SII-SWORD/CoKE huggingface dataset:
Ctr copper transporter (Cop_transporter)
Type: Family

This entry represents the high-affinity copper transporter Ctr1 proteins. The redox active metal copper is an essential cofactor in critical biological processes such as respiration, iron transport, oxidative stress protection, hormone production, and pigmentation. A widely conserved family of high-affinity copper transport proteins (Ctr proteins) mediates copper uptake at the plasma membrane . A series of clustered methionine residues in the hydrophilic extracellular domain, and an MXXXM motif in the second transmembrane domain, are important for copper uptake. These methionines probably coordinate copper during the process of metal transport .
YTH domain (YTH_domain)
Type: Domain

The YTH (YT521-B homology) domain has been suggested to be an evolutionarily conserved m6A-dependent RNA binding domain . Proteins containing this domain includes mammalian YTHD and YTDC proteins, Arabidopsis CPSF30 (At1g30460), budding yeast Pho92 and fission yeast Mmi1.

In Saccharomyces cerevisiae, Pho92 is a post-transcriptional regulator that regulates Pho4 mRNA stability by binding to the 3'-UTR in a phosphate-dependent manner. Its YTH domain exhibits RNA-binding activity . In Schizosaccharomyces pombe, Mmi1 has been identified as eliminating meiosis-specific mRNAs .
Nucleolar protein 14 (Nop14)
Type: Family

Nucleolar protein 14 (Nop14) is involved in nucleolar processing of pre-18S ribosomal RNA and has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm .
Svp26/Tex261 (Svp26/Tex261)
Type: Family

This entry includes Svp26 from yeasts and Tex261 from animals. Budding yeast Svp26 is a integral membrane protein found in the ER and early Golgi compartment . It functions as an ER exit adaptor protein of mannosyltransferases Mnt2 and Mnt3 . The function of Tex261 is not clear.
Domain of unknown function DUF397 (DUF397)
Type: Domain

The function of this family is unknown. It has been suggested that some members of this family are regulators of transcription.
Peptidase, C-terminal, archaeal/bacterial (Peptidase_C_arc/bac)
Type: Domain

This domain is normally found at the C terminus of secreted archaeal and bacterial peptidases, the majority of which belong to MEROPS peptidase families M4 (vibriolysin,

), M09 (microbial collagenases ColA, ColQ1 and ColT

), M28 (aminopeptidase Ap1,

) and S8 (subtilisin family peptidases,

).
Mre11, DNA-binding (Mre11_DNA-bd)
Type: Domain

This entry represents the DNA binding domain of Double-strand break repair protein Mre11 and similar eukaryotic sequences.

The MRN complex is a multi-subunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2, and is involved in checkpoint signalling, double-strand break (DSB) repair, DNA replication, maintenance of telomere integrity and meiosis, promoting genomic stability . Mre11 has an intrinsic DNA-binding activity that is stimulated by Rad50 on its own or in combination with Nbs1 . This protein dimerises via phosphodiesterase domains flanked by an α/β capping domain, which creates a U-shaped particle with a broad DNA/Rad50 binding cleft .
NOT2/NOT3/NOT5, C-terminal (NOT2/3/5_C)
Type: Domain

The Ccr4-Not complex controls mRNA metabolism at multiple levels in eukaryotic cells . This complex is a major cytoplasmic deadenylase consisting of a combination of at least nine subunits, four of which have deadenylase activity . The conserved core of the CCR4-NOT complex consists of two major modules: a catalytic module comprising two deadenylases (CAF1 or its paralogue POP2, and CCR4a or its paralogue CCR4b) and the NOT module, which minimally consists of NOT1, NOT2 and NOT3 .

This entry represents the C-terminal domain of NOT2, NOT3 and NOT5 (subunits 2, 3 and 5 of the complex). The C-terminal regions of NOT2 and NOT3 contain a conserved SH3-like NOT-box domain which mediates NOT-module assembly .
Ground-like domain (Ground-like_dom)
Type: Domain

This group of proteins contain one or more copies of the ground-like domain, which are specific to Caenorhabditis elegans and Caenorhabditis briggsae. It has been proposed that the ground-like domain containing proteins may bind and modulate the activity of Patched-like membrane molecules, reminiscent of the modulating activities of neuropeptides .
Sof1-like protein (Sof1)
Type: Domain

Sof1 is essential for cell growth and is a component of the nucleolar rRNA processing machinery .
Influenzavirus B, glycoprotein NB (InfluenzaB_glycoprotein_NB)
Type: Family

The NB glycoprotein is found in Influenza type B virus. It forms putative viral proton channel and may play a role in virus entry .
Jaagsiekte sheep retrovirus, Vpu (JSRV_Vpu)
Type: Family

This short protein has no known function and is found in Jaagsiekte sheep retrovirus. Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung tumour of sheep known as sheep pulmonary adenomatosis. JSRV exhibits a simple genetic organisation, characteristic of the type D and type B retroviruses, with the canonical retroviral sequences gag, pro, pol and env encoding the structural proteins of the virion and an additional open reading frame (Vpu/orf-x), of approximately 500 bp overlapping pol .
Arv1 protein (Arv1)
Type: Family

Arv1 is a transmembrane protein, with potential zinc-binding motifs, that mediates sterol homeostasis. Its action is important in lipid homeostasis, which prevents free sterol toxicity . Arv1 contains a homology domain (AHD), which consists of an N-terminal cysteine-rich subdomain with a putative zinc-binding motif, followed by a C-terminal subdomain of 33 amino acids. The C-terminal subdomain of the AHD is critical for the protein's function . In yeast, Arv1p is important for the delivery of an early glycosylphosphatidylinositol GPI intermediate, GlcN-acylPI, to the first mannosyltransferase of GPI synthesis in the ER lumen . It is important for the traffic of sterol in yeast and in humans. In eukaryotic cells, it may fuction in the sphingolipid metabolic pathway as a transporter of ceramides between the ER and Golgi . Arabidopsis thaliana has been shown to encode 2 ARV proteins (ARV1 and ARV2) both of which contain the AHD domain. This family also includes ARV2 from A. thaliana .
Capsid protein (Capsid_protein)
Type: Family

Capsid protein (CA1, also known as VP1) self-assembles to form the virion icosahedral capsid with a T=1 symmetry. This very small capsid (25 nm in diameter) allows the virus to be very stable in the environment and resistant to some disinfectants, including detergents. It is essential for the initial attachment to host receptors. After attachment, the virus is endocytosed and traffics to the nucleus. The capsid protein binds and transports the viral genome and Rep across the nuclear envelope .
Nuclear fusion protein Kar5 (Nuclear_fusion_Kar5)
Type: Family

Nuclear fusion protein KAR5 is an integral membrane protein that is thought to be required for the fusion of nuclear envelopes during karyogamy .
Flagellar protein FlgP (FlgP)
Type: Family

This family includes FlgP from Vibrio cholerae, which is part of an operon with two genes, flgO and flgP, positively regulated by FlrC, the activator of class III flagellar genes. FlgP is an outer membrane lipoprotein required for motility that functions as a colonization factor .
Protein of unknown function DUF401 (DUF401)
Type: Family

Members of this family are predicted to have 10 transmembrane regions.
Domain of unknown function DUF402 (DUF402)
Type: Domain

This β-barrel domain is found in Cytidylyl-2-hydroxypropylphosphonate hydrolase from Streptomyces wedmorensis (FomD), a protein encoded in the fosfomycin biosynthesis gene cluster . This domain is also found in Ntdp (nucleoside tri- and diphosphatase, also known as Sa1684) from Staphylococcus aureus and related prokaryotic proteins.

FomD is a protein encoded in the fosfomycin biosynthesis gene cluster , which hydrolyses (S)-HPP-CMP to give (S)-HPP and CMP in the presence of Mn2 or Co2 . It also hydrolyses cytidylyl 2-hydroxyethylphosphonate (HEP-CMP), which is a biosynthetic intermediate before C-methylation. FomD structure revealed that it has a β-barrel fold consisting of a large twisted antiparallel β-sheet. It has a conserved Tyr residue which activates a water molecule to promote nucleophilic attack on the phosphorus atom of the phosphonate moiety .
Rv2567-like, DUF403 (DUF403)
Type: Domain

This domain is found at the C-terminal of the uncharacterised protein Rv2567 from Mycobacterium tuberculosis and similar bacterial sequences. It is predicted to be α-helical and contains a conserved ER motif. In many members of this group this domain covers the whole length of the protein.
Copper resistance lipoprotein NlpE (Cu-R_lipoprotein_NlpE)
Type: Family

This family represents a bacterial outer membrane lipoprotein that is necessary for signalling by the Cpx pathway . This pathway responds to cell envelope disturbances and increases the expression of periplasmic protein folding and degradation factors. While the molecular function of the NlpE protein is unknown, it may be involved in detecting bacterial adhesion to abiotic surfaces. NlpE from Escherichia coli and Salmonella typhi is also known to confer copper tolerance in copper-sensitive strains of E. coli, and may be involved in copper efflux and delivery of copper to copper-dependent enzymes .
CidB/LrgB family (CidB/LrgB)
Type: Family

The two products of the lrgAB operon are potential membrane proteins. LrgA and LrgB are antiholin-like proteins thought to control murein hydrolase activity and penicillin tolerance and to inhibit the holin-like proteins from the cidAB operon, CidA and CidB . The regulatory processes by these proteins is still largely unknown.

This family represents LrgB and CidB.
TQO small subunit DoxD (DoxD)
Type: Domain

is a subunit of the terminal quinol oxidase present in the plasma membrane of Acidianus ambivalens, with calculated molecular mass of 20.4kDa . Thiosulphate:quinone oxidoreductase (TQO) is one of the early steps in elemental sulphur oxidation. A novel TQO enzyme was purified from the thermo-acidophilic archaeon A. ambivalens and shown to consist of a large subunit (DoxD) and a smaller subunit (DoxA). The DoxD-and DoxA-like two subunits are fused together in a single polypeptide in

.
Circularly permuted ATPgrasp domain (CP_ATPgrasp)
Type: Domain

This ATP-grasp domain is present both as catalytically active and inactive versions. Contextual analysis suggests that it functions in a distinct peptide synthesis/modification system that additionally contains a transglutaminase, an NTN-hydrolase, the Alpha-E domain, and a transglutaminase fused N-terminal to a circularly permuted COOH-NH2 ligase. The inactive forms are often fused N-terminal to the Alpha-E domain .
TIP41-like protein (TIP41-like)
Type: Family

In budding yeast, TIP41 interacts with TAP42 to regulate protein phosphatase activity . In mammalian cells, TIP41-like protein (TIPRL) does not directly bind TAP42, but rather primarily interacts with PP2A, PP4 or PP6 catalytic subunits. TIPRL inhibits PP4 activity to allow for H2AX phosphorylation and the subsequent DNA damage response .
TAP46-like protein (TAP46-like)
Type: Family

This entry represents a family of proteins involved in the regulation of phosphatases. It includes TAP46 and TAP42, as well as others.

TAP46 is involved in the positive regulation of the TOR signaling pathway in plants, acting as a negative regulator of PP2A catalytic activity .

The TOR signalling pathway activates a cell-growth program in response to nutrients . TIP41 interacts with TAP42 and negatively regulates the TOR signalling pathway .
Vesicle transport protein, Got1/SFT2-like (Vesicle_transpt_Got1/SFT2)
Type: Family

Traffic through the yeast Golgi complex depends on a member of the syntaxin family of SNARE proteins, Sed5, present in early Golgi cisternae. Got1 is thought to facilitate Sed5-dependent fusion events . This is a family of sequences derived from eukaryotic proteins. They are similar to a region of a SNARE-like protein required for traffic through the Golgi complex, SFT2 protein (

) . This is a conserved protein with four putative transmembrane helices, thought to be involved in vesicular transport in later Golgi compartments .
tRNA A64-2'-O-ribosylphosphate transferase (Rit1)
Type: Family

This entry includes tRNA A64-2'-O-ribosylphosphate transferase Rit1 from budding yeasts. Rit1 is a phospho-ribosyl transferase that exclusively modifies the initiator tRNA (tRNAMet(i)) by the addition of a 2'-O-ribosyl phosphate group to Adenosine 64 . This entry also includes the C3F10.06c protein from Schizosaccharomyces pombe.
Low temperature viability protein Ltv1 (Ltv1)
Type: Family

The low-temperature viability protein Ltv1 is required for 40S subunit biogenesis in yeast . It may facilitate the incorporation of Rps3, Rps10, and Asc1/RACK1 into the small ribosomal subunit head .
Rtr1/RPAP2 domain (Rtr1/RPAP2_dom)
Type: Domain

This entry represents a domain found in RPAP2 (RNAP II associated polypeptide) protein and the yeast Rtr1 proteins. It has been suggested that this family of proteins are regulators of core RNA polymerase II function .
B-block binding subunit of TFIIIC (TFIIIC_Bblock-bd)
Type: Domain

Yeast transcription factor IIIC (TFIIIC) is a multisubunit protein complex that interacts with two control elements of class III promoters called the A and B blocks. This family represents the subunit within TFIIIC involved in B-block binding . Although defined as a yeast protein, it is also found in a number of other organisms.
Aerobactin siderophore biosynthesis, IucA/IucC, N-terminal (Aerobactin_biosyn_IucA/IucC_N)
Type: Domain

Bacteria solve the iron supply problem caused by the insolubility of Fe(3) by synthesizing iron-complexing compounds, called siderophores, and by using iron sources of their hosts, such as haem and iron bound to transferrin and lactoferrin. Escherichia coli, as an example of a Gram-negative bacterium, forms sophisticated Fe(3)-siderophore and haem transport systems across the outer membrane. IucA and IucC catalyse discrete steps in biosynthesis of the siderophore aerobactin from N epsilon-acetyl-N epsilon-hydroxylysine and citrate .

This entry also includes SbnC, SbnE and SbnF from Staphylococcus aureus. They are involved in staphyloferrin B biosynthesis. SbnC is a staphyloferrin B synthase. SbnE is a L-2,3-diaminopropanoate--citrate ligase. SbnF is a 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate synthase .

It also includes Bisucaberin biosynthesis protein C that is involved in the biosynthesis of the siderophore bisucaberin , as well as AnkE which is responsible of the production of NK13650 B via ligation of citrate to the ankD product .

This entry represents the N-terminal domain of both IucA/IucC. The C-terminal domain of this family of proteins is related to the FhuF iron transporter proteins.
ST7 (ST7)
Type: Family

The ST7 (for suppression of tumorigenicity 7) protein is thought to be a tumour suppressor gene . It localises to the cytoplasm and plasma membrane and may mediate tumor suppression by regulating genes that are involved in oncogenic pathways and/or maintain cellular structure . The molecular function of this protein is uncertain.
Phosphoesterase (Phosphoesterase)
Type: Family

This entry includes both bacterial phospholipase C enzymes (

) and eukaryotic acid phosphatases (

).
FxsA cytoplasmic membrane protein (FxsA)
Type: Family

This is a bacterial family of cytoplasmic membrane proteins. It includes two transmembrane regions. The molecular function of FxsA is unknown, but in Escherichia coli its overexpression has been shown to alleviate the exclusion of phage T7 in those cells with an F plasmid.
Haem-binding uptake, Tiki superfamily, ChaN (Cofac_haem-bd_dom)
Type: Domain

This entry represents a domain found in ChaN family members. ChaN is a family of putative bacterial lipoproteins necessary for the uptake of haem-iron. The structure of

,

, comprises a large parallel β-sheet with flanking α-helices and a smaller domain consisting of α-helices. Two cofacial haem groups bind in a pocket formed by a dimer of two ChaN monomers .

Proteins containing this domain also include protein RETICULATA-RELATED from Arabidopsis. They may play a role in leaf development .
GPI mannosyltransferase 2 (PIG-V/Gpi18)
Type: Family

This entry represents GPI mannosyltransferase 2, also known as PIG-V in humans or Gpi18 in fungi. PIG-V is a mannosyltransferase that transfers the second mannose in glycosylphosphatidylinositol (GPI) biosynthesis . GPI is a glycolipid that anchors many proteins to the eukaryotic cell surface .
Golgi to ER traffic protein 4 (GET4)
Type: Family

In budding yeast, Get4 is part of the GET complex that inserts the tail-anchored (TA) proteins into the endoplasmic reticulum membrane . In humans, Get4 is part the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and facilitates their proper delivery to the endoplasmic reticulum, or alternatively promotes their sorting to the proteasome where they undergo degradation . The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane .
Phospholipid methyltransferase (Phopholipid_MeTrfase)
Type: Family

This family includes Saccharomyces cerevisiae phospholipid methyltransferase

, which has a broad substrate specificity of unsaturated phospholipids , and related enzymes such as methanethiol S-methyltransferase (

), which catalyses the methylation of methanethiol to yield dimethylsulphide (a volatile compound important in climate regulation) .
Small-subunit processome, Utp21 (SSU_processome_Utp21)
Type: Domain

A large ribonuclear protein complex is required for the processing of the small-ribosomal-subunit rRNA -the small-subunit (SSU) processome . This preribosomal complex contains the U3 snoRNA and at least 40 proteins, which have the following properties:

They are nucleolar.

They are able to coimmunoprecipitate with the U3 snoRNA and Mpp10 (a protein specific to the SSU processome).

They are required for 18S rRNA biogenesis.

There appears to be a linkage between polymerase I transcription and the formation of the SSU processome; as some, but not all, of the SSU processome components are required for pre-rRNA transcription initiation. These SSU processome components have been termed t-Utps. They form a pre-complex with pre-18S rRNA in the absence of snoRNA U3 and other SSU processome components. It has been proposed that the t-Utp complex proteins are both rDNA and rRNA binding proteins that are involved in the initiation of pre18S rRNA transcription. Initially binding to rDNA then associating with the 5' end of the nascent pre18S rRNA. The t-Utpcomplex forms the nucleus around which the rest of the SSU processome components, including snoRNA U3, assemble . From electron microscopy the SSU processome may correspond to the terminal knobs visualised at the 5' ends of nascent 18S rRNA.

Utp21 is a component of the SSU processome, which is required for pre-18S rRNA processing. It interacts with Utp18 .
Programmed cell death protein 2, C-terminal (PDCD2_C)
Type: Domain

PDCD2 is localized predominantly in the cytosol of cells situated at the opposite pole of the germinal centre from the centroblasts as well as in cells in the mantle zone. It has been shown to interact with BCL6, an evolutionarily conserved Kruppel-type zinc finger protein that functions as a strong transcriptional repressor and is required for germinal centre development. The rat homologue, Rp8, is associated with programmed cell death in thymocytes.
Transposase (putative), gypsy type (Transposase_28)
Type: Domain

This domain is found in a family of plant gene products and is thought to be related to gypsy type transposons.
RNA-dependent RNA polymerase, bunyaviral (RNA_pol_bunyavir)
Type: Domain

The bunyaviruses are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein is encoded by the small (S) genomic RNA. The L segment codes for an RNA polymerase. This family contains the RNA dependent RNA polymerase on the L segment.
Sugar-binding domain, putative (Sugar-bd_dom_put)
Type: Domain

This probable domain is found in bacterial transcriptional regulators such as DeoR, SorC and CggR. One of these proteins,

, has an N-terminal helix-turn-helix

that binds to DNA. This domain is probably the ligand regulator binding region. SorC is regulated by sorbose and other members of this family are likely to be regulated by other sugar substrates. CggR regulates the gapA operon in B. subtilis .

It is worth noting that the DeoR in this entry is represented by the protein, UniProt P39140, from Bacillus subtilis. Not the DeoR, UniProt P0ACK5, from E. coli. Despite sharing the same name, these two proteins do not share protein sequence similarity .
Kynurenine formamidase/cyclase-like (KFase/CYL)
Type: Family

Kynurenine formamidase catalyses the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation . The proteins contain a conserved motif HXGTHXDXPXH that is likely to form a part of the active site.

This family also includes cyclase-like proteins from plants. They are involved in responses to abiotic stress, and could function as polyketide cyclases . Isatin hydrolase (

), characterised from the bacterium Labrenzia aggregata, is also a member of this family. It is a manganese-binding enzyme that hydrolyses the cyclic amide bond (lactam) of isatin (1H-indole-2,3-dione) to yield isatinate (2-(2-aminophenyl)-2-oxoacetate), during the degradation of the plant hormone indole-3-acetic acid (IAA) .
Lipoprotein-associated domain (Lipoprotein-assoc_dom)
Type: Domain

This presumed domain is about 100 amino acids in length. It is found in lipoproteins of unknown function. The domain is found in up to five copies in some proteins.
Tumour protein D52 (TPD52)
Type: Family

The hD52 gene was originally identified through its elevated expression level in human breast carcinoma . Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family. These proteins have an N-terminal coiled-coil that allows members to form homo- and heterodimers with each other .
Foot protein 3 (Mfp-3)
Type: Family

Mytilus foot protein-3 (Mfp-3) is a highly polymorphic protein family located in the byssal adhesive plaques of blue mussels .
FMN-binding (FMN-bd)
Type: Domain

This conserved region includes the FMN-binding site of the NqrC protein as well as the NosR and NirI regulatory proteins. This domain is post-translationally flavinylated and may facilitate electron transfer, resembling multiheme cytochromes .

It is also found in NADH:(hydroxy)cinnamate reductase subunit CrdB that catalyzes the reduction of the double bond in cinnamate, p-coumarate, caffeate, and ferulate under anaerobic conditions with NADH or methyl viologen as the electron donor .
MIT domain (MIT_dom)
Type: Domain

The MIT domain forms an asymmetric three-helix bundle. It is found in vacuolar sorting proteins, spastin (probable ATPase involved in the assembly or function of nuclear protein complexes), and a sorting nexin, which may play a role in intracellular trafficking.

A 'variant' MIT domain has been described at the N-terminal region of a related AAA-ATPase, mammalian katanin p60 represented in

.
Htaa (Htaa)
Type: Domain

This domain is found in HtaA, a secreted protein implicated in iron acquisition and transport .
Protein of unknown function DUF411 (DUF411)
Type: Family

The function of the members of this bacterial protein family is unknown. Some members may be involved in conferring cation resistance.
Uncharacterised protein family UPF0208 (UPF0208)
Type: Family

This family consists of bacterial uncharacterised proteins.
Protein of unknown function DUF413 (DUF413)
Type: Family

This is a family of uncharacterised proteins.