment of minor head injury and blood-brain barrier disruption .
Protein S100-A11 (S100A11)
Type: Family

S100A11 belongs to the S100 calcium-binding family. S100A11 has several biological functions. It is a ligand of RAGE (receptor for advanced glycation end products) and may be involved in the process of low-grade inflammation to osteoarthritis progression . S100A11 is a dual mediator for growth regulation in human keratinocytes . It binds to annexin I and plays a critical role in regulating growth of normal and malignant squamous epithelial cells . S100A11 could inhibit actin-activated myosin ATPase activity by binding to actin in the presence of Ca2+ .
Protein S100-A1 (S100-A1)
Type: Family

S100A1 belongs to the S100 calcium-binding family . S100A1 plays a critical role in cardiac performance, blood pressure regulation and skeletal muscle function . S100A1 interacts with protein phosphatase 5 (PP5) via TPR repeats; the interaction is calcium-dependent and modulates PP5 activity .
Protein S100-Z (S100Z)
Type: Family

S100Z belongs to the S100 calcium-binding family . The function of S100Z is unclear. S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca2+-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control. S100Z is normally expressed in various tissues, with its highest level of expression being in spleen and leukocytes . Preliminary structural data suggests that S100Z is homodimer, however a heterodimer with S100P has been reported. S100Z is capable of binding calcium ions. When calcium binds to S110Z, the protein experiences a conformational change, which exposes hydrophobic surfaces on the protein. In comparison with their normal tissue counterparts, S100Z gene expression appears to be deregulated in some tumour tissues .
E3 ubiquitin-protein ligase SH3RF3, RING finger, HC subclass (SH3RF3_RING-HC_Zfn)
Type: Domain

SH3RF3 (or POSH2) is a scaffold protein that function as an E3 ubiquitin-protein ligase. It contains an N-terminal RING finger domain and four SH3 domains. It belongs to the POSH family, which includes POSH1, POSH2 and POSH3 .

This entry represents the N-terminal C3HC4-type RING-HC finger of SH3RF3.
Endophilin-B1, SH3 domain (SH3GLB_SH3)
Type: Domain

Endophilin-B1 is a BAR and SH3 (Src homology 3) domain-containing protein and a member of the endophilin family that is localised predominantly to intracellular membranes. It regulates the membrane dynamics of various intracellular compartments such as mitochondria and autophagosome formation in fibroblast .

This entry represents the C-terminal SH3 domain of Endophilin-B1.
Thrombospondin-3, coiled-coil domain (TSP3_CC)
Type: Domain

Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers . EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

TSP3 may be involved in the regulation of skeletal maturation .

This entry represents the N-terminal coiled coil region of TSP3. It forms a pentameric left-handed coiled coil with a channel that is a unique carrier for lipophilic compounds. The pentamer is stabilized by inter-subunit disulfide bonds formed between cysteine residues adjacent to the C-terminal end of the coiled coil region .
E3 ubiquitin-protein ligase SH3RF2, RING finger, HC subclass (SH3RF2_RING-HC_Zfn)
Type: Domain

SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation . It may also play a role in cardiac functions together with protein phosphatase 1 . SH3RF2 contains an N-terminal RING finger domain and three SH3 domains.

This entry represents the N-terminal C3HC4-type RING-HC finger of SH3RF2 and similar proteins from vertebrates.
PDZ and LIM domain protein 1, LIM domain (PDLIM1_LIM)
Type: Domain

This entry represents the C-terminal Lim domain of PDLIM1, which function as an adaptor or scaffold to support the assembly of multimeric protein. This domain shows two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms .

PDZ and LIM domain protein 1 (PDZ-LIM1, also known as CLP-36) is a member of the PDZ-LIM family of adapter proteins that have been implicated in cytoskeleton organisation, neuronal signalling, cell lineage specification, organ development, and oncogenesis . Several PDZ-LIM proteins are predominantly expressed in striated muscle. However, CLP36 is expressed in several nonmuscle tissues .
CLP36 binds to alpha-actinin-1 and may direct alpha-actinin-1 to specific actin structures . CLP36 also recruits the Clik1 kinase to actin stress fibres in nonmuscle cells .
A-kinase anchor protein 12 (AKAP12)
Type: Family

A-kinase anchor protein 12 (AKAP12) is an anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC) . AKAP12 may play a tumor/angiogenesis suppressor role .
Protein CASC3 (CASC3)
Type: Family

MLN51 (also known as CASC3) is a component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism . It stimulates the ATPase and RNA-helicase activities of EIF4A3 . In humans, it is overexpressed in breast cancer . The structure of the EJC containing MLN51 has been resolved .