SII-SWORD/CoKE huggingface dataset:
Probable oxidoreductase YoaE, C-terminal (YoaE_C)
Type: Domain

This domain is a conserved molybdopterin-binding C-terminal region found in probable oxidoreductase YoaE and related proteins.

The MopB domain is found in a wide variety of molybdenum- and tungsten-containing enzymes, including formate dehydrogenase-H (Fdh-H) and -N (Fdh-N), several forms of nitrate reductase (Nap, Nas, NarG), dimethylsulfoxide reductase (DMSOR), thiosulfate reductase, formylmethanofuran dehydrogenase, and arsenite oxidase. Molybdenum is present in most of these enzymes in the form of molybdopterin, a modified pterin ring with a dithiolene side chain, which is responsible for ligating the Mo. In many bacterial and archaeal species, molybdopterin is in the form of a dinucleotide, with two molybdopterin dinucleotide units per molybdenum. These proteins can function as monomers, heterodimers, or heterotrimers, depending on the protein and organism .
E3 ubiquitin-protein ligase MSL2 (MSL2)
Type: Family

E3 ubiquitin-protein ligase MSL2 (MSL2; [ec:6.3.2.-]) is an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. It is a component of MSL complex, first identified in Drosophila . MSL2 is a putative DNA-binding protein required for X chromosome dosage compensation in Drosophila males. Its expression is sex specifically regulated by Sex-lethal. Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3 are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation). MSL2 plays a critical role in translation and/or stability of MSL1 in males. In complex with MSL1, it acts as an E3 ubiquitin ligase that promotes ubiquitination of histone H2B. MSL2 contains a C3HC4-type RING-HC finger and a metallothionein-like domain with eight conserved and two non-conserved cysteines, as well as a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions

The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 .
Transcription regulator HTH-like (HTH-like)
Type: Homologous_superfamily

Numerous bacterial transcription regulatory proteins bind DNA via a helix-turn-helix (HTH) motif. This entry defines the ligand-binding and dimerisation domain of HTH-type transcriptional regulators.
Pelle, death domain (Pelle_death)
Type: Domain

This entry represents the death domain (DD) of the protein kinase Pelle from Drosophila melanogaster and similar proteins . In Drosophila, interaction between the DDs of Tube and Pelle is an important component of the Toll pathway, which functions in establishing dorsoventral polarity in embryos and in mediating innate immune responses to pathogens. Tube and Pelle transmit the signal from the Toll receptor to the Dorsal/Cactus complex . Pelle also functions in photoreceptor axon targeting .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Flagellar hook-basal body protein, FlgE/F/G-like (FlgE/F/G-like)
Type: Homologous_superfamily

This superfamily represents three closely related flagellar proteins usually denoted FlgE, FlgF and FlgG.

The basal body, found in FlgF and FlgG, constitutes a major portion of the flagellar apparatus of proteobacteria and spirochete. It consists of four rings (L,P,S, and M) mounted on a central rod . The flagellar hook, found in FlgE, is a short, curved, extracellular structure located between the basal body and the filament of the protein . The rod and hook are directly connected to each other. Their subunit proteins have similar folds, but differences in the domain orientations result in the distinct mechanical functions of the flagellar rod and hook .
CRADD, Death domain (CRADD_Death)
Type: Domain

This is the death domain of RAIDD (RIP-associated ICH-1 homologous protein with a death domain), also known as CRADD (Caspase and RIP adaptor). RAIDD is an adaptor protein that together with the p53-inducible protein PIDD and caspase-2, forms the PIDDosome complex, which is required for caspase-2 activation and plays a role in mediating stress-induced apoptosis. RAIDD contains an N-terminal Caspase Activation and Recruitment Domain (CARD), which interacts with the caspase-2 CARD, and a C-terminal DD, which interacts with the DD of PIDD .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
ASAP1, BAR domain (ASAP1_BAR)
Type: Domain

ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity . It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL . ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain .

This entry represents the BAR domain of ASAP1. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains .
DCC-interacting protein 13-alpha, BAR domain (DP13A_BAR)
Type: Domain

Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling . They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains . Vertebrates contain two APPL proteins, DCC-interacting protein 13-alpha and beta (DP13A and B, also known as APPL1 and APPL2, respectively). DP13A interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and function as an adaptor linked to to regulate many processes such as cell proliferation, immune response, endosomal trafficking and cell metabolism .
Tom40 (Tom40)
Type: Family

Tom40 forms a channel in the mitochondrial outer membrane with a pore about 1.5 to 2.5 nanometers wide. It functions as a transport channel for unfolded protein chains and forms a complex with Tom5, Tom6, Tom7, and Tom22. The primary receptors Tom20 and Tom70 recruit the unfolded precursor protein from the mitochondrial-import stimulating factor (MSF) or cytosolic Hsc70. The precursor passes through the Tom40 channel and through another channel in the inner membrane, formed by Tim23, to be finally translocated into the mitochondrial matrix. The process depends on a proton motive force across the inner membrane and requires a contact site where the outer and inner membranes come close . Tom40 is also involved in inserting outer membrane proteins into the membrane, most likely not via a lateral opening in the pore, but by transfering precursor proteins to an outer membrane sorting and assembly machinery .
RIP1, Death domain (RIP1_Death)
Type: Domain

RIP kinases serve as essential sensors of cellular stress. Vertebrates contain several types containing a homologous N-terminal kinase domain and varying C-terminal domains . RIP1 harbours a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accumulation affecting inflammatory responses, innate immunity, stress responses, and cell survival .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
MAX gene-associated protein, basic Helix-Loop-Helix-zipper domain (MAX_gene-associated_bHLHzip)
Type: Domain

MAX gene-associated protein (MGA) is a dual-specificity transcription factor, acting as a repressor or an activator and binding to 5'-AATTTCACACCTAGGTGTGAAATT-3'. MGA regulates genes targeted by MYC-MAX, suppressing transcriptional activation by MYC and inhibiting MYC-dependent cell transformation. MGA binds DNA via a T-Box . MGA is a component of the MLL1 complex .

This entry represents the basic Helix-Loop-Helix-zipper (bHLHzip) domain found in MGA.
Netrin receptor UNC5A-D (UNC5A-D)
Type: Family

This entry represents uncoordinated-5 (UNC-5) family, whose members include Unc5A, B, C and D from vertebrates and Unc5 from invertebrates.

UNC-5 proteins are transmembrane netrin receptors that play a crucial role in axon guidance and neuronal development. Upon binding to secreted netrins (netrin-1, -3, and -4), these receptors mediate axonal repulsion of neuronal growth cones, contributing to proper nervous system patterning . In addition to axonal guidance, UNC-5 receptors are involved in neuronal migration, blood vessel patterning, cell-cell adhesion, cell migration, and apoptosis . Structurally, they possess an extracellular region comprising two immunoglobulin-like repeats and two thrombospondin type-I modules, along with an intracellular region containing ZU-5, UPA, and death domains (DD), which facilitate downstream signalling .
E3 ubiquitin-protein ligase RING2, RAWUL domain (RING2_RAWUL_dom)
Type: Domain

E3 ubiquitin-protein ligase RING2 (

) mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub) , which is a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals . RING2 is a component of the PRC1 complex , and other chromatin-associated Polycomb (PcG) complexes such as BCOR . It is also a component of the MLL1/MLL complex .

