SII-SWORD/CoKE huggingface dataset:
GlmU, C-terminal LbH domain (GlmU_C_LbH)
Type: Domain

This entry represents the C-terminal LbH domain that possesses the acetyltransferase activity. It catalyzes the CoA-dependent acetylation of GlcN-1-phosphate to GlcNAc-1-phosphate. The LbH domain contains 10 turns, each containing three imperfect tandem repeats of a hexapeptide repeat motif (X-[STAV]-X-[LIV]-[GAED]-X. The acetyltransferase active site is located at the interface between two subunits of the active LbH trimer .

N-Acetylglucosamine-1-PO(4) uridyltransferase (GlmU,

) is a trimeric bifunctional enzyme that catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-GlcNAc.

The X-ray crystal structure of Escherichia coli GlmU in complex with UDP-GlcNAc and CoA has been determined to 2.1 A resolution and reveals a two-domain architecture that is responsible for these two reactions . The C-terminal domain is responsible for the CoA-dependent acetylation of Glc-1-PO(4) to GlcNAc-1-PO(4) and displays the longest left-handed parallel β-helix (LbetaH or LbH) observed to date. The acetyltransferase active site defined by the binding site for CoA makes use of residues from all three subunits and is positioned beneath an open cavity large enough to accommodate the Glc-1-PO(4) acetyl acceptor. The N-terminal domain catalyzes uridyl transfer from UTP to GlcNAc-1-PO(4) to form the final products UDP-GlcNAc and pyrophosphate. This domain is composed of a central seven-stranded β-sheet surrounded by six α-helices in a Rossmann fold-like topology.
YhfW, C-terminal Rieske domain (YhfW_C)
Type: Domain

This entry represents the C-terminal Rieske domain found in YhfW, which is a protein of unknown function with an N-terminal DadA-like (glycine/D-amino acid dehydrogenase) domain and a C-terminal Rieske domain. The Rieske domain is a [2Fe-2S] cluster binding domain involved in electron transfer. It is commonly found in Rieske non-heme iron oxygenase (RO) systems such as naphthalene and biphenyl dioxygenases, as well as in plant/cyanobacterial chloroplast b6f and mitochondrial cytochrome bc(1) complexes. YhfW is found in bacteria, some eukaryotes and archaea .
ALG11 mannosyltransferase (ALG11)
Type: Family

GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) is involved in N-linked oligosaccharide synthesis . It is highly conserved, with homologues in fission yeast, worms, flies, and plants . It catalyses the sequential transfer of two alpha1,2-linked mannose residues from GDP-mannose to Man3GlcNAc2-PP-Dol forming the Man5GlcNAc2-PP-Dol intermediate at the cytosolic side of the ER before flipping to the luminal side. Alg11 contains three hydrophobic transmembrane-spanning helices found in the N-terminal domain .
Ino80 subunit 1 (Ies1)
Type: Family

Ino80 subunit 1 (Ies1) is a component of the INO80 chromatin remodelling complex .

The INO80 complex is involved in transcriptional regulation, DNA replication and probably DNA repair. It remodels chromatin by increasing nucleosome mobility thus allowing access to enzymes that process DNA. Hydrolysis of ATP is required and the INO80 component is an ATPase . The complex in yeast is composed of at least ARP4, ARP5, ARP8, RVB1, RVB2, TAF14, NHP10, IES1, IES3, IES4, IES6, ACT1, IES2, IES5 and INO80 .
ASAP1, SH3 domain (ASAP1_SH3)
Type: Domain

ASAPs (ASAP1, ASAP2, and ASAP3) function as Arf-specific GTPase-activating proteins (GAPs), participate in rhodopsin trafficking, are associated with tumor cell metastasis, modulate phagocytosis, promote cell proliferation, facilitate vesicle budding, Golgi exocytosis, and regulate vesicle coat assembly via a Bin/Amphiphysin/Rvs domain . Each member has a BAR, PH, Arf GAP, Ank repeat and proline rich domains. ASAP1 and ASAP2 also have a SH3 domain at the C terminus . ASAP1 has been implicated in regulating cell motility and invasion .

This entry represents the SH3 domain of ASAP1.
Rotavirus VP4, membrane interaction domain superfamily (Rota_VP4_MID_sf)
Type: Homologous_superfamily

The spike protein VP4 is a key component of the membrane penetration apparatus of rotavirus. This entry represents the VP4 membrane interaction domain superfamily.

The VP4 membrane interaction domain is divided into two subdomains. The first one has a complexed all-β fold and the second one has a coiled-coil (trimeric) helical region.
Uncharacterised protein HP_1531 (HP_1531)
Type: Homologous_superfamily

This entry represents a small group of highly conserved proteins from bacteria, in particular Helicobacter species. The structure is a bundle of α helices. The function is not known.
Phosphoribosyl-AMP cyclohydrolase domain superfamily (PRib_AMP_CycHydrolase_sf)
Type: Homologous_superfamily

The phosphoribosyl-AMP cyclohydrolase

catalyses the third step in the histidine (his) biosynthetic pathway:

5-phosphoribosyl-AMP H
2
O = 5-(5-phospho-D-ribosylaminoformimino)-1-(5-phospho-ribosyl) imidazole-4-carboxamide

It requires Zn
2
ions for activity .

Methanobacterium phosphoribosyl-AMP cyclohydrolase HisI is a dimer; each monomer is composed of four β-hairpins .
MbtH-like domain superfamily (MbtH-like_sf)
Type: Homologous_superfamily

This superfamily contains a domain found in the MbtH protein (

) as well as at the N terminus of the antibiotic synthesis protein NIKP1. This domain is about 70 amino acids long and contains 3 fully conserved tryptophan residues. Many of the members of this family are found in known antibiotic synthesis gene clusters.

The structure of a 72-amino acid domain from the MbtH-like family has been solved (PA2412). It contains a central three-stranded antiparallel β-sheet, organized in a beta2-beta1-beta3 topology, followed by two α-helices .
Putative hydro-lyase (Putative_hydro-lyase)
Type: Homologous_superfamily

This superfamily represents a domain found in various putative hydro-lyases. It is also found as an N-terminal domain in mitochondrial D-glutamate cyclase. The structure of this domain has a complex fold, consisting of two α+β subdomains, one is inserted in the other.
VASP tetramerisation domain superfamily (VASP_sf)
Type: Homologous_superfamily

Vasodilator-stimulated phosphoprotein (VASP) is an actin cytoskeletal regulatory protein. This superfamily corresponds to the tetramerisation domain which forms a right handed α helical coiled coil structure .
SPy1572-like superfamily (SPy1572-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain from an uncharacterised protein SPy1572 and homologues found in Streptococcus. The structure of this domain is an antiparallel hairpin that forms an open bundle homodimer.
Antitoxin CbeA superfamily (CbeA_sf)
Type: Homologous_superfamily

This is a superfamily of cognate antitoxins to the CbtA toxins that act by inhibiting the polymerisation of cytoskeletal proteins (see

). These are classified as a type IV toxin-antitoxin system . The superfamily includes three proteins from E. coli YagB, YeeU and YfjZ, which act not by forming a complex with CbtA but through acting as antagonists to the CbtA toxicity, by stabilising the CbtA target proteins. For example, YeeU binds directly to both MreB and FtsZ and enhances the bundling of their filaments in vitro. YeeU is also able to neutralise the toxicity caused by other MreB and FtsZ inhibitors, such as A22 [S-(3, 4-dichlorobenzyl)isothiourea] for MreB, and SulA and DicB for FtsZ . Thus CbeA, for cytoskeleton bundling-enhancing factor A, is proposed as a general name for all of these antitoxin proteins.

The molecular structure has a β(2)-α-β(3) fold arranged in two layers (alpha/beta).
MtlR-like superfamily (MtlR-like_sf)
Type: Homologous_superfamily

The mannitol operon of Escherichia coli, encoding the mannitol-specific enzyme II of the phosphotransferase system (MtlA) and mannitol phosphate dehydrogenase (MtlD) contains an additional downstream open reading frame which encodes the mannitol repressor (MtlR). Although it is involved in the repression of the expression of the mannitol operon it does not bind the operator/promoter regulatory region of this operon. MtlR and homologous protein YggD belong to a new class of transcription factors in bacteria that may regulate gene expression indirectly as a part of a larger transcriptional complex .

The structure of MtlR is multihelical with an 8-helical up-and-down bundle.
YorP domain superfamily (YorP_sf)
Type: Homologous_superfamily

YorP is a 71 residue protein found in bacteria. As it is also found in a bacteriophage it might be of viral origin. The structure is of an α helix between two of five β strands. The function is unknown.
Nucleosome-remodeling factor subunit BPTF (BPTF)
Type: Family

This entry includes the nucleosome-remodeling factor subunits BPTF (vertebrates) and NURF301 (Drosophila melanogaster), which are components of the NURF (nucleosome-remodeling factor) complex . The NURF complex catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin . The HMGA/HMGI(Y)-like DNA-binding site of NURF301 facilitates nucleosome sliding . BPTF binds histone H3K4me3 via its PHD zinc finger domain , and interacts with the myc-associated zinc finger protein MAZ, altering its transcriptional activity, and the Kelch-like Ech-associated protein KEAP1 .
GbiG N-terminal domain superfamily (GbiG_N_sf)
Type: Homologous_superfamily

Cobalt-precorrin-5A hydrolase CbiG is specific for anaerobic cobalamin (vitamin B12) biosynthesis. CbiG, which shows homology with CobE of the aerobic pathway, participates in the conversion of cobalt-precorrin 5 into cobalt-precorrin 6 . CbiG is responsible for the opening of the delta-lactone ring and extrusion of the C2-unit . The aerobic pathway uses molecular oxygen to trigger the events at C-20 leading to contraction and expulsion of the C2-unit as acetic acid from a metal-free intermediate, whereas the anaerobic route involves the internal delivery of oxygen from a carboxylic acid terminus to C-20 followed by extrusion of the C2-unit as acetaldehyde, using cobalt complexes as substrates .

This superfamily represents the N terminus domain of CibG. The structure of this domain has three layers (α/β/α) with a mixed β-sheet of six strands, where the strand 5 is antiparallel to the rest.
NSP1 globular domain superfamily, betacoronavirus (NSP1_glob_sf_bCoV)
Type: Homologous_superfamily

Nonstructural protein 1 (NSP1) is a critical virulence factor of coronaviruses (CoV) and plays key roles in suppressing host gene expression, which facilitates viral replication and immune evasion. NSP1 is a characteristic feature of alpha and betacoronavirus, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses . NSP1 binds to the 40S ribosomal subunit and inhibits host translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs , while viral mRNAs are less susceptible to NSP1-mediated inhibition of translation, because of their 5'-end leader sequence . NSP1 also suppresses the host innate immune functions by inhibiting type I interferon expression and host antiviral signalling pathways. The C-terminal domain binds to the mRNA entry tunnel interfering with mRNA binding (

) . NSP1 consists of a globular domain arranged in a mixed parallel/antiparallel 6-stranded β-barrel with an α-helix covering one end of the barrel and another helix alongside the barrel . In addition to the globular domain, bCoV NSP1s have a C-terminal domain .
Tp47 lipoprotein, middle and C-terminal domain (Tp47_mid_C_dom)
Type: Homologous_superfamily

The middle and C-terminal domains of the unusual penicillin-binding protein (PBP) Tp47 have an immunoglobulin-like fold. The C-terminal domain is mainly characterised by an immunoglobulin fold with two opposing β-sheets that form the typical barrel-like structure. In contrast to the classical immunoglobulin fold, however, this has an additional β-strand inserted after strand 3. Also, the strands are connected by rather large loops. Helices are inserted between strands 2 and 3 and between strands 4 and 5. In contrast to the C-terminal domain, the middle domain contains only the characteristic seven-stranded barrel and short loops. As in domain C, a single α-helical turn is inserted between strands 2 and 3. The C-terminal domain interacts with the middle domain via a surface that has a slightly concave, goblet-like shape.

Tp47 is unusual in that it displays beta-lactamase activity, and thus it does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP .
Capsid assembly scaffolding protein Gp7 (Gp7)
Type: Homologous_superfamily

The Gp7 protein contains a DNA-binding function and may have a role in mediating the structural transition from prohead to mature virus and also scaffold release . Gp7 is arranged within the capsid as a series of concentric shells .

The structure of Gp7 forms a dimer that resemble arrows, with a four-helix bundle composing the arrowhead and a coiled coil forming the tail .
Chromobox protein homologue 3, chromo domain (CBX3_chromo_domain)
Type: Domain

Chromobox protein homologue 3 (CBX3, also known as HP1 gamma) is a component of heterochromatin that binds histone H3 tails methylated at 'Lys-9' which leads to epigenetic repression . By interacting with MIS12 complex, it is involved in the formation of a functional kinetochore . It recruits NIPBL to sites of DNA damage at double-strand breaks . It is a component of the E2F6.com-1 and PER complexes. The PER complex controls the circadian clock .

This entry represents the CHRomatin Organization Modifier (chromo) domain of CBX3.
Histone-lysine N-methyltransferase EHMT2, SET domain (SET_EHMT2)
Type: Domain

Histone-lysine N-methyltransferase EHMT2 (

) mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin . H3K9me is a specific tag for repression of epigenetic transcription, recruiting HP1 proteins to methylated histones. EHMT2 also monomethylates 'Lys-56' of histone H3 (H3K56me1) during the G1 phase of the cell cycle , and methylates 'Lys-27' of histone H3 (H3K27me) . EHMT2 also dimethylates other proteins , including 'Lys-373' of p53 . EHMT2 forms a heterodimer with EHMT1 , and is a component of the E2F6.com-1 complex in G0 phase . EHMT2 contains seven ankyrin repeats which bind the monomethylated RELA subunit of NF-kappa-B, a SET domain which interacts with WIZ , and a pre-SET domain that binds three zinc ions via cysteine residues .

This entry covers the the pre-SET and SET domains.
Histone-lysine N-methyltransferase EHMT1, SET domain (SET_EHMT1)
Type: Domain

Histone-lysine N-methyltransferase EHMT1, (

) mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin . H3K9me is a specific tag for repression of epigenetic transcription, recruiting HP1 proteins to methylated histones. EHMT1 also methylates 'Lys-27' of histone H3 (H3K27me), but weakly . EHMT1 also dimethylates other proteins, including 'Lys-373' of p53 . EHMT1 forms a heterodimer with EHMT2 , and is a component of the E2F6.com-1 complex in G0 phase . EHMT1 contains eight ankyrin repeats which bind the monomethylated RELA subunit of NF-kappa-B, a SET domain which interacts with WIZ , and a pre-SET domain that binds three zinc ions via cysteine residues .

This entry covers the pre-SET and SET domains.
Polycomb group RING finger protein 6, C3HC4-type RING finger (PCGF6_RING-HC)
Type: Domain

Polycomb group RING finger protein 6 (PCGF6 or MBLR) is a transcriptional repressor . It may activate KDM5D histone demethylase, which modulates the levels of histone H3K4Me3 . PCGF6 is a component of the Polycomb group (PcG) multiprotein PRC1-like complex , in which it regulates RNF2 ubiquitin ligase activity , and the E2F6.com-1 complex . PCGF6 contains a RING-type zinc finger.

This entry represents the C3HC4-type RING-HC finger of PCGF6.
AT-rich interactive domain-containing protein 1B, ARID domain (ARID_ARID1B)
Type: Domain

AT-rich interactive domain-containing protein 1B (ARID1B or BAF250b) is part of the SWI/SNF-like ATP-dependent chromatin remodelling complex that regulates gene expression through regulating nucleosome remodelling . In humans there are two BAF250 isoforms, BAF250a/ARID1A and BAF250b/ARID1B . Both BAF250a and BAF250b bind DNA non-specifically . BAF250b is also a component of the BAF , SWI/SNF-like EBAFb , npBAF and nBAF complexes , which remodel chromatin. ARID1B exhibits tumour-suppressor activities in pancreatic cancer cell lines [

, [cite:]]. Mutations in the ARID1B gene cause Coffin-Siris syndrome, exhibiting developmental defects, and haplo-insufficiency of ARID1B, a frequent cause of intellectual disability . Moreover, mutations in the ARID1B gene have been found in many cancers .

This entry represents the ARID/BRIGHT DNA binding domain of ARI1B. It binds DNA in a non-sequence-specific manner similar to ARID1A .
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D 1, SWIB domain (SMARCD1_SWIB_dom)
Type: Domain

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (SMARCD1 or BAF60A) is a component of several complexes that remodel chromatin, a mechanism by which selected genes are transcriptionally activated or repressed. The complexes are SWI/SNF, which changes chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner ; BAF ; and the npBAF and nBAF, which are neuron-specific . SMARCD1 also interacts with the BRG1/SMARCA4 chromatin-remodeling complex .

This entry also includes Brahma-associated protein of 60kDa (BAP60) from Drosophila melanogaster which anchors the Brahma complex to a specific promoter site. The Brahma complex is the equivalent of the yeast SWI/SNF complex .

