SII-SWORD/CoKE huggingface dataset:
Spermatogenesis-associated protein 46-like (Spt46-like)
Type: Family

This family is found in chordata. The deletion of Spata46 in mice resulted in subfertility with abnormal sperm head shape and a failure of sperm-egg fusion . Spata46 has also been shown to localize to the nuclear membrane by a transmembrane region in the N-terminal.
Domain of unknown function DUF5604 (DUF5604)
Type: Domain

This domain is often found in the N-terminal region of proteins carrying the SET domain, such as the SETDB1 protein from Humans. SETDB1 is a histone methyltransferase that suppresses gene expression and modulates heterochromatin formation through H3K9me2/3 .
Urease subunit beta-alpha, linker domain (Urease_linker)
Type: Domain

This domain is present in plant ureases and corresponds to the gap region between the C terminus of the beta-chain Urease beta subunit and the N terminus of the alpha-chain Urease alpha-subunit, N-terminal domain . It is suggested that this region is required for the stability of the putative transmembrane β-barrel .
Cas12a, nuclease domain (Cas12a_NUC)
Type: Domain

This is a nuclease (NUC) domain found in Cas12a, an RNA-guided endonuclease of a type V CRISPR-Cas system. Structural and functional analysis indicate that this domain is involved in DNA cleavage .
Fatty acid synthase, meander beta sheet domain (FAS_meander)
Type: Domain

This domain is found in fungal fatty acid synthase beta chain proteins .
SMODS and SLOG-associating 2TM effector domain 1 (SLATT_1)
Type: Domain

The SLATT domain contains two transmembrane helices. SLATT domains are generally predicted to function as pore-forming effectors in a class of conflict systems which are reliant on the production of second messenger nucleotide or nucleotide derivatives. SLATT domains are predicted to initiate cell suicide responses upon their activation. This SLATT domainy is often C-terminally fused to the SLATT_3 (

), and is typically operonically linked to either inactive TIR domains or SLOG domains which could act as regulators of the SLATT channels. In relatively rare instances, it is genomically linked as a standalone domain to the RelA/SpoT nucleotide synthetase and the predicted NA37/YejK sensor domain .
Synaptotagmin-like, mitochondrial and lipid-binding domain (SMP_C2CD2L)
Type: Domain

This is a lipid transport domain found in phospholipid transfer proteins such as C2CD2L-like (also known as TMEM24). The TMEM24-SMP domain is shown to bind glycerolipids with a preference for phosphatidylinositol (PI). The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and hence insulin secretion. The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP for (tubular lipid-binding proteins) it adopts TULIP fold with two α helices and a highly curved antiparallel β sheet forming a cornucopia-like structure .
TRIF, N-terminal (TRIF_N)
Type: Domain

The N-terminal domain of TRIF/TICAM-1 has a structure that consists of eight antiparallel helices . This domain believed to be involved in self-regulation of TRIF by interacting with its TIR domain .
Aldos-2-ulose dehydratase/isomerase (AUDH), Cupin domain (AUDH_Cupin)
Type: Domain

The enzyme aldos-2-ulose dehydratase/isomerase (AUDH) participates in carbohydrate secondary metabolism, catalyzing the conversion of glucosone and 1,5-d-anhydrofructose to the secondary metabolites cortalcerone and microthecin, respectively. Crystal structure analysis revealed that the enzyme subunit is built up of three domains, an N-terminal seven-bladed propeller, a bicupin and a C-terminal lectin domain. This entry describes the second Cupin domain (residues 574-739) composed of two antiparallel sheets that build up the jellyroll sandwich fold formed from four and five β-strands. This cupin domain in AUDH is found to contain a zinc binding site where the metal site is located at the bottom of the cleft formed by the β-sandwich, as observed in many cupins .
PilN biogenesis protein dimerization domain (PilN_bio_d)
Type: Domain

This domain is found in PilN type IV pilus biogenesis protein present in Thermus thermophiles. PilN is an integral inner membrane protein needed for the formation of type IV pilus. This domain forms a dimer which is mediated by symmetric contacts between residues in alpha-1, beta-1, beta-3 and alpha-3 .
CopZ, zinc binding domain (Znf_CopZ)
Type: Domain

This entry represents the N-terminal domain of the copper chaperone CopZ protein, which delivers Cu+ directly to the transmembrane transport sites of copper-exporting P-type ATPase A (CopA) . This domain contains a mononuclear metal centre for zinc binding .
SAV_6107-like HEPN (HEPN_SAV_6107)
Type: Domain

This entry represents the HEPN domain found in SAV_6107 .
RPN1, N-terminal (RPN1_N)
Type: Domain

The 26S proteasome is the major ATP-dependent protease in eukaryotes which plays a key role in intracellular protein degradation .

This domain is found at the N terminus of the 26S proteasome regulatory subunit RPN1 (also known as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2)) . The domain is formed by an array of α-helices .
RPA-related protein RADX (RADX)
Type: Family

RADX is an RPA-like, single-stranded DNA binding protein recruited to replication forks to maintain genome stability . It has been shown to modulate stalled fork protection by antagonizing RAD51 .
Large ribosomal subunit protein bL17m, C-terminal, fungi (Ribosomal_bL17m_C)
Type: Domain

This is the C-terminal domain of mitochondrial large ribosomal subunit protein bL17m found in yeast .
Argonaute, PAZ domain (Ago_PAZ)
Type: Domain

This entry represents the PAZ domain found in argonaute from Thermus thermophilus and Synechococcus elongatus . Argonaute has a central role in the RNA interference pathway by mediating the maturation of small interfering RNA (siRNA) through initial degradation of the passenger strand, followed by guide-strand-mediated sequence-specific cleavage of target mRNA. The nucleic-acid-binding channel is thought to be positioned between the PAZ and PIWI domain .
26S proteasome regulatory subunit RPN5, C-terminal domain (RPN5_C)
Type: Domain

This entry represents the C-terminal domain of the 26S proteasome regulatory subunit RPN5. This helical domain can be found adjacent to the PCI domain. The 26S proteasome is the major ATP-dependent protease in eukaryotes that consists of three subcomplexes: the lid, the base, and the core. The helices found at the C terminus of each lid subunit form a helical bundle that directs the ordered self-assembly of the lid subcomplex. This domain which comprises the tail of RPN5 along with the tail of RPN9, are important for RPN12 binding to the lid .
Plasmodium host cell traversal SPECT1 (SPECT1)
Type: Domain

This domain is found in SPECT1 (sporozoite microneme protein essential for cell traversal). It is formed of a four α-helix bundle with a 'hook'-like feature at one end. These helices in parallel or antiparallel alignment .
CxC6 like cysteine cluster associated with KDZ (CxC6)
Type: Domain

This entry represents a predicted Zinc chelating domain inserted into the core of the KDZ transposase domain .
Fatty acid synthase subunit alpha, acyl carrier domain (Fas_alpha_ACP)
Type: Domain

This is the acyl carrier domain (ACP) found in fatty acid synthase subunit alpha (FAS2). The fungal type I fatty acid synthase (FAS) is a 2.6 MDa multienzyme complex, catalyzing all necessary steps for the synthesis of long acyl chains. To be catalytically competent, the FAS must be activated by a posttranslational modification of the central acyl carrier domain (ACP) by an intrinsic phosphopantetheine transferase (PPT) .
Spermine synthase, N-terminal (SpmSyn_N)
Type: Domain

This is the N-terminal domain found in human spermine synthase. The N-terminal domain, which forms the major part of the dimerization interface, shows a considerable structural similarity to the AdoMetDC-like fold (S-adenosylmethionine decarboxylase, the enzyme that forms the aminopropyl donor substrate). Deletion of the N-terminal domain led to a complete loss of spermine synthase activity, suggesting that dimerization may be required for activity. The N-terminal domain (amino acids 1-117) includes seven β-strands and two α-helices .
Leukemia inhibitory factor receptor, N-terminal (LIFR_N)
Type: Domain

This domain can be found in leukemia inhibitory factor receptor (LIFR). LIFR is a cell surface receptor that mediates the actions of LIF and other interleukin-6 type cytokines through the formation of signalling complexes with gp130. This is the N-terminal domain, referred to as domain 1, which contains conserved disulfide bonds between Cys-10 to Cys-20 and Cys-37 to Cys-45 .
REase, AHJR-like (AHJR-like)
Type: Domain

This REase fold has been shown to fuse to HEPN(DUF86) .
Retroviral integrase, C-terminal SH3 domain (SH3_11)
Type: Domain

This is the carboxy-terminal domain (CTD) found in retroviral integrase, an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The CTD adopts an SH3-like fold. Each CTD makes contact with the phosphodiester backbone of both viral DNA molecules, essentially crosslinking the structure .
Protein of unknown function DUF5557 (DUF5557)
Type: Family

This is a family of unknown function found in primates.
DNA-Binding protein G5P, Pseudomonas (SS_DBP_Pseudomonas)
Type: Family

This entry includes single-stranded DNA binding protein G5P encoded by the filamentous Pseudomonas bacteriophage Pf3 .
Protein of unknown function DUF5535 (DUF5535)
Type: Family

This is a family of unknown function found in mammals.
IL-3 receptor alpha chain, N-terminal (IL3Ra_N)
Type: Domain

Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Structure of IL-3 receptor alpha chain (IL3Ra) in complex with the anti-leukemia antibody CSL362 reveals that the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), contains the CSL362 binding epitope. Furthermore, NTD of IL3Ra adopts a typical fibronectin type III (FnIII) fold .
Hydroquinone 1,2-dioxygenase large subunit, N-terminal (PnpCD_PnpD_N)
Type: Domain

This is the N-terminal domain of the alpha subunit, known as PnpD, of Hydroquinone 1,2-dioxygenase (PnpCD) present in Pseudomonas sp. strain WBC-3. PnpCD is the key enzyme in the degradation pathway of pollutant para-nitrophenol (PNP). The N-terminal domain residues Trp-76 and Phe-79 are indispensable in the formation of the active site pocket. The N-terminal domain also plays a vital role in formation of the heterotetrameric structure. Structural homologs of the N-terminal domain exhibit the nature to bind nucleic acids but due to the steric effect of the C-terminal domain, this N-terminal domain cannot bind nucleic acids .
E3 ubiquitin-protein ligase CHFR, cysteine rich domain with multizinc binding (CHFR_Znf-CRD)
Type: Domain

This is a cysteine rich domain which contains four zinc-binding regions (binding five zinc ions) found in CHFR, an E3 ubiquitin-protein ligase . CHFR interacts with Poly(ADP-ribose) (PAR) through a 20-amino acid PAR binding zinc finger region (PBZ) found at the C-terminal end of this cysteine-rich domain (i.e. the 4th region towards the C-terminal). CHFR lacking PBZ does not co-localize with nuclear PAR foci in interphase cells and cannot rescue antephase checkpoint function despite retaining autoubiquitination activity. Hence it has been suggested that the CHFR-PAR interaction is an important part of the antephase checkpoint and could form part of the checkpoint sensor for cellular stress and microtubule poisons or be required for proper localization of CHFR. The PBZ region of CHFR contains two adenine binding sites .
Closterovirus 1a polyprotein, central region (Zemlya)
Type: Family

This family represents an alignment of the Zemlya region of closteroviruses. The alignment of the 1a polyprotein of the Closteroviridae family members revealed that this region was not conserved in other genera. The homologs of the Zemlya region are not found in other viral or cellular proteins. This region is named "the Zemlya region" (zemlya)-is the Russian word for "earth", meaning that its conserved amino acid sequence represents a solid ground within the highly variable central region of 1a polyporotein. It is composed of four predicted α-helices, alphaA to alphaD, and contains three conserved positions: i) a strictly conserved glutamate (E) in helix alphaA (E1291 in Beet yellows closterovirus (BYV)); ii) a strictly conserved proline (P1380) in alphaD; and iii) a conserved basic position (arginine or lysine; R1384 in BYV). The presence of a conserved proline in helix alphaD is noteworthy because prolines are strongly disfavoured in helices; this proline most probably induces a kink in the helix. Functional studies have suggested that most part of the Zemlya region, targets the ER and remodels the ER membranes. More specifically, deletion analysis and substitutions of the conserved hydrophobic amino acid residues suggest a role of the putative amphipathic helix1368-1385 (alphaD) in the formation of globules. Hence it was proposed that this specific region in 1a protein protein may be involved in the biogenesis of closterovirus .
Exostosin, GT47 domain (Exostosin_GT47)
Type: Domain

There are five identified human EXT family proteins (EXT1, EXT2, EXTL1, EXTL2 and EXTL3), which are members of the hereditary multiple exostoses family of tumor suppressors . They are glycosyltransferases required for the biosynthesis of heparan sulfate. Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterised by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses . Mutations in two homologous genes, EXT1 and EXT2, are responsible for the EXT syndrome. The human and mouse EXT genes have at least two homologues in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. EXT1 and EXT2 have both been shown to encode glycosyltransferases involved in the chain elongation step of heparan sulphate biosynthesis .

In addition to a b-glucuronyltransferase domain, exostosins contain an additional alpha 1,4-N-acetylglucosaminyltransferase domain that belongs to family GT64 . Activities of both exostosin GT domains are required for synthesizing the backbone of glycosaminoglycan, heparan sulfate. In plants, many genes have been shown to encode proteins with significant sequence similarity to the exostosin b-glucuronyltransferase domain and therefore are grouped into family GT47 . This entry represents the GT47 domain of exostosins.
Repeat of unknown function DUF5633 (DUF5633)
Type: Repeat

This entry represents a 40 residue repeat that is often found in tandem in a small set of bacterial cell surface proteins. The function of this region is not known.
Htr2, transmembrane domain (Htr2)
Type: Domain

Archaebacterial photoreceptors mediate phototaxis by regulating cell motility through two-component signaling cascades like those found in chemotaxis signaling chains of enteric bacteria. The photoreceptor sensory rhodopsin II from N. pharaonis (NpSRII) in complex with its cognate transducer NpHtrII serves as a system for transmembrane signal transfer. This entry is for the transmembrane domain of the transducer HtrII. Studies suggest that conformation changes of the NpSRII/NpHtrII complex may be crucial for the mechanism of signal propagation spanning the membrane domain and feeding into the HAMP domain . Furthermore, HtrII in H. salinarum not only transmits the signal from the photoreceptor SRII but also operates as a chemoreceptor.
PH0542 repeat (PH0542)
Type: Repeat

Repeat found in PH0542 showing some sequence similarity to HEAT repeat.
GK1464-like domain (GK1464-like_dom)
Type: Domain

This entry represents a domain found in a group of bacterial proteins, including GK1464 from Geobacillus kaustophilus.
DD-reactivating factor swiveling domain (DDR_swiveling)
Type: Domain

AdoCbl-dependent diol dehydratase (DD) (

) is one of the enzymes that catalyzes the conversion of 1,2-propanediol, 1,2-ethanediol, and glycerol to the corresponding aldehydes. A DD-reactivating factor (DDR) is responsible for the rapid reactivation of the inactivated holoDD in the presence of AdoCbl, ATP, and Mg2+. DDR exists as a dimer of heterodimer (α-β)2. The alpha subunit has four domains: ATPase domain, swiveling domain, linker domain, and insert domain. The beta subunit, composed of a single domain, has a similar fold to the beta subunit of diol dehydratase (DD). This entry describes the swiveling domain of DDR, which structurally connects the beta subunit and the ATPase domain of the other alpha subunit. Furthermore, the beta subunit moves with the swiveling domain while the linker domain acts as a flat spring or a hinge for the domain movement of the swiveling domain .
RalF, C-terminal Sec-7 capping domain (RalF_SCD)
Type: Domain

This is the C-terminal domain of RalF protein present in Legionella pneumophilia. RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. This domain forms a cap over the active site in the Sec7 domain and so is referred to as the Sec7-capping domain .
GatD, N-terminal (GatD_N)
Type: Domain

This is the N-terminal domain of GatD protein present in Pyrococcus abyssi. Two GatD and two GatE associate to form a tetramer complex. The tetramer complex is able to mature Glutamic acid-tRNA Glutamine into Glutamine-tRNA Glutamine, a necessary step in the translation of proteins. The N-terminal domain is involved in anchoring GatD to GatE in order to form the tetramer .
Asparaginase/glutaminase, C-terminal (Asparaginase_C)
Type: Domain

This domain is found at the C terminus of asparaginase enzymes.

L-Asparaginases (

) hydrolyse L-asparagine to L-aspartate and ammonia. Enzymes with asparaginase activity play an important role in the metabolism of all living organisms . Enzymes capable of converting L-asparagine to L-aspartate can be classified as bacterial-type or plant-type L-asparaginase. Bacterial-type L-asparaginase are further divided into subtypes I and II, defined by their intra-/extra-cellular localization, substrate affinity, and oligomeric form. Homologous bacterial-type L-asparaginase are found in all kingdoms of life. Furthermore, bacterial-type L-asparaginase are related to other enzymes, including:

Bacterial L-glutaminase-asparaginase (

) .

Archaeal GatD subunit of Glu-tRNA amidotransferase (Glu-AdT) .

Mammalian lysophospholipase (

), which is believed to play a major role in the hydrolytic degradation of lysophosphatidylcholine .
Arabinosyltransferas, concanavalin like domain (Arabino_trans_N)
Type: Domain

Arabinosyltransferase is involved in arabinogalactan (AG) biosynthesis pathway in mycobacteria. AG is a component of the macromolecular assembly of the mycolyl-AG-peptidoglycan complex of the cell wall. This enzyme has important clinical applications as it is believed to be the target of the antimycobacterial drug Ethambutol . This entry represents the concanavalin like domain found at the N terminus of arabinosyltransferas.
LD-carboxypeptidase, C-terminal (Peptidase_S66C)
Type: Domain

This entry represents the C-terminal domain of the LD-carboxypeptidase A. Muramoyl-tetrapeptide carboxypeptidase or LD-carboxypeptidase A hydrolyses a peptide bond between a di-basic amino acid and the C-terminal D-alanine in the tetrapeptide moiety in peptidoglycan. This cleaves the bond between an L- and a D-amino acid. The function of this activity is in murein recycling . Proteins containing this domain also include the microcin c7 self-immunity protein

and microcin immunity protein MccF .
Large ribosomal subunit protein mL59 domain (Ribosomal_mL59_dom)
Type: Domain

This domain can be found in mitochondrial large ribosomal subunit protein mL59 (also known as MRPL25) from Saccharomyces cerevisiae . mL59 is known to partially stabilize a change in the rRNA path prior to helix 82-ES1 ultimately leading to the stabilization of the phosphate backbone of the tRNA acceptor stem. It is worth noting that the domain is encoded in the nucleus and imported from the cytoplasm .
4-hydroxyphenylacetate decarboxylase small gamma subunit, C-terminal (HpdC_C)
Type: Domain

This is a C-terminal domain found in 4-hydroxyphenylacetate decarboxylase small gamma subunit (

), which catalyzes the last reaction in the fermentative production of p-cresol from tyrosine. The C-terminal domain [4F-4S] cluster bears structural similarity to high-potential iron-sulfur proteins (HiPIPs). HiPIPs have an N-terminal extension of 20-40 residues, so the structural similarity is limited to their Fe/S cluster-binding scaffold. Furthermore, despite of the weak amino acid sequence identity, the cluster binding motifs are remarkably similar to H/CX2CX12-13CX16-17C for the gamma-subunit and CX2CX13-19CX14-19C for HiPIPs .
5-hmdU DNA kinase (HMUDK/HMUD1)
Type: Family

5-hmdU DNA kinase (HMUDK) and 5-hmdU DNA kinase 1 (HDMU1) are P-loop nucleotide kinases that phosphorylates 5-hydroxymethyluracil (5hmdU) into 5-phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome . HMUDK also transfers glutamate to 5-pyrophosphoryloxymethyldeoxyuridine (5-PPmdU) to produce 5-Nalpha-glyutamylthymidine (Nalpha-GluT) . These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system .
Heparinase II, C-terminal (HepII_C)
Type: Domain

Heparinase II (HepII) is an 85kDa dimeric enzyme that depolymerizes both heparin and heparan sulfate glycosaminoglycans . The protein is composed of three domains: an N-terminal α-helical domain, a central two-layered β-sheet domain, and a C-terminal domain forming a two-layered β-sheet. The C-terminal domain contains nine β-strands packed together in a manner resembling a β-barrel .
Cellular tumor antigen p53, transactivation domain 2 (p53_TAD2)
Type: Domain

This is a N-terminal transactivation domain (TAD) domain 2 found in p53 proteins. In p53 two TAD domains are found termed TAD1 (residues 1-39) and TAD2 (residues 40-61), both of which have been shown to be able to independently activate gene transcription and are intrinsically disordered protein domains that adopt a helical conformation for at least part of their length when bound. This inherent flexibility allows the TADs to adapt to and bind a broad range of proteins. This entry describes TAD2 which can independently interact with Taz2 domain of the histone acetyltransferase p300 . It has also been shown to bind to OB-fold domain of replication protein 70 A (RPA) as well as the pleckstrin homology (PH) domain of the p62 and Tfb1 subunits of human and yeast TFIIH .
Monalysin, Pore-forming domain (PF_Monalysin)
Type: Domain

This domain is found in Monalysin Pore-forming Toxin which is a type of β-barrel pore-forming toxin protein found in Pseudomonas entomophila. Monalysin forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers to form a pore. The domain is composed of a central twisted β-sheet composed of three antiparallel β-strands (β3, β6, and β8/9) and flanked by the pore-forming segment and the C-terminal region on either side. The pore-forming domain (residues 102-170) is located between strands β3 and β6, and is formed from two antiparallel β-strands connected by three α-helices, α3, α4, and α5. The C-terminal region forms a long α-helix followed by a small hairpin and a short α-helix .