SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase, 7kDa polypeptide, chordopoxviral (RNA_pol_7kDa_chordopoxvir)
Type: Family

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

This family consists of several Chordopoxvirus DNA-directed RNA polymerase 7kDa polypeptide sequences. DNA-dependent RNA polymerase catalyses the transcription of DNA into RNA .
Chorion S36/S38 (Chorion_S36/S28)
Type: Family

This family consists Drosophila chorion proteins S36 and S38, which are involved in chorion membrane formation. The proteins consist of a central domain and two flanking 'arms'. The central domain contains tandemly repetitive peptides, which apparently generate a secondary structure of β-sheet strands alternating with β-turns, most probably, forming a twisted β-pleated sheet or β-barrel .
Chorion S16 (Chorion_S16)
Type: Family

Correct eggshell formation relies on a complex series of events that relies on expression, cleavage and transport of various proteins at appropriate times. In Drosophila, the eggshell framework is laid down between the developing oocyte and the overlying follicle cells during late oogenesis. Five distinct layers are observed in Drosophila eggshells: the oocyte proximal vitelline membrane, a lipid wax layer, the inner chorion layer, the endochorion and exochorion layers .

The inner chorion layer is continuous and characterised by its periodic structure. Genes encoding chorion proteins are expressed from oocyte development stage 11 onwards. Chorion synthesis occurs during the last 5-6 hours of oogenesis and demands the production of large amounts of protein. Amplification of the two chorion gene clusters meets demand for large scale protein production and expression is precisely regulated through tight transcriptional control of the chorion genes. Chorion proteins may be described according to the times at which they are expressed in the follicular cells: developmentally early (s36, s38), middle (s19, s16) or late (s18, s15).

This family consists of several examples of the Drosophila melanogaster specific chorion protein S16. The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary .
Chromadorea ALT (Chromadorea_ALT)
Type: Family

This family consists of several ALT protein homologues found in nematodes. Lymphatic filariasis is a major tropical disease caused by the mosquito borne nematodes Brugia and Wuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. ALT-1 and the closely related ALT-2 have been found to be strong candidates for a future vaccine against Homo sapiens filariasis .
Citrus tristeza virus P18 (CTV_P18)
Type: Family

This family contains the P18 proteins of citrus tristeza virus (CTV). CTV is a member of the closterovirus group and is one of the more complex single-stranded RNA viruses. Assembly of the viral genome into virions is a critical process of the virus life cycle often defining the ability of the virus to move within the plant and to be transmitted horizontally to other plants. Closteroviridae virions are polar helical rods assembled primarily by a major coat protein, but with a related minor coat protein at one end. It is the only virus family that encodes a protein with similarity to cellular chaperones, a 70kDa heat-shock protein homologue (HSP70h). Deletion mutagenesis reveals that p33, p6, p18, p13, p20, and p23 genes are not needed for virion formation. Their function is unknown .
Clavanin (Clavanin)
Type: Family

This family consists of clavanin proteins from the haemocytes of the invertebrate Styela clava (Sea squirt), a solitary tunicate. The family is made up of four α-helical antimicrobial peptides, clavanins A, B, C and D. The tunicate peptides resemble magainins in size, primary sequence and antibacterial activity. Synthetic clavanin A displays comparable antimicrobial activity to magainins and cecropins. The presence of α-helical antimicrobial peptides in the haemocytes of a urochordate suggests that such peptides are primeval effectors of innate immunity in the vertebrate lineage .
Collagen-binding surface protein Cna-like, B-type domain (Collagen-bd_Cna-like_B-typ_dom)
Type: Domain

This entry represents a repeated B region domain found in the collagen-binding surface protein Cna in Staphylococcus aureus, as well as other related domains. Cna has a non-repetitive, collagen-binding A region

