SII-SWORD/CoKE huggingface dataset:
3-dehydroquinate synthase, C-terminal domain (DHQS_C)
Type: Domain

This entry represents the C-terminal domain of 3-dehydroquinate synthase (DHQS) and related proteins. This domain contains most of the residues involved in catalysis and in substrate and Zn2+ binding . This domain is also found in AROM proteins which are pentafunctional enzymes that catalyse 5 consecutive enzymatic reactions in prechorismate polyaromatic amino acid biosynthesis.

The 3-dehydroquinate synthase (DHQS) domain can exist in isolation or as a domain in the pentafunctional AROM polypeptide (

) . 3-dehydroquinate synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate . This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids. DHQS consists of an N-terminal Rossmann-fold domain and a C-terminal α-helical domain. The active site is located in a cleft between the two domains.
ZPR1, jelly-roll domain (ZPR1_jr_dom)
Type: Domain

This entry represents the jelly-roll domain found in ZPR1 family.

This entry consists of zinc finger protein ZPR1 and ZPR1-like proteins. The function of ZPR1 from archaea and eukaryotes is not yet clear. However, Zpr1 from yeast acts as a protein folding chaperone for elongation factor 1-alpha . ZPR1 is present in both the cytoplasm and nucleoplasm and its subcellular distribution changes during proliferation . ZPR1 binds to the cytoplasmic tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and is a component of downstream signalling of both EGFR and FGFR signalling . Upon stimulation by EGF, ZPR1 directly binds the eukaryotic translation elongation factor-1alpha (eEF-1alpha) to form ZPR1/eEF-1alpha complexes, an interaction that is essential for normal cellular proliferation . It has been associated with susceptibility to type 2 diabetes and is downregulated in patients with spinal muscular atrophy . ZPR1 interacts with complexes formed by SMN , and may act as a modifier that affects the severity of SMA.
SH3BP4, C-terminal helical domain (SH3BP4_C)
Type: Domain

The domain represented by this entry is predicted to fold into a mainly helical structure with a DEATH domain-like topology.

This entry includes SH3 domain-binding protein 4 (SH3BP4) and related proteins such as Metastasis-associated in colon cancer protein 1 (MACC1). SH3BP4 binds and negative regulates Rag GTPase complex. This binding abrogates the interaction of mTORC1 with Rag GTPase complex and the recruitment of mTORC1 to the lysosome, thus inhibiting amino acid-induced mTORC1 activation and cell growth and promoting autophagy . MACC1 acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. It promotes cell motility, proliferation and tumor growth and metastasis in vivo .
SH3BP4, UPA-like domain (UPA_SH3BP4)
Type: Domain

The domain represented by this entry is predicted to fold into a β-sandwich with Ig-like topology and significant similarity to UPA domain.

This entry includes SH3 domain-binding protein 4 (SH3BP4) and related proteins such as Metastasis-associated in colon cancer protein 1 (MACC1). SH3BP4 binds and negative regulates Rag GTPase complex. This binding abrogates the interaction of mTORC1 with Rag GTPase complex and the recruitment of mTORC1 to the lysosome, thus inhibiting amino acid-induced mTORC1 activation and cell growth and promoting autophagy . MACC1 acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. It promotes cell motility, proliferation and tumor growth and metastasis in vivo .
SH3BP4, DEATH domain-like (DEATH_SH3BP4)
Type: Domain

This domain is found towards the C-terminal of SH3BP4 and MACC1. This domain, which is often found N-terminal to

, is predicted to show a DEATH domain-like all-α structure.

This entry includes SH3 domain-binding protein 4 (SH3BP4) and related proteins such as Metastasis-associated in colon cancer protein 1 (MACC1). SH3BP4 binds and negative regulates Rag GTPase complex. This binding abrogates the interaction of mTORC1 with Rag GTPase complex and the recruitment of mTORC1 to the lysosome, thus inhibiting amino acid-induced mTORC1 activation and cell growth and promoting autophagy . MACC1 acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. It promotes cell motility, proliferation and tumor growth and metastasis in vivo .
BTBD17, TRAF domain (TRAF_BTBD17)
Type: Domain

This domain is found in human BTB/POZ domain-containing protein 17 and related proteins. It is predicted to adopt a β-sandwich with permuted Ig-like topology. It has a significant sequence and structural similarity to TRAF domains.
LYR motif containing domain, plants (LYRM_2_plant)
Type: Domain

This domain is found in uncharacterised plant proteins. It is predicted to fold into a three helical up-and-down bundle. It shares sequence similarity to LYR motif containing domains and has the motif conserved.
CPAF-like, PDZ domain (PDZ_CPAF-rel)
Type: Domain

This domain is found in fungal proteins that share global similarity to chlamydial protease/proteasome-like activity factor (CPAF). Amongst these proteins are peptidase S41 family proteins phomP1, phomP1' and ustP. This domain is predicted to adopt PDZ-like fold and shares sequence similarity with CPAF PDZ domain.
NOMO, eighth prealbumin-like domain (NOMO_8th)
Type: Domain

This domain is found in the NOMO family of proteins. This entry represents the eighth domain that is predicted to fold into a β-sandwich with prealbumin-like topology.

NOMO family of proteins includes NOMO1, NOMO2, NOMO3. These proteins are components of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . They play an important role in the protein topogenesis and cells lacking these components show reduced multipass protein stability . NOMO proteins are multidomain proteins.
NOMO, sixth transthyretin-like domain (NOMO_6th)
Type: Domain

This domain is found in NOMO family of proteins and has a weak sequence similarity to transthyretin-like domains. It is predicted to adopt a similar structure that consists of seven-stranded β-sandwich. NOMO proteins are predicted to contain a tandem of twelve transthyretin-like domains of which this is the sixth.

NOMO family of proteins includes NOMO1, NOMO2, NOMO3. These proteins are components of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . They play an important role in the protein topogenesis and cells lacking these components show reduced multipass protein stability . NOMO proteins are multidomain proteins.
NOMO, third transthyretin-like domain (NOMO_3rd)
Type: Domain

This domain is found in NOMO family of proteins which has a weak sequence similarity to transthyretin-like domains and it is predicted to adopt similar structure that consists of seven-stranded β-sandwich. NOMO are predicted to contain a tandem of twelve transthyretin-like domains and this domain is the third in the tandem.

NOMO family of proteins includes NOMO1, NOMO2, NOMO3. These proteins are components of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . They play an important role in the protein topogenesis and cells lacking these components show reduced multipass protein stability . NOMO proteins are multidomain proteins.
NOMO, fifth transthyretin-like domain (NOMO_5th)
Type: Domain

This domain is found in NOMO family and related proteins. NOMO proteins are predicted to contain a tandem of twelve Transthyretin-like domains and this domain is the fifth in the tandem.

NOMO family of proteins includes NOMO1, NOMO2, NOMO3. These proteins are components of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . They play an important role in the protein topogenesis and cells lacking these components show reduced multipass protein stability . NOMO proteins are multidomain proteins.
NOMO, C-terminal transthyretin-like domain (NOMO_12th)
Type: Domain

This domain is found at the C-terminal of NOMO family of proteins. The domain represented by this entry has a weak sequence similarity to transthyretin-like domains and it is predicted to adopt similar structure that consists of seven-stranded β-sandwich.

NOMO family of proteins includes NOMO1, NOMO2, NOMO3. These proteins are components of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . They play an important role in the protein topogenesis and cells lacking these components show reduced multipass protein stability . NOMO proteins are multidomain proteins.
NPAS4, bHLH domain (bHLH_NPAS4)
Type: Domain

This bHLH domain is found in the family of Neuronal PAS domain-containing protein 4 (NPAS4). NPAS4 is a transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus . It binds to DNA but efficient DNA binding requires dimerisation with another bHLH protein, such as ARNT, ARNT2 or BMAL1 .
Nuclear receptor coactivator 1-3, bHLH domain (bHLH_NCOA1-3)
Type: Domain

This bHLH domain is found in nuclear receptor coactivators NCOA1, NCOA2, and NCOA3. The NCOAs bind to nuclear hormone receptors in a ligand-dependent manner and mediate the transcriptional activation of the downstream target genes in response to hormones, metabolites, xenobiotics, and drugs. They are transcriptional coactivators for steroid receptors and nuclear receptors . NCOA2 and NCOA1 are required to control energy balance between white and brown adipose tissues . NCOA2 is also a critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression .
Nuclear receptor coactivator 3, basic helix-loop-helix (NCOA3_bHLH)
Type: Domain

This entry represents the N-terminal basic helix-loop-helix domain of Nuclear receptor coactivator 3.

NCoA-3, also termed ACTR, or amplified in breast cancer 1 protein (AIB-1), or CBP-interacting protein (pCIP), or Class E basic helix-loop-helix protein 42 (bHLHe42), or receptor-associated coactivator 3 (RAC-3), or steroid receptor coactivator protein 3 (SRC-3), or thyroid hormone receptor activator molecule 1 (TRAM-1), is a bHLH-PAS steroid/nuclear receptor-associated coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. It also plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin.
HTH 3-helical bundle (HTH_70)
Type: Domain

This domain is found in uncharacterised plant proteins. It shares significant sequence similarity to HTH 3-helical bundle domains and it is predicted to adopt similar structure.
Mmc1, C-terminal domain (Mmc1_C)
Type: Domain

This domain is found at the C-terminal of Mmc1 from Schizosaccharomyces pombe (

) and related proteins. Mmc1 functions in concert with the mitochondrial contact site and cristae organizing system (MICOS) complex to promote normal mitochondrial morphology and respiratory function . This domain is predicted to adopt a globular structure composed mainly of α-helices. Some of them are predicted to be transmembrane and as such it is likely that this domain may associates with membrane. It was proposed that Mmc1 stabilises cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane .
Putative ionotropic receptor, ligand binding domain (LBD_receptor)
Type: Domain

This domain is found in a set of putative arthropod ionotropic receptors. It is predicted to adopt an α/β structure with similarity to known ligand binding domains of ionotropic receptors such as

.
SPEF2, C-terminal domain (SPEF2_C)
Type: Domain

This domain is found in the axoneme central apparatus (CA) associated proteins such as Chlamydomonas Central pair complex 1 (CPC1,

) and its mammalian orthologues Sperm flagellar protein 2 (SPEF2) . CPC1 is located at C1 microtubule. Most of the distal components of the C1b projection bind CPC1 and its correct recruitment and positioning is critical to the formation of the C1b projection, and ciliary motility in Chlamydomonas and humans . CPC1 serves as the rachis of the entire C1b arm. This domain is predicted to fold into two EF-hand pairs that seem to lack the Ca2+-coordinating residues.
Neurotrophin 1, N-terminal (NT_N)
Type: Domain

This domain is found N-terminal in fruit fly Neurotrophin 1 (NT) and related proteins from arthropods. NT binds to Toll-7 and probably acts as its ligand in promoting motor axon targeting and neuronal survival in the central nervous system (CNS) . In larvae, NT is involved in the negative regulation of the tracheal immune response to bacterial infection by acting as a ligand for the Toll-related receptor Tollo . This domain is predicted to fold into a globular structure consisting of α-helices. It is frequently found N-terminal to

.
Type I-B CRISPR Cas8b, N-terminal domain (Cas8b_N)
Type: Domain

This entry represents the N-terminal domain of Type I-B CRISPR Synechocystis Cas8b and related proteins.

Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Cas8b subunit displays very low sequence similarity with the large subunits of any other known type I CRISPR systems. Cas8b N-terminal domain is involved in PAM recognition . The C-terminal domain of Cas8b and three Cas11b small subunits together form the inner 'belly' of the cascade integral complex. They provide support for the non-target strand within the full R-loop state structure .
Type I-B CRISPR Cas8b, C-terminal domain (Cas8b_C)
Type: Domain

This entry represents the C-terminal domain of Type I-B CRISPR Synechocystis Cas8b and related proteins.

Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Cas8b subunit displays very low sequence similarity with the large subunits of any other known type I CRISPR systems. Cas8b N-terminal domain is involved in PAM recognition . The C-terminal domain of Cas8b and three Cas11b small subunits together form the inner 'belly' of the cascade integral complex. They provide support for the non-target strand within the full R-loop state structure .
Cds6, C-terminal domain (Cds6_C)
Type: Domain

This entry represents the C-terminal domain of Cds6 from H. pylori (

), a cell shape-determining protein that plays key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. It is also involved in deglycosylation of the flagellar protein FlaA. This domain adopts NTF2-like topology . This domain contains a putative binding pocket for pseudaminic acid suggesting this domain may function as pseudaminase .
K1 capsule-specific polysaccharide lyase, C-terminal domain (K1-lyase_C)
Type: Domain

This entry represents the C-terminal domain of K1 capsule-specific polysaccharide lyase from Klebsiella phages and related proteins. This domain adopts a β-sandwich fold .

K1-lyase functions as a receptor binding protein (RBP) and mediates the attachment to the host capsular exopolysaccharides . This enzyme possesses a lyase activity that specifically degrades the K1-type polysaccharides of Klebsiella pneumoniae capsule .
Meg (Meg)
Type: Domain

This entry includes Maternally expressed gene (Meg) family of proteins, a multigene family expressed in maize that encodes cysteine-rich proteins. The founding member of the family, Meg1, is required for normal development of the basal endosperm transfer cell layer and is involved in the allocation of maternal nutrients to growing seeds . Expansion of Meg family involves potentially adaptive functional and structural transitions . In most members this entry covers the full length, while in Meg5 it is found at the C-terminal.
Immune protein Tis1 (Tis1_ImmP)
Type: Family

Tas1 is a type VI secretion effector in the pathogen Pseudomonas aeruginosa that synthesises (p)ppApp. Its cognate immunity protein Tis1 is represented by this entry. Binding of the immunity protein probably neutralises Tas1-mediated toxicity by inducing structural rearrangement in the acceptor nucleotide binding site of the enzyme .
Tape measure protein PB2, N-terminal (TMP_PB2_N)
Type: Domain

This entry represents the N-terminal conserved region of the Tape measure protein PB2 and related proteins found mainly in T5-like phages. PB2 functions as a tape measure protein that serves as a base for tail tube protein polymerisation and acts as a template for tail length determination . This protein fills the tail tube with its long coiled-coil domain and is expelled during the conformation changes that follow T5 binding to host FhuA receptor . The tape measure protein N-terminal region is organised within the tail tube in a three-stranded parallel α-helical coiled coil which makes direct contact with the genomic DNA .
Tape measure protein PB2, C-terminal (TMP_PB2_C)
Type: Domain

This entry represents the C-terminal conserved region of the Tape measure protein PB2 and related proteins found mainly in T5-like phages. PB2 functions as a tape measure protein that serves as a base for tail tube protein polymerisation and acts as a template for tail length determination . This protein fills the tail tube with its long coiled-coil domain and is expelled during the conformation changes that follow T5 binding to host FhuA receptor . The tape measure protein C-terminal region is composed of two α-helices that are organised in an extended L-shape. The C-terminal region of the TMP was found within the tail tip suggesting that the tail tip complex returns to its original state after DNA ejection .
SU10 adaptor protein (SU10_adaptor)
Type: Family

This entry represents adaptor proteins found in SU10-like bacteriophages and prophages. The dodecamer of SU10 adaptor proteins forms the interface between the dodecamer of portal proteins and hexamer of nozzle proteins . The adaptor complex provides six attachment sites for long tail fibres, each of which is formed by a trimer of long tail fibre proximal proteins and a trimer of long tail fibre distal proteins. The adaptor protein of SU10 has the same domain organisation as those of phages T7 and KP32. Its structure consists of an α-helical bundle domain composed of intertwined N- and C-terminal helices; and a β-sandwich long tail fibre dock domain .
Effector protein Avr2-like (Avr2-like)
Type: Family

This entry represents Fusarium oxysporum Avr2 effector protein (

) and similar sequences from ascomycetes. Avr2 targets a conserved defence mechanism in different hosts. It also suppresses FLS2-mediated immune responses, such as growth inhibition, ROS production, MAPK activation and callose deposition following flagellin22 treatment . Avr2 folds into a β-sandwich with some similarity to TRAF domains.
T2SS substrate NttC-like (NttC-like)
Type: Family

This entry represents the T2SS protein NttC from Legionella pneumophila (

) and related proteins found mainly in other Legionella species. NttC has a key role during L.pneumophila infection of Vermamoeba vermiformis and Willaertia magna amoebas. It folds into an Ig-like β-sandwich containing ten β-strands and an α-helix which provides one of the pair cysteines involved in the disulfide bond formation. NttC is unusual in that it lacks a compact core and instead contains a buried internal cavity . This cavity was proposed to bind a variety of organic molecules .
T2SS substrate NttA (NttA)
Type: Domain

This entry represents the type II secretion system substrate NttA from Legionella pneumophila and related proteins found mainly in Legionellales species. Homologues of NttA are also found outside Legionella genus. NttA contains and N-terminal disordered region followed by a globular all-α helical domain consisting of four α-helices . NttA was shown to interact with phosphoinositides with a clear preference for phosphatidylinositol -3,5-biphosphate [PtdIns(3,5)P2] . NttA is likely targeted to host organelles, such as the Legionella containing vacuole, during intracellular infection.
T2SS substrate NttE-like (NttE-like)
Type: Family

This entry represents the type II secretion system substrate NttE from Legionella pneumophila (

) and related proteins found mainly in Legionellales species. NttE structure is composed of two intertwined α/β domains, each of which consists of an antiparallel β-sheet and α-helices packed on it . This protein forms stable dimers and the dimer interface is contributed by the C-terminal domain. The N-terminal domain of NttE is mobile which is likely essential for its function in modifying the bacterial cell surface and/or during intracellular infection .
SrfA-like, pseudomonas (SrfA-like_pseudomonas)
Type: Family

This entry represents the Stress Response Facilitator A SrfA from Pseudomonas aeruginosa (

) and similar sequences from Pseudomonas species. SrfA was shown to play a positive role in the sigma(22)-dependent activation of the algD promoter under stress in both sessile and planktonic conditions . This protein folds into an α-helical hairpin.
Anti-CRISPR Suppressor AcrIIA4-like (AcrIIA4-like)
Type: Family

This entry represents Anti-CRISPR Suppressor AcrIIA4 proteins encoded by Listeria monocytogenes prophages, including

. AcrIIA4 preferentially targets critical residues essential for PAM duplex recognition, as well as it blocks target DNA access to the key catalytic residues lining the RuvC pocket of Cas9 . AcrIIA4 adopts a fold composed of a three-stranded β-sheet with three α-helices positioned along one face of the β-sheet .
Probiotic-derived p8-like (P8-like)
Type: Family

This entry represents the Probiotic-derived p8 protein from Lactobacillus rhamnosus and related proteins found mainly in Lactobacillales. P8 has anti-cancer properties in colorectal cancer (CRC) cells via inducing apoptosis through regulation of Ring finger protein 152 (RNF152) and thus inhibiting the development of CRC . P8 adopts a globular structure consisting of a three-helical bundle (

).
THSD1, N-terminal domain (THSD1_N)
Type: Domain

This domain is found N-terminal in human Thrombospondin type-1 domain-containing protein 1 (THSD1) and similar proteins mainly found in vertebrates. THSD1 is involved in endothelial cell to extracellular matrix adhesion . THSD1 forms a multimeric protein complex with FAK/talin/vinculin, wherein THSD1 promotes talin binding to FAK but not to vinculin, a key step in nascent adhesion assembly . The domain represented by this entry is predicted to adopt Ig-like β-sandwich.

Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers . EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.