SII-SWORD/CoKE huggingface dataset:
FRMD4A/B, FERM domain C-lobe (FRMD4A/B_FERM_C)
Type: Domain

FERM domain-containing protein 4A (FRMD4A) is part of the Par-3/FRMD4A/cytohesin-1 complex that activates Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodelling and epithelial polarization. The Par-3/Par-6/aPKC/Cdc42 complex regulates the conversion of primordial adherens junctions (AJs) into belt-like AJs and the formation of linear actin cables. When primordial AJs are formed, Par-3 recruits scaffolding protein FRMD4A which connects Par-3 and the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-1 .

FERM domain-containing protein 4B (FRMD4B, also called GRP1-binding protein, GRSP1) is a novel member of GRP1 signalling complexes that are recruited to plasma membrane ruffles in response to insulin receptor signalling. The GRSP1/FRMD4B protein contains a FERM protein domain as well as two coiled coil domains and may function as a scaffolding protein. GRP1 and GRSP1 interact through the coiled coil domains in the two proteins .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites .
Shewanella-like phosphatase, metallophosphatase domain (MPP_Shelphs)
Type: Domain

Shewanella-like protein phosphatase (SLP phosphatase) is highly conserved in all plants, mosses, and green algae, with members also found in select fungi, protists, and bacteria. This entry includes nucleus-encoded Arabidopsis SLP phosphatases, AtSLP1 and AtSLP2 . This entry also includes cold-active protein-tyrosine phosphatase (CAPTPase) from Shewanella sp. .
FARP1/FARP2/FRMD7, FERM domain C-lobe (FARP1/FARP2/FRMD7_FERM_C)
Type: Domain

Proteins containing this domain include FARP1, FARP2 and FRMD7. FARP1 and FARP2 are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases . FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons . They are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains.

FRMD7 (FERM domain-containing protein 7) and Caenorhabditis elegans CFRM3 have a FERM domain that is closely related to that in FARP1 and FARP2. Both have unknown functions. They contain an N-terminal FERM domain, a PH domain, followed by a FA (FERM adjacent) domain . FRMD7 has been linked to Idiopathic congenital nystagmus , an infant-onset disease with the typical features of bilateral ocular oscillations, visual impairment, and abnormal head movement .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites .
ERM family, FERM domain C-lobe (ERM_FERM_C)
Type: Domain

This entry represents the C-lobe of FERM domain found in the ERM family members, including ezrin, radixin, moesin and merlin. They are composed of a N-terminal FERM (ERM) domain, a coiled coil region (CRR), and a C-terminal domain CERMAD (C-terminal ERM association domain) which has an F-actin-binding site (ABD). Two actin-binding sites have been identified in the middle and N-terminal domains. Merlin is structurally similar to the ERM proteins, but instead of an actin-binding domain (ABD), it contains a C-terminal domain (CTD), just like the proteins from the 4.1 family. Activated ezrin, radixin and moesin are thought to be involved in the linking of actin filaments to CD43, CD44, ICAM1-3 cell adhesion molecules, various membrane channels and receptors, such as the Na+/H+ exchanger-3 (NHE3), cystic fibrosis transmembrane conductance regulator (CFTR), and the beta2-adrenergic receptor . The ERM proteins exist in two states, a dormant state in which the FERM domain binds to its own C-terminal tail and thereby precludes binding of some partner proteins, and an activated state, in which the FERM domain binds to one of many membrane binding proteins and the C-terminal tail binds to F-actin .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites .
MYLIP, FERM domain C-lobe (MYLIP_FERM_C)
Type: Domain

MYLIP/IDOL is a regulator of the LDL receptor (LDLR) pathway via the nuclear receptor liver X receptor (LXR). In response to cellular cholesterol loading, the activation of LXR leads to the induction of MYLIP expression. MYLIP stimulates ubiquitination of the LDLR on its cytoplasmic tail, directing its degradation. The LXR-MYLIP-LDLR pathway provides a complementary pathway to sterol regulatory element-binding proteins for the feedback inhibition of cholesterol uptake. MYLIP has an N-terminal FERM domain and in some cases a C-terminal RING domain .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites .
Krev interaction trapped protein 1, FERM domain C-lobe (KRIT1_FERM_C)
Type: Domain

