SII-SWORD/CoKE huggingface dataset:
UPF0524 family (UPF0524_fam)
Type: Family

The proteins matched by this entry belong to the UPF0524 family. Their function is unknown.
FAM199X family (FAM199X_fam)
Type: Family

Proteins matched by this entry belong to the FAM199 family. Their function is unknown.
Transmembrane protein 179 (TMEM179)
Type: Family

This entry represents a group of transmembrane proteins with unknown function.
GPI-GalNAc transferase PGAP4 (PGAP4)
Type: Family

This family represents the Golgi-resident GPI-GalNAc transferase PGAP4 (also known as TMEM246). It contains three transmembrane domains, this contrasts with other Golgi glycosyltransferases composed of a single domain. It contains a catalytic site, a DXD-like motif for UDP-GalNAc donor binding and residues thought to be involved in acceptor binding. PGAP4 is required for the initial step of GPI-GalNAc biosynthesis .
Cilia- and flagella-associated protein 221 (CFAP221)
Type: Family

Cilia- and flagella-associated protein 221 (Cfap221, also known as PCDP1) plays an important role in ciliary and flagellar biogenesis and motility . It is expressed in spermatogenic cells and motile ciliated epithelial cells. Mutations in PCDP1 gene cause primary ciliary dyskinesia (PCD), which is characterised by sinusitis, male infertility, hydrocephalus, and situs inversus .
Coiled-coil domain-containing protein 157 (CCDC157)
Type: Family

This entry represents a group of coiled-coil domain-containing proteins. Their function is not clear.
Schlafen family (Schlafen)
Type: Family

The Schlafen (SLFN) family includes several mouse and human member genes that have been implicated in important functions, such as the control of cell proliferation, induction of immune responses, and the regulation of viral replication . Mouse and human SLFN proteins are regulated by interferons (IFNs) . All SLFNs contain an unique Slfn box. SLFN family is comprised of 3 groups, based on the size of the encoded proteins :

Group1: Slfn1, Slfn2, and Slfn Like 1.

Group2: Slfn3, Slfn4 and Slfn12.

Group3: Slfn5, Slfn8-11, Slfn13 and Slfn14.

Comparing to group1 proteins, group2 and 3 proteins contain an extra SWADL domain C terminus to the AAA domain. Group3 proteins also possess a large extension C terminus to their SWADL domain. This C-terminal extension is homologous to the superfamily I of DNA/RNA helicases . It has been proposed that the divergent AAA ATPase domain may function as an RNA-binding domain .

This entry also includes orthopoxvirus sequences. Analyses indicate that a member of the Schlafen family was horizontally transferred from murine rodents to orthopoxviruses, where it is hypothesised to play a role in allowing the virus to survive host immune defense mechanisms .
Enhancer of split M4 family (Malpha/m4/m2)
Type: Family

In Drosophila, the majority of Notch target genes known so far is located in the Enhancer of split complex (E(spl)-C), encoding small basic helix-loop-helix (bHLH) proteins that presumably act as transcriptional repressors. E(spl)-C contains three additional Notch responsive, non-bHLH genes: m4 and ma, which are structurally related, and m2 .

This entry represents the E(spl) m4 family, which act as antagonists of the Notch signal in the process of adult sensory organ precursor singularisation .
Interactor of constitutive active ROPs (ICR)
Type: Family

Interactor of constitutive active ROPs (ICR) family includes ICR1-4 from plants. ICR1 acts as a scaffold, mediating interaction of ROPs with different proteins . ROPs (Rho-related GTPases) are a subfamily of Rho small GTPases from plants.
Prostate and testis expressed protein 2 (PATE2)
Type: Family

Prostate and testis expressed protein 2 (PATE2, also known as PATE-M) belongs to the PATE family and is expressed in prostate and testis .

PATE proteins are secreted, small, cysteine-rich proteins selectively expressed in male reproductive tissues (prostate, testis, epididymis, seminal vesicle).This proteins include 10 cysteine residues conforms to a consensus cysteine pattern found in a well-conserved large family of three-fingered proteins (TFPs), characterised by a distinct disulfide bonding pattern between 8 and 10 cysteine residues . Critical roles of the PATE (Pate)-like proteins in activities related not only to fertility and reproduction but also to neuronal activity. Neurons and sperm share many common "neuron specific" receptors. Nicotinic acetylcholine receptors (nACHR) subunits alpha7, 9, 3, 5 and beta 4 have all been demonstrated to be present in human sperm and the alpha-7 subunit likely exists as a homomer in the posterior post-acrosomal and neck regions of sperm. Human acrosome reaction initiated by acetylcholine involves the alpha-7 nAChR . Common functionality of nAChR in both reproductive and neuronal tissues thus reconciles the neuro-modulatory activity of the PATE (Pate)-like proteins.
Transmembrane protein 74-like (TMEM74-like)
Type: Family

This entry represents a group of transmembrane proteins from chordates with unknown function.
DNA polymerase epsilon catalytic subunit (POL2)
Type: Family

DNA polymerase epsilon catalytic subunit (also known as POL2) is a catalytic subunit of DNA polymerase epsilon, which is a a high-fidelity polymerase participating in chromosomal DNA replication . It contains both polymerase and 3'-5'-exonuclease domains . Its 3'-5'-exonuclease domain ensures a particularly low error rate . POL2 also plays a role in DNA repair and is linked to cancer . Its structure has been solved .
STEEP-like (STEEP-like)
Type: Family

This entry includes protein STEEP (CXorf56) from humans and related proteins.

STEEP1 is a molecular adapter that stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport . STEEP interacts with STING and enables STING signaling by promoting ER exit .
VPS35 endosomal protein sorting factor-like (VPS35L)
Type: Family

VPS35L is part of the retriever complex involved in retromer-independent endosomal cargo recycling .
SERTA domain-containing protein 4 (SERTAD4)
Type: Family

SERTA domain-containing protein 4 (SERTAD4) is highly expressed in adult murine epidermal tissues and in digits. The function of the SERTA domain is unknown, but proteins containing this domain have been linked to cell cycle progression and chromatin remodelling. SERTAD4 resides predominantly in the nucleus throughout all stages of the cell cycle .
Lipid droplet assembly factor 1 (LDAF1)
Type: Family

LDAF1, also known as Promethin, is expressed in a variety of mammalian tissues including the adipose tissue, heart, kidney, and at lower levels in lung, liver, skeletal muscle and testis. It is up-regulated in liver with hepatic adiposis caused by PPARgamma (peroxisome proliferator-activated receptor-gamma) overexpression .

LDAF1 has been shown to form a lipid droplet assembly complex with seipin .
DNA ligase 4 (LIG4)
Type: Family

DNA ligase 4 (LIG4) is involved in DNA double-strand break repair . In higher eukaryotes it forms a complex with XRCC4, which is responsible for the ligation step during the DNA-PK-dependent non-homologous end joining (D-NHEJ) . The Ku component of the DNA-PK (DNA-dependent protein kinase) complex contributes to the recruitment of the LIG4-XRCC4 complex at the DNA break site .
HAUS augmin-like complex subunit 7-like (Haus7-like)
Type: Family

Haus7 is a component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex, and this interaction is required for spindle assembly, chromosome segregation and cytokinesis .
Transmembrane protein 168 (TMEM168)
Type: Family

This is a family of uncharacterised transmembrane proteins.
Shieldin complex subunit 2 (FAM35A)
Type: Family

This entry refers to Shieldin complex subunit 2 (also known as Protein FAM35A or RINN2). Shieldin complex is composed of REV7, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and RINN3 (C20ORF196), and plays an important role in repair of DNA double-stranded breaks .
FAM193 family (FAM193)
Type: Family

Proteins in this family are not characterised.
Integral membrane protein GPR137 (GPR137)
Type: Family

This family of uncharacterised proteins includes transmembrane 7 superfamily member 1-like proteins.
OSGIN 1/2 (OSGIN1/2)
Type: Family

This entry represents OSGIN 1, OSGIN 2 and related proteins found in animals such as F30B5.4 an uncharacterised protein from Caenorhabditis elegans.

The oxidative stress-induced growth inhibitor 1 (OSGIN1) regulates the differentiation and proliferation of normal cells through the regulation of cell death . It has also been identified as a possible as a flavin-dependent monooxygenase . OSGIN2 may be involved in meiosis or the maturation of germ cells.
Large ribosomal subunit protein bL25, L25 domain (Ribosomal_L25_dom)
Type: Domain

This entry represents the N-terminal domain of the long-form of the large ribosomal subunit protein bL25, also known as General stress protein CTC (CTC-like). The L25 domain covers the full length of the protein in the short-form of bL25 (L25-like).

Ribosomal protein bL25, previously known as L25, is an RNA binding protein, that binds 5S rRNA . Ribosomal protein bL25 has a long-form and a short-form. The long-form is represented by the general stress protein Ctc of Bacillus subtilis, which has now been localised to ribosomes , and ribosomal protein TL5 of Thermus thermophilus. CTC is a known stress protein, and proteins of this family are believed to have two functions, acting as both ribosomal and stress proteins. In Escherichia coli, cells deleted for L25 were found to be viable; however, these cells grew slowly and had impaired protein synthesis capability. In Bacillus subtilis, CTC is induced under stress conditions and located in the ribosome; it has been proposed that CTC may be necessary for accurate translation under stress conditions . Members of this group of proteins are mostly found in bacteria, with a few exceptions such as plants.

Ribosomal protein L25 of Escherichia coli and Haemophilus influenzae appear to be orthologous, but consist only of the N-terminal half of Ctc and TL5. Both short (L25-like) and full-length (CTC-like) members of this group bind the E-loop of bacterial 5S rRNA .
D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site 1 (D-isomer_DH_CS1)
Type: Conserved_site

A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be specific for the D-isomer of their substrate have been shown to be functionally and structurally related . All these enzymes have similar enzymatic activities and are structurally related.

This is a glycine-rich conserved site located in the central section of these enzymes, which probably corresponds to the NAD-binding domain.
D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site (D-isomer_DH_CS)
Type: Conserved_site

A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be specific for the D-isomer of their substrate have been shown to be functionally and structurally related . All these enzymes have similar enzymatic activities and are structurally related.

This entry includes two conserved sites that contain a number of conserved charged residues, some of which may play a role in the catalytic mechanism.
Urease nickel binding site (Urease_Ni-bd)
Type: Binding_site

Urease (urea amidohydrolase,

) is a nickel-binding enzyme that catalyses the hydrolysis of urea to carbon dioxide and ammonia . Historically, it was the first enzyme to be crystallized (in 1926). It is mainly found in plant seeds, microorganisms and invertebrates. In plants, urease is a hexamer of identical chains. In bacteria , it consists of either two or three different subunits (alpha, beta and gamma).

Urease binds two nickel ions per subunit; four histidine, an aspartate and a carbamated-lysine serve as ligands to these metals; an additional histidine is involved in the catalytic mechanism . The urease domain forms an (α/β)(8) barrel structure with structural similarity to other metal-dependent hydrolases, such as adenosine and AMP deaminase and phosphotriesterase.

This entry represents a conserved region that contains two histidines that bind one of the nickel ions.
MTH1187/YkoF-like (MTH1187/YkoF-like)
Type: Homologous_superfamily

This domain superfamily is found in uncharacterised protein MTH1187 and its yeast orthologue YBL001C (also known of Ecm15) and putative hydroxymethyl pyrimidine (HMP)/thiamine binding proteinin YkoF . They consist of a ferredoxin-like fold.
DNA-directed RNA polymerase subunit delta (RpoE)
Type: Family

This entry includes DNA-directed RNA polymerase subunit delta from Bacillus subtilis.

The delta protein is a dispensable subunit of Bacillus subtilis RNA polymerase (RNAP) that has major effects on the biochemical properties of the purified enzyme. In the presence of delta, RNAP displays an increased specificity of transcription, a decreased affinity for nucleic acids, and an increased efficiency of RNA synthesis because of enhanced recycling . The delta protein, contains two distinct regions, an ordered N-terminal domain and a glutamate and aspartate residue-rich C-terminal region, unordered and flexible . It participates in both the initiation and recycling phases of transcription and also in the adaptation to changes in the environment.
Sulphite reductase [NADPH] flavoprotein, alpha chain, Proteobacteria (CysJ_Proteobact)
Type: Family

Escherichia coli NADPH-sulphite reductase (SiR) is a multimeric hemoflavoprotein composed of eight alpha-subunits (SiR-FP) and four beta-subunits (SiR-HP) that catalyses the six electron reduction of sulphite to sulphide. This is one of several activities required for the biosynthesis of L-cysteine from sulphate. The alpha component of NADPH-sulphite reductase is a flavoprotein, the beta component is a hemoprotein . The flavoprotein component catalyses the electron flow from NADPH to FAD to FMN to the hemoprotein component.

This entry describes a clade of NADPH-dependent sulphite reductase flavoprotein subunit alpha from Proteobacteria. The proteins bind one FAD and one FMN as prosthetic groups and contains an NADPH-binding domain .
Glutathione peroxidase active site (GPX_AS)
Type: Active_site

The catalytic site of glutathione peroxidases contains a conserved residue which is either a cysteine or, in many eukaryotic glutathione peroxidase, a selenocysteine . This entry represents the region around this active site residue.

Glutathione peroxidase (GSHPx) (

) is an enzyme that catalyses the reduction of hydroxyperoxides by glutathione . Its main function is to protect against the damaging effect of endogenously formed hydroxyperoxides.

In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In addition to these characterised forms, the sequence of a protein of unknown function has been shown to be evolutionary related to those of GSHPx's.

Escherichia coli protein btuE, a periplasmic protein involved in the transport of vitamin B12, is also evolutionary related to GSHPx's; the significance of this relationship is not yet clear.
Glutathione peroxidase conserved site (GPX_CS)
Type: Conserved_site

This entry represents a highly conserved octapeptide located in the central section of glutathione peroxidase.

Glutathione peroxidase (GSHPx) (

) is an enzyme that catalyses the reduction of hydroxyperoxides by glutathione . Its main function is to protect against the damaging effect of endogenously formed hydroxyperoxides.

In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In addition to these characterised forms, the sequence of a protein of unknown function has been shown to be evolutionary related to those of GSHPx's.
Pyroglutamyl peptidase I, bacterial-type (PGP-I_bact-type)
Type: Family

This group of cysteine peptidases belong to MEROPS peptidase family C15 (pyroglutamyl peptidase I, clan CF). The type example being pyroglutamyl peptidase I of Bacillus amyloliquefaciens. There are similarities in structure between members of clan CF and members of three clans of metallopeptidases (MC, MF and MH) and all four are included in the same superfamily (phosphorylase/hydrolase-like fold) by the SCOP database. Members of clan CF have an α/β/α sandwich fold .

Pyroglutamyl peptidase I (also known as pyrrolidone carboxyl peptidase, Pcp or PYRase) is an exopeptidase that hydrolytically removes the pGlu from pGlu-peptides or pGlu-proteins . PYRase has been found in prokaryotes and eukaryotes where at least two different classes have been characterised: the first containing bacterial and animal type I PYRases, and the second containing animal type II and serum PYRases. Type I and bacterial PYRases are soluble enzymes, while type II PYRases are membrane-bound. The primary application of PYRase has been its utilisation for protein or peptide sequencing, and bacterial diagnosis . The conserved residues Cys-144 and His-168 have been identified by inhibition and mutagenesis studies .

This family consist of bacterial and archaeal type I PYRases.
Diphosphomevalonate decarboxylase (Mev_diP_decarb)
Type: Family

This group of enzymes belongs to the GHMP kinase domain superfamily. GHMP kinases are a unique class of ATP-dependent enzymes (the abbreviation of which refers to the original members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) . Enzymes belonging to this superfamily contain three well-conserved motifs, the second of which has the typical sequence Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala and is involved in ATP binding . The phosphate binding loop in GHMP kinases is distinct from the classical P-loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P-loop-containing proteins . GHMP kinases display a distinctly bilobal appearance with their N-terminal subdomains dominated by a mixed β-sheet flanked on one side by α-helices and their C-terminal subdomains containing a four stranded anti-parallel β-sheet .
UDP-N-acetylglucosamine 2-epimerase WecB-like (WecB-like)
Type: Family

This entry includes UDP-N-acetylglucosamine 2-epimerase WecB from Enterobacteriaceae and UDP-2,3-diacetamido-2,3-dideoxy-D-glucuronate 2-epimerase WbpI from Pseudomonas aeruginosa. WecB is involved in the enterobacterial common antigen biosynthesis, which is part of bacterial outer membrane biogenesis. It catalyses the reversible epimerization at C-2 of UDP-N-acetylglucosamine (UDP-GlcNAc) and thereby provides bacteria with UDP-N-acetylmannosamine (UDP-ManNAc), the activated donor of ManNAc residues . WbpI is involved in the LPS O-antigen biosynthesis, which is part of bacterial outer membrane biogenesis. It catalyses the epimerization of UDP-2,3-diacetamido-2,3-dideoxy-alpha-D-glucuronic acid (UDP-alpha-D-GlcNAc3NAcA) to UDP-2,3-diacetamido-2,3-dideoxy-alpha-D-mannuronic acid (UDP-alpha-D-ManNAc3NAcA) .

This entry also includes UDP-N-acetylglucosamine 2-epimerase homolog from Methanococcus maripaludis at locus MMP0357 which despite its similarity with the UDP-N-acetylglucosamine 2-epimerase enzymes, does not possess detectable UDP-GlcNAc 2-epimerase activity
Fructose-bisphosphate aldolase class-I active site (Aldolase_I_AS)
Type: Conserved_site

Fructose-bisphosphate aldolase (

) is a glycolytic enzyme that catalyses the reversible aldol cleavage or condensation of fructose-1,6-bisphosphate into dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate. There are two classes of fructose-bisphosphate aldolases with different catalytic mechanisms: class I enzymes do not require a metal ion, and are characterised by the formation of a Schiff base intermediate between a highly conserved active site lysine and a substrate carbonyl group, while the class II enzymes require an active-site divalent metal ion. This entry represents the class I enzymes.

In vertebrates, three forms of this enzyme are found: aldolase A is expressed in muscle, aldolase B in liver, kidney, stomach and intestine, and aldolase C in brain, heart and ovary. The different isozymes have different catalytic functions: aldolases A and C are mainly involved in glycolysis, while aldolase B is involved in both glycolysis and gluconeogenesis. Defects in aldolase A cause Glycogen storage disease 12 (GSD12) , while defects in aldolase B result in hereditary fructose intolerance .

This conserved site represents the sequence around the lysine involved in the Schiff-base.
Centriole, cilia and spindle-associated protein (CSAP)
Type: Family

In zebrafish, CSAP (centriole, cilia and spindle-associated protein) plays a role in embryonic development, including proper left-right asymmetry formation. In human tissue culture cells it colocalises with polyglutamylated tubulin to centrioles, spindle microtubules, and cilia .
Nephrocystin-4 (NPHP4)
Type: Family

All nephrocystin proteins (NPHPs) localise to primary cilia, which are critical regulators of several cell signalling pathways for embryonic development and tissue homeostasis.
Transmembrane protein 179B (TMEM179B)
Type: Family

This family of transmembrane proteins is functionally uncharacterised.
Ribonuclease MRP subunit P24-like (Rmp24-like)
Type: Family

This protein family includes human Ribonuclease MRP subunit P24 (Rmp24, also known as C18orf21) and similar animal proteins. Rmp24 is required for the activity of human RNase MRP but not RNase P .
Nucleotide cyclase (Nucleotide_cyclase)
Type: Homologous_superfamily

A common fold is found in the adenylyl and guanylyl cyclase catalytic domain and the diguanylate cyclase (DGC or GGDEF) domain. It consists of a ferredoxin-like fold with additional secondary structures. Though the fold of the GGDEF domain is similar to adenylate cyclase, the nucleotide-binding mode is substantially different .
EFG1/Phd1/StuA family (EFG1/Phd1/StuA)
Type: Family

This entry represents a group of fugal proteins that contain a HTH APSES-type DNA-binding domain. Proteins in this entry include:

EFG1 (enhanced filamentous growth protein 1) from Candida albicans. EFG1 is a transcriptional regulator of the switch between 2 heritable states, the white and opaque states .

Transcriptional activator Phd1 and its paralog, Sok2, from Saccharomyces cerevisiae. Phd1 is a transcriptional activator that enhances pseudohyphal growth . Sok2 plays a general regulatory role in the cyclic AMP-dependent protein kinase-stimulated (PKA) signal transduction pathway by regulating the expression of genes important in growth and development .

Cell pattern formation-associated protein StuA from Emericella nidulans. StuA is required for the orderly differentiation and spatial organisation of cell types of the conidiophore .
J domain-containing protein 1-like (JDP1-like)
Type: Family

This entry represents JDP1, also known as DnaJ homologue subfamily C member 12 (DNAJC12), which is a J domain-containing protein with unknown function . Its expression in breast cancer cells is associated with its estrogen receptor status .