SII-SWORD/CoKE huggingface dataset:
Exocyst complex component Sec3, PIP2-binding N-terminal domain (Sec3-PIP2_bind)
Type: Domain

This is the N-terminal domain of fungal and eukaryotic Sec3 proteins. Sec3 is a component of the exocyst complex that is involved in the targeting and tethering of post-Golgi secretory vesicles to fusion sites on the plasma membrane prior to SNARE-mediated fusion. This N-terminal domain contains a cryptic pleckstrin homology (PH) fold, and all six positively charged lysine and arginine residues in the PH domain predicted to bind the phosphatidylinositol 4,5-bisphosphate (PIP2) head group are conserved. In fission yeast, polarised exocytosis for growth relies on the combined action of the exocyst at cell poles and myosin-driven transport along actin cables .
AP2-like integrase, N-terminal domain (AP2-like_int_N)
Type: Domain

This entry represents the AP2-like domains found N-terminal in a variety of phage integrase proteins, including the ICEBs1 integrase from Bacillus subtilis . Presumably these domains are DNA-binding.
FAM177 family (FAM177)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 134 and 205 amino acids in length.
Dihydroprymidine dehydrogenase domain II (DPD_II)
Type: Domain

Domain II of the enzyme dihydroprymidine dehydrogenase binds FAD. Dihydroprymidine dehydrogenase catalyses the first and rate-limiting step of pyrimidine degradation by converting pyrimidines to the corresponding 5,6- dihydro compounds . This domain carries two Fe4-S4 clusters.
CST complex subunit CTC1, plant (CTC1_plant)
Type: Family

This entry represents the conserved telomere maintenance Component 1 (CTC1) protein from plants. In Arabidopsis thaliana, AtCTC1 localises to telomeres, interacts with AtSTN1 and plays an role in telomere maintenance . AtCTC1 also interacts with lagging-strand replication machinery . AtCTC1 is a component of the plant CST complex .
Flagellar motor switch protein FliG, N-terminal domain (FliG_N)
Type: Domain

This is the N-terminal domain of the flagellar rotor protein FliG .
Immunity protein 15 (Imm15)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and several conserved polar and hydrophobic residues. Proteins containing this domain are present in heterogeneous polyimmunity loci in polymorphic toxin systems .
TTDN1/Protein SICKLE (TTDN1/SICKLE)
Type: Family

This entry includes animal M-phase-specific PLK1-interacting protein (also known as TTDN1) and plant protein SICKLE.
Tumor protein p53-inducible protein 11 (TP53I11)
Type: Family

p53 is a tumour suppressor that suppresses tumour development by inducing stable growth arrest or cell apoptosis . The expression of p53 induces the transcription of several genes, including the TP53I11 (also known as PIG11) gene, which expresses the tumor protein p53-inducible protein 11 . The function of this protein is not clear.
Rapamycin-insensitive companion of mTOR, N-terminal domain (Pianissimo_N)
Type: Domain

The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that forms two functionally distinct complexes, mTROC1 and mTORC2, important for nutrient and growth-factor signalling. Rictor (rapamycin-insensitive companion of mTOR) is a component of mTORC2 . There is a regulatory link between the two mTOR complexes, whereby Rictor phosphorylation by mTORC1 regulates mTORC2 signalling . Over-expression of Rictor increases mTORC2 activity and promotes cell growth and motility .

This domain is the N-terminal conserved section that may include several individual domains.
Pianissimo family (Pianissimo_fam)
Type: Family

Protein pianissimo (PiaA) is a component of the target of rapamycin complex 2 (TORC2) in Dictyostelium . This complex regulates cell growth, chemotaxis, signal relay and the actin cytoskeleton. Homologues of PiaA are found in Saccharomyces cerevisiae (TSC11/AVO3) , Schizosaccaromyces pombe (Ste20) , and vertebrates, where it is also known as Rictor (rapamycin-insensitive companion of mTOR) .

Rictor, together with Sin1, is believed to function as an adaptor protein controlling the mTORC2 substrate binding and specificity. Rictor is known to have a role in cytoskeleton regulation and cell migration . It is likely that rictor regulates cell morphology and migration by playing a role as the indispensable component of mTORC2 and also by carrying mTORC2-independent functions.
AP-4 complex subunit epsilon-1, C-terminal (AP4E1_C)
Type: Domain

This domain is found in the C-terminal of the AP-4 complex subunit epsilon-1 (AP4E1). Epsilon-1 is a subunit of novel type of clathrin- or non-clathrin-associated protein coat involved in targeting proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system .
RNA guanine-N7 methyltransferase activating subunit (RAMAC)
Type: Family

This entry represents RNA guanine-N7 methyltransferase activating subunit (RAMAC; also known as RNMT-activating mini protein, RAM), which is an essential component of the mRNA-capping methyltransferase RNMT:RAMAC complex required for mRNA cap methylation . RAM consists of an N-terminal RNMT-activating domain and a C-terminal RNA-binding domain .

In eukaryotes, the 7-methylguanosine cap added to the 5' end of mRNA is required for efficient gene expression. In mammals, methylation of the guanosine cap requires RNMT (RNA guanine-7 methyltransferase) . The interaction between RNMT and RAM enhances the mRNA binding capacity and cap methyltransferase activity .
TerY-C metal binding domain (TerY-C)
Type: Domain

TerY-C is found C-terminal to TerY-like vWA domains in some proteins . It has 8 conserved metal chelating cysteines or histidines. It occasionaly occurs as solos .
Clustered mitochondria protein, N-terminal (CLU_N)
Type: Domain

This entry represents the N-terminal domain of the clustered mitochondria protein, also known as clueless protein in Drosophila. The function of this domain is not known. This domain is found in association with

.
Immunity protein 68 (Imm68)
Type: Family

This entry represents the predicted immunity protein with an α+β fold and a conserved glutamate residue. This protein is often fused to one or more immunity domains in poly-immunity proteins .
Lsm, C-terminal (Lsm_C)
Type: Domain

This domain is found at the C terminus of archaeal Lsm (like-Sm) proteins .
Modulator of retrovirus infection (MRI)
Type: Family

CYREN is a cell-cycle-specific inhibitor of classical non-homologous end joining (cNHEJ) that promotes error-free repair by homologous recombination during the S and G2 phases (when sister chromatids are present) . It was originally known as MRI (modulator of retrovirus infection), as it was isolated as a gene that could reverse the resistance to retroviral infection in a mutant cell line .
Protein Njmu-R1 (Njmu-R1)
Type: Family

This entry represents the eukaryotic protein Njmu-R1, which may play a role in spermatogenesis. In humans, it is found in chromosome 17 open reading frame 75 (C17orf75). It forms a complex with WDR11, which acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 .
Siroheme synthase, central domain (Sirohaem_synthase_central)
Type: Domain

This is the central domain of a multifunctional enzyme which catalyses the biosynthesis of sirohaem. Both of the catalytic activities of this enzyme (precorrin-2 dehydrogenase (

) and sirohydrochlorin ferrochelatase (

)) are located in the N-terminal domain of this enzyme,

.
WASH complex subunit 7, central domain (WASH-7_central)
Type: Domain

This entry represents the central, conserved region of WASH complex subunit 7 (WASH7), also known as subunit 4 or KIAA1033 . The WASH complex is present at the surface of endosomes and recruits and activates the Arp2/3 complex to induce mediated actin nucleation. The WASH complex plays a key role in the fission of tubules that serve as transport intermediates during endosome sorting .
WASH complex subunit 7, C-terminal (WASH-7_C)
Type: Domain

This entry represents the C-terminal region of WASH complex subunit 7 (WASH7), also known as subunit 4 or KIAA1033 . The WASH complex is present at the surface of endosomes and recruits and activates the Arp2/3 complex to induce mediated actin nucleation. The WASH complex plays a key role in the fission of tubules that serve as transport intermediates during endosome sorting . This C-terminal domain is predicted to include a transmembrane region.
SCAR/WAVE family (SCAR/WAVE_fam)
Type: Family

This entry represents the SCAR/WAVE family. Members in this family include actin-binding protein WASF1-3 (WAVE 1-3), protein SCAR 1-4, protein WAVE5 and SCAR-like proteins.

SCAR/WAVE family members are downstream effector molecules receiving information from multiple signalling pathways and responding by promoting the actin nucleating activity of the ubiquitous Arp2/3 complex . They are part of the WAVE complex that regulates lamellipodia formation in animals and maintains cell shape in plants . WAVE1 is also involved in the regulation of mitochondrial dynamics .
WASH1 (WASH1)
Type: Family

This entry represents members of the WASH1 family, which are components of the WASH complex that is present at the surface of endosomes and activates the Arp2/3-mediated F-actin polymerisation . WASH1 contains N-terminal WASH homology regions (also known as the WAHD domain, which covers the WHD1/EVH1 and WHD2 domains), a proline-rich region and a C-terminal WH2 domain . WASH1 localises to early endosomal subdomains through an essential interaction with FAM21 via its WHD1 domain and directly binds tubulin through its WHD2 domain, while linking to Arp2/3-mediated F-actin polymerisation via its C-terminal WH2 domain .
ClpA/B, conserved site 2 (ClpA/B_CS2)
Type: Conserved_site

The ClpA/B family of ATP-binding proteins includes the regulatory subunit of the ATP-dependent protease Clp, ClpA; heat shock proteins ClpB, 104 and 78; and chloroplast proteins CD4a (ClpC) and CD4b . The proteins are thought to protect cells from stress by controlling the aggregation and denaturation of vital cellular structures. They vary in size, but share two conserved regions of about 200 amino acids that each contains an ATP-binding site .

This entry represents a conserved site found in the second conserved region.

Proteins containing this site are listed below:

Escherichia coli clpA, which acts as the regulatory subunit of the ATP- dependent protease clp.

Rhodopseudomonas blastica clpA homolog.

Escherichia coli heat shock protein clpB and homologues in other bacteria.

Bacillus subtilis protein mecB.

Yeast heat shock protein 104 (gene HSP104), which is vital for tolerance to heat, ethanol and other stresses.

Neurospora heat shock protein hsp98.

Yeast mitochondrial heat shock protein 78 (gene HSP78) .

CD4A and CD4b, two highly related tomato proteins that seem to be located in the chloroplast.

Trypanosoma brucei protein clp.

Porphyra purpurea chloroplast encoded clpC.
Holliday junction resolvase-related (Holliday_junct_resolvase-rel)
Type: Family

This family contains predicted bacterial endonucleases which are distantly related to archaeal Holliday junction resolvases.
Serine proteases, V8 family, histidine active site (V8_his_AS)
Type: Active_site

A number of prokaryotic proteases have been shown to be evolutionary related; their catalytic activity is provided by a charge relay system similar to that of the trypsin family of serine proteases but which probably evolved by independent convergent evolution. The sequence around the residues involved in the catalytic triad (aspartic acid, serine and histidine) are completely different from that of the analogous residues in the trypsin serine proteases and can be used as signatures specific to that category of proteases. The proteases which are known to belong to this family are listed below.

Staphylococcus aureus V8 proteinase, which preferentially cleaves peptide bonds on the carboxyl-terminal side of aspartate and glutamate and which is widely used in protein sequencing studies.

Bacillus licheniformis glutamate specific endopeptidase (GSE) , which like V8 cleaves on the carboxyl-terminal side of acidic residues, but with a strong preference for glutamate.

Bacillus subtilis extracellular "metalloprotease" (gene mpr) .

Staphylococcus aureus exfoliative (or epidermolytic) toxins A (gene eta) and B (gene etb). These toxins cause impetigous diseases commonly referred to as staphylococcal scalded skin syndrome (SSSS) and have been shown to possess proteolytic activity.

This entry represents the histidine active site of serine proteases from the V8 family.
Lin-54 family (Lin-54_fam)
Type: Family

This entry represents the lin-54 family of proteins. Members include lin-54 and tesmin. Lin-54 is a component of the DREAM (MuvB/DRM) complex, which represses cell cycle-dependent genes in quiescent cells and plays a role in the cell cycle-dependent activation of G2/M genes . Tesmin may have a role in spermatogenesis .
Retinoblastoma protein family (RB_fam)
Type: Family

This entry represents the retinoblastoma protein family, including retinoblastoma-associated protein (RB, also known as pRb, RB, p1051), retinoblastoma-like protein 1 (RBL1, also known as p107) and retinoblastoma-like protein 2 (RBL2, also known as RB2 or p130). Members of this family contain a conserved domain named the 'pocket' that interacts with the LXCXE motif found in viral proteins, such as SV40 large T antigen . Therefore, this family is also called the pocket protein family.

In humans, RB is a tumour suppressor linked to several major cancers . RB forms complexes with E2Fs and represses gene expression by recruiting chromatin remodeling factors, such as histone deacetylases (HDACs) to E2F-responsive promoters . This interaction regulates genes necessary for DNA replication and cell cycle. Phosphorylation of RB family by CDK and cyclin complexes leads to release of the repressor complex and enables E2F-dependent gene expression . Apart from E2Fs, RB also interacts with other transcription factors that govern cell differentiation .
Apoptosis-stimulating of p53 protein 1, RA domain (ASPP1_RA)
Type: Domain

ASPP1 (apoptosis-stimulating of p53 protein) is a member of the ASPP protein family (Apoptosi-Stimulating Protein of p53) that activates the p53-mediated apoptotic response. It functions as a tumour suppressor and coordinates with p53 to protect haematopoietic stem cell (HSC) pool integrity, guarding against haematological malignancies . The ASPP family of proteins may be a target for cancer therapy .

This entry represents the RA domain present at the N terminus of ASSP1, which is a ubiquitin-like domain.
RelA-associated inhibitor (iASPP)
Type: Family

This entry represents RelA-associated inhibitor (also known as iASPP), which is a regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins . iASPP is an ankyrin-repeat-, SH3-domain- and proline-rich-region-containing proteins that is homologous with ASPP1 and ASPP2 (

).
Proline-rich nuclear receptor coactivator-like, proline rich region (PNRC-like_rgn)
Type: Conserved_site

This entry represents a conserved proline-rich region found in the Proline-rich nuclear receptor coactivator 1/2 (PNRC 1/2) and related eukaryotic proteins including Enhancer of mRNA-decapping protein 1/2 (Edc1/2). This region contains a conserved YAGxxF sequence motif at the beginning, known as 'activation motif', followed by Px[PA]xxxPxPxF motif, described as 'Dcp1 binding motif'. In Edc1, the latter interacts with the aromatic groove of Dcp1 EVH1 domain and thereby enhances the catalytic activity of the decapping enzyme. The recognition of this Edc1 motif by the Dcp1 EVH1 domain is reminiscent of the interactions that are observed between proline-rich sequences and, e.g., WW, SH3, and GYF domains . In all cases, the central motif in the proline-rich sequence contacts a surface exposed cluster of aromatic residues in the protein domain. Mutation in the YAGxxF motif results in loss of ability to activate the decapping complex .

Proline-rich nuclear receptor coactivator 1 (PNRC1) and proline-rich nuclear receptor coactivator 2 (PNRC2) represent a new type of nuclear receptor co-regulatory proteins . PNRC1 may play a role in signal transduction . PNRC2 may be involved in nonsense-mediated mRNA decay (NMD) .

PNRC2 has been shown to play an important role in controlling the energy balance between energy storage and energy expenditure .
Voltage-gated potassium channel (VG_K_chnl)
Type: Family

This entry represents the the voltage-gated Kv channel and the KCNQ channel. KCNQ channels differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain.

Potassium channels are the most diverse group of the ion channel family . They are important in shaping the action potential, and in neuronal excitability and plasticity . The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups : the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K
+
channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers . In eukaryotic cells, K
+
channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes . In prokaryotic cells, they play a role in the maintenance of ionic homeostasis .

All K
+
channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K
+
selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K
+
across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo-or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K
+
channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K
+
channels; and three types of calcium (Ca)-activated K
+
channels (BK, IK and SK) . The 2TM domain family comprises inward-rectifying K
+
channels. In addition, there are K
+
channel alpha-subunits that possess two P-domains. These are usually highly regulated K
+
selective leak channels.
Small ribosomal subunit protein uS17, archaeal/eukaryotic (Ribosomal_uS17_arc/euk)
Type: Family

This entry represents ribosomal uS17 proteins, previously known as S17 in archaea and S11 in eukaryotes.

The ribosomal proteins catalyse ribosome assembly and stabilise the rRNA, tuning the structure of the ribosome for optimal function. Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA . The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein uS17 is known to bind specifically to the 5' end of 16S ribosomal RNA in Escherichia coli (primary rRNA binding protein), and is thought to be involved in the recognition of termination codons. Experimental evidence has revealed that uS17 has virtually no groups exposed on the ribosomal surface.
G protein-coupled receptor 18 orphan (GPR18)
Type: Family

Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels . GPR18 , GPR55 , GPR119

show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands . However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR .

This entry represents G protein-coupled receptor 18, also known as N-arachidonyl glycine receptor. It has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors . Recent research also supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18 .
However, the pairing of GPR18 with N-arachidonoylglycine (NAGly) and tetrahydrocannabinol (THC) was not reproduced in two studies based on beta-arrestin assays . So, until further research allows a more definitive decision the function and nomenclature GPR18 is still being debated .