SII-SWORD/CoKE huggingface dataset:
Outer membrane porin G (Outer_membrane_porin_G)
Type: Family

Porins are channel proteins in the outer membrane of Gram-negative bacteria which mediate the uptake of molecules required for growth and survival. Escherichia coli OmpG forms a 14 stranded β-barrel and in contrast to most porins, appears to function as a monomer . The central pore of OmpG is wider than other E. coli porins and it is speculated that it may form a non-specific channel for the transport of larger oligosaccharides .
RQC domain (RQC_domain)
Type: Domain

This entry represents the RQC domain, which is a DNA-binding domain found only in RecQ family enzymes . RecQ family helicases can unwind G4 DNA, and play important roles at G-rich domains of the genome, including the telomeres, rDNA, and immunoglobulin switch regions. This domain has a helix-turn-helix structure and acts as a high affinity G4 DNA binding domain . Binding of RecQ to Holliday junctions involves both the RQC and the HRDC domains.
U3 small nucleolar RNA-associated protein 15, C-terminal (U3_snoRNA-assocProt_15_C)
Type: Domain

This entry represents the C-terminal domain of the U3 small nucleolar RNA-associated protein 15 (UTP15). This protein is involved in nucleolar processing of pre-18S ribosomal RNA, and is required for optimal pre-ribosomal RNA transcription by RNA polymerase I together with a subset of U3 proteins required for transcription (t-UTPs). UTP15 is a component of the ribosomal small subunit (SSU) processome, which is a large ribonucleoprotein (RNP) required for processing of precursors to the small subunit RNA, the 18S, of the ribosome . This domain is found C-terminal to the WD40 repeat (

). UTP15 associates with U3 snoRNA, which is ubiquitous in eukaryotes and is required for nucleolar processing of pre-18S ribosomal RNA .
Histidine kinase, N-terminal (Histidine_kinase_N)
Type: Domain

This domain is found at the N-terminal of sensor histidine kinase proteins.
Protein of unknown function DUF1999 (DUF1999)
Type: Family

This family contains a putative Fe-S binding reductase (

) whose structure adopts an α and β fold.
Protein of unknown function DUF2000 (DUF2000)
Type: Family

This is a family of proteins of unknown function. The structure of one of the proteins in this family has been shown to adopt an α β fold.
Phage tail tube protein (DUF2001)
Type: Family

This is a family of phage tail tube proteins including protein XkdM from phage-like element PBSX protein (

) whose structure adopts a β barrel flanked with α helical regions .
Proteinase inhibitor I42, chagasin (Prot_inh_I42_chagasin)
Type: Domain

Chagasin is a reversible inhibitor of papain-like cysteine proteases . Chagasin has a β-barrel structure, which is a unique variant of the immunoglobulin fold with homology to human CD8alpha .
Thrombin light chain (Thrombin_light_chain)
Type: Domain

Thrombin is a Na+-activated, allosteric serine protease that functions in blood homeostasis, inflammation and wound healing . Thrombin (or coagulation factor II) is an enzyme that cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, and (in complex with thrombomodulin) protein C . Sodium binding is the major driving force behind the procoagulant, prothrombotic and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C . Prothrombin is activated on the surface of a phospholipid membrane where factor Xa removes the activation peptide and cleaves the remaining part into light and heavy chains. This domain corresponds to the light chain of thrombin.
FGFR1 oncogene partner (FOP), N-terminal dimerisation domain (FOP_dimerisation-dom_N)
Type: Domain

Fibroblast growth factor receptor 1 (FGFR1) oncogene partner (FOP) is a centrosomal protein that is involved in anchoring microtubules to centrosomes. This domain includes a Lis-homology motif. It forms an α-helical bundle and is involved in dimerisation .
Protein of unknown function DUF2002 (DUF2002)
Type: Family

This entry represents a group of putative cytoplasmic proteins. The structure of these proteins form an antiparallel β sheet and contain some α helical regions.
RNA synthesis protein NSP10, coronavirus (RNA_synth_NSP10_CoV)
Type: Domain

Non-structural protein NSP10 is involved in RNA synthesis. It is synthesised as part of a replicase polyprotein, whose cleavage generates many non-structural proteins . NSP10 has a mixed α/β fold comprised of five α-helices contains, one 3(10)-helix, and three β-strands (

) and it is rich in cysteines, featuring two zinc fingers with Cx(2)-C-x(5)-H-x(6)-C and C-x(2)-C-x(7)-C-x-C motifs . Twelve identical subunits assemble to form a unique spherical dodecameric architecture, which is proposed to be a functional form of the ExoN/MTase coactivator domain

The small NSP10 protein is among the more conserved coronavirus proteins and a critical cofactor for activation of multiple replicative enzymes. It interacts with NSP14 and NSP16 acting as a scaffolding protein and regulating their respective exonuclease (ExoN) and ribose-2'-O-MTase (2'-O-MTase) activities , mediating the stabilization of the SAM binding pockets of NSP16 and NSP14. When binding to the N-terminal of NSP14, NSP10 allows the ExoN active site to adopt a stably closed conformation, allowing efficient hydrolysis of dsRNA . Efficient catalytic activity of NSP16 depends on heterodimerization with NSP10. The structure of the SARS-CoV-2 NSP10/NSP16 heterodimer revealed that it is extremely similar to that of its SARS-CoV-1 homologue .

One NSP10 residue, Tyr-96, is of particular interest. The aromatic nature of Tyr-96 plays a crucial role in the NSP10-NSP16 interaction and in the activation of the NSP16 2'-O-MTase activity as well as in the NSP10-NSP14 interaction. This residue is specific for SARS-CoV NSP10, and is a phenylalanine in other coronavirus homologues .
Man1/Src1-like, C-terminal (Man1/Src1-like_C)
Type: Domain

MAN1 is an integral protein of the inner nuclear membrane which binds to chromatin associated proteins and plays a role in nuclear organisation. The C-terminal nucleoplasmic region forms a DNA binding winged helix and binds to Smad . This C-terminal tail is also found in S. cerevisiae and is thought to consist of three conserved helices followed by two downstream strands .
PUB domain (PUB_domain)
Type: Domain

The PUB (also known as PUG) domain is found in peptide N-glycanase where it functions as a AAA ATPase binding domain . This domain is also found on other proteins linked to the ubiquitin-proteasome system.

It has α(2)-β-α(2)-α(2)-α fold. It is composed of a cluster of helices with a small antiparallel β-sheet on one side. It presents topological similarity to the fold of an extended R3H domain.
EndoU ribonuclease, C-terminal (EndoU_C)
Type: Domain

This entry represents the EndoU domain found at the C-terminal of EndoU endoribonucleases, which carries out a conserved RNA processing function. The EndoU domain cleaves RNA at uridylates and release 2',3'-cyclic phosphodiester ends. The EndoU domain is an α/β domain, that contains nine α-helices and three antiparallel β-sheets; the latter are clustered on one side of the domain, whereas the α-helices are largely on the other side . It contains a conserved trio of catalytic residues, two histidines and a lysine.

EndoU is a family of metal-dependent endoribonucleases that is broadly conserved among eukaryotes . EndoU family members have RNA-binding and endoribonuclease activities and appear to be involved in many aspects of
biology, including small nucleolar RNA biogenesis, endoplasmic reticulum (ER) network formation, immune response, and neurodegeneration:

Xenopus laevis endoribonuclease XendoU is responsible for processing the intron encoded U16 and U86 small nucleolar RNAs (snoRNAs) .

Human EndoU, also known as PP11 (placental protein 11), has an endoribonuclease activity with placental tissue specificity .

Drosophila melanogaster CG2145 and DendoU endoribonucleases .

Caenorhabditis elegans endu-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress .
RNA helicase UPF1, Cys/His rich zinc-binding domain (UPF1_CH/ZBD)
Type: Domain

UPF1 (or regulator of nonsense transcripts 1 homologue) is an essential RNA helicase that detects mRNAs containing premature stop codons and triggers their degradation. Together with UPF2 and UPF3, forms a surveillance complex, in which UPF2 acts as a bridge between UPF1 and UPF3. UPF2 and UPF3 are nonenzymatic components of the complex that stimulate the activity of UPF1 . UPF1 has a N-terminal cysteine/histidine-rich zinc-binding domain (CH/ZBD), a regulatory 1B domain, followed by a helicase core that belongs to superfamily 1 (SF1).

This is the N-terminal CH/ZBD which contains 3 zinc binding motifs that interacts with UPF2 and it also has a cis-inhibitory effect on the ATPase activity. After binding to UPF2, the CH/ZBD suffers a large conformational change that causes the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity . This domain is an unique combination of three zinc-binding motifs arranged into two tandem modules related to the RING-box and U-box domains of ubiquitin ligases .
Ribosome biogenesis protein Nop16 (Ribosome_biogenesis_Nop16)
Type: Family

Nucleolar protein 16 (Nop16) is a protein involved in the biogenesis of the 60S ribosomal subunit.
APC membrane recruitment protein (AMER)
Type: Family

This entry includes APC membrane recruitment protein 1/2/3 (Amer1/2/3). Amer1, also known as WTX, binds to the tumour suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing beta-catenin degradation . Amer2 is a negative regulator of Wnt/beta-catenin signaling involved in neuroectodermal patterning .

WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia .
Uncharacterised protein YqeY/Aim41 (YqeY/Aim41)
Type: Family

This entry consist of uncharacterised proteins from bacteria, such as YqeY from Bacillus subtilis, and Aim41/YOR215C from yeast. Altered inheritance of mitochondria protein 41 (Aim41/YOR215C) is a protein of unknown function. It was detected in highly purified mitochondria in high-throughput studies, and null mutant displays reduced frequency of mitochondrial genome loss . Aim41/YOR215C is not an essential gene.
Vacuolar R-SNARE Nyv1, longin domain (Vacuolar_R-SNAR_Nyv1_longi_dom)
Type: Domain

SNARE-mediated fusion typically results in the formation a complex consisting of three Q-SNAREs and one R-SNARE. R-SNAREs that contain a profilin-like fold in their N-terminal domains have been termed longins. The genome of the yeast Saccharomyces cerevisiae encodes five R-SNAREs of which three (Sec22, Ykt6, and Nyv1) have the longin domain. It is important to note that the given longin domain (LD) is not restricted to R-SNAREs and has been identified in a variety of proteins .

This entry represents the N-terminal longin domain of Nyv1. This domain contains a YXXomega-like sorting motif (Y31GTI34), which is responsible for the AP3-dependent vacuolar localization of Nyv1 .
Sterol regulatory element-binding protein 1, C-terminal (Sre1_C)
Type: Domain

This entry represents the C-terminal domain of the sterol regulatory element-binding protein 1 (Sre1). Sre1 is a transcriptional activator required for transcription of genes required for adaptation to anaerobic growth like those implicated in the nonrespiratory oxygen-consumptive biosynthetic pathways of sterol, heme, sphingolipid, and ubiquinone biosynthesis .
Wbp11/ELF5/Saf1, N-terminal domain (Wbp11/ELF5/Saf1_N)
Type: Domain

This entry represents WW domain-binding protein 11 (or Saf1 in Schizosaccharomyces pombe), which may play a role in the regulation of pre-mRNA processing and EARLY FLOWERING 5, which acts as a repressor of flowering in Arabidopsis thaliana .

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.
ER membrane protein complex subunit 7, beta-sandwich domain (Beta_sandwich_EMC7)
Type: Domain

This is the β-sandwich domain found in ER membrane protein complex subunit 7 (EMC7) , which is an integral membrane component of the EMC. EMC is widely conserved and involved in membrane protein biogenesis. It mediates the insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins in an energy-independent manner, both post-translational insertion of tail-anchored proteins and co-translational insertion of multipass membrane proteins . This entry includes UPF0620 protein C83.10 from S. pombe, an orthologue from animal EMC7.

This domain is also found in nodal modulators, which have been identified as part of a protein complex that participates in the nodal signalling pathway during vertebrate development .
Signal recognition particle receptor, beta subunit (SRP_receptor_beta_su)
Type: Family

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

The SR receptor is a monomer consisting of the loosely membrane-associated SR-alpha homologue FtsY, while the eukaryotic SR receptor is a heterodimer of SR-alpha (70kDa) and SR-beta (25kDa), both of which contain a GTP-binding domain . SR-alpha regulates the targeting of SRP-ribosome-nascent polypeptide complexes to the translocon . SR-alpha binds to the SRP54 subunit of the SRP complex. The SR-beta subunit is a transmembrane GTPase that anchors the SR-alpha subunit (a peripheral membrane GTPase) to the ER membrane . SR-beta interacts with the N-terminal SRX-domain of SR-alpha, which is not present in the bacterial FtsY homologue. SR-beta also functions in recruiting the SRP-nascent polypeptide to the protein-conducting channel.

The beta subunit of the signal recognition particle receptor (SRP) is a transmembrane GTPase, which anchors the alpha subunit to the endoplasmic reticulum membrane .
Eukaryotic translation initiation factor 3 subunit E, N-terminal (eIF3e_N)
Type: Domain

This entry represents the N-terminal domain of the eukaryotic translation initiation factor 3 subunit E. EIF3 is required in protein synthesis in mammalian cells and, together with other initiation factors, stimulates binding of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit to form the 48 S initiation complex . The eIF3 complex also prevents premature association of the 40 and 60 S ribosomal subunits and interacts with other initiation factors involved in start codon selection. EIF3 has at least 13 protein components (eIF3a-m or 1-13), where subunits h, i, k, and m are likely to be on the periphery of the complex . Subunit 6 is produced by the int6 gene, one of the frequent integration sites for mouse mammary tumor viruses .
Cryptic/Cripto, CFC domain (Cryptic/Cripto_CFC-dom)
Type: Domain

This entry represents the CFC domain found in the membrane protein Cripto (or teratocarcinoma-derived growth factor) and Cryptic proteins. CFC is approximately 40 residues long, compacted by three internal disulphide bridges, and binds Alk4 via a hydrophobic patch. CFC is structurally homologous to the VWFC-like domain .

Cryptic is involved in the correct establishment of the left-right axis. It may play a role in mesoderm and/or neural patterning during gastrulation .

Cripto is a protein overexpressed in many tumours and structurally similar to the C-terminal extracellular portions of Jagged 1 and Jagged 2 .
RNA cap guanine-N2 methyltransferase (RNA_cap_Gua-N2-MeTrfase)
Type: Family

RNA cap guanine-N2 methyltransferases such as Schizosaccharomyces pombe (Fission yeast) trimethylguanosine synthase (Tgs1) and Giardia lamblia (Giardia intestinalis) Tgs2, catalyse the methylation step(s) for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure . Trimethylguanosine synthase is specific for guanine, and N7 methylation must precede N2 methylation. This enzyme is required for pre-mRNA splicing, pre-rRNA processing and small ribosomal subunit synthesis. As such, this enzyme plays a role in transcriptional regulation.
Vacuolar ATPase assembly integral membrane protein Vma21 (Vma21)
Type: Family

The vacuolar ATPase assembly integral membrane protein Vma21 is required for the assembly of the integral membrane sector (V0 component) of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum .
Multivesicular body sorting factor 12 (Mvb12)
Type: Domain

Mvb12 is a subunit of the ESCRT-I core complex involved in ubiquitin-dependent sorting of proteins into the endosome. Mvb12 may regulate the interactions of ESCRT-I with cargo and other proteins of the ESCRT machinery to efficiently coordinate cargo sorting and release of ESCRT-I from the multivesicular body .

The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. ESCRT (endosomal sorting complex required for transport)-I, -II and -III complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles . Various Ub-binding domains (UBDs), such as UIM, UEV and NZF are found in such machineries .
HIRA B motif (HIRA_B_motif)
Type: Conserved_site

The HirA B (Histone regulatory homologue A binding) motif is the essential binding interface between

and ASF1a, of approx. 40 residues. It forms an antiparallel β-hairpin that binds perpendicular to the strands of the β-sandwich of ASF1a N-terminal core domain, via β-sheet, salt bridge and van der Waals interactions . The two histone chaperone proteins, HIRA and ASF1a, form a heterodimer with histones H3 and H4. HIRA is the human orthologue of Hir proteins known to silence histone gene expression and create transcriptionally silent heterochromatin in yeast, flies, plants and humans.
CRISPR system endoribonuclease Csx1-like, HEPN domain (Csx1-like_HEPN)
Type: Domain

CRISPR system endoribonuclease Csx1 is a metal-independent, endoribonuclease that acts selectively on ssRNA and cleaves specifically after adenosines, as part of the type III-B CRISP-Cas system and it is homologous to Csm6 , sharing the same domain domain architecture consisting of a CARF domain at the N-terminal that is relatively well conserved, and a HEPN nuclease domain at the C-terminal. This entry represents the HEPN domain, which is has less conservation except for the typical R-X4-H motif.

Cas are a group of proteins associated with clustered regularly interspaced short palindromic repeats - CRISPS - of DNA found in nearly half of bacterial and archaeal genomes.
Signal transduction histidine kinase RcsC, alpha-beta loop, C-terminal (Sig_transdc_His_kin_a/b-loop_C)
Type: Domain

This domain is found in the C terminus of the signal transduction response regulator (phospho-relay) kinase RcsC, between the ATP-binding region (

) and the receiver region (

). This domain forms a discrete α/β/loop structure . The Rcs signalling pathway controls a variety of physiological functions like capsule synthesis, cell division or motility in prokaryotes. The Rcs regulation cascade, involving a multi-step phosphorelay between the two membrane-bound hybrid sensor kinases RcsC and RcsD and the global regulator RcsB, is, up to now, one of the most complicated regulatory systems in bacteria .
Rab-binding domain FIP-RBD (Rab-bd_FIP-RBD)
Type: Domain

The Rab11 GTPase regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis. A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognise the active form of Rab11. FIPs are diverse in sequence length and composition toward their N-termini, presumably a feature that underpins their specific roles in Rab11-mediated vesicle trafficking. They have been divided into three subfamilies (classe I, II, and III)on the basis of domain architecture. Class I FIPs comprises a subfamily of three proteins (Rip11/pp75/FIP5, Rab-coupling protein (RCP), and FIP2) that possess an N-terminal C2 domain, localize to recycling endosomes, and regulate plasma membrane recycling. The class II subfamily consists of two proteins (FIP3/eferin/arfophilin and FIP4) with tandem EF hands and a proline-rich region. Class II FIPs localize to recycling endosomes, the trans-Golgi network, and have been implicated in the regulation of membrane trafficking during cytokinesis. The class III subfamily consists of a single protein, FIP1, which does not contain obvious homology domains or motifs other than the FIP-RBD .

The FIP-RBD domain is also found in Rab6-interacting protein Erc1/Elks. Erc1 is the regulatory subunit of the IKK complex and probably recruits IkappaBalpha/NFKBIA to the complex . It may be involved in the organisation of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. It may also be involved in vesicle trafficking at the CAZ, as well as in Rab-6 regulated endosomes to Golgi transport .

The FIB-RBD domain consists of an N-terminal long α-helix, followed by a 90 degrees bend at a conserved proline residue, a 3(10) helix and a C-terminal short β-strand, adopting an "L" shape. The long α-helix forms a parallel coiled-coil homodimer that symmetrically interacts with two Rab11 molecules on both sides, forming a quaternary Rab11-(FIP)2-Rab11 complex. The Rab11-interacting region of FIP-RBD is confined to the C-terminal 24 amino acids, which cover the C-terminal half of the long α-helix and the short β-strand .