SII-SWORD/CoKE huggingface dataset:
TAF15/EWS/TLS family (TET_fam)
Type: Family

This entry represents the multi-functional TET (TAF15/EWS/TLS) or FET (FUS/EWS/TLS) protein family.

TAF15/EWS/TLS family members include human FUS (Fused in liposarcoma), EWS (Ewing Sarcoma) and TAF15 (TATA binding associated factor 15), and the Drosophila orthologue Cabeza. They are RNA binding proteins that contain a transcriptional-activation domain (EAD), 3 glycine-arginine (RGG) rich regions, an RNA-binding domain (RBD), and a zinc finger domain . They are involved in transcription and alternative splicing. They are subjected to different environmental signals that induce post-translational modifications in their RBD and in the RGG domains, thus modulating their activity . TAF15/EWS/TLS play important roles in oncogenesis and neuronal disease .
Allene oxide cyclase superfamily (Allene_oxi_cyc_sf)
Type: Homologous_superfamily

This superfamily consists of several plant specific allene oxide cyclase proteins (

). The allene oxide cyclase (AOC)-catalysed step in jasmonate (JA) biosynthesis is important in the wound response of tomato .
Protein kinase C, PB1 domain (PB1_aPKC)
Type: Domain

PB1 domain is an essential modular domain of the atypical protein kinase C (aPKC), which in complex with Par6 and Par3 proteins is crucial for establishment of apical-basal polarity of animal cells . The PB1 domain of Par6 forms a hetero-dimer with the PB1 domain of aPKC.

PB1 domain is a modular domain mediating specific protein-protein interaction which play roles in many critical cell processes. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. Interactions of PB1 domains with other protein domains have been described as noncanonical PB1-interactions . The aPKC protein contains a type I/II PB1 domain.
Plant La-related protein, RNA recognition motif (La-rel_plant_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of plant La-like proteins related to the La autoantigen. A variety of La-related proteins (LARPs or La ribonucleoproteins), with differing domain architecture, appear to function as RNA-binding proteins in eukaryotic cellular processes .
Mitogen-activated protein kinase kinase kinase 2/3, PB1 domain (PB1_MEKK2/3)
Type: Domain

The PB1 domain is present in the two mitogen-activated protein kinase kinases MEKK2 and MEKK3 which are two members of the signaling kinase cascade involved in angiogenesis and early cardiovascular development. The PB1 domain of MEKK2 (and/or MEKK3) interacts with the PB1 domain of another member of the kinase cascade, MAP2K5/MEK5 .

A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. Interactions of PB1 domains with other protein domains have been described as noncanonical PB1-interactions . The MEKK2 and MEKK3 proteins contain a type II PB1 domain.
La-related protein 6, RNA recognition motif (LARP6_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of LARP6.

LARP6 (also known as acheron) is a novel member of the lupus antigen (La) family. LARP6 has been found to regulate the stability and translation of collagen mRNAs by binding to a stem-loop structure in the 5'UTR of type I and type III collagen mRNAs . It can also bind to the developmental transcription factor CASK-C and form a complex with Id (inhibitor of differentiation) transcription factors . It shuttles between the nucleus and cytoplasm and participates in the nuclear export of collagen mRNAs .

LARP6 is structurally related to the La autoantigen and contains a La motif (LAM), nuclear localization and export (NLS and NES) signals, and an RNA recognition motif (RRM) .
CENP-B, dimerisation domain superfamily (Dimerisation_CENP-B_sf)
Type: Homologous_superfamily

Centromere protein B (CENP-B) interacts with centromeric heterochromatin in chromosomes and binds to a specific subset of alphoid satellite DNA, called the CENP-B box. CENP-B may organise arrays of centromere satellite DNA into a higher order structure, which then directs centromere formation and kinetochore assembly in mammalian chromosomes.

The CENP-B dimerisation domain is composed of two α-helices, which are folded into an antiparallel configuration. Dimerisation of CENP-B is mediated by this domain, in which monomers dimerise to form a symmetrical, antiparallel, four-helix bundle structure with a large hydrophobic patch in which 23 residues of one monomer form van der Waals contacts with the other monomer. This CENP-B dimer configuration may be suitable for capturing two distant CENP-B boxes during centromeric heterochromatin formation .
Mitochondrial cytochrome c oxidase subunit VIc/VIIs (Cytochrome_c_oxidase_VIc/VIIs)
Type: Family

Cytochrome c oxidase (CcO;

), a 13 subunit complex, is the terminal oxidase in the mitochondrial electron transport chain. Cytochrome c oxidase is the component of the respiratory chain that catalyses the reduction of oxygen to water .

This
entry contains of cytochrome c oxidase subunit VIc (also known as Cytochrome c oxidase subunit 6C), which is found only in eukaryotes and its specific function remains unclear. It has been reported that the relative concentrations of some nuclear encoded CcO subunits, including subunit VIc, compared to those of the mitochondrial encoded subunits, are altered significantly during the progression of prostate cancer .

This entry also includes Dictyostelium cytochrome c oxidase VIIs (also known as Cytochrome c oxidase subunit 7s), an alternative subunit VII isoform produced under hypoxia .
Neutrophil cytosol factor 2, PB1 domain (PB1_P67)
Type: Domain

NADPH oxidase is a multisubunit complex that assembles during phagocytosis to generate reactive oxygen species. NCF2 (p67-phox), NCF1 (p47-phox) are required for activation of the phagocyte NADPH oxidase. The activators p67-phox and p47-phox form a ternary complex together with adaptor protein p40-phox, which participates in activation of the phagocyte oxidase by regulating membrane recruitment of p67-phox and p47-phox .

A PB1 domain is present in p67-phox. p40-phox associates with p67-phox via binding of the p40-phox PC motif to the p67-phox PB1 domain .

PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. Interactions of PB1 domains with other protein domains have been described as noncanonical PB1-interactions . The p67-phox proteins contain a type II PB1 domain.
LARP7, RNA recognition motif 1 (LARP7_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of La-related protein 7 (LARP7), an oligopyrimidine-binding protein that binds to the highly conserved 3'-terminal U-rich stretch (3' -UUU-OH) of 7SK RNA. LARP7 is a stable component of the 7SK small nuclear ribonucleoprotein (7SK snRNP) . It intimately associates with all the nuclear 7SK and is required for 7SK stability . LARP7 also acts as a negative transcriptional regulator of cellular and viral polymerase II genes, acting by means of the 7SK snRNP system. It plays an essential role in the inhibition of positive transcription elongation factor b (P-TEFb)-dependent transcription, which has been linked to the global control of cell growth and tumorigenesis .

LARP7 contains a La motif (LAM) and an RNA recognition motif (RRM1) at the N-terminal region, which mediates binding to the U-rich 3' terminus of 7SK RNA. LARP7 also carries another putative RRM domain at its C terminus.
Rrp7A, RNA recognition motif (Rrp7A_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Rrp7A, a homologue of yeast ribosomal RNA-processing protein 7 (Rrp7p), and mainly found in Metazoa. Rrp7p is an essential yeast protein involved in pre-rRNA processing and ribosome assembly, and is speculated to be required for correct assembly of rpS27 into the pre-ribosomal particle . In contrast, the cellular function of Rrp7A remains unclear currently. Rrp7A harbors an N-terminal RNA recognition motif (RRM) and a C-terminal Rrp7 domain.
Protein NLP, PB1 domain (PB1_NLP)
Type: Domain

A PB1 domain is present in NIN like proteins (NLP), key transcription factors in a process of establishment of symbiosis between legumes and nitrogen fixing bacteria (Rhizobium) and nitrate signalling in other plants . NLPs carry a PB1 domain at their C terminus .
NADPH oxidase regulator NoxR, PB1 domain (PB1_NoxR)
Type: Domain

The PB1 domain is present in the Epichloe festucae NoxR protein (NADPH oxidase regulator), a key regulator of NADPH oxidase isoform, NoxA . NoxA is essential for growth control of the fungal endophyte in plant tissue in the process of symbiotic interaction between a fungi and its plant host. The Epichloe festucae p67(phox)-like regulator, NoxR, is dispensable in culture but essential in plants for the symbiotic interaction . The PB1 domain of NoxR is essential for localization to the hyphal tip .
Nrd1/Seb1, RNA recognition motif (Nrd1/Seb1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of budding yeast Nrd1 and fission yeast Seb1. Nrd1 is a novel heterogeneous nuclear ribonucleoprotein (hnRNP)-like RNA-binding protein. It is part of the Nrd1-Nab3-Sen1 (NNS) complex that is involved in the termination and processing of short RNA polymerase II transcripts .

Nrd1 contains an RNA recognition motif (RRM), a short arginine-, serine-, and glutamate-rich segment similar to the regions rich in RE and RS dipeptides (RE/RS domains) in many metazoan splicing factors, and a proline- and glutamine-rich C-terminal domain (P+Q domain) similar to domains found in several yeast hnRNPs. Disruption of NRD1 gene is lethal to yeast cells. Its N-terminal domain is sufficient for viability, which may facilitate interactions with RNA polymerase II where Nrd1 may function as an auxiliary factor. By contrast, the RRM, RE/RS domains, and P+Q domain are dispensable .

Seb1 is an RNA-binding protein essential for cell viability and bound directly to Rpb7 subunit of RNA polymerase II. Seb1 does not function in NNS-like termination. Instead, Seb1 coordinates cotranscriptional 3' end processing and polyadenylation site selection . It also contains one RRM motif and a region rich in arginine-serine dipeptides (RS domain) .
RBM4, RNA recognition motif 1 (RBM4_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of vertebrate RNA-binding protein 4 (RBM4).

RBM4 is a ubiquitously expressed splicing factor that has two isoforms, RBM4A (also known as Lark homologue) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 is a RNA-binding protein involved in diverse cellular processes that include alternative splicing of pre-mRNA, translation, and RNA silencing . RBM4 contains two N-terminal RNA recognition motifs (RRMs), a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. The RRMs, in combination with the C-terminal region, are responsible for the splicing function of RBM4 .
RBM4, RNA recognition motif 2 (RBM4_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of vertebrate RNA-binding protein 4 (RBM4).

RBM4 is a ubiquitously expressed splicing factor that has two isoforms, RBM4A (also known as Lark homologue) and RBM4B (also known as RBM30), which are very similar in structure and sequence. RBM4 is a RNA-binding protein involved in diverse cellular processes that include alternative splicing of pre-mRNA, translation, and RNA silencing . RBM4 contains two N-terminal RNA recognition motifs (RRMs), a CCHC-type zinc finger, and three alanine-rich regions within their C-terminal regions. The RRMs, in combination with the C-terminal region, are responsible for the splicing function of RBM4 .
LARP5, RNA recognition motif (LARP5_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of LARP5 (also known as LARP4B), a cytosolic protein that co-sediments with polysomes and accumulates upon stress induction in cellular stress granules. It can interact with the cytosolic poly(A) binding protein 1 (PABPC1) and the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit . LARP5 may function as a stimulatory factor of translation through bridging mRNA factors of the 3' end with initiating ribosomes . Like other La-related proteins (LARPs) family members, LARP5 contains a La motif (LAM) and an RNA recognition motif (RRM) .
Sorting Nexin 1, PX domain (PX_SNX1)
Type: Domain

The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .

SNX1 harbors a Bin/Amphiphysin/Rvs (BAR) domain (

), which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1 . SNX1 is components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi . The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex .

This entry represents the SNX1 PX domain.
Sorting nexin 4, PX domain (PX_SNX4)
Type: Domain

Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .

SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain . SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor .

This entry represents the SNX4 Phox Homology (PX) domain.
LARP4, RNA recognition motif (LARP4_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of LARP4, a cytoplasmic factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP) . It may play a role in promoting translation by stabilizing mRNA. LARP4 is structurally related to the La autoantigen. Like other La-related proteins (LARPs) family members, LARP4 contains a La motif (LAM) and an RNA recognition motif (RRM) .
Fe-S cluster assembly domain superfamily (FSCA_dom_sf)
Type: Homologous_superfamily

Iron-sulphur (FeS) clusters are important cofactors for numerous proteins involved in electron transfer, in redox and non-redox catalysis, in gene regulation, and as sensors of oxygen and iron. These functions depend on the various FeS cluster prosthetic groups, the most common being [2Fe-2S] and [4Fe-4S] . FeS cluster assembly is a complex process involving the mobilisation of Fe and S atoms from storage sources, their assembly into [Fe-S] form, their transport to specific cellular locations, and their transfer to recipient apoproteins. So far in bacteria, three FeS assembly machineries have been identified that are capable of synthesising all types of [Fe-S] clusters: ISC (iron-sulphur cluster), SUF (sulphur assimilation), and NIF (nitrogen fixation) systems.

The ISC system is conserved in eubacteria and eukaryotes (mitochondria) and has broad specificity, targeting general FeS proteins . It is encoded by the isc operon (iscRSUA-hscBA-fdx-iscX). IscS is a cysteine desulphurase, which obtains S from cysteine (converting it to alanine) and serves as a S donor for FeS cluster assembly. IscU and IscA act as scaffolds to accept S and Fe atoms, assembling clusters and transferring them to recipient apoproteins. HscA is a molecular chaperone and HscB is a co-chaperone. Fdx is a [2Fe-2S]-type ferredoxin. IscR is a transcription factor that regulates expression of the isc operon. IscX (also known as YfhJ) appears to interact with IscS and may function as an Fe donor during cluster assembly .

The SUF system is an alternative pathway to the ISC system that operates under iron starvation and oxidative stress. It is found in eubacteria, archaea and eukaryotes (plastids). The SUF system is encoded by the suf operon (sufABCDSE), and the six encoded proteins are arranged into two complexes (SufSE and SufBCD) and one protein (SufA). SufS is a pyridoxal-phosphate (PLP) protein displaying cysteine desulphurase activity. SufE acts as a scaffold protein that accepts S from SufS and donates it to SufA . SufC is an ATPase with an unorthodox ATP-binding cassette (ABC)-like component. SufA is homologous to IscA , acting as a scaffold protein in which Fe and S atoms are assembled into [FeS] cluster forms, which can then easily be transferred to apoprotein targets.

In the NIF system, NifS and NifU are required for the formation of metalloclusters of nitrogenase in Azotobacter vinelandii, and other organisms, as well as in the maturation of other FeS proteins. Nitrogenase catalyses the fixation of nitrogen. It contains a complex cluster, the FeMo cofactor, which contains molybdenum, Fe and S. NifS is a cysteine desulphurase. NifU binds one Fe atom at its N-terminal, assembling an FeS cluster that is transferred to nitrogenase apoproteins . Nif proteins involved in the formation of FeS clusters can also be found in organisms that do not fix nitrogen .
Calcipressin-1, RNA recognition motif (RCAN1_RRM)
Type: Domain

This entry represent the RNA recognition motif (RRM) of RCAN1.

Calcipressin-1 (RCAN1, also known as DSCR1) is a calcineurin inhibitor that inactivates nuclear factor of activated T cells (NFATc) activity . It is expressed in the primitive ventricle of the heart and during neurogenesis . It is a phosphoprotein that increases its capacity to inhibit calcineurin when phosphorylated at the FLISPP motif, and this phosphorylation also controls the half-life of calcipressin 1 by accelerating its degradation . The DSCR1 (Down syndrome critical region 1) gene is present in the region of human chromosome 21, trisomy of which is associated with congenital heart defects observed in Down syndrome .
Nucleoside diphosphate kinase-like domain (NDK-like_dom)
Type: Domain

This entry represents the Nucleoside diphosphate kinase-like domain that contains an α/β fold. It is also found at the C-terminal of retinitis pigmentosa 2 protein (XRP2/RP2) . XRP2, a GTPase-activating protein, is required for the maintenance of rod and cone photoreceptor cells in the retina . NDK is a hexamer composed of identical subunits with a novel mononucleotide binding fold. Each subunit contains an α/β domain with a four stranded, anti-parallel β-sheet .

Nucleoside diphosphate kinases (

) (NDK) are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. They provide NTPs for nucleic acid synthesis, CTP for lipid synthesis, UTP for polysaccharide synthesis and GTP for protein elongation, signal transduction and microtubule polymerisation.

NDK are proteins of 17 Kd that act via a ping-pong mechanism in which a histidine residue is phosphorylated, by transfer of the terminal phosphate group from ATP. In the presence of magnesium, the phosphoenzyme can transfer its phosphate group to any NDP, to produce an NTP.

NDK isozymes have been sequenced from prokaryotic and eukaryotic sources. It has also been shown that the Drosophila awd (abnormal wing discs) protein, is a microtubule-associated NDK. Mammalian NDK is also known as metastasis inhibition factor nm23. The sequence of NDK has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism .
Neutrophil cytosol factor 1, PX domain (PX_p47phox)
Type: Domain

The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species . p47phox is required for activation of NADH oxidase and plays a role in translocation .

Neutrophil cytosol factor 1 (also known as p47phox) contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity . The PX domain of p47phox is also involved in protein-protein interaction.
LARP7, RNA recognition motif 2 (LARP7_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of La-related protein 7 (LARP7).