SII-SWORD/CoKE huggingface dataset:
Zinc finger C2HC RNF-type (ZF_C2HC_RNF)
Type: Domain

This entry includes the C2HC RNF-type zinc finger.

Ubiquitination is a post-translational modification that mediates the covalent attachment of ubiquitin (Ub), a small, highly conserved, cytoplasmic protein of 76 amino acid residues, to target proteins. This conjugation is catalyzed by the sequential action of three enzymes: Ub-activating (E1) enzyme, Ub-conjugating (E2) enzyme and Ub ligase (E3). A large number of RING finger (RNF) proteins are present in eukaryotic cells and the majority of them are believed to act as E3 ubiquitin ligases. The closely related proteins RNF125/TRAC-1, RNF114 (also known as Zpf313), RNF138 (or NARF) and RNF166 contain, apart from the RING domain, a C2HC (Cys2-His-Cys)- and two C2H2 (Cys2-His2)-type zinc fingers, as well as an ubiquitin interacting motif (UIM) .

Some proteins known to contain a C2HC RNF-type zinc finger are listed below:

Mammalian RNF125/T-cell RING protein in activation 1 (TRAC-1)/, a positive regulator of T-cell activation. It negatively regulates RIG-1 mediated antiviral activity via conjugating ubiquitin chains to RIG-1 and MDA5, leading to their degradation by the proteasome.

Vertebrate RNF114, acts as negative regulator of NF-kappaB-dependent transcription. It interacts with A20 in T cells and modulates A20 ubiquitylation.

Vertebrate RNF138, likely involved in regulating homologous recombination repair pathway.

Vertebrate RNF166, potentiates the RNA virus-induced production of IFN-beta via enhancing the ubiquitination of TRAF3 and TRAF6.
NEMO, Zinc finger (NEMO_ZF)
Type: Domain

This entry represents the C-terminal CCHC-type Zinc Finger (ZF) domain of NEMO. This domain can also be found in other regulators of NF-kappaB, such as Optineurin and ABIN2 .
Zinc finger C2H2 AKAP95-type (ZF_C2H2_AKAP95)
Type: Domain

This entry represents the C2H2 AKAP95-type zinc finger.

A-kinase (or PKA)-anchoring protein AKAP95 is a member of the AKAP-family that binds to regulatory subunits of protein kinase A (PKA) and localizes PKA to various distinct locations and structures within cells. AKAP95 is a zinc-finger protein implicated in mitotic chromosome condensation by acting as a targeting molecule for the condensin complex. In addition to anchoring the regulatory subunit (RII) of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), AKAP95 binds chromatin at mitosis. It harbours two zinc fingers, designated ZF1 and ZF2. ZF1 mediates the binding of AKAP95 to DNA. ZF2 is dispensable for chromatin binding; however it may substitute for ZF1 when the latter is rendered non-functional by mutation .
Translationally controlled tumour protein (TCTP) domain (TCTP)
Type: Domain

The translationally controlled tumor proteins (TCTPs, such as p21, p23 and histamine releasing factor (HRF)) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in a variety of cellular functions, including microtubule stabilization, cell cycle, apoptosis, and cytokine release. TCTP is ubiquitously expressed in all eukaryotic organisms from protozoa such as Plasmodium sp. to plants and mammals .

The TCTP domain structure comprises four β-sheets, designated A-D, and three main helices, designated H1-H3, connected in a complex topology. A central feature of the structure is the four-stranded sheet A, against one face of which packs the three-stranded sheet B and the small helix H1. Helix H3 packs against part of the opposite face of sheet A. Helix H2 packs against helix H3 (forming an α-helical hairpin). The final major structural feature is the two-stranded sheet C, which protrudes from the core globular structure formed by the rest of the domain .

This entry represents the TCTP domain.
Inner tegument protein (HSV_ITP)
Type: Family

This entry represents the inner tegument proteins from Herpesviridae, which are involved in cytosolic trafficking of capsids .
Terpene cyclase-like 1, C-terminal domain (Terpene_cyclase-like_1_C)
Type: Domain

Enzymes in this subgroup generally have two domains, with the C-terminal domain being a member of this subgroup and the N-terminal domain being a member of the terpene cyclase-like 1 N-terminal subgroup in the isoprenoid synthase class II superfamily. It has been suggested that this gene family be designated tps (for terpene synthase). Sequence comparisons reveal similarities between the monoterpene (C10) synthases, sesquiterpene (C15) synthases and the diterpene (C20) synthases. It has been split into six subgroups on the basis of phylogeny, called Tpsa-Tpsg .
RH1 domain (RH1)
Type: Domain

This is the RILP homology 1 (RH1) protein-protein interaction domain found at the N-terminal of Rab36-binding proteins including Rab interacting lysosomal proteins (RILP), RILP1/2 NK-interacting protein 3 (JIP3) and NK-interacting protein 4 (JIP4). This domain binds to the myosin Va globular tail domain (MyoVa-GTD) .

The RH1 (RILP homology 1) protein-protein interaction domain is found in the following animal Rab36-binding proteins:

Rab interacting lysosomal proteins (RILP),

RILP-like 1 (RILP-L1),

RILP-like 2 (RILP-L2),

JNK-interacting protein 3 (JIP3),

JNK-interacting protein 4 (JIP4).

It binds to the myosin Va globular tail domain (MyoVa-GTD) in mainly hydrophobic interactions.

The RH1 domain adopts an all-helical structure and forms a homodimer with a four-helix bundle conformation to interact with MyoVa-GTD. The RH1 homodimer is structurally separated into two parts, the N-terminal four-helix bundle formed by alpha2 and alpha3N and the C-terminal coiled-coil formed by alpha3C. The four-helix bundle in the RH1 dimer is mainly stabilised by forming a hydrophobic core. The N-terminal small helix (alpha1) and its following loop pack on alpha2 from the same molecule and alpha3 from the neighbouring molecule and thus contribute to the bundle stability. The RH1 homodimer is further strengthened by a coiled coil formed by the C-terminal half of the alpha3-helix .
RH2 domain (RH2)
Type: Domain

This entry represents the entire RH2 domain.

The RH2 (RILP homology 2) Rab-binding domain is found in the following animal proteins :

Rab interacting lysosomal proteins (RILP), which interacts with Rab7, Rab34, and Rab36.

RILP-like 1 (RILP-L1), which interacts with Rab12, Rab34, and Rab36.

RILP-like 2 (RILP-L2), which interacts with Rab34 and Rab36.

JNK-interacting protein 3 (JIP3), which interacts with Rab36 alone.

JNK-interacting protein 4 (JIP4), which interacts with Rab36 alone.

The RH2 domain is folded into a long helix alpha1 and a short helix alpha2 connected by a very tight loop. The RH2 domain forms a tightly associated four helices homodimer in which both helices alpha1 and alpha2 are involved in dimerisation. Such a homodimer binds to two separate Rab-GTP molecules on opposite sides, with both helices involved in the interaction with Rab. In the complex interface, although each Rab-GTP interacts with both helices of the RH2 domain, these two helices are contributed by two different molecules, with helix alpha1 coming from one protomer and helix alpha2 from the other protomer .
Deoxyuridine 5'-triphosphate nucleotidohydrolase (HSV_DUT)
Type: Family

This family of Herpesviridae deoxyuridine 5-triphosphate nucleotidohydrolases produces dUMP from dUTP, decreasing the intracellular concentration of dUTP to help avoid uracil incorporation into viral DNA .
POTRA domain (POTRA)
Type: Domain

The polypeptide-transport-associated (POTRA) domain is a module found in members of the FtsQ/DivIB, ShlB, CGI51 (with one repeat), Toc75, YTFM (with three repeats) and D15 (with five repeats) protein families. The POTRA domains are hypothesized to mediate protein-protein interactions, nucleate β-strands formation in nascent outer membrane proteins (OMPs) and have chaperone-like activity .

The POTRA domain fold comprises a three-stranded β-sheet overlaid with a pair of antiparallel helices. The order of secondary-structure elements is β-α-α-β-β; the first and second β-strands form the two edges of the sheet, with the β3 strand sandwiched between them. The conserved residues that define the POTRA domains are primarily in the hydrophobic core or loop regions, suggesting that they are important for the structural integrity of POTRA domain .

Some proteins known to contain a POTRA domain are listed below:

Escherichia coli outer membrane protein assembly factor BamA, involved in assembly and insertion of β-barrel proteins into the outer membrane.

Escherichia coli cell division protein FtsQ.

Bacillus subtilis cell division protein DivIB.

Serratia marcescens hemolysin transporter protein ShlB, a virulence-factor transporter that is present in the outer membrane.

Arabidopsis thaliana chloroplastic protein TOC75, mediates the insertion of proteins targeted to the outer membrane of chloroplasts.

