SII-SWORD/CoKE huggingface dataset:
cDENN domain (cDENN_dom)
Type: Domain

This entry represents the core or cDENN domain.

The tripartite DENN (Differentially Expressed in Normal and Neoplastic Cells) domain is an evolutionarily conserved protein module found in several proteins involved in Rab-mediated processes and, in some cases, regulation of MAPK (Mitogen-Activated Protein Kinase) signalling pathways and related proteins in eukaryotic organisms. The DENN domain consists of three subdomains: uDENN (upstream DENN)

, the core DENN domain

, and dDENN (downstream DENN)

, which are structurally distinct but functionally interconnected due to their roles in Rab GTPase activation. Recent studies have confirmed the DENN domain's function as a guanine nucleotide exchange factor (GEF) for Rab GTPases, facilitating the exchange of GDP for GTP to activate Rabs. This activity has been demonstrated for various DENN proteins, such as DENND1A and DENND1B, which specifically activate Rab35, and DENND2B, which serves as a GEF for Rab10 and Rab13, influencing processes like primary ciliogenesis and epithelial cancer development .

The tripartite structure of the DENN domain, comprising uDENN, DENN itself, and dDENN, features distinct patterns of sequence conservation and variable interdomain lengths that suggest functional specialisation. Structural studies have revealed conserved residues critical for Rab binding and catalytic activity, emphasising the role of DENN domains in spatially and temporally regulating membrane trafficking events . Additionally, DENN domains are often associated with other domains such as RUN

, PLAT

, which may further enhance their functional versatility in cellular signalling pathways .

Some proteins known to contain a tripartite DENN domain include:

Human mitogen-activated protein kinase activating protein containing death domain (MADD)

, orthologous to Rab3GEP

Human SET domain-binding factor 1 (SBF1)

Human DENN domain-containing protein 2B

Human C-myc promoter-binding protein

In Arabidopsis, SCD1 is a unique gene encoding for the only protein containing a complete DENN domain. SCD1 is part of a protein complex that interacts with the exocyst complex and the RabE1 family of GTPases. It is also involved in activating innate immune responses against bacteria .

Recent findings highlight the broader target spectrum of DENN domains than previously appreciated. For example, DENND2B interacts with Rab35 as both an effector and a GEF at intercellular bridges during cytokinesis. These discoveries underscore the importance of DENN domain proteins in regulating diverse cellular processes such as vesicle trafficking, signal transduction, ciliogenesis, and cancer progression .
Glycophorin (Glycophorin)
Type: Family

Proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Glycophorin A (PAS-2) and glycophorin B (PAS-3) belong to the MNS blood group system and are associated with antigens that include M/N, S/s, U, He, Mi(a), M(c), Vw, Mur, M(g), Vr, M(e), Mt(a), St(a), Ri(a), Cl(a), Ny(a), Hut, Hil, M(v), Far, Mit, Dantu, Hop, Nob, En(a), ENKT, amongst others.

Glycophorin A is the major sialoglycoprotein of the erythrocyte membrane . Structurally, glycophorin A consists of an N-terminal extracellular domain, heavily glycosylated on serine and threonine residues, followed by a transmembrane region and a C-terminal cytoplasmic domain. Other glycophorins in this entry such as Glycophorin B and Glycophorin E represent minor sialoglycoproteins in the erythrocyte membrane.
Large ribosomal subunit protein uL15, conserved site (Ribosomal_uL15_CS)
Type: Conserved_site

This entry represents a conserved region in the C-terminal section of the large ribosomal subunit protein uL15, which is found in al cellular organisms.

Large ribosomal subunit protein uL15 was previously known as L15. In Escherichia coli, L15 is known to bind the 23S rRNA. Ribosomal protein, L15 from bacteria and plant chloroplasts (nuclear-encoded) belong to this family. Vertebrate L27a, Tetrahymena thermophila L29 and fungal L27a (L29, CRP-1, CYH2) also are members of this group.

