SII-SWORD/CoKE huggingface dataset:
SH3-like domain, bacterial-type (SH3-like_bac-type)
Type: Domain

SH3 domains are widespread among metazoan intracellular signalling proteins and typically bind proline-rich polypeptides. This SH3 domain is a prokaryotic homologue. It might have two possible functions: (1) promoting survival of a pathogen within the invaded cell by modulating pathways controlled by SH3 domains; or (2) promoting invasion by binding to receptors on eukaryotic cells .

SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues . They are found in a great variety of intracellular or membrane-associated proteins for example, in a variety of proteins with enzymatic activity, in adaptor proteins, such as fodrin and yeast actin binding protein ABP-1.

The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β-sheets. The linker regions may contain short helices. The surface of the SH3-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions. The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes .
Intron encoded nuclease repeat (Intron_nuc_1_rpt)
Type: Repeat

This is a repeat of unknown function, but possibly involved in DNA-binding via a helix-turn-helix motif.
B-box, C-terminal (Bbox_C)
Type: Domain

The B-box C-terminal domain is a coiled coil region C-terminal to (some) B-Box domains (

). It is found in Tripartite motif-containing protein 2/3/67/66, E3 ubiquitin-protein ligase TRIM9/TRIM33/TRIM23/TRIM45/TRIM37, Fibronectin type III and similar proteins.
Orange domain (Orange_dom)
Type: Domain

The Orange domain is a motif of ~35 amino acids present in eukaryotic DNA-binding transcription repressors, which regulate cell differentiation, embryonic patterning and other biological processes in both vertebrates and invertebrates. The Orange domain is located just C-terminal to a basic helix-loop-helix (bHLH) domain in the bHLH-Orange (bHLH-O) proteins. This family of bHLH repressors is related to the Drosophila hairy and Enhancer-of-split proteins, wherein the Orange domain was first described and also named helix III/IV region . The transcription of many vertebrate bHLH-O genes is regulated by the Notch signaling pathway, which controls fate decisions and other developmental processes. Orange domain proteins function as transcription repressors involved in the regulation of differentiation, anteroposterior segmentation and sex determination in flies .

Four subfamilies of bHLH-Orange proteins have been identified, i.e. hairy, Enhancer of split, Hey (also named HRT or Hesr) and Stra13 (also named SHARP, DEC, CLAST or BHLHB2) . All these Orange domain proteins have the bHLH domain and except for the Stra13 subfamily, the other subfamily members have a conserved tetrapeptide motif in the C-terminal extremity. The C-terminal motif of the hairy and Enhancer of split proteins is WRPW and this binds the transcriptional corepressor groucho/TLE. For the Hey subfamily members the C-terminal motif is YXXW. The Orange domain may confer specificity of function to different family members and/or it may be involved in dimerization .
Endonuclease III-like, iron-sulphur cluster loop motif (Endonuclease3_FeS-loop_motif)
Type: Conserved_site

Endonuclease III (

) is a DNA repair enzyme which removes a number of damaged pyrimidines from DNA via its glycosylase activity and also cleaves the phosphodiester backbone at apurinic / apyrimidinic sites via a beta-elimination mechanism . The structurally related DNA glycosylase MutY recognises and excises the mutational intermediate 8-oxoguanine-adenine mispair . The 3-D structures of Escherichia coli endonuclease III and catalytic domain of MutY have been determined. The structures contain two all-alpha domains: a sequence-continuous, six-helix domain (residues 22-132) and a Greek-key, four-helix domain formed by one N-terminal and three C-terminal helices (residues 1-21 and 133-211) together with the Fe4S4 cluster. The cluster is bound entirely within the C-terminal loop by four cysteine residues with a ligation pattern Cys-(Xaa)6-Cys-(Xaa)2-Cys-(Xaa)5-Cys which is distinct from all other known Fe4S4 proteins. This structural motif is referred to as a Fe4S4 cluster loop (FCL) . Two DNA-binding motifs have been proposed, one at either end of the interdomain groove: the helix-hairpin-helix (HhH) and FCL motifs. The primary role of the iron-sulphur cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone by forming the loop of the FCL motif .
Ataxin, AXH domain (Ataxin_AXH_dom)
Type: Domain

Spinocerebellar ataxia type 1 is late-onset neurodegenerative diseases caused by the expansion of a CAG triplet repeat in the SCA1 gene. This results in the lengthening of a polyglutamine tract in the gene product ataxin-1 producing a toxic gain of function that results in neuronal death.
OAR domain (OAR_dom)
Type: Domain

This 14 amino acid motif has been identified within the C-terminal region of several paired-like homeodomain (HD) containing proteins . It was named OAR domain after the initials of otp, aristaless, and rax . Although it has been proposed that this domain could be important for transactivation and be involved in protein-protein interactions or DNA binding , its function is not yet known. Some proteins known to contain a OAR domain include human RIEG, defects in which are the cause of Rieger syndrome ; human OG12X and Mus musculus (Mouse) Og12x, whose function is not yet known ; vertebrate Rax, which plays a role in the proliferation and/or differentiation of retinal cells ; Drosophila DRX, which appears to be important in brain development ; and human SHOX, encoded by the short stature homeobox-containing gene.
Ancestral KRAB domain (aKRAB)
Type: Domain

This domain of about 70 amino acid residues is related to the Krueppel-associated box (KRAB) domain and has been recently stratified as the ancestral KRAB domain (aKRAB). Sequence analysis revealed that these sequences have a motif that can also be traced in invertebrates, whose homologues still exist in mammals, including humans, in the PR/SET domain 9 (PRDM9) and synovial sarcoma X breakpoint (SSX) orthologous and paralogous groups . This domain is found in the N-terminal ends of PRDM9 and proteins belonging to the SSX family . Proteins of the SSX family lack the C2H2-type zinc finger which is invariably found in proteins containing the KRAB domain.

Although the aKRAB domains of SSX1 and SSX2 contribute to the repressive activity of these proteins, transcriptional repression is mainly mediated by an auxiliary region located in their C terminus, called KRAB-B . Hence, unlike the canonical KRAB domain, the aKRAB domain is only a weak transcriptional repression domain, as seen in human PRDM9, which neither silences transcription nor interacts with TRIM28/KAP1 .
Zinc finger, BED-type (Znf_BED)
Type: Domain

The BED finger, which was named after the Drosophila proteins BEAF and DREF, is found in one or more copies in cellular regulatory factors and transposases from plants, animals and fungi. The BED finger is an about 50 to 60 amino acid residues domain that contains a characteristic motif with two highly conserved aromatic positions, as well as a shared pattern of cysteines and histidines that is predicted to form a zinc finger. As diverse BED fingers are able to bind DNA, it has been suggested that DNA-binding is the general function of this domain .

Some proteins known to contain a BED domain are listed below:

Animal, fungal and plant AC1 and Hobo-like transposases.

Caenorhabditis elegans protein dpy-20, a predicted cuticular-gene transcriptional regulator.

Drosophila BEAF (boundary element-associated factor), which is thought to be involved in chromatin insulation.

Drosophila DREF, a transcriptional regulator for S-phase genes.

Tobacco 3AF1 and tomato E4/E8-BP1, which are light- and ethylene-regulated DNA binding proteins that contain two BED fingers .
WRKY domain (WRKY_dom)
Type: Domain

The WRKY domain is a 60 amino acid region that is defined by the conserved amino acid sequence WRKYGQK at its N-terminal end, together with a novel zinc-finger-like motif. The WRKY domain is found in one or two copies in a superfamily of plant transcription factors involved in the regulation of various physiological programs that are unique to plants, including pathogen defence, senescence, trichome development and the biosynthesis of secondary metabolites. The WRKY domain binds specifically to the DNA sequence motif (T)(T)TGAC(C/T), which is known as the W box. The invariant TGAC core of the W box is essential for function and WRKY binding . Some proteins known to contain a WRKY domain include Arabidopsis thaliana ZAP1 (Zinc-dependent Activator Protein-1) and AtWRKY44/TTG2, a protein involved in trichome development and anthocyanin pigmentation; and wild oat ABF1-2, two proteins involved in the gibberelic acid-induced expression of the alpha-Amy2 gene.

Structural studies indicate that this domain is a four-stranded β-sheet with a zinc binding pocket, forming a novel zinc and DNA binding structure . The WRKYGQK residues correspond to the most N-terminal β-strand, which enables extensive hydrophobic interactions, contributing to the structural stability of the β-sheet.
Anti-sigma factor antagonist (Anti-sigma_ant)
Type: Family

An anti-sigma factor antagonist is an anti-anti-sigma factor, which relieves inhibition of sigma factor activity by the anti-sigma factor. Examples include the Bacillus subtilis SpoIIAA protein, which, in its phosphorylated form, acts as an anti-anti-sigma factor to relieve SpoIIAB inhibition of sigma F; and the anti-sigma B factor antagonist, RsbV, which counteracts the RsbW-mediated inhibition of sigma B by binding to RsbW.
HAMP domain (HAMP_dom)
Type: Domain

The HAMP domain (present in Histidine kinases, Adenyl cyclases, Methyl-accepting proteins and Phosphatases) is an approximately 50-amino acid α-helical region common to chemoreceptors and histidine kinases that is present in several multidomain sensor proteins that participate in a variety of signal transduction processes. It is found in bacterial sensor and chemotaxis proteins and in eukaryotic histidine kinases. The bacterial proteins are usually integral membrane proteins and part of a two-component signal transduction pathway. One or several copies of the HAMP domain can be found in association with other domains, such as the histidine kinase domain, the bacterial chemotaxis sensory transducer domain, the PAS repeat, the EAL domain, the GGDEF domain, the protein phosphatase 2C-like domain, the guanylate cyclase domain, or the response regulatory domain. It has been suggested that the HAMP domain possesses a role of regulating the phosphorylation or methylation of homodimeric receptors by transmitting the conformational changes in periplasmic ligand-binding domains to cytoplasmic signalling kinase and methyl-acceptor domains .
Signal transduction histidine kinase, dimerisation/phosphoacceptor domain (HisK_dim/P_dom)
Type: Domain

This entry represents the dimerisation and phosphoacceptor domain found in some histidine kinases. Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and the phosphotransfer from aspartyl phosphate back to ADP or to water . The homodimeric domain includes the site of histidine autophosphorylation and phosphate transfer reactions. The structure of the homodimeric domain comprises a closed, four-helical bundle with a left-handed twist, formed by two identical α-hairpin subunits .
Sugar/inositol transporter (Sugar/inositol_transpt)
Type: Family

This family includes sugar transporters and the myo-inositol transporters.

The sugar transporters belong to a superfamily of membrane proteins responsible for the binding and transport of various carbohydrates, organic alcohols, and acids in a wide range of prokaryotic and eukaryotic organisms . These integral membrane proteins are predicted to comprise twelve membrane spanning domains. It is likely that the transporters have evolved from an ancient protein present in living organisms before the divergence into prokaryotes and eukaryotes . In mammals, these proteins are expressed in a number of organs .
Fatty acid synthesis PlsX protein (FA_synthesis)
Type: Family

The plsX gene is part of the bacterial fab gene cluster which encodes several key fatty acid biosynthetic enzymes . The plsX gene encodes a poorly understood enzyme of phospholipid metabolism .
Photosystem I PsaF, reaction centre subunit III (PSI_PsaF)
Type: Family

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. Subunit III (or PsaF) is one of at least 14 different subunits that compose the photosystem I reaction centre (PSI-RC) .
NqrDE/RnfAE (NqrDE/RnfAE)
Type: Family

This is a family of integral membrane proteins including Rdf complex subunits RnfA and RnfE and Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) subunits NqrD and NqrE . The Rnf complex is a ferredoxin:NAD+ oxidoreductase that appears to translocate different ions (protons or sodium) in different bacteria . The similarity of RnfD to NADH-ubiquinone oxidoreductases was previously noted .
Rotavirus non-structural protein 2 (Rotavirus_NSP2)
Type: Family

Rotavirus non-structural protein 2 (NSP2) is a basic protein which possesses RNA-binding activity and is essential for genome replication . It may also be important for viral RNA packaging.
Thymidylate synthase ThyX (Thymidylate_synthase_ThyX)
Type: Family

All cellular organisms need thymidylate (dTMP) for the replication of their chromosomes, as dTMP is required for the biosynthesis of dTTP, a building block of DNA. Cells can produce thymidylate either de novo from dUMP or incorporate thymidine using thymidine kinase. The de novo pathway of dTMP synthesis requires a specific enzyme, thymidylate synthase, which methylates dUMP at position 5 of the pyrimidine ring. There are two pathways for thymidylate synthesis, each utilising a different thymidylate synthase enzyme: ThyA (

) and ThyX (

) . Both enzymes convert dUMP to dTMP, but there is no sequence identity between the two enzymes, and their mechanisms of action differ . Only ThyX uses FAD as cofactor.

The well studied thyA proteins catalyse the reductive methylation reaction of dUMP, with methylenetetrahydrofolate (CH(2)H(4)folate) serving as one-carbon donor and as source of reductive power. On the other hand the thyX family of thymidylate synthases contains FAD that is tightly bound by a novel fold. FAD mediates hydride transfer from NADPH during catalysis. Consequently, in the reaction catalysed by thyX, CH(2)H(4)folate serves only as a carbon donor and tetrahydrofolate (and not dihydrofolate as in the case of thyA) is produced .
African swine fever virus, TBK1 inhibitor DP96R (ASFV_DP96R)
Type: Family

This entry represents TBK1 inhibitor DP96R from African swine fever virus. DP96R is involved in virus immune evasion through the inhibition of the phosphorylation of the host proteins TBK1 and IKKB .
Spindlin/spermiogenesis-specific protein (SPIN/Ssty)
Type: Family

Spindlin (Spin) and Ssty were first identified for their involvement in gametogenesis. Spindlin was identified as a maternal transcript present in the unfertilised egg and early embryo, and was subsequently shown to interact with the spindle apparatus during oogenesis, and may therefore be important for mitosis . In addition, spindlin appears to be a target for cell cycle-dependent phosphorylation, and as such may play a role in cell cycle regulation during the transition from gamete to embryo . Ssty is a multi-copy, Y-linked spermatogenesis-specific transcript that appears to be required for normal spermatogenesis . Ssty may play an analogous role to spindlin in sperm cells, namely during the transition from sperm cells to early embryo, and in mitosis.
CobN/magnesium chelatase (CobN/Mg_chltase)
Type: Family

This family contains a domain common to the cobN protein and to magnesium protoporphyrin chelatase. CobN may play a role in cobalt insertion reactions and is implicated in the conversion of precorrin-2 to cobyrinic acid in cobalamin biosynthesis . Magnesium protoporphyrin chelatase is involved in chlorophyll biosynthesis as the third subunit of light-independent protochlorophyllide reductase in bacteria and plants .
CoA-transferase family III (CoA-Trfase_fam_III)
Type: Family

This entry represents family III CoA-transferases.

CoA-transferases are found in organisms from all kingdoms of life. They catalyse reversible transfer reactions of coenzyme A groups from CoA-thioesters to free acids. There are at least three families of CoA-transferases, which differ in sequence and reaction mechanism:

Family I consists of CoA-transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most use succinyl-CoA or acetyl-CoA as CoA donors.

Family II consists of the homodimeric alpha-subunits of citrate lyase and citramalate lyase (

,

). These enzymes catalyse the transfer of acyl carrier protein (ACP) with a covalently bound CoA derivative, but can accept free CoA thioesters as well.

Family III consists of formyl-CoA:oxalate CoA-transferase , succinyl-CoA:(R)-benzylsuccinate CoA-transferase , (E)-cinnamoyl-CoA:(R)-phenyllactate CoA-transferase , succinyl-CoA:mesaconate CoA-transferase and butyrobetainyl-CoA:(R)-carnitine CoA-transferase . These CoA-transferases occur in prokaryotes and eukaryotes, and catalyse CoA-transfer reactions in a highly substrate-and stereo-specific manner .
Oligosaccharyl transferase, STT3 subunit (Oligo_trans_STT3)
Type: Family

N-linked glycosylation is a ubiquitous protein modification, and is essential for viability in eukaryotic cells. A lipid-linked core-oligosaccharide is assembled at the membrane of the endoplasmic reticulum and transferred to selected asparagine residues of nascent polypeptide chains by the oligosaccharyl transferase (OTase) complex .

This family consists of the oligsacharyl transferase STT3 subunit and related proteins. The STT3 subunit is part of the oligosccharyl transferase (OTase) complex of proteins and is required for its activity . In eukaryotes, OTase transfers a lipid-linked core-oligosaccharide to selected asparagine residues in the ER. In the archaea STT3 occurs alone, rather than in an OTase complex, and is required for N-glycosylation of asparagines .
CAAX prenyl protease 2/Lysostaphin resistance protein A-like domain (Rce1/LyrA-like_dom)
Type: Domain

This entry represents a domain found in CAAX prenyl protease 2 from Saccharomyces cerevisiae (RCE1), its human homologue, Lysostaphin resistance protein A from Staphylococcus aureus (LyrA), putative intramembrane proteases (IMPs), and similar sequences found in bacteria, eukaryotes and archaea. This domain shows an all-α configuration .

Rce1 from S. cerevisiae is a type II CAAX prenyl protease that processes all farnesylated and geranylgeranylated CAAX proteins. It is an integral membrane endoprotease localized to the endoplasmic reticulum that mediates the cleavage of the carboxyl-terminal three amino acids from CaaX proteins. It is involved in processing the Ras family of small GTPases, the gamma-subunit of heterotrimeric GTPases, nuclear lamins, and protein kinases and phosphatases . Three residues of S. cerevisiae Rce1 -E156, H194 and H248- are critical for catalysis . The structure of Rce1 from the archaea Methanococcus (MmRce1) suggests that this group of proteins represents a novel IMP family, the glutamate IMPs .
Small auxin-up RNA (SAUR_fam)
Type: Family

This entry represents a group of plant auxin-responsive proteins, known as small auxin-up RNA (SAUR) . The first SAUR gene was originally identified in soybean hypocotyls . SAUR genes are mainly expressed in growing hypocotyls or other elongating tissues, implying that they play a role in the regulation of cell elongation . SAUR proteins may provide a mechanistic link between auxin and plasma membrane H+-ATPases (PM H+-ATPases) in Arabidopsis thaliana .
SXP/RAL-2 family protein Ani s 5-like, cation-binding domain (ANIS5_cation-bd)
Type: Domain

This domain is found in proteins from nematodes, including SXP/RAL-2 family protein Ani s 5 (ANIS5) from Anisakis simplex, and comprises two conserved motifs: SXP1 and SXP2 . Although the function of this domain is not clear, structural information from ANIS5 revealed an α helical arrangement with a Calmodulin-like fold. Functional studies indicates that ANIS5 can bind magnesium and calcium, suggesting that this domain plays a role in cation binding . These proteins are interesting targets to develop control strategies against the diseases caused by parasites.
Putative outer membrane protein (Put_OMP)
Type: Family

Helicobacter pylori is a causative agent of gastritis and peptic ulceration in humans. As the first step towards development of a vaccine against H. pylori infection, many attempts have been made to identify protective antigens. Potential targets for vaccine development are H. pylori-specific proteins that are surface-exposed and highly antigenic.

This family consists of putative outer membrane proteins, mainly from H. pylori.
Aminoglycoside N(3)-acetyltransferase-like (Amioglycoside_AcTrfase)
Type: Family

This family consists of bacterial aminoglycoside N(3)-acetyltransferases (

) that catalyse the reaction :
Acetyl-Co + a 2-deoxystreptamine antibiotic = CoA + N3'-acetyl-2-deoxystreptamine antibiotic
. The enzyme can use a range of antibiotics with 2-deoxystreptamine rings as acceptor for its acetyltransferase activity, this inactivates and confers resistance to gentamicin, kanamycin, tobramycin, neomycin and apramycin amongst others. For the kanamycin group antibiotics acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin reflecting the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin .

This entry also includes CMP-5'-(N-hydroxy-3-aminopropyl)phosphonate acetyltransferase FrbF catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate .
Flavodoxin-like fold (Flavodoxin_fold)
Type: Domain

This entry represents a domain with a flavodoxin-like fold.

Proteins with this domain include bacterial and eukaryotic NAD(P)H dehydrogenase (quinone)

. These enzymes catalyse the NAD(P)H-dependent two-electron reductions of quinones and protect cells against damage by free radicals and reactive oxygen species . This enzyme uses a FAD cofactor. The equation for this reaction is NAD(P)H + acceptor = NAD(P)(+) + reduced acceptor. This enzyme is also involved in the bioactivation of prodrugs used in chemotherapy . This domain is also found in acyl carrier protein phosphodiesterase

. This enzyme converts holo-ACP to apo-ACP by hydrolytic cleavage of the phosphopantetheine residue from ACP .