SII-SWORD/CoKE huggingface dataset:
Aquaporin 10 (Aquaporin_10)
Type: Family

Aquaporins form water-specific channels that provide the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Aquaporin amino acid sequences contain two tandem repeats, each containing three transmembrane (TM) domains and a pore-forming loop, with the signature motif Asn-Pro-Ala (NPA).

Aquaporin-10 (AQP10) forms a water channel required to promote glycerol/urea permeability and water transport across cell membranes . AQP10 may contribute to water transport in the upper portion of small intestine. The family is expressed exclusively in duodenum and jejunum. The highest expression in absorptive epithelial cells is at the tips of villi within the jejunum . It was initially reported that AQP10 had poor water and no glycerol/urea permeabilities . However, this has been disputed, and may be due to identification of an incompletely spliced form, which has no conserved sixth TM domain .
E3 ubiquitin-protein ligase RNF31-like (RNF31-like)
Type: Family

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .

The fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates, is also included in this group of proteins. It has been shown to play a role in heat-stress response , as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila .
NAD(P) transhydrogenase, alpha subunit (NADP_transhyd_a)
Type: Family

NAD(P) transhydrogenase (

), a tetramer composed of 2 alpha and 2 beta subunits, is an integral membrane protein that couples the proton transport across the membrane to the reversible transfer of hydride ion equivalents between NAD and NADP. This family is the is the alpha subunit. An alternate name is pyridine nucleotide transhydrogenase alpha subunit. The N-terminal region is homologous to alanine dehydrogenase. In some species, such as Rhodospirillum rubrum, the alpha chain is replaced by two shorter chains, both with some homology to the full-length alpha chain modelled here. These score below the trusted cut-off.
DNA transformation protein TfoX-like, gammaproteobacteria (TfoX-like_gammaprotbact)
Type: Family

This entry represents TfoX/Sxy-type transcriptional regulators, which may play a key role in the development of genetic competence by regulating the expression of late competence-specific genes .

TfoX from Haemophilus influenzae positively regulates genes required for DNA transformation (late competence-specific genes) in association with CRP .

Protein Sxy from Escherichia coli, also known as TfoX induces low levels of natural DNA uptake by inducing transcription of the competence genes (the CRP-S regulon) required for DNA transformation .

Members of this family are found in gammaproteobacteria.
Signal recognition particle subunit SRP68 (SRP68)
Type: Family

The signal recognition particle (SRP) is a large ribonucleoprotein complex that targets secretory and membrane proteins to the endoplasmic reticulum membrane . The mammalian SRP contains a 303-nucleotide SRP RNA and six proteins, named SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72. Among them, the two largest, SRP68 and SRP72, form a stable SRP68/72 heterodimer of unknown structure, which is required for sorting secretory proteins . SRP68 binds to SRP RNA directly, while SRP72 binds the SRP RNA largely via non-specific electrostatic interaction. The binding of SRP72 with SRP RNA enhances the affinity of SRP68 for the RNA.
Di-c-type haem protein, MauG/cytochrome c peroxidase (MauG/Cytc_peroxidase)
Type: Family

This family consists of di-c-heme containing proteins MauG and cytochrome peroxidases.

MauG catalyses a six-electron oxidation required for posttranslational modification of a precursor of methylamine dehydrogenase (preMADH) to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor involved in methylamine metabolism . MauG contains two heme c binding sites with a Ca2+ ion linked to the two heme. This structure is also found in heme-containing peroxidases. It seems that tightly-bound Ca2+ is critical for the activity of a variety of peroxidases . MauG does not function primarily as a peroxidase, but can use H2O2 to catalyse posttranslational modifications of its protein substrate. This suggests that MauG may have originally been a peroxidase and then evolved to acquire its new function .

Cytochrome-c peroxidase IdrP1/2 from Pseudomonas are involved in iodate respiration. They may reduce the H2O2 produced by IdrA/IdrB to H2O, using a reduced cytochrome c as the electron donor .
Threonine synthase, bacterial/archaeal (Thr_Synthase_bac/arc)
Type: Family

Threonine synthase (

) catalyses the conversion of O-phospho-L-homoserine and water into L-threonine and orthophosphate, using pyridoxal phosphate as a cofactor. The pyridoxal-phosphate binding site is a Lys (K) residue. The enzyme is distantly related to the serine/threonine dehydratases which are also pyridoxal-phosphate dependent enzymes .

This entry represents the a group of threonine synthases from bacteria and archaea.
Antitoxin DinJ (DinJ)
Type: Family

DinJ is an antitoxin component of a toxin-antitoxin (TA) module. It is a labile antitoxin that counteracts the effect of the YafQ toxin . It forms a heterotetrameric complex with YafQ and the structure of this complex revealed that the N-terminal region of DinJ folds into a ribbon-helix-helix motif that dimerises for DNA recognition, and the C-terminal portion of each DinJ wraps around a YafQ molecule . Together, they they bind their own promoter, and by analogy to other TA modules probably repress its expression. Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation .
Alkaline phosphatase, prokaryotic (Alkaline_phosphatase_prok)
Type: Family

This entry represents a prokaryotic family of alkaline phosphatases.
Type IV secretion system protein VirB8/PtlE (VirB8/PtlE)
Type: Family

Bacterial type IV secretion systems mediate the transfer of macromolecular substrates into various target cells, including the transfer of virulence proteins into eukaryotic host cells. The virB operon constitutes a major determinant of virulence . It mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. VirB-dependent changes of human endothelial cell (HEC) function include massive cytoskeletal rearrangements, a proinflammatory activation by nuclear factor NF-kappa-B, inhibition of early and late events of apoptosis, leading to an increased cell survival, and, at high infection doses, a cytostatic or cytotoxic effect, which interferes with a potent VirB-independent mitogenic activity .
Lipopolysaccharide export system protein LptC (LptC)
Type: Family

LptC is involved in the translocation of lipopolysaccharide (LPS) from the inner membrane to the outer membrane in Gram-negative bacteria . It facilitates the transfer of LPS from the inner membrane to a periplasmic chaperone, LptA .
L-arabinose-binding periplasmic protein (AraF)
Type: Family

Periplasmic L-arabinose-binding protein (ABP) is involved in the high-affinity L-arabinose membrane transport system. It binds with high affinity to arabinose, but can also bind D-galactose (at approximately 2-fold lower affinity) and D-fucose (at approximately 40-fold lower affinity) .

The periplasmic ABP consists of two α/β globular domains connected by a three-stranded hinge, a Venus flytrap-like domain, which undergoes a transition from an open to a closed conformational state upon ligand binding. Moreover, ABP is homologous to the ligand-binding domain of eukaryotic receptors such as metabotropic glutamate receptor (mGluR) and DNA-binding transcriptional repressors such as LacI and GalR .
Inner membrane protein YgjV (YgjV)
Type: Family

This family consists of inner membrane proteins, including YgjV. Their functions are unknown.
Protein RseC (RseC)
Type: Family

RseC is thought to be a positive regulator of sigmaE activity . However, an rseC mutant was reported to show wild-type sigmaE activity under inducing conditions or non-inducing conditions . RseC plays a role in reduction of the SoxR iron-sulphur cluster, along with proteins encoded by the rsxABCDGE operon . Salmonella typhimurium RseC is involved in thiamine synthesis .
Tat proofreading chaperone DmsD-type (DmsD-type)
Type: Family

DmsD binds to the twin-arginine signal peptide of DmsA and TorA , although this latter binding is controversial . It could be required for the biogenesis of DMSO reductase rather than for the targeting of DmsA to the inner membrane . It may be part of a chaperone cascade complex that facilitates a folding-maturation pathway for the substrate protein .

This family also includes the chaperon protein YcdY . YcdY acts as a chaperone that increases YcdX activity, maybe by facilitating the correct insertion of the zinc ions into the catalytic site of YcdX. It is involved in the swarming motility process .
Signal recognition particle, SRP72 subunit (SRP72)
Type: Family

SRP72 is a core component of the signal recognition particle ribonucleoprotein complex that functions in targeting nascent secretory proteins to the endoplasmic reticulum membrane . SRP72 binds the 7S RNA only in presence of SRP68 .
PRAME (PRAME)
Type: Family

Preferentially expressed antigen of melanoma (PRAME) was first isolated as a human melanoma antigen by cDNA expression cloning using melanoma-reactive cytotoxic Tcells (CTL). PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies and solid tumours, including melanomas, sarcomas, head and neck cancers, small-cell lung carcinomas and renal cell cancers. In normal tissues, PRAME expression has been reported in testis and low levels are found in endometrium, ovaries and adrenals . However, the PRAME gene is also expressed, although at a lower intensity, in CD34+ stem cells from healthy donors, which might constitute a problem for its application as a target in tumour immunotherapy . Epigenetic events represent the main mechanism regulating the expression of PRAME including DNA methylation of several promoter regions .
Immunity protein SdpI (SdpI)
Type: Family

SdpI is an immunity protein that provides protection for the cell against the toxic effects of its own SdpC killing factor and that functions as a receptor/signal transduction protein as well. It responds to the SdpC toxin by sequestering the SdpR autorepressor at the membrane. Sequestration relieves repression and stimulates synthesis of immunity protein .
Low specificity L-threonine aldolase, bacteria (Low_specificity_L-TA_bact)
Type: Family

Proteins in this family catalyze the cleavage of L-allo-threonine and L-threonine to glycine and acetaldehyde. The protein from Pseudomonas sp. strain NCIMB 10558 has also been shown to act on L-erythro-phenylserine, L-threo-phenylserine, L-beta-3,4-methylenedioxyphenylserine and L-beta-3,4-dihydroxyphenylserine .
tRNA wybutosine synthesizing protein 2 (tRNA_wybutosine_synth_prot_2)
Type: Family

tRNA wybutosine-synthesizing protein 2 is an S-adenosyl-L-methionine-dependent transferase that acts as a component of the wybutosine biosynthesis pathway. It catalyses the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S-adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14) to produce wybutosine-86 . Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA.
Glyoxalase/dioxygenase/EhpR (Glyoxalase/dOase/EhpR)
Type: Family

This protein familiy consists of glyoxalases, bleomycin/phenazine resistance proteins, and dioxygenases. It includes phenazine resistance protein EhpR. In Enterobacter agglomerans, EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. EhpR is evolutionarily related to glyoxalase I and type I extradiol dioxygenases .
Baseplate protein GpP (Baseplate_GpP)
Type: Family

Baseplate protein Ggp exists as an homotrimer and forms a hub-like structure with an inner diameter of 25 Angstroms through which DNA can presumably pass during infection .
Potassium/proton antiporter subunit KhtT (K(+)/H(+)_antiporter_KhtT)
Type: Family

KhtT(YhaT) modulates the activity of the potassium/proton antiporter YhaU. The transporter is composed of the integral membrane protein YhaU and the regulatory protein KhtT .
Sigma-E factor negative regulatory protein RseA (RseA)
Type: Family

Sigma-E is important for the induction of proteins involved in heat shock response. RseA binds sigma-E via its N-terminal domain, sequestering sigma-E and preventing transcription from heat-shock promoters . Activation of the the sigma(E)-dependent extracytoplasmic stress response requires the regulated proteolysis of RseA , leading to an increase in the free pool of sigma(E) .
Tissue plasminogen activator (Tissue_plasm_act)
Type: Family

Tissue-type plasminogen activator is a serine peptidase belonging to MEROPS peptidase family S1 (chymotrypsin family, clan PA(S)), subfamily S1A.

The fibrinolytic system is the mechanism by which blood clots are dissolved via the plasmin-mediated degradation of fibrin into soluble end products. The system is activated by urokinase-type plasminogen activator (uPA;

) or by tissue-type plasminogen activator (tPA;

; this family), which are enzymes that convert the inactive proenzyme plasminogen to the active protease plasmin .

tPA is mainly involved in the activation of circulating plasminogen, while uPA activates cell-bound plasminogen after binding to a specific uPA receptor (uPAR).

Following the signal sequence and propeptide regions, tPA typically contains a fibronectin type I (FN1) domain, an EGF-type domain, two kringle domains and a trypsin domain. However, there are members missing FN1 or EGF or one of the kringles.

This entry also includes salivary plaminogen activators from the vampire bat (
Desmodus rotundus
).
HTH-type transcriptional regulator RamB (HTH_RamB)
Type: Family

This entry includes the HTH-type transcriptional regulator RamB (Rv0465c/MT0481) and PrpR. In Corynebacterium glutamicum RamB controls the expression of several genes involved in acetate metabolism . In Mycobacterium tuberculosis RamB is involved in the control of the glyoxylate cycle and its paralogue PrpR in the regulation of the methylcitrate pathway . Family members contain a helix-turn-helix (HTH) motif, which is a major structural motif capable of binding DNA. Many proteins with this motif have been shown to regulate gene expression.

This entry also includes RSP_2186 (also known as PccR) from Rhodobacter sphaeroides. RSP_2186 is a transcriptional regulator that controls pccB expression, and consequently, PCC (propionyl-CoA carboxylase) activity .
DNA-binding protein, MJ1563 type (MJ1563)
Type: Family

This family includes DNA-binding protein MJ1563, putative HTH-type transcriptional regulator yvbF, uncharacterised protein yuaC, and putative HTH-type transcriptional regulator yvaV. All family members are predicted to have a helix-turn-helix (HTH) motif, which is a major structural motif capable of binding DNA. Many proteins with this motif have been shown to regulate gene expression.
Beta-galactosidase 1-like (B-gal_1-like)
Type: Family

This entry represents a subset of the glycosyl hydrolase 35 family, including beta-galactosidase (B-gal), B-gal-1, B-gal-1-like, B-gal-8, B-gal-17. Mammalian beta-galactosidase is a lysosomal enzyme (gene GLB1) which cleaves the terminal galactose from gangliosides, glycoproteins, and glycosaminoglycans and whose deficiency is the cause of the genetic disease Gm(1) gangliosidosis (Morquio disease type B).
Alpha-2-macroglobulin, proteobacteria (A2MG_proteobact)
Type: Family

This family includes Alpha-2-macroglobulin from Escherichia coli (A2MG, YfhM) and similar proteins from proteobacteria. YfhM protects the bacterial cell from host peptidases, functioning by a 'trapping' mechanismthat consists in the cleavage of the bait-region domain by host peptidases leading to a global conformational change, which results in entrapment of the host peptidase and activation of the thioester bond that covalently binds the attacking host peptidase . It may protect the entire periplam, including the lipoproteins anchored to the periplasmic side of the outer membrane, against intruding endopeptidases .
TenA_E protein (TenA_E)
Type: Family

The TenA family of proteins occurs in prokaryotes, plants and fungi; it has two subfamilies, one (TenA_C) has an active-site cysteine, the other (TenA_E) doesn not. TenA_E proteins mediate amidohydrolase and aminohydrolase steps in the salvage of thiamin breakdown products .
Maleate isomerase/Arylmalonate decarboxylase (MaiA/AMDase)
Type: Family

Maleate isomerase catalyses the conversion of maleate to fumarate . This family also includes proteins described as arylmalonate decarboxylases .
Protein adenylyltransferase SoFic-like (SoFic-like)
Type: Family

This family of proteins includes the adenosine monophosphate-protein transferase SoFic from Shewanella oneidensis (

). Family members contain a fido domain that mediates the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins .
Submaxillary gland androgen-regulated protein like (SMR-like)
Type: Family

This entry includes submaxillary gland androgen-regulated proteins SMR1,SMR2, SMR3. This entry also includes opiorphin prepropeptide from humans.
Solute binding protein, TakP-like (SBP_TakP-like)
Type: Family

This entry represents a group of periplasmic solute-binding proteins that are part of tripartite ATP-independent periplasmic (TRAP) transport systems, including the periplasmic protein TakP, which is involved in the uptake of alpha-keto acids ; periplasmic protein All3028, which specifically binds monocarboxylate 2-oxoacids ; and TTHA0766, which binds binds L-lactate .
Coiled-coil domain-containing protein 81 (CCD81)
Type: Family

Proteins in this family contain coiled-coil domains. The function of this family is unclear.
CXC chemokine 16 (CXCL16)
Type: Family

This entry represents a novel chemokine, chemokine (C-X-C motif) ligand 16 (CXCL16), has been identified that is a member of the C-X-C family , it is also called SR-PSOX. Despite possessing the CXC motif, however, it is distantly related to the other family members and has greatest sequence similarity to members of the C-C family . CXCL16 also differs in structure from the other family members (all of which are secreted proteins) and contains a TM domain linked to the chemokine domain by a heavily glycosylated mucin stalk. This structure is similar to that of the CX3C chemokine ligand 1 (CX3C chemokine fractalkine), the only other known chemokine with a TM domain. CXCL16 has been found to be expressed in the spleen, lymph nodes, Peyer's patches and thymus. In non-lymphoid tissues, CXCL16 is found in the lung, small intestine, kidney, heart and liver . The chemokine appears to be expressed as a membrane-bound cell surface ligand on antigen presenting cells (APCs), such as B cells and macrophages . CXCL16 can also be shed from the cell surface in an active, soluble form . These two forms may have different functions. Expression of CXCL16 is upregulated by exposure to inflammatory stimuli.

CXCL16 induces a strong chemotactic response. It induces calcium mobilisation and binds to chemokine receptor CXCR6 and HIV-coreceptor Bonzo . It also acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis . Expression of CXCL16 is induced by the inflammatory cytokines IFN-gamma and TNF-alpha .

Chemokines are proteins that have important physiological and pathophysiological roles in a wide range of acute and chronic inflammatory processes . Chemokines exert their biological effects by binding to cell surface receptors. Their sequences are similar and are characterised by a 4-cysteine motif: the family can be divided according to whether the first 2 Cys residues are adjacent (the C-C family), separated by an intervening residue (the C-x-C family), have only one of the first two Cys residues (C chemokines), or contain both cysteines, separated by three intervening residues (C-x3-C chemokines).
FMRFamide-related peptide/Growth hormone-releasing peptide (FMRFamide-related/fGRP)
Type: Family

This family includes both FMRFamide-related peptides and growth hormone-releasing peptides.

FMRFamide-related peptides are neurotransmitters, hormone-like substances and tumor suppressor peptides . Neuropeptide RFRP-1 acts as a potent negative regulator of gonadotropin synthesis and secretion. Neuropeptides NPSF and NPVF efficiently inhibit forskolin-induced production of cAMP, but RFRP-2 shows no inhibitory activity. Neuropeptide NPVF blocks morphine-induced analgesia. FMRFamide-related peptides may act in concert with kisspeptin, through opposing affects, to regulate the activity of gonadotropin-releasing hormone (GnRH) neurons across the seasons, leading to an annual change in fertility and the cyclical seasonal transition from non-breeding to breeding season .