SII-SWORD/CoKE huggingface dataset:
Type II secretion system protein GspM, periplasmic domain superfamily (T2SS_M_periplasmic_sf)
Type: Homologous_superfamily

GspM is part of the inner membrane component of the type II secretion system (T2SS). It consists of a short cytosolic N-terminal domain, a transmembrane domain, and a C-terminal periplasmic domain. The precise function of this protein is unknown . However, though in Vibrio cholerae, the EpsM protein interacts with the EpsL protein, and also forms homodimers .

The periplasmic domain forms a sandwich consisting of two α-helices and a four-stranded antiparallel β-sheet . The overall fold is a circular permutation of the ferredoxin fold. In the dimer, a deep cleft with a polar rim and a hydrophobic bottom made by conserved residues is located between the monomers. This cleft contains an extra electron density suggesting that this region might serve as a binding site of an unknown ligand or part of a protein partner.
Glycoside hydrolase, family 2, conserved site (Glyco_hydro_2_CS)
Type: Conserved_site

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase 2

comprises enzymes with several known activities; beta-galactosidase (

); beta-mannosidase (

); beta-glucuronidase (

).

These enzymes contain a conserved glutamic acid residue which has been shown , in Escherichia coli lacZ (

), to be the general acid/base catalyst in the active site of the enzyme.

This entry represents a conserved site of glycoside hydrolase 2.
GSKIP domain superfamily (GSKIP_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain of GSK3-beta interaction protein (GSKIP), which binds to GSK3beta . It is also found as a short domain towards the N terminus in clustered mitochondria protein, also known as clueless in Drosophila, which is involved in proper cytoplasmic distribution of mitochondria .
Glycoside hydrolase, family 2, active site (Glyco_hydro_2_AS)
Type: Active_site

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase 2

comprises enzymes with several known activities; beta-galactosidase (

); beta-mannosidase (

); beta-glucuronidase (

).

These enzymes contain a conserved glutamic acid residue which has been shown , in Escherichia coli lacZ (

), to be the general acid/base catalyst in the active site of the enzyme.

This pattern signature contains the active site glutamic acid residue.
Herpesvirus major capsid protein, upper domain superfamily (Herpes_MCP_upper_sf)
Type: Homologous_superfamily

The Herpesvirus major capsid protein (MCP) is the principal protein of the icosahedral capsid, forming the main component of the hexavalent and probably the pentavalent capsomeres. The capsid shell consists of 150 MCP hexamers and 12 MCP pentamers. One pentamer is found at each of the 12 apices of the icosahedral shell, and the hexamers form the edges and 20 faces . The MCP can be considered as having three domains: floor, middle and upper. The floor domains form a thin largely continuous layer, or shell, and are the only parts that interact directly to form intercapsomeric connections. They also interact with the internal scaffolding protein during capsid assembly . The remainder of the protein extends radially outward from the capsid producing the hexamer and pentamer capsomere structures. The middle domains are involved in binding to the triplexes that lie between and link adjacent capsomeres . The upper domains form the tops of the hexamer and pentamer towers and are the binding sites for the small capsid protein VP26 in the hexons and for tegument proteins in the pentons.

The upper domain of MCP forms a pyramid structure composed predominantly of loops and α-helices . This domain appears to form a compact, stable structure and may act as a rigid core around which the more flexible middle and floor domains are able to undertake the conformational changes required for capsid assembly.
NarG-like domain (NarG-like_domain)
Type: Domain

The NarG-like domain was originally characterised in the molybdo-bis(molybdopterin guanine dinucleotide) (Mo-bisMGD) cofactor-binding subunit NarG from nitrate reductase subunit. It is also found in homologous subunits from other oxidorectuases such as the coenzymeB--coenzymeM heterodisulphide reductase subunit E. Structurally this domain is composed of four α-β subdomains that are organised around the catalytic centre of the enzyme complex . Subdomains II and III are organised around the Mo-bisMGD cofactor.
FAM105 (FAM105)
Type: Family

This entry represents the FAM105 family, including FAM105A (OTULINL) and FAM105B (OTULIN). Otulin is an ubiquitin thioesterase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response . FAM105A shares a high degree of similarity with protein otulin; however, FAM105A lacks the conserved active site at position 139 which is replaced by an Asp residue, and does not show deubiquitinase activity .
Inactive ubiquitin thioesterase OTULINL (OTULINL)
Type: Family

An approximately 350-residue amino acid polypeptide, designated protein FAM105A (also known as OTULINL), has been identified in a range of vertebrates. It shares a high degree of similarity with protein FAM105B (also known as OTULIN), an ubiquitin thioesterase. Despite their similarity, FAM105A lacks the conserved active site at position 139 which is replaced by an Asp residue, and does not show deubiquitinase activity .
Ubiquitin thioesterase otulin (Otulin)
Type: Family

Otulin (also known as FAM105B) belongs to the ovarian tumour (OTU) deubiquitinases (DUBs) family . It specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response . It associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates .
FAM175 family (FAM175)
Type: Family

Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 , BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) , and uncharacterised plant proteins.

It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 . Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC - the protein does not interact with BRCA1, but binds polyubiquitin . The primary sequences of these proteins contain an MPN-like domain .
BRISC complex, Abraxas 1 subunit (BRISC_Abraxas1)
Type: Family

This entry represents the Abraxas 1 protein.

Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 , BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) , and uncharacterised plant proteins.

It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 . Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC - the protein does not interact with BRCA1, but binds polyubiquitin . The primary sequences of these proteins contain an MPN-like domain .
BRISC complex, Abraxas 2 subunit (BRISC_Abraxas2)
Type: Family

This entry represents the Abraxas 2 protein.

Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 , BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) , and uncharacterised plant proteins.

It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 . Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC - the protein does not interact with BRCA1, but binds polyubiquitin . The primary sequences of these proteins contain an MPN-like domain .
FAM175 family, plant (FAM175_plant)
Type: Family

This entry represents the plant members of FAM175.

Members of protein family FAM175 include the BRCA1-A complex subunit Abraxas 1 , BRISC complex subunit Abraxas 2 or Abro1 (Abraxas brother protein 1) , and uncharacterised plant proteins.

It is thought that BRCA1-A complex subunit Abraxas acts as a central scaffold protein responsible for assembling the various components of the BRCA1-A complex, and mediates recruitment of BRCA1 . Similarly, Abro1 probably acts as a scaffold facilitating assembly of the various components of BRISC - the protein does not interact with BRCA1, but binds polyubiquitin . The primary sequences of these proteins contain an MPN-like domain .
FAM25 (FAM25)
Type: Family

A small, approximately 90-residue amino acid polypeptide, designated protein FAM25, has been identified in human and mouse. Its function is currently unknown.
Brefeldin A-sensitivity protein 4 (Brefeldin_A-sensitivity_4)
Type: Family

Brefeldin is a lactone antibiotic produced by fungi such as Eupenicillum brefeldianum. It both inhibits protein transport between the endoplasmic reticulum (ER) and the Golgi apparatus, and induces retrograde transport from the Golgi to the ER, leading to protein accumulation within the ER. Screening of a deletion-strain collection for mutants sensitive or resistant to drugs that affect intracellular transport has revealed a number of mutants sensitive to brefeldin A: e.g., deletion of the BRE4 gene was shown to result in brefeldin A-sensitivity . The BRE4 gene product is predicted to contain 10 transmembrane (TM) domains, suggesting that it is likely to be an integral membrane protein, potentially involved in intracellular vesicle transport .
FAM138 (FAM138)
Type: Family

A number of genes are expressed exclusively in the retina, where they appear to control the specialised functions of various different cell types . One of these retinal genes (termed FAM138A/B/C/F) is found within a region of subtelomeric DNA and exhibits polymorphic distribution among multiple chromosomes . This gene encodes a putative 85-amino acid polypeptide (also known as retina-specific protein F379) that shares a high level of similarity with the retinal protein FAM138D; both also include a well-conserved N-terminal domain that is shared by a wide range of proteins, including podocalyxin-like protein 1, proto-oncogene c-Rel, suppressor of G2 allele of SKP1 homologue, and ubiquitin carboxyl-terminal hydrolase 19.
Autism susceptibility gene 2 protein (AUTS2)
Type: Family

AUTS2 is a novel gene identified in a monozygotic twin pair with autism; its translation product is a large protein containing 1,295 amino acids . Following DNA sequence analysis of autism subjects and controls, no autism-specific mutation was observed. Association and linkage analyses were also negative. It is hence considered unlikely that AUTS2 is an autism suspecptibility gene for idiopathic autism, although it may be the gene responsible for the disorder in the twins in this study . The AUTS2 gene product shares a high level of similarity with the so-called fibrosin-1-like protein, a functionally uncharacterised polypeptide that contains C-terminal Ala-rich and Pro-rich regions.
Dynein-f, intermediate chain IC97/Dnai7-like (IC97/Dnai7-like)
Type: Family

Dynein-f, also known as dynein I1, is an inner-arm dynein complex comprising two different heavy chains together with a number of intermediate and light chains. In Chlamydomonas, IC97 is the intermediate chain of the Dynein-f complex. This entry includes IC97 (

) and its homologues, including CASC1 (also known as Dnai7) from humans .

The CAncer Susceptibility Candidate 1 (CASC1) gene is expressed in lung tissues, and is a strong candidate for the pulmonary adenoma susceptibility 1 (Pas1) locus, the major determinant of strain variation in lung tumour susceptibility . There appears to be a strong correlation between functional polymorphism of CASC1 and lung tumour suspectibility in mice .

Different mouse strains fall into two genotype groups (susceptible and intermediate) according to differences in the 60th codon of the CASC1 gene . The mouse CASC1 gene shares 81% similarity with the human equivalent; the role of CASC1 in human lung-cancer risk may nevertheless differ from that in mice .
Ubiquinol-cytochrome-c reductase complex assembly factor 4, vertebrates (UQCC4_vert)
Type: Family

This family represents the ubiquinol-cytochrome-c reductase complex assembly factor 4 (UQCC4) from vertebrates, a family of proteins that was discovered in a screen of Bos taurus placental ESTs. The B. taurus member of this family was named cattle cerebrum and skeletal muscle-specific transcript 1 (CCSMST1) , hence the alternative name of the family. UQCC4 is required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation .
FAM153 (FAM153)
Type: Family

Several distinct antigens (designated NY-REN-1 to NY-REN-65) that are reactive with autologous IgG have been identified in renal cancer patients . Of these, renal carcinoma antigen NY-REN-7 (also termed protein FAM153) belongs to a small conserved family of proteins whose function is, as yet, unknown.
Cyclin-dependent kinase 2-interacting protein (Cyclin-dep_Kinase_2_interact)
Type: Family

Cyclin-dependent kinase 2-interacting protein (CINP) is a component of the active cyclin E/Cdk2 and cyclin A/Cdk2 complexes . It is phopshorylated by Cdc7, but not by Cdk2 . CINP has also been shown to bind to chromatin in a replication-dependent manner, and to associate with Origin Recognition Complex-2 (ORC2)-containing complexes and minichromosome maintenance/DNA replication licensing complex, MCM . It has been proposed that CINP is part of the Cdc7-dependent mechanism of origin firing, and constitutes a physical link between Cdk2 and Cdc7 complexes at the origins .
Pre-mRNA-splicing factor Brr1 (Brr1)
Type: Family

PRE-mRNA splicing is catalysed by the spliceosome, a large dynamic complex composed of five small nuclear RNAs (snRNAs) and more than 80 proteins. Brr1 (Bad Response to Refrigeration protein 1) is a component of spliceosomal snRNPs . Brr1 is a nuclear protein involved in mRNA splicing and required for snRNA accumulation and snRNP biogenesis . It interacts with histone protein HTA1 and associates with the spliceosome during snRNA and snRNP production .
Aurora borealis protein (Aurora_borealis_protein)
Type: Family

Aurora-A, a protein kinase required for centrosome maturation, spindle assembly and asymmetric protein localisation during mitosis, is activated by Aurora borealis protein at the onset of the mitotic cycle . Bora is a nuclear protein in interphase cells, but is excluded from the nucleus and translocates to the cytoplasm in a Cdc2-dependent manner when the cell enters mitosis . It has been suggested that activation of Cdc2 initiates the release of Bora into the cytoplasm, where it binds and activates Aurora-A .
FPRL1/chemotaxis inhibitory protein (FLIPR/CHIPS)
Type: Family

Formyl Peptide Receptor-Like 1 (FPRL1)-inhibitory protein (also termed FLIPr) has been shown to inhibit calcium mobilisation in neutrophils . There is evidence that FLIPr binds to FPRL1 and, at higher concentrations, to FPR , impairing the leukocyte response to FPRL1 agonists. It has revealed unknown inflammatory ligands during S.aureus infection and, as an FPRL1 antagonist, may facilitate development of therapeutic agents in FPRL1-mediated inflammatory diseases .

Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a . CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound .

CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation . By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown .

The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy . This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism . The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation . The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) .
Aquaporin 6 (Aquaporin_6)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

Aquaporin-6 forms a water-specific channel that participates in distinct physiological functions, such as glomerular filtration, tubular endocytosis and acid-base metabolism. It is found in the kidney and gastrointestinal tract , and is also localised in the inner ear of mammals . It is a pH-regulated anion channel , and has been found to bind calmodulin in a calcium-dependent manner, possibly providing a vital clue to its physiological role in the kidney .
FPRL1 inhibitory protein (FLIPR)
Type: Family

Formyl Peptide Receptor-Like 1 (FPRL1)-inhibitory protein (also termed FLIPr) has been shown to inhibit calcium mobilisation in neutrophils . There is evidence that FLIPr binds to FPRL1 and, at higher concentrations, to FPR , impairing the leukocyte response to FPRL1 agonists. It has revealed unknown inflammatory ligands during S.aureus infection and, as an FPRL1 antagonist, may facilitate development of therapeutic agents in FPRL1-mediated inflammatory diseases .
Liver X receptor (Liver_X_rcpt)
Type: Family

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.

Liver X receptors (LXRs) are nuclear receptors that regulate the metabolism of several important lipids, including oxysterols . There are two LXR isoforms, termed alpha and beta, which, upon activation, form heterodimers with retinoid X receptors and bind to an LXR response element found in the promoter region of their target genes. In addition to their involvement in lipid metabolism, LXRs also act as key regulators of macrophage function, and have roles in inflammation and immunity .
Placentin (Placentin)
Type: Family

The insulin family of proteins groups together several evolutionarily related active peptides : these include insulin , relaxin , insect prothoracicotropic hormone (bombyxin) , insulin-like growth factors (IGF1 and IGF2) , mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain.

Placenta insulin-like peptide, also known as placentin, was initially identified by cDNA library screening . Placentin may participate in the cellular proliferation and/or differentiation processes during placental development .