SII-SWORD/CoKE huggingface dataset:
Kelch-like protein 25, BTB/POZ domain (KLHL25_BTB_POZ_dom)
Type: Domain

Kelch-like protein 25 (KLHL25, also known as ENC-2) serves as a substrate-specific adapter in the Cul3-dependent ubiquitin ligase complex that targets hypophosphorylated 4E-BP1 (4E-binding protein 1) for degradation . 4E-BPs regulate the activity of eIF4E, a mRNA 5' cap-binding protein and a major target for translational control .

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 found in KLHL25.
Kelch-like protein 23, BTB/POZ domain (BTB_POZ_KLHL23)
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 23 (KLHL23) belongs to the KLHL family . KLHL23 overexpression is associated with increased cell proliferation and invasion in gastric cancer. Downregulation of KLHL23 is associated with invasion, metastasis, and poor prognosis of hepatocellular carcinoma and pancreatic cancer . This entry represents the BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.
Kelch-like protein 38, BACK domain (KLHL38_BACK)
Type: Domain

Kelch-like protein 38 (KLHL38) belongs to the KLHL family . Its function 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 32, BTB/POZ domain (BTB_POZ_KLHL32)
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 32 (KLHL32), also called BTB and kelch domain-containing protein 5 (BKLHD5) , contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. Deletion of KLHL32 may be associated with Tourette syndrome and obsessive-compulsive disorder . Its function is not clear.

This entry represents the BTB/POZ domain of KLHL32, a common protein-protein interaction module of about 100 amino acids.
Kelch-like protein 41/41b, BTB/POZ domain (KLHL41_KL41B_BTB_POZ_dom)
Type: Domain

This entry represents the N-terminal BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of mammal KLHL41, fish KL41B and related proteins from vertebrates.

Kelch-like protein 41 (KLHL41), also known as sarcosin or Krp1, is involved in skeletal muscle development and differentiation . KLHL41 binds to Nebulin, an actin-binding protein that regulates the actin filament length. It also binds Nebulin-related anchoring protein (N-RAP), an actin-binding protein expressed in skeletal and cardiac muscle tissues . KLHL41 is localised between laterally fusing myofibrils in adult skeletal muscle and plays an important role in the correct functioning of adult skeletal muscle cells . Mutations in its gene lead to nemaline myopathy-9 (NEM9), a muscle disorder characterised by the onset of muscle weakness in early infancy .

This group of proteins also includes the orthologue from fish Kelch-like protein 41b (KL41B), which is involved in skeletal muscle development and maintenance .

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 .
MTMR7, protein tyrosine phosphatase domain (MTMR7_PTP)
Type: Domain

Myotubularin-related protein 7 (MTMR7) is a member of the myotubularin (MTM) family. MTMR9 is a binding partner of MTMR7, and binding of MTMR9 increases the phosphatase activity of MTMR7 . MTMR9 and MTMR7 may be involved in regulating T-helper (Th) cells differentiation .

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 .

MTMR7 contains a N-terminal PH-GRAM domain (

), a Rac-induced recruitment domain (RID) domain, an active Protein Tyrosine Phosphatase (PTP) domain (this entry), a SET-interaction domain, and a C-terminal coiled-coil region.
Myotubularin-related protein 10, protein tyrosine phosphatase domain (MTMR10_PTP)
Type: Domain

The family of myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain . Myotubularin-related protein 10 (MTMR10) is a probable pseudophosphatase.

This entry represents the inactive Protein Tyrosine Phosphatase (PTP) domain of MTMR10 .
Kelch-like protein 22, BACK domain (KLHL22_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 .

Kelch-like protein 22 (KLHL22) is a substrate-specific adaptor of the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. It targets Polo-like kinase 1 (PLK1) and regulates its kinetochore localisation during mitosis . The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation .
Myotubularin-related protein 12, protein tyrosine phosphatase-like pseudophosphatase domain (MTMR12_PTP)
Type: Domain

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 .

Myotubularin-related protein 12 (MTMR12), also known 3-phosphatase adapter protein (3-PAP), belongs to the myotubularin family. It is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularin intracellular location . Knockdown of the mtmr12 gene in zebrafish results in skeletal muscle defects and impaired motor function .

This entry represents the protein tyrosine phosphatase-like pseudophosphatase domain of MTMR12.
Kelch-like protein 21, BTB/POZ domain (BTB/POZ_KLHL21)
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 21 (KLHL21) is a substrate adaptor protein in the Cul3-KLHL21 E3 ubiquitin ligase complex required for efficient chromosome alignment and cytokinesis. During cytokinesis, it localises to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region . KLHL21 also targets IkappaB kinase-beta to regulate nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) signaling negatively . This entry represents the BTB/POZ domain.
Kelch-like protein 3, BACK domain (KLHL3_BACK)
Type: Domain

Kelch-like protein 3 (KLHL3) is a substrate adaptor protein in the CUL3-KLHL3 E3 ubiquitin ligase complex. It targets WNK4 kinase 1 for ubiquitination and degradation, which in turn regulates electrolyte homeostasis . Mutations in the KLHL3 gene cause cause pseudohypoaldosteronism type II (PHAII), which is a rare Mendelian syndrome featuring hypertension and hyperkalemia resulting from constitutive renal salt reabsorption and impaired K(+) secretion . The CUL3-KLHL3 E3 ligase complex may regulate blood pressure via its ability to interact with and ubiquitylate WNK isoforms .

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 (BTB and C-terminal Kelch) domain of KLHL3.
Gigaxonin, BACK domain (KLHL16_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 .

Gigaxonin (also known as KLHL16) regulates microtubule-associated protein 1B (MAP1B), which is involved in maintaining the integrity of cytoskeletal structures and promoting neuronal stability . Gigaxonin belongs to the KLHL family. Mutations in the gigaxonin gene cause giant axonal neuropathy (GAN), which is a devastating sensory and motor neuropathy . Gigaxonin binds to the ubiquitin-activating enzyme E1 through its N-terminal BTB domain, while the carboxy-terminal kelch repeat domain interacts directly with the light chain (LC) of MAP1B. It may serve as an ubiquitin substrate adaptor protein that controls MAP1B-LC degradation . This entry represents the BACK domain of gigaxonin, localized between the BTB the kelch repeats domains.
Kelch-like protein 30, BACK domain (KLHL30_BACK)
Type: Domain

Kelch-like protein 30 (KLHL30) belongs to the KLHL family . Its function 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 14, BTB/POZ domain (KLHL14_BTB_POZ)
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 14 (KLHL14) belongs to the KLHL family . Its is also known as Printor (protein interactor of torsinA). It selectively binds to the ATP-free form, but not to the ATP-bound form of torsinA, suggesting a role for Printor as a cofactor rather than a substrate of the AAA+ protein torsinA and is implicated in dystonia pathogenesis .

This entry represents the BTB/POZ domain of KLHL14, a common protein-protein interaction module of about 100 amino acids.
Kelch repeat and BTB domain-containing protein 2, BTB/POZ domain (BTB_POZ_KBTBD2)
Type: Domain

KBTBD2, also called BTB and kelch domain-containing protein 1 (BKLHD1), plays an essential role in the regulation of insulin-signaling pathway. It is a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase, which targets p85alpha, the regulatory subunit of the phosphoinositol-3-kinase (PI3K) heterodimer, causing p85alpha ubiquitination and proteasome-mediated degradation. This entry represents the BTB/POZ domain .

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 .
MTMR1, protein tyrosine phosphatase domain (MTMR1_PTP)
Type: Domain

MTMR1 (myotubularin-related protein 1) is a lipid phosphatase that uses phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] as substrates . MTMR1 is abnormally expressed in myotonic dystrophy type1 (DM1) and in myotonic dystrophy type 2 (DM2), in correlation with muscle pathological features .

This entry represents the active Protein Tyrosine Phosphatase (PTP) domain of MTMR1. This large domain is composed of seven β-strands and sixteen α-helices .

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 .