SII-SWORD/CoKE huggingface dataset:
Cyclin Y (Cyclin_Y)
Type: Family

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .

This group represents cyclin Y (also known as cyclin X) and related cyclins. Cyclin Y is a positive regulatory subunit of the cyclin-dependent kinase CDK14/PFTK1. Cyclin Y acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway .
Long-chain-alcohol oxidase (Long_Oxdase)
Type: Family

The long-chain alcohol oxidase (FAO) acts as the second enzyme in the omega-oxidation pathway of lipid degradation in yeast . Four homologues have been described in Arabidopsis thaliana: AtFAO1, AtFAO3, AtAFO4a, and AtFAO4b .
DNA-binding protein MutS2, archaea (DNA-bd_MutS2_arc)
Type: Family

MutS2 from archaea has ATPase and non-specific DNA-binding activities. It does not have any detectable mismatch-specific DNA binding activity .
Nucleotide-sugar transporter-related (UCP036436)
Type: Family

This entry represents a predicted permease related to nucleotide-sugar transporters. Proteins in this entry include solute carrier family 35 member F6 (SLC35F6, also known as C2orf18) from humans and PH domain-containing rcdII from Dictyostelium discoideum. SLC35F6 is involved in the maintenance of mitochondrial membrane potential in pancreatic ductal adenocarcinoma (PDAC) cells. It promotes pancreatic ductal adenocarcinoma (PDAC) cell growth .
LytTR stand-alone protein (LyTR_stand-alone)
Type: Family

Members of this group are stand-alone forms of the LytTR DNA-binding domain . One of them is BlpS from Streptococcus pneumoniae. BlpS is encoded together with the components of the two-component system Blp, which also contains another LytTR-containing protein, the response regulator BlpR . The Blp system is closely related to quorum-sensing systems regulating cell density-dependent phenotypes, such as the development of genetic competence or the production of antimicrobial peptides in lactic acid bacteria, and is a peptide-sensing system that controls the
blp
regulon. The
blp
regulon is composed of genes for regulation, synthesis, export, and processing of Blps (bacteriocin-like peptides) . The exact function of BlpS is not clear.
Urease accessory protein UreE (UreE)
Type: Family

Urease and other nickel metalloenzymes are synthesised as precursors devoid of the metalloenzyme active site. These precursors then undergo a complex post-translational maturation process that requires a number of accessory proteins.

Members of this group are nickel-binding proteins required for urease metallocentre assembly . They are believed to function as metallochaperones to deliver nickel to urease apoprotein . It has been shown by yeast two-hybrid analysis that UreE forms a dimeric complex with UreG in Helicobacter pylori 26695 . The UreDFG-apoenzyme complex has also been shown to exist and is believed to be, with the addition of UreE, the assembly system for active urease . The complexes, rather than the individual proteins, presumably bind to UreB via UreE/H recognition sites.

The structure of Klebsiella aerogenes UreE reveals a unique two-domain architecture with one domain structurally related to a heat shock protein and the second to the Atx1 copper metallochaperone . Significantly, the metal-binding sites in UreE and Atx1 are distinct in location and types of residues despite the relationship between these proteins and the mechanism for UreE activation of urease is proposed to be different from the thiol ligand exchange mechanism used by the copper metallochaperones.

Most members of this group contain a histidine-rich C-terminal motif that is involved in, but not solely responsible for, binding nickel ions in K. aerogenes UreE . However, internal ligands, not the histidine residues at the C terminus, are necessary for UreE to assist in urease activation in K. aerogenes , even though the truncated protein lacking the His-rich region binds two nickel ions instead of six. In H. pylori and some other organisms, the terminal histidine-rich binding sites are absent, but the internal histidine sites are present, and the latter probably function as nickel donors.
Acetaldehyde/propionaldehyde dehydrogenase, EutE/PduP-related (Acetald_propionald_DH-rel)
Type: Family

Members of this group function in ethanolamine and propanediol degradation pathways. Both pathways require coenzyme B12 (adenosylcobalamin, AdoCbl). Bacteria that harbor these pathways can use ethanolamine as a source of carbon and nitrogen, or propanediol as a sole carbon and energy source, respectively.

The EutE protein is a putative CoA-dependent aldehyde dehydrogenase (

) proposed to catalyse the second step of the coenzyme B12 (adenosylcobalamin, AdoCbl)-dependent pathway of ethanolamine degradation , converting acetaldehyde into acetyl-CoA. Mutational analysis has shown that EutE is involved in ethanolamine degradation and, on the basis of sequence similarity to AdhE alcohol dehydrogenase/acetaldehyde dehydrogenase (

) and aldehyde dehydrogenases, it is believed to be an acetaldehyde dehydrogenase. Ethanolamine degradation pathway enzymes, including EutE, are encoded by the eut operon .

PduP is encoded by the propanediol (pdu) operon and is involved in propanediol utilization . The pathway of 1,2-propanediol degradation starts with the conversion of 1,2-propanediol to propionaldehyde by an AdoCbl-dependent propanediol dehydratase. Then, propionaldehyde is oxidized by propionaldehyde dehydrogenase to propionyl-CoA. Subsequently, propionyl-CoA can be metabolized either aerobically into pyruvate (presumably in three steps) or anaerobically into propionate (presumably in two steps) . PduP is closely related to EutE and, therefore, has been predicted to be a CoA-dependent aldehyde dehydrogenase used in the pdu pathway for the conversion of propionaldehyde to propionyl-CoA .

Propanediol utilization is thought to be important for natural Salmonella populations, since propanediol is produced by the fermentation of the common plant sugars rhamnose and fucose . More than 1% of the Salmonella enterica genome is devoted to the utilization of propanediol and cobalamin biosynthesis. In vivo expression technology has indicated that propanediol utilization genes may be important for growth in host tissues, and competitive index studies with mice have shown that pdu mutations confer a virulence defect . The pdu operon is contiguous and coregulated with the cobalamin (B12) biosynthesis cob operon, indicating that propanediol catabolism may be the primary reason for de novo B12 synthesis in Salmonella .

On the basis of sequence analysis, it has been suggested that the pdu/cob genes were lost by a common ancestor of Escherichia coli and Salmonella enterica and were reintroduced as a single fragment into the Salmonella lineage by a single horizontal gene transfer event from an exogenous source .
Sirohaem synthase (Sirohaem_synth)
Type: Family

Sirohaem synthase (CysG), a multifunctional enzyme of the sirohaem and cobalamin (vitamin B12) biosynthesis pathways, represents a fusion between uroporphyrin-III C-methyltransferase (SUMT) and precorrin-2 oxidase/chelatase. Therefore, in some bacteria, all four reactions of sirohaem biosynthesis are catalysed by one multifunctional enzