SII-SWORD/CoKE huggingface dataset:
Spore coat protein S-like (CotS-like)
Type: Family

This entry represents a group of proteins mainly from an endospore-forming group within firmicutes, including Spore coat protein S/I (COTS/I), Endospore coat-associated protein YutH and Uncharacterized protein YsxE from Bacillus subtilis. YutH has been shown to be involved in spore coat assmebly .
FERM domain-containing protein 4A/B (FRMD4A/B)
Type: Family

This entry includes FRMD4A/B from humans and mice, and similar animal proteins.

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 .
Peptidase M20A (Pept_M20A)
Type: Family

This entry represents the MEROPS peptidase subfamily M20A (clan MH), which includes human N-fatty-acyl-amino acid synthase/hydrolase PM20D1, Carboxypeptidase S from Saccharomyces cerevisiae and similar eukaryotic and bacterial sequences. PM20D1 is a secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase . Carboxypeptidase S, which is used for certain peptides as sole nitrogen source, has a preference for releasing an amino acid attached to Gly . The peptidases of this protein family have two catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu and His. The catalysed reaction involves the release of an N-terminal amino acid, usually neutral or hydrophobic, from a polypeptide .

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
JNK-interacting protein 1 (JIP1_scaffold)
Type: Family

This entry represents the JNK (c-Jun N-terminal kinase)-interacting proteins (JIP) scaffold family, a group of scaffold proteins that regulate signalling by stress-activated MAPKs (mitogen-activated protein kinase) , including C-Jun-amino-terminal kinase-interacting protein 1/2 from humans (JIP1/2). These proteins selectively mediate JNK signalling by aggregating specific components of the MAPK cascade to form a functional JNK signalling module and are required for JNK activation in response to excitotoxic stress . They regulate the activation of MAPK8/JNK1 and differentiation of CD8+ T-cells . JIP-1 from Drosophila melanogaster, also known as JNK-interacting protein 1, is known to play roles in fast axonal transport that are important for neuron structure and function . Members of this family are found in animals.
Hydrogenase maturation factor HoxX-like (HoxX-like)
Type: Family

This entry represents Hydrogenase maturation factor HoxX from Bradyrhizobium diazoefficiens and similar proteins predominantly found in bacteria and fungi. HoxX is involved in the post-translational processing of the hydrogenase large subunit .
DCC-interacting protein 13-alpha/beta (DP13A/B)
Type: Family

This entry includes DCC-interacting protein 13-alpha/beta from humans (DIP13A/B, also known as APPL1/2) and similar proteins predominantly found in vertebrates. DIP13A/B are multifunctional adapter proteins that bind to various membrane receptors, nuclear factors and signalling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism . DIP13B may also affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor .
rRNA methyltransferase 1, mitochondrial (MRM1)
Type: Family

This entry includes rRNA methyltransferase 1, mitochondrial (MRM1) from mammals and yeast, and similar proteins from eukaryotes, which are SpoU-type (class IV) methyltransferases . MRM1 from humans is a S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyses the formation of 2'-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA .
Gentisate 1,2-dioxygenase-like (GDO-like)
Type: Family

This entry represents Gentisate 1,2-dioxygenase (GDO) from Ralstonia sp., and similar proteins predominantly found in bacteria and fungi. GDO catalyses the oxygen-dependent ring fission of gentisate between the carboxyl and proximal hydroxyl groups at positions 1 and 2 of the aromatic ring to form maleyl pyruvate .
KN motif and ankyrin repeat domain-containing protein 1-4 (KANK1-4)
Type: Family

This entry represents KN motif and ankyrin repeat domain-containing protein 1 (KANK1-4) from humans and similar animal proteins. KANK1 is involved in the control of cytoskeleton formation by regulating actin polymerization. It inhibits actin fibre formation, cell migration and fibronectin-mediated cell spreading. This protein is involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. . Kank1 from mouse, during cell division, may regulate DAAM1-dependent RHOA activation that signals centrosome maturation and chromosomal segregation. It may also be involved in contractile ring formation during cytokinesis . KANK2 is involved in regulation of caspase-independent apoptosis, in the negative control of vitamin D receptor signalling pathway and in actin stress fibres formation . These proteins have been associated with nephrotic syndrome .
Glutaredoxin-1 (GLRX1)
Type: Family

This entry represents Glutaredoxin-1 (GLRX1) and similar proteins predominantly found in animals and poxvirus. The animal members of this protein family have glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. They reduce low molecular weight disulfides and proteins. Viral members have thioltransferase and dehydroascorbate reductase activities .
Head-tail connector protein gp6/gp15-like (Gp6_gp15-like)
Type: Family

Members of this family include the proteins gp6 and gp15 from bacteriophage HK97 and SPP1, respectively . They are critical in the assembly of the connector, a specialised structure that serves as an interface for head and tail attachment, as well as a point at which DNA exits the head during infection by the bacteriophage. They form dodecameric ring structures that comprise the middle ring of the connector, located between the portal protein (attached to the head) and the gp7/gp16 ring (attached to the tail). They are components of the mature phage and the absence or mutation of HK97 gp6 or SPP1 gp15, respectively, result in defective head-tail joining and the absence of mature phage particles. The genome maps of HK97 and SPP1 show that genes encoding gp6 and gp15 are in the same relative position on the genome, located adjacent to the major capsid protein (MCP) gene and in between head and tail genes .

This entry also includes proteobacterial prophages.
Upf1-like, C-terminal helicase domain (SF1_C_Upf1)
Type: Domain

This entry represents the C-terminal helicase domain of Upf1-like family helicases.

The Upf1-like helicase family includes UPF1, HELZ, Mov10L1, Aquarius, IGHMBP2 (SMUBP2), and similar proteins . They are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA .
RNA-binding protein 12B, RNA recognition motif 4 (RRM4_RBM12B)
Type: Domain

This entry represents the RRM4 of RBM12B which contains five distinct RNA binding motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains) . Its biological role remains unclear.
Nop12, RNA recognition motif 2 (RRM2_Nop12p-like)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of Nop12p, which is encoded by YOL041C from Saccharomyces cerevisiae . It is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures. Nop12p shares high sequence similarity with nucleolar protein 13 (Nop13p). Both, Nop12p and Nop13p, are not essential for growth. However, unlike Nop13p that localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent, Nop12p is localized to the nucleolus. Nop12p contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains).
Serine/arginine-rich splicing factor 4/6, RNA recognition motif 2 (RRM2_SRSF4/6)
Type: Domain

This is the RNA recognition motif 2 (RRM2) in serine/arginine (SR) proteins serine/arginine-rich splicing factor 4 (SRSF4 or SRp75 or SFRS4), 6 (SRSF6, also known as pre-mRNA-splicing factor SRP55) and related proteins. SRSF4 plays an important role in both constitutive and alternative, splicing of many pre-mRNAs . It can shuttle between the nucleus and cytoplasm. Members in this family contain two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), followed by a C-terminal RS domains rich in serine-arginine dipeptides . SRSF6 plays a role in constitutive splicing and modulates the selection of alternative splice sites. It plays a role in the alternative splicing of MAPT/Tau exon 10 . It binds to alternative exons of TNC pre-mRNA and promotes the expression of alternatively spliced TNC. SRSF6 plays a role in wound healing and in the regulation of keratinocyte differentiation and proliferation via its role in alternative splicing .
Stimulator of interferon genes protein, C-terminal (STING_C_chordates)
Type: Domain

This entry represents the C-terminal domain of STING proteins from chordates.

STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation . STING is also a signalling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localised in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain .
Replication factor A, C-terminal, eukaryotes (Euk_RPA1_DBD_C)
Type: Domain

This entry is found at the C terminus of Replication factor A and similar proteins from eukaryotes and corresponds to ssDNA-binding domain (DBD)-C

Replication factor A (RP-A, also known as replication protein A 70kDa DNA-binding subunit) binds and subsequently stabilises single-stranded DNA intermediates and thus prevents complementary DNA from reannealing. It also plays an essential role in several cellular processes in DNA metabolism, including replication, recombination and repair of DNA . RPA also mediates specific interactions between various nuclear proteins. In animals, plants, and fungi, RPA is a heterotrimer with subunits of 70kDa (RPA1), 32kDa (RPA2), and 14kDa (RPA3).
FCA, RNA recognition motif 1 (RRM1_FCA)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of FCA.

The flowering time control protein FCA is a RNA-binding protein and a critical component of the autonomous flowering pathway, which induces flowering by suppressing the floral repressor FLOWERING LOCUS C (FLC) . It plays a role in alternative polyadenylation of its own pre-mRNA and antisense FLC RNA. It can also serve as a chromatin remodelling factor that mediates histone demethylation of FLC chromatin, causing suppression of FLC expression . FCA contains two RNA recognition motifs (RRMs).
CwlT-like, lysozyme domain (CwlT-like_lysozyme)
Type: Domain

This domain is also present in poorly characterised proteins, namely the pneumococcal vaccine antigen A and YocA from B. subtilis .

CwlT is a bifunctional cell wall hydrolase containing an N-terminal lysozyme domain and a C-terminal NlpC/P60 endopeptidase domain, and has been implicated in the spread of transposons . This entry represents the N-terminal domain which acts as a N-acetylmuramidase that cleaves the bond between N-acetylmuramic acid and N-acetyl-D-glucosamine (MurNAc-GlcNAc) in peptidoglycan . It has structural similarities with lytic transglycosylases and lysozyme G. CwlT is required for ICEBs1 conjugation for which the muramidase activity is essential .
Transmembrane 6 superfamily member 1/2 (TM6SF1-like)
Type: Family

This family includes transmembrane 6 superfamily members 1 (TM6SF1) and 2 (TM6SF2), and similar proteins. TM6SF1 is a widely expressed lysosomal transmembrane protein that may be suitable as a lysosomal marker . These proteins act as regulators of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content which may function as sterol isomerases . Polymorphism of its paralog, TM6SF2, has been associated with the risk for hepatocellular carcinoma, and a variant of the gene has been found to impact the processing of lipids in the liver and the small intestine, causing non-alcoholic fatty liver disease (NAFLD) .
Membrane insertase YidC/ALB, C-terminal (YidC_ALB_C)
Type: Domain

This entry represents the C-terminal domain of membrane insertase YidC from bacteria, ALBINO3-like proteins from plants and similar proteins.

YidC is a bacterial membrane protein which is required for the insertion and assembly of inner membrane proteins . The well-characterised YidC protein from Escherichia coli and its close homologues contain a large N-terminal periplasmic domain (

). This protein interacts with SecYEG protein-conducting channel and the accessory proteins SecDF-YajC to form the bacterial holo-translocon (HTL) .
Thymocyte nuclear protein 1-like, EVE domain (THYN1-like_EVE)
Type: Domain

This entry represents the EVE domain of thymocyte nuclear protein 1 from mammals and its orthologue from S. pombe. This entry also includes uncharacterised sequences from bacteria and archaea.
Diphosphoinositol polyphosphate phosphohydrolase-like, NUDIX domain (DDP-like_NUDIX)
Type: Domain

This entry represents the NUDIX domain from diphosphoinositol polyphosphate phosphohydrolases, such as NUDT3, NUDT4, NUDT11 from human, which cleave a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), P-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that they may play a role in signal transduction . NUT3/4/11 can also catalyse the hydrolysis of diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) but not diadenosine 5',5'''-P1,P5-pentaphosphate (Ap5A) and the major reaction products are ADP and p4a from Ap6A. They also hydrolyse 5-phosphoribose 1-diphosphate . DDP1 and aps1, the orthologues from yeast, are also included in this entry . DDP1 also has endopolyphosphatase activity .

This domain is also found in some poorly characterised NUDIX hydrolases from plants, such as NUDT4 and NUDT16, and uncharacterised bacterial sequences.

Members of the Nudix hydrolase superfamily catalyse the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. require a divalent cation, such as Mg2 or Mn2, for their activity and contain a highly conserved 23-residue nudix motif (GX5EX7REUXEEXGU, where U = I, L or V), which functions as a metal binding and catalytic site. In general, the role of the nudix hydrolase is to sanitize the nucleotide pools and to maintain cell viability, thereby serving as surveillance and 'house-cleaning' enzymes .
Magnesium transporter CorA-like (CorA-like)
Type: Family

This entry represents a group of uncharacterised bacterial sequences related to the Escherichia coli CorA-Salmonella typhimurium ZntB (EcCorA-ZntB_like) family of the MIT superfamily of essential membrane proteins involved in transporting divalent cations (uptake or efflux) across membranes. The functional diversity of MIT transporters may also be due to minor structural differences regulating gating, substrate selection, and transport .
MSF-type transporter YcaD-like (MFS_YcaD-like)
Type: Family

This family is composed of Escherichia coli MFS-type transporter YcaD, Bacillus subtilis MFS-type transporter YfkF, and similar proteins. They are uncharacterised transporters belonging to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
ERI-1-like, DEDDh 3'-5' exonuclease domain (ERI-1_3'hExo-like)
Type: Domain

This entry represents the DEDDh-type DnaQ-like 3'-5' exonuclease domain from human 3'-5' exoribonucleases 1-3 (ERI-1-3, ERI-1 is also known as 3'hExo), ERI-1 from C.elegans and related proteins from plants and bacteria. These are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. ERI-1 has been implicated in the degradation of small interfering RNAs (RNAi) . 3'hExo participates in the degradation of histone mRNAs . This entry also includes Snipper (Snp) from Drosophila (

,

) which is a non-essential exonuclease that efficiently degrades structured RNA and DNA substrates as long as there is a minimum of 2 nucleotides in the 3' overhang to initiate degradation. Snp is not a functional homologue of either ERI-1 or 3'hExo .
Lipocalin Blc-like domain (Lipocalin_Blc-like_dom)
Type: Domain

This entry represents the lipocalin/cytosolic fatty-acid binding domain of Bcl and similar proteins predominantly found in bacteria and plants.

Escherichia coli bacterial lipocalin (Blc, also known as YjeL) is an outer membrane lipoprotein involved in the storage or transport of lipids necessary for membrane maintenance under stressful conditions. Blc has a binding preference for lysophospholipids . This entry also includes eukaryotic lipocalins such as Arabidopsis thaliana temperature-induced lipocalin-1 (TIL) which is involved in thermotolerance, oxidative, salt, drought and high light stress tolerance, and is needed for seed longevity by ensuring polyunsaturated lipids integrity .

These proteins have a large β-barrel ligand-binding cavity. Lipocalins are mainly low molecular weight extracellular proteins that bind principally small hydrophobic ligands, and form covalent or non-covalent complexes with soluble macromolecules, as well as membrane bound-receptors. They participate in processes such as ligand transport, modulation of cell growth and metabolism, regulation of immune response, smell reception, tissue development and animal behavior. Cytosolic fatty-acid binding proteins, also bind hydrophobic ligands in a non-covalent, reversible manner, and have been implicated in intracellular uptake, transport and storage of hydrophobic ligands, regulation of lipid metabolism and sequestration of excess toxic fatty acids, as well as in signaling, gene expression, inflammation, cell growth and proliferation, and cancer development.
RNase MRP protein 1, RNA binding domain (RMP1_RBD)
Type: Domain

RMP1, also called RNA-processing protein RMP1, or RNase MRP 23.6 kDa subunit, functions as part of ribonuclease MRP (RNase MRP), which is involved in rRNA processing in mitochondria. RNase MRP complex consists of an RNA moiety and at least 10 protein subunits including POP1, POP3, POP4, POP5, POP6, POP7, POP8, RMP1, RPP1 and SNM1, many of which are shared with the RNase P complex. RMP1 is required for proper rRNA processing. The entry represents a conserved region of RMP1, which is responsible for the RNA binding .
Ribonuclease MRP protein subunit RMP1 (RMP1)
Type: Family

RMP1, also called RNA-processing protein RMP1, or RNase MRP 23.6 kDa subunit, functions as part of ribonuclease MRP (RNase MRP), which is involved in rRNA processing in mitochondria. RNase MRP complex consists of an RNA moiety and at least 10 protein subunits including POP1, POP3, POP4, POP5, POP6, POP7, POP8, RMP1, RPP1 and SNM1, many of which are shared with the RNase P complex. RMP1 is required for proper rRNA processing .
Centromere-binding protein 1-like, bHLHzip domain (bHLHzip_scCBP1-like)
Type: Domain

This entry represents the basic Helix-Loop-Helix-zipper (bHLHzip) domain found in CBF1 from Saccharomyces cerevisiae and similar fungal proteins. This domain is also found in psilocybin cluster transcription regulator (PsiR) from psychedelic mushroom, which is a transcription factor that may regulate the expression of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine-derived natural product .

CBP-1, also termed centromere promoter factor 1 (CPF1), or centromere-binding factor 1 (CBF1), is a bHLHzip protein that is required for chromosome stability and methionine prototrophy. It binds as a homodimer to the centromere DNA elements I (CDEI, GTCACATG) region of the centromere that is required for optimal centromere function .
Anaerobic sulfatase maturating enzyme, SPASM domain (SPASM_anSME)
Type: Domain

This entry represents the iron-sulfur cluster-binding SPASM domain of anSME and similar proteins from prokaryotes.

Anaerobic sulfatase maturating enzyme (anSME) is a radical S-adenosylmethionine (SAM) enzyme that catalyses, under anaerobic conditions, the co- or post-translational modification of arylsulfatases to form a catalytically essential formylglycine (FGly) residue to perform their hydrolysis function, removing sulfate groups from a wide array of substrates . Radical SAM enzymes are characterised by a conserved CxxxCxxC motif, which coordinates the conserved iron-sulfur cluster that is involved in the reductive cleavage of SAM and generates a 5'-deoxyadenosyl radical, which in turn abstracts a hydrogen from the appropriately positioned carbon atom of the substrate. Radical SAM (RS) enzymes with a C-terminal SPASM domain contain at least one other iron-sulfur cluster; anSME contains two auxillary 4Fe-4S clusters in its SPASM domain .