This entry represents the RING finger- and WD40-associated ubiquitin-like (RAWUL) domain of RING2 and similar proteins from vertebrates.
Death domain-containing protein CRADD (CRADD)
Type: Family

CRADD (Caspase and RIP adaptor, also known as RAIDD) is an adaptor protein that together with the p53-inducible protein PIDD and caspase-2, forms the PIDDosome complex, which is required for caspase-2 activation and plays a role in mediating stress-induced apoptosis . It contains an N-terminal CARD, which interacts with the caspase-2 CARD, and a C-terminal Death domain (DD), which interacts with the DD of PIDD .
MALT1, death domain (MALT1_Death)
Type: Domain

MALT1 (MEROPS identifier C14.026) is a paracaspase that cleaves its substrates on the C-terminal side of an arginine residue . It is a key regulator of antigen-induced NF-kappaB activation in the adaptive immune response . Upon antigen stimulation MALT1 acts as a scaffold for a protein complex formed with CARMA1 (also known as CARD11) and Bcl10, the CBM complex. The CBM complex links AgR (antigen receptor) triggering to NF-kappaB activation .

This entry represents the death domain of MALT1.
Selenoprotein P (SeP)
Type: Family

Selenoprotein P (SeP, also known as SEPP1) is a plasma protein which contains 10 selenocysteine residues per polypeptide . It serves as an essential selenium transporter for bones . It contains both a catalytic domain and a C-terminal Se-delivery domain. Several isoforms of SeP with different peptide length have been found to be in cellular extracts and in plasma .
Nitrate reductase alpha subunit-like, MopB domain (MopB_CT_Nitrate-R-NarG-like)
Type: Domain

This entry represents the C-terminal molybdopterin dinucleotide-binding (MopB) domain of respiratory nitrate reductase A (NarGHI) alpha chain (NarG) and related proteins. Under anaerobic conditions in the presence of nitrate, E. coli synthesizes the cytoplasmic membrane-bound quinol-nitrate oxidoreductase (NarGHI), which reduces nitrate to nitrite and forms part of a redox loop generating a proton-motive force. Found in prokaryotes and some archaea, NarGHI usually functions as a heterotrimer. The alpha chain contains the molybdenum cofactor-containing Mo-bisMGD catalytic subunit .
Peroxiredoxin-5-like (PRX5-like)
Type: Family

PRX5-like proteins belongs to the peroxiredoxin (PRX) family . PRX5 is a homodimeric thioredoxin (TRX) peroxidase widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol . The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction . Budding yeast PRX5 homologue, Ahp1, may act as both a peroxidase and a receptor for alkylhydroperoxides . Pmp20 from fission yeast may act as a chaperone rather than a peroxidase .

As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs .
Tetrathionate reductase subunit A, MopB domain (MopB_CT_Tetrathionate)
Type: Domain

This entry represents the molybdopterin-binding C-terminal domain of tetrathionate reductase, catalytic subunit A (TtrA) ; respiratory arsenate As(V) reductase, catalytic subunit (ArrA) ; and other related proteins.
Chromo domain-containing protein cec-4 (Cec-4)
Type: Family

Caenorhabditis elegans Cec-4 is a chromodomain protein that binds preferentially mono-, di-, or tri-methylated H3K9. It is necessary for endogenous heterochromatin anchoring, but not for transcriptional repression. Perinuclear sequestration of chromatin during development may help to restrict cell differentiation programs .
Acetylene hydratase, MopB domain (MopB_CT_Acetylene-hydratase)
Type: Domain

The acetylene hydratase of Pelobacter acetylenicus is a tungsten iron-sulfur protein involved in the fermentation of acetylene to ethanol and acetate . This entry represents the molybdopterin-binding C-terminal domain of acetylene hydratase.
Peptidoglycan deacetylase PgdA-like (PgdA-like)
Type: Family

This family is represented by a peptidoglycan deacetylase (HP0310, HpPgdA) from the Gram-negative pathogen Helicobacter pylori. HpPgdA has the ability to bind a metal ion at the active site and is responsible for a peptidoglycan modification that counteracts the host immune response. It functions as a homotetramer. The monomer is composed of a 7-stranded barrel with detectable sequence similarity to the 6-stranded barrel NodB homology domain of polysaccharide deacetylase (DCA)-like proteins in the CE4 superfamily, which removes N-linked or O-linked acetyl groups from cell wall polysaccharides. In contrast to typical NodB-like DCAs, HpPgdA does not exhibit a solvent-accessible polysaccharide binding groove, suggesting that the enzyme binds a small molecule at the active site .

