SII-SWORD/CoKE huggingface dataset:
Homez, homeobox domain (Homez_homeobox_dom)
Type: Domain

Homez contains three atypical homeobox domains, two leucine zipper-like motifs and an acidic domain and belongs to the superfamily of homeobox-containing proteins. The presence of leucine zippers suggests that Homez can function as a homo or heterodimer in the nucleus . It is thought that the first leucine zipper and homeodomain 1 (HD1) of Homez is responsible for dimerisation and HD2 has a specific DNA-binding activity. Homez is also thought to function as a transcriptional repressor due to the acidic region in its C-terminal domain . Homez is involved in a complex regulatory network .

This entry represents a homeobox domain found in Homez (HD3).
Bcl-2-interacting killer (Bcl2-int_killer)
Type: Family

Bcl-2-interacting killer promotes cell death in a manner similar to the death-promoting members of the Bcl-2 family, Bax and Bak. Its death-promoting activity can be suppressed by coexpression of Bcl-2, Bcl-XL, EBV-BHRF1 and E1B-19kDa proteins, suggesting that it may be a common target for both cellular and viral anti-apoptotic proteins .
Dishevelled C-terminal (Dishevelled_C-dom)
Type: Domain

Wnt proteins constitute a large family of secreted signalling molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Wg) (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt signal transduction proceeds initially via binding to their cell surface receptors -the so-called frizzled proteins. This activates the signalling functions of B-catenin and regulates the expression of specific genes important in development . More recently, however, several non-canonical Wnt signalling pathways have been elucidated that act independently of B-catenin. In both cases, the transduction mechanism requires dishevelled protein (Dsh), a cytoplasmic phosphoprotein that acts directly downstream of frizzled . In addition to its role in Wnt signalling, Dsh is also involved in generating planar polarity in Drosophila and has been implicated in the Notch signal transduction cascade. Three human and mouse homologues of Dsh have been cloned (DVL-1 to 3); it is believed that these proteins, like their Drosophila counterpart, are involved in signal transduction. Human and murine orthologues share more than 95% sequence identity and are each 40-50% identical to Drosophila Dsh.

Sequence similarity amongst Dsh proteins is concentrated around three conserved domains: at the N terminus lies a DIX domain (mutations mapping to this region reduce or completely disrupt Wg signalling); a PDZ (or DHR) domain, often found in proteins involved in protein-protein interactions, lies within the central portion of the protein (point mutations within this module have been shown to have little effect on Wg-mediated signal transduction); and a DEP domain is located towards the C terminus and is conserved among a set of proteins that regulate various GTPases (whilst genetic and molecular assays have shown this module to be dispensable for Wg signalling, it is thought to be important in planar polarity signalling in flies ). Therefore the requirement of these domains for distinct signaling pathways varies: the DIX domain is essential for B-catenin activation, the DEP domain is implicated in the activation of the JNK pathway, while the PDZ domain is required for both .

This entry represents a domain found in the C-terminal of Dsh proteins.
Tbk1/Ikki binding domain (TBD)
Type: Domain

The Tbk1/Ikki binding domain (TBD) is a 40 amino acid domain able to bind kinases which is essential for poly(I:C)-induced IRF activation . The domain is found in the SINTBAD, TANK and NAP1 proteins. This domain is predicted to form an α-helix with residues essential for kinase binding clustering on one side .
Voltage-gated Na+ ion channel, cytoplasmic domain (Na_trans_cytopl)
Type: Domain

This is a large cytoplasmic domain towards the start of voltage-dependent sodium ion channel proteins in eukaryotes.
Tuberin, N-terminal (Tuberin_N)
Type: Domain

This entry represents the N-terminal domain of tuberin which is functionally uncharacterised.
Serine/threonine-protein kinase mTOR domain (mTOR_dom)
Type: Domain

This entry represents a domain found in serine/threonine-protein kinase mTOR (target of rapamycin), a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals . In Saccharomyces cerevisiae, the TOR proteins, TOR1 and TOR2, regulate growth in a rapamycin-sensitive manner . This domain consists of HEAT repeats .
DnaJ-like protein C11, C-terminal (DnaJ-like_C11_C)
Type: Domain

Chaperone DnaJ was originally characterised from Escherichia coli as a 41kDa heat shock protein. DnaJ has a modular structure consisting of a J-domain, a proximal G/F-domain, and a distal zinc finger domain, followed by less conserved C-terminal sequences. Since then, a large number of DnaJ-related proteins containing a J-domain have been characterised from a variety of different organisms. In the genome of Arabidopsis thaliana a total of 89 J-domain proteins have been identified .

This entry represents a C-terminal domain found in some eukaryotic DnaJ-like proteins, including member 11 from the subfamily C1 and protein DnaJ 13 from Arabidopsis. DNAJC11 is a mitochondrial outer membrane protein involved in mitochondrial biogenesis and in the response to microenvironment changes and requirements. The J-domain mediates its mitochondrial localization, while this domain is critical for protein-protein interactions .
Inner membrane protein YejM, N-terminal (YejM_N)
Type: Domain

This entry represents an uncharacterised domain found in the N-terminal of inner membrane protein YejM from Gammaproteobacteria.
Fungal ligninase, C-terminal (Ligninase_C)
Type: Domain

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Peroxidases are found in bacteria, fungi, plants and animals. Fungal ligninases are extracellular haem enzymes involved in the degradation of lignin. They include lignin peroxidases (LiPs), manganese-dependent peroxidases (MnPs) and versatile peroxidases, which combine the substrate-specificity characteristics of the other two . In MnP, Mn
2+
serves as the reducing substrate .

It is commonly thought that the plant polymer lignin is the second most abundant organic compound on Earth, exceeded only by cellulose. Higher plants synthesise vast quantities of insoluble macromolecules, including lignins. Lignin is an amorphous three-dimensional aromatic biopolymer composed of oxyphenylpropane units. Biodegradation of lignins is slow - it is probable that their decomposition is the rate-limiting step in the biospheric carbon-oxygen cycle, which is mediated almost entirely by the catabolic activities of microorganisms. The white-rot fungi are able extensively to decompose all the important structural components of wood, including both cellulose and lignin. Under the proper environmental conditions, white-rot fungi completely degrade all structural components of lignin, with ultimate formation of CO
2
and H
2
O. The first step in lignin degradation is depolymerisation, catalysed by the LiPs (ligninases). LiPs are secreted, along with hydrogen peroxide (H
2
O
2
), by white-rot fungi under conditions of nutrient limitation. The enzymes are not only important in lignin biodegradation, but are also potentially valuable in chemical waste disposal because of their ability to degrade environmental pollutants .

To date, 3D structures have been determined for LiP and MnP from Phanerochaete chrysosporium (White-rot fungus), and for the fungal peroxidase from Arthromyces ramosus . All these proteins share the same architecture and consist of 2 all-alpha domains, between which is embedded the haem group. The helical topography of LiPs is nearly identical to that of yeast cytochrome c peroxidase (CCP) , despite the former having four disulphide bonds, which are absent in CCP (MnP has an additional disulphide bond at the C terminus).

This C-terminal domain is found in fungal ligninases. It is about 80 amino acids in length and forms an extended structure on the surface of the peroxidase domain

.
RNA helicase HrpA, C-terminal (HrpA_C)
Type: Domain

This entry represents the uncharacterised C-terminal domain of HrpA.
Variable lymphocyte receptor, C-terminal (Variable_lymphocyte_rcpt_C)
Type: Domain

This uncharacterised C-terminal domain is found in variable lymphocyte receptor proteins from lamprey and hagfish (cyclostome taxon). They consist of leucine-rich repeats (LRR) that
are assembled into functional receptors through somatic diversification of the incomplete germ-line VLR gene in lamprey and hagfish .
Domain of unknown function DUF3444 (DUF3444)
Type: Domain

This entry represents an uncharacterised domain. This domain is found in DnaJ, cytosine-specific methyltransferases, and members from the zinc finger, C3HC4 type family.
DNA-directed RNA polymerase subunit beta/EpuA (RNApol_su_b/EpuA)
Type: Family

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

This entry represents the short 60-residue long bacterial family that is the beta subunit of the DNA-directed RNA polymerase, likely to be

It is membrane-bound and is referred to by the name EpuA.
Splicing factor SF3a60 /Prp9 subunit, C-terminal (SF3a60/Prp9_C)
Type: Domain

The mature U2 snRNP (small nuclear ribonucleoprotein particle) relies on the spliceosome assembly for its function, which involves the Splicing factor 3a (SF3a), an evolutionary eukaryotic conserved heterotrimeric complex, essential for pre-mRNA splicing . This complex includes three subunits: SF3a60, SF3a66 and SF3a120 in the human complex, being Prp9, Prp11 and Prp21 the counterparts in Saccharomyces cerevisiae. SF3a60 possess a highly conserved C2H2-type zinc-finger domain at the C-terminal, while Prp9 has two such domains; SF3a66 and Prp11 contain one C2H2-type zinc-finger domain and SF3a120/Prp21 has two suppressor-of-white-apricot and prp21/spp91 (SURP) domains, followed by a short segment of charged residues. The SURP2 domain of SF3a120/Prp21 has a role in SF3a60/Prp9 binding, however, SURP1 domain function is unknown. The yeast structure shows that Prp9 interacts with Prp21 via a bidentate-binding mode, and Prp21 is wrapped around Prp11 .

This entry represents the C-terminal region of SF3a60 subunit (also known as SF3a3 and Spliceosome-associated protein 61 or Prp9 from yeast) from SF3a complex, found in eukaryotes. This domain has two conserved sequence motifs: PIP and CEICG. It contains a zinc-finger domain of the C2H2-type which might be important for RNA binding and protein-protein interactions with components of the SF3b complex .
Retinoblastoma-associated protein, N-terminal (RB_N)
Type: Domain

This domain is found in N-terminal of the retinoblastoma-associated protein. It is found in association with

and

. This domain is typically between 124 to 150 amino acids in length and has a single completely conserved residue W that may be functionally important.
Notch, C-terminal (Notch_C)
Type: Domain

This domain can be found at the C terminus of notch and notch-related proteins.
Peptidase M1, alanyl aminopeptidase, C-terminal (Peptidase_M1_pepN_C)
Type: Domain

This domain, which contains a conserved FSAPV sequence motif, is found in the C-terminal of alanyl aminopeptidases that belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA).

The M1 family of zinc metallopeptidases contains a number of distinct, well-separated clades of proteins with aminopeptidase activity. Several are designated aminopeptidase N,

, after the Escherichia coli enzyme, suggesting a similar activity profile (see

for a description of catalytic activity).

This group of zinc metallopeptidases belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA); the majority are identified as alanyl aminopeptidases (proteobacteria) that are closely related to E. coli PepN and presumed to have a similar (not identical) function. Nearly all are found in proteobacteria, but members are found also in cyanobacteria, plants, and apicomplexan parasites . This family differs greatly in sequence from the family of aminopeptidases typified by Streptomyces lividans PepN (

) and from the membrane bound aminopeptidase N family in animals.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
Conserved oligomeric Golgi complex, subunit 2, N-terminal (COG_su2_N)
Type: Domain

This entry represents the N-terminal domain of subunit 2 of the COG complex. The COG complex comprises eight proteins COG1-8 and plays critical roles in Golgi structure and function and it is involved in retrograde vesicular trafficking within the Golgi apparatus. . COG complex,together with exocyst, Golgi-associated retrograde protein (GARP) and Dsl1 complexes, is a member of the CATHR (complexes associated with tethering containing helical rods) family sharing an evolutionary origin and structural features .
COG complex component, COG2, C-terminal (COG_complex_COG2_C)
Type: Domain

The COG complex comprises eight proteins (COG1-8) and plays critical roles in Golgi structure and function. It is necessary for retrograde trafficking in the Golgi apparatus and for protein glycosylation . COG complex, together with exocyst, Golgi-associated retrograde protein (GARP) and Dsl1 complexes, is a member of the CATHR (complexes associated with tethering containing helical rods) family sharing an evolutionary origin and structural features . This domain is found in the C-terminal of COG complex subunit 2 proteins and consists of a conserved α-helical bundle. In Arabidopsis, COG2 forms a complex with FPP3/VETH1 and FPP2/VETH2 and ensures the correct secondary cell wall (SCW) deposition pattern by recruiting exocyst components to cortical microtubules in xylem cells during secondary cell wall deposition .
Serine/threonine-protein kinase haspin, C-terminal (GSG2_C)
Type: Domain

This domain may be a potential Haspin-related leucine-zipper. A leucine zipper was proposed to be present towards the C-terminal of human Haspin, (upstream of the current family) ; however, as this domain would appear to span several helices and be largely within a loop structure , the actual zipper might be further downstream, and be represented by this entry, which is the very C-terminal part of the Schizosaccharomyces pombe sequence.
NAD(P) transhydrogenase, alpha subunit, C-terminal (NADP_transhyd_a_C)
Type: Domain

This entry represents the C-terminal domain of NAD(P) transhydrogenase, alpha subunit.
UPF0606 protein KIAA1549 (KIAA1549)
Type: Family

This family includes KIAA1549 from human (

) which has been implicated in pilocytic astrocytomas . In the majority of cases of pilocytic astrocytomas a tandem duplication produces an in-frame fusion of the gene encoding this protein and the BRAF oncogene. The resulting fusion protein has constitutive BRAF kinase activity and is capable of transforming cells. More recently, KIAA1549 has been described to play a role in photoreceptor function .
Sulfatase, conserved site (Sulfatase_CS)
Type: Conserved_site

Sulphatases

are enzymes that hydrolyse various sulphate esters. The sequence of different types of sulphatases are available and have shown to be structurally related ; these include:

arylsulphatase A

(ASA), a lysosomal enzyme which hydrolyses cerebroside sulphate;

arylsulphatase B

(ASB), which hydrolyses the sulphate ester group from N-acetylgalactosamine 4-sulphate residues of dermatan sulphate;

arylsulphatase C (ASD) and E (ASE);

steryl-sulphatase

(STS), a membrane bound microsomal enzyme which hydrolyses 3-beta-hydroxy steroid sulphates;

iduronate 2-sulphatase precursor

(IDS), a lysosomal enzyme that hydrolyses the 2-sulphate groups from non-reducing-terminal iduronic acid residues in dermatan sulphate and heparan sulphate;

N-acetylgalactosamine-6-sulphatase

, which hydrolyses the 6-sulphate groups of the N-acetyl-d-galactosamine 6-sulphate units of chondroitin sulphate and the D-galactose 6-sulphate units of keratan sulphate;

glucosamine-6-sulphatase

(G6S), which hydrolyses the N-acetyl-D-glucosamine 6-sulphate units of heparan sulphate and keratan sulphate;

N-sulphoglucosamine sulphohydrolase

(sulphamidase), the lysosomal enzyme that catalyses the hydrolysis of N-sulpho-d-glucosamine into glucosamine and sulphate;

sea urchin embryo arylsulphatase

;

green algae arylsulphatase

, which plays an important role in the mineralisation of sulphates;

and arylsulphatase

from Escherichia coli (aslA), Klebsiella aerogenes (gene atsA) and Pseudomonas aeruginosa (gene atsA).

This entry represents two conserved sites for the sulphatase family located in the N-terminal region. The SULPHATASE_1 site contains the conserved arginine which could be implicated in the catalytic mechanism; it is located four residues after a position that, in eukaryotic sulphatases, is a conserved cysteine which has been shown to be modified to 2-amino-3-oxopropionic acid. In prokaryotes, this cysteine is replaced by a serine.
Smad anchor for receptor activation-like, Smad-binding domain (SARA-like_SBD)
Type: Domain

This entry represents the Smad-binding domain (SBD) of SARA, which is also known as Zinc finger FYVE domain-containing protein 9. This domain consists of a rigid coil, an α-helix, and a β-strand, and interacts with Smad2 . It is found C-terminal to the FYVE zinc finger domain (

).

Smad proteins mediate transforming growth factor-beta (TGF-beta) signalling from the transmembrane serine-threonine receptor kinases to the nucleus. SARA (Smad anchor for receptor activation) recruits Smad2 to the TGF-beta receptors for phosphorylation .
Extracellular sulfatase, C-terminal (Extracellular_sulfatase_C)
Type: Domain

This uncharacterised domain is found in the C-terminal region of extracellular sulphatase proteins.
Inhibitor of growth protein, N-terminal histone-binding (ING_N_histone-binding)
Type: Domain

Histones undergo numerous post-translational modifications, including acetylation and methylation, at residues which are then probable docking sites for various chromatin remodelling complexes. Inhibitor of growth proteins (INGs) specifically bind to residues that have been thus modified. INGs carry a well-characterised C-terminal PHD-type zinc-finger domain, binding with lysine 4-tri-methylated histone H3 (H3K4me3), as well as this N-terminal domain that binds unmodified H3 tails. Although these two regions can bind histones independently, together they increase the apparent association of the ING for the H3 tail.

This entry represents the N-terminal histone binding domain found in inhibitor proteins.
Huntingtin, N-terminal, HEAT repeats 2 (Huntingtin_N_HEAT_rpt-2)
Type: Repeat

This entry represents the second set of HEAT repeats of the N-terminal domain from Huntingtin (Htt) . It is separated from the rest of the domain (

) by an unstructured region. This repeated domain is less than 40 amino acids in length and is present in huntingtin protein (Htt). Htt is expressed in many tissues, with various expression levels and is involved in a number of cellular functions. However, its exact function is not yet clear. An abnormal polyglutamine (polyQ) expansion in this protein causes Huntington's disease (HD), a progressive autosomal-dominant neurodegenerative disease characterised by an uncontrolled motor movement known as chorea, cognitive disorder and depression . Htt consists of multiple HEAT repeats organised in N-terminal, bridge and C-terminal domains , which function as a scaffold that mediates interactions with binding partners.
CRISPR-associated protein Cmr2, N-terminal (CRISPR-assoc_Cmr2_N)
Type: Domain

This domain family is typically between 101 and 138 amino acids in length and is found in subunit Crm2 of the CRISPR RNA-Cas protein complex (Cmr complex) .
Pherophorin (Pherophorin)
Type: Domain

This domain is found in a family of plant proteins that are frequently annotated as pherophorin . The domain often occurs twice and is typically between 147 and 160 amino acids in length.
Domain of unknown function DUF3870 (DUF3870)
Type: Domain

This domain is found in the C-terminal region of the putative pore-forming toxin YP_001301288.1 from Bacteroides vulgatus ATCC3 , suggesting that the domain may have a lytic function.
Domain of unknown function DUF3857 (DUF3857)
Type: Domain

This domain is based on the first domain of the PDB structure 3KD4 (residues 1-228). It is structurally similar to domains in other hydrolases, eg. M1 family aminopeptidase, despite lack of any significant sequence similarity. The domain is N-terminal to a transglutaminase domain, which is found in many proteins known to have transglutaminase activity. The function of this domain is unknown.