Human sorting and assembly machinery component 50 (SAM50), plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes.
Exonuclease I, SH3-like domain (EXOI_SH3)
Type: Domain

In bacteria, exonuclease I (ExoI) is a monomeric processive 3'-5' exonuclease that degrades single-stranded DNA. The enzyme has been implicated as primarily being involved in repairing frameshift mutations. ExoI consists of three domains: an N-terminal nuclease domain with homology to the proofreading domain of E. coli DNA polymerase I and other DnaQ superfamily enzymes, a central domain with a portion that resembles an SH3 domain fold and a C- terminal α-helical domain. While a typical SH3-like domain consists of five or six antiparallel β-strands that form a compact β-sandwich, the β-sandwich of the SH3-like domain in ExoI is surrounded by α-helices, resulting in a substantially elaborated fold .

This entry represents the ExoI SH3-like domain.
Exonuclease I, C-terminal alpha-helical domain (EXOI_C)
Type: Domain

In bacteria, exonuclease I (ExoI) is a monomeric processive 3'-5' exonuclease that degrades single-stranded DNA. The enzyme has been implicated as primarily being involved in repairing frameshift mutations. ExoI consists of three domains: an N-terminal nuclease domain with homology to the proofreading domain of E. coli DNA polymereae I and other DnaQ superfamily enzymes, a central domain with a portion that resembles an SH3 domain fold and a C- terminal α-helical domain. While a typical SH3-like domain consists of five or six antiparallel β-strands that form a compact β-sandwich, the β-sandwich of the SH3-like domain in ExoI is surrounded by α-helices, resulting in a substantially elaborated fold .

This entry represents the ExoI C-terminal α-helical domain.
DNA-directed DNA polymerase T4 type (DPOL_T4)
Type: Family

This entry represents a family of DNA-directed DNA polymerases. In bacteriophage T4, the enzyme has been shown to be part of a multienzyme complex required for the synthesis of DNA . The enzymes also posses exonuclease activity and are able to to proofread misincorporated nucleotides .
CULT domain (CULT)
Type: Domain

The cereblon protein, originally identified in a screen for mutations causing mild mental retardation, is a major target of thalidomide and its derivatives, and is responsible for the teratogenic effects of the drug. Cereblon owes its name to its involvement in brain development and to its Lon N-terminal domain. Cereblon proteins occur throughout eukaryotes, however not in fungi. Cereblon is a cofactor of damaged DNA-binding protein 1 (DDB1), which acts as the central component of an E3 ubiquitin ligase complex and regulates the selective degradation of key proteins in DNA repair, replication and transcription. Binding of thalidomide to a C-terminal region in cereblon alters the E3 ubiquitin ligase activity of the complex, which may in turn cause its teratogenic effects. The thalidomide-binding region of cereblon is a conserved domain, CULT (for Cereblon domain of Unknown activity, binding cellular Ligands and Thalidomide), carrying several invariant cysteine and tryptophan residues. The CULT domain is also found as the sole domain in a family of secreted proteins from animals and in a family of bacterial proteins occurring primarily in gamma-proteobacteria. Given the invariant nature of the CULT domain between animals and bacteria, a natural ligand universal to all domains of life seems plausible. The nature of the binding pocket, an aromatic cage of three tryptophan residues, suggests a role in the recognition of cationic ligands .

The CULT domain is a member of the β-tent fold, which consists of two four-stranded, antiparallel β-sheets that are oriented at an approximately right angle and pinned together at the top via a structural zinc ion. The thalidomide binding site is formed within the larger, C-terminal β-sheet. A third of the domain, including the thalidomide binding pocket, only folds upon ligand binding .
Yippee domain (Yippee)
Type: Domain

The Yippee-like (YPEL) family proteins share homology to drosophila Yippee, a zinc finger binding protein. YPEL proteins are found in essentiallly all the eukaryotes and hence they must play important roles in the maintenance of life. Subcellular localization of all YPEL proteins to the centrosomes and the mitotic apparatus suggest their role in the mitosis-associated function. YPEL proteins contain a Yippee domain, which is a putative zinc-finger-like, metal-binding domain .

The Yippee domain contains two cysteine pairs that are fifty-two amino acids appart (C-X(2)-C-X(52)-C-X(2)-C) and could be part of a metal (zinc) binding pocket .
Mis18 domain (Mis18)
Type: Domain

The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Centromere protein A (CENP-A) is a histone H3 variant and an essential component of centromeres. Mis18 proteins are involved in the priming of centromeres for recruitment of CENP-A. They possess two structurally distinct domains: an N-terminal globular domain mainly comprised of β-strands and a C-terminal α-helical domain. The oligomerization of Mis18, mediated by its conserved N-terminal globular domain, is crucial for its centromere localization and function .

The Mis18 domain is mainly comprised of β-strands and has two conserved C-x-x-C motifs, which are signatures motifs present in metal
ion-binding proteins. The overall fold of the Mis18 domain is formed by antiparallel β-sheets: a three stranded (β1-β2-β9: β-sheet I)
and a six stranded (β3-β4-β8-β7-β6-βa5: β-sheet II) sheet, arranged approximately perpendicular to each other. The two β-sheets are held together by a Zn(2+) ion coordinated via the C-x-x-C motifs from loops L1 and L5. The Mis18 domain contains a cradle-shaped pocket that is implicated in
protein/nucleic acid binding, which is required for Mis18 function .
hSac2 domain (hSac2)
Type: Domain

Sac2 is an evolutionary conserved protein in multicellular organisms from nematode to human. Sac2 orthologues are also found in fungi genera such as Aspergillus species and Yarrowia lipolytica, but is absent in Saccharomyces cerevisiae. Sac2 is a phosphatidylinositol (PI) 4-phosphatase that specifically hydrolyzes phosphatidylinositol 4-phosphate (PI(4)P) to phosphatidylinositol. Besides the conserved N-terminal Sac1 domain, Sac2 contains a unique homology domain, homology Sac2 (hSac2), followed by a proline-rich C-terminal portion with various lengths in different species. The hSac2 domain plays a role in Sac2 dimerization and intracellular localization. The hSac2 domain is also found in proteins encoded by the transformation-related protein 63 regulated 1 (TPRG1) and the tumor protein p63 regulated gene 1-like genes (TPRG1L) .

The hSac2 domain has a PH domain-like fold and consists of a core of two perpendicularly apposed β sheets with a C-terminal α helix that seals the gap between the two sheets. In addition to the core, hSac2 has an extra N-terminal α helix and a short β strand in the C-terminal end .
Gemini of Cajal bodies-associated protein 8 (GEMIN8)
Type: Family

GEMIN8 proteins are found in the nuclear bodies called gems (Gemini of Cajal bodies) that are often in proximity to Cajal (coiled) bodies themselves. They are also found in the cytoplasm . The family is part of the SMN (survival motor neurone) complex that plays an essential role in spliceosomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing in the nucleus. GEMIN8 binds directly to SMN1 and mediates the interaction of the GEMIN6-GEMIN7 heterodimer .
Type II secretion system (T2SS), protein M subtype b (T2SSM_b)
Type: Family

The T2SMb family is conserved in Proteobacteria and Actinobacteria, and differs from the T2SM proteins in Vibrio spp.
Ornithine aminotransferase, bacterial type (Ornith_aminotrans_bact)
Type: Family

This entry represents bacterial ornithine aminotransferase, which catalyzes the interconversion of ornithine to glutamate semialdehyde and is a control for arginine catabolism .
Peptidyl-tRNA hydrolase, archaea (Pept_tRNA_hydro_arch)
Type: Family

Peptidyl-tRNA hydrolases are enzymes that release tRNAs from peptidyl-tRNA during translation .

This entry represents peptidyl-tRNA hydrolase from archaea.
Venom allergen 3, insect (P14a_insect)
Type: Family

Venom allergen 3 from the fire ant
Solenopsis invicta
causes an allergic reaction, and is the commonest cause of insect-related venome allergy in the south-eastern United States . The tertiary structure has been solved . This entry also includes allergen Tab y 5.0101 from horsefly salivary glands and several Tabinhibitin proteins and antigen 5 like allergen Cul n 1 from biting midge salivary glands .
Nucleoside transporter ENT1/ENT2 (ENT1/ENT2)
Type: Family

This entry represents equilibrative nucleoside transporters (ENT) 1 and 2 in eukaryotic organisms. Both ENT 1 and 2 import and export nucleosides across the membrane (equilibrative transportation). ENT1 (also known as Slc29a1) is inhibited by low concentrations of nitrobenzylmercaptopurine riboside (NBMPR), whereas ENT2 (also known as Slc29a2) is much less sensitive . This entry also includes adenoside transporters in yeast.

Nucleosides are hydrophilic molecules and require specialised transport proteins for permeation of cell membranes. There are two types of nucleoside transport processes: equilibrative bidirectional processes driven by chemical gradients and inwardly directed concentrative processes driven by an electrochemical gradient . The two types of nucleoside transporters are classified into two families: the solute carrier (SLC) 29 and SLC28 families, corresponding to equilibrative and concentrative nucleoside transporters, respectively .

Equilibrative nucleoside transporters (ENTs) are integral membrane proteins which enable the movement of hydrophilic nucleosides and nucleoside analogues down their concentration gradients across cell membranes. ENT family members have been identified in humans, mice, fish, tunicates, slime molds, and bacteria .
WhiB-like iron-sulfur binding domain (4FE4S_WBL)
Type: Domain

Members of the WhiB-like (Wbl) family are found in actinobacteria and are implicated in the regulation of developmental processes. All WhiB- like proteins have four conserved cysteine residues where two of them are in a C-X-X-C motif. The four cysteine residues are proposed to act as the ligands for a [4Fe-4S] cluster. Wbl-mediated transcription regulation is dependent upon the presence or absence and state (nitrosylated or non-nitrosylated) of the [4Fe-4S] cluster .

This entry represents the Wbl-type 4Fe-4S domain.
Cleavage and polyadenylation specificity factor subunit 6, RNA recognition motif (CPSF6_RRM)
Type: Domain

This entry represents the N-terminal RNA recognition motif (RRM) of CPSF6, which mediates the interaction with the cleavage factor CFIm25 in human. It also serves to enhance RNA binding and facilitate RNA looping .

CPSF6, also known as CFIm68, is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation . It has been shown to bind HIV-1 capsid and connect HIV-1 preintegration complexes to intranuclear trafficking pathways that link integration to transcriptionally active chromatin .
CPSF6/7 (CPSF6/7)
Type: Family

This entry includes cleavage and polyadenylation specificity factor subunit 6/7 (CPSF6/7) from mammals and CG7185 from Drosophila melanogaster. This entry also includes proteins from fungi and plants.

CPSF6/7 are components of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation . These proteins are components of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs .
CPSF7, RNA recognition motif (CPSF7_RRM)
Type: Domain

This entry represents the RNA recognition motif of CPSF7.

CPSF7 (or CFIm59) is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation, it activates directly the mRNA 3'-processing machinery . CPSF7 contains an N-terminal RNA recognition motif (RRM), a central proline-rich region, and a C-terminal RS-like domain. The N-terminal RRM of CPSF7 mediates the interaction with CPSF5 (or CFIm25). It also serves to enhance RNA binding and facilitate RNA looping .
Protein elav, RNA recognition motif 1 (Elav_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Drosophila embryonic lethal abnormal vision (ELAV) protein.
Nop12, RNA recognition motif 1 (Nop12_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Nop12 from Saccharomyces cerevisiae. It is a novel nucleolar protein required for pre-25S rRNA processing and normal rates of cell growth at low temperatures. Nop12 shares high sequence similarity with nucleolar protein 13 (Nop13). Both, Nop12 and Nop13, are not essential for growth. However, unlike Nop13 that localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent, Nop12 is localized to the nucleolus . Nop12 contains two RNA recognition motifs (RRMs).
Scaffold attachment factor B1/2, RNA binding domain (SAFB1_2_RBD)
Type: Domain

This entry represents the RNA binding domain (RBD) of SAFB1 and SAFB2.

Scaffold attachment factor B (SAFB) family members include SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM. They contain an N-terminal DNA-binding (SAF-A/B, Acinus and PIAS, SAP) domain, an RNA-binding domain (RBD) and an C-terminal arginine/glycine motif RGG/RG domain. Their RGG/RG domain, which partially overlaps with a putative coiled-coil domain, is most conserved and is likely to be involved in protein-protein interactions .

SAFB1 belongs to the scaffold attachment factor B (SAFB) family. It has many functions such as transcriptional repression and RNA splicing. It may also have a role in chromatin organisation. It is involved in in numerous cellular processes including cell growth, stress response, and apoptosis . It plays an important role in cancer, particularly in breast tumourigenesis .

SAFB2 is a homologue of SAFB1 that function as an estrogen receptor corepressor and can also inhibit cell proliferation .
Sorting nexin-4 (SNX4)
Type: Family

Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .

SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain . SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor .