SII-SWORD/CoKE huggingface dataset:
Kelch-like protein 26, BTB/POZ domain (BTB_POZ_KLHL26)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 26 (KLHL26) is encoded by the klhl26 gene, which is regulated by p53 via fuzzy tandem repeats. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein . This entry represents the BTB/POZ domain, a common protein-protein interaction module of about 100 amino acids .
Kelch repeat and BTB domain-containing protein 3, BTB/POZ domain (BTB/POZ_KBTBD3)
Type: Domain

This entry represents the BTB/POZ domain of Kelch repeat and BTB domain-containing protein 3 (KBTBD3), whose function is not clear.

The BTB superfamily includes KLHL (Kelch-like), KBTBD (Kelch repeat and BTB domain-containing), and KLHDC (Kelch domain-containing) subfamilies, which encompass structurally related molecules that differ in the types and numbers of their protein domains. The domain composition can appear to vary depending on the protein domain prediction program. For example, KLHL29, KLHL31, KLHL40, and KLHL41 were previously assigned within the KBTBD family as KBTBD9, KBTBD1, KBTBD5, and KBTBD10 respectively. KBTBD proteins have typically one BTB/POZ domain, occasionally a BACK domain, and two to four Kelch motifs .
MTMR4, protein tyrosine phosphatase domain (MTMR4_PTP)
Type: Domain

Myotubularin-related protein 4 (MTMR4) is a member of the myotubularin (MTM) family. It is the only family member that possesses a FYVE domain (a zinc finger domain) at its C terminus . MTMR4 has dual-specificity phosphatase activity that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate . MTMR4 has a unique distribution to endosomes and has been shown to function in early and recycling endosomes ; through phosphatidylinositol 3-phosphate turnover in phagosome membranes regulates phagocytosis and phagosome maturation . MTMR4 attenuates TGF-beta signalling by dephosphorylating intracellular signalling mediator R-Smads . Similarly, it acts as a negative modulator for the homeostasis of bone morphogenetic proteins (BMPs) signalling .

This entry represents the active Protein Tyrosine Phosphatase (PTP) domain of MTMR4.

The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [

,

, . The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway . MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases . The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer .
MTMR8, protein tyrosine phosphatase domain (MTMR8_PTP)
Type: Domain

Myotubularin-related protein 8 (MTMR8) is a catalytically active member of the myotubularin (MTM) family, which possess 3-phosphatase activity dephosphorylating phosphatidylinositol-3-phoshate [PI(3)P] and phosphatidylinositol-3,5-bisphosphate [PI(3,5)P]. MTMR8 dimerises with the catalytically inactive MTMR9. Complex formation increases its catalytic activity and alters the substrate specificity; the MTMR8/R9 complex prefers PI(3)P as a substrate and reduces cellular PtdIns(3)P levels . The MTMR8/R9 complex inhibits autophagy . In zebrafish, MTMR8 has been shown to cooperate with PI3K to regulate actin filament modeling, and vascular and muscle development .

This entry represents the active Protein Tyrosine Phosphatase (PTP) domain of MTMR8. Its catalytic activity is inhibited by oxidation and is reversibly reactivated by reduction .

The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [

,

, . The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway . MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases . The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer .
Kelch-like protein 24, BTB/POZ domain (BTB_POZ_KLHL24)
Type: Domain

Kelch-like protein 24 (KLHL24, also known as kainate receptor-interacting protein for GluR6 (KRIP6) or protein DRE1) belongs to the KLHL family . is necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity. KLHL24 is a component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates ubiquitination of KRT14 and controls its levels during keratinocyte differentiation [

,

,

,

,

. KLHL24 binds to and regulates the GluR6a kainate receptor . It also modulates the interaction of PICK1 with GluR6 kainate receptors . Kainate receptors (KAR) are ionotropic receptors that respond to the neurotransmitter glutamate and have been implicated in epilepsy, stroke, Alzheimer's and neuropathic pain .

This entry represents the BTB/POZ domain.

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .
Kelch-like protein 15, BTB/POZ domain (BTB_POZ_KLHL15)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 15 (KLHL15) is a substrate-specific adaptor for the Cullin3 E3 ubiquitin-protein ligase complex that targets the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits . It also plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR), by targeting the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. KLHL15 contains a BTB domain and kelch repeats, characteristics of a kelch family protein .

This entry represents the BTB/POZ domain of KLHL15, a common protein-protein interaction module of about 100 amino acids.
Kelch-like protein 7, BTB/POZ domain (BTB/POZ_KLHL7)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 7 (KLHL7) belongs to the KLHL family . It serves as a substrate-specific adapter in the Cul3-dependent ubiquitin ligase complex and is linked to autosomal dominant retinitis pigmentosa (adRP) . This entry represents the BTB/POZ domain.
Kelch-like protein 35, BTB/POZ domain (KLHL35_BTB_POZ_dom)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 35 (KLHL35) belongs to the KLHL family . Its function is not clear. Significant differences in the DNA methylation pattern of the KLHL35 gene have been associated with abdominal aortic aneurysm (AAA) and hepatocellular carcinoma .

This entry represents the N-terminal BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of KLHL35 and similar proteins from vertebrates.
Ephrin type-A receptor 4, SAM domain (EphA4_SAM)
Type: Domain

This entry represents the SAM domain of EPH-A4. It is a C-terminal potential protein-protein interaction domain .

Ephrin receptors (Ephs) are a group of receptor tyrosine kinases that are activated in response to binding ephrin ligands residing on adjacent cells, leading to contact-dependent bidirectional signalling into neighbouring cells .

Ephrin type-A receptor 4 (EphA4) is highly promiscuou; it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands . It is involved in development , supporting spine maturation , axon guidance and assembly of neuronal locomotor circuits . EphA4 is the most abundant ephrin receptor in the nervous system. Mice lacking the EphA4 exhibit pronounced axonal regeneration and functional recovery following spinal cord injury . In humans EphA4 has been proposed to be a key actor in neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) . Inhibition of the EphA4-ephrin interaction has been considered as a useful strategy for promoting axon regeneration in the nervous system and a pharmacological tool to treat neurodegenerative disease patients .
Kelch-like protein 18, BTB/POZ domain (KLHL18_BTB/POZ)
Type: Domain

This entry represents the BTB/POZ domain found in Kelch-like protein 18 (KLHL18), which belongs to the KLHL family .

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .
Kelch-like protein 31, BTB/POZ domain (BTB_POZ_KLHL31)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

Kelch-like protein 31 (KLHL31) is also called BTB and kelch domain-containing protein 6 (BKLHD6), Kelch repeat and BTB domain-containing protein 1 (KBTBD1) . It is a transcriptional repressor in the MAPK/JNK signaling pathway to regulate cellular functions . Its overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). It is linked to skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5 .

This entry represents the BTB/POZ domain of KLHL31, a common protein-protein interaction module of about 100 amino acids.
Kelch-like protein 5, BTB/POZ domain (KLHL5_BTB/POZ)
Type: Domain

This entry represents the BTB/POZ domain found in Kelch-like protein 5 (KLHL5), which belongs to the KLHL family . The function of KLHL5 is not clear .

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .
Kelch-like protein 40, BTB/POZ domain (KLHL40_BTB/POZ_dom)
Type: Domain

Kelch-like protein 40 (KLHL40, also known as Kbtbd5) belongs to the KLHL family . Mutations in the KLHL40 gene cause severe autosomal-recessive nemaline myopathy, which is a congenital myopathy that can result in lethal muscle dysfunction . Kbtbd5 may serve as an adapter in the Cul3-dependent ubiquitin ligase complex during myogenic differentiation .

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of KLHL40.
Kelch-like protein 10, BTB/POZ domain (KLHL10_BTB/POZ)
Type: Domain

Kelch-like protein 10 (KLHL10) belongs to the KLHL family . It may serve as an adapter in the Cul3-dependent ubiquitin ligase complex during spermatogenesis. It is required for male fertility in mice .

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .
Kelch-like protein 33, BACK domain (KLHL33_BACK)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

This entry represents the BACK domain of Kelch-like protein 33 (KLHL33) , whose function is not clear.
Aurora kinase A (AURKA)
Type: Domain

Aurora kinase A (AURKA, also known as Aurora 2) is a mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. It associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in regulating centrosome maturation and separation and bipolar spindle assembly . It also plays an important role in the spindle checkpoint regulation . Aurora A promotes mitotic entry by controlling activation of Cyclin-B/Cdk-1. It regulates the progression of mitosis by phosphorylation of multiple substrates, such as Polo-like kinase-1, ajuba, enhancer of filamentation 1, BORA, TPX2, PLK-1, astrin, growth arrest and DNA damage-inducible 45alpha, transforming acidic coiled-coil containing protein 3 (TACC3) and centrosomin . During mitotic exit, AURKA is targeted for degradation through its interaction with the multi-subunit E3-ubiquitin ligase anaphase promoting complex/cyclosome (APC/C) .

The Aurora kinases are highly conserved serine/threonine kinases that regulate chromosomal alignment and segregation during mitosis and meiosis. Three mammalian Aurora kinases, Aurora A, B and C, have been identified. They all contain a protein kinase domain and a destruction box (D-box) recognised by the multi-subunit E3-ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), which mediates their proteasomal degradation. However, their N-terminal domain share little sequence identity and confer unique protein-protein interaction abilities among the Aurora kinases . They are differentially expressed at high levels in rapidly dividing tissues such as hematopoietic cells (A and B) and germ cells (C only). Their expression is low or absent in most adult tissues due to their lower rates of proliferation .