SII-SWORD/CoKE huggingface dataset:
tRNA (32-2'-O)-methyltransferase regulator THADA-like, C-terminal TPR repeats region (THADA-like_TPR_C)
Type: Domain

This region of predicted of tetratricopeptide-like repeats is found towards the C-terminal end of human tRNA (32-2'-O)-methyltransferase regulator THADA and its homologues in eukaryotes, including tRNA (32-2'-O)-methyltransferase regulator trm732 from Schizosaccharomyces pombe and Saccharomyces cerevisiae . Together with methyltransferase FTSJ1, THADA methylates the 2'-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs . This entry is often found associated with

.
tRNA (32-2'-O)-methyltransferase regulator THADA-like, TPR repeats region (THADA-like_TPR)
Type: Domain

This region of predicted of tetratricopeptide-like repeats is found in human tRNA (32-2'-O)-methyltransferase regulator THADA and its homologues in eukaryotes, including tRNA (32-2'-O)-methyltransferase regulator trm732 from Schizosaccharomyces pombe and Saccharomyces cerevisiae . Together with methyltransferase FTSJ1, THADA methylates the 2'-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs . This entry is often found associated with

.
Integrin beta-like protein A-E, N-terminal (SibA-E_N)
Type: Domain

This entry represents the N-terminal Ig-like domain (according to structure predictions) of Integrin beta-like proteins A-E (SibA-E) from Dictyostelium discoideum and similar sequences from lower eukaryotes and and bacteria.

The SibA (Similar to Integrin Beta) protein is a type I transmembrane protein, and its cytosolic, transmembrane and extracellular domains contain features also found in integrin beta chains. This protein is involved in cellular adhesion to substrate or phagocytic particles . The conserved cytosolic domain of SibA interacts with talin, a well-characterised partner of mammalian integrins . Based on these similarities it was speculated that the cellular adhesion mechanisms are similar in Dictyostelium and in mammalian cells, and that observations in the Dictyostelium model system can be extrapolated to mammalian cells .
Zer-1-like, leucine-rich repeats region (LRR_Zer-1)
Type: Domain

This region of leucine-rich repeats (LRR) is found in Zyg eleven-related protein 1 from Caenorhabditis elegans (Zer-1), human Protein zer-1 homolog and similar eukaryotic proteins. C. elegans Zer-1 functions as a target recruitment subunit in the E3 ubiquitin ligase complex zer-1-cul-2-elc-1 . Its human homologue serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC and acts to target substrates bearing N-terminal degrons for proteasomal degradation with the first four residues of substrates being the key recognition elements .
Integrin beta-like protein A-E, second Ig-like domain (Ig_SibA-E_2nd)
Type: Domain

This entry represents the second Ig-like domain (according to structure predictions) of Integrin beta-like proteins A-E (SibA-E) from Dictyostelium discoideum and similar sequences from lower eukaryotes and some bacterial species.

The SibA (Similar to Integrin Beta) protein is a type I transmembrane protein, and its cytosolic, transmembrane and extracellular domains contain features also found in integrin beta chains. This protein is involved in cellular adhesion to substrate or phagocytic particles . The conserved cytosolic domain of SibA interacts with talin, a well-characterised partner of mammalian integrins . Based on these similarities it was speculated that the cellular adhesion mechanisms are similar in Dictyostelium and in mammalian cells, and that observations in the Dictyostelium model system can be extrapolated to mammalian cells .
Integrin beta-like protein A-E, third Ig-like domain (Ig_SibA-E_3rd)
Type: Domain

This entry represents the third Ig-like domain (according to structure predictions) of Integrin beta-like proteins A-E (SIBA-E) from Dictyostelium discoideum and similar sequences mainly from lower eukaryotes.

The SibA (Similar to Integrin Beta) protein is a type I transmembrane protein, and its cytosolic, transmembrane and extracellular domains contain features also found in integrin beta chains. This protein is involved in cellular adhesion to substrate or phagocytic particles . The conserved cytosolic domain of SibA interacts with talin, a well-characterised partner of mammalian integrins . Based on these similarities it was speculated that the cellular adhesion mechanisms are similar in Dictyostelium and in mammalian cells, and that observations in the Dictyostelium model system can be extrapolated to mammalian cells .
UBP34/UBP24/USP9X/USP9Y-like, ARM repeat region (ARM_UBP34_24_USP9X_Y)
Type: Domain

This entry represents an ARM-repeats domain found in ubiquitin carboxyl-terminal hydrolases (UCHs), such as human UBP24, UBP34, USP9X and USP9Y and the orthologues from Drosophila. UCHs are thiol proteases that recognise and hydrolyse the peptide bond at the C-terminal glycine of ubiquitin . UBP24 regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53 . USP9X and USP9Y are involved in deubiquitination of target proteins .
Integrin beta-like protein A-E, immunoglobulin-like domain (Ig_SibA-E)
Type: Domain

This immunoglobulin-like domain (Ig-like) is found in Integrin beta-like protein A-E from Dictyostelium discoideum (SibA-E) and similar sequences mainly found in lower eukaryotes and some bacterial species.

The SibA (Similar to Integrin Beta) protein is a type I transmembrane protein, and its cytosolic, transmembrane and extracellular domains contain features also found in integrin beta chains. This protein is involved in cellular adhesion to substrate or phagocytic particles . The conserved cytosolic domain of SibA interacts with talin, a well-characterised partner of mammalian integrins . Based on these similarities it was speculated that the cellular adhesion mechanisms are similar in Dictyostelium and in mammalian cells, and that observations in the Dictyostelium model system can be extrapolated to mammalian cells .
A-kinase anchor protein 17A/B (AK17A/B)
Type: Family

This entry includes human AK17A and its orthologue from mouse, AK17B. AK17A was originally reported as the pseudoautosomal or X inactivation escape gene 7 (XE7) and as B-lymphocyte antigen precursor . It has been suggested that AKAP-17A is an alternative splicing factor and an SR-related splicing protein that interacts with the classical SR protein ASF/SF2 and the SR-related factor ZNF265 . Additional studies have indicated that AKAP-17A is a dual-specific protein kinase A anchoring protein (AKAP) that can bind both type I and type II protein kinase A (PKA) with high affinity and co-localizes with the catalytic subunit of PKA in nuclear speckles as well as the splicing factor SC35 in splicing factor compartments. It is involved in regulation of pre-mRNA splicing possibly by docking a pool of PKA in splicing factor compartments .
Alkylglycerol monooxygenase, C-terminal (AGMP_C)
Type: Domain

This entry includes Alkylglycerol monooxygenase (AGMO, also known as TMEM195) which is a glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids . These lipids are essential components of brain membranes . This is the C-terminal domain which may adopt a four helical bundle fold.
Allantoinase, composite domain (ALN_composite)
Type: Domain

This entry represents the N-terminal region of the composite domain of Allantoinase (ALN), a protein that catalyses the conversion of allantoin (5-ureidohydantoin) to allantoate by hydrolytic cleavage of the five-member hydantoin ring . The composite domain of metal-dependent hydrolases has a pseudo-barrel fold that is interrupted by the catalytic β/α domain.
IQCH-like, ATP-grasp (ATP-grasp_IQCH)
Type: Domain

This domain is found in human IQ domain-containing protein H (IQCH) and similar eukaryotic and bacterial sequences. IQCH may play a regulatory role in spermatogenesis . IQCH contains an IQ motif (a short calmodulin-binding motif containing conserved Ile and Gln residues). It also contains a PreATP-grasp domain, an ATP-grasp domain (this entry) and an α/β-Hammerhead-like C-terminal domain in an arrangement very similar to the one found in PGM1

and Human glycinamide ribonucleotide synthetase

.
AP-5 complex subunit zeta-1, C-terminal TPR domain (TPR_AP5Z1_C)
Type: Domain

This entry represents the C-terminal region of human AP-5 complex subunit zeta-1 (AP5Z1, also known as SPG48), which consists of tetratricopeptide repeats (TPRs).

Adaptor protein (AP) complexes facilitate the trafficking of cargo from one membrane compartment of the cell to another by recruiting other proteins to particular types of vesicles. AP-5 is involved in trafficking proteins from endosomes towards other membranous compartments . There are genetic links between AP-5 and hereditary spastic paraplegia, a group of human genetic disorders characterised by progressive spasticity in the lower limbs . AP5Z1 is part of AP-5, a probable fifth adaptor protein complex that may be involved in endosomal transport. This protein has been associated with hereditary spastic paraplegia .
AP-5 complex subunit zeta-1, N-terminal TPR domain (TPR_AP5Z1_N)
Type: Domain

This entry represents the N-terminal region of human AP-5 complex subunit zeta-1 (AP5Z1, also known as SPG48), which consists of
tetratricopeptide-like repeats (TPRs).

Adaptor protein (AP) complexes facilitate the trafficking of cargo from one membrane compartment of the cell to another by recruiting other proteins to particular types of vesicles. AP-5 is involved in trafficking proteins from endosomes towards other membranous compartments . There are genetic links between AP-5 and hereditary spastic paraplegia, a group of human genetic disorders characterised by progressive spasticity in the lower limbs . AP5Z1 is part of AP-5, a probable fifth adaptor protein complex that may be involved in endosomal transport. This protein has been associated with hereditary spastic paraplegia .
Vacuolar sorting receptor, thioredoxin-like domain (VSR_TRX)
Type: Domain

This entry represents the thioredoxin (TRX)-like domain found in vacuolar sorting receptors (VSRs) from plants. These proteins are involved in clathrin-coated vesicles sorting from Golgi apparatus to vacuoles . This domain is located in the central region of VSRs, between the N-terminal protease-associated (PA) domain (

) and the C-terminal epidermal growth factor (EGF)-like (

) domains. The domain has a thioredoxin-like fold but its exact function in VSRs is not fully understood. It may be involved in protein-protein interactions or potentially in disulfide bond isomerisation of cargo proteins. It contains multiple disulfide bonds , including a CxxxC motif that is structurally conserved with the CxxC active site motif found in canonical thioredoxins, and is involved in intermolecular interactions that contribute to the formation of VSR trimers, which may be important for VSR function. It may play a role in the pH and calcium-dependent binding and release of cargo proteins by VSRs during vacuolar protein sorting.
Laminin subunit beta-4-like, alpha-helical domain (LAMB4_dom)
Type: Domain

This domain is found in human Laminin subunit beta-4 (LAMB4) and in similar proteins from vertebrates. LAMB4 is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components. This domain is found associated with several copies of

. It is predicted to adopt an all-α configuration.
Hemicentin-1-like, von Willebrand factor A domain (HMCN1-like_VWA)
Type: Domain

This domain is found in human Hemicentin-1 (HMCN1), von Willebrand factor A domain-containing protein 7 (VWA7), Protein irg-7 from Caenorhabditis elegans and similar sequences.

HMCN1 is involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibres and broadening, flattening and elongation of podocytes . HMCN1 is also implicated in the organisation of the basement membrane and may contribute to cleavage furrow maturation during cytokinesis in embryos .

VWA7 is found in the major histocompatibility complex class III region and it is likely implicated in lung cancers

Irg-7 plays a role in innate immunity and probably in the regulation of longevity .
VWA7, N-terminal domain (VWA7_N)
Type: Domain

This domain is found N-terminal in the human VWA7 and related proteins. This domain is usually followed by

.

VWA7 is found in the major histocompatibility complex class III region and it is likely implicated in lung cancers

The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders
. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins . Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events (e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands . A number of human diseases arise from mutations in VWA domains.
Laminin/attractin/netrin-like, EGF domain (LMN_ATRN_NET-like_EGF)
Type: Domain

This entry represents EGF-like domains found in laminin subunits (LMN alpha, beta, gamma), attractin (ATRN), netrins (NET) and related animal proteins. ATRN is involved in the initial immune cell clustering during inflammatory response and may regulate chemotactic activity of chemokines. It may play a role in melanocortin signalling pathways that regulate energy homeostasis and hair colour . It was thought to have dipeptidase activity but it was shown later to lack that activity . Laminins are crucial for the formation of stable basement membranes and organising receptor complexes and cytoskeletal components. Netrins control guidance of central nervous system commissural axons and peripheral motor axons, serving as survival factors and regulating apoptosis .
Large ribosomal subunit protein bL9m, N-terminal domain (MRP-L9_N)
Type: Domain

This domain is found at the N-terminal of human Large ribosomal subunit protein bL9m (MRP-L9) and similar proteins specific to vertebrates. MRP-L9 is a structural component of the large subunit of the ribosome . It shows two β-sheets connected by a loop .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Serine/threonine-protein kinase WNK, CCTL2 domain (CCTL2_WNK)
Type: Domain

This is the CCT-like domain 2 (CCTL2) from animal WNK proteins (WNK1-4), which are serine/threonine-protein kinase components of the WNK-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signalling survival, and proliferation . The exact function of this domain is not clear, it has been suggested that it may play a regulatory function .
WRKY19-like, zinc finger domain (Znf_WRKY19)
Type: Domain

This entry represents a small zinc finger domain found in the probable WRKY transcription factor 19 from Arabidopsis thaliana (WRKY19) and similar proteins from plants and lower eukaryotes. Structure prediction suggests that this protein may have an array of these domains that wrap around the major groove of DNA. This group includes proteins that function as transcription factors, specifically interacting with the W box, a common elicitor-responsive cis-acting element. Additionally, these proteins may also act as disease resistance proteins with serine/threonine-protein kinase activity.
Leucine-rich repeat domain (LRR_15)
Type: Domain

This domain is found in uncharacterised fungal proteins. It is composed of leucine-rich repeats.
Lipocalin domain, nematodes (Lipocalin_dom_nem)
Type: Domain

This entry represents a lipocalin domain usually found in nematode uncharacterised proteins. Lipocalins are transporters for small hydrophobic molecules, such as lipids, steroid hormones, bilins, and retinoids. The structure is an eight-stranded β-barrel. In some proteins this domain is attached to Cullin-like domains suggesting a possible role in scaffolding E3 ligase complexes. This family appears to be most similar to

.
LRRD1, death domain (DD_LRRD1)
Type: Domain

This entry represents the C-terminal death domain (DD) found in LRRD1 protein and related proteins from vertebrates. LRRD1 was recently identified as a component of the radial spokes (RS3) in the mammalian motile cilia that along with Sperm-specific RS3 protein STKLD1, interact with EFCAB5 to further stabilise the structure .
TTC3/DZIP3/RBM44-like, helical domain (TTC3/DZIP3/RBM44-like_helical)
Type: Domain

This domain is found in human E3 ubiquitin-protein ligase TTC3, E3 ubiquitin-protein ligase DZIP3 and similar sequences predominantly found in vertebrates. TTC3 catalyses the formation of 'Lys-48'- polyubiquitin chains and regulates Akt signalling, TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation, neuronal differentiation and cell proliferation . This domain is predicted to adopt an α-helical configuration.
E3 ubiquitin-protein ligase TTC3, winged helix turn helix domain (wHTH_TTC3)
Type: Domain

This domain is found in human E3 ubiquitin-protein ligase TTC3, which catalyses the formation of 'Lys-48'-polyubiquitin chains and regulates Akt signalling, TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation, neuronal differentiation and cell proliferation . This domain is predicted to adopt a winged helix-turn-helix (wHTH) fold.
TTC3/DZIP3-like, helical domain (TTC3/DZIP3-like_helical)
Type: Domain

This domain is found in human E3 ubiquitin-protein ligase TTC3, E3 ubiquitin-protein ligase DZIP3 and similar sequences predominantly found in vertebrates. TTC3 catalyses the formation of 'Lys-48'- polyubiquitin chains and regulates Akt signalling, TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation, neuronal differentiation and cell proliferation . This domain is predicted to adopt an α-helical configuration.
PHD-type zinc finger, plants (PHD_dom_pln)
Type: Domain

This presumed PHD-type zinc finger domain is found in a group of uncharacterised plant proteins.
MCM8/REC, winged helix domain (MCM8/REC_WHD)
Type: Domain

Minichromosome maintenance 8 (MCM8) is a member of the minichromosome maintenance family, which possesses helicase and ATPase activity. It interacts with MCM9 and participates in homologous recombination repair . The domain represented by this entry is located at the C terminus of MCM8. It adopts a winged helix fold and it has a DNA binding activity .

This domain is also found in DNA replication licensing factor REC, a distant MCM homologue, which has no, or only a minor, role in DNA repair and recombination in somatic cells .
Mechanosensitive ion channel protein 2/3, C-terminal (Msl2-3_C)
Type: Domain

This entry represents the C-terminal domain of Mechanosensitive ion channel proteins 2 and 3 from Arabidopsis and related plant sequences. These channels open in response to stretch forces in the membrane lipid bilayer and control plastid size, shape, and perhaps division during normal plant development by altering ion flux in response to changes in membrane tension . They act as a component of the chloroplast division machinery . These channels are closely related to MscS from bacteria.
Mediator of RNA polymerase II transcription subunit 14, C-terminal domain (Med14_C)
Type: Domain

This entry represents a domain found in the human Mediator of RNA polymerase II transcription subunit 14 (Med14) and related proteins. This domain located at the C terminus and predicted to adopt a globular α/β structure.

Med14 is a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors . Med14 along with Med17 are scaffold subunits in nucleating Mediator . The major portion of Med14 exists in the Head-Shoulder module of the Mediator and consists of nine tandem repeats (RM1 to RM9), which are arranged in an atypical right-handed helix .
Mediator of RNA polymerase II transcription subunit 14, RM5 (RM5_Med14)
Type: Domain

This entry represents a domain found in the human Mediator of RNA polymerase II transcription subunit 14 (Med14) and related proteins. This entry represents repeat RM5.

Med14 is a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors . Med14 along with Med17 are scaffold subunits in nucleating Mediator . The major portion of Med14 exists in the Head-Shoulder module of the Mediator and consists of nine tandem repeats (RM1 to RM9), which are arranged in an atypical right-handed helix .