SII-SWORD/CoKE huggingface dataset:
Glycosyl hydrolases family 10, active site (GH10_AS)
Type: Active_site

The microbial degradation of cellulose and xylans requires several types of enzymes such as endoglucanases (

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family F or as the glycosyl hydrolases family 10 .

This entry represents one of the conserved regions in these enzymes, which is centred on a conserved glutamic acid residue that has been shown , in the exoglucanase from Cellulomonas fimi, to be directly involved in glycosidic bond cleavage by acting as a nucleophile.
Helper-component proteinase (HC-Pro) cysteine protease (CPD) domain (HC_PRO_CPD_dom)
Type: Domain

This entry represents the CPD domain of the HC-Pro protein.

Potyviruses form one of the most numerous groups of plant viruses and are a major cause of crop loss worldwide. The helper-component proteinase (HC-Pro) is an indispensable, multifunctional protein of members of the genus Potyvirus and other viruses of the family Potyviridae. It is directly involved in diverse steps of viral infection, such as aphid plant-to-plant transmission, polyprotein processing, and suppression of host antiviral RNA silencing. HC-Pro is generally divided into three functional domains: a N-terminal domain, a central region, and a cysteine protease domain (CPD) in the C-terminal region. The HC-Pro CPD domain has a protease activity that autocatalytically cleaves a Gly-Gly dipeptide at its own C terminus to release HC-Pro from the rest of the viral polyprotein. Cysteine and histidine residues form the catalytic dyad at the active site. The HC-Pro CPD domain constitutes the peptidase family C6 of the CA clan .

The HC-Pro CPD domain adopts a compact oval-shaped α/β fold. The secondary structure elements include four α-helices (alpha1-alpha4) and two short β-strands (beta1 and beta2) arranged in the order alpha1-alpha2-alpha3-beta1-beta2-alpha4. In addition, two 3(10) helices are located between alpha3 and beta1 and downstream of alpha4. The four helices form a helix bundle packed against one face of a short β-hairpin formed by strands beta1 and beta2. The catalytic residue Cys is located at the N terminus of helix alpha1, and the other catalytic residue His is located on strand beta2. The substrate binding cleft is lined by the loop connecting helices alpha2 and alpha3 and the N-terminal region of helix alpha1 on one side and by strand beta2 on the other side .
F-BAR domain (F_BAR_dom)
Type: Domain

All eukaryotic cells are surrounded by a plasma membrane, and they also
contain multiple membrane-based organelles and structures inside cells. Thus
membrane remodeling is likely to be important for most cellular activities and
development. The Bin-Amphiphysin-Rvs (BAR) domain superfamily of proteins has
been found to play a major role in remodeling cellular membranes linked with
organelle biogenesis, membrane trafficking, cell division, cell morphology and
cell migration. The BAR domain superfamily of proteins is evolutionarily
conserved with representative members present from yeast to man. Currently
there are three distinct families of BAR domain proteins: classical BAR, F-BAR (FCH-BAR e.g., Fes/CIP4 homology BAR e.g., Toca-1) and I-
BAR (inverse-BAR e.g., IRSp53). The classical BAR, F-BAR, and I-BAR domains
are structurally similar homodimeric modules with antiparallel arrangement of
monomers .

The F-BAR domain is emerging as an important player in membrane remodeling
pathways. F-BAR domain proteins couple membrane remodeling with actin dynamics
associated with endocytic pathways and filopodium formation. F-BAR domain
containing proteins can be categorized into five sub-families based on their
phylogeny which is consistent with the additional protein domains they
possess, for example, RhoGAP domains, Cdc42 binding sites,
SH2 domains, SH3 domains and tyrosine
kinase domains .

The N-terminal part (about one third) of the F-BAR domain was previously
characterised as an FCH (FER-CIP4 homology) domain. However, the region of
sequence similarity extends to an adjacent region with a coiled-coil (CC)
structure. Hence, the F-BAR domain (FCH+CC, ~300 amino acids) has also been
called extended FC (EFC) domain. The F-BAR domain plays a role in dimerization
and membrane phospholipid binding. It binds specifically to certain kinds of
lipids and acts as a a dimeric membrane-binding curvature effector .

The F-BAR domain is composed of five helices. Its structure is composed of a
short N-terminal helix, three long α-helices, and a short C-terminal helix
followed by an extended peptide of 17 amino acids .
Peptidase family M60 domain (Peptidase_M60_dom)
Type: Domain

The peptidase family M60 domain belongs to the Merops zincin superfamily of zinc-requiring metalloproteases (clan MA, subclan MA(E)). The peptidase family M60 domain contains the metal-binding consensus motif HExxH. The two histidine residues are ligands of the catalytic Zn(2) and the glutamic acid residue is involved in nucleophilic attack. An additional conserved glutamic acid is found approximately 20 residues from the first histidine within the metal-binding motif. The second conserved glutamic acid potentially acts as a third proteous Zn(2) ligand. The peptidase family M60 domain targets complex host glycoproteins, such as mucins .

Some proteins known to contain a peptidase family M60 domain are listed below:

Baculovirus viral enhancing factor (VEF), also known as Enhancin, a metalloprotease that enhances viral infection by degrading the peritrophic membrane (PM) of the insect midgut.

Bacteria enhancin-like metalloproteases.

Mammalian FAM115 family proteins (also known as TRPM8 channel-associated factor 1-3).
CBP/p300-type histone acetyltransferase domain (CBP_P300_HAT)
Type: Domain

Histone acetyltransferase (HAT) enzymes play important roles in the regulation of chromatin assembly, RNA transcription, DNA repair and other DNA-templated reactions through the lysine side-chain acetylation of histones and other transcription factors. HATs fall into at least four different families based on sequence conservation within the HAT domain. This includes Gcn5/PCAF, CBP/p300, Rtt109 and MYST families. The different HAT families contain a structurally conserved central region associated with acetyl-Coenzyme A (Ac-CoA) cofactor binding but distinct catalytic mechanisms and structurally divergent flanking regions that mediate different chromatin regulatory functions. Protein acetylation extends beyond histones to other nuclear proteins and even cytoplasmic proteins to regulate diverse biological processes including the regulation of cell cycle, vesicular trafficking, cytoskeleton reorganisation and metabolism.

CREB-binding protein (CBP)/p300 proteins are involved in various physiological events including proliferation, differentiation and apoptosis. CBP/p300 proteins contain several well-defined protein-interaction domains as well as a centrally located 380-residue HAT domain .

The overall fold of the CBP/p300-type HAT domain consists of a central β-sheet comprising seven β-strands surrounded by nine α-helices and several loops .

Some proteins known to contain a cBP/p300-type HAT domain are listed below:

Animal CBP (also known as KAT3A), a coactivator for the cAMP-responsive transcription factor CREB.

Animal p300 (also known as KAT3B), binds to the adenoviral oncoprotein E1A.

Arabidopsis thaliana HACs, involved in the ethylene signaling pathway (HAC1, HAC2, HAC4, HAC5 and HAC12). All the HAC members share the CBP/p300- type HAT domain; however, the HAT domain of HAC1 but not that of HAC2 possesses acetyltransferase activity, while the situation had not been tested in the other HAC members .
Filoviruses VP35 interferon inhibitory domain (VP35_IID)
Type: Domain

The Filoviridae family of viruses, which includes marburgvirus (MARV) and
ebolavirus (EBOV), can cause intermittent outbreaks that often result in high
fatality rates. The family consists of five species of EBOV, Zaire, Reston,
Sudan, Tai Forest, and Bundibugyo; one species of MARV; and a proposed genus
Cuevavirus possessing a single species Lloviu cuevavirus. MARV and EBOV share
a common genome organisation but show important differences in replication
complex formation, cell entry, host tropism, transcriptional regulation, and
immune evasion .

Filoviruses counteract innate immunity through the multifunctional viral
protein (VP) 35 proteins, which perform critical roles in viral RNA synthesis,
virus assembly, and virus structure. VP35 contains an N-terminal coiled-coil
domain required for its oligomerisation and a C-terminal interferon (IFN)
inhibitory domain (IID). Mutations within the VP35 IID result in loss of host
immune suppression. The N terminus provides a critical oligomerisation
function, which facilitates efficient IFN inhibition through elements located
at the C terminus of VP35. The VP35 IID can also bind dsRNA and VP35-mediated
IFN antagonism correlates with dsRNA-binding activity .

This entry represents the C-terminal interferon inhibitory (IID) domain of VP35, also known as RNA-binding domain (RBD) IID is made of a stretch of about 120 residues that folds
independently. The VP35 IID structure is organised into 2 subdomains: an N-
terminal α-helical subdomain and a C-terminal β-sheet subdomain. The α-helical subdomain consists of a four helix bundle, while the β-sheet subdomain is formed by four antiparallel β-strands as well as an α-helix and a type II polyproline helix. The VP35 IID structure contains 2 basic patches that are highly conserved among members of the Filoviridae family. The first basic patch is located in the helical subdomain and its functional significance remains unknown. The second one, the so-called central basic patch, is located in the β-sheet subdomain and contains residues that are required for dsRNA binding and IFN inhibition .
SAM-binding methyltransferase MPBQ/MBSQ (SAM_MPBQ_MSBQ_MT)
Type: Domain

This entry represents a domain found in a subgroup of the SAM-binding methyltransferase family. Proteins containing this domain include MPBQ/MSBQ methyltransferase from plants .
Yjdj-type Gcn5-related N-acetyltransferase (GNAT_YJDJ)
Type: Domain

The N-acetyltransferases (NAT) ([ec:2.3.1.-]) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction implicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodeling. The Gcn5-related N-acetyltransferases (GNAT) catalyse the transfer of the acetyl from the CoA donor to a primary amine of the acceptor. The GNAT proteins share a domain composed of four conserved sequence motifs A-D . This GNAT domain is named after yeast GCN5 (from General Control Nonrepressed) and related histone acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residues
of amino terminal histone tails, resulting in transcription activation. Another category of GNAT, the aminoglycoside N-acetyltransferases, confer antibiotic resistance by catalysing the acetylation of amino groups in aminoglycoside antibiotics . GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes .

The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 β strands (B) and 4 helices (H) in the topology B1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may be from the same monomer or contributed by another . Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core , while the N-terminal motif C (B1-H1) is less conserved.

The entry represents the NAGS-type GNAT domain .
EngA-type guanine nucleotide-binding (G) domain (G_ENGA)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

EngA (Essential neisserial GTPase A) proteins belong to TrmE-Era-EngA-YihA- Septin like superfamily of TRAFAC class and form a unique family of bacterial GTPases with two G domains in tandem, namely GD1 and GD2, followed by a C- terminal KH-like domain. They have been shown to interact with the bacterial ribosome and to be involved in its biogenesis .

The EngA-type G domains consist of ~159-170 amino acid residues and show sequence homology to the Era-type G domain. The EngA-type G domain has thus also been termed Der, because it has double Era-like G domains . The EngA- type G domain is composed of 5 α helices and 6 β sheets linked by characteristic loops constituting switch I and II. Each EngA- type G domain contains conserved residues organised in five distinct motifs numbered G1-G5. In the G1/Walker A motifs of EngA (Gx(4)GKS) or P-loop, the two invariant lysine residues are known to coordinate the phosphate of nucleotide. G2 (DxxG) belongs to the loop forming switch I and interacts with a Mg(2+) ion as well as the G3/Walker B motif (DxxG). G4 has a characteristic NKxD sequence that is unique to GTPases and provides specificity to GTP. The G5 motif (SA) is less obvious.
OBG-type guanine nucleotide-binding (G) domain (G_OBG)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

Within the translation factor-related (TRAFAC) class of P-loop GTPases, the OBG family comprises a group of high-molecular mass GTPases conserved from bacteria to eukaryotes. The OBG family consists of :

Obg from bacteria and eukaryotes .

DRG from eukaryotes and archaea. DRG proteins may regulate fundamental cellular processes through RNA binding .

Nog1 from eukaryotes and archaea. It is involved in the assembly of the large ribosomal subunit.

Yyaf/YchF from bacteria and eukaryotes. It consists of a central G domain, flanked by a coiled-coil domain and a TGS (ThrRS, GTPase, SpoT) domain. Members of this subfamily bind and hydrolyse ATP more efficiently than GTP .

Ygr210 from archaea and fungi.

The OBG-type G domain has a mononucleotide binding fold typical for the P-loop NTPases. A six-stranded mostly parallel β-sheet is flanked by α-helices on both sides. The OBG-type G domain contains five characteristic sequence motifs, termed G1-G5, involved in nucleotide binding and hydrolysis. The G1/Walker A motif (GXXXXGK(S/T)), also referred to as P-loop, helps to position the triphosphate moiety of the bound nucleotide. The G2 (X(T/S)X) and G3/Walker B (hhhDXXG) motifs are involved in the coordination of a Mg(2)+ ion that is required for nucleotide binding and hydrolysis. Specificity in nucleotide binding is conferred by the G4 motif, which has a (N/T)KXD signature in guanine nucleotide binding P-loop NTPases. The G5 motif ((T/G)(C/S)A) supports guanine base recognition .
TrmE-type guanine nucleotide-binding domain (G_TrmE)
Type: Domain

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

TrmE (also called MnmE, ThdF or MSS1) contains a canonical G domain and is conserved in all three kingdoms of life. It is involved in the modification of uridine bases (U34) at the first anticodon (wobble) position of tRNAs decoding two-family box triplets. TrmE is organised as a multidomain protein consisting of an ~220-amino acid N-terminal domain, probably required for self-assembly, a middle GTPase domain, of about 160 residues, and an ~75-amino acid C-terminal domain, which contains a highly conserved CxGK motif. TrmE contains at least four of the five conserved nucleotide-binding motifs G1 (GxxxxGK[ST] or P- loop), G2 (T), G3 (DxxG) and G4 ([NT]KxD). The totally invariant alanine in the SA[KL] (G5) motif of Ras anGalph proteins is less well conserved .

TrmE functions as a molecular switch GTPase, and apparently uses a conformational change associated with GTP hydrolysis to promote the tRNA modification reaction, in which the conserved cysteine in the C-terminal domain is thought to function as a catalytic residue. In bacteria that are able to survive in extremely low pH conditions, TrmE regulates glutamate-dependent acid resistance .

This entry represents the TmrE-type G domain. The structure of the TrmE-type G domain consists of a a canonical Ras-like fold: central four-stranded β-sheet flanked by five α-helices. It dimerises in a potassium-dependent manner .
Serpin E3 (Serpin_E3)
Type: Family

Serpin E3 is a member of clade E (nexin, plasminogen activator inhibitor type 1) of the serpin (serine peptidase inhibitor) family . Its function is not known.

Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins . Others, such as ovalbumin, are incapable of protease inhibition and serve other functions .
ELL/occludin family (ELL/occludin)
Type: Family

This entry represents the ELL/occludin family. Occludin is found in the tight junction and may play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier . ELL is a family of RNA polymerase II elongation factors. It is bound stably to elongation-associated factors 1 and 2, EAFs, and together these act as a strong regulator of transcription activity by direct interaction with Pol II. ELL binds to pol II on its own but the affinity is greatly increased by the cooperation of EAF .
Antizyme inhibitor 1 (Azin1)
Type: Family

Antizymes (AZs) are polyamine-induced proteins that promote degradation of ornithine decarboxylase (ODC), the key enzyme in the polyamine biosynthetic pathway . AZs also negatively regulate polyamine transport into the cells through an unknown mechanism . AZs are in turn regulated by antizyme inhibitors (AZIN1 and AZIN2), which are proteins homologous to ODC that bind to AZs and counteract their negative effect on ODC .

AZIN1 is expressed in most tissues of mouse and participates in polyamine metabolism and cell growth . AZIN1 is induced by various proliferative stimuli and repressed by polyamines, forming a negative feedback loop .
Syntaxin-3, SNARE motif (STX3_SNARE)
Type: Domain

Syntaxin-3 (STX3) belongs to the syntaxin family, whose members are involved in docking of synaptic vesicles at presynaptic active zones . It interacts with the SNARE regulator Munc18-2 and plays a role in mast cells degranulation . It plays an important role in trafficking pathways of cytokines in neutrophil granulocytes . Mutations have been implicated in human microvillus inclusion disease (MVID), a disorder of the differentiation of intestinal epithelium .

This entry represents the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) motif of SYN3, which consist of coiled-coil helices.
PHD finger protein 1, PHD finger 1 (PHF1_PDH-finger1)
Type: Domain

This entry represents the first PHD finger of PHF1.

PHD finger protein 1 (PHF1) is a polycomb group (PcG) protein that plays a role in H3K27 methylation and Hox gene silencing . The Tudor domain of human PHF1 recognises both H3K36me3 and H3tK27me3 . The interaction between PHF1 and H3K36me3 stabilises the nucleosome in a conformation in which the nucleosomal DNA is more accessible to DNA-binding regulatory proteins . PHF1 is also involved in the response to DNA double-strand breaks and acts as a positive regulator of the p53 pathway .
Nestin (Nestin)
Type: Family

Nestin is an intermediate filament protein. However, nestin cannot form homodimers to form intermediate filaments due to its short N-terminal; it can only form heterodimers and heterotetramers by binding with other intermediate filament proteins, particularly the class 3 proteins vimentin and alpha-internexin . It is believed to be a neural stem cell marker during central nervous system (CNS) development , although it is also expressed in other tissues . Nestin has been found to be involved in tumour angiogenesis .
XIAP-associated factor 1, C-terminal superfamily (XAF1_C_sf)
Type: Homologous_superfamily

XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonises the caspase-inhibitory activity of XIAP . It is a tumor suppressor that is frequently inactivated in many human cancers. It forms a positive feedback loop with p53 and acts as a molecular switch in p53-mediated cell-fate decisions favoring apoptosis over cell-cycle arrest .

This entry represents the C-terminal domain which is functionally identified as XIAP(RING)-binding domain of XAF1 .
Stonin-2, Mu homology domain (STON2_MHD)
Type: Domain

Stonin-2 is a stonin family protein involved in synaptic vesicle recycling. It is an adaptor-like protein that serves as a linker between the endocytic proteins AP-2 and Eps15, and the calcium-sensing synaptic vesicle (SV) protein synaptotagmin 1 .

Stonin family members are conserved clathrin adaptor complex AP-2mu-related factors that may act as cargo-specific sorting adaptors in endocytosis. They are conserved from C. elegans to humans, but are not found in prokaryotes or yeasts. Their protein structure consists of an N-terminal proline- and serine-rich domain, a central stonin homology domain (SHD), and a C-terminal Mu homology domain that may adopt a conformation similar to the C-terminal sorting signal binding domain of AP-2mu (C-mu2) .

This entry represents the Mu homology domain (MHD) of Stonin-2.
Latrophilin-1, , transmembrane domain (Latrophilin-1_TM)
Type: Domain

Latrophilins are a family of secretin-like GPCRs that can be subdivided
into 3 subtypes: Latrophilin-1 (LPH1), -2 (LPH2), and -3 (LPH3). LPH1, also known as Adhesion G protein-coupled receptor L1 (Adgrl1), is a brain-specific calcium independent receptor of alpha-latrotoxin (LTX), a neurotoxin present in black widow spider venom which triggers massive exocytosis from presynaptic nerve terminals . It is the affinity of this form of the receptor for LTX that gives the family its name.

Two endogenous ligands for latrophilins have been described, teneurin-2 and FLRT3 . LPH1 has been shown to bind Lasso (a splice variant of teneurin-2). LPH1 and Lasso interact across intercellular and synaptic junctions, suggesting an involvement in synaptic functions . Latrophilins are potential synaptic cell-adhesion molecules that interact trans-synaptically with teneurins and FLRTs .

This entry represents the seven-transmembrane helix domain of LPH1.
E3 ubiquitin-protein ligase RNF213 (RNF213)
Type: Family

RNF213 functions as ubiquitin ligase and AAA+ ATPase, and plays a role in vascular development through mechanical processes in the cell . It contains a RING finger domain, which is a well-established ubiquitin ligase domain that covalently modifies substrate proteins with ubiquitin and stimulates the proteasomal protein degradation. It also functions as an ATPase through its AAA+ ATPase modules . The RNF213 gene is a susceptibility gene for moyamoya disease, an idiopathic vascular disorder of intracranial arteries .