SII-SWORD/CoKE huggingface dataset:
HTH-type transcriptional repressor KstR2, C-terminal (KstR2_TetR_C)
Type: Domain

This entry represents the TetR-like C-terminal domain found in HTH-type transcriptional repressor KstR2 as well as fatty acid metabolism regulator proteins. In Mycobacterium smegmatis, KstR2 is involved in cholesterol catabolism , while YsiA in Bacillus subtilis is involved in fatty acid degradation .

TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity . The TetR proteins identified in overm ultiple genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response . TetR regulates the expression of the membrane-associated tetracycline resistance protein, TetA, which exports the tetracycline antibiotic out of the cell before it can attach to the ribosomes and inhibit protein synthesis . TetR blocks transcription from the genes encoding both TetA and TetR in the absence of antibiotic. The C-terminal domain is multi-helical and is interlocked in the homodimer with the helix-turn-helix (HTH) DNA-binding domain .
TRPM, SLOG domain (TRPM_SLOG)
Type: Domain

This entry represents the SLOG-like domain found in several eukaryotic channels including diverse ciliate channels and the TRPM class of animal ion channels. The SLOG (SMF/DprA-LOG) domain adopts a three-layered α/β sandwich Rossmannoid fold. It is positioned near the N terminus of all TRPM channels and is predicted to play a regulatory role for the channel in potentially recognizing a universal nucleotide or nucleotide-derived ligand .
Haloacid dehalogenase-like hydrolase (HAD_2)
Type: Family

The haloacid dehalogenase (HAD) superfamily includes a diverse range of enzymes that use an asp carboxylate as a nucleophile .
PRDM4, zinc ribbon domain (PRDM4_Znf)
Type: Domain

This is a zinc ribbon domain found in PRDM4 (Schwann cell factor 1, SC-1), a member of the PR protein family. PRDM4 is a transcriptional regulator that has been implied in transduction of nerve growth factor signals via the p75 neurotrophin receptor and in cell growth arrest. The short motif is also present in several other PR proteins including human PRDM6 (PRISM), PRDM7, PRDM9 (meisetz), PRDM10 (tristanin), PRDM11, and PRDM15. The conservation of cysteine and histidine residues suggested that this 20 amino acid motif binds zinc, hence the name 'PR zinc knuckle' to distinguish it from the longer (30 amino acid) C2H2-like zinc fingers that are located C-terminally of the PR domain. The PR zinc knuckle fold is similar to that of Gag-knuckles (a β-hairpin providing two zinc ligands followed by a short helix or a loop providing the other two zinc ligands) and zinc ribbons (two β-hairpins, each providing two zinc ligands) .
PIN-like domain (PIN7)
Type: Domain

This is a bacterial PIN-like domain of unknown function .
Mub B2-like domain (Mub_B2)
Type: Domain

This entry corresponds to the Mub B2 domain . This domain is related to the Mub B1 domain and may be involved in mucin binding.
YitH/HolE, acetyltransferase (GNAT) domain (YitH/HolE_GNAT)
Type: Domain

This domain can be found in YitH, a putative N-acetyltransferase from Bacillus subtilis and HolE, an acyltransferase that catalyses the formation of pseudomonic acid C-holothin (PAC-holothin), a thiomarinol analogue, from pseudomonoyl-CoA C (PAC-CoA) and holothin .
THUMP-like domain (Thump-like)
Type: Domain

This is a domain of unknown function found in bacteria.
Bacterial Ig domain (Big_6)
Type: Domain

This domain is found in a wide variety of extracellular bacterial proteins often in multiple tandem copies.
Transcription factor IIIC subunit Tfc1/Sfc1, triple barrel domain (Tfc1/Sfc1_N)
Type: Domain

TFIIIC1 is a multisubunit DNA binding factor that serves as a dynamic platform for assembly of pre-initiation complexes on class III genes. This entry represents the N-terminal triple barrel domain of the Tfc1/Sfc1 subunit. Tfc1/Sfc1 holds a key position in TFIIIC, exerting both upstream and downstream influence on the TFIIIC-DNA complex by rendering the complex more stable. Once bound to tDNA-intragenic promoter elements, TFIIIC directs the assembly of TFIIIB on the DNA, which in turn recruits the RNA polymerase III (pol III) and activates multiple rounds of transcription .
RecC, C-terminal (RecC_C)
Type: Domain

This entry corresponds to the C-terminal domain of the RecC protein. This domain has a PD(D/E)XK like fold. Deleting this domain eliminates RecD assembly within the RecBCD complex .
Defence against restriction A, C-terminal (DarA_C)
Type: Domain

This is a mostly α-helical domain found in polyvalent proteins of phages and prophages . In Phage P1, the DarA protein is a component of the phage P1 head .
SMODS/Ubiquitin system-associated 2TM effector domain (SUa-2TM)
Type: Domain

This is a predicted pore-forming effector domain observed exclusively in conserved genome contexts with the SMODS nucleotide synthetases and the bacterial ubiquitin conjugation systems .
AIMP2, thioredoxin-like domain (AIMP2_thioredoxin)
Type: Domain

This is a thioredoxin like domain found in AIMP2 proteins (aminoacyl tRNA synthetase complex interacting multifunctional protein 2). AIMP2 is a component of human multi-tRNA synthetase complex (MSC). MSC is a macromolecular protein complex consisting of nine different ARSs and three ARS-interacting multifunctional proteins (AIMPs) .
Adaptive response protein AidB, N-terminal (AidB_N)
Type: Domain

This is the N-terminal domain of adaptive response protein AidB present in E. coli. AidB is upregulated in response to small doses of DNA-methylating agents initiates a response that mitigates the mutagenic and cytotoxic effects of DNA methylation. Tetramer formation is thought to be carried out by the N-terminal domain .
Dis3-like cold-shock domain 2 (Dis3_CSD2)
Type: Domain

This domain has an OB fold and is found in the Dis3l2 protein . This domain along with CSD1 binds to RNA.
Domain of unknown function DUF5645 (DUF5645)
Type: Domain

This is a domain of unknown function found in insects. Some family members carry a FR47-like domain (

) on their C terminus.
Peptidase C12, C-terminal domain (UCH_C)
Type: Domain

This is the C-terminal domain found in eukaryotic UCH37 proteins (also known as Ubiquitin carboxyl-terminal hydrolase isozyme L5, UCHL5). UCH37 is a subunit of two complexes: INO80, which performs ATP-dependent sliding of nucleosomes for transcriptional regulation and DNA repair, and the 26S proteasome, which performs ATP-dependent proteolysis of polyubiquitylated proteins in the cytosol and nucleus. Recruitment to the proteasome is mediated by the C-terminal domain of RPN13 (also known as ADRM1). Recruitment to INO80 is mediated by the N-terminal domain of NFRKB. Structural and biochemical analysis reveal that RPN13 and NFRKB make similar interactions with the UCH37 C-terminal domain but have very different interactions with the catalytic UCH domain that are activating in the case of RPN13 and highly inhibitory in the case of NFRKB .
Toxin complex C-like repeat (TcC-like_repeat)
Type: Repeat

Toxin complexes (Tcs) are virulence factors of many bacteria which are composed of bacterial protein toxins that form large, multisubunit complexes. Tcs mode of action is to perforate the host membrane and transfer toxic enzymes into the host cell. Tc protein subunits can be classified as either type A, B or C. This entry describes a single repeat unit, as found in TcC-like proteins such as toxin subunits YenC1 and 2 from Yersinia entomophaga .
Glycosyl hydrolases 38, beta-1 domain (GH38_beta-1)
Type: Domain

The enzymatic hydrolysis of alpha-mannosides is catalyzed by glycoside hydrolases (GH), termed alpha-mannosidases. Streptococcal (Sp) GH38 alpha-mannosidase active on N-glycans and possibly O-glycans. SpGH38 structure can be considered as five domains: an N-terminal α/β-domain, a three-helix bundle and three predominantly β-sheet domains. This is the first of the three β-sheet domains found in GH38, termed Beta-1. Structural analysis indicate that the beta-1 domain bows outward from the protein core, is involved in dimer interactions whilst also forming a lid 'above' and somewhat into the active centre of its dimer .
Domain of unknown function DUF5523 (DUF5523)
Type: Domain

This entry represents a domain of unknown function found in Eukaryotes. Many (but not all) proteins matched by this entry, such as the human protein Coiled-coil and C2 domain-containing protein 2A (

), also contain

and

domains at the C-terminal region.
Putative DNA-binding domain (DBD_HTH)
Type: Domain

This is a putative DNA-binding protein dimerization domain found bacterial proteins such as CD3330, (a transposon-related DNA-binding protein from Clostridium difficile). Crystal structure analysis suggests that CD3330 N terminus is involved in dimer formation and also in crystal packing but the C terminus is open to solvent .
APOBEC3H (APOBEC3H)
Type: Family

APOBEC3H deaminases act as restriction factors in the innate response to retroviruses and various retroelements .
SAS-6 coiled-coil domain (SAS6_CC)
Type: Domain

This is a coiled-coil domain found at the C terminus of spindle assembly abnormal protein 6 (Sas6). The highly conserved protein SAS-6 constitutes the centre of the cartwheel assembly that scaffolds centrioles early in their biogenesis. Structural analysis of Sas6 show that similar to XLF and XRCC4, it forms a parallel coiled-coil dimer .
Proline utilization A, N-terminal (PutA_N)
Type: Domain

This domain is found in Proline utilization A (PutA) proteins present in Geobacter sulfurreducens. PutA are bifunctional peripheral membrane flavoenzymes that catalyze the oxidation of l-proline to l-glutamate and couple the oxidation of imported proline imported to the reduction of membrane-associated quinones. This domain is located at the N terminus and is referred to as the alpha domain. The hydrocarbon tail of Zwittergent 3-12 binds to an exposed hydrophobic patch of the alpha domain which contains aromatic and nonpolar residues. The domain may be involved in membrane association .
PPAF-2-like, Clip domain (PPAF-2-like_Clip)
Type: Domain

This domain is found in Prophenoloxidase-activating factor (PPAF)-II present in the beetle Holotrichia diomphalia. PPAF-II is indispensable for the generation of the active phenoloxidase leading to melanization, a major defense mechanism of insects. This domain is the clip domain and it is thought to tightly associate with regions I-III of the serine protease-like (SPL) domain. The clip domain is a protein-interaction module that plays an essential role in the binding and activation of PO76s via its central cleft .

This domain is also found in clip-domain serine protease homologues (cSPHs), including A3 from Aedes aegypti and CLA8/30 from Anopheles gambiae, the vector of malaria parasites. These proteins are non-catalytic, but critical for the activation of prophenoloxidase (PPO) in the melanization response, playing an essential role in the innate immune response against bacteria, fungi and protozoa infection .
LACTB2, winged helix domain (LACTB2_WH)
Type: Domain

This winged helix domain is found at the C terminus of LACTB2, which is a metallo-beta-lactamase protein .
Protease Do-like, PDZ domain (DEGP_PDZ)
Type: Domain

This entry contains the second PDZ domain from serine protease Do-like proteins such as DEGP2/9 . This domain is involved in cage assembly.

This entry also includes DegP homologue from Plasmodium falciparum, a serine protease that also acts as a protein chaperone . It plays a role in the parasite development in host erythrocytes possibly by protecting it against thermal and oxidative stresses.
Bacterial Glycosyl hydrolase family 3, C-terminal (Bac_GH3_C)
Type: Domain

This is the C-terminal domain of the glycoside hydrolase family 3 (PF18034).
RiboL-PSP-HEPN (HEPN_RiboL-PSP)
Type: Domain

RiboL-PSP-HEPN is fused to endoRNase L-PSP and in operon with ParB .
CdaR, GGDEF-like domain (CdaR_GGDEF)
Type: Domain

This domain is distantly related to the GGDEF domain. This domain can be found in carbohydrate diacid regulator (CdaR), PutR and related proteins. PutR is a transcriptional activator .
Roquin II (ROQ_II)
Type: Domain

The ROQ domain, found in the protein Roquin (and in the C. elegans protein 'regulation of longevity by E3 ubiquitin-protein ligase') is composed of three subdomains, I, II and III. This entry represents the second domain, ROQ II. Structural analysis reveals similarity of domain II to the helix-turn-helix (HTH) fold .
Glycoside hydrolase 131, catalytic N-terminal (GH131_N)
Type: Domain

This is the N-terminal domain found in glycoside hydrolase family 131 (GH131A) protein observed in Coprinopsis cinerea. GH131A exhibits bifunctional exo-beta-1,3-/-1,6- and endo-beta-1,4 activity toward beta-glucan. This domain is catalytic in nature though the catalytic mechanism of C. cinerea GH131A is different from that of typical glycosidases that use a pair of carboxylic acid residues as the catalytic residues. In the case of GH131A, Glu98 and His218 may form a catalytic dyad and Glu98 may activate His218 during catalysis .
Nicotinate/nicotinamide phosphoribosyltransferase (N/Namide_PRibTrfase)
Type: Domain

Nicotinate phosphoribosyltransferase (

) is the rate-limiting enzyme that catalyses the first reaction in the NAD salvage synthesis . Members in this family can be split into two further subfamilies represented in

and

. Members in

have a different (longer) spacing of several key motifs and have an additional C-terminal domain of up to 100 residues. However, one argument suggesting that this family represents the same enzyme is that no species has a member of both subfamilies. Another is that the gene encoding this protein is located near other NAD salvage biosynthesis genes in Nostoc and in at least four different Gram-positive bacteria.

Nicotinamide phosphoribosyl transferase (NAMPT) catalyses the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD . NAMPT is also known as pre-B cell colony-enhancing factor (PBEF) or visfatin.
DAPG hydrolase, PhiG domain (DAPG_hydrolase)
Type: Domain

This domain is found in 2,4-diacetylphloroglucinol hydrolase PhiG present in Pseudomonas fluorescens. 2,4-diacetylphloroglucinol hydrolase is the gene product of PhiG that is responsible for cleaving toxic 2,4-diacetylphloroglucinol (DAPG). The small N-terminal region of the domain is involved in dimerization through hydrogen bonding of the dimer interface. The C-terminal catalytic region resembles the tetracenomycin aromatase/cyclase and has a Bet v1-like fold. DAPG PhiG is the first discovered hydrolase whose catalytic domain belongs to the Bet v1-like fold, rather than the classical α/β-fold hydrolases .
YhcG, N-terminal (YhcG_N)
Type: Domain

This domain can be found at the N terminus of YhcG from E.coli. YhcG was identified in association with DNA processing enzymes, including the restriction complexes HsdMRS and McrABC, the integrases IntF and IntS, and the recombinase PinE .
Cas6b N-terminal (Cas6b_N)
Type: Domain

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci play a pivotal role in the prokaryotic host defense system against invading genetic materials. The CRISPR loci are transcribed to produce CRISPR RNAs (crRNAs), which form interference complexes with CRISPR-associated (Cas) proteins to target the invading nucleic acid for degradation . Four Cas proteins (Cas5, Cas6b, Cas7 and Cas8b) are proposed to form a Type I-B Cascade complex that mediates the antiviral defense .
Nicotinamide phosphoribosyltransferase, N-terminal domain (DUF5598)
Type: Domain

This is the N-terminal domain found in Nicotinamide phosphoribosyltransferase (NAMPT). NAMPT captures nicotinamide (NAM) and replenishes the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase reactions .
Oligosaccharyltransferase insert domain (OST_IS)
Type: Domain

This is a domain found in the oligosaccharyltransferase AGLB (Dolichyl-phosphooligosaccharide-protein glycotransferase 1) from P. furiosus. This is an oligosaccharyltransferase which catalyses the transfer of a heptasaccharide, containing one hexouronate and two pentose residues, onto peptides in an Asn-X-Thr/Ser-motif-dependent manner. This domain is inserted into the central core (CC) domain and hence is referred to as the insert (IS) domain. This IS domain contains a disulphide bond .
Baseplate upper protein, immunoglobulin like domain (BppU_IgG)
Type: Domain

This is a β-sandwich immunoglobulin fold domain, which resembles the plexin-A2 C-terminal domain in structure. In baseplate upper protein (BppU, also known as ORF48) trimer, this domain plays part in surrounding the Dit hexameric core .
RlmI-like, PUA domain (RlmI-like_PUA)
Type: Domain

This entry represents the RNA-binding PUA domain which co-occurs N-terminal to SAM-dependent methyltransferase domains, found in Escherichia coli RlmI (rRNA large subunit methyltransferase gene I, also called YccW) and Thermus thermophilus methyltransferase RlmO (

), which are 5-methylcytosine methyltransferases (m5C MTases) that play a role in modifying 23S rRNA. This entry also includes Pyrococcus horikoshii PH1915 (

)that may play a role as a 5-methyluridine MTase, and/or perform similar roles .
Bartonella effector protein, BID domain (Bep_BID)
Type: Domain

This entry is the BID (Bep intracellular delivery) domain located at the C-terminal of Bartonella effector proteins (Beps). It functions as a secretion signal in a subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It mediates transfer of (1) relaxases and the attached DNA during bacterial conjugation, and (2) numerous Beps during protein transfer into host cells infected by pathogenic Bartonella species. Crystal structures of several representative BID domains show a conserved fold characterised by a compact, antiparallel four-helix bundle topped with a hook .
PP2A regulatory subunit B'', EF-hand domain (EF-hand_13)
Type: Domain

This entry represents an EF-hand domain found in one of the regulatory B subunits of PP2A .
Antitoxin VbhA (VbhA)
Type: Domain

VbhT is a bacterial Fic protein of the mammalian pathogen B. schoenbuchensis. It is composed of an N-terminal FIC domain and a C-terminal BID domain. FIC domains are known to catalyse adenylylation (also called AMPylation). This entry represents VbhA, an antitoxin that binds FIC domain (filamentation induced by cyclic AMP) of VbhT and inhibits its activity. It inhibits the adenylylation activity of VbhT by positioning close to the putative ATP-binding site, hence competing with ATP binding .
N-acetylglucosamine-1-phosphotransferase subunit alpha/beta, regulatory domain (GNPTAB_reg)
Type: Domain

The Golgi enzyme UDP-GlcNAc-lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase), an alpha2beta2gamma2 hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes . GNPTAB encodes the alpha and beta subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III alpha-beta. The alpha-beta subunits contain three identifiable domains separated by so-called spacer regions. This domain is part of the first spacer region, Spacer-1 . Studies indicate that GlcNAc-1 lacking spacer-1 exhibits enhanced phosphorylation of several non-lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of GlcNAc-1, it is suggested to rename 'spacer-1' the 'regulatory-1' domain .
Protein of of unknown function DUF5547 (DUF5547)
Type: Family

This is a family of unknown function found in mammals.
ATPase RavA-like, AAA lid domain (RavA-like_AAA_lid)
Type: Domain

This entry represents the α-helical AAA+ lid domain that is found to the C terminus of AAA domains.

Proteins containing this domain include RavA, which functions as an ATPase .
CxC5 like cysteine cluster associated with KDZ (CxC5)
Type: Domain

A predicted Zinc chelating domain present N-terminal to the KDZ transposase domain .
Vms1-associating treble clef domain (VATC)
Type: Domain

This entry represents the treble clef fold domain found at C terminus of many, but not all, Vms1/ANKZF1-like proteins .
Glutaminase, EF-hand domain (Glutaminase_EF-hand)
Type: Domain

This EF-hand domain is found at the N terminus of the human glutaminase enzyme .
Beta-xylosidase, C-terminal Concanavalin A-like domain (GH43_C2)
Type: Domain

This domain is found to the C terminus of the glycoside hydrolase (

) domain. This domain adopts a concanavalin A-like fold.
Domain of unknown function DUF5644 (DUF5644)
Type: Domain

This is a helical domain of unknown function found in Helicobacterial proteins of unknown function.
MotY N-terminal domain (MotY_N)
Type: Domain

The bacterial flagellar motor is a rotary motor complex composed of various proteins. MotX and MotY are essential for the Na+-driven flagellar motor motility of Vibrio, Shewanella and Aeromonas species. MotY is main component for T-ring formation and absence of MotY completely disrupt the T-ring formation . This is the N-terminal domain of MotY which is shown to be essential for motility and responsible for the interaction with both MotX and the basal body. Functional analysis suggests that MotY-N connects the basal body to MotX and that the PomA/PomB complex associates with MotX to form the functional stator complex around the rotor. MotY-N alone does not associate strongly with the basal body, but the partial T-ring structure made of the MotY-N/MotX complex is sufficient to allow at least a few PomA/PomB stator complexes to be incorporated into the motor .
RABX5, catalytic core helical domain (DUF5601)
Type: Domain

This domain is found in the catalytic core RABEX-5 present in Homo sapiens. RABEX, also known as Rab GTPase exchange factors, regulate endocytic trafficking through activation of the Rab families RAB5, RAB21 and RAB22. The domain is helical in nature .
ClpA/ClpB, AAA lid domain (ClpA/ClpB_AAA_lid)
Type: Domain

This entry represents the α-helical AAA+ lid domain that is found to the C terminus of AAA domains.

Proteins containing this domain include ClpA/B . These proteins are thought to protect cells from stress by controlling the aggregation and denaturation of vital cellular structures. They vary in size, but share a domain which contains an ATP-binding site.
C->U-editing enzyme APOBEC-1 (APOBEC1)
Type: Family

This entry includes APOBEC1 from animals. APOBEC1 is a catalytic component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the APOB mRNA .
Immunomodulating metalloprotease helical domain (IMPa_helical)
Type: Domain

IMPa is an immunomodulator metalloprotease that belongs to the peptidase M60 family. This entry represents the helical domain found N-terminal to the Ig domain .
Fatty acid synthase type I, helical (FASI_helical)
Type: Domain

This domain is found in the fatty acid synthase (FAS) type I complex found in Actinobacteria such as Mycobacterium smegmatis and fungal species such as Thermomyces lanuginosus. FAS is a homo-hexameric enzyme that catalyzes synthesis of fatty acid precursors of mycolic acids. This domain is composed of dimerization module 1 (DM1) and four-helix bundle (4HB), both of which are conserved parts of the acetyl transferase .