, followed by instances of this B region repetitive unit. The B region has one to four 23kDa repeat units (B1-B4) each with a prealbumin-like β-sandwich fold of seven strands in two sheets with a Greek key topology . Each B repeat unit has two highly similar domains (D1 and D2) placed side-by-side; both D1 and D2 are included in this entry. The domain appears to form a stalk that presents the ligand binding domain away from the bacterial cell surface. Cna is a collagen-binding MSCRAMM (Microbial Surface Component Recognizing Adhesive Matrix Molecules), and is necessary and sufficient for S. aureus cells to adhere to cartilage .
HssA/B family related (HssA/B-related)
Type: Family

This entry include a group of Dictyostelium discoideum (Slime mould) proteins, including hssA/B proteins. HssA (also known as NK20) is a high-glycine-serine-rich small protein (8.37kDa), which has strong homology to previously reported cyclic-adenosine-monophosphate-inducible 2C and 7E proteins . This protein may form extended coil structures . The serine-rich chaperone protein 1 (hssl63) suppresses aggregation of proteins with long polyglutamine tracts by protoming their degradation by the proteasome .
Collagen binding domain (Collagen-bd_dom)
Type: Domain

The domain fold is a jelly-roll, composed of two antiparallel β-sheets and two short α-helices . A groove on β-sheet I exhibited the best surface complementarity to the collagen. This site partially overlaps with the peptide sequence previously shown to be critical for collagen binding. Recombinant proteins containing single amino acid mutations designed to disrupt the surface of the putative binding site exhibited significantly lower affinities for collagen.
Copper resistance protein D domain (Cu-R_CopD_dom)
Type: Domain

Copper sequestering activity displayed by some bacteria is determined by copper-binding protein products of the copper resistance operon (cop). CopD, together with CopC, perform copper uptake into the cytoplasm .
Accessory protein 5b, avian coronavirus (Acc_prot_5b_avian_CoV)
Type: Family

Avian infectious bronchitis virus, a member of Coronaviridae family, has a single-stranded positive-sense RNA genome, which is 27 kb in length. Gene 5 contains two (5a and 5b) open reading frames . This entry represents the host translation inhibitor 5b (ORF 5b, also known as accessory protein 5b) which is involved in host translation shut off without degrading host RNA. It suppresses host gene expression which facilitates evasion from host type I interferon immune response .
Lycopene cyclase (CrtY)
Type: Family

Lycopene cyclases generate provitamin A carotenoids which are essential building blocks for cyclic xanthophylls involved in photosynthesis and regulatory networks. The cyclization of lycopene is the final step in carotenoid biosynthesis and may proceed via one of two pathways: the formation of a β-ring by beta-cyclase, or an ε-ring by epsilon-cyclase. Epsilon-cyclase adds only one ring, forming the monocyclic δ-carotene, whereas beta-cyclase introduces a ring at both ends of lycopene to form the bicyclic β-carotene . Lycopene cyclases are widely distributed across taxonomic groups and have structural diversity. Four partly related families of lycopene cyclases are known: CrtY, CrtL (β-ionone end group producing), CrtL (η-ionone end group producing) and CrtL (capsanthin/capsorubin synthase).

This family consists of several bacterial Lycopene cyclase (CrtY) proteins (also known as Lycopene beta-cyclase). Lycopene cyclase is a key enzyme which converts the acyclic carotenoid lycopene into the cyclic carotenoid β-carotene . It is thought that CrtY lycopene cyclases use reduced flavin adenine dinucleotide (redFAD) as a cofactor, which provides stabilisation of a positively charged or partially positively charged intermediate . Lycopene cyclase is a non-redox flavoprotein.
CsbD-like domain (CsbD)
Type: Domain

CsbD is a bacterial general stress response protein. Its expression is mediated by sigma-B, an alternative sigma factor . The exact role of CsbD in stress response is unclear.

This entry represents CsbD, and related proteins.
Transcriptional regulator CtsR (CtsR)
Type: Family

This family consists of several transcriptional repressor of class III stress gene (CtsR) proteins, mainly from Firmicute species. CtsR of Listeria monocytogenes negatively regulates the clpC, clpP and clpE genes belonging to the CtsR regulon .
Cypovirus polyhedrin, Cypovirus 1 type (Cypo_polyhedrin_Cypovirus1)
Type: Family

This family consists of several Cypovirus polyhedrin proteins mostly from Cypovirus 1. Polyhedrin is known to form a crystalline matrix (polyhedra) in infected insect cells .
Dystroglycan, C-terminal (DAG1_C)
Type: Domain

Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in Homo sapiens. The protein product is cleaved into two non-covalently associated subunits, [alpha] (N-terminal) and [beta] (C-terminal). In skeletal muscle the dystroglycan complex works as a transmembrane linkage between the extracellular matrix and the cytoskeleton [alpha]-dystroglycan is extracellular and binds to merosin ([alpha]-2 laminin) in the basement membrane, while [beta]-dystroglycan is a transmembrane protein and binds to dystrophin, which is a large rod-like cytoskeletal protein, absent in Duchenne muscular dystrophy patients. Dystrophin binds to intracellular actin cables. In this way, the dystroglycan complex, which links the extracellular matrix to the intracellular actin cables, is thought to provide structural integrity in muscle tissues .

The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. There is also evidence which suggests the function of dystroglycan as a part of the signal transduction pathway because it is shown that Grb2, a mediator of the Ras-related signal pathway, can interact with the cytoplasmic domain of dystroglycan. In general, aberrant expression of dystrophin-associated protein complex underlies the pathogenesis of Duchenne muscular dystrophy, Becker muscular dystrophy and severe childhood autosomal recessive muscular dystrophy. Interestingly, no genetic disease has been described for either [alpha]- or [beta]-dystroglycan.

Dystroglycan is widely distributed in non-muscle tissues as well as in muscle tissues. During epithelial morphogenesis of kidney, the dystroglycan complex is shown to act as a receptor for the basement membrane. Dystroglycan expression in Mus musculus brain and neural retina has also been reported. However, the physiological role of dystroglycan in non-muscle tissues has remained unclear .
Protein phosphatase inhibitor 1 (PPP1R1A/B/C)
Type: Family

This entry represents the protein phosphatase inhibitor 1 (IPP-1) family, which consists of PPP1R1A/B/C. They are involved in signal transduction and are endogenous inhibitors of protein phosphatase-1 . PPP1R1B, also known as DARPP-32, has a key role in many neurotransmitter pathways throughout the brain and has been shown to be involved in controlling receptors, ion channels and other physiological factors including the brain's response to drugs of abuse, such as cocaine, opiates and nicotine. If phosphorylated, DARPP-32 can inhibit protein-phosphatase-1 . DARPP-32 is reciprocally regulated by the two neurotransmitters that are most often implicated in schizophrenia - dopamine and glutamate. Dopamine activates DARPP-32 through the D1 receptor pathway and disables DARPP-32 through the D2 receptor. Glutamate, acting through the N-methyl-d-aspartate receptor, renders DARPP-32 inactive. A mutant form of DARPP-32 has been linked with gastric cancers .
Dynein 1 light intermediate chain (Dynein1_light_intermed_chain)
Type: Family

Cytoplasmic dynein is a large multisubunit complex involved in retrograde transport and the positioning of various organelles. The light intermediate chains (LICs) of cytoplasmic dynein consist of multiple isoforms, which undergo post-translational modification to produce a large number of species. Proteins in this entry include Dil1 from fission yeasts and DC1L1/2 from mammals. DC1L1 is required for progress through the spindle assembly checkpoint .
DNA methyltransferase 1-associated 1 (DMAP1)
Type: Domain

This entry represents a domain found in DNA methyltransferase 1-associated protein 1 (DMAP1).
DREPP family (DREPP)
Type: Family

This family contains several plant plasma membrane proteins termed DREPPs as they are developmentally regulated plasma membrane polypeptides , including the salt stress root protein RS1 and plasma membrane-associated cation-binding protein 1 (PCAP1). DREPPs are thought to be signal proteins .
Uncharacterised protein family Ycf33 (Uncharacterised_Ycf33)
Type: Family

This family, Ycf33, contains several plant, cyanobacterial and algal chlorplast encoded proteins of unknown function. The family is exclusively found in phototrophic organisms and may therefore play a role in photosynthesis.
MnmC-like methyltransferase (MnmC-like_methylTransf)
Type: Domain

This domain represents a S-adenosyl-L-methionine (SAM)-dependent methyltransferase. It is often found in association with

in the bifunctional enzyme MnmC, where it is responsible for catalysing the transfer of a methyl group from S-adenosyl-L-methionine to 5-aminomethyl-2-thiouridine to form 5-methylaminomethyl-2-thiouridine .
Domain of unknown function DUF753 (DUF753)
Type: Domain

This entry contains sequences which are repeated in several uncharacterised proteins from Drosophila melanogaster.
Putative 3TM holin, Phage holin 3 (Phage_holin_3_7)
Type: Family

This is a family of putative proteobacterial phage three-transmembrane-domain holins.
Protein of unknown function DUF755 (DUF755)
Type: Domain

This family is predominated by ORFs from Anelloviridae. The function of this family remains to be determined.
Bacterial phospholipase C, C-terminal domain (PLipase_C_C)
Type: Domain

This domain is found, normally as a tandem repeat, at the C terminus of bacterial phospholipase C proteins.
Protein PBDC1, metazoa/fungi (PBDC1_metazoa/fungi)
Type: Family

This entry represents the family of protein PBDC1 (polysaccharide biosynthesis domain-containing protein 1). Proteins in this entry are from fungi and animals. The budding yeast PBDC1 homologue is known as YPL225W.

Protein PBDC1 homolog from S. cerevisiae also known as Ypl225w (Chp1, Chaperone 1 for eEF1A) functions as a co-translational chaperone by forming dual interactions with the eEF1A G domain nascent chain and the UBA domain of ribosome-bound nascent polypeptide-associated complex . This protein primes the eEF1A nascent chains for binding to GTP as part of a folding mechanism which is tightly coupled to chaperone recycling .
Tumor necrosis factor alpha-induced protein 8-like (TNFAIP8-like)
Type: Family

Four tumor necrosis factor alpha-induced protein 8-like proteins have been identified: TNFAIP8 (also known as TIPE), TIPE1, TIPE2 and TIPE3. Overexpressed TIPE in cells can reduce cell death in vitro and increase tumor growth in vivo . By contrast, TIPE2 has been demonstrated to be an inhibitor of Ras and to have a pro-apoptotic ability. TIPE1 could upregulate the pro-apoptotic members of the B-cell leukemia/lymphoma (Bcl)-2 family of proteins .
Protein of unknown function DUF759, Borrelia species (DUF759_BOR_spp)
Type: Family

This entry consists of several uncharacterised proteins from Borrelia species including Borrelia burgdorferi and Borrelia garinii.
Protein of unknown function DUF760 (DUF760)
Type: Family

This entry represents a family of uncharacterised proteins, including chloroplastic UV-B-induced protein At3g17800 from Arabidopsis.
Protein of unknown function DUF761, plant (DUF761_pln)
Type: Family

This family consists of several plant proteins of unknown function, including pathogen-associated molecular patterns-induced protein A70 from Arabidopsis thaliana, which is induced during Pseudomonas syringae infection by jasmonic acid and wounding .
Protein of unknown function DUF762, Coxiella burnetii (DUF762_COXBU)
Type: Family

This family consists several of several uncharacterised proteins from the bacterium Coxiella burnetii. C. burnetii is the causative agent of the Q fever disease.
Protein of unknown function DUF763 (DUF763)
Type: Family

This family consists of several uncharacterised bacterial and archaeal proteins of unknown function.
Protein of unknown function DUF764, Borrelia species (DUF764_BOR_spp)
Type: Family

This entry consists of several uncharacterised proteins from Borrelia species including Borrelia burgdorferi and Borrelia garinii.
Circovirus Orf6 (Circovirus_Orf6)
Type: Family

This family consists of several short (27-30aa) porcine and bovine circovirus ORF6 proteins of unknown function.
JNK1/MAPK8-associated membrane protein (JAMP)
Type: Family

JAMP is a Jun N-terminal kinase 1 (JNK1)-associated membrane protein. It associates with JNK1 through its C-terminal domain and regulates the duration of JNK1 activity in response to diverse stress stimuli . It is an important component for coordinated clearance of misfolded proteins from the ER .
Protein of unknown function DUF768 (DUF768)
Type: Family

This family consists of several uncharacterised hypothetical proteins mostly from alphaproteobacteria.
Protein of unknown function DUF769 (DUF769)
Type: Family

This family consists of several uncharacterised hypothetical proteins of unknown function from Xylella fastidiosa, the organism that causes Pierce's disease in plants.
Protein of unknown function DUF771 (DUF771)
Type: Family

This entry includes Bacteriophage bIL285, Orf7. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This entry consists of uncharacterised ORFs found in Bacteriophage and Lactococcus lactis.
Transposase InsH, N-terminal (Transposase_InsH_N)
Type: Domain

This presumed domain is found at the N terminus of Transposase InsH for insertion sequence element IS5A from Escherichia coli (strain K12) and other related transposases found in bacteria and archaea.
CDK5 regulatory subunit-associated protein 3 (CDK5RAP3)
Type: Family

CDK5RAP3 (also known as C53 or LZAP) serves as a probable tumour suppressor initially identified as a CDK5R1 interactor controlling cell proliferation . It negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation . It also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint . It has been shown to bind Wip1 and stimulates its phosphatase activity .
Rv2714-like (Rv2714-like)
Type: Family

This family, previously known as DUF774, consists of uncharacterised proteins predominantly found in Actinomycetes, including Rv2714 (

) from Mycobacterium tuberculosis. This protein adopts a trimeric configuration, in which each monomer is organised into two domains: a central β-sheet of eight strands flanked by three α-helices at the N-terminal and four α-helices at the C-terminal . Members of this family were thought to be orthologues of the eukaryotic proteasome assembly chaperone 2 (PAC2), however, they don't appear to function as proteasome assembly chaperones . The function of these proteins remains unknown.
Hikeshi-like, N-terminal domain (Hikeshi-like_N)
Type: Domain

This entry represents a domain found at the N-terminal of human Hikeshi and its orthologues OPI10 from other eukaryotes. Hikeshi acts as a specific nuclear import carrier for HSP70 proteins following heat-shock stress; it acts by mediating the nucleoporin-dependent translocation of ATP-bound HSP70 proteins into the nucleus . The N-terminal domain shows a jelly-roll/β-sandwich fold with two layers of β-sheets consisting of three and five and five antiparallel β-strands .
Protein of unknown function DUF776 (DUF776)
Type: Family

This family consists of several highly related Mus musculus and Homo sapiens proteins of unknown function.
Protein of unknown function DUF777, Borrelia species (DUF777_BOR_spp)
Type: Family

This family consists of several hypothetical proteins of unknown function, found in Borrelia burgdorferi and Borrelia garinii.
TMEM222/RTE1 (TMEM222/RTE1)
Type: Family

This entry includes TMEM222 from animals and RTE1 (REVERSION-TO-ETHYLENE SENSITIVITY1) from Arabidopsis. RTE1 is positive regulator of the ETR1 ethylene receptor . This entry also includes Arabidopsis RTE1 homologue, RTH, which acts via RTE1 in regulating ethylene responses and signaling .
Protein of unknown function DUF779 (DUF779)
Type: Family

This family consists of several bacterial proteins of unknown function.
Protein of unknown function DUF780, Caenorhabditis species (DUF780_CAE_spp)
Type: Family

This family consists of several short proteins of unknown function found in Caenorhabditis species.
Leg1 (Leg1)
Type: Family

This entry represents liver-enriched gene 1 protein (Leg1). It has been suggested that Leg1 might function as a novel secreted regulator for the liver development .
Circovirus Orf3 (Circovirus_Orf3)
Type: Family

This family consists of porcine circovirus ORF3 protein which plays a role in modulating host cell signalling by binding to and degrading host RGS16 . This protein is not necessary for virus replication .