SII-SWORD/CoKE huggingface dataset:
CXC Chemokine domain (CXC_Chemokine_domain)
Type: Domain

This entry represents the CXC chemokine domain. Chemokines are clustered based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members contain an RCxC motif which may be a general requirement for binding to CXC chemokine receptors; those with the ELR motif are chemotatic for neutrophils and have been shown to be angiogenic, while those without the motif act on T and B cells, and are typically angiostatic; exist as monomers and dimers, but are believed to be functional as monomers; found only in vertebrates and a few viruses .

Many low-molecular weight factors secreted by cells including fibroblasts, macrophages and endothelial cells, in response to a variety of stimuli such as growth factors, interferons, viral transformation and bacterial products, are structurally related . Most members of this family of proteins seem to have mitogenic, chemotactic or inflammatory activities. These small cytokines are also called intercrines or chemokines. They are cationic proteins of 70 to 100 amino acid residues that share four conserved cysteine residues involved in two disulphide bonds, as shown in the following schematic representation:

+------------------------------------+
| |
xxxxxxxxxxxxxxxxxxxxxxCxCxxxxxxxxxxxxxxxxxxxxxxxCxxxxxxxxxxxxCxxxxx
| |
+-------------------------+

'C': conserved cysteine involved in a disulphide bond.

Chemokines can be sorted into main groups based on the spacing of the two amino-terminal cysteines. In the first group (see

), the two cysteines are separated by a single residue (C-x-C), while in the second group (see

), they are adjacent (C-C).
Porin domain, Gram-negative type (Gram_neg_porin_domain)
Type: Domain

Porins form aqueous channels for the diffusion of small hydrophillic molecules across the outer membrane . Individual 16-strand anti-parallel β-barrels form a central pore, and trimerizes through mainly hydrophobic interactions at the interface. Trimers are stabilized by hytrophillic clamping of Loop L2. Loop 3 bends into the pore, creating an elliptical constriction of about 7 x 11 angstroms, large enough to allow passage of a glucose molecule without steric hindrance. Removal of the C-terminal residue (usually Phe) destabilizes the trimer and removal of the 16th β-sheet abolishes trimerization. Unlike typical membrane proteins, porins lack long hydrophobic stretches. Short turns are found at the smooth, periplasmic end, longer irregular loops are found at the rough, extracellular end. The C-terminal residue forms a salt bridge with the N terminus .

This entry represents the structural domain found in Gram-negative bacterial porins.
DNA-directed RNA polymerases I and III subunit AC40 (RNAPI/III_AC40)
Type: Family

The eukaryotic AC40 subunit (also known as RPAC1) of RNA polymerase (RNAP) I and RNAP III is involved in the assembly of RNAP subunits. RNAP is a large multi-subunit complex responsible for the synthesis of RNA. It is the principal enzyme of the transcription process, and is a final target in many regulatory pathways that control gene expression in all living cells. At least three distinct RNAP complexes are found in eukaryotic nuclei: RNAP I, RNAP II, and RNAP III. RNAP I is responsible for the synthesis of ribosomal RNA precursor, while RNAP III functions in the synthesis of 5S and tRNA. The AC40 subunit is the equivalent of the RPB3 subunit of RNAP II . The RPB3 subunit is similar to the bacterial RNAP alpha subunit in that it contains two subdomains: one subdomain is similar the eukaryotic Rpb11/AC19/archaeal L subunit which is involved in dimerization; and the other is an inserted β sheet subdomain. The RPB3 subunit heterodimerizes with the RPB11 subunit, and together with RPB10 and RPB12, anchors the two largest subunits, RPB1 and RPB2, and stabilizes their association. The homology of AC40 to RPB3 suggests a similar function. The AC40 subunit is likely to associate with the RPB11 counterpart, AC19, to form a heterodimer, which stabilizes the association of the two largest subunits of RNAP I and RNAP III .
Patatin-like phospholipase domain-containing protein 4 (PNPLA4)
Type: Family

Patatin-like phospholipase domain-containing protein 4 (PNPLA4), also known as GS2 (gene sequence-2) or iPLA2-eta (calcium-independent phospholipase A2), shows both lipase and transacylation activities . GS2 lipase is expressed in various tissues, predominantly in muscle and adipocytes tissue. It is also expressed in keratinocytes and shows retinyl ester hydrolase, acylglycerol, TG hydrolase, and PLA2 activity .
Patatin-like phospholipase domain-containing protein 2 (PNPLA2)
Type: Domain

Patatin-like phospholipase domain-containing protein 2 (PNPLA2) plays a key role in the hydrolysis of stored triacylglycerols and is also known as adipose triglyceride lipase (ATGL) . Members of this family share a patatin domain, initially discovered in potato tubers . ATGL is expressed in white and brown adipose tissue at high mRNA levels. Mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) lead to neutral lipid storage disease (NLSD), which is characterised by the accumulation of triglycerides in multiple tissues . ATGL mutations are also commonly associated with severe forms of skeletal and cardiomyopathy. ATGL is regulated by insulin . PNPLA2/ATGL is also known as TTS-2.2 (transport-secretion protein 2.2), iPLA2-zeta (calcium-independent phospholipase A2), and desnutrin .
Trans-isoprenyl diphosphate synthases, head-to-head (Trans_IPPS_HH)
Type: Domain

This entry represents a domain found in Trans-Isoprenyl Diphosphate Synthases.

Trans-Isoprenyl Diphosphate Synthases (Trans_IPPS) catalyze a head-to-head (HH) (1'-1) condensation reaction . This entry includes squalene and phytoene synthases which catalyze the 1'-1 condensation of two 15-carbon (farnesyl) and 20-carbon (geranylgeranyl) isoprenyl diphosphates, respectively . The catalytic site consists of a large central cavity formed by mostly antiparallel α helices with two aspartate-rich regions (DXXXD) located on opposite walls . These residues mediate binding of prenyl phosphates . A two-step reaction has been proposed for squalene synthase (farnesyl-diphosphate farnesyltransferase) in which, two molecules of FPP react to form a stable cyclopropylcarbinyl diphosphate intermediate, and then the intermediate undergoes heterolysis, isomerization, and reduction with NADPH to form squalene, a precursor of cholesterol. The carotenoid biosynthesis enzyme, phytoene synthase (CrtB), catalyses the condensation reaction of two molecules of geranylgeranyl diphosphate to produce phytoene, a precursor of beta-carotene . These enzymes produce the triterpene and tetraterpene precursors for many diverse sterol and carotenoid end products and are widely distributed among eukaryota, bacteria, and archaea .
Lipase, N-terminal (Lipase_N)
Type: Domain

This entry includes the catalytic, N-terminal domain of pancreatic lipase-like enzymes.

Triglyceride lipases (

) are lipolytic enzymes that hydrolyse ester linkages of triglycerides . Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher vertebrates, pancreatic, hepatic and gastric/lingual. These lipases are closely related to each other and to lipoprotein lipase (

), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL) . The most conserved region in all these proteins is centred around a serine residue which has been shown to participate, with an histidine and an aspartic acid residue, in a charge relay system. Such a region is also present in lipases of prokaryotic origin and in lecithin-cholesterol acyltransferase (

) (LCAT) , which catalyzes fatty acid transfer between phosphatidylcholine and cholesterol.
Endolysin/autolysin (Endolysin_autolysin)
Type: Domain

Endolysins and autolysins are found in viruses and bacteria, respectively . The ds DNA phages of eubacteria use endolysins or muralytic enzymes in conjunction with hollin, a small membrane protein, to degrade the peptidoglycan found in bacterial cell walls . Similarly, bacteria produce autolysins to facilitate the biosynthesis of its cell wall hetropolymer peptidoglycan and cell division . Both endolysin and autolysin enzymes cleave the glycosidic beta 1,4-bonds between the N-acetylmuramic acid and the N-acetylglucosamine of the peptidoglycan.

This entry represents the lysozyme domain found in endolysins, autolysins and lysozymes.
R2-like ligand binding oxidase (R2LOX)
Type: Family

Two types of ferritin-like proteins have been identified that use a bimetallic Mn/Fe cofactor to perform chemically divergent oxidative reactions: the R2 subunit of class Ic ribonucleotide reductase, and R2-like ligand-binding oxidase (R2lox) . In the case of R2c, the cofactor acts as a transient one-electron oxidant, whereas R2lox is capable of performing a two-electron oxidation reaction, representing a distinct functional group among R2 homologues .
Ribonucleotide reductase small subunit (RNR_small)
Type: Family

The beta (small) subunit of ribonucleotide reductase (RNR) is a member of a broad superfamily of ferritin-like diiron-carboxylate proteins.
Methioninyl-tRNA synthetase core domain (MetRS_core)
Type: Domain

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Methionine tRNA synthetase (MetRS, also known as methionine tRNA ligase), a class I aminoacyl-tRNA synthetases, aminoacylates the 2'-OH of the nucleotide at the 3' of the appropriate tRNA. MetRS, which consists of the core domain and an anti-codon binding domain, functions as a monomer. However, in some species the anti-codon binding domain is followed by an EMAP domain. In this case, MetRS functions as a homodimer. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the characteristic class I 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. As a result of a deletion event, MetRS has a significantly shorter core domain insertion than IleRS, ValRS, and LeuR. Consequently, the MetRS insertion lacks the editing function .

This entry represents the catalytic core domain of MetRS.
MTH1175 domain (MTH1175_dom)
Type: Domain

This entry represents a domain found in MTH1175.

MTH1175 is an uncharacterised conserved protein belonging to a family of iron-molybdenum cluster-binding proteins that includes NifX, NifB, and NifY, all of which are involved in the synthesis of an iron-molybdenum cofactor (FeMo-co) that binds the active site of the dinitrogenase enzyme . This domain is a predicted small-molecule-binding domain (SMBD) with an α/β fold that is present either as a stand-alone domain (e.g. NifX and NifY) or fused to another conserved domain (e.g., NifB); however, its function is still undetermined . The SCOP database suggests that this domain is most similar to structures within the ribonuclease H superfamily. This conserved domain is represented in two of the three major divisions of life (bacteria and archaea) .
Npc2 like, ML domain (ML_Npc2-like)
Type: Domain

The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like β-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins:

Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein -Npc2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes .

House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus .

This entry refers to the ML domain found in metazoan Npc2 as well and some similar proteins.
ML domain, phosphatidylinositol/phosphatidylglycerol transfer protein (ML_PG-PI_TP)
Type: Domain

The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like β-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins:

Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein -Npc2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes .

House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus .

This entry refers to the ML domain found in phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP). PG/PI-TP has been shown to bind phosphatidylglycerol and phosphatidylinositol, but the biological significance of this is still obscure .
Transaldolase/Fructose-6-phosphate aldolase, archaeal/bacterial (TSA/FSA_arc/bac)
Type: Family

Transaldolase (TAL) is an enzyme of the pentose phosphate pathway (PPP) found almost ubiquitously in the three domains of life (Archaea, Bacteria, and Eukarya). TAL shares a high degree of structural similarity and sequence identity with fructose-6-phosphate aldolase (FSA) . They both belong to the class I aldolase family . Their protein structures have been revealed .

This entry refers to transaldolase/fructose-6-phosphate aldolase found in archea and bacteria.
DPS-like protein, ferritin-like diiron-binding domain (DPSL_diiron-bd_dom)
Type: Domain

Dps-like proteins are members of the broad superfamily of ferritin-like diiron-carboxylate proteins, which are non-haem iron storage proteins . The Dps-like protein from Sulfolobus solfataricus is structurally related to a class of DNA-binding protein from starved cells (Dps). It has been experimentally characterised and shown to self-assemble into a hollow dodecameric protein cage having tetrahedral symmetry, which uses H2O2 to oxidize Fe(II) to Fe(III), storing the oxide as a mineral core on the interior surface of the protein cage. Members of the Dps-like family may therefore be involved in the mitigation of oxidative damage .

This entry represents the ferritin-like diiron-binding domain of Dps-like proteins from archaea and bacteria. Many of the conserved residues of a diiron centre are present in this domain.
NAD(P) binding domain of glutamate dehydrogenase (NAD_bind_Glu_DH)
Type: Domain

Glutamate dehydrogenase (DH) is a multidomain enzyme that catalyzes the reaction from glutamate to 2-oxyoglutarate and ammonia in the presence of NAD or NADP. It is present in all organisms . Enzymes involved in ammonia assimilation are typically NADP+-dependent, while those involved in glutamate catabolism are generally NAD+-dependent . This entry represents the C-terminal domain.
p21 activated kinase binding domain (PAK_BD)
Type: Domain

PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases. It is also known as the Cdc42/Rac interactive binding (CRIB) motif. It has been shown to inhibit transcriptional activation and cell transformation mediated by the Ras-Rac pathway. This subgroup of CRIB/PBD-domains is found N-terminal of Serine/Threonine kinase domains in PAK and PAK-like proteins .
Alkanal monooxygenase (Alkanal_monooxygenase)
Type: Family

Alkanal monooxygenases, also known as bacterial luciferases, are flavin monoxygenases. Molecular oxygen is activated by reaction with reduced flavin mononucleotide (FMNH2) and reacts with an aldehyde to yield the carboxylic acid, oxidized flavin (FMN) and a blue-green light . Bacterial luciferases are heterodimers made of alpha and beta subunits which are homologous . The single active centre is on the alpha subunit. The alpha subunit has a stretch of 30 amino acid residues that is not present in the beta subunit. The beta subunit does not contain the active site and is required for the formation of the fully active heterodimer. The beta subunit does not contribute anything directly to the active site. Its role is probably to stabilize the high quantum yield conformation of the alpha subunit through interactions across the subunit interface.
NFkappaB IPT domain (IPT_NFkappaB)
Type: Domain

This entry represents the IPT (Immunoglobulin-like fold, Plexins, Transcription factors) domain, also known as TIG (Transcription factor ImmunoGlobin), of the transcription factor NFkappaB and related transcription factors. NFkappaB is considered a central regulator of stress responses, activated by different stressful conditions, including physical stress, oxidative stress, and exposure to certain chemicals. NFkappaB blocking cell apoptosis in several cell types, gives it an important role in cell proliferation and differentiation .
WASP family, EVH1 domain (WASPfam_EVH1)
Type: Domain

The entry refers to the EVH1 domain found in WASP family proteins.

The EVH1 (WH1, RanBP1-WASP) domain is found in multi-domain proteins implicated in a diverse range of signalling, nuclear transport and cytoskeletal events. This domain of around 115 amino acids is present in species ranging from yeast to mammals. Many EVH1-containing proteins associate with actin-based structures and play a role in cytoskeletal organisation. EVH1 domains recognise and bind the proline-rich motif FPPPP with low-affinity, further interactions then form between flanking residues .

WASP family proteins contain an EVH1 (WH1) in their N-terminals which bind proline-rich sequences in the WASP interacting protein. Proteins of the RanBP1 family contain a WH1 domain in their N-terminal region, which seems to bind a different sequence motif present in the C-terminal part of RanGTP protein .

The actin nucleation-promoting factor WAS (WASP; also called Bee1p) and its homologue N (neuronal)-WASP are signal transduction proteins that promote actin polymerisation in response to upstream intracellular signals . Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive disease, characterised by eczema, immunodeficiency, and thrombocytopenia . The majority of patients with WAS, or a milder version of the disorder, X-linked thrombocytopenia (XLT), have point mutations in the EVH1 domain of WASP . WASP is an actin regulatory protein consisting of an N-terminal EVH1 domain, a basic region (B), a GTP binding domain (GBP), a proline rich region, a WH2 domain, and a verprolin-cofilin-acidic motif (VCA) which activates the actin-related protein (Arp)2/3 actin nucleating complex . The B, GBD, and the proline-rich region are involved in autoinhibitory interactions that repress or block the activity of the VCA. Yeast members lack the GTP-binding domain. The EVH1 domains are part of the PH domain superfamily .
Epidermal growth factor receptor kinase substrate, phosphotyrosine-binding domain (EPS8_PTB)
Type: Domain

Epidermal growth factor receptor kinase substrate (EPS8) is a regulator of Rac signaling . It consists of a phosphotyrosine-binding (PTB) and an SH3 domain.

PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules . This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether . In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine . PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains .

The entry refers to the PTB domain found in EPS8, part of the Dab-like subgroup.
Tensin, phosphotyrosine-binding domain (Tensin_PTB)
Type: Domain

The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) of tensin tends to be found at the C terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (

) domain and a region similar to the tumour suppressor PTEN . The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif . The PTB domain is also found in the epidermal growth factor receptor kinase substrate 8 (EPS8).

PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains .

This entry refers to the PTB domain found in Tensin, part of the Dab-like subgroup.
FAM43A/B, phosphotyrosine-binding domain (FAM43A/B_PTB)
Type: Domain

This entry refers to the PTB domain found in FAM43A/B.

The function of family with sequence similarity 43, member A (FAM43A) is currently unknown. Human FAM43A is located on chromosome 3 at location 3q29. It encodes a 3182 base pair mRNA which possesses one Pleckstrin homology-like domain. The mRNA translates into a hydrophilic protein that is predicted to localise in the nucleus. The FAM43A gene is conserved through a broad range of vertebrates. It is highly conserved from chimpanzees to zebrafish.

Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organise the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. Due to structural differences, PTB domains are divided into three groups represented by phosphotyrosine-dependent IRS-like, phosphotyrosine-dependent Shc-like, and phosphotyrosine-independent Dab-like PTBs. The last two PTBs have been named as phosphotyrosine interaction domain (PID or PI domain). PID domain has an average length of about 160 amino acids .
YtcJ like (YtcJ-like)
Type: Family

This entry includes YtcJ_like metal dependent amidohydrolases and homologues. YtcJ is a Bacillus subtilis ORF of unknown function . The Arabidopsis homologue LAF3 has been identified as a factor required for photochrome A signalling . This entry also includes N-substituted formamide deformylase nfdA from Arthrobacter pascens .