Ribosomal uL18 protein from a number of archaebacteria show homology to both the eukaryotic eL18 and eubacterial ribosomal protein uL15 , an observation which has been seen to substantiate the belief that archaea represent an evolutionary stage between bacteria and eukaryotes .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Large ribosomal subunit protein uL16, eukaryotes/archaea (Ribosomal_uL16_euk_arch)
Type: Family

This family consists of large ribosomal subunit protein uL16 from archaea and eukaryotes (in the latter were previously known as L10) .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Cytochrome b5-like heme/steroid binding domain (Cyt_B5-like_heme/steroid-bd)
Type: Domain

Cytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases . There are two homologous forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of oxidoreductases consists of the juxtaposition of a heme-binding domain homologous to that of b5 and either a flavodehydrogenase or a molybdopterin domain. These enzymes are:

Lactate dehydrogenase (EC 1.1.2.3) , an enzyme that consists of a flavodehydrogenase domain and a heme-binding domain called cytochrome b2.

Nitrate reductase (EC 1.7.1.-), a key enzyme involved in the first step of nitrate assimilation in plants, fungi and bacteria . Consists of a molybdopterin domain, a heme-binding domain called cytochrome b557, as well as a cytochrome reductase domain.

Sulfite oxidase (EC 1.8.3.1) , which catalyses the terminal reaction in the oxidative degradation of sulfur-containing amino acids. Also consists of a molybdopterin domain and a heme-binding domain.

Yeast acyl-CoA desaturase 1 (EC 1.14.19.1; gene OLE1). This enzyme contains a C-terminal heme-binding domain.

Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.

Proteins containing a cytochrome b5-like domain also include:

TU-36B, a Drosophila muscle protein of unknown function .

Fission yeast hypothetical protein SpAC1F12.10c (C1F12.10c).

Yeast Irc21 (YMR073c), a putative protein with unknown function.
Phosducin (Phosducin)
Type: Family

The outer and inner segments of vertebrate rod photoreceptor cells contain phosducin, a soluble phosphoprotein that complexes with the beta/gamma-subunits of the GTP-binding protein, transducin. Light-induced changes in cyclic nucleotide levels modulate the phosphorylation of phosducin by protein kinase A . The protein is thought to participate in the regulation of visual phototransduction or in the integration of photo-receptor metabolism. Similar proteins have been isolated from the pineal gland and it is believed that the functional role of the protein is the same in both retina and pineal gland .
WW domain (WW_dom)
Type: Domain

The WW domain is a short conserved region in a number of unrelated proteins, which folds as a stable, triple stranded β-sheet. This short domain of approximately 40 amino acids, may be repeated up to four times in some proteins . The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a conserved Pro. The WW domain binds to proteins with particular proline-motifs, [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs . It is frequently associated with other domains typical for proteins in signal transduction processes.

A large variety of proteins containing the WW domain are known. These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein of unknown function; vertebrate YAP protein, substrate of an unknown serine kinase; Mus musculus (Mouse) NEDD-4, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae (Baker's yeast) RSP5, similar to NEDD-4 in its molecular organisation; Rattus norvegicus (Rat) FE65, a transcription-factor activator expressed preferentially in liver; Nicotiana tabacum (Common tobacco) DB10 protein, amongst others.
Aldehyde ferredoxin oxidoreductase, C-terminal (OxRdtase_Ald_Fedxn_C)
Type: Domain

This entry represents the C-terminal region of the the aldehyde ferredoxin oxidoreductase (AOR) family enzymes, containing the α-helical structural domains 2 and 3 .

Enzymes of the aldehyde ferredoxin oxidoreductase (AOR) family contain a tungsten cofactor and an 4Fe4S cluster and catalyse the interconversion of aldehydes to carboxylates . This family includes AOR, formaldehyde ferredoxin oxidoreductase (FOR), glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), all isolated from hyperthermophilic archea ; carboxylic acid reductase found in clostridia ; and hydroxycarboxylate viologen oxidoreductase from Proteus vulgaris, the sole member of the AOR family containing molybdenum . GAPOR may be involved in glycolysis , but the functions of the other proteins are not yet clear. AOR has been proposed to be the primary enzyme responsible for oxidising the aldehydes that are produced by the 2-keto acid oxidoreductases .
Phosphate transporter (Phos_transporter)
Type: Family

The PHO-4 family of transporters includes the phosphate-repressible phosphate permease (PHO-4) from Neurospora crassa, which is probably a sodium-phosphate symporter and the Low-affinity inorganic phosphate transporter PitA from Escherichia coli, whose activity impacts bacterial growth in low Mg2+ conditions . This family also includes the human leukemia virus receptor .
RNA-directed RNA polymerase, C-terminal domain (RNA-dir_pol_C)
Type: Domain

This entry represents the C-terminal domain of the RNA-directed RNA polymerase (RdRp) found in many positive strand RNA eukaryotic viruses. It is part of the genome polyprotein that contains other polypeptides such as coat proteins VP1 to VP4, core proteins P2A to P2C and P3A, genome-linked protein VPG and picornain 3C (

).