This entry also includes peptidoglycan deacetylase-like protein FGM2 from Gibberella zeae, its function is unknown.
YdeP-like, MopB domain (MopB_CT_YdeP)
Type: Domain

This entry represents the molybdopterin-binding C-terminal domain found in YdeP and related uncharacterised proteins. YdeP is involved in acid resistance .
Sensor histidine kinase TorS, sensor domain (Sensor_TorS)
Type: Domain

TorS is part of the trimethylamine-N-oxide (TMAO) reductase (Tor) pathway, which consists TorT, a periplasmic binding protein that binds TMAO; TorS, a sensor histidine kinase that forms a complex with TorT, and TorR, the response regulator. The Tor pathway is involved in regulating a cellular response to trimethylamine-N-oxide (TMAO), a terminal electron receptor in anaerobic respiration . TorS consists of a periplasmic sensor domain, as well as a HAMP domain, a histidine kinase domain, and a receiver domain .
SbnI-like, N-terminal (SbnI-like_N)
Type: Domain

Siderophore staphylobactin biosynthesis protein SbnI of Staphylococcus aureus is a ParB/Spo0J like protein required for the expression of genes in the sbn operon, which is responsible for staphyloferrin B (SB) biosynthesis. SnbI forms dimers and binds DNA upstream of sdnD. SbnI binds heme, which inhibits DNA binding of SbnI, leading to a suppression of sbn operon expression . SbnI is a free serine kinase that generates O -phospho-l-serine for staphyloferrin B biosynthesis in Staphylococcus aureus .
Butyrophilin subfamily 3, PRY/SPRY domain (SPRY_PRY_BTN3)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of butyrophilin family 3A (BTN3A). Duplication events have led to three paralogues in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterised by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells .

The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg .
RGS6, RGS domain (RGS6_RGS)
Type: Domain

This entry represents the RGS domain of RGS6 (regulator of G-protein signaling 6). RGS6 is a member of the R7 RGS protein subfamily. Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control .
GAS7, F-BAR domain (GAS7_F-BAR)
Type: Domain

Growth Arrest Specific protein 7 (GAS7) is mainly expressed in the brain and is required for neurite outgrowth . It may also play a role in the protection and migration of embryonic stem cells . Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment . GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain.
Butyrophilin subfamily 1/2, SPRY/PRY domain (SPRY/PRY_BTN1/2)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminal of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterised by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilisation of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions . Duplication events have led to three paralogues of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3 . In humans, only BTN2A1 has been functionally characterised; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalisation receptor for HIV-1, HCV, and other pathogens . BTN2A2 mRNA is expressed in circulating human immune cells.
PICK1, BAR domain (PICK1_BAR)
Type: Domain

Protein Interacting with C Kinase 1 (PICK1) is highly expressed in brain and testes. It plays a key role in the trafficking of AMPA receptors, which are critical for regulating synaptic strength and may be important in cellular processes involved in learning and memory . PICK1 is also critical in the early stages of spermiogenesis. Mice deficient in PICK1 are infertile and show characteristics of the human disease globozoospermia such as round-headed sperm, reduced sperm count, and severely impaired sperm motility . PICK1 may also be involved in the neuropathogenesis of schizophrenia .

PICK1 contains an N-terminal PDZ domain and a C-terminal BAR domain , also designated as AH (arfaptin homology) domain . BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of PICK1 is necessary for its membrane localization and activation .
Ret finger protein-like, SPRY/PRY domain (SPRY/PRY_RFPL)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of Ret finger protein-like (RFPL) protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex . The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains . The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway .