SII-SWORD/CoKE huggingface dataset:
4Fe-4S domain (4Fe-4S_dom)
Type: Domain

The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is functional in the acetyl-CoA pathway of autotrophic carbon fixation in various bacteria and acrchaea, where it is essential for the biosynthesis of acetyl- CoA. CoFeSP acts in two methylation reactions: the transfer of a methyl group from methyltransferase (MeTr)-bound methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site cluster A of acetyl-CoA synthase (ACS). CoFeSP is a heterodimer consisting of a large subunit (CfsA) and a small subunit (CfsB). The large subunit has three domains: an amino (N)-terminal 4Fe-4S domain, a TIM barrel domain and a carboxy (C)-terminal domain that binds CoBeta-aqua-(5,6-dimethylbenzimiddazolylcobamide) (corrinoid). Methylation of CoFeSP only occurs in the low potential Co(I) state, which can be sporadically oxidized to the inactive Co(II) state, making its reductive reactivation necessary. The low-potential [4Fe-4S]2(+)/1(+) cluster is involved in the reductive reactivation of CoFeSP and is able to transfer electrons to cob(II)amide from NiFe-containing carbon monoxyde dehydrogenase (CODH), pyruvate:ferredoxin oxydoreductase or reduced ferredoxins .

The 4Fe-4S domain lacks homology to the 4Fe-4S ferredoxin-type iron-sulfur binding domain, but is also found in bacterial electron transport complex protein RnfB .

The 4Fe-4S domain consists of four helices (three α-helices from H1-H3 and one 3(10)-helix with the order alphaH1-alphaH2-3(10)H-alphaH3). This four-helix-bundle-like architecture positions the four cysteinyl ligands of the [4Fe-4S] cluster. The iron-sulfur cluster binding motif Cys-X(2)-Cys-X(4)-Cys-X(16)-Cys is located at loops connecting alphaH1 and alphaH2, connecting 3(10)H and alphaH3, and at the end of alphaH2. The [4Fe-4S] cluster is placed near the surface of the 4Fe-4S domain, but is shielded from the solvent by hydrophobic amino acids .

This entry represents the 4Fe-4S domain.
ORMDL family (ORMDL)
Type: Family

ORMDL family members include ORMDL1/2/3 from humans and their homologues, such as protein Orm1 and Orm2 from budding yeasts. ORMDLs may be involved in protein folding in the endoplasmic reticulum . In budding yeast, Orm1 and Orm2 proteins mediate sphingolipid homeostasis .
Actin-related protein 2/3 complex subunit 3 (ARPC3)
Type: Family

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility . In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. It promotes homologous recombination (HR) repair in response to DNA damage, leading to drive motility of double-strand breaks (DSBs) . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This family represents the ARPC3/p21-ARC subunit.
Protein HGH1 N-terminal (Protein_HGH1_N)
Type: Domain

This entry represents a domain within Protein HGH1, of unknown function. It is found N-terminal to another domain of unknown function (

).
Protein HGH1 C-terminal (Protein_HGH1_C)
Type: Domain

This entry represents a domain within Protein HGH1, of unknown function. It is found C-terminal to another domain of unknown function (

).
CCR4-Not complex component, Not N-terminal domain (Not_N)
Type: Domain

The Ccr4-Not complex (Not1, Not2, Not3, Not4 and Not5) is a global regulator of transcription that affects genes positively and negatively and is thought to regulate transcription factor TFIID . This domain is the N-terminal region of the Not proteins.
Na(+)/H(+) antiporter subunit F-like (MrpF/PhaF-like)
Type: Family

Members of this family are predicted to be integral membrane proteins with three transmembrane regions, involved in regulation of pH. PhaF is part of a potassium efflux system involved in pH regulation. It is also involved in symbiosis in Rhizobium meliloti (Sinorhizobium meliloti) . MrpF is a part of a Na
+
/H
+
antiporter complex, also involved in pH homeostasis. MrpF is thought to be an efflux system for Na
+
and cholate . The Mrp system in Gram-positive species may also have primary energisation capacities .
RNase L inhibitor RLI-like, possible metal-binding domain (RNaseL-inhib-like_metal-bd_dom)
Type: Domain

This is part of a possible metal-binding domain in endoribonuclease RNase L inhibitor. It is found at the N-terminal end of RNase L inhibitor proteins, adjacent to the 4Fe-4S binding domain,

. Also often found adjacent to

in uncharacterised proteins. The RNase L system plays a major role in the anti-viral and anti-proliferative activities of interferons . It is a component of the multifactor complex (MFC) involved in translation initiation and it is required for the processing and nuclear export of the 60S and 40S ribosomal subunits, playing a role in ribosome biogenesis [

,

. Inhibitory activity requires concentration-dependent association of RLI with RNase L .
ABC-type glycine betaine transport system, substrate-binding domain (ABC_Gly_betaine_transp_sub-bd)
Type: Domain

This domain is a part of a high affinity multicomponent binding-protein-dependent transport system involved in bacterial osmoregulation. This domain is often fused to the permease component of the transporter complex. It is often found in integral membrane proteins or proteins predicted to be attached to the membrane by a lipid anchor. Glycine betaine is involved in protection from high osmolarity environments for example in Bacillus subtilis . OpuBC is closely related and involved in choline transport. Choline is necessary for the biosynthesis of glycine betaine . L-carnitine is important for osmoregulation in Listeria monocytogenes. This domain is found also in proteins binding l-proline (ProX), histidine (HisX), trimethylamine N-oxide (TMAO) and taurine (TauA).
Protein of unknown function DUF378 (DUF378)
Type: Family

These are predicted membrane proteins of unknown function. The majority of the proteins have two predicted transmembrane regions.
Cysteine-rich small domain (Zf-like)
Type: Domain

This is a probable metal-binding domain. It is found in a probable precorrin-3B C17-methyltransferase from Methanobacterium thermoautotrophicum, that catalyses the methylation of C-17 in precorrin-3B to form precorrin-4.
Methyltransferase Ppm1/Ppm2/Tcmp (Ppm1/Ppm2/Tcmp)
Type: Family

This entry includes a group of methyltransferases such as leucine carboxyl methyltransferase 1 (known as Ppm1 in yeast and LCMT1 in mammals), leucine carboxyl methyltransferase 2 (Ppm2/LCMT2) and O-methyltransferase TcmP.
YbaK/aminoacyl-tRNA synthetase-associated domain (YbaK/aa-tRNA-synth-assoc-dom)
Type: Domain

Bacterial prolyl-tRNA synthetases and some smaller paralogues, YbaK and ProX, can hydrolyse misacylated Cys-tRNA(Pro) or Ala-tRNA(Pro) . The small bacterial protein Ybak preferentially hydrolyses Cys-tRNA(Pro) and Cys-tRNA(Cys) . ProX functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro) . Prolyl-tRNA synthetases main function is to catalyse the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro) .

This entry represents a domain characteristic of Ybak and ProX, that can also be found with other domains in prolyl-tRNA synthetases.
Sulphur relay, TusB/DsrH (Sulphur_relay_TusB/DsrH)
Type: Family

The three proteins TusB, TusC, and TusD form a heterohexamer responsible for a sulphur relay reaction . In large numbers of proteobacterial species, this complex acts on a Cys-derived persulphide moiety, delivered by the cysteine desulphurase IscS to TusA, then to TusBCD. The activated sulphur group is then transferred to TusE (DsrC), then by MnmA (TrmU) for modification of an anticodon nucleotide in tRNAs for Glu, Lys, and Gln .

The sulphur relay complex TusBCD is also found, under the designation DsrEFH, in phototrophic and chemotrophic sulphur bacteria, such as Chromatium vinosum and Allochromatium vinosum . In these organisms, it seems the primary purpose is related to sulphur flux, such as oxidation from sulphide to molecular sulphur to sulphate .
CCR4-NOT transcription complex subunit 9 (CNOT9)
Type: Family

This entry includes CCR4-NOT transcription complex subunit 9 (CNOT9 or Rcd1). Mammalian CNOT9 is a component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation .
Per1-like (Per1-like)
Type: Family

PER1 is required for GPI-phospholipase A2 activity and is involved in lipid remodelling of GPI-anchored proteins . PER1 is part of the CREST superfamily . Human PERLD1 is a functional homologue of PER1, and is also known as PGAP3. Mutations in PGAP3 cause hyperphosphatasia with mental retardation syndrome .
DNA polymerase delta, subunit 4 (DNA_pol_delta_4)
Type: Family

DNA polymerase delta (Pol delta) is responsible for effective DNA replication, playing a key role in the elongation of both the leading and the lagging strands of DNA and the maturation of Okazaki fragments . It consists of four subunits: the catalytic and largest subunit p125, p50 that interacts with p125 to form the core enzyme, p68 which interacts with p50, and a fourth subunit, p12, that bridges p125 and p50, stabilising its interaction .

This entry represents the p12 subunit (also called subunit 4), which increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity in the Pol delta4 tetramer complex . p12 is PCNA-binding protein, as it contains a N-terminal PCNA-binding motif. Under conditions of DNA replication stress, it is required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb . This subunit is involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites . p12 plays a major role in Pol delta4 catalytic functions while its degradation is required for the conversion of Pol delta4 to Pol delta3 in the cellular response to DNA damage, as Pol delta3 has an enhanced proofreading activity .
Xylanolytic transcriptional activator, regulatory domain (XnlR_reg_dom)
Type: Domain

This domain is present in the large family of fungal zinc cluster transcription factors that contain an N-terminal GAL4-like C6 zinc binuclear cluster DNA-binding domain (

) , including Xylanolytic transcriptional activator (XnlR) and related transcriptional factors. It has been suggested that this region plays a regulatory role and it is between the DNA-binding domain and the C-terminal acidic region.

XlnR is involved in the regulation of extracellular cellulolytic and xylanolytic genes and in the regulation of the intracellular activities of D-xylose catabolic genes in the pentose catabolic pathway (PCP) in response to the presence of D-xylose .
Origin recognition complex, subunit 2 (ORC2)
Type: Family

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 . ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle . ORC directs DNA replication throughout the genome and is required for its initiation . ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex . Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase . Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase .

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) . ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers .

This entry represents subunit 2, which binds the origin of replication. It plays a role in chromosome replication and mating type transcriptional silencing.
Rod shape-determining protein MreC (MreC)
Type: Family

MreC (murein formation C) is involved in the rod shape determination in Escherichia coli, and more generally in cell shape determination of bacteria whether or not they are rod-shaped .
Signal recognition particle receptor, alpha subunit, N-terminal (Sig_recog_particle_rcpt_asu_N)
Type: Domain

This entry represents the alpha subunit of the SR receptor.

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .

The SR receptor is a monomer consisting of the loosely membrane-associated SR-alpha homologue FtsY, while the eukaryotic SR receptor is a heterodimer of SR-alpha (70kDa) and SR-beta (25kDa), both of which contain a GTP-binding domain . SR-alpha regulates the targeting of SRP-ribosome-nascent polypeptide complexes to the translocon . SR-alpha binds to the SRP54 subunit of the SRP complex. The SR-beta subunit is a transmembrane GTPase that anchors the SR-alpha subunit (a peripheral membrane GTPase) to the ER membrane . SR-beta interacts with the N-terminal SRX-domain of SR-alpha, which is not present in the bacterial FtsY homologue. SR-beta also functions in recruiting the SRP-nascent polypeptide to the protein-conducting channel.
Peroxin 13, N-terminal (Peroxin-13_N)
Type: Domain

Peroxin-13 is a component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor . This complex forms a large import pore which can be opened to a diameter of about 9 nm . Members of this group of proteins also contain an SH3 domain (

).
Transcription initiation factor Rrn11 (TIF_Rrn11)
Type: Family

The RNA polymerase I specific transcription initiation factor Rrn11 is a member of a multiprotein complex essential for the initiation of transcription by RNA polymerase I, together with Rrn6 and Rrn7 subunits . Binding to the DNA template is dependent on the initial binding of other factors . Rrn11 contains a tetratricopeptide repeats (TPRs) and interacts with Rrn6 and Rrn7 to form the core factor (CF), which resembles a right hand holding the DNA molecule between the fingers and the palm. The palm is composed of the N-terminal regions of both Rrn11 and Rrn6, the thumb is composed of the C-terminal of Rrn11, and the fingers and knuckles are composed of Rrn7 and the C-terminal half of Rrn6, respectively .
Exocyst complex component EXOC6/Sec15 (EXOC6/Sec15)
Type: Family

Sec15 is a component of the exocyst complex involved in the the tethering of post-Golgi Golgi secretory vesicles to the plasma membrane during exocytosis and plays a role in several cellular functions such as cell polarisation, cytokinesis, ciliogenesis and tumour invasion. The exocyst is one of the members of the complexes associated with tethering containing helical rods (CATCHR), together with COG, GARP, and Dsl1 complexes, which share a fold consisting of α-helical bundles forming a rod structure . Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner .
SRS domain (SRS_dom)
Type: Domain

Toxoplasma gondii is a persistent protozoan parasite capable of infecting almost any warm-blooded vertebrate. The surface of Toxoplasma is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member. SRS proteins mediate attachment to host cells and interface with the host immune response to regulate the virulence of the parasite. SAG1 is composed of two disulphide linked SRS domains. These have 6 cysteines that form 1-6,2-5 and 3-4 pairings. The structure of the immunodominant SAG1 antigen reveals a homodimeric configuration . The SRS domain is found in a single copy in the SAG2 proteins. This family of surface antigens are found in other apicomplexans.
Cell shape-determining protein MreD (Cell_shape_determining_MreD)
Type: Family

The MreD (murein formation D) protein is involved in bacterial cell shape determination . Most rod-shaped bacteria depend on MreB and RodA to achieve either a rod shape or some other non-spherical morphology such as coil or stalk formation. MreD is encoded in an operon with MreB, and often with RodA and PBP-2 as well. It is highly hydrophobic (therefore somewhat low-complexity) and highly divergent, and therefore cannot always be identified on the basis of sequence similarity.
Nicotinate phosphoribosyltransferase family (Nic_PRibTrfase-Fam)
Type: Family

Nicotinate phosphoribosyltransferase (

) is the rate-limiting enzyme that catalyses the first reaction in the NAD salvage synthesis . Members in this family can be split into two further subfamilies represented in

and

. Members in

have a different (longer) spacing of several key motifs and have an additional C-terminal domain of up to 100 residues. However, one argument suggesting that this family represents the same enzyme is that no species has a member of both subfamilies. Another is that the gene encoding this protein is located near other NAD salvage biosynthesis genes in Nostoc and in at least four different Gram-positive bacteria.
Nucleoporin interacting component Nup93/Nic96 (Nucleoporin_int_Nup93/Nic96)
Type: Family

Nup93/Nic96 is a component of the nuclear pore complex. It is required for the correct assembly of the nuclear pore complex . In Saccharomyces cerevisiae, Nic96 has been shown to be involved in the distribution and cellular concentration of the GTPase Gsp1 . The structure of Nic96 has revealed a mostly α helical structure .
DNA repair protein Rad52/59/22 (Rad52_Rad59_Rad22)
Type: Family

The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-beta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to Rad52. These proteins contain two helix-hairpin-helix motifs .
Trafficking protein particle complex subunit (TRAPPC)
Type: Family

This entry includes a group of trafficking protein particle complex subunit (TRAPPC) proteins, such as TPPC1/4 from humans and Trs23/Bet5 from yeasts.
Vps53, N-terminal (Vps53_N)
Type: Domain

Vps53 complexes with Vps52 and Vps54 to form a multi-subunit complex called Golgi-Associated Retrograde Protein complex (GARP) involved in retrograde transport from early and late endosomes to late Golgi . They are members of the CATCHR (complexes associated with tethering containing helical rods) which includes the exocyst, COG, GARP, and DSL1 complexes which have structural and functional similarities. This is the N-terminal coiled-coil domain .
Glycosyl transferase, family 28, C-terminal (Glyco_trans_28_C)
Type: Domain

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Glycosyltransferase family 28

comprises enzymes with a number of known activities; 1,2-diacylglycerol 3-beta-galactosyltransferase (

); 1,2-diacylglycerol 3-beta-glucosyltransferase (

); beta-N-acetylglucosamine transferase (

).
Structural analysis suggests the C-terminal domain contains the UDP-GlcNAc binding site.
SlyX (SlyX)
Type: Family

The SlyX protein has no known function. It is short, less than 80 amino acids, and its gene is found close to the slyD gene. The SlyX protein has a conserved PPH(Y/W) motif at its C terminus. The protein may be a coiled-coil structure.
CD20-like family (CD20-like)
Type: Family

This entry includes B-lymphocyte antigen CD20 and other members of the membrane-spanning 4-domains subfamily A (MS4A), and closely related TMEM176 proteins . It also includes sarcospan and some uncharacterised proteins.
DNA primase large subunit, eukaryotic/archaeal (DNA_primase_lsu_euk/arc)
Type: Family

DNA primase is the polymerase that synthesises small RNA primers for the Okazaki fragments made during discontinuous DNA replication. Primases are grouped into two classes, bacteria/bacteriophage and archaeal/eukaryotic. The proteins in the two classes differ in structure and the replication apparatus components. Archaeal/eukaryotic core primase is a heterodimeric enzyme consisting of a small catalytic subunit (PriS or Pri1) and a large subunit (PriL or Pri2). In the yeast Saccharomyces cerevisiae the small subunit is 48kDa and the large subunit 58kDa . In eukaryotic organisms, a heterotetrameric enzyme formed by DNA polymerase alpha, the B subunit and two primase subunits has primase activity. Although the catalytic activity and the the ATP binding site reside within PriS , the PriL subunit is essential for primase function as disruption of the PriL gene in yeast is lethal. PriL is composed of two structural domains. Several functions have been proposed for PriL such as stabilization of the PriS, involvement in synthesis initiation, improvement of primase processivity, determination of product size and transfer of the products to DNA polymerase alpha . Primase function has also been demonstrated for human and mouse primase subunits .