SII-SWORD/CoKE huggingface dataset:
Phosphatidylserine decarboxylase, bacterial/eukaryotic (PSD-B)
Type: Family

This entry represents Phosphatidylserine decarboxylase proenzyme and similar sequences mainly found in eukaryotes and bacteria. Phosphatidylserine decarboxylase (PSD,

) is synthesised as a single chain precursor. Generation of the pyruvoyl active site from a Ser is coupled to cleavage of a Gly-Ser bond between the larger (beta) and smaller (alpha chains). This enzyme catalyses the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). It is an integral membrane protein.

Phosphatidylserine decarboxylases (PSDs) have been classified in two types. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha and beta subunits .
Phosphatidylserine decarboxylase, prokaryotic type 1 (PSD_type1_pro)
Type: Family

This entry represents the prokaryotic type 1 subfamily.

Phosphatidylserine decarboxylase plays a pivotal role in the synthesis of phospholipid by the mitochondria. The substrate phosphatidylserine is synthesized extramitochondrially and must be translocated to the mitochondria prior to decarboxylation .
Phosphatidylserine decarboxylases

is responsible for conversion of phosphatidylserine to phosphatidylethanolamine and plays a central role in the biosynthesis of aminophospholipids .

Phosphatidylserine decarboxylases (PSDs) have been classified in two types. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha and beta subunits .
Phosphatidylserine decarboxylase, prokaryotic type 2 (PSD_type2_pro)
Type: Family

Although most bacterial PSDs belong to type 1, some are classified in type 2. They are found mainly in Clostridium, Fusobacterium and Chlamydia. This entry represents the type 2 subfamily.

Phosphatidylserine decarboxylase plays a pivotal role in the synthesis of phospholipid by the mitochondria. The substrate phosphatidylserine is synthesized extramitochondrially and must be translocated to the mitochondria prior to decarboxylation .
Phosphatidylserine decarboxylases

is responsible for conversion of phosphatidylserine to phosphatidylethanolamine and plays a central role in the biosynthesis of aminophospholipids .

Phosphatidylserine decarboxylases (PSDs) have been classified in two types. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into alpha and beta subunits .
MICOS subunit Mic26, fungi (Mic26_fungi)
Type: Family

This entry represents Mic26 from fungi.
MICOS complex subunit MIC26/MIC27, animal (MIC26/MIC27_animal)
Type: Family

This entry represents MICOS complex subunit MIC26, and its paralogue, MIC27, from animals. The MICOS complex is a central player determining mitochondrial cristae structure and formation of crista junctions .
Protein PRRC2 (PRRC2)
Type: Family

This entry includes PRRC2 (proline-rich and coiled-coil-containing protein 2, also known as BAT2) family members, including PRRC2A/B/C, from animals . PRRC2A may play a role in the regulation of pre-mRNA splicing .
Helicase HerA-like C-terminal (HerA_C)
Type: Domain

HerA is a DNA helicase able to utilise either 3' or 5' single-stranded DNA extensions for loading and subsequent DNA duplex unwinding . It forms a complex with NurA nuclease, this complex has the 5'-3' DNA end resection activity and is essential for cell viability in the crenarchaeon Sulfolobus islandicus .

HerA consists of three domains: an N-terminal β-barrel domain (

), a central domain comprising a RecA-like catalytic core (ATPase domain) and a four-helix bundle , and the C-terminal domain represented in this entry.
Outer dynein arm-docking complex subunit 3 (ODAD3)
Type: Family

ODAD3 (also known as CCDC151) is a component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule . It is involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules . It is required for motile cilia function in animals. It also has additional non-motile functions in vertebrates, such as regulation of primary cilium length, and being involved in proper orientation of cell divisions in the pronephros and correct establishment of left-right asymmetry . Mutations in the ODAD3 gene cause primary ciliary dyskinesia .
Microfibrillar-associated protein 1 (MFAP1)
Type: Family

MFAP1 is a component of the elastin-associated microfibrils . Drosophila MFAP1 binds to Prp38, a tri-small nuclear ribonucleoprotein component, and is required for pre-mRNA processing and G2/M progression .
Glycine/inosamine-phosphate amidinotransferase (AmidinoTrfase)
Type: Family

This family contains glycine (

) and inosamine (

) amidinotransferases, which are involved in creatine and streptomycin biosynthesis, respectively. This entry also includes L-arginine:L-lysine amidinotransferase from Pseudomonas savastanoi pv. phaseolicola, involved in the biosynthesis of phaseolotoxin, a nonhost-specific toxin that plays a key role in the development of the halo blight disease of beans. This enzyme is closely related to glycine amidinotransferase .
Exosome complex component Rrp43 (Rrp43)
Type: Family

Rrp43 is a non-catalytic core component of exosome, which is a 3'-5' exoribonuclease complex that functions both in the nucleus and in the cytoplasm to either degrade or process RNA .
Dimethylarginine dimethylaminohydrolase-like (DDAH-like)
Type: Family

Mammalian dimethylarginine dimethylaminohydrolases DDAH1 and DDAH2 have homology with microbial arginine deiminases , all of them are included in this entry.

DDAH hydrolyzes both N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA), two nitric oxide synthase (NOS) inhibitors to yield L-citrulline and the corresponding alkylamine . This way DDAH relieves the inhibition of NOS and promotes NO biosynthesis. Therefore, DDAH1 protects against cardiovascular disease by metabolising the risk factor ADMA, being a target for ADMA-lowering therapies .

Two isoforms exist, DDAH1 and DDAH2, encoded by different genes and have 50% identity in their amino acid sequences. Both proteins are widely expressed in multiple tissues at high levels in endothelial cells, kidney, and liver, with DDAH1 being more abundant in tissues that express neuronal NOS and DDAH2 is more abundant highly vascularized tissues that express the endothelial NOS isoform (heart, lungs, and placenta) and in immune tissues that can express iNOS . DDAH2 is incapable of metabolising ADMA and its substrate is currently unknown, and it may be a drug target through an ADMA-independent pathway with biological effects in regulation of angiogenesis, diabetes, and immune responses .
Trichohyalin (TCHH)
Type: Family

The trichohyalin gene is a member of the "fused" gene family. Trichohyalin is a large structural protein abundant in the inner root sheath (IRS) of anagenic (growing) hair follicles and other sites of hard cornification . It associates with intermediate filaments and associates in regular arrays with keratin intermediate filaments.

In humans, a number of genes specifying structural proteins expressed late during epidermal differentiation have been identified and found to be clustered on chromosome 1q21. Therefore, this region is named the epidermal differentiation complex (EDC). The proteins encoded by the EDC genes can be classified into three groups: the precursor proteins of the CE, the S100 family and the "fused" gene family . In some classification, the "fused gene" family is classified as a subgroup within the S100 gene family .

The "fused" gene family members contain EF hands and internal tandem repeats. It consists of profilaggrin, trichohyalin, repetin, hornerin, the profilaggrin-related protein and cornulin (encoded by c1orf10). They are associated with keratin intermediate filaments and partially cross-linked to the cell envelope (CE) .
COP9 signalosome, subunit CSN8 (COP9_CSN8)
Type: Family

The COP9 signalosome (CSN) is a conserved protein complex that regulates the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes , which leads to a decrease in Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 . Protein kinases CK2 and D, which phosphorylate proteins such as cJun and p53 resulting in their degradation by the ubiquitin-26S proteasome system, also binds to CSN . The mammalian CSN typically consistis of eight subunits designated CSN1-CSN8. The fission yeast possesses a smaller version of the CSN, consisting only of six subunits, whereas a more distant CSN-like complex has been described in Saccharomyces cerevisiae .

In the complex, CSN8, which is the smallest subunit, probably interacts directly with CSN3, CSN4 and CSN7 (CSN7A or CSN7B). It is necessary for assembly of the complex . CSN8 plays an important role in maintaining the proper duration of the G1 phase of the cell cycle .
Centriolar coiled-coil protein of 110kDa (CCP110)
Type: Family

CCP110 is a centriole protein implicated in the regulation of cell division , centrosome duplication , centriole length and in the suppression of ciliogenesis . Its levels and localization to the centrosome are tightly regulated in a cell cycle dependent manner . CP110 has been shown to interact with two calcium-binding proteins, centrin and calmodulin (CaM), to regulate cytokinesis .
A-kinase-interacting protein 1 (AKIP1)
Type: Family

AKIP1 regulates the effect of the cAMP-dependent protein kinase (PKAc) signalling pathway on the NF-kB activation cascade . AKIP1 binds PKA and co-localises with the NF-kB subunit p65 . In humans, there are three splice variants, whereas only the full-length protein is present in rodents . AKIP1 seems to act as a modulator of PKA in NF-kappaB signalling; different splice variants have been shown to repress or enhance NF-kB transcription .
PLAC1 family (PLAC1_fam)
Type: Family

This family consists of placenta-specific protein 1 (PLAC1), oocyte-secreted protein 1/2/3/4 (Oosp1/2/3/4). PLAC1 may play a role in placental development , while Oosp1 may regulate oogenesis and certain liver functions .
TPA-induced transmembrane protein (TTMP)
Type: Family

TTMP (C3orf52) was identified as a gene upregulated after treatment with the potent tumour promoter TPA (12-O-Tetradecanoylphorbol-13-acetate). It encodes a single-pass transmembrane protein localized to the endoplasmic reticulum .
Calcium-dependent secretion activator (CAPS)
Type: Family

This entry includes calcium-dependent secretion activators (CAPS) from animals, including CAPS1/2 from humans and unc-31 from worms.
Protein SZT2 (SZT2)
Type: Family

Szt2 (seizure threshold 2), also known as TIGR (transcript increased in glutamate resistance) is a peroxisomal protein implicated in resistance to oxidative stress. It is not a functional superoxide dismutase (SOD), but might be involved in SOD activity . In mammals, it may serve an important role in the central nervous system . Szt2 is part of the KICSTOR complex, which functions in the amino acid-sensing branch of the TORC1 signaling pathway .
Secreted and transmembrane protein 1 (SECTM1)
Type: Family

Secreted and transmembrane protein 1 (SECTM1), also known as protein K-12, has been identified as a ligand for CD7, an immunoglobulin superfamily molecule with a role in T- and NK-cell activation and cytokine production . SECTM1 is a potent costimulatory ligand for T cell proliferation and is induced by IFN-gamma .

The human genome contains only one SECTM gene, while the mouse genome contains two (SECTM1A and SECTM1B) .
BMP/retinoic acid-inducible neural-specific protein (BRINP)
Type: Family

This entry represents the BMP/retinoic acid-inducible neural-specific protein (BRINP) family, including BRINP1/2/3.

BRINP proteins are involved in neurogenesis and brain development. These proteins play a role in inhibiting neuronal cell proliferation by negatively regulating cell cycle progression, particularly by suppressing the G1/S transition in postmitotic neurons. This regulation is essential for proper brain development and the functioning of GABAergic neurons. Additionally, certain BRINP proteins have been implicated in promoting the proliferation, migration, and invasion of pituitary gonadotrope cells when overexpressed, suggesting a potential role in pituitary tumour development. BRINP proteins are also characterised by their responsiveness to BMP and retinoic acid, which are key signalling molecules in neural-specific pathways .
B-cell lymphoma/leukemia 10/E10 (BCL10/E10)
Type: Family

This entry includes animal B-cell lymphoma/leukemia 10 (BCL10) and Equine herpesvirus protein E10.

In lymphoid cells BCL10 plays a critical role in the activation of the transcription factor nuclear factor kappa B (NF-kB) downstream of a variety of immune receptors, including the TCR, B cell receptor, NK-cell receptors, C type family lectin receptors, Ig family receptors and G protein-coupled receptors . Activation of NF-kB through receptor-mediated pathways requires BCL10 to form a complex (known as CBM) with the paracaspase MALT1 and with CARD-containing adaptor protein CARMA . BCL10 is involved in the regulation of apoptosis; a BCL10 gene tanslocation is found in mucosa-associated lymphoid tissue (MALT) lymphomas . BCL10 is involved in the adaptive and innate immune response .
Protein EVI2B (EVI2B)
Type: Family

EVI2B is a gene lying within an intron of the neurofibromatosis type 1 (NF1) gene . As NF1, it might be involved in differentiation of melanocytes and keratinocytes .
Protein phosphatase 1 regulatory subunit 17 (PPP1R17)
Type: Family

Protein phosphatase 1 regulatory subunit 17, also known as G-substrate, is a substrate for cGMP-dependent protein kinase (PKG) and is primarily located in cerebellar Purkinje cells . G-substrate phosphorylated by PKG inhibits the catalytic subunit of both protein phosphatase-1 and -2A . G-substrate regulates cerebellum-dependent long-term memory and it acts as a neuroprotectant in the ventral tegmental area and retina .
Mediator of RNA polymerase II transcription subunit 32 (MED32)
Type: Family

MED32 is a component of the Mediator complex in plants. The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes . MED32 is required for recruitment of the Mediator complex and RNA polymerase II to CBF-controlled cold-responsive genes . Med32 mutants are affected in root development and leaf senescence, phenotypes possibly associated to redox changes .
DNA-binding protein BIN4 (BIN4)
Type: Family

BIN4 (also known as MIDGET) is a plant-specific, DNA binding protein that acts as a component of the plant DNA topoisomerase VI complex. BIN4 is required for endoreduplication . Loss of BIN4 triggers an ATM- and ATR-dependent DNA damage response in postmitotic cells, and this response coincides with the upregulation of the cyclin B1;1 gene, suggesting a functional link between DNA damage response and endocycle control .
Transketolase family (Transketolase_fam)
Type: Family

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.

1-deoxyxylulose-5-phosphate synthase (DXP synthase) is an enzyme so far found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer during catalysis . This entry represents the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This group of proteins includes transketolase enzymes

and 2-oxoisovalerate dehydrogenase beta subunit

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.
Transketolase, C-terminal domain (Transketolase_C)
Type: Domain

The C-terminal domain of transketolase has been proposed as a regulatory molecule binding site .

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70kDa subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.
CLAVATA3/ESR (CLE)-related protein, plant (CLE_plant)
Type: Family

This entry represents a group of the CLAVATA3/ESR (CLE)-related proteins, including CLE 16/17/21/22 from Arabidopsis. They are extracellular signal peptides that regulate cell fate . They may act as suppressors of plant stem cell differentiation .
C-terminally encoded peptide (CEP)
Type: Family

This entry includes CEP proteins from Arabidopsis thaliana, including CEP2/CEP5-10. They may serve as negative regulators that mediate environmental influences on plant development . They are extracellular signalling peptides that may regulate primary root growth rate and systemic nitrogen (N)-demand signalling. They mediate up-regulation of genes involved in N uptake and assimilation pathways . CEP5 represses plant growth rate, it regulates shoot gravitropic responses .
Cilia- and flagella-associated protein 45 (CFAP45)
Type: Family

Cilia- and flagella-associated protein 45, also known as coiled-coil domain-containing protein 19 (CCDC19) or nasopharyngeal epithelium specific protein (NESG1), has been identified in humans as a tumour suppressor . It activates the expression of miR-184, which suppresses the expression of C-Myc, a key oncogenic transcription factor.
Fasciclin-like arabinogalactan protein (Plant_FLA)
Type: Family

This entry includes fasciclin-like arabinogalactan proteins (FLAs) from plants. FLAs are a subclass of arabinogalactan proteins involved in plant growth, development and response to abiotic stress . They not only contain one or two AGP-like glycosylated regions, but also include one or two fasciclin (FAS) domains, which is an ancient cell adhesion domain conserved from bacteria to animals .

The FLAs can be classified in four groups (A-D) based on phylogenetic analysis . This entry represents a group that includes FLA1-8, FLA10 and FLA14.
EP300-interacting inhibitor of differentiation (EID)
Type: Family

The EID family members have been identified as a family of negative regulators of cellular differentiation. The family consists of EID-1 (E1A-like inhibitor of differentiation 1, also known as EP300-interacting inhibitor of differentiation 1), EID2, and EID-3/EID-2B. EID-1 seems to inhibit differentiation by blocking p300 histone acetyltransferase activity, while EID-2 inhibits differentiation through binding to class I histone deacetylases (HDACs) . EID-3 acts both as inhibitor of CBP/p300-dependent transcription and can also blocks muscle differentiation by binding to class I HDACs .
E3 ubiquitin-protein ligase RNF180 (RNF180)
Type: Family

RNF180 (also known as Rines: RING finger protein in neural stem cells) is an integral membrane protein located mainly on the cytoplasmic side of the endoplasmic reticulum. It promotes polyubiquitination and degradation by the proteasome pathway of ZIC2. It is thought that it is involved in modulation of neuronal function, such as regulation of synaptic structure and synaptic plasticity due to its high expression in mature brain. It has been related to neurodegenerative diseases and to disorders associated with emotion . Methylation of RNF180 has been linked to gastric cancer .
BZR family (BZR)
Type: Family

Brassinosteroids (BRs) are essential steroid hormones that regulate plant growth and development . This entry represents the BZR (BRASSINAZOLE-RESISTANT) family, whose members include BZR1 and BZR2 (BES1) from Arabidopsis . BZR1 is a transcriptional repressor and a positive regulator of the brassinosteroid (BR) signalling pathway that mediates both downstream BR responses and negative feedback regulation of BR biosynthesis . It interacts with REPRESSOR OF ga1-3 (RGA), a member of the DELLA family of transcriptional regulators that inhibits the GA signaling pathway in Arabidopsis thaliana . BZR2/BES1 cooperates with MYB30 to regulate brassinosteroid-induced gene expression . It also interacts with other transcription factors such as BIM1 and AtMYB30, as well as putative histone demethylases ELF6 and REF6 .
Gem-associated protein 4 (GEMIN4)
Type: Family

Gemin4 is one of the core components of the SMN complex, which contains survival motor neuron (SMN), the seven Gemin proteins (Gemin2-8), and Unrip. The complex is closely associated with the splicing small nuclear ribonucleoproteins (U snRNPs), which are the subunits of the spliceosome and consist of a U snRNA, the Sm core proteins and several proteins unique to the various RNPs . SMN and Gemin4 both interact specifically with the U snRNA and the Sm core proteins, suggesting they facilitate the assembly by forming a bridge between the two components .

The Gemin4 protein has also been referred to an important molecule in the RNA-induced silencing complex (RISC) that participates in the mature process of miRNAs .
Signaling threshold-regulating transmembrane adapter 1 (Sit1)
Type: Family

SIT (or Sit1) is a transmembrane adapter protein that negatively regulates signalling from the T-cell receptor (TCR) . SIT regulates T cell development and peripheral homeostasis.
VPRBP/DCAF1 family (VPRBP/DCAF1)
Type: Family

This entry represents the VPRBP/DCAF1 family, whose members include protein VPRBP from mammals , protein mahjong form fruit flies and DCAF1 from worms and plants . They are the substrate recognition component of the E3 ubiquitin-protein ligase complex.