This entry represents the SWIB domain of SMARCD1.
Gp37-like domain superfamily (Gp37-like)
Type: Homologous_superfamily

The structure of Gp37 consists of a unit of helices and β sheets that crystallises into a beautiful asymmetrical dodecameric barrel-structure, of two six-membered rings one on top of the other. It is expressed in bacteria but is of viral origin, as it is found in phage BcepMu and is probably a pathogenesis factor .
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D 3, SWIB domain (SMARCD3_SWIB_dom)
Type: Domain

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (SMARCD3 or BAF60C) is a component of several complexes that remodel chromatin, a mechanism by which selected genes are transcriptionally activated or repressed. The complexes are SWI/SNF, which changes chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner ; BAF ; and the npBAF and nBAF, which are neuron-specific . SMARCD3 is known to interact with a number of proteins, including SMARCA4/BRG1/BAF190A and the homeobox protein PBX1 .

This entry represents the SWIB domain of SMARCD3.
PHD finger protein 10, PHD finger 1 (PHF10_PHD_finger_1)
Type: Domain

PHD finger protein 10 (PHF10 or BAF45A) is a component of the npBAF complex, which remodels chromatin, a mechanism by which selected genes are transcriptionally activated or repressed .

The npBAF and nBAF complexes are found in neural progenitor cells. The npBAF complex is composed of at least ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. During development, as neural stem cells differentiate post-mitotic chromatin remodeling mechanism occurs, accompanied by a change in the composition of the npBAF complex to form the nBAF complex. The subunits ACTL6A/BAF53A and PHF10/BAF45A are exchanged for ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth .

This entry represents the first PHD finger of PHF10.
Neuronal acetylcholine receptor (Neuro_actylchol_rec)
Type: Homologous_superfamily

This entry represents different subunits of the acetylcholine receptor (AChR) and the neuronal acetylcholine receptor. These receptors are neurotransmitter ligand-gated ion channels. After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses .

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence .
XRCC4-like, N-terminal domain superfamily (XRCC4-like_N_sf)
Type: Homologous_superfamily

XRCC4 is essential for non-homologous DNA end joining (NHDJ) in eukaryotes, which is required for double-strand break repair, and V(D)J recombination in immunoglobulin and T-cell receptor genes. XRCC4 forms a complex with DNA ligase IV, and acts as a regulatory element required for the stability and activity of the ligase. XRCC4 forms an elongated dumb-bell-like tetramer consisting of a C-terminal stalk that interacts with DNA ligase IV and an N-terminal globular head. The N-terminal head domain consists of a β sandwich and a helix-turn-helix (HTH) motif, which may be involved in DNA binding .

This N-terminal domain is structurally similar in XRCC4 and non-homologous end-joining factor 1, also known as XRCC4-like (XLF), consisting of seven-stranded antiparallel β-sandwich with a helix-turn-helix motif inserted between β-strands 4 and 5 .
Chaperonin-like RbcX superfamily (Chaperonin_RbcX_sf)
Type: Homologous_superfamily

The RbcX protein has been identified as having a chaperonin-like function as it assists in the correct assembly of RbcL and RbcS subunits during RuBisCO biogenesis and it is also required to reach its maximal activity . The rbcX gene is juxtaposed to and cotranscribed with rbcL and rbcS encoding RubisCO in Anabaena sp. (strain CA / ATCC 33047) . Crystal structure studies revealed that RbcX is composed almost exclusively of α-helices, which form an unusual four-helix bundle. Additionally, all known RbcX proteins exist as homodimers (RbcX2). The central cleft of this homodimer binds the C-terminal of a RbcL monomer, stabilizing it, and the peripheral region of RbcX2 binds a second RbcL monomer, which allows the RbcL homodimers to be in the correct orientation .

RbcX forms a homodimer with two cooperating RbcL-binding regions . It is composed of five helices per subunit with irregular array of short and long helices, it also has an unusually long protruding C-terminal helix .
L,D-transpeptidase central domain-like superfamily (LD_TPept-like_central_sf)
Type: Homologous_superfamily

This entry represents the putative catalytic central domain found in ykuD protein, a L,D-transpeptidase belonging to the ErfK/YbiS/YcfS/YnhG family .

This domain contains a putative catalytic site with a tetrad of invariant His123, Gly124, Cys139, and Arg141. The stereochemistry of this active site shows similarities to peptidotransferases and sortases, and suggests that the enzymes of this family may play an important role in cell wall biology .