SII-SWORD/CoKE huggingface dataset:
Photosystem antenna protein-like superfamily (PS_II_antenna-like_sf)
Type: Homologous_superfamily

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This entry represents the intrinsic antenna proteins CP43 (PsbC) and CP47 (PsbB) found in the reaction centre of PSII. These polypeptides bind to chlorophyll a and beta-carotene and pass the excitation energy on to the reaction centre . This entry also includes the iron-stress induced chlorophyll-binding protein CP43' (IsiA), which evolved in cyanobacteria from a PSII protein to cope with light limitations and stress conditions. Under iron-deficient growth conditions, CP43' associates with PSI to form a complex that consists of a ring of 18 or more CP43' molecules around a PSI trimer, which significantly increases the light-harvesting system of PSI. IsiA can also provide photoprotection for PSII .
Stathmin superfamily (Stathmin_sf)
Type: Homologous_superfamily

Stathmin (from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules . However, when phosphorylated, its destabilisation ability is significantly reduced .
MTMR7, PH-GRAM domain (MTMR7_PH-GRAM)
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 PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. This entry represents the PH-GRAM domain of MTMR7.
MTMR10, PH-GRAM domain (MTMR10_PH-GRAM)
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.

MTMR10 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, and a SET interaction domain. It contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. This entry represents the PH-GRAM domain of MTMR10.
Creatinase/aminopeptidase-like (Creatinase/aminopeptidase-like)
Type: Homologous_superfamily

This entry contains proteins that belong to MEROPS peptidase family M24 (clan MG), which share a common structural-fold, the "pita-bread" fold. The fold contains both α helices and an anti-parallel β sheet within two structurally similar domains that are thought to be derived from an ancient gene duplication. The active site, where conserved, is located between the two domains. The fold is common to methionine aminopeptidase (

), aminopeptidase P (

), prolidase (

), agropine synthase and creatinase (

). Though many of these peptidases require a divalent cation, creatinase is not a metal-dependent enzyme .
TBC1D8, PH-GRAM domain 1 (TBC1D8_PH-GRAM1)
Type: Domain

TBC1D8 may act as a GTPase-activating protein for Rab family protein(s). TBC1D8 contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the first repeat of the PH-GRAM domain. The domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
2Fe-2S ferredoxin-like superfamily (2Fe-2S_ferredoxin-like_sf)
Type: Homologous_superfamily

Ferredoxins are small, acidic, electron transfer proteins that are ubiquitous in biological redox systems. They have either 4Fe-4S, 3Fe-4S, or 2Fe-2S cluster. Among them, ferredoxin with one 2Fe-2S cluster per molecule are present in plants, animals, and bacteria, and form a distinct Ferredoxin family . They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe-2S cluster is ligated. This conserved region is also found as a domain in various metabolic enzymes.

Several structures of the 2Fe-2S ferredoxin-type domain have been determined . The domain is classified as a β-grasp, which is characterised as having a β-sheet comprised of four β-strands and one α-helix flanking the sheet. The two Fe atoms are coordinated tetrahedrally by the two inorganic S atoms and four cysteinyl S atoms.
TBC1D8B, PH-GRAM domain 1 (TBC1D8B_PH-GRAM1)
Type: Domain

TBC1D8B may act as a GTPase-activating protein for Rab family protein(s). TBC1D8B contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
Band 7/SPFH domain superfamily (Band_7/SPFH_dom_sf)
Type: Homologous_superfamily

The band-7 protein family comprises a diverse set of membrane-bound proteins characterised by the presence of a conserved domain, the band-7 domain, also known as SPFH or PHB domain . The exact function of the band-7 domain is not known, but examples from animal and bacterial stomatin-type proteins demonstrate binding to lipids and the ability to assemble into membrane-bound oligomers that form putative scaffolds . A variety of proteins belong to this family. These include the prohibitins, cytoplasmic anti-proliferative proteins and stomatin, an erythrocyte membrane protein. Bacterial HflC protein also belongs to this family.

Note: Band 4.1 and Band 7 proteins refer to human erythrocyte membrane proteins separated by SDS polyacrylamide gels and stained with coomassie blue .
TCB1D9/TCB1D9B, PH-GRAM domain 1 (TCB1D9/TCB1D9B_PH-GRAM1)
Type: Domain

TBC1D9 and TCB1D9B may act as GTPase-activating proteins for Rab family protein(s). TBC1D9 and TCB1D9B contain two N-terminal PH-GRAM domains and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the first repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
TBC1D8B, PH-GRAM domain 2 (TBC1D8B_PH-GRAM2)
Type: Domain

TBC1D8B may act as a GTPase-activating protein for Rab family protein(s). TBC1D8B contains an N-terminal PH-GRAM domain and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
TBC1D8, PH-GRAM domain 2 (TBC1D8_PH-GRAM2)
Type: Domain

TBC1D8 may act as a GTPase-activating protein for Rab family protein(s). TBC1D8 contains two N-terminal PH-GRAM domains and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
TCB1D9/TCB1D9B, PH-GRAM domain 2 (TCB1D9/TCB1D9B_PH-GRAM2)
Type: Domain

TBC1D9 and TCB1D9B may act as a GTPase-activating proteins for Rab family protein(s). TBC1D9 and TCB1D9B contain two N-terminal PH-GRAM domains and a C-terminal Rab-GTPase-TBC (Tre-2, BUB2p, and Cdc16p) domain. This entry represents the second repeat of the PH-GRAM domain. The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. The GRAM domain is part of a larger motif with a pleckstrin homology (PH) domain fold .
Plant myosin, class XI, motor domain (MYSc_Myo11)
Type: Domain

Plant-specific type XI myosins are involved in organelle transport . The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. It is a molecular motor, which utilizes ATP hydrolysis to generate directed movement toward the plus end along actin filaments .
Large-conductance mechanosensitive channel MscL (MscL_channel)
Type: Homologous_superfamily

Mechanosensitive ion channels (MscL) play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. MscL is a protein which forms a channel organised as a homopentamer, with each subunit containing two transmembrane regions . Prokaryotes harbor a large-conductance mechanosensitive channel (gene mscL) that opens in response to stretch forces in the membrane lipid bilayer and participate in the regulation of osmotic pressure changes within the cell . MscL has a conserved domain architecture which comprises an amphipathic α-helix (S1) that lies along the cytoplasmic membrane, a highly conserved first transmembrane domain (TM1) that forms the pore constriction, a periplasmic loop, a second transmembrane domain (TM2) that faces the lipid membrane, and a linker that leads to a cytoplasmic α-helical bundle .
WW domain superfamily (WW_dom_sf)
Type: Homologous_superfamily

The WW domain is a short conserved region in a number of unrelated proteins, which folds as a stable, triple stranded β-sheet. This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins . The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a conserved Pro. The WW domain binds to proteins with particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs . It is frequently associated with other domains typical for proteins in signal transduction processes.

A large variety of proteins containing the WW domain are known. These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein of unknown function; vertebrate YAP protein, substrate of an unknown serine kinase; Mus musculus (Mouse) NEDD-4, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae (Baker's yeast) RSP5, similar to NEDD-4 in its molecular organisation; Rattus norvegicus (Rat) FE65, a transcription-factor activator expressed preferentially in liver; Nicotiana tabacum (Common tobacco) DB10 protein, amongst others.
Aldehyde ferredoxin oxidoreductase-like, C-terminal (Tungsten_al_ferr_oxy-like_C)
Type: Homologous_superfamily

Enzymes of the aldehyde ferredoxin oxidoreductase (AOR) family contain a tungsten cofactor and an 4Fe4S cluster and catalyse the interconversion of aldehydes to carboxylates . This family includes AOR, formaldehyde ferredoxin oxidoreductase (FOR), glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), all isolated from hyperthermophilic archea ; carboxylic acid reductase found in clostridia ; and hydroxycarboxylate viologen oxidoreductase from Proteus vulgaris, the sole member of the AOR family containing molybdenum . GAPOR may be involved in glycolysis , but the functions of the other proteins are not yet clear. AOR has been proposed to be the primary enzyme responsible for oxidising the aldehydes that are produced by the 2-keto acid oxidoreductases .

This entry represents the C-terminal region of the the aldehyde ferredoxin oxidoreductase (AOR) family enzymes, containing the α-helical structural domains 2 and 3 .
Plant myosin class VIII, motor domain (MYSc_Myo8)
Type: Domain

These plant-specific type VIII myosins has been associated with endocytosis, cytokinesis, cell-to-cell coupling and gating at plasmodesmata . The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases.
Class IX myosin, motor domain (MYSc_Myo9)
Type: Domain

Myosin IX is a processive single-headed motor, which might play a role in signalling. Class IX myosins contain a GTPase-activating protein (GAP) domain in their tail region, which allows them to negatively regulate small Rho GTPases . This entry represents the catalytic (head) domain, which has ATPase activity and belongs to the larger group of P-loop NTPases. The single head of class IX myosin exhibits characteristics of a processive motor .
Somatomedin B-like domain superfamily (Somatomedin_B-like_dom_sf)
Type: Homologous_superfamily

Somatomedin B (SMB), a serum factor of unknown function, is a small cysteine-rich peptide, derived proteolytically from the N terminus of the cell-substrate adhesion protein vitronectin . Cys-rich somatomedin B-like domains are found in a number of proteins , including ectonucleotide pyrophosphatase/phosphodiesterase family member proteins (previously known as plasma-cell membrane glycoprotein) and placental protein 11 (also known as Poly(U)-specific endoribonuclease), which appears to possess amidolytic activity.

The SMB domain of vitronectin has been demonstrated to interact with both the urokinase receptor and the plasminogen activator inhibitor-1 (PAI-1) and the conserved cysteines of the NPP1 somatomedin B-like domain have been shown to mediate homodimerisation .

The SMB domain contains eight Cys residues, arranged into four disulphide bonds. It has been suggested that the active SMB domain may be permitted considerable disulphide bond heterogeneity or variability, provided that the Cys25-Cys31 disulphide bond is preserved. The three dimensional structure of the SMB domain is extremely compact and the disulphide bonds are packed in the centre of the domain forming a covalently bonded core . The structure of the SMB domain presents a new protein fold, with the only ordered secondary structure being a single-turn α-helix and a single-turn 3(10)-helix .
tRNA-splicing ligase RtcB-like superfamily (RtcB-like_sf)
Type: Homologous_superfamily

RctB is a RNA ligase that mediates the joining of broken tRNA-like stem-loop structures in case of tRNA damage. It probably participates to tRNA restriction-repair by ligating broken tRNA-like stem-loop structures with 2',3'-cyclic phosphate and 5'-OH ends to form a splice junction with a 2'-OH, 3',5'-phosphodiester . In worms, this protein has as a neuroprotective role in the age-dependent degeneration of dopamine neurons .
Seven-hairpin glycosidases (Seven-hairpin_glycosidases)
Type: Homologous_superfamily

Glycoside hydrolase family 47

comprises enzymes with only one known activity; alpha-mannosidase (

).

Alpha-mannosidase is involved in the maturation of Asn-linked oligo-saccharides . The enzyme hydrolyses terminal 1,2-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide man(9)(glcnac)(2) in a calcium-dependent manner. The mannose residues are trimmed away to produce, first, man(8)glcnac(2), then a man(5)(glcnac)(2) structure.

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
SH3-like domain superfamily (SH3-like_dom_sf)
Type: Homologous_superfamily

SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues . They are found in a great variety of intracellular or membrane-associated proteins for example, in a variety of proteins with enzymatic activity, in adaptor proteins, such as fodrin and yeast actin binding protein ABP-1.

The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β-sheets. The linker regions may contain short helices. The surface of the SH3-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions. The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes .

The crystal structure of the SH3 domain of the cytoskeletal protein spectrin, and the solution structures of SH3 domains of phospholipase C (PLC-y) and phosphatidylinositol 3-kinase p85 alpha-subunit, have been determined . In spite of relatively limited sequence similarity, their overall structures are similar. The domains belong to the α+β structural class, with five to eight β-strands forming 2 tightly-packed, anti-parallel β-sheets arranged in a barrel-like structure, and intervening loops sometimes forming helices. Conserved aliphatic and aromatic residues form a hydrophobic core (A11, L23, A29, V34, W42, L52 and V59 in PLC-y ) and a hydrophobic pocket on the molecular surface (L12, F13, W53 and P55 in PLC-y). The conserved core is believed to stabilise the fold, while the pocket is thought to serve as a binding site for target proteins. Conserved carboxylic amino acids located in the loops, on the periphery of the pocket (D14 and E22), may be involved in protein-protein interactions via proline-rich regions. The N- and C-terminal are packed in close proximity, indicating that they are independent structural modules.
Class XX myosin, motor domain (MYSc_Myo20)
Type: Domain

These class XX myosins are primarily insect myosins with such members as Drosophila, Daphnia, and mosquitoes. Class XX myosin in Drosophila (DmMyo20) is encoded by dash, which functions as a downstream component of the Fat signaling pathway, influencing growth and gene expression during development . These myosins contain a motor domain followed by a single IQ motif. The motor (head) domain of DmMyo20 does not does not function as a molecular motor. Instead, it binds to actin filaments in an ATP-independent manner and enhances the interaction between actin filaments and protein Zyx102, a downstream component of the Fat pathway .
PDZ superfamily (PDZ_sf)
Type: Homologous_superfamily

PDZ domains (also known as Discs-large homologous regions (DHR) or GLGF)) are found in diverse signalling proteins in bacteria, yeasts, plants, insects and vertebrates . PDZ domains can occur in one or multiple copies and are nearly always found in cytoplasmic proteins. They bind either the carboxyl-terminal sequences of proteins or internal peptide sequences . In most cases, interaction between a PDZ domain and its target is constitutive, with a binding affinity of 1 to 10 microns. However, agonist-dependent activation of cell surface receptors is sometimes required to promote interaction with a PDZ protein. PDZ domain proteins are frequently associated with the plasma membrane, a compartment where high concentrations of phosphatidylinositol 4,5-bisphosphate (PIP2) are found. Direct interaction between PIP2 and a subset of class II PDZ domains (syntenin, CASK, Tiam-1) has been demonstrated.
Class XIX myosin, motor domain (MYSc_Myo19)
Type: Domain

Monomeric myosin-XIX (Myo19) functions as an actin-based motor for mitochondrial movement in vertebrate cells . It contains a variable number of IQ domains. Human myo19 contains a motor domain, three IQ motifs, and a short tail . The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases. The head domain is a molecular motor with actin-activated ATPase activity .
SOCS box-like domain superfamily (SOCS_box-like_dom_sf)
Type: Homologous_superfamily

The SOCS box was first identified in SH2-domain-containing proteins of the suppressor of cytokines signalling (SOCS) family but was later also found in:

the WSB (WD-40-repeat-containing proteins with a SOCS box) family,

the SSB (SPRY domain-containing proteins with a SOCS box) family,

the ASB (ankyrin-repeat-containing proteins with a SOCS box) family,

and ras and ras-like GTPases .

The SOCS box found in these proteins is an about 50 amino acid C-terminal domain composed of two blocks of well-conserved residues separated by between 2 and 10 non-conserved residues . The C-terminal conserved region is an L/P-rich sequence of unknown function, whereas the N-terminal conserved region is a consensus BC box , which binds to the Elongin BC complex . It has been demonstrated that this association couple bound proteins to the ubiquitination or proteasomal compartments .
Class XVII myosin, motor domain (MYSc_Myo17)
Type: Domain

Mcs1, also known as chitin synthase 8, is a fungal protein that contains a myosin-17 motor domain and can travel along both microtubules and F-actin. Mcs1 works in cooperation with myosin-5 and kinesin-1 and in opposition to dynein in the secretion of cell wall-forming fungal chitin synthases. Successful exocytosis requires the motor domain of Mcs1, which captures and tethers the vesicles prior to secretion .