SII-SWORD/CoKE huggingface dataset:
MHC class I-like antigen recognition-like (MHC_I-like_Ag-recog)
Type: Domain

Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus . MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.

MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain (light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains.

This entry represents MHC antigen-recognition-like domains from:

MHC class I, alpha-1 and alpha-2 domains

MHC class I homologue gammadelta T-cell ligand

MHC class I related Ulbp3

MHC class I related Fc (IgG) receptor, alpha-1 and alpha-2 domains

MHC class I related CD1, alpha-1 and alpha-2 domains

MHC class I related zinc-alpha-2-glycoprotein ZAG (fat depleting factor)

Immunomodulatory protein m144, alpha-1 and alpha-2 domains

Haemochromatosis protein Hfe, alpha-1 and alpha-2 domains

Endothelial protein C receptor (phospholipid-binding protein)

NK cell ligand RAE-1 . RAE-1 proteins (alpha, beta, delta, and gamma) are distant major histocompatibility complex (MHC) class I homologues, comprising isolated alpha-1 alpha-2 domains, and lack alpha3 domains .
MHC classes I/II-like antigen recognition protein (MHC_I/II-like_Ag-recog)
Type: Homologous_superfamily

Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.

This superfamily represents MHC class I and II-like antigen-recognition domains from:

MHC class II, N-terminal domains of alpha and beta chains

MHC class I, alpha-1 and alpha-2 domains

MHC class I related proteins, such as gammadelta T-cell ligand , Ulbp3 , Fc (IgG) receptor (alpha-1 and -2 domains) , CD1 (alpha-1 and -2 domains) , zinc-alpha-2-glycoprotein ZAG (fat depleting factor)

Immunomodulatory protein m144, alpha-1 and alpha-2 domains

Haemochromatosis protein Hfe, alpha-1 and alpha-2 domains

NK cell ligand RAE-1 beta

Endothelial protein C receptor (phospholipid-binding protein)
Peptidase S1A, enteropeptidase (Pept_S1A_enterop)
Type: Family

Enteropeptidase (

) originally called enterokinase, belongs to MEROPS peptidase family S1 (chymotrypsin family, clan PA(S)), subfamily S1A. It is the protease in mammalian intestinal brush border that is responsible for generation of active trypsin from trypsinogen; trypsin, in turn, activates other digestive enzymes. The mature enteropeptidase has heavy and light chains, connected by a disulphide bond and derived from a single precursor molecule. The light chain comprises the carboxyl-terminal domain of the precursor and contains the trypsin domain (

). Near the amino end of the heavy chain is a region that may be a signal sequence or signal-anchor. The remainder of the heavy chain comprises a series of domains: SEA, which is likely heavily glycosylated; the first of two Low density lipoprotein-receptor class A domains; the first of two CUB domains; MAM; CUB;Low density lipoprotein-receptor class A domains and SRCR.

For additional information please see .
Beta-eliminating lyase family (Beta-eliminating_lyase)
Type: Family

Tryptophanase (tryptophan indole-lyase, TNase) (

) and tyrosine phenol-lyase (TPL) (

) are related pyridoxal-phosphate dependent homotetrameric enzymes that catalyse the reversible hydrolytic cleavage of L-tryptophan or L-tyrosine to indole or phenol, respectively, and ammonium pyruvate. These two enzymes are very similar in sequence and structure, but show strict substrate specificity. Both TNase and TPL may react by a rare S(E)2-type mechanism . Collectively, these enzymes are known as the beta-eliminating lyase family.
Iron-dependent fumarate hydratase (Fe_dep_fumarate_hydratase)
Type: Family

Iron-dependent fumarate hydratase, or fumarase, is a bacterial enzyme that converts malate to fumarate. There are three fumarase proteins in Escherichia coli, FumA, FumB, and FumC, which fall into two biochemically distinct classes: class I (FumA, FumB) are dimeric enzymes and class II (FumC) are tetrameric enzymes, the latter sharing homology with eukaryotic enzymes . This entry represents the class I enzymes. FumA functions in the citric acid cycle, accounting for 80% of the fumarase activity when the bacteria grows aerobically. FumB functions in the generation of fumarate as an anaerobic electron acceptor in the fermentative pathway that leads to the production of succinate.
Growth factor, vaccinia C11R type (GF_C11R)
Type: Family

Virus-encoded growth factors (GF) are important for the virulence of poxviruses. They act to promote the growth of their host cell through their binding to host ErbB receptor tyrosine kinases, which in turn activate the MAPK pathway. These growth factors are related to mammalian epidermal growth factor (EGF), one of several host ErbB ligands. The viral GFs are potent mitogens, acting to prevent host receptor degradation and ubiquitination, which leads to sustained signal transduction. Growth factors from different poxviruses display unique patterns of specificity to host ErbB receptors: VGF (vaccinia virus GF) binds primarily to ErbB-1 homodimers, MGF (myxoma virus GF) binds to ErbB-2/ErbB-3 heterodimers, and SFGF (Shope fibroma virus GF) binds to different ErbB receptors .
Glia maturation factor (GMF)
Type: Family

This entry represents glia maturation factor beta and gamma (GMFB/GMFG), Aim7 from budding yeasts and Gmf1 from fission yeasts. GMF family proteins do not interact with actin, but instead bind to Arp2/3 complex. They sever actin-Arp2/3 complex branch junctions by a cofilin-like mechanism .

Human GMFB was initially identified as a growth and differentiation factor acting on neurons as well as glia in the vertebrate brain. GMFB is produced predominantly in the thymus, and may have roles in both intracellular signal transduction and T cell development .

Fission yeast Gmf1 is an actin depolymerising factor involved in the control of the disassembly of actin patches . Aim7 binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation .
Poxvirus, TNF-alpha receptor-II (Poxvirus_TNF_rcpt-II)
Type: Family

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.

TNF exerts its function mainly through two TNF receptors, TNF-1 and TNF-2, which are expressed on nearly all cells of the body. This entry represents TNF-2.

TNFs and their receptors can select and kill virus-infected cells .

Poxviruses are large DNA viruses that encode many proteins capable of interfering with host immune functions, including soluble versions of cytokine receptors such as vTNFalpha-2 (viral TNFalpha receptor 2). These soluble cytokine receptors effectively block cytokine activity and modulate viral virulence. The C22L type receptor in vaccinia virus is equivalent to the CrmB (cytokine response modifier B) protein in cowpox virus .
Ezrin/radixin/moesin (ERM)
Type: Family

This entry represents ERM family of proteins.

The ERM family consists of three closely-related proteins, ezrin, radixin and moesin . Ezrin was first identified as a constituent of microvilli , radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions , and moesin as a heparin binding protein , which is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance . Members of this family have been associated with axon-associated Schwann cell (SC) motility and the maintenance of the polarity of these cells . A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein) . ERM molecules contain 3 domains, an N-terminal globular domain, an extended α-helical domain and a charged C-terminal domain . Ezrin, radixin and merlin also contain a polyproline region between the helical and C-terminal domains. The N-terminal domain is highly conserved, and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain . ERM proteins crosslink actin filaments with plasma membranes. They co-localise with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains . The α-helical region is involved in intramolecular masking of protein-protein interaction sites which regulates the activity of this proteins .
Alpha-s2 casein (Alpha-s2_casein)
Type: Family

Caseins are the major protein component of milk, functioning as nutritive carriers of both amino acids and minerals in milk. They are phosphoproteins that can be classified into two families, the kappa-casein family and the alpha-s1, alpha-s2 and beta-casein family, the later displaying considerable species variation . This entry represents the alpha-s2 caseins, highly phosphorylated peptides that occur as different isoforms. Alpha-s2 casein is known as epsilon-casein in mouse, gamma-casein in rat and casein-A in guinea pig.
Complement control protein C3/B5 (CCP_VACV_C3/B5)
Type: Family

This entry represents receptors of complement activation (RCA), including B5, also known as Protein OPG190, and Complement control protein C3 from Vaccinia virus. B5 binds complement components C3 and C1q . This protein plays a role in the dissolution of the outermost membrane of extracellular enveloped virions (EV) to allow virion entry into host cells. Participates also in wrapping mature virions (MV) to form enveloped virions (EV) . C3 is involved in modulating the host inflammatory response by blocking both classical and alternative pathways of complement activity through its ability to bind host complement components C3b and C4b (complement 3b and 4b, respectively) . By blocking complement activation at multiple sites, these proteins can down-regulate pro-inflammatory chemotactic factors (C3a, C4a, and C5a), resulting in reduced cellular influx and inflammation.
Transcription initiation factor TFIID subunit 1, animal (TAF1_animal)
Type: Family

Transcription initiation factor TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. The complex includes TATA binding protein (TBP) and various TBP-associated factors (TAFS). TFIID is a RNA polymerase II-specific TATA-binding protein-associated factor (TAF) that is essential for viability.

This group represents a transcription initiation factor TFIID subunit 1 (TAF1), animal type .
Amyloidogenic glycoprotein, copper-binding (Amyloid_glyco_Cu-bd)
Type: Domain

Amyloid-beta precursor protein (APP, or A4) is associated with Alzheimer's disease (AD), because one of its breakdown products, amyloid-beta (A-beta), aggregates to form amyloid or senile plaques . Mutations in APP or in proteins that process APP have been linked with early-onset, familial AD. Individuals with Down's syndrome carry an extra copy of chromosome 21, which contains the APP gene, and almost invariably develop amyloid plaques and Alzheimer's symptoms.

APP is important for the neurogenesis and neuronal regeneration, either through the intact protein, or through its many breakdown products . APP consists of a large N-terminal extracellular region containing heparin-binding and copper-binding sites, Kunitz domain, E2 domain, a short hydrophobic transmembrane domain, and a short C-terminal intracellular domain. The N-terminal region is similar in structure to cysteine-rich growth factors and appears to function as a cell surface receptor, contributing to neurite growth, neuronal adhesion, axonogenesis and cell mobility . APP acts as a kinesin I membrane receptor to mediate the axonal transport of beta-secretase and presenilin 1. The N-terminal domain can regulate neurite outgrowth through its binding to heparin and collagen I and IV, which are components of the extracellular matrix. APP is also coupled to apoptosis-inducing pathways, and is involved in copper homeostasis/oxidative stress through copper ion reduction, where copper-metallated APP induces neuronal death . The C-terminal intracellular domain appears to be involved in transcription regulation through protein-protein interactions. APP can promote transcription activation through binding to APBB1/Tip60, and may bind to the adaptor protein FE65 to transactivate a wide variety of different promoters.

APP can be processed by different sets of enzymes:

In the non-amyloidogenic (non-plaque-forming) pathway, APP is cleaved by alpha-secretase to yield a soluble N-terminal sAPP-alpha (neuroprotective) and a membrane-bound CTF-alpha. CTF-alpha is broken-down by presenilin-containing gamma-secretase to yield soluble p3 and membrane-bound AICD (nuclear signalling).

In the amyloidogenic pathway (plaque-forming), APP is broken down by beta-secretase to yield soluble sAPP-beta and membrane-bound CTF-beta. CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact.

This entry represents a copper-binding domain found within the extracellular domain, which is at the N-terminal of amyloidogenic glycoproteins such as amyloid-beta precursor protein (APP, or A4). The copper-binding domain has a dodecin-like fold consisting of a 2-layer α/β topology .
Isopentenyl-diphosphate delta-isomerase, FMN-dependent (IPdP_isomerase)
Type: Family

This entry represents the bacterial and archaeal isopentenyl-diphosphate delta-isomerase (IPP isomerase). IPP isomerase catalyses the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), and is a key enzyme in the biosynthesis of isoprenoids via the mevalonate pathway. The bacterial and archaeal IPP isomerase (type 2 enzyme) differs from that found in eukaryotes (type 1 enzyme), and requires NADPH, magnesium, and FMN for activity .
Protein VP3, rotavirus (VP3_Rotav)
Type: Family

Viral protein 3 (VP3) specifically binds to GTP and contains mRNA guanylyltransferase and mRNA (guanine-N(7)-)-methyltransferase activities. It is a multifunctional enzyme involved in mRNA capping. It catalyses the formation of the 5' cap structure on the viral plus-strand transcripts . Structure analyses revealed that it contains a variable N-terminal domain, a central guanine-N7-methyltransferase domain with an additional inserted domain, and a C-terminal guanylyltransferase and RNA 5'-triphosphatase domain. The insertion in the guanine-N7-methyltransferase domain is a ribose-2'-O-methyltransferase domain for most rotavirus species .
L-aspartate dehydrogenase (L-Asp_DH)
Type: Family

This group contains aspartate dehydrogenases that belong to a unique class of amino acid dehydrogenases.

The structure of Thermotoga maritima TM1643 has been found to contain an N-terminal Rossmann fold domain (which binds the NAD(P)
+
cofactor) and a C-terminal α/β domain . This suggested that TM1643 may be a dehydrogenase with the active
site located at the interface between the two domains. Enzymatic characterisation of TM1643 revealed that it possesses NAD or NADP-dependent dehydrogenase activity toward L-aspartate but no aspartate oxidase activity . The product of the aspartate dehydrogenase activity is also iminoaspartate. It has been suggested that two different enzymes, an oxidase and a dehydrogenase, may have evolved to catalyse the
first step of NAD biosynthesis . Members of this group share some structural similarity to several other NAD(P)
+
-dependent oxidoreductases, including inositol 1-phosphate synthase, dihydrodipicolinate reductase, and ASA-DH .

It has been proposed that in Thermotoga maritima, TM1643 catalyses the first reaction of de novo biosynthesis of NAD from aspartate, and it produces iminoaspartate required for this pathway. The formation of an enzyme complex between TM1643 and NadA, the next enzyme of the pathway, may allow the channeling of this unstable product directly to the NadA active site .

This family also includes putative L-aspartate dehydrogenases from eukaryotes.
Pyrophosphate-dependent phosphofructokinase PfpB (PfpB_PPi_PFK)
Type: Family

Diphosphate--fructose-6-phosphate 1-phosphotransferase catalyses the addition of phosphate from diphosphate (PPi) to fructose 6-phosphate to give fructose 1,6-bisphosphate (

). The enzyme is also known as pyrophosphate-dependent phosphofructokinase. The usage of PPi-dependent enzymes in glycolysis presumably frees up ATP for other processes .

represents the ATP-dependent 6-phosphofructokinase enzyme contained within Phosphofructokinase. This entry contains primarily bacterial, plant alpha, and plant beta sequences. These may be dimeric nonallosteric enzymes (bacteria) or allosteric heterotetramers (plants) .
DNA mismatch repair Msh2-type (DNA_mismatch_repair_Msh2)
Type: Family

Mismatch repair (MMR) is one of five major DNA repair pathways, the others being homologous recombination repair, non-homologous end joining, nucleotide excision repair, and base excision repair. The mismatch repair system recognises and repairs mispaired or unpaired nucleotides that result from errors in DNA replication. The most extensively studied general MMR system is the MutHLS pathway of the bacterium Escherichia coli. In the first step of the MutHLS pathway, the MutS protein (in the form of a dimer) binds to the site of a mismatch in double-stranded DNA. Through a complex interaction between MutS, MutL and MutH, a section of the newly replicated DNA strand (and thus the strand with the replication error) at the location of the mismatch bound by MutS is targeted for removal . Homologues of MutS have been found in many species including eukaryotes, Archaea and other bacteria, and together these proteins have been grouped into the MutS family.

This entry represents a subset of the MutS family members, including Msh2. Msh2 (MutS homologue 2) has a dual role in DNA repair and apoptosis. Msh2 acts as a heterodimer with Msh6, which together function to recruit the Mlh (MutL homologue) - Pms (post-meiotic segregation) heterodimer, and to replace the mispaired base .
Uncharacterised protein family UPF0302 (UPF0302)
Type: Family

There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.
Uncharacterised conserved protein, caspase-like (UCP_caspase_lke)
Type: Family

This group represents a family of cyanobacterial proteins, which have no known function. The N-terminal region, of members of this family, has homology to the caspase-hemoglobinase domain .
N-acetylglutamate synthase, fungal (GlcNAc_Synth_fun)
Type: Family

N -Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymatic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by L-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined .

The pathway from glutamate to arginine is:

NAGS; N-acetylglutamate synthase (

) (glutamate to N-acetylglutamate)

NAGK; N-acetylglutamate kinase (

) (N-acetylglutamate to N-acetylglutamate-5P)

N-acetyl-gamma-glutamyl-phosphate reductase (

) (N-acetylglutamate-5P to N-acetylglumate semialdehyde)

Acetylornithine aminotransferase (

) (N-acetylglumate semialdehyde to N-acetylornithine)

Acetylornithine deacetylase (

) (N-acetylornithine to ornithine)

Arginase (

) (ornithine to arginine)

This group represents a N-acetylglutamate synthase, belonging to the Ascomycetes .
Uncharacterised protein family Treponema vWA (Uncharacterised_Tp_vWA)
Type: Family

Members of this group are related to the 76kDa protein of unknown function from Treponema. The proteins contain a vWA domain.
Rubisco LSMT methyltransferase, plant (Rubisco_LSMT_MeTrfase_plant)
Type: Family

In pea (Pisum sativum), the protein-lysine methyltransferase (PsLSMT, also known as RBCMT) catalyses the trimethylation of Lys-14 in the large subunit (LS) of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) . Arabidopsis homologue of RBCMT, LSMT, is a protein-lysine methyltransferase methylating chloroplastic fructose 1,6-bisphosphate aldolases . The sequence conservation pattern and structure analysis of the SET domain provides clues regarding the possible active site residues of the domain. There are three conserved sequence motifs in most of the SET domain. The N-terminal motif (I) has characteristic glycines. The central motif (II) has a distinct pattern of polar and charged residues (Asn, His). The C-terminal conserved motif (III) has a characteristic dyad of polar residues and the hydrophobic residue tyrosine.