Structural studies indicate that these proteins form the "right hand" structure found in all oligonucleotide polymerases, containing thumb, finger and palm domains, and also the additional bridging finger and thumb domains unique to RNA-directed RNA polymerases .

Remdesivir, a recent treatment approved for Covid-19 disease, directly interacts with this region of the RdRp (NSP12) from SARS-CoV-2 and explains its mechanism of action via delayed-chain termination .
Diacylglycerol kinase, catalytic domain (Diacylglycerol_kinase_cat_dom)
Type: Domain

The DAG-kinase catalytic domain or DAGKc domain is present in mammalian lipid kinases, such as diacylglycerol (DAG), ceramide and sphingosine kinases, as well as in related bacterial proteins . Eukaryotic DAG-kinase (

) catalyses the phosphorylation of DAG to phosphatidic acid, thus modulating the balance between the two signaling lipids. At least ten different isoforms have been identified in mammals, which form 5 groups characterised by different functional domains, such as the calcium-binding EF hand (see

), PH (see

), SAM (see

) , DAG/PE-binding C1 domain (see

) and ankyrin repeats (see

) .
Transposase, mutator type (Transposase_mutator)
Type: Family

Autonomous mobile genetic elements such as transposon or insertion sequences (IS) encode an enzyme, transposase, that is required for excising and inserting the mobile element. Transposases have been grouped into various families . The mutator family of transposases consists of a number of elements that include, mutator from maize, IsT2 from Thiobacillus ferrooxidans, Is256 from Staphylococcus aureus, Is1201 from Lactobacillus helveticus, Is1081 from Mycobacterium bovis, IsRm3 from Rhizobium meliloti and others.
MCM domain (MCM_dom)
Type: Domain

Proteins shown to be required for the initiation of eukaryotic DNA replication share a highly conserved domain of about 210 amino-acid residues . The latter shows some similarities with that of various other families of DNA-dependent ATPases. Eukaryotes seem to possess a family of eight proteins that contain this domain. They were first identified in yeast where most of them have a direct role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called 'minichromosome maintenance proteins' with gene symbols prefixed by MCM. These six proteins are:

MCM2, also known as cdc19 (in S.pombe).

MCM3, also known as DNA polymerase alpha holoenzyme-associated protein P1, RLF beta subunit or ROA.

MCM4, also known as CDC54, cdc21 (in S.pombe) or dpa (in Drosophila).

MCM5, also known as CDC46 or nda4 (in S.pombe).

MCM6, also known as mis5 (in S.pombe).

MCM7, also known as CDC47 or Prolifera (in A.thaliana).

MCM8, also known as as REC (in Drosophila).

MCM

These proteins are evolutionarily related and belong to the AAA+ superfamily. They contain the Mcm family domain, which includes motifs that are required for ATP hydrolysis (such as the Walker A and B, and R-finger motifs). Mcm2-7 forms a hexameric complex which is the replicative helicase involved in replication initiation and elongation, whereas Mcm8 and Mcm9 from and separate one, conserved among many eukaryotes except yeast and C. elegans. Mcm8/9 complex play a role during replication elongation or recombination, being involved in the repair of double-stranded DNA breaks and DNA interstrand cross-links by homologous recombination. Drosophila is the only organism that has MCM8 without MCM9, involved in meiotic recombination .
Small ribosomal subunit protein uS14 (Ribosomal_uS14)
Type: Family

uS14 is one of the proteins from the small ribosomal subunit. In Escherichia coli, uS14 is known to be required for the assembly of 30S particles and may also be responsible for determining the conformation of 16S rRNA at the A site. It belongs to a family of ribosomal proteins that include bacterial, algal and plant chloroplast uS14, cyanelle uS14, archaebacteria Methanococcus vannielii uS14, as well as yeast mitochondrial MRP2, yeast RPS29A/B, and mammalian RPS29.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Small ribosomal subunit protein eS17 (Ribosomal_eS17)
Type: Family

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped in this family of ribosomal proteins, eS17 (RPS17) . They include, vertebrate, Drosophila and Neurospora crassa (crp-3) eS17's as well as yeast eS17a (RP51A) and eS17b (RP51B) and archaebacterial eS17 .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .