SII-SWORD/CoKE huggingface dataset:
Carbohydrate binding module family 11 (CBM11)
Type: Domain

This entry represents

, which binds both beta-1,4-glucan and beta-1,3-1,4-mixed linked glucans.

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose . However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see .
Carbohydrate binding module family 15 (CBM15)
Type: Domain

This entry represents

which binds to xylan and xylooligosaccharides .

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose . However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see .
Carbohydrate-binding module family 19 (CBM19)
Type: Domain

This entry represents

which consists of 60-70 residues with chitin-binding function.

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity. A few exceptions are CBMs in cellulosomal scaffolding proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose . However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Previous classification of cellulose-binding domains were based on amino acid similarity. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII. For a detailed review on the structure and binding modes of CBMs see .
Plasmid replication protein C, N-terminal (RepC_N)
Type: Domain

Proteins in this group have homology with the RepC protein of Agrobacterium Ri and Ti plasmids . repABC plasmids are widely distributed among alphaproteobacteria; all repABC operons contain at least three protein-encoding genes: repA, repB and repC. The first two genes encode proteins involved in plasmid segregation, whereas repC encodes a protein crucial for replication. The origin of replication maps within the repC gene . RepC is rate limiting for pT181 replication and it is likely that pT181 replication is regulated at the level of RepC synthesis . This entry represents the N-terminal HTH domain of plasmid replication protein RepC.
Major surface protein 1B (MSP1b)
Type: Family

The major surface protein (MSP1) of the cattle pathogen Anaplasma is a heterodimer comprised of MSP1a and MSP1b. This family is the MSP1b chain. The MSP1
proteins are putative adhesins for bovine erythrocytes .
Trans-activating transcriptional regulator (TATR)
Type: Family

This family of trans-activating transcriptional regulators (TATR), also known as intermediate early protein 1, are common to the Nucleopolyhedroviruses .
RNA-directed RNA polymerase beta-chain (RNArep_beta)
Type: Family

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This is a family of Leviviridae RNA replicases.
MobA/VirD2-like, nuclease domain (Endonuclease_MobA/VirD2)
Type: Domain

Relaxases/mobilisation proteins are required for the horizontal transfer of genetic information contained on plasmids that occurs during bacterial conjugation. The relaxase, in conjunction with several auxiliary proteins, forms the relaxation complex or relaxosome. Relaxases nick duplex DNA in a specific manner by catalysing trans-esterification . The VirD2 protein is a T-DNA border endonuclease from Rhizobium radiobacter that is important for the transfer and integration of a defined segment (T-DNA) of Ti plasmid DNA into the plant nuclear genome leading to tumour formation. VirD2 cleaves at a unique site within both 24 bp direct repeats flanking the T-DNA .

This entry represents the nuclease domain of VirD2 and related proteins such as Rlx, TraI, cryptic plasmid protein C, relaxase LtrB and MbeA.
EspA-like secreted protein (EspA)
Type: Family

EspA, together with EspB, EspD and Tir are exported by a type III secretion system. These proteins are essential for attaching and effacing lesion formation. EspA is a structural protein and a major component of a large, transiently expressed, filamentous surface organelle which forms a direct link between the bacterium and the host cell .
Protein of unknown function DUF276 (DUF276)
Type: Family

This family is specific to Borrelia burgdorferi (Lyme disease spirochete). The protein is encoded on extrachromosomal DNA and is of unknown function.
Saccharopine dehydrogenase, NADP binding domain (Sacchrp_dh_NADP-bd)
Type: Domain

This entry represents the NADP binding domain of saccharopine dehydrogenase. In some organisms, this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase. The saccharopine dehydrogenase can also function as a saccharopine reductase .

Saccharopine dehydrogenase (

) catalyses the condensation of l-alpha-aminoadipate-delta-semialdehyde (AASA) with l-glutamate to give an imine, which is reduced by NADPH to give saccharopine . Saccharopine is an intermediate in lysine metabolism.

Homospermidine synthase (HSS) (

) catalyses the synthesis of the polyamine homospermidine from 2 putrescine molecules in an NAD
+
-dependent reaction . HSS evolved from the alternative spermidine biosynthetic pathway enzyme carboxyspermidine dehydrogenase and the structure of HSS is related to lysine metabolic enzymes .
Domain of unknown function DUF281 (DUF281)
Type: Domain

This domain is found in a number of worm proteins and has no known function. The boundaries of the presumed domain are rather uncertain.
Pneumovirus NS1 protein (Pneumo_NS1)
Type: Family

This non-structural protein is one of two found in pneumoviruses. The protein is about 140 amino acids in length. The NS1 protein appears to be important for efficient replication but not essential . The NS1 protein has been shown by yeast two-hybrid to interact with the viral P protein . This protein is also known as the 1C protein. It has also been shown that NS1 can potently inhibit transcription and RNA replication .
NGN domain (NGN-domain)
Type: Domain

Spt5p and prokaryotic NusG are shown to contain a novel 'NGN' domain. The combined NGN and KOW motif regions of Spt5 form the binding domain with Spt4 . Spt5 complexes with Spt4 as a 1:1 heterodimer snf this Spt5-Spt4 complex regulates early transcription elongation by RNA polymerase II and has an imputed role in pre-mRNA processing via its physical association with mRNA capping enzymes. The Schizosaccharomyces pombe core Spt5-Spt4 complex is a heterodimer bearing a trypsin-resistant Spt4-binding domain within the Spt5 subunit .
Cryptochrome/DNA photolyase, FAD-binding domain (Cryptochr/Photolyase_FAD-bd)
Type: Domain

This entry represents a multi-helical domain found in the C terminus of the cryptochrome proteins and DNA photolyases. It acts as a FAD-binding domain .

The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals .
Carbohydrate binding X2 domain (Carbo-bd_X2)
Type: Domain

This domain binds to cellulose and to bacterial cell walls. It is found in glycosyl hydrolases and in scaffolding proteins of cellulosomes (multiprotein glycosyl hydrolase complexes). In the cellulosome it may aid cellulose degradation by anchoring the cellulosome to the bacterial cell wall and by binding it to its substrate . This domain has an Ig-like fold .
Auxiliary Activity family 9, catalytic domain (AA9_LPMO)
Type: Domain

This entry represents the lytic polysaccharide monooxygenase (LPMO) domain of AA9 .

Although weak endoglucanase activity has been demonstrated in several members of this family , they lack the clustered conserved catalytic acidic amino acids present in most glycoside hydrolases. Many members of this family lack measurable cellulase activity on their own, but enhance the activity of other cellulolytic enzymes. They are therefore unlikely to be true glycoside hydrolases . The substrate-binding surface of this family is a flat Ig-like fold . This family of enzymes were originally classified as glycoside hydrolases (GH61) and they have been reclassified as the Auxiliary Activity Family 9 (

, ) of CAZy.
Winged helix-turn-helix transcription repressor, HrcA DNA-binding domain (WHTH_HrcA_DNA-bd)
Type: Domain

Prokaryotic cells have a defence mechanism against a sudden heat-shock stress. Commonly, they induce a set of proteins that protect cellular proteins from being denatured by heat. Among such proteins are the GroE and DnaK chaperones whose transcription is regulated by a heat-shock repressor protein HrcA. HrcA is a winged helix-turn-helix repressor that negatively regulates the transcription of dnaK and groE operons by binding the upstream CIRCE (controlling inverted repeat of chaperone expression) element. In Bacillus subtilis this element is a perfect 9 base pair inverted repeat separated by a 9 base pair spacer.

This domain represents the winged helix-turn-helix DNA-binding domain which is located close to the N terminus of HrcA. This domain is also found at the N terminus of a set of uncharacterised proteins that have two C-terminal CBS domains.
Protein-PII uridylyltransferase, N-terminal (GlnD_Uridyltrans_N)
Type: Domain

This domain is found associated with an N-terminal cyclic nucleotide-binding domain (

) and two CBS domains (

). This domain, normally represents the C-terminal region, is uncharacterised; however, it seems to be similar to the nucleotidyltransferase domain (

), conserving the DXD motif, which strongly suggests that proteins containing this domain are also nucleotidyltransferases.
Aspartate/homoserine dehydrogenase, NAD-binding (Asp/hSer_DH_NAD-bd)
Type: Domain

This entry represents the NAD(P)-binding domain of aspartate and homoserine dehydrogenase. Asparate dehydrogenase (

) is strictly specific for L-aspartate as substrate and catalyses the first step in NAD biosynthesis from aspartate. The enzyme has a higher affinity for NAD+ than NADP+ .

Note that the C terminus of the protein contributes a helix to this domain that is not covered by this entry.

Homoserine dehydrogenase (

) catalyses the third step in the aspartate pathway; the NAD(P)-dependent reduction of aspartate beta-semialdehyde into homoserine . Homoserine is an intermediate in the biosynthesis of threonine, isoleucine, and methionine. The enzyme can be found in a monofunctional form, in some bacteria and yeast, or a bifunctional form consisting of an N-terminal aspartokinase domain and a C-terminal homoserine dehydrogenase domain, as found in bacteria such as Escherichia coli and in plants. Structural analysis of the yeast monofunctional enzyme (

) indicates that the enzyme is a dimer composed of three distinct regions; an N-terminal nucleotide-binding domain, a short central dimerisation region, and a C-terminal catalytic domain . The N-terminal domain forms a modified Rossman fold, while the catalytic domain forms a novel α-β mixed sheet.

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .
CO dehydrogenase flavoprotein, C-terminal (CO_DH_flav_C)
Type: Domain

Proteins containing this domain form structural complexes with other known families, such as

and

. The carbon monoxide (CO) dehydrogenase of Oligotropha carboxidovorans is a heterotrimeric complex composed of a apoflavoprotein, a molybdoprotein, and an iron-sulphur protein. It can be dissociated with sodium dodecylsulphate . CO dehydrogenase catalyses the oxidation of CO according to the following equation :
CO + H2O = CO2 + 2e + 2H+

Subunit S represents the iron-sulphur protein of CO dehydrogenase and is clearly divided into a C- and an N-terminal domain, each binding a [2Fe-2S] cluster .
HELP motif (HELP)
Type: Conserved_site

This entry represents the HELP (Hydrophobic ELP) motif found in animal EMAP and EMAP-like proteins (ELPs). These proteins are involved in the formation of the mitotic spindle and interphase microtubule network and for normal proliferation of neuronal progenitor cells in the developing brain and normal brain development . HELP is not an independent domain, it is part of the hydrophobic core that joints the two β-propellers contributing blades 1 and 14 that are buried at the interface between them . These β-propellers have been defined as TAPE (tandem atypical propeller in EMLs) domain. This motif is essential for the folding of the TAPE domain, which binds alpha/beta-tubulin .
MoeA, N-terminal and linker domain (MoeA_linker/N)
Type: Domain

This entry represents the N-terminal and linker domains of the MoeA protein. One of these two structural domains contains the conserved DGXA motif. These two domains are found in proteins involved in biosynthesis of molybdopterin cofactor. MoeA facilitates molybdenum incorporation at low levels of molybdate . However, the exact molecular function of this region is uncertain .

The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism .
MoeA, C-terminal, domain IV (MoeA_C_domain_IV)
Type: Domain

The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism .

This domain is found in proteins involved in biosynthesis of molybdopterin cofactor however the exact molecular function of this domain is uncertain. The structure of this domain is known and forms an incomplete β barrel.
dDENN domain (dDENN_dom)
Type: Domain

This entry represents the dDENN domain.

The tripartite DENN (Differentially Expressed in Normal and Neoplastic Cells) domain is an evolutionarily conserved protein module found in several proteins involved in Rab-mediated processes and, in some cases, regulation of MAPK (Mitogen-Activated Protein Kinase) signalling pathways and related proteins in eukaryotic organisms. The DENN domain consists of three subdomains: uDENN (upstream DENN)

, the core DENN domain

, and dDENN (downstream DENN)

, which are structurally distinct but functionally interconnected due to their roles in Rab GTPase activation. Recent studies have confirmed the DENN domain's function as a guanine nucleotide exchange factor (GEF) for Rab GTPases, facilitating the exchange of GDP for GTP to activate Rabs. This activity has been demonstrated for various DENN proteins, such as DENND1A and DENND1B, which specifically activate Rab35, and DENND2B, which serves as a GEF for Rab10 and Rab13, influencing processes like primary ciliogenesis and epithelial cancer development .

The tripartite structure of the DENN domain, comprising uDENN, DENN itself, and dDENN, features distinct patterns of sequence conservation and variable interdomain lengths that suggest functional specialisation. Structural studies have revealed conserved residues critical for Rab binding and catalytic activity, emphasising the role of DENN domains in spatially and temporally regulating membrane trafficking events . Additionally, DENN domains are often associated with other domains such as RUN

, PLAT

, which may further enhance their functional versatility in cellular signalling pathways .

Some proteins known to contain a tripartite DENN domain include:

Human mitogen-activated protein kinase activating protein containing death domain (MADD)

, orthologous to Rab3GEP

Human SET domain-binding factor 1 (SBF1)

Human DENN domain-containing protein 2B

Human C-myc promoter-binding protein

In Arabidopsis, SCD1 is a unique gene encoding for the only protein containing a complete DENN domain. SCD1 is part of a protein complex that interacts with the exocyst complex and the RabE1 family of GTPases. It is also involved in activating innate immune responses against bacteria .

Recent findings highlight the broader target spectrum of DENN domains than previously appreciated. For example, DENND2B interacts with Rab35 as both an effector and a GEF at intercellular bridges during cytokinesis. These discoveries underscore the importance of DENN domain proteins in regulating diverse cellular processes such as vesicle trafficking, signal transduction, ciliogenesis, and cancer progression .
uDENN domain (uDENN_dom)
Type: Domain

The tripartite DENN (Differentially Expressed in Normal and Neoplastic Cells) domain is an evolutionarily conserved protein module found in several proteins involved in Rab-mediated processes and, in some cases, regulation of MAPK (Mitogen-Activated Protein Kinase) signalling pathways and related proteins in eukaryotic organisms. The DENN domain consists of three subdomains: uDENN (upstream DENN)

, the core DENN domain

, and dDENN (downstream DENN)

, which are structurally distinct but functionally interconnected due to their roles in Rab GTPase activation. Recent studies have confirmed the DENN domain's function as a guanine nucleotide exchange factor (GEF) for Rab GTPases, facilitating the exchange of GDP for GTP to activate Rabs. This activity has been demonstrated for various DENN proteins, such as DENND1A and DENND1B, which specifically activate Rab35, and DENND2B, which serves as a GEF for Rab10 and Rab13, influencing processes like primary ciliogenesis and epithelial cancer development .

The tripartite structure of the DENN domain, comprising uDENN, DENN itself, and dDENN, features distinct patterns of sequence conservation and variable interdomain lengths that suggest functional specialisation. Structural studies have revealed conserved residues critical for Rab binding and catalytic activity, emphasising the role of DENN domains in spatially and temporally regulating membrane trafficking events . Additionally, DENN domains are often associated with other domains such as RUN

, PLAT

, which may further enhance their functional versatility in cellular signalling pathways .

Some proteins known to contain a tripartite DENN domain include:

Human mitogen-activated protein kinase activating protein containing death domain (MADD)

, orthologous to Rab3GEP

Human SET domain-binding factor 1 (SBF1)

Human DENN domain-containing protein 2B

Human C-myc promoter-binding protein

In Arabidopsis, SCD1 is a unique gene encoding for the only protein containing a complete DENN domain. SCD1 is part of a protein complex that interacts with the exocyst complex and the RabE1 family of GTPases. It is also involved in activating innate immune responses against bacteria .

Recent findings highlight the broader target spectrum of DENN domains than previously appreciated. For example, DENND2B interacts with Rab35 as both an effector and a GEF at intercellular bridges during cytokinesis. These discoveries underscore the importance of DENN domain proteins in regulating diverse cellular processes such as vesicle trafficking, signal transduction, ciliogenesis, and cancer progression .

This entry represents the uDENN domain.
Helicase-associated (Helicase_assoc)
Type: Domain

This short domain can be found in multiple copies in helicase proteins. The domain is predicted to contain 3 α helices. The function of this domain may be to bind nucleic acid.