KRIT1, also known as CCM1, a Rap1-binding protein, is expressed in endothelial cells where it is present in cell-cell junctions and associated with junctional proteins . Together with CCM2/MGC4607 and CCM3/PDCD10, KRIT1 constitutes a set of proteins, mutations of which are found in cerebral cavernous malformations which are characterised by cerebral haemorrhages and vascular malformations in the central nervous system. KRIT-1 possesses four ankyrin repeats, a FERM domain, and multiple NPXY sequences, one of which is essential for integrin cytoplasmic domain-associated protein-1alpha (ICAP1alpha) binding and all of which mediate binding of CCM2. KRIT-1 localisation is mediated by its FERM domain .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites .
Purple acid phosphatase, metallophosphatase domain (MPP_PAP)
Type: Domain

This entry represents the whole binuclear metal centre domain. It is mainly found in purple acid phosphatases (PAPs) and related acid phosphatases. This domain contains two key components: a Calcineurin-like phosphoesterase domain

, which is a conserved domain found in enzymes that catalyze phosphoester hydrolysis and a Purple acid phosphatase C-terminal domain

, which contributes to the overall structure and function of PAPs. The most conserved regions in the Calcineurin-like domain center around the metal-chelating residues. The structure typically comprises two sandwiched β-sheets flanked by α-helical segments, with the binuclear metal center located at the interface between two symmetrical halves of the molecule. This domain arrangement allows PAPs to perform their characteristic phosphatase activity under acidic conditions .

Purple acid phosphatases (PAPs) (

) are a family of binuclear metallohydrolases that break down phosphate esters and anhydrides in acidic conditions; they have been identified in plants, animals, and fungi. The best-characterised enzyme is from kidney bean, and that enzyme binds Fe
3+
and Zn
2+
ions. The metals bound differ according to source species; for example, the enzyme from sweet potato binds iron and manganese . The structure of the kidney bean enzyme has been solved and shows a disulfide-linked homodimer, with each monomer having a two-domain structure . Human acid phosphatase type 7 is also known as purple acid phosphatase long form. It is associated with bone resorption and microbial killing through its phosphatase activity and hydroxyl radical production . While most of the PAPs are active on a wide range of substrates, some PAPs display higher activity on phytate or 2-phosphoenolpyruvate (PEP) .
Myosin VII, FERM domain C-lobe, repeat 1 (MyoVII_FERM_C1)
Type: Domain

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3) . The C-lobe/F3 within the FERM domain is part of the PH domain family. This entry represents the C-lobe of the MyoVII first FERM domain.

MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1) . Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo .
Myosin VII, FERM domain C-lobe, repeat 2 (MyoVII_FERM_C2)
Type: Domain

MyoVII, a MyTH-FERM myosin, is an actin-based motor protein essential for a variety of biological processes in the actin cytoskeleton function. Mutations in MyoVII leads to problems in sensory perception: deafness and blindness in humans (Usher Syndrome), retinal defects and deafness in mice (shaker 1) . Myosin VIIAs have plus (barbed) end-directed motor activity on actin filaments and a characteristic actin-activated ATPase activity. MyoVII consists of a conserved spectrin-like, SH3 subdomain N-terminal region, a motor/head region, a neck made of 4-5 IQ motifs, and a tail consisting of a coiled-coil domain, followed by a tandem repeat of myosin tail homology 4 (MyTH4) domains and partial FERM domains that are separated by an SH3 subdomain and are thought to mediate dimerization and binding to other proteins or cargo .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3) . The C-lobe/F3 within the FERM domain is part of the PH domain family. This entry represents the C-lobe of the MyoVII second FERM domain.
Myosin-XV, FERM domain C-lobe (MyoXV_FERM_C)
Type: Domain

MyoXV is a MyTH-FERM myosin, which are actin-based motor proteins essential for a variety of biological processes in actin cytoskeleton function. Specifically MyoXV functions in the actin organization in hair cells of the organ of Corti. Mutations in human MyoXVa causes non-syndromic deafness, DFNB3 , and the mouse shaker-2 mutation . MyoXV consists of a N-terminal motor/head region, a neck made of 1-3 IQ motifs, and a tail that consists of either a myosin tail homology 4 (MyTH4) domain followed by an SH3 domain and a MyTH-FERM domain, as in rat Myo15, or two MyTH-FERM domains separated by a SH3 domain as in human Myo15A. The MyTH-FERM domains are thought to mediate dimerization and binding to other proteins or cargo .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3) . This entry represents the C-lobe of the Myo15 FERM domain.
DNA double-strand break repair protein Mre11, N-terminal metallophosphatase domain (Mre11_N)
Type: Domain

