SII-SWORD/CoKE huggingface dataset:
D-alanyl transfer protein DltB (DltB)
Type: Family

Members of this protein family are DltB, part of a four-gene operon for D-alanyl-lipoteichoic acid biosynthesis that is present in the vast majority of low-GC Gram-positive organisms . It is an O-acyltransferase that catalyzes D-alanylation of both teichoic acid and lipoteichoic acid (LTA) . D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall .
SCIFF radical SAM maturase (SCIFF_rSAM_maturase)
Type: Family

Members of this protein family are predicted SPASM domain-containing radical SAM enzymes universally associated with Six Cysteines in Forty-Five protein, or SCIFF (

), a predicted ribosomal natural product precursor that is nearly universal in the class Clostridia. Similarity of this family to radical SAM maturases (e.g. PqqE and subtilosin A maturase) found in the vicinity of other peptide precursors suggests this protein is the SCIFF radical SAM maturase . The SCIFF family member called thermocellin was shown to undergo a thioether crosslink from the sulfur atom of one of the Cys residues to the gamma-carbon of a Thr residue side chain .
3'-RNA ribose 2'-O-methyltransferase, Hen1, bacterial (3'-RNA_MeTfrase_Hen1_bac)
Type: Family

This entry represents bacterial Hen1, which is a 3' terminal RNA ribose 2'-O-methyltransferase that is involved in bacterial RNA repair . Hen1 forms a heterotetramer with Pnkp. The heterotetramer has been shown to repair transfer RNAs cleaved by ribotoxins in vitro .
Colanic acid biosynthesis, acetyltransferase, WcaB (Colanic_acid_synth_WcaB)
Type: Family

This protein family is one of the acetyl transferases involved in the biosynthesis of colanic acid, an exopolysaccharide expressed in Enterobacteraceae species .
Polynucleotide kinase-phosphatase, bacterial (PNKP_bac)
Type: Family

Members of this family are the bacterial polynucleotide kinase-phosphatase (Pnkp) enzymes that prepare broken RNA termini for sealing by RNA ligase . Their genes co-occur with genes for the 3' terminal RNA ribose 2'-O-methyltransferase Hen1, and the pair are thought to form a bacterial RNA repair cassette, where a combination of Pnkp (RNA repair) and Hen1 (RNA modification) serves to first repair RNA damage from ribotoxins and then perform a modification that prevents the damage from recurring .
Pyridoxamine 5-phosphate oxidase, FMN-dependent (Pyridox_Oxase_FMN-dep)
Type: Family

Pyridoxamine 5'-phosphate oxidase (

) is an enzyme that is involved in the de novo synthesis of pyridoxine (vitamin B6) and pyridoxal phosphate. It oxidizes pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P. The enzyme requires the presence of flavin mononucleotide (FMN) as a cofactor, although there is some evidence that coenzyme F420 may perform this role in some species .

This entry represents a subfamily of pyridoxamine 5'-phosphate oxidases, mainly from species that lack the capability to synthesize F420. Family members therefore most likely bind FMN.
AIR synthase-related protein, sll0787 family (AIR_synthase-rel_sll0787)
Type: Family

This entry represents a family of uncharacterised proteins, including sll0787 from Synechocystis sp. PCC 6803. They resemble the C-terminal region of MSMEG_0567 from Mycobacterium smegmatis, where the N-terminal is a GNAT family N-acetyltransferase.
PPOX class F420-dependent enzyme, MSMEG_5819/OxyR family (MSMEG_5819/OxyR)
Type: Family

F420 (or 8-hydroxy-5-deazaflavin) is a coenzyme involved in redox reactions in methanogens. A Genome Properties metabolic reconstruction for F420 biosynthesis shows that slightly over 10 percent of all prokaryotes with fully sequenced genomes, including about two thirds of the Actinomycetales, make F420. This subfamily within the PPOX family occurs in at least 19 distinct species of F420 producers and is likely to bind F420 rather than FMN (flavin mononucleotide or riboflavin-5'-phosphate). The member OxyR was shown in
Streptomyces rimosus
to use F420 to catalyze a C5a-C11a reduction in tetracycline or oxytetracycline biosynthesis , and OxyR is also known as 5a,11a-dehydrotetracycline/5a,11a-dehydrooxytetracycline reductase.
His-Xaa-Ser system radical SAM maturase HxsC (rSAM_paired_HxsC)
Type: Family

This entry describes HxsC, one of a pair of uncharacterised radical SAM proteins, regularly found in the context of a small protein with four or more repeats of the tripeptide His-Xaa-Ser (HXS). This enzyme may be be part of a peptide modification system.
Oxamate carbamoyltransferase subunit AllG, helical domain (OXTCase_su_AllG_h-dom)
Type: Homologous_superfamily

This superfamily represents a domain found in the N-terminal region of a conserved protein (YlbE) of unknown function from Escherichia coli K12. It consists of a mainly α orthogonal bundle

. This domain is associated with and immediately N-terminal to another domain of unknown function defined by

(DUF1116).

Tis domain is found in Oxamate carbamoyltransferase subunit AllG which is a component of a carbamoyltransferase involved in the anaerobic nitrogen utilization via the assimilation of allantoin . It catalyses the conversion of oxalurate (N-carbamoyl-2-oxoglycine) to oxamate and carbamoyl phosphate.
ATPase, F1/V1 complex, beta/alpha subunit, C-terminal (ATPase_F1/V1_b/a_C)
Type: Homologous_superfamily

This entry represents a domain that is found at the C terminus of the F1 ATP synthase beta subunit and in the C terminus of the V-ATPase alpha and beta subunits.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
MSMEG_0567 GNAT N-acetyltransferase (MSMEG_0567_GNAT)
Type: Domain

This entry includes proteins that belong to the GNAT family (

), in which numerous characterised examples, though not all, are shown to be N-acetyltransferases or to interact with acetyl-CoA. In some instances, this is the N-terminal GNAT domain while in other members represents the full length, such as in sll0787 from Synechocystis sp. PCC 6803 (

). This domain occurs in a sparsely distributed biosynthetic cluster that occurs in Actinobacteria, Cyanobacteria, and Proteobacteria.
tRNA-dihydrouridine synthase, putative, C-terminal (tRNA-dHydroUridine_Synthase_C)
Type: Homologous_superfamily

This entry represents a C-terminal four-helix bundle domain found in tRNA-dihydrouridine synthases .
Alternate ATP synthase, F1 complex, subunit epsilon (Alt_ATP_synth_F1_esu)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

A small number of taxonomically diverse prokaryotic species have what appears to be a second ATP synthase, in addition to the normal F1F0 ATPase in bacteria and A1A0 ATPase in archaea. These enzymes use ion gradients to synthesize ATP, and in principle may run in either direction. This entry represents the F1 epsilon subunit of this apparent second ATP synthase .
MYXO-CTERM protein-sorting domain (MYXO-CTERM)
Type: Domain

This entry describes MYXO-CTERM, a C-terminal putative protein sorting domain, analogous to LPXTG (

) and PEP-CTERM (

). It is largely restricted to the Myxococcales, a division of the Deltaproteobacteria .
Ammonium transporter AmtB-like domain (NH4_transpt_AmtB-like_dom)
Type: Domain

This ammonium transporter domain consists of a duplication of 2 structural repeats of five helices each plus one extra C-terminal helix. It has been described as a channel that spans the membrane 11 times .
TM1646-like domain superfamily (TM1646-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain consisting of a four helix bundle found in uncharacterised proteins.
NifT/FixU barrel-like domain superfamily (NifT/FixU_barrel-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a barrel-like domain found in bacterial proteins NifT/FixU/MosB.

The function of NifT is unknown although it is thought that the protein may be involved in biosynthesis of the FeMo cofactor of nitrogenase, although perturbation of nifT expression in Klebsiella pneumoniae has only a limited effect on nitrogen fixation .
NusG, domain 2 (NusG_dom2)
Type: Domain

This domain consists of two-sandwiched four-stranded antiparallel sheets. It is found in transcription factor NusG, where it represents domain 2 and is inserted in domain 1 . However, most NusG proteins are missing this domain. In other cases this domain is found in isolation . NusG is a regulator of Rho-dependent transcription termination , but the function of this domain is unknown.
Flagellar assembly factor FliW domain superfamily (Flagellar_assmbl_FliW_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain of flagellar assembly factor FliW. It consists mainly of a β roll.
MM3350-like superfamily (MM3350-like_sf)
Type: Homologous_superfamily

This domain superfamily is found in several uncharacterised proteins of unknown function. It consists of five α helices and a β roll.
von Hippel-Lindau disease tumour suppressor, alpha domain (VHL_alpha_dom)
Type: Domain

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologues are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterised putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF-independent cellular processes. Germline VHL mutations cause renal cell carcinomas, haemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilise microtubules and foster the maintenance of primary cilia. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B .

Von Hippel-Lindau disease tumour suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in β-sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain and, significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL .

This entry represents the alpha domain of VHL.
eRF1, domain 1 (eRF1_1_sf)
Type: Homologous_superfamily

The release factor eRF1 terminates protein biosynthesis by recognising stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known . The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase centre. A conserved groove on domain 1 is proposed to form the codon recognition site .

This entry represents the first domain of eRF1.
AICAR transformylase, insert domain superfamily (AICAR_Tfase_insert_dom_sf)
Type: Homologous_superfamily

This domain is found in the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase

(AICARFT). AICARFT can be part of a bifunctional enzyme catalysing the last two steps in
de novo
purine biosynthesis and having also an IMP (Inosine monophosphate) cyclohydrolase

(IMPCHase) functional domain. The bifunctional enzyme forms an intertwined dimer where each monomer is composed of two separate functional domains.

This superfamily represents a small alpha domain inserted into the AICARFT formyltransferase domain .
AICAR transformylase, duplicated domain superfamily (AICAR_Tfase_dup_dom_sf)
Type: Homologous_superfamily

This domain is found in the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase

(AICARFT). AICARFT can be part of a bifunctional enzyme catalysing the last two steps in
de novo
purine biosynthesis and having also an IMP (Inosine monophosphate) cyclohydrolase

(IMPCHase) functional domain. The bifunctional enzyme forms an intertwined dimer where each monomer is composed of two separate functional domains.

This superfamily represents a duplicated domain in AICARFT consisting of a three layer α-β-α sandwich .
Phosphopentomutase DeoB cap domain superfamily (Phosphopentomutase_DeoB_cap_sf)
Type: Homologous_superfamily

Phosphopentomutase is involved in the purine and pyrimidine salvage pathway of nucleotide synthesis. It catalyses a phosphotransfer on ribose and deoxyribose, converting D-ribose 1-phosphate to D-ribose 5-phosphate, and 2-deoxy-D-ribose 1-phosphate to 2-deoxy-D-ribose 5-phosphate . Phosphopentomutase is composed of a core domain and a cap domain. This superfamily represents the cap domain .
von Hippel-Lindau disease tumour suppressor, beta domain (VHL_beta_dom)
Type: Domain

von Hippel-Landau (pVHL) protein, the gene product of VHL, is a critical regulator of the ubiquitous oxygen-sensing pathway. It is conserved throughout evolution, as its homologues are found in organisms ranging from mammals to Drosophila and Caenorhabditis. pVHL acts as the substrate recognition component of an E3 ubiquitin ligase complex. Several proteins have been identified as pVHL-binding proteins that are subject to ubiquitin-mediated proteolysis; the best characterised putative substrates are the alpha subunits of the hypoxia-inducible factor (HIF1alpha, HIF2alpha, and HIF3alpha). In addition to HIF degradation, pVHL has been implicated to be involved in HIF-independent cellular processes. Germline VHL mutations cause renal cell carcinomas, haemangioblastomas and pheochromocytomas in humans. pVHL can bind to and direct the proper deposition of fibronectin and collagen IV within the extracellular matrix. It works to stabilise microtubules and foster the maintenance of primary cilia. It also has been reported to promote the stabilization and activation of p53 in a HIF-independent manner and, in neuronal cells, promote apoptosis by down-regulation of Jun-B .

Von Hippel-Lindau disease tumour suppressor (VHL) has two domains: a roughly 100-residue N-terminal domain rich in β-sheet (beta domain) and a smaller α-helical domain (alpha domain), held together by two linkers and a polar interface. A large portion of the alpha domain surface, and a small portion of the beta domain interact with ElonginC. About half of the tumorigenic mutations map to the alpha domain and its residues that contact ElonginC. The remaining mutations map to the beta domain and, significantly, to a beta domain surface patch uninvolved in ElonginC binding. This suggests that two intact macromolecular binding sites may be required for the tumor suppressor effects of VHL .

This entry represents the beta domain of VHL.
Translation initiation factor 2, alpha subunit, middle domain superfamily (TIF2_asu_middle_sf)
Type: Homologous_superfamily

This superfamily represents an α-helical domain is found between the S1 N-terminal domain and the α-β C-terminal domain in the alpha subunit of translation initiation factor 2 . It consists of a bundle of two orthogonally packed α-hairpins.
Translation initiation factor 2, alpha subunit, C-terminal (TIF2_asu_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the translation initiation factor 2 alpha subunit. It adopts an α-β fold, containing five β strands, two α helices, and one loosely associated C-terminal α helix .
Apical membrane antigen 1 domain superfamily (Apmem_Ag1_dom_sf)
Type: Homologous_superfamily

A novel antigen of Plasmodium falciparum has been cloned that contains a hydrophobic domain typical of an integral membrane protein. The antigen is designated apical membrane antigen 1 (AMA-1) by virtue of appearing to be located in the apical complex . AMA-1 appears to be transported to the merozoite surface close to the time of schizont rupture.

The 66kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian malaria, possesses vaccine-related properties believed to originate from a receptor-like role in parasite invasion of erythrocytes . The sequence of PK66 is conserved throughout plasmodium, and shows high similarity to P. falciparum AMA-1. Following schizont rupture, the distribution of PK66 changes in a coordinate manner associated with merozoite invasion. Prior to rupture, the protein is concentrated at the apical end, following which it distributes itself entirely across the surface of the free merozoite. Immunofluorescence studies suggest that, during invasion, PK66 is excluded from the erythrocyte at, and behind, the invasion interface .

This superfamily represents the C-terminal domain of the Apical membrane antigen 1.
Nucleoplasmin core domain (Nucleoplasmin_core_dom)
Type: Domain

This entry represents the core structural domain for the nucleoplasmin (Np) family of histone chaperone proteins. This core domain is formed by an 8-stranded β barrel .

The three branches of the Np family, including nucleophosmin (NO38/B23), nucleoplasmin (Np), and nucleoplasmin-like proteins (NLP), bind core histones and assemble nucleosomes
in vitro
assays. Even though they have different histone preferences, it has been suggested that Np family members may share a general mechanism for binding histones .
Cytochrome f transmembrane anchor (Cyt-f_TM)
Type: Homologous_superfamily

The cytochrome b6f integral membrane protein complex transfers electrons between the two reaction centre complexes of oxygenic photosynthetic membranes, and participates in formation of the transmembrane electrochemical proton gradient by also transferring protons from the stromal to the internal lumen compartment. The cytochrome b6f complex contains four polypeptides: cytochrome f (285 aa); cytochrome b6 (215 aa); Rieske iron-sulphur protein (179 aa); and subunit IV (160 aa) . In its structure and functions, the cytochrome b6f complex bears extensive analogy to the cytochrome bc1 complex of mitochondria and photosynthetic purple bacteria; cytochrome f (cyt f) plays a role analogous to that of cytochrome c1, in spite of their different structures .

The 3D structure of Brassica rapa (Turnip) cyt f has been determined . The lumen-side segment of cyt f includes two structural domains: a small one above a larger one that, in turn, is on top of the attachment to the membrane domain. The large domain consists of an anti-parallel β-sandwich and a short haem-binding peptide, which form a three-layer structure. The small domain is inserted between β-strands F and G of the large domain and is an all-beta domain. The haem nestles between two short helices at the N terminus of cyt f. Within the second helix is the sequence motif for the c-type cytochromes, CxxCH (residues 21-25), which is covalently attached to the haem through thioether bonds to Cys-21 and Cys-24. His-25 is the fifth haem iron ligand. The sixth haem iron ligand is the alpha-amino group of Tyr-1 in the first helix . Cyt f has an internal network of water molecules that may function as a proton wire . The water chain appears to be a conserved feature of cyt f.

This entry represents the transmembrane anchor domain of the cytochrome f subunit. It consists of a single transmembrane helix.
YopX-like, N-terminal (YopX-like_N)
Type: Homologous_superfamily

This superfamily represents a domain found in ORF041 from Bacteriophage 37, which forms a β sandwich structure similar to the N-terminal domain of YopX (

).
Ureidoglycolate lyase domain superfamily (Ureidoglycolate_lyase_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain of ureidoglycolate lyase, and consists of a β structure known as a jelly roll.
NDT80 DNA-binding domain (NDT80_DNA-bd_dom)
Type: Domain

The NDT80 DNA-binding domain is found in the following proteins, which might all be involved in sensing nutritional status :

Yeast meiosis-specific transcription factor NDT80, the key transcription factor that ultimately allows the continuation of meiosis after the successful completion of recombination.

Emericella nidulans phoG (xprG), a transcriptional activator involved in the response to nutrient limitation.

Emericella nidulans putative uncharacterised protein AN6015.2.

Neurospora crassa transcription factor vib-1, involved in the control of heterokaryon incompatibility.

Neurospora crassa related to acid phosphatase NCU04729.

Neurospora crassa related to meiosis-specific protein NDT80 NCU09915.

The proteolytically resistant core NDT80 DNA-binding domain reveals a central β-sandwich characteristic of an s-type Ig fold. The β-sandwich contains a three-stranded sheet composed of strands a, b and e, packed against a four-stranded sheet composed of strands c', c, f and g. Each sheet of the β-sandwich contains an additional β-strand, as well as a variety of peripheral secondary structure elements. The NDT80 DNA-binding domain contains an N-terminal extension, which consists of a β-hairpin and a loop .
Bacteriophage PBS2, uracil-glycosylase inhibitor (Phage_PBS2_Ugi)
Type: Homologous_superfamily

DNA glycosylases excise damaged or unconventional bases in DNA and initiate the base excision repair (BER) pathway to maintain genomic integrity. Of these, uracil-DNA glycosylase (UDG) excises uracil from DNA by cleavage of the N-glycosidic bond between uracil and deoxyribose sugar. Uracil residues in DNA arise as a result of deamination of cytosine or incorporation of dUMP by DNA polymerase. Generally, the latter event is kept to a minimum by the presence of dUTPase which helps maintain a low level of dUTP. UDGs are inhibited by free uracil and some of its derivatives. Another category of UDG inhibitors is represented by Bacillus subtilis phage PBS1 and PBS2 encoded inhibitor protein Ugi and phage T5 induced proteins. PBS2 Ugi is a heat stable, acidic, low molecular weight protein of 9.5kDa, which interacts with UDG in a 1:1 molar stoichiometry to form a complex that does not dissociate under physiological conditions.

This entry is represents the structural domain of the uracil-DNA glycosylase inhibitor protein from Bacillus phage PBS2 . The structure of the Escherichia coli uracil-DNA glycosylase complex with uracil-DNA glycosylase inhibitor (Ugi) protein from Bacillus phage PBS2 has been determined, Ugi folds into an α-β-α sandwich structure formed by five-stranded antiparallel β-strands and two helices .