SII-SWORD/CoKE huggingface dataset:
Histone transcription regulator 3/CABIN1 (Hir3/CABIN1)
Type: Family

This entry includes histone transcription regulator 3 (Hir3) from fungi and calcineurin-binding protein 1 (CABIN1) from animals. Hir3 is part of the HIR complex, a nucleosome assembly complex that regulates histone gene transcription . Human CABIN1 is a functional member of the HUCA (HIRA/UBN1/CABIN1/ASF1a) complex, which is a histone H3.3 chaperone complex involved in nucleosome assembly and chromatin heterochromatinisation in senescent human cells .
Integrator complex subunit 7 (INTS7)
Type: Family

Integrator complex subunit 7 (INTS7) is a component of the integrator complex which is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The integrator complex interacts with the C-terminal tail of the largest subunit of RNA-polymerase II to promote 3'-snRNA processing . INTS7 interacts with INTS1 and INTS2 making extensive contacts with each other, nucleating the assembly of the whole INTAC complex . In zebrafish, C. elegans and Drosophila, INTS7 has been found to be essential for normal development .
ETS homologous factor, SAM Pointed domain (EHF_SAM_Pointed_dom)
Type: Domain

This entry represents the Sterile alpha motif (SAM)/Pointed domain of EHF, a putative protein-protein interaction domain.

Members of this group of proteins are potential targets for cancer therapy .

ETS homologous factor (EHF, ESE-3) is an epithelial-specific transcriptional activator that plays a role in regulating epithelial cell differentiation and proliferation . It also regulates gene pathways critical for epithelial response to injury . It regulates the expression of a variety of genes by binding to the GGAA/T core sequence in cooperation with other transcription factors and co-factors .
Death-inducer obliterator 1, PHD finger (DIDO1_PHD)
Type: Domain

The human death-inducer obliterator (Dido) gene encodes three splicing variants: Dido1, 2, and 3 . Dido1, the shortest isoform, is a putative transcription factor that plays an important role in regulating embryonic stem cell maintenance . It has been implicated in apoptosis and development and is a tumour suppressor .

This entry represents the highly conserved plant homeodomain (PHD) finger, which is responsible for the binding of histone H3 with a higher affinity for trimethylated lysine 4 (H3K4me3) and necessary to modulate cell differentiation and division .
Zinc finger protein 638, RNA recognition motif 1/2 (ZNF638_RRM1/2)
Type: Domain

Zinc finger protein 638 (ZNF638, also known as NP220) is a transcription factor that binds to cytidine clusters in double-stranded DNA . It interacts with splicing regulators and influences alternative splicing and may control adipogenesis through regulation of the relative amounts of differentiation-specific isoforms . ZNF638 also mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 .

This entry represents the two RNA recognition motifs (RRM) of ZNF638.
Interleukin enhancer-binding factor 3, first DSRM (DSRM1_ILF3)
Type: Domain

Interleukin enhancer-binding factor 3 (IFL3, also known as DRBP76, MPP4, NFAR, nuclear factor of activated T-cells 90 kDa (NF90), or translational control protein 80) is a RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons . The alternative splicing of the ILF3 gene generates two ubiquitous proteins, interleukin enhancer binding factor 3 (IFL3) and Nuclear Factor 90 (NF90). They have an identical N-terminal domain of 701 amino acids and a specific C-terminal domain of 210 and 15 amino acids, respectively .

NF90 and its isoforms are involved in transcription, translation, mRNA export and microRNA biogenesis. They are involved in DNA and RNA virus replication .
Exosome complex component RRP45 (Rrp45)
Type: Family

Rrp45, also known as EXOSC9, is a core component of the RNA exosome complex which participates in a multitude of cellular RNA processing and degradation events .

The conserved core of the exosome complex, the major eukaryotic 3' --> 5' exonuclease, consists of nine subunits that form a ring similar to the phosphorolytic bacterial PNPase and archaeal exosome . The complex functions in the accurate processing of nuclear RNA precursors and in the degradation of RNAs in both the nucleus and the cytoplasm .
Negative elongation factor E (NELFE)
Type: Family

Negative elongation factor E (NELFE) is an essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II . The NELF complex is found in higher eukaryotes, but is absent in some species of nematodes, S. cerevisiae, and plants. It may repress transcription by inducing transcriptional pausing and can be regulated by integrator complex subunits (INTScom) .
E3 ubiquitin-protein ligase DZIP3, C3H2C3-type RING finger (DZIP3_RING-H2_finger)
Type: Domain

DZIP3 is a RNA-binding ubiquitin-protein ligase that targets H2AK119 (lysine 119 of histone H2A) . It interacts with CARM1 (coactivator-associated arginine methyltransferase 1) through its RING domain and may act as a coactivator of ERalpha target gene expression
.

This entry represents the C-terminal C3H2C3-type RING-H2 finger of DZIP3.
Eukaryotic translation initiation factor 4B, RNA recognition motif (EIF-4B_RRM)
Type: Domain

Eukaryotic translation initiation factor 4B (eIF-4B) is a multi-domain RNA-binding protein that promotes association of messenger RNA to the 40S ribosomal subunit during translation initiation . eIF-4B can form a complex with eIF4F and can modulate the helicase activity of eIF4A . It has also been shown to interact specifically with the internal ribosome entry sites (IRES) of several picornaviruses which facilitate cap-independent translation initiation .

This entry represents the RNA recognition motif (RRM) of eIF-4B and similar proteins.
ROD1, RNA recognition motif 4 (PTBP3_RRM4)
Type: Domain

This entry represents the RNA recognition motif 4 of ROD1 (also known as polypyrimidine tract-binding protein 3, PTBP3), which is an RNA-binding protein highly expressed in hematopoietic cells . It is a functional homologue of fission yeast Nrd1 and may be involved in differentiation control . It also plays a role in nonsense-mediated mRNA decay (NMD) . Several ROD1 isoforms can be generated by alternative splicing and translation initiation . Rod1 contains four repeats of RNA recognition motifs (RRM).
Phospholipase A2, aspartic acid active site (PLA2_Asp_AS)
Type: Active_site

This entry represents the PLA2 active site aspartic acid and also contains three cysteines involved in disulfide bonds.

Phospholipase A2 (

) (PLA2 or PLA2G1B) is a small lipolytic enzyme that releases fatty acids from the second carbon group of glycerol. It is involved in a number of physiologically important cellular processes, such as the liberation of arachidonic acid from membrane phospholipids . It plays a pivotal role in the biosynthesis of prostaglandin and other mediators of inflammation. PLA2 has four to seven disulphide bonds and binds a calcium ion that is essential for activity. Within the active enzyme, the alpha amino group is involved in a conserved hydrogen-bonding network linking the N-terminal region to the active site. The side chains of two conserved residues, His and Asp, participate in the catalytic network.

Many PLA2's are widely distributed in snakes, lizards, bees, and mammals. In mammals, there are at least four forms: pancreatic, membrane-associated, as well as two less well characterised forms. The venom of most snakes contains multiple forms of PLA2 . Some of them are presynaptic neurotoxins, which inhibit neuromuscular transmission by blocking acetylcholine release from the nerve termini.

Some of the proteins in this family are allergens . Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Api m 1.
Phospholipase A2, histidine active site (PLA2_histidine)
Type: Active_site

This entry represents the PLA2 active site histidine and contains three cysteines involved in disulfide bonds.

Phospholipase A2 (

) (PLA2 or PLA2G1B) is a small lipolytic enzyme that releases fatty acids from the second carbon group of glycerol. It is involved in a number of physiologically important cellular processes, such as the liberation of arachidonic acid from membrane phospholipids . It plays a pivotal role in the biosynthesis of prostaglandin and other mediators of inflammation. PLA2 has four to seven disulphide bonds and binds a calcium ion that is essential for activity. Within the active enzyme, the alpha amino group is involved in a conserved hydrogen-bonding network linking the N-terminal region to the active site. The side chains of two conserved residues, His and Asp, participate in the catalytic network.

Many PLA2's are widely distributed in snakes, lizards, bees, and mammals. In mammals, there are at least four forms: pancreatic, membrane-associated, as well as two less well characterised forms. The venom of most snakes contains multiple forms of PLA2 . Some of them are presynaptic neurotoxins, which inhibit neuromuscular transmission by blocking acetylcholine release from the nerve termini.

Some of the proteins in this family are allergens . Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.

The allergens in this family include allergens with the following designations: Api m 1.
Cas9-type HNH domain (HNH_CAS9)
Type: Domain

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR associated) system is a naturally occuring, adaptative microbial immune system for defense against invading phages and other mobile genetic elements. Type II CRISPR-Cas systems use an RNA-guided DNA endonuclease, Cas9, to generate double strand breaks in invasive DNA during an adaptative bacterial immune response. Cas9 proteins are abundant across the bacterial kingdom, but vary widely in both sequence and size. All known Cas9 enzymes contain an HNH domain that cleaves the DNA strand complementary to the guide RNA sequence (target strand), and a RuvC nuclease domain required for cleaving the noncomplementary strand (non-target strand), yielding double strand DNA breaks (DSBs) .

The Cas9-type HNH nuclease domain contains a two-stranded antiparallel β sheet flanked by two α-helices on each side . This entry covers the entire Cas9-type HNH domain.
Serine proteases, trypsin family, serine active site (TRYPSIN_SER)
Type: Active_site

The catalytic activity of the serine proteases from the trypsin family is provided by a charge relay system involving an aspartic acid residue hydrogen- bonded to a histidine, which itself is hydrogen-bonded to a serine. The sequences in the vicinity of the active site serine and histidine residues are well conserved in this family of proteases . A partial list of proteases known to belong to the trypsin family is shown below.

Acrosin.

Blood coagulation factors VII, IX, X, XI and XII, thrombin, plasminogen, and protein C.

Cathepsin G.

Chymotrypsins.

Complement components C1r, C1s, C2, and complement factors B, D and I.

Complement-activating component of RA-reactive factor.

Cytotoxic cell proteases (granzymes A to H).

Duodenase I.

Elastases 1, 2, 3A, 3B (protease E), leukocyte (medullasin).

Enterokinase (EC 3.4.21.9) (enteropeptidase).

Hepatocyte growth factor activator.

Hepsin.

Glandular (tissue) kallikreins (including EGF-binding protein types A, B, and C, NGF-gamma chain, gamma-renin, prostate specific antigen (PSA) and tonin).

Plasma kallikrein.

Mast cell proteases (MCP) 1 (chymase) to 8.

Myeloblastin (proteinase 3) (Wegener's autoantigen).

Plasminogen activators (urokinase-type, and tissue-type).

Trypsins I, II, III, and IV.

Tryptases.

Snake venom proteases such as ancrod, batroxobin, cerastobin, flavoxobin,and protein C activator.

Collagenase from common cattle grub and collagenolytic protease from Atlantic sand fiddler crab.

Apolipoprotein(a).

Blood fluke cercarial protease.

Drosophila trypsin like proteases: alpha, easter, snake-locus.

Drosophila protease stubble (gene sb).

Major mite fecal allergen Der p III.

In addition to proteins from eukaryotic species listed above, are a number of bacterial family members, including:

Achromobacter lyticus protease I.

Lysobacter alpha-lytic protease.

Streptogrisin A and B (Streptomyces proteases A and B).

Streptomyces griseus glutamyl endopeptidase II.

Streptomyces fradiae proteases 1 and 2.

This entry represents the serine active site of serine proteases belonging to peptidase family S1.
EXPERA domain (EXPERA)
Type: Domain

The EXPERA (EXPanded EBP superfamilly) domain is conserved among the following protein families:

Vertebrate TM6SF1 (Transmembrane 6 Superfamily Member 1).

Vertebrate TM6SF2 (Transmembrane 6 Superfamily Member 2).

Eukaryotic MAC30 (Meningioma-associated protein 30) also known as TMEM97 (Transmembrane protein 97), mainly localized in the endoplasmic reticulum (ER).

Eukaryotic EBP (Emopamil binding protein), an enzyme with a D8, D7 sterol isomerase activity that catalyzes the transposition of a double bond from C8=C9 to C7=C8 in the sterol B-ring.

The EXPERA domain contains four transmembrane regions and is likely to possess a sterol isomerase catalytic activity .
Glycoside hydrolase family 11, active site 2 (GH11_AS_2)
Type: Active_site

The microbial degradation of cellulose and xylans requires several types of enzymes such as endoglucanases (

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family G or as the glycosyl hydrolases family 11 .

The GH11 domain folds into a jelly-roll shape likened to a partially closed right hand. Several anti-parallel β-strands bend almost 90deg to produce a substrate-binding groove characteristic of the GH11 domain active sites. Two catalytic Glu residues face each other from opposite sides of the groove. The hydrolysis reaction is believed to follow a double- displacement mechanism, with one Glu residue acting as a general acid/base catalyst and the other as a nucleophile.

This entry represents a second conserved region found in these enzymes that is centred on glutamic acid residues. The other conserved region is represented in

. In Bacillus pumilis xylanase, this site is necessary for catalytic activity .
Hotdog acyl-CoA thioesterase (ACOT)-type domain (HOTDOG_ACOT)
Type: Domain

The HotDog domain is widespread in eukaryotes, bacteria, and archaea and is involved in a range of cellular processes, from thioester hydrolysis, to phenylacetic acid degradation and transcriptional regulation of fatty acid biosynthesis. The HotDog domain has a mixed α+β fold structure, which adopts a five- to seven-stranded antiparallel β-sheet as the 'bun' wrapping around a central α-helix sausage .

The largest HotDog domain subfamily represents over a hundred acyl-CoA thioesterases (ACOTs) that are widespread throughout the prokaryotic kingdom, with members also found in eukaryotes. This group of enzymes catalyze the hydrolysis of acyl-CoA thioesters to free fatty acids and coenzyme A (CoA- SH). The subfamily includes thioesterases with activity towards medium and long chain acyl-CoAs (medium chain acyl-CoA hydrolase and cytosolic long-chain acyl-CoA hydrolase/brain acyl-CoA hydrolase (BACH) respectively) and also cytoplasmic acetyl-CoA hydrolase (CACH), which hydrolyzes acetyl-CoA to acetate and CoA-SH. Brown-fat-inducible thioesterase (BFIT), a cold-induced protein found in brown adipose tissue (BAT) is also included in this group. Both BFIT and CACH possess a StAR-related lipid-transfer (START) domain that is involved in lipid binding, consistent with the role of BFIT and CACH in lipid metabolism. Duplication of the HotDog domain and recruitment of the START domain seems to be a mammalian innovation .

The HotDog ACOT-type domain consists of a five-stranded β-sheet with topology beta1/beta3/beta4/beta5/beta2 that wraps around a central five-turn α helix, alpha1, positioned between beta1 and beta2 .
Peptidase family A1 domain (PEPTIDASE_A1)
Type: Domain

This entry represents domain found in the peptidase A1 family.

This entry also includes a probable inactive secreted aspartyl protease from Malassezia globosa, which may promote an inflammatory immune response in the host when the host skin barrier is breached . It has no detectable protease activity in vitro that could be due to the active site motif diverging from the canonical Asp-X-Gly-X motif (where X is Thr or Ser) to containing a Tyr residue (Asp-Ser-Gly-Tyr) .

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.
LETM1-like, ribosome-binding domain (LETM1-like_RBD)
Type: Domain

Mitochondrial ribosomes synthesise core subunits of the inner membrane
respiratory chain complexes. In mitochondria, ribosomes are mainly membrane
associated and translation is tightly coupled to the inner mitochondrial
membrane. Mdm38/Letm1 is a conserved membrane receptor for mitochondrial
ribosomes and specifically involved in respiratory chain biogenesis.These proteins play a role in potassium and hydrogen ion exchange . Some features found in LETM1, such as a transmembrane domain and a CK2 and PKC phosphorylation site , are relatively conserved throughout the family. Deletion of LETM1 is thought to be involved in the development of Wolf-Hirschhorn syndrome in humans .

This entry represents the Letm1 ribosome-binding domain (RBD) of Letm1 from animals and MDM38 from yeast. This domain is necessary and sufficient for
interaction with mitochondrial ribosomes. It exhibits a predominantly α-helical compact fold and contains extended, highly charged
surface patches. The conserved regions most probably represent interaction
sites for ribosomal RNA or protein subunits, or for proteins involved in
mitochondrial protein biogenesis .
Glycosyl hydrolase 11 domain (GH11_dom)
Type: Domain

The microbial degradation of cellulose and xylans requires several types of enzymes such as endoglucanases (

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family G or as the glycosyl hydrolases family 11 (GH11) .

The GH11 domain folds into a jelly-roll shape likened to a partially closed right hand. Several anti-parallel β-strands bend almost 90deg to produce a substrate-binding groove characteristic of the GH11 domain active sites. Two catalytic Glu residues face each other from opposite sides of the groove. The hydrolysis reaction is believed to follow a double- displacement mechanism, with one Glu residue acting as a general acid/base catalyst and the other as a nucleophile.
Serine carboxypeptidases, histidine active site (Ser_caboxypep_his_AS)
Type: Active_site

All known carboxypeptidases are either metallo carboxypeptidases or serine carboxypeptidases (

and

). The catalytic activity of the serine carboxypeptidases, like that of the trypsin family serine proteases, is provided by a charge relay system involving an aspartic acid residue hydrogen-bonded to a histidine, which is itself hydrogen-bonded to a serine . Proteins known to be serine carboxypeptidases include:

Barley and wheat serine carboxypeptidases I, II, and III .

Yeast carboxypeptidase Y (YSCY) (gene PRC1), a vacuolar protease involved in degrading small peptides.

Yeast KEX1 protease, involved in killer toxin and alpha-factor precursor processing.

Fission yeast sxa2, a probable carboxypeptidase involved in degrading or processing mating pheromones .

Penicillium janthinellum carboxypeptidase S1 .

Aspergullus niger carboxypeptidase pepF.

Aspergullus satoi carboxypeptidase cpdS.

Vertebrate protective protein / cathepsin A , a lysosomal protein which is not only a carboxypeptidase but also essential for the activity of both beta-galactosidase and neuraminidase.

Mosquito vitellogenic carboxypeptidase (VCP) .

Naegleria fowleri virulence-related protein Nf314 .

Yeast hypothetical protein YBR139w.

Caenorhabditis elegans hypothetical proteins C08H9.1, F13D12.6, F32A5.3, F41C3.5 and K10B2.2.

In higher plants and fungi serine carboxypeptidases are found in the cell vacuoles. In animal cells serine carboxypeptidases are found lysosomes .

The sequences surrounding the active site histidine residue are highly conserved in all these serine carboxypeptidases.