Mre11 (also known as SbcD in Escherichia coli) is a subunit of the MRX protein complex. This complex includes: Mre11, Rad50, and Xrs2/Nbs1, and plays a vital role in several nuclear processes including DNA double-strand break repair, telomere length maintenance, cell cycle checkpoint control, and meiotic recombination, in eukaryotes. During double-strand break repair, the MRX complex is required to hold the two ends of a broken chromosome together. In vitro studies show that Mre11 has 3'-5' exonuclease activity on dsDNA templates and endonuclease activity on dsDNA and ssDNA templates . In addition to the N-terminal phosphatase domain, the eukaryotic MRE11 members of this family have a C-terminal DNA binding domain. MRE11-like proteins are found in prokaryotes and archaea was well as in eukaryotes. Mre11 belongs to the metallophosphatase (MPP) superfamily.
Myosin X, FERM domain C-lobe (MyoX_FERM_C)
Type: Domain

MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance . It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.

MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C terminus. The MyoX FERM domain binds to the NPXY motif of several beta-integrins, a key family of cell surface receptors that are involved in cell adhesion and migration. In addition to beta-integrins, the FERM domain binds to the cytoplasmic domains of the netrin receptors DCC (deleted in colorectal cancer) and neogenin . The FERM domain also forms a supramodule with its MyTH4 domain which binds to the negatively charged E-hook region in the tails of alpha- and beta-tubulin forming a proposed motorized link between actin filaments and microtubules .

The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3) . This entry represents the C-lobe of the MyoX FERM domain.
Otoconin-90, phospholipase A2-like domain (Otoconin-90)
Type: Domain

Otoconin-90 (OC90) is a major protein of the otoconia, a calcium carbonate structure in the saccule and utricle of the ear that is essential for perception of gravity and maintenance of balance . OC90 contains two globular domains homologous to secretory phospholipase A2 (PLA2) connected by a linker segment. The PLA2-like domains in otoconins may have lost their metal-binding sites .
Toll-interacting protein, CUE domain (TOLIP_CUE)
Type: Domain

Tollip (Toll-interacting protein) is a component of the IL-1RI pathway which contains an N-terminal C2 domain and a C-terminal CUE domain. Tollip binds to the cytoplasmic TIR domain of IL-1Rs after IL-1 stimulation. It is sufficient for recruitment of IRAK to IL-1Rs and negatively regulates IL-1-induced signaling by inhibiting IRAK phosphorylation. In addition, Tollip directly interacts with toll-like receptors TLR2 and TLR4, and plays an inhibitory role in TLR-mediated cell activation through suppressing phosphorylation and kinase activity of IRAK. Moreover, Tollip can associate with GAT domains of Tom1 and its related proteins Tom1L1 and Tom1L2, and facilitate the recruitment of clathrin onto endosomes .
Activating signal cointegrator 1 complex subunit 2, CUE domain (ASCC2_CUE)
Type: Domain

This entry represents the CUE domain found in ASCC2 and related proteins.
NEDD4-binding protein 2, CUE domain (N4BP2_CUE)
Type: Domain

This entry represents the CUE domain found at the N terminus of N4BP2.
N4BP2 has been identified as BCL-3-binding protein (B3BP), a protein that interacts with the bcl-3 gene product and participates in connecting transcriptional activation and genetic recombination of the Ig gene . In addition to BCL-3, it also interacts with p300/CBP histone acetyltransferases. N4BP2 shows intrinsic ATP binding and hydrolyzing activity. It contains an N-terminal ATP-binding region that is responsible for the interaction with BCL-3 and p300/CBP. N4BP2 also functions as a 5'-polynucleotide kinase that can transfer a phosphate group to the 5' end of DNA and RNA substrates. Moreover, N4BP2 contains a C-terminal MutS-related domain that possesses nicking endonuclease activity and may play a role in DNA mismatch repair (MMR) .
YfcE-like, metallophosphatase domain (MPP_YfcE)
Type: Domain

YfcE is a manganase-dependent metallophosphatase, found in bacteria and archaea, that cleaves bis-p-nitrophenyl phosphate, thymidine 5'-monophosphate-p-nitrophenyl ester, and p-nitrophenyl phosphorylcholine, but is unable to hydrolyze 2',3 ' or 3',5' cyclic nucleic phosphodiesters, and various phosphomonoesters, including p-nitrophenyl phosphate . This entry also includes the Bacilus subtilis YsnB and Methanococcus jannaschii MJ0936 proteins . This domain belongs to the metallophosphatase (MPP) superfamily.
RNA polymerase II degradation factor 1, CUE domain (DEF1_CUE)
Type: Domain

DEF1, also called RRM3-interacting protein 1, is an RNA Polymerase II (RNAPII) degradation factor that may be required to couple arrested RNAPII to the proteasome to facilitate its degradation . It also has a role modulating RNA polymerase II transcription . It contains a CUE domain that is responsible for the binding of ubiquitin.
Vacuolar protein sorting-associated protein 9, CUE domain (Vps9_CUE)
Type: Domain

Vps9 is a cytosolic yeast protein required for localization of vacuolar proteins, such as the soluble vacuolar hydrolases CPY and PrA . It may bind and act as an effector of a Rab GTPase and plays a role in vacuolar protein sorting (VPS) pathway. Vps9 contains a region called GBH domain that is related to mammalian Ras-binding proteins, Rin1 and JC265, and may negatively regulate Ras-mediated signaling in yeast Saccharomyces cerevisiae. This entry represents the N-terminal CUE domain that interacts specifically with monoubiquitin and regulates intramolecular monoubiquitylation .
Acid sphingomyelinase/endopolyphosphatase, metallophosphatase domain (ASMase/PPN1_MPP)
Type: Domain

Acid sphingomyelinase (ASMase) is a ubiquitously expressed phosphodiesterase which hydrolyses sphingomyelin in acid pH conditions to form ceramide, a bioactive second messenger, as part of the sphingomyelin signalling pathway. ASMase is localised at the noncytosolic leaflet of biomembranes (for example the luminal leaflet of endosomes, lysosomes and phagosomes, and the extracellular leaflet of plasma membranes) . ASMase-deficient humans develop Niemann-Pick disease . This disease is characterised by lysosomal storage of sphingomyelin in all tissues. Although ASMase-deficient mice are resistant to stress-induced apoptosis, they have greater susceptibility to bacterial infection . The latter correlates with defective phagolysosomal fusion and antibacterial killing activity in ASMase-deficient macrophages .
Polyadenylate-binding protein-interacting protein 5/6/7, CUE domain (CID5/6/7_CUE)
Type: Domain

This entry represents the CUE domain found in a group of plant proteins, including CID5/6/7. CID7 contains an N-terminal PABC-interacting domain (PAM2 or PABP-interacting motif 2) which is also found in the human Paip1 and Paip2. It functions as an interaction partner of the PABC domain of Arabidopsis thaliana Poly(A)-binding proteins. It also harbours an ubiquitin-associated (UBA)-like CUE domain and a C-terminal small MutS-related (SMR) domain . CID5 (also known as IPD1) has been shown to regulate the endocycle leading to hypocotyl elongation . The biological function of CID6 is unclear.
Cue5/Don1, CUE domain (Cue5/Don1_CUE)
Type: Domain

This entry represents the CUE domain found in fungal Cue5 protein and its paralogue, Don1. Cue5 contains a CUE domain which exhibits weak ubiquitin binding properties. Cue5 can function as a ubiquitin-ATG8 adapter and thus mediating autophagic clearance of ubiquitin conjugates under starvation conditions . Don1 is a subunit of the leading edge protein (LEP) complex (Ssp1-Ady3-Don1-Irc10) that forms a ring-like structure at the leading edge of the prospore membrane (PSM) during meiosis II .
CUE domain-containing protein 3, CUE domain (Cue3_CUE)
Type: Domain

This entry represents the CUE domain found in fungal Cue3 proteins. Cue3 may be involved in the intramolecular monoubiquitination . This domain can also be found in uncharacterised proteins from invertebrates.