SII-SWORD/CoKE huggingface dataset:
Bardet-Biedl syndrome 1 protein, GAE domain (GAE_BBS1)
Type: Domain

This entry represents the GAE domain of BBS1, found at the C terminus. It adopts a β-sandwich fold . This domain mediates interactions with other subunits (BBS8 and BBS9) of the complex.

Bardet-Biedl syndrome is characterised by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation . Bardet-Biedl syndrome proteins (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10) form the BBSome complex, which functions as a coat complex required for sorting of specific membrane proteins to the primary cilia . The ciliary trafficking function of BBSome is regulated by LZTFL1 (Leucine-zipper transcription factor-like 1) .

Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype . Of the 12 known BBS genes, BBS1 is the most commonly mutated .

This entry includes BBS1, is the most important BBSome subunit for cargo recognition as it mediates the interaction of the GTP-bound Arf-like GTPase ARL6 with the BBSome, a critical step in the recruitment of the BBSome to membranes .
Gem-associated protein 5, RBS domain (GEMI5_RBS)
Type: Domain

This entry represents the RNA-binding domains RBS1 and RBS2 found at the C-terminal of Gem-associated protein 5 (GEMI5) from vertebrates. The RBS1 domain is involved in the recognition of viral IRES elements and cellular RNAs. This domain is intrinsically unstructured and interacts with RNA through conserved Arg and aromatic residues .

GEMI5 is a component of the survival of motor neurons (SMN) complex, that binds small nuclear RNAs (snRNAs). The SMN complex assembles the heptameric Sm protein core on snRNAs playing a critical role in the biogenesis of small nuclear ribonucleoproteins (snRNPs) . GEMI5 is also implicated in translation control, and gene expression reprogramming . GEMI5 from animals share a domain architecture consisting of two N-terminal β-propellers followed by a TPR domain and a C-terminal RNA-binding domain.
Gem-associated protein 5, TPR domain (TPR_GEMI5)
Type: Domain

This entry represents the TPR domain found towards the C-terminal of Gem-associated protein 5 (GEMI5) from animals and related eukaryotic sequences. The TPR domain in GEMI5 mediates the dimerisation of the protein . This is possible thanks to the helical repeats stretched in an α-solenoid rod that provides an extensive flat surface for self-dimerisation . Mutations in this domain have been shown to cause a neurodevelopmental disorder characterised by cerebellar atrophy, intellectual disability (ID), and motor dysfunction . Also included in this entry is protein rigor mortis (RIG), the orthologue from Drosophila melanogaster . RIG, apart from being a component of the survival motor neuron (SMN) complex, it is a nuclear receptor-interacting protein required for the response to steroid hormone ecdysone during larval development .

GEMI5 is a component of the survival of motor neurons (SMN) complex, that binds small nuclear RNAs (snRNAs). The SMN complex assembles the heptameric Sm protein core on snRNAs playing a critical role in the biogenesis of small nuclear ribonucleoproteins (snRNPs) . GEMI5 is also implicated in translation control, and gene expression reprogramming . GEMI5 from animals share a domain architecture consisting of two N-terminal β-propellers followed by a TPR domain and a C-terminal RNA-binding domain.
BP74, N-terminal domain (BP74_N)
Type: Domain

This domain is found at the N-terminal of the Cyclic AMP-inducible protein BP74 from Dictyostelium discoideum and related proteins. The BP74 gene is a cyclic AMP-regulated and expressed during the Dictyostelium development . This domain is predicted to fold into an open β-barrel capped with two α-helices.
BPM/SPOP, BACK domain (BACK_BPM_SPOP)
Type: Domain

This entry represent the BACK domain present in BPM proteins from plants, SPOP from animals and related sequences.

BPM proteins are part of the Cullin E3 ubiquitin ligase complexes playing a role as substrate-specific adaptors of CUL3-based E3 ligases in the ubiquitin-proteasome pathway . They bind at least three families of transcription factors: ERF/AP2 class I, homeobox-leucine zipper and R2R3 MYB, playing an important role in plant flowering, seed development and abiotic stress response . SPOP, also known as HIB homologue 1 or Roadkill homologue 1 in humans, is an adaptor protein that forms a complex with Cul3, cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, and is involved in ubiquitination of BMI1, H2AFY, and the death-associated protein 6 (DAXX) . This domain is involved in dimerisation together with the BTB domain (

), resulting in linear higher-order oligomers .
Gem-associated protein 5, second beta-propeller domain (Beta-prop_GEMI5_2nd)
Type: Domain

This entry represents the second β-propeller found in Gem-associated protein 5 (GEMI5) from vertebrates and its orthologue from Drosophila melanogaster, Protein rigor mortis (RIG). The β-propellers in GEMI5 bind small nuclear RNAs (snRNAs) playing a critical role in the assembly of the heptameric Sm protein core on snRNAs and the biogenesis of small nuclear ribonucleoproteins (snRNPs) . Apart of being a component of the survival motor neuron (SMN) complex, it is a nuclear receptor-interacting protein required for the response to steroid hormone ecdysone during larval development in which this domain acts as a specific protein-protein interaction domain .

GEMI5 is a component of the survival of motor neurons (SMN) complex, that binds small nuclear RNAs (snRNAs). The SMN complex assembles the heptameric Sm protein core on snRNAs playing a critical role in the biogenesis of small nuclear ribonucleoproteins (snRNPs) . GEMI5 is also implicated in translation control, and gene expression reprogramming . GEMI5 from animals share a domain architecture consisting of two N-terminal β-propellers followed by a TPR domain and a C-terminal RNA-binding domain.
BT_1020-like, N-terminal beta-propeller (Beta-prop_BT_1020)
Type: Domain

This entry represents the N-terminal region of BT_1020 from Bacteroides thetaiotaomicron (

), which covers part of its 5-bladed β-propeller domain. It is usually found associated with

.
BTBDG, BTB/POZ domain (BTB_BTBDG)
Type: Domain

This entry represents the BTB/POZ domain found at the N-terminal of BTB/POZ domain-containing protein 16 (BTBDG) from animals. The function of BTBDG is not clear.
Gene 1 ring forming protein domain (G1RFP_dom)
Type: Domain

This entry represents a domain found in an uncharacterised family of bacteriophage proteins annotated as gene 1. These proteins form a pair of α-helices that interact with each other. These proteins are predicted to form large ring structures, with 13-15 subunits having the highest predicted scores. Once the rings are formed they have a strongly negatively charged exterior.
General transcription factor 3C polypeptide 1, winged-helix domain (WH_GTF3C1)
Type: Domain

This is the winged-helix (WH) domain found at the N-terminal of human General transcription factor 3C polypeptide 1 (GTF3C1, also known as TFIIIC220) and similar eukaryotic sequences. GTF3C1 is required for RNA polymerase III-mediated transcription. It binds to the box B promoter element.TFIIIC assembles the initiation complex TFIIIB-TFIIIC-tDNA, sufficient for RNA polymerase III recruitment and function.
C-Maf-inducing protein, PH domain (PH_CMIP)
Type: Domain

This entry represents the PH domain found in C-Maf-inducing protein and related proteins from animals. The human C-Maf-inducing protein is involved in T-cell signalling pathways . Proteins containing this domain are implicated in the regulation of immune responses, particularly in the differentiation and function of T-helper cells. The human isoform 2 of C-Maf-inducing protein has a specific role in the T-helper 2 (Th2) signalling pathway, linking T-cell receptor-mediated signals to the activation of the c-Maf transcription factor, which is a key regulator of Th2-specific responses .
C2 domain-containing protein 5, forth YbjQ-like domain (C2CD5_YbjQ-like_dom)
Type: Domain

This domain is found in human C2 domain-containing protein 5 (C2CD5) and similar proteins mainly from animals. C2CD5 is required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes. This domain is predicted to show a β-sheet and an α-helix.

C2CD5, also known as CDP138 or KIAA0528, is a C2 domain-containing phosphoprotein. It is a substrate for protein kinase Akt2, and it may be involved in the regulation of GLUT4 vesicle-plasma membrane fusion in response to insulin. The C2 domain of C2CD5 was shown to be capable of binding Ca(2+) and lipid membranes . Other studies indicate that C2CD5 is a CDK5- and FIBP-interacting protein, forming a complex with these proteins that is involved in cell proliferation and migration .
C2 domain-containing protein 5, YbjQ-like domain (C2CD5_YbjQ-rel_dom)
Type: Domain

This domain is found in several copies in human C2 domain -containing protein 5 (C2CD5) and similar proteins predominantly found in animals. C2CD5 is required for insulin-stimulated glucose transport and glucose transporter SLC2A4 /GLUT4 translocation to the plasma membrane in adipocytes. This domain is predicted to show a β-sheet and an α-helix.

C2CD5, also known as CDP138 or KIAA0528, is a C2 domain-containing phosphoprotein. It is a substrate for protein kinase Akt2, and it may be involved in the regulation of GLUT4 vesicle-plasma membrane fusion in response to insulin. The C2 domain of C2CD5 was shown to be capable of binding Ca(2+) and lipid membranes . Other studies indicate that C2CD5 is a CDK5- and FIBP-interacting protein, forming a complex with these proteins that is involved in cell proliferation and migration .
Gem-associated protein 5, first beta-propeller (Beta-prop_GEMI5_1st)
Type: Domain

This entry represents the first β-propeller found at the N-terminal of Protein rigor mortis (RIG) from Drosophila melanogaster, also known as Gem-associated protein 5 (GEMI5), the orthologue of GEMI5 from vertebrates . RIG, apart from being a component of the survival motor neuron (SMN) complex, it is a nuclear receptor-interacting protein required for the response to steroid hormone ecdysone during larval development .

GEMI5 is a component of the survival of motor neurons (SMN) complex, that binds small nuclear RNAs (snRNAs). The SMN complex assembles the heptameric Sm protein core on snRNAs playing a critical role in the biogenesis of small nuclear ribonucleoproteins (snRNPs) . GEMI5 is also implicated in translation control, and gene expression reprogramming . GEMI5 from animals share a domain architecture consisting of two N-terminal β-propellers followed by a TPR domain and a C-terminal RNA-binding domain.
DmsR-like, N-terminal (DmsR-like_N)
Type: Domain

This domain is found at the N-terminal of Dimethyl sulfoxide reductase transcriptional activator from Haloferax volcanii (DmsR), Transcriptional regulator NarO from Haloferax volcanii, and similar proteins from halobacteria. DmsR is required for anaerobic respiration on dimethyl sulfoxide (DMSO) . NarO activates transcription of the denitrifying genes under anaerobic conditions . This domain is predicted to adopt an α-β structure. It is often found associated with

.
GEX2, N-terminal Ig-like domain (Ig_GEX2_N)
Type: Domain

This domain is found at the N-terminal of Arabidopsis GAMETE EXPRESSED 2 (GEX2) and related plant proteins. GEX2 is localised at the sperm membrane and contains a number of extracellular Ig-like domains. GEX2 is required for gamete attachment . The domain represented by this entry adopts a β-sandwich structure with an Ig-like topology.
DNA polymerase delta/zeta catalytic subunit, N-terminal domain (DPOD/Z_N)
Type: Domain

This domain is found towards the N-terminal of DNA polymerase delta catalytic subunit (DPOD or POL3) and DNA polymerase zeta catalytic subunit (DPOZ or REV3) from Saccharomyces cerevisiae and similar eukaryotic protein sequences. POL3 is the catalytic component of DNA polymerase delta (DNA polymerase III), which participates in chromosomal DNA replication. REV3 is a nonessential DNA polymerase required for DNA damage induced mutagenesis . This domain shows an α-β configuration .
ZIC1-5/GLI1-3like, C2H2 zinc finger (Znf-C2H2_ZIC1-5/GLI1-3-like)
Type: Domain

This entry represents the C2H2 zinc finger. This class is described approximately by the motif CXWXXCXnHXRXHTGEK.

This entry includes a group of zinc finger transcription regulators, including GLI1-3, GLIS1-3 and ZIC1-5 from humans.

GLI1-3 are central effectors of the Hedgehog (Hh) pathway in vertebrates . GLI1 is an obligatory activator, whereas GLI2 and GLI3 carry activator and repressor functions . The full-length GLI3 form, after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while its C-terminally truncated form acts as a repressor (GLI3R). GLI3 participates in the patterning and growth of many organs, including the central nervous system (CNS) and limbs .

ZIC1-5 are transcriptional activators that control several developmental processess . ZIC3 is required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. It binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3' . ZIC4/5 show DNA-binding activity to the Gli-binding sequence (GLIS), similar to ZIC1-3 proteins

]. ZIC5 is essential for neural crest development, converting cells from an epidermal fate to a neural crest cell fate .

GLIS1-3 play key roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Glis1-3 share a highly homologous zinc finger domain (ZFD) containing five Cys2-His2-type zinc finger (ZF) motifs with members of the Gli and Zic family .
ZNF598/HEL2, C2H2 zinc finger (Znf-C2H2_ZNF598/HEL2)
Type: Domain

This entry represents the C2H2-type zinc finger in Hel2 from Schizosaccharomyces pombe (also known as RQT complex subunit ubiquitin-protein ligase E3 subunit Rqt1) and E3 ubiquitin-protein ligase ZNF598 from humans. These proteins act as a ribosome collision sensors: specifically recognise and bind collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation .

ZNF598 plays a key role in the ribosome quality control (RQC), a pathway that takes place when the ribosome has stalled during translation, leading to degradation of nascent peptide chains. ZNF598 is activated when ribosomes are stalled following translation of prematurely polyadenylated mRNAs . Independently of its role in RQC, this protein may also act as a negative regulator of interferon-stimulated gene expression . ZNF598 is associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammalian (m4EHP) through binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian .

HEL2 in addition to its role in the ribosome quality control, also acts as an activator of the No-Go decay (NGD) pathway by mediating polyubiquitination of monoubiquitinated RPS3/uS3 and RPS7/es7. RPS3/uS3 and RPS7/es7 are first monoubiquitinated by MAG2 and MOT2/NOT4, respectively, and HEL2 mediates formation of 'Lys-63'-linked polyubiquitin chains on monoubiquitin, leading to activation of the NGD pathway in a CUE2-mediated endonucleolytic cleavage . Hel2 is involved ubiquitination and degradation of excess histones .
CTCF-like, C2H2 zinc finger (Znf-C2H2_CTCF)
Type: Domain

This entry represents C2H2 zinc finger domains found in multiple copies in a number of transcriptional regulators such as BCL11A, CTCF, ZNF142.

CTCF is a multifunctional chromatin-binding factor that plays a central role in organising the three-dimensional structure of the genome. It binds to specific DNA sequences, forms chromatin loops and anchors DNA to nuclear structures such as the lamina. CTCF defines the boundaries between active and repressive chromatin regions by interacting with chromatin insulators, regulating communication between enhancers and promoters and contributing to gene silencing across long genomic distances. It also plays a key role in epigenetic regulation, allele-specific gene expression, and X chromosome inactivation. CTCF helps maintain unmethylated DNA regions by preferentially binding to unmethylated sites, participates in chromatin remodelling and nucleosome positioning, and supports sister chromatid cohesion through its structural functions . CTCF acts as transcriptional activator and also as a repressor of the MYC gene .

BCL11B is a key regulator of both the differentiation and survival of T-lymphocytes during thymocyte development in mammals. It is essential for modulating the responsiveness of haematopoietic stem cells to chemotactic signals by controlling the expression of CCR7 and CCR9 receptors, which guide progenitor cell migration from the bone marrow to the thymus. In activated CD4+ T-lymphocytes, BCL11B enhances the expression interleukin-2 by regulating the IL2 promoter. It also functions as a tumour suppressor in T-cell lymphomas, potentially acting within the P53-signalling pathway, and represses transcription through direct binding to a GC-rich response element independently of TFCOUP2. BCL11A is involved in the regulation of the developmental switch from gamma- to beta-globin . This protein is associated with the BAF SWI/SNF chromatin remodelling complex . BCL11A specifically binds to 5'-GGCCGG-3' sequences and functions mainly as a transcriptional repressor .
C3G9, VBS-like domain (VBS_C3G9)
Type: Domain

This domain is found in the uncharacterised protein C3G9.05 from S. pombe and related fungal proteins. It is predicted to adopt a four-helical up-and-down bundle with significant similarity to VBS-like domains.
GIR1-like, zinc ribbon domain (Zn-ribbon_GIR1)
Type: Domain

This domain is found in the Protein GL2-INTERACTING REPRESSOR 1 and 2 (GIR1/2), and Protein salt-induced and EIN3/EIL1-dependent 1 (SIED1) from Arabidopsis thaliana and related plant proteins. Proteins containing this domain are involved in the modulation of root hair development and act as negative regulators in this process. They may function as adapter proteins, interacting with other proteins to control gene expression related to root hair formation . Additionally, some proteins are implicated in ethylene-dependent salt stress responses, where they play a role in reducing the accumulation of reactive oxygen species, thereby protecting the plant from oxidative damage . This domain contains a pair of conserved cysteine residues and is predicted to adopt a fold typical for zinc-ribbon domains.
GLAA-B, beta-barrel domain II (Beta-barrel_GLAA-B_II)
Type: Domain

This entry represents the second β-barrel domain found in Alpha-1,3-galactosidase A-B (GLAA-B) from bacteria. This proteins share a domain architecture consisting of a core β-helix surrounded by two small β-barrel domains (domains I and II), which are involved in protein dimerisation. The α-helix of domain II folds over and along the wall of the active site of the adjacent monomer, with several residues protruding into the cleft that contains the active site pocket . Proteins GLAA-B are alpha-galactosidases grouped in the GH110 subfamily by its narrow subtract specificity. These proteins remove branched alpha-1,3-linked galactose residues present in blood group B antigens .
Glucosamine inositolphosphorylceramide transferase 1, N-terminal (GINT1_N)
Type: Domain

This is the N-terminal domain of Glucosamine inositolphosphorylceramide transferase 1 from Arabidopsis thaliana (GINT1), a member of the Glycosyltransferase Family 64 that is involved in glycosylinositolphosphorylceramide and sphingolipid glycosylation . This domain is predicted to adopt a five-bladed β-propeller fold.
C962R-like, N-terminal AEP domain (AEP_C962R)
Type: Domain

This AEP domain is found N-terminal in the C962R protein from African swine fever virus and related proteins. C962R protein possesses both DNA polymerisation and DNA unwinding activities. This protein adopts a ring-shaped conformation and the N-terminal AEP domain is responsible for the DNA polymerisation activity . The C962R AEP domain utilises similar two-cation-assisted mechanism in catalysis as observed in distantly related bacterial and archaeal AEP domains. It adopts an α/β structure (

).
GRF-like, zinc ribbon domain (Zn_ribbon_GRF_2)
Type: Domain

This domain is found in a group of uncharacterised proteins mainly from fungi. It is predicted to adopt a zinc ribbon fold and it is closely related to GRF type zinc fingers (

).
HPS5, TPR domain (TPR_HPS5)
Type: Domain

This entry represents the TPR domain found at the C-terminal of HPS5 protein from vertebrates, a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2) and which has a role in the endo-lysosomal dynamics of skin fibroblasts . Its mutation or absence has been linked to Hermansky-Pudlak type 5 syndrome (HPS-5) in mammals, a disease characterised by defects in lysosome-related organelles such as melanosomes and platelet dense granules . The specific function of this domain is unknown.
HPS5, TPR domain, insects (TPR_HPS5_insects)
Type: Domain

This entry represents the TPR domain found at the C-terminal of HPS5 protein from insects, a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2) . Its mutation or absence has been linked to eye-colour mutations . The function of this domain is unknown.
DNA polymerase zeta catalytic subunit, N-terminal (REV3_N)
Type: Domain

This domain is found at the N-terminal end of DNA polymerase zeta catalytic subunit (REV3) from Saccharomyces cerevisiae and similar eukaryotic sequences. REV3 is a nonessential DNA polymerase involved in DNA repair, mitochondrial DNA repair and translesion synthesis. This domain shows a mainly β-configuration . It is often found N-terminal to

.
Cadherin-related hmr-1, EGF domain (EGF_Hmr-1)
Type: Domain

This domain is found towards the C-terminal of Cadherin-related hmr-1 from Caenorhabditis elegans and related nematode sequences, a calcium-dependent cell adhesion protein required for adherens junction assembly and connecting adherens junctions to the cytoskeleton .
Capsid protein Vp20 (Vp20_capsid)
Type: Domain

This entry represents the capsid protein Vp20 from apple-latent spherical virus (ALSV) and related picorna-like plant viruses. This protein is encoded in a polyprotein that is cleaved into three capsid proteins, Vp25, Vp20 and Vp24, which all have jellyroll folds and form one protomer; 60 copies of this unit compose one virion. Vp25, Vp20 and Vp24 contribute to capsid stabilisation . Vp25 and Vp20 form more extensive interactions with their neighbours and likely form a rigid capsid frame that supports the looser Vp24 protrusions .
DNA repair protein RAD5A, UBA domain (UBA_RAD5A)
Type: Domain

This is the UBA domain found at the N-terminal of DNA repair protein RAD5A from Arabidopsis thaliana and similar plant sequences. RAD5A functions in error-free postreplication DNA repair or DNA-damage tolerance (DTT) pathway . It is required for homologous recombination (HR) induced by DNA double-strand break (DSB) in somatic cells .
DNA repair protein rhp7, treble clef domain (Znf_Tbcl_Rhp7)
Type: Domain

This domain is found in the DNA repair protein rhp7 and related fungal proteins. Rhp7 is involved in nucleotide excision repair. It is forming a complex with Rhp16 which was shown to be essential for global genome repair in S.pombe . The domain represented by this entry is predicted to adopt a treble clef fold. It contains a pair of two highly conserved CxxC sequence motifs.