SII-SWORD/CoKE huggingface dataset:
Zinc finger, TTF-type (Znf_TTF)
Type: Domain

The TTF zinc finger domain is found in transposases and transcription factors. It is present in eukaryotic proteins but has not been identified in any from fungi and nematodes.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
VPS10 (VPS10)
Type: Domain

Yeast Vps10p is a receptor for sorting and transport of the soluble vacuolar hydrolase carboxypeptidase Y to the lysosome-like vacuole . In mammalian cells, proteins containing this domain are involved in the transport of lipoproteins and sorting of endosomal proteins. They may also act as receptors for some neuropeptides.

The N terminus of murine brain SorCS contains two putative cleavage sites for the convertase furin which mark the beginning of the VPS10 domain, which is followed by a module of imperfect leucine-rich repeats and a transmembrane domain. The short intracellular C terminus contains consensus signals for rapid internalization. The identified putative binding motifs for SH2 and SH3 domains are unique in the family of VPS10 domain receptors. SorCS is predominantly expressed in brain, but also in heart, liver, and kidney. SorCS transcripts detected by in situ hybridization in the murine central nervous system point to a neuronal expression .
MD domain (MD_domain)
Type: Domain

MD is a domain of unknown function found in a number of Caenorhabditis elegans and Caenorhabditis briggsae hypothetical proteins.
PAN-3 domain (PAN-3_domain)
Type: Domain

PAN domains have significant functional versatility fulfilling diverse biological functions by mediating protein-protein or protein-carbohydrate interactions . These domains contain a hair-pin loop like structure, similar to knottins, but the pattern of disulphide bonds differs.

The PAN-3 or CW is a domain associated with a number of Caenorhabditis elegans hypothetical proteins.
Cellulose binding, type IV (Cellulose-bd_IV)
Type: Domain

This entry represents a type IV cellulose binding domain. It is a sub-domain of the carbohydrate-binding module, family 6 (

).

Regarding the function, it shows endohydrolysis of 1,4-beta-d-xylosidic linkages in xylans .
Fucolectin tachylectin-4 pentraxin-1 (FTP1)
Type: Domain

Lectins, a group of proteins that bind to cell surface carbohydrates and play important roles in innate immunity, are widely used experimentally to distinguish cell types and to induce cell proliferation. Eel serum lectins have been useful as anti-H hemagglutinins and also in lectin histochemistry as fucose-binding lectins (fucolectins). The fucose-binding lectins are secretory proteins and have unique structures among the lectins, exhibiting only weak similarities to frog pentraxin, horseshoe crab tachylectin-4, and fly fw protein .

This entry represents a domain identified in all the Japanese eel (Anguilla japonica) fucolectins. It can also be found in the N terminus of at least one frog pentraxin (

).
ADAM, cysteine-rich domain (ADAM_Cys-rich)
Type: Domain

A Disintegrin and Metalloproteinase (ADAM) is a family of proteolytic enzymes that regulate shedding of membrane-bound proteins, growth factors, cytokines, ligands and receptors . This group of proteins are fundamental to many control processes in development and homeostasis, and they are linked to pathological states .

ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain (MEROPS peptidase family M12B). All members of the ADAM family display a common domain organisation -a pro-domain, the metalloprotease, disintigrin, cysteine-rich, epidermal-growth factor like, and transmembrane domains and a C-terminal cytoplasmic tail. They possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signalling.

ADAMs are membrane-anchored proteases that proteolytically modify cell surface and extracellular matrix (ECM) in order to alter cell behaviour.

They are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain .

The ADAM cysteine-rich domain is not found in plant, archaeal, bacterial or viral proteins. The cysteine-rich domain complements the binding capacity of the disintegrin domain, and perhaps imparts specificity to disintegrin domain-mediated interactions. It has been shown that the cysteine-rich domain of ADAM13 regulates the protein's metalloprotease activity .
Peptide N glycanase, PAW domain (Peptide_N_glycanase_PAW_dom)
Type: Domain

The PAW domain (present in PNGases and other worm proteins) is found as a single copy at the C terminus of metazoan peptide:N-glycanase (PNGase) and in multiple copies in hypothetical Caenorhabditis elegans proteins peptide:N-glycanases (PNGases) . The C-terminal PAW domain of PNGase binds to the mannose moieties of N-linked oligosaccharide chains .

The PAW domain is a slightly elongated molecule and displays a β-sandwich architecture, which is composed of two layers, containing nine and eight antiparallel β-strands, respectively, and three additional short helices .

Some proteins known to contain a PAW domain are listed below:

Animal peptide:N-glycanase (PNGase)

, catalyses the deglycosylation of several misfolded N-linked glycoproteins by cleaving the bulky glycan chain before the proteins are degraded by the proteasome.

Caenorhabditis elegans putative uncharacterised protein C17B7.5.
RNA polymerase Rpb4/RPC9, core (RNA_pol_Rpb4/RPC9_core)
Type: Domain

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.

A major role in the regulation of eukaryotic protein-coding genes is played by the gene-specific transcriptional regulators, which recruit the RNA polymerase II holoenzyme to the specific promoter. The Rpb4 and Rpb7 subunits of yeast RNA polymerase II form a heterodimeric complex essential for promoter-directed transcription initiation. The Rpb4-Rpb7 complex is not required for stable recruitment of polymerase to active preinitiation complexes, suggesting that Rpb4-Rpb7 mediates an essential step subsequent to promoter binding .

This entry represents a domain present in DNA-directed RNA polymerase II subunit Rpb4 and DNA-directed RNA polymerase III subunit RPC9.
RNA polymerase archaeal subunit P/eukaryotic subunit RPABC4 (RNAP_P/RPABC4)
Type: Family

This family includes the DNA-directed RNA polymerases I, II, and III subunit RPABC4 (also known as RPC10 and ABC10-alpha) and archaeal polymerase subunit P .

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.
RNA polymerase, N-terminal (RNA_pol_N)
Type: Domain

The task of transcribing nuclear genes is shared between three RNA polymerases in eukaryotes: RNA polymerase (pol) I synthesizes the large rRNA, pol II synthesizes mRNA and pol III synthesizes tRNA and 5S rRNA . Pol I transcription is localised to discrete sites called nucleoli; these can be likened to ribosome factories, in which rRNA is synthesised by pol I in the fibrillar centres and then processed and assembled into ribosomes in the surrounding granular regions . Prokaryotes, in contrast, posses a single RNA polymerase, with transcription being controlled by the particular signam factor interacting with the catalytic core.

This entry describes an N-terminal conserved region which can be found in the largest subunits of prokaryoptic and eukaryotic RNA polymerases.
Cytochrome b561/ferric reductase transmembrane (Cyt_b561/ferric_Rdtase_TM)
Type: Domain

Cytochromes b561 constitute a class of intrinsic membrane proteins containing two haem molecules that are involved in ascorbate (vitamin C) regeneration. They have been suggested to function as electron transporters, shuttling electrons across membranes from ascorbate to an acceptor molecule. The one-electron oxidation product of ascorbate, monodehydro-ascorbate (MDHA) has been shown to function as an electon acceptor for mammalian and plant cytochromes b561. The cytochrome b561-catalysed reduction of MDHA results in the regeneration of the fully reduced ascorbate molecule. Cytochromes b561 have been identified in a large number of phylogenetically distant species, but are absent in prokaryotes. Most species contain three or four cytochrome b561 paralogous proteins .

Members of the cytochrome b561 protein family are characterised by a number of structural features, likely to play an essential part in their function. They are highly hydrophobic proteins with six transmembrane helices (named TMH1 through TMH6), four conserved histidine residues, probably coordinating the two haem molecules, and predicted substrate-binding sites for ascorbate and MDHA . The functionally relevant and structurally most conserved region in the cytochrome b561 family is the TMH2 to -5 4-helix core with an amino acid composition that is very well conserved in the inner surface and somewhat less conserved in the outer surface of the core. The two terminal helices (TMH1 and TMH6) are less conserved .

The entry represents a conserved region containing six transmembrane helices, found in cytochrome b651 and homologous proteins including some ferric reductases.
LIS1 homology motif (LisH)
Type: Conserved_site

The 33-residue LIS1 homology (LisH) motif is found in eukaryotic intracellular proteins involved in microtubule dynamics, cell migration, nucleokinesis and chromosome segregation. The LisH motif is likely to possess a conserved protein-binding function and it has been proposed that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The LisH motif is found associated to other domains, such as WD-40, SPRY, Kelch, AAA ATPase, RasGEF, or HEAT
.

The secondary structure of the LisH domain is predicted to adopt a two α-helices fold .
CTLH, C-terminal LisH motif (CTLH_C)
Type: Domain

The 33-residue LIS1 homology (LisH) motif (

) is found in eukaryotic intracellular proteins involved in microtubule dynamics, cell migration, nucleokinesis and chromosome segregation. The LisH motif is likely to possess a conserved protein-binding function and it has been proposed that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The LisH motif is found associated to other domains, such as WD-40 (see

), SPRY, Kelch, AAA ATPase, RasGEF, or HEAT (see

) .

The secondary structure of the LisH domain is predicted to be two α-helices .

Some proteins known to contain a LisH motif are listed below:

Animal LIS1. It regulates cytoplasmic dynein function. In Homo sapiens (human) children with defects in LIS1 suffer from Miller-Dieker lissencephaly, a brain malformation that results in severe intellectual disability, epilepsy and an early death.

Emericella nidulans (Aspergillus nidulans) nuclear migration protein nudF, the orthologue of LIS1.

Eukaryotic RanBPM, a Ran binding protein involved in microtubule nucleation.

Eukaryotic Nopp140, a nucleolar phosphoprotein.

Mammalian treacle, a nucleolar protein. In human, defects in treacle are the cause of Treacher Collins syndrome (TCS), an autosomal dominant disorder of craniofacial development.

Animal muskelin. It acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component thrombospondin 1.

Animal transducin beta-like 1 protein (TBL1).

Plant tonneau.

Arabidopsis thaliana LEUNIG, a putative transcriptional corepressor that regulates AGAMOUS expression during flower development.

Fungal aimless RasGEF.

Leishmania major katanin-like protein.

The C-terminal to LisH (CTLH) motif is a predicted α-helical sequence of unknown function that is found adjacent to the LisH motif in a number of these proteins but is absent in other (e.g. LIS1) . The CTLH domain can also be found in the absence of the LisH motif, like in:

Arabidopsis thaliana (Mouse-ear cress) hypothetical protein MUD21.5.

Saccharomyces cerevisiae yeast protein RMD5.
Sel1-like repeat (Sel1-like)
Type: Repeat

Sel1-like repeats are tetratricopeptide repeat sequences originally identified in a Caenorhabditis elegans receptor molecule which is a key negative regulator of the Notch pathway . Mammalian homologues have since been identified although these mainly pancreatic proteins have yet to have a function assigned.
Glycosyl transferase CAP10 domain (CAP10)
Type: Domain

The CAP10 domain is found in glycosyltransferases from animals, plants and fungi. Rumi is a Drosophila protein with a CAP10 domain that functions as a protein O-glucosyltransferase. In human and mouse, three potential homologues exist: one with a high degree of identity to Drosophila Rumi (52%), and two others with lower degrees of identity but including a CAP10 domain (KDELC1 and KDELC2) . Rumi catalyzes the transfer of glucose and/or xylose from UDP-glucose and UDP-xylose, respectively, to a serine within the consensus Cys-Xaa-Ser-Xaa-Pro-Cys) in epidermal growth factor repeats, such as those found in coagulation factors F7, F9 and NOTCH proteins. Notch signaling is regulated by Notch glucosylation and glucosylation is required for the correct folding and cleavage of Notch .

CAP10 from Cryptococcus neoformans encodes a xylosyltransferase . This pathogenic fungus, which most commonly affects the central nervous system and causes fatal meningoencephalitis primarily in patients with AIDS, produces a thick extracellular polysaccharide capsule which is well recognised as a virulence factor. The CAP10 domain is required for capsule formation and virulence . The capsule is primarily made of two xylose-containing polysaccharides, glucuronoxylomannan and galactoxylomannan, and the glycosyltransferase transfers xylose to alpha-1,3-dimannoside in a beta-1,2-linkage .
CARP motif (CARP_motif)
Type: Domain

This entry represents the CARP motif, which occurs as a tandem repeat in the C-terminal of many cyclase-associated proteins (CAPs), as well as in tubulin binding cofactor C and the X-linked retinitis pigmentosa 2 protein (RP2).
HTH CenpB-type DNA-binding domain (HTH_CenpB_DNA-bd_dom)
Type: Domain

The CENPB-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 70-75 amino acids, present in eukaryotic centromere proteins and transposases. The domain is named after the mammalian major centromere autoantigen B or centromere protein B (CENP-B), which is a fundamental centromere component of chromosomes. The N terminus of CENP-B contains two DNA-binding HTH domains, which bind to adjacent major grooves of DNA. The N terminus of CENP-B is formed by a psq-type HTH domain and C-terminal to this domain lies the CENPB-type HTH domain. These two HTH domains together bind specifically to a 17-base-pair sequence, the CENP-B box, which occurs in alpha-satellite DNA in human centromeres .

The structure of the CENPB-type HTH domain is composed of three α-helices. The second and third helices connected via a turn comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs. In CENP-B this domain recognises site 3 of the CENP-B box, while the preceding psq-type HTH binds site 1 of the CENP-B box, and a connecting linker loop binds in the minor groove of DNA and recognises site 2 .

Some proteins known to contain a CENPB-type HTH domain:

Mammalian centromere protein B (CENP-B), associated with the centromere and specifically binding DNA to the CENP-B box.

Mammalian jerky protein, involved in epileptic seizures in mice .

Mammalian Pogo transposases and tigger transposable elements .

Fission yeast ARS-binding protein 1 (abp1) and CENP-B homologue proteins (CBHP-1 and 2), which are centromere proteins .

Candida albicans protein PDC2 (Pyruvate DeCarboxylase 2) .

Fungal transposases.
Uncharacterised protein family DM11, Drosophila melanogaster (Uncharacterised_DM11_DROME)
Type: Family

This family consists of a group of Drosophila melanogaster proteins of unknown function. A number of these proteins are expressed in nonneuronal auxiliary cells within two nested subsets of chemosensory sensilla on the front legs of male D. melanogaster, suggesting they may be involved in pheromone response . These proteins are predicted to have a single transmembrane domain at their amino terminus, probably to serve as a signal peptide, suggesting that they are soluble and secreted.
DM10 domain (DM10_dom)
Type: Domain

This entry represents the DM10 domain, which consists of approximately 105 residues whose function is unknown. The DM10 domain has been identified in only two types of proteins: nucleoside diphosphate kinases (which contain a single copy of the DM10 domain) and in an uncharacterised class of proteins (which contain multiple copies of DM10 domains).

The nm23-H7 class of nucleoside diphosphate kinase (NDK7;

) consists of an N-terminal DM10 domain and two functional catalytic NDK domains . In Chlamydomonas, this protein (termed p40) is tightly associated with the flagellar axoneme.

The DM10 domain exists in multiple copies in an uncharacterised class of proteins that includes Chlamydomonas Rib72 and mammalian EF-hand domain-containing protein 1 and EF-hand domain-containing family member C2, EFHC1/2. Rib72 and EFHC1 each contain three repeated copies of the DM10 domain followed by a C-terminal domain containing two EF-hands that are predicted to bind calcium ions. Orthologous proteins are present in many other organisms that contain motile cilia including mouse, rat, Ciona, sea urchin, Leishmania, and trypanosomes. However, no obvious Rib72/EFHC1 relative has been identified in higher plants, or in the Caenorhabditis elegans genome, which encodes only one DM10 domain-containing protein.

In Chlamydomonas, and possibly mammals, DM10 domain-containing proteins are tightly bound to the flagellar doublet microtubules. This suggests that DM10 domains might act as flagellar NDK regulatory modules or as units specifically involved in axonemal targeting or assembly .

DM10 domains have the same organisation of secondary structural elements, a pleckstrin homology (PH)-like fold, which includes seven β strands, with a short 3-4 residue helix after the first strand, and a more extended α helical region at the C-terminal .
PQ-loop repeat (PQ-loop_rpt)
Type: Repeat

Some membrane bound proteins possess a pair of repeats each spanning two transmembrane helices connected by a loop . The PQ motif found on loop 2 is critical for the localisation of cystinosin to lysosomes . However, the PQ motif appears not to be a general lysosome-targeting motif. It is thought to possess a more general function; most probably this involves a glutamine residue .