SII-SWORD/CoKE huggingface dataset:
Pleckstrin homology domain-containing family S member 1 (PLEKHS1)
Type: Family

The function of Pleckstrin homology domain-containing family S member 1 (PLEKHS1) is not clear.
Rho guanine nucleotide exchange factor 39 (ARHGEF39)
Type: Family

ARHGEF39 (also known as C9orf100) is a member of the Dbl-family guanine nucleotide exchange factors. It promotes cell proliferation and migration in hepatocellular carcinoma . It may contribute to cell proliferation and migration in gastric cancer via Akt signalling and predicts poor prognosis in non-small cell lung cancer patients .
Homeobox protein NOBOX (NOBOX)
Type: Family

NOBOX is an oocyte-specific transcription factor essential for folliculogenesis and expression of many germ cell-specific genes in mice . It regulates the expression of Pad6, a peptidylarginine deiminase in the oocyte . It has also been shown to function in regulation of embryonic genome activation, pluripotency gene expression, and blastocyst cell allocation in cattle . Mutations of the NOBOX gene have been linked to primary ovarian insufficiency .
Zinc finger MYND domain-containing protein 15 (ZMY15)
Type: Family

Zinc finger MYND domain-containing protein 15 (ZMYND150 is a histone deacetylase-dependent transcriptional repressor that plays a role in spermiogenesis . Mutations of the ZMYND15 gene have been linked to azoospermia .
Receptor-type tyrosine-protein phosphatase O (PTPRO)
Type: Family

PTPRO, also known as GLEPP1, is a receptor protein-tyrosine phosphatase containing an extracellular region that contains eight fibronectin FN III repeats and a single intracellular catalytic domain. GLEPP1 plays a role in axonal guidance , promotes osteoclastic bone resorption , mediates chemotaxis and can act as a tumour suppressor . Besides "full-length" GLEPP1, which is expressed in kidney and brain, a shorter variant exists that lacks the eight FN III repeats in the extracellular domain, called PTPROt, PTPphi, or PTP-oc, and is expressed in the hematopoietic lineage only, including osteoclasts .
Four and a half LIM domains protein 1 (Fhl1)
Type: Family

Four and a half LIM domains protein 1 (FHL1) play an essential role in skeletal muscle growth and differentiation, acts as a scaffolding protein in sarcomere assembly and is a regulator of skeletal muscle mass and energy metabolism . It has been shown to bind to Myosin-binding protein C, regulating myosin filament formation and sarcomere assembly . Mutations of the FHL1 gene cause skeletal and heart muscle myopathy . It contains an N-terminal zinc finger/half LIM domain, followed by 4 complete LIM domains.
Perilipin-1 (PLIN1)
Type: Family

Perilipin-1 (PLIN1) localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. It interacts with the CIDE-N domain of Fsp27 and increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth . Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human .
Chromobox protein homolog 7 (CBX7)
Type: Family

PcG proteins form large multiprotein complexes (PcG bodies) which are involved in the stable repression of genes involved in development, signaling or cancer via chromatin-based epigenetic modifications. Mammalian PRC1 includes canonical (cPRC1) and non-canonical complexes; cPRC1, contains four core subunits including one CBX protein (CBX2, CBX4, and CBX6-CBX8) that binds H3K27me3. CBX family members have different affinity for H3K27me3, with CBX7 having the highest binding capability .

This entry represents CBX7 . In pluripotent cells, CBX7 is the main PRC1-associated Cbx protein and plays an important role in the maintenance of pluripotency .
Inositol-pentakisphosphate 2-kinase, N-terminal lobe (IP5_2-K_N_lobe)
Type: Homologous_superfamily

This superfamily represents the N-terminal lobe found in inositol-pentakisphosphate 2-kinases (also known as inositol 1,3,4,5,6-pentakisphosphate 2-kinase, Ins(1,3,4,5,6)P5 2-kinase, InsP5 2-kinase, and IP5 2-K). This enzyme phosphorylates Ins(1,3,4,5,6)P5 to form Ins(1,2,3,4,5,6)P6 (also known as InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, nonhomologous end-joining, endocytosis and ion channel regulation .

The IP5 2-K fold consists of two lobes connected by a hinge, referred to as N-terminal lobe and C-terminal lobe. The N-terminal lobe has an α/β fold, the core of this lobe being formed by an antiparallel and twisted main β-sheet comprised of five β-strands. The C-terminal lobe is almost twice the size of the N-terminal lobe and also has an α/β fold. The β-strands form an antiparallel twisted β-sheet. The α-helices in this lobe are distributed in three noncontinuous regions that emerge from the β-sheet and comprise almost half of the protein, they are involved in the inositide binding (CIP-lobe) .
Spike glycoprotein, N-terminal domain superfamily (Spike_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of the betacoronavirus spike glycoprotein, which mainly functions as a receptor binding domain . The spike protein on coronavirus envelopes recognises receptors through the activities of a receptor-binding subunit S1 before it fuses viral and host membranes through the activities of a membrane-fusion subunit S2. S1 contains two independent domains, an N-terminal domain (NTD) and a C domain, both of which can function as viral receptor-binding domains . The NTD is a 13-stranded β-sandwich with two antiparallel β-sheets stacked against each other through hydrophobic interactions and has an overall galectin fold.
FANCL, UBC-like domain 3 superfamily (FANCL_d3_sf)
Type: Homologous_superfamily

This superfamily represents the third of three UBC-like domains found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Structurally, it consists of 3 α helices and 4 β strands.

FancL is the ubiquitin ligase protein that mediates ubiquitination of FancD2, a key step in the DNA damage pathway . FancL belongs to the multisubunit Fanconi anemia (FA) complex, which is composed of subunits: FancA, FancB, FancC, FancE, FancF, FancG, FancL/PHF9 and FancM. The WD repeats are required for interaction of FancL with other subunits of the FA complex .

In humans defects in FancL are a cause of Fanconi anemia (FA) , and the FA complex is not found in FA patients. FA is a genetically heterogeneous, autosomal recessive disorder characterised by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
MvaI/BcnI restriction endonuclease, catalytic domain (MvaI_BcnI_cat)
Type: Homologous_superfamily

This superfamily represents the catalytic domain of some type IIP restriction endonucleases such as BcnI and MVal.

BcnI cleaves duplex DNA containing the sequence CC/SGG, where S is G or C, and MvaI cleaves the sequence CC/WGG, where W is an A or a T nucleotide. Both generate staggered products with single nucleotide 5'-overhangs. Both enzymes bind duplex DNA in 1:1 stoichiometric ratio. Structural studies have shown that both Mval and BcnI show a two-lobe architecture. According to their function the two lobes have been termed catalytic lobe and recognition lobe, as the former contains all active site residues and the latter is involved in sequence recognition. The recognition lobe contains all the residues that interact specifically with the major groove of DNA and most likely mediates sequence discrimination. The catalytic lobe also contributes some of the minor groove interactions with DNA, which are unlikely to play a major role in sequence discrimination .
MvaI/BcnI restriction endonuclease, recognition domain (MvaI_BcnI_rec)
Type: Homologous_superfamily

This superfamily represents the recognition domain of some type IIP restriction endonucleases such as BcnI and Mval.

BcnI cleaves duplex DNA containing the sequence CC/SGG, where S is G or C, and MvaI cleaves the sequence CC/WGG, where W is an A or a T nucleotide. Both generate staggered products with single nucleotide 5'-overhangs. Both enzymes bind duplex DNA in 1:1 stoichiometric ratio. Structural studies have shown that both Mval and BcnI show a two-lobe architecture. According to their function the two lobes have been termed catalytic lobe and recognition lobe, as the former contains all active site residues and the latter is involved in sequence recognition. The recognition lobe contains all the residues that interact specifically with the major groove of DNA and most likely mediates sequence discrimination. The catalytic lobe also contributes some of the minor groove interactions with DNA, which are unlikely to play a major role in sequence discrimination .
Cyanuric acid hydrolase/Barbiturase, repeating unit B (AtzD/Barbiturase_RUB)
Type: Homologous_superfamily

Cyanuric acid hydrolases (AtzD) and barbiturases are homologous and found almost exclusively in bacteria . AtzD hydrolyses cyanuric acid to release carboxybiuret, which spontaneously decarboxylates to biuret . Barbiturase catalyses the ring-opening of barbituric acid to ureidomalonic acid . Although the AtzD/barbiturase family have previously been suggested to belong to the amidohydrolase superfamily, bioinformatics analysis and the lack of bound metals imply that this might not be the case .

Their structure is comprised of three repeating units (RUs) that share the same structure as one another; they have been designated RU A, B and C. Each RU is comprised of a four strand antiparallel β-sheet and two helices .

This superfamily represents the RU B found in Cyanuric acid hydrolase/Barbiturase.
Cyanuric acid hydrolase/Barbiturase, repeating unit C (AtzD/Barbiturase_RUC)
Type: Homologous_superfamily

Cyanuric acid hydrolases (AtzD) and barbiturases are homologous and found almost exclusively in bacteria . AtzD hydrolyses cyanuric acid to release carboxybiuret, which spontaneously decarboxylates to biuret . Barbiturase catalyses the ring-opening of barbituric acid to ureidomalonic acid . Although the AtzD/barbiturase family have previously been suggested to belong to the amidohydrolase superfamily, bioinformatics analysis and the lack of bound metals imply that this might not be the case .

Their structure is comprised of three repeating units (RUs) that share the same structure as one another; they have been designated RU A, B and C. Each RU is comprised of a four strand antiparallel β-sheet and two helices .

This superfamily represents the RU C found in Cyanuric acid hydrolase/Barbiturase.
Cyanuric acid hydrolase/Barbiturase, repeating unit A (AtzD/Barbiturase_RUA)
Type: Homologous_superfamily

Cyanuric acid hydrolases (AtzD) and barbiturases are homologous and found almost exclusively in bacteria . AtzD hydrolyses cyanuric acid to release carboxybiuret, which spontaneously decarboxylates to biuret . Barbiturase catalyses the ring-opening of barbituric acid to ureidomalonic acid . Although the AtzD/barbiturase family have previously been suggested to belong to the amidohydrolase superfamily, bioinformatics analysis and the lack of bound metals imply that this might not be the case .

Their structure is comprised of three repeating units (RUs) that share the same structure as one another; they have been designated RU A, B and C. Each RU is comprised of a four strand antiparallel β-sheet and two helices .

This superfamily represents the RU A found in Cyanuric acid hydrolase/Barbiturase.
LOR/SDH bifunctional enzyme, conserved domain superfamily (LOR/SDH_bifunc_enz_cons_dom_sf)
Type: Homologous_superfamily

Lysine-oxoglutarate reductase/Saccharopine dehydrogenase (LOR/SDH) is a bifunctional enzyme. LOR is also known as LKR (lysine-ketoglutarate reductase), and thus LOR/SDH is sometimes termed LKR/SDH. This superfamily represents the conserved region, commonly found immediately N-terminal to saccharopine dehydrogenase conserved region in eukaryotes .
Phenol hydroxylase domain superfamily (Phenol_hydroxylase_sf)
Type: Homologous_superfamily

Phenol hydroxylase (PH) belongs to a family of bacterial multicomponent monooxygenases (BMMs) with carboxylate-bridged diiron active sites. These enzymes effect dioxygen activation and subsequent hydrocarbon substrate oxidation at diiron active sites located within hydrophobic pockets in the alpha-subunits of the 200-250kDa heterodimeric, (α-β-gamma)2, hydroxylase protein .
Bunyavirus nucleocapsid (N) , C-terminal domain (Bunya_nucleocap_C)
Type: Homologous_superfamily

Orthobunyavirus are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein (also known as nucleoprotein) is encoded on the small (S) genomic RNA. The N protein is the major component of the nucleocapsids. This protein is thought to interact with the L protein, virus RNA and/or other N proteins .

This superfamily represents the C-terminal domain found in Bunyavirus nucleocapsid (N) protein. It is made up of 6 α helices. Some residues of this domain make up the 'C-arm' which makes intimate contact with core domains of neighbouring molecules to form a tightly-bound network throughout the crystal.
Bunyavirus nucleocapsid (N) , N-terminal domain (Bunya_nucleocap_N)
Type: Homologous_superfamily

Orthobunyavirus are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein (also known as nucleoprotein) is encoded on the small (S) genomic RNA. The N protein is the major component of the nucleocapsids. This protein is thought to interact with the L protein, virus RNA and/or other N proteins .

This superfamily represents the N-terminal domain found in Bunyavirus nucleocapsid (N) protein.
Zinc finger, TRAF-type, N-terminal (Znf_TRAF_N)
Type: Homologous_superfamily

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This superfamily represents the N terminus of TRAF zinc finger domains, found in different proteins including mammalian signal transducers associated with the cytoplasmic domain of the 75kDa tumour necrosis factor receptor . There is no information related with the specific function of this N-terminal subdomain.
Nibrin, second BRCT domain superfamily (Nibrin_BRCT2_sf)
Type: Homologous_superfamily

This entry represents the second BRCT domain of Nibrin (or Nbs1), a component of the MRN (Mre11-Rad50-Nbs1) complex that is involved in the DNA damage response. This domain (BRCT2) is identified through nuclear magnetic resonance (NMR) spectroscopy structure determination. It is downstream from BRCT1 domain and has no significant amino acid sequence homology to other BRCT domains. However, it has the α/β topology characteristic of BRCT domains in other proteins, but differs markedly in having a disordered long loop inserted between α β strand and an α helix. BRCT2 is essential for an MDC1-dependent relocalisation of Nbs1 to DNA damage sites .

Structurally, BRCT2 is composed of 4 parallel β-strands and 5 α-helices.
Arenavirus glycoprotein, zinc binding domain (Arena_glycoprot_zinc-bd)
Type: Homologous_superfamily

Arenaviridae are single stranded RNA viruses. The arenaviridae S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein .

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin arenavirus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. It has been established that it is the heterologous glycoprotein that protects against JUNV challenge. A recombinant vaccinia virus that expresses JUNV glycoprotein precursor (VV-GJun) protected seventy-two percent of the animals inoculated with two doses of VV-GJun against the lethal JUNV challenge .

The GPC complex contains a cleaved stable signal peptide (SSP) in addition to the canonical receptor-binding (G1) and transmembrane fusion (G2) subunits. SSP is essential for intracellular transport of the GPC complex to the cell surface and for its membrane-fusion activity.

This superfamily represents the zinc binding domain of GPC, available data is derived from studies on Junin arenavirus (JUNV). The face of the domain that contains the two zinc-binding clusters is well conserved among arenaviruses, and cluster II serves as a binding site for Cys-57 in the SSP. It is believed that the zinc-mediated anchoring of SSP contributes to positioning the ectodomain loop of SSP relative to the G2 ectodomain to modulate membrane fusion .
IFT81, N-terminal domain superfamily (IFT81_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in IFT81 (Intraflagellar transport protein 81) proteins. Crystal structure analysis revealed that IFT81-N adopts the fold of a calponin homology (CH) domain with structural similarity to the kinetochore complex component NDC80 with microtubule (MT)-binding properties. Functional analysis show that IFT74 and IFT81 form a tubulin-binding module required for ciliogenesis. It is suggested that IFT81-N binds the globular domain of tubulin to provide specificity, and IFT74-N recognizes the beta-tubulin tail to increase affinity .
WIYLD domain superfamily (WIYLD_dom_sf)
Type: Homologous_superfamily

This superfamily represents the plant-specific WIYLD domain, named based on the pattern of the most conserved residues . This is a ubiquitin-binding domain that adopts a four-helix bundle structure, in contrast to the three-helix bundles of other ubiquitin binding domains. It is found in histone-lysine N-methyltransferase SUVR4 and related proteins SUVR1 and SUVR2. SUVR4 is an active histone methyltransferase with a preference for H3K9me1 and ubiquitin binding mediated by this domain facilitates the addition of two methyl groups to monomethylated lysine 9 of histone H3 . SUVR2 has no histone methyltransferase activity and is involved in transcriptional gene silencing . SUVR2 forms a complex with SUVR1 and associates with the SNF2-related chromatin-remodeling proteins. No histone methyltransferase activity has been detected for SUVR1 neither .
Poxvirus domain superfamily (Poxvirus_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in a group of Poxvirus Bcl-2-like proteins that function as immunomodulators to evade the host innate immune response through the inhibition of apoptosis or blocking the activation of pro-inflammatory transcription factors, such as interferon (IFN) regulatory factor-3 (IRF-3) and nuclear factor-kappaB (NF-kappaB)

]. This entry includes IFN signaling evasion protein OPG029 and Protein OPG200 from Vaccinia virus. OPG029, also known as C6L, prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factors 3/IRF3 and 7/IRF7, transcription factors critical for the induction of interferons alpha and beta . OPG200, also called B14, contributes to virulence by binding to the host IKBKB subunit of the IKK complex and preventing host NF-kappa-B activation in response to pro-inflammatory stimuli such as TNF-alpha or IL1B .
T3SS negative regulator GrlR domain superfamily (GrlR_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in GrlRs, a family of negative regulators of T3SS also involved in lipid binding .
Structurally, GrlR consists of a typical β-barrel fold with eight β-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two β-barrels maintain its dimeric architecture. A unique surface-exposed EDED (Glu-Asp-Glu-Asp) motif is identified to be critical for GrlA-GrlR interaction and for the repressive activity of GrlR .

The locus of enterocyte effacement (LEE) is essential for virulence of enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). It is comprised of 41 proteins which encode for T3SS proteins in addition to three associated regulators: Ler, GrlA and GrlR. GrlA positively regulates the expression of ler, the first gene in the LEE1 operon, which in turn regulates the expression of various downstream genes involved in T3SS biogenesis. GrlR binds directly to GrlA and functions as an anti-regulator .
GCM domain, large subdomain (GCM_large)
Type: Homologous_superfamily

GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been identified in proteins belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian homologues . In GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 residues. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved.

The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' . The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues . The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding . The GCM domain is a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain . The GCM domain consists of a large and a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five-and three-stranded β-sheets, respectively, with three small helical segments packed against the same side of the two β-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded β-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the β-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

This superfamily represents the large domain found in the GCM motif.