SII-SWORD/CoKE huggingface dataset:
Shiga-like toxin, subunit A (Shiga-like_toxin_subunit_A)
Type: Family

This entry represents subunit A of Shiga-like toxin also known as rRNA N-glycosidase;

), which are responsible for inactivation of the ribosome. Shiga-like toxins are produced by Shigella dysenteriae and by bacteriophage that infect Escherichia coli cells . These toxins contain a single A subunit that has N-glycosidase activity and multiple copies of the B subunit that binds to the membrane glycolipid, globotriaosylceramide (Gb3). The A subunit is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits. It catalyses the endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
Alpha-1B-glycoprotein/leukocyte immunoglobulin-like receptor (A1B_glyco/leuk_Ig-like_rcpt)
Type: Family

This group represents alpha-1B-glycoproteins and several leukocyte immunoglobulin-like receptors. There are five domains in human alpha 1B-glycoprotein. Mongoose antihemorrhagic factor (AHF1) is a protein, which is homologous to human alpha 1BG, and a supergene family of immunoglobulins .

Alpha-1B-glycoproteins have been found associated with a number of diseases. They have been detected in the urine of children with steroid-resistant minimal change nephrotic syndrome (SRINS) . It is also found associated with bladder cancer, having been detected in all tumor-bearing patient samples but not samples obtained from non-tumor-bearing individuals . When the 1694 bp was cloned from human liver Marathon cDNA, which is the alpha-1B glycoprotein precursor gene, it was found that it may be a novel member of immunoglobulin superfamily and could be involved in cell recognition and the regulation of cell behavior .

Polymorphism of Alpha-1-B-glycoprotein (A1BG) has been found in the plasma of several human populations of the Indian subcontinent .
Protein-tyrosine phosphatase, receptor type R/non-receptor type 5 (Tyr_Pase_rcpt_R/non-rcpt_5)
Type: Family

This group represents two related tyrosine-protein phosphatases; receptor type R and non-receptor type 5.
Receptor-type tyrosine-protein phosphatase C (Ptprc)
Type: Family

Receptor-type tyrosine-protein phosphatase C, also known as CD45, is a tyrosine-protein phosphatase required for T-cell activation through the antigen receptor . It acts as a positive regulator of T-cell co-activation upon binding to DPP4 (CD26) .
Receptor tyrosine-protein phosphatase, alpha/epsilon-type (Tyr_Pase_rcpt_a/e-type)
Type: Family

This entry represents receptor tyrosine-protein phosphatases (PTP) (

), including both alpha type and epsilon type. PTP catalyses the dephosphorylation of protein tyrosine phosphate to protein tyrosine, and appear to play a pivotal role in insulin receptor signalling. It can exist as a single-pass membrane protein or in the cytoplasm. PTP-alpha is as a positive regulator of Src and Src family kinases, acting to dephosphorylate and activate Src. As such, PTP-alpha affects transformation and tumourigenesis, inhibition of proliferation and cell cycle arrest, mitotic activation of Src, integrin signalling, neuronal differentiation and outgrowth, and ion channel activity . PTP-epsilon is a negative regulator of insulin signalling, where the cytosolic form has been shown to act in skeletal muscle and the receptor-type enzyme has been shown to act in primary hepatocytes and liver .
Monocyte differentiation antigen CD14 (Monocyte_diff_Ag_CD14)
Type: Family

This group represents a monocyte differentiation antigen CD14.
Phospholipase A2 inhibitor, gamma type (PLipase_A2-inh_b-type)
Type: Family

This entry represents gamma-type phospholipase A2 inhibitors (PLI) found in a variety of snakes, including Elapidae and Viperidae. Phospholipase A2 (PLA2;

) is a calcium-dependent enzyme that is involved in inflammatory processes such as the liberation of free arachidonic acid from the membrane pool for the biosynthesis of eicosanoids. Both Elapidae and Viperidae contain PLA2 enzymes in their venoms , which can exhibit a wide variety of pharmacological effects including neurotoxicity and myotoxicity. As a result, these snakes must contain PLI in their blood in order to protect themselves from leakage of their own venom PLA2s into the circulatory system. Venomous snakes have three distinct types of PLA2-inhibitory proteins: PLI-alpha, PLI-beta, and PLI-gamma, being PLI-gamma the most abundant ones .

Phospholipase A2 inhibitor CNF, a gamma-type PLI, inhibits the PLA2 activity of crotoxin (CTX) by replacing the acid subunit (CA) in the CTX complex . It has a proinflammatory action through activation of important main signalling pathways for human leukocytes, in vitro . In mice phrenic nerve-diaphragm muscle preparations it abolishes both the muscle-paralyzing and muscle-damaging activities of CTX .
Truncated hemoglobin, group 1 (Hemoglobin_trunc_I)
Type: Family

This entry represents a group of haemoglobin-like proteins found in eubacteria, cyanobacteria, protozoa, and plants, but not in animals or yeast . Truncated hemoglobins (TrHbs) have a truncated 2-over-2 rather than the canonical 3-over-3 α-helical sandwich fold . The variability of the amino acid residues of the heme pocket suggested their partition into three groups that share less than 30% sequence similarity with each other . This entry includes:

HbN (or GlbN): a truncated haemoglobin-like protein that binds oxygen cooperatively with a very high affinity and a slow dissociation rate, which may exclude it from oxygen transport. It appears to be involved in bacterial nitric oxide detoxification and in nitrosative stress .

Cyanoglobin (or GlbN): a truncated haemoprotein found in cyanobacteria that has high oxygen affinity, and which appears to serve as part of a terminal oxidase, rather than as a respiratory pigment .
Large ribosomal subunit protein mL60 (Ribosomal_mL60)
Type: Family

This group represents the large ribosomal subunit protein mL60 from fungi, previously known as Mrpl31 . mL60 is a component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain. The mitoribosomes are attached to the mitochondrial inner membrane and translation products are cotranslationally integrated into the membrane .
Clathrin, heavy chain (Clathrin_heavy_chain)
Type: Family

This group represents a clathrin heavy chain.

Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin consists of three heavy chain subunits, which are the main structural component of the clathrin vesicle coat, and three light chain molecules that interact with the heavy chains to self-assemble into a three-legged triskelion structure. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies .
AP-1/2/4 complex subunit beta (AP_complex_bsu_1_2_4)
Type: Family

The adaptor protein complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules . Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Subunits of clathrin-associated adaptor protein complex 1 play a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or in endosomes.

This group represents an adaptor protein complex, beta subunit.
Spectrin, beta subunit (Spectrin_bsu)
Type: Family

Spectrins are involved in the support of general membrane integrity, stabilisation of cell-cell interactions, axonal growth, normal functioning of the Golgi complex and organisation of synaptic vesicles . Spectrin is a tetrameric actin cross-linking protein, which contains two alpha and two beta subunits. Two genes for alpha-spectrin and five for beta-spectrin have been identified in both mice and humans, each of which is alternatively spliced to produce multiple spectrin isoforms . Beta-spectrins are more diverse than alpha-spectrin, and include mammalian erythrocytic beta-spectrin, non-erythroid beta-spectrin/Fodrin (beta-G, the general form of beta-spectrin expressed in multiple tissues), a novel beta-G spectrin (ELF1-4) that lacks the C-terminal PH (pleckstrin homology) domain, the brain-specific SPTBN2, and beta-V spectrin.

ELF (

), a modulator of the Smad adaptor proteins involved in the TGF-beta signalling pathway, was originally identified from endodermal stem/progenitor cells committed to foregut lineage . ELF is a beta-spectrin that is important for distinct functional membrane generation, protein sorting, cell adhesion and the development of a polarized differentiated epithelial cell . ELF-deficient mice display disruption of transforming growth factor-beta (TGF-beta) signalling by Smad proteins . Evidence from null mutants of ELF confirms that ELF is a novel beta-G spectrin and not an isoform of beta-spectrins . Aberrations in Elf's involvement in Smad4 localization and subsequent activation of Smad4 could result in tumourigenesis.
Casein, beta (Casein_beta)
Type: Family

This group represents the milk protein beta-casein. The protein binds to calcium at its phosphorylated regions. The calcium then binds the caseins together and forms micelles. Beta-casein has as important role in the determination of the surface properties of the micelles .
G-protein subunit beta 1-5 (G-protein_beta_1-5)
Type: Family

This entry represents the Guanine nucleotide-binding protein subunit beta 1-5 (G-protein subunit beta). This protein is a modulator in various transmembrane signalling systems. The beta and gamma subunits are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

Guanine nucleotide binding proteins (G-proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (

), beta (

) and gamma (

) . G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation . At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal . The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins or by covalent modifications .

G protein alpha subunits are 350-400 amino acids in length and have molecular weights in the range 40-45kDa. Seventeen distinct types of alpha subunit have been identified in mammals. These fall into 4 main groups on the basis of both sequence similarity and function: alpha-S (

), alpha-Q (

), alpha-I (

)and alpha-12(

) .

The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli . G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions.
Acyl-CoA-binding domain-containing protein 5 (ACBD5)
Type: Family

ACBD5 is an acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. It binds medium- and long-chain acyl-CoA esters .
L-selectin (L-selectin)
Type: Family

L-selectin is an adhesion receptor in leukocytic cells that mediates the capture of leukocytes from the blood stream and the subsequent rolling along the vascular endothelium. This event is the first step in the adhesion cascade, which enables leukocytes to migrate out of the vasculature into surrounding tissues during inflammation . L-selectin also regulates the recirculation of lymphocytes between blood and lymph nodes via high endothelial venules .

L-Selectin is a type I transmembrane protein comprising an N-terminal lectin domain, an epidermal growth factor (EGF)-like domain, two short consensus repeats, a membrane-spanning region and a short 17-amino acid cytoplasmic domain .
Plasminogen-related (Plasminogen-rel)
Type: Family

This group represents a plasminogen-related protein.
Small leucine-rich proteoglycan, class I, decorin/asporin/byglycan (SLRP_I_decor/aspor/byglycan)
Type: Family

This group represents a family of class I small leucine-rich proteoglycan (SLRPs), including decorin, asporin and byglycan . They bind to multiple receptors and are involved in controlling cell growth, morphogenesis and immunity .
Chordin (Chordin)
Type: Family

This entry represents the chordin family. Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their action is regulated by corresponding BMP inhibitors. Chordin, a BMP inhibitor, as well as BMP-2, is expressed during osteogenic differentiation of human mesenchymal stem cells. Chordin increases BMP-2 bioavailability. The potential of suppressing BMP inhibitors is emerging as a biological therapeutic target in bone tissue engineering .
Nuclear hormone receptor family 5-like (NR5-like)
Type: Family

The nuclear hormone receptor subfamily 5 includes group A member 1 (NR5A1) or steroidogenic factor 1 (SF-1), group A member 2 (NR5A) or liver receptor homologue-1, and FTZ-F1 (group A member 3) and FTZ-F1 beta (group B member 1) from Drosophila . SF-1 is a key regulator for steroid biosynthesis and essential for sexual differentiation and formation of the primary steroidogenic tissues . NR5A2 is involved in bile acid/cholesterol homeostasis and in the development of some human cancers .

Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands . The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner . In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.

NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.
Seminal plasma protein, PDC-109-like (Seminal_plasma_PDC-109-like)
Type: Family

This entry represents seminal plasma proteins, including PDC-109, BSP-A3, HSP-1 and pB1. On ejaculation, sperm becomes coated with these proteins, which are secreted by male accessory sex glands. These proteins play a role in forming an oviductal sperm reservoir by enabling sperm to bind to oviductal epithelium . PDC-109 could enhance the fertilising capacity of spermatozoa upon interaction with heparin-like glycosaminoglycans present in the female genital tract . PDC-109 and BSP-A3 exert both stimulatory and inhibitory actions on the release of pituitary gonadotropins. Protein pB1 may form a complex with spermadhesin AQN-1 which possesses phosphorylcholine-binding activity .
Transferrin (Transferrin)
Type: Family

Transferrins are eukaryotic iron-binding glycoproteins with the ability to bind ferric iron with high affinity in the cleft of each of two homologous lobes. They control the level of free iron in biological fluids . Members of the family include blood serotransferrin (siderophilin), milk lactotransferrin (lactoferrin), egg white ovotransferrin (conalbumin), membrane-associated melanotransferrin and saxiphilin from the American bullfrog (
Lithobates catesbeiana
), which binds to the neurotoxin saxitoxin . Family members that do no bind iron have also been discovered, including inhibitor of carbonic anhydrase (ICA), which strongly binds to and inhibits certain isoforms of carbonic anhydrase .
Hemopexin (Hemopexin)
Type: Family

Hemopexin (HPX) is the plasma protein with the highest binding affinity to haem among known proteins . It binds haem and transports it to the liver for breakdown and iron recovery, after which the free HPX returns to the circulation . It has been suggested that HPX is mainly responsible for the transportation of haem thus preventing both haem-catalysed oxidative damage and haem-bound iron loss .
SPARC-like protein 1 (SPARC-like_p1)
Type: Family

This group represents a SPARC-like (Secreted Protein Acidic and Rich in Cysteine) protein 1 (SPARCL1; also known as Hevin). SPARCL1 is a secreted glycoprotein, belonging to SPARC family of matricellular proteins . SPARCL1 is downregulated in various tumours and may have a tumor-suppressor function .
Transcriptional enhancer factor, metazoa (TEF_metazoa)
Type: Family

Proteins in the transcriptional enhancer factor family (also known as TEAD family, includes TEAD 1 to 4) play a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumour suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. TEAD transcription factors act by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction . This entry includes protein Scalloped from
Drosophila melanogaster
which in combination with protein Vestigial promotes wing formation , and in combination with Yorkie which promotes transcriptional activity and movement of Yorkie to the nucleus .
POU-domain transcription factor, class 3 (TF_POU_3)
Type: Family

This group represents a group of POU-domain transcription factors, brain type (class III). They are thought to be involved brain development .

The POU factors interact with canonical octamer sequence ATGCAAAT through its POU-specific (POU-S) domain and POU homeodomain (POU-H). The POU homeodomain of the class III factors interacts with a noncanonical target sequence in the FM enhancer, which drives transcription of Otx2, an essential player in rostral brain development .
Legume lectin (L-lectin)
Type: Family

This group represents L-type lectins from plants, including leukoagglutinins which bind sialic acid .

Lectins are carbohydrate-binding proteins. Leguminous lectins form one of the largest lectin families and resemble each other in their physicochemical properties, though they differ in their carbohydrate specificities. They bind either glucose/mannose or galactose . Carbohydrate-binding activity depends on the simultaneous presence of both a calcium and a transition metal ion . The exact function of legume lectins is not known, but they may be involved in the attachment of nitrogen-fixing bacteria to legumes and in the protection against pathogens .

Some legume lectins are proteolytically processed to produce two chains, beta (which corresponds to the N-terminal) and alpha (C-terminal) . The lectin concanavalin A (conA) from jack bean is exceptional in that the two chains are transposed and ligated (by formation of a new peptide bond). The N terminus of mature conA thus corresponds to that of the alpha chain and the C terminus to the beta chain . Though the legume lectins monomer is structurally well conserved, their quaternary structures vary widely .
Surface antigen, Rickettsia type (Surface_antigen_Rickettsia)
Type: Family

This group represents a surface antigen, Rickettsia type.
Actobindin (Actobindin)
Type: Family

This group represents an actobindin; a 9.8kDa protein from Acanthamoeba castellanii . It belongs to a group of G-actin binding proteins including actobindin, twinfilin, and profilin . Actobindin consists of two beta-thymosin repeats . It inhibits nucleation of new actin filaments and facilitates elongation of existing polarized filaments in actively motile regions . Actobindin does not form a stable complex with actin dimers but causes the accumulation of dimers that are unable to nucleate polymerisation or self-associate .
Major outer membrane lipoprotein Lpp (MOM_Lpp)
Type: Family

This entry represents the Major outer membrane lipoprotein (Lpp, also known as murein lipoprotein), which controls the distance between the inner and outer membranes . This abundant protein contains lipids in its N-terminal which anchor it to the outer membrane. This is the only protein known to bind covalently to the peptidoglycan network (PGN) but it also binds it through non-covalent interactions. About one-third of the Lpp is bound to the cell wall and the rest is free in the periplasm. Lpp have a structural function mediating the interactions between the outer membrane and PGN to assure the correct distance between them and contributes to the structural and functional integrity of the cell membrane . The role of the periplasm free Lpp remains unknown.
Endoribonuclease VapD (VapD)
Type: Family

This entry represents the virulence-associated protein, VapD type, found in bacteria. These proteins are defined by a conserved region found at the N terminus of the protein . The crystal structure VapD from Helicobacter pylori, which showed endoribonuclease activity, was solved by X-ray chrystallography, showing a modified ferredoxin-like fold, very similar to that of the Cas2 family. It was also related to toxin-antitoxin (TA) systems, sltho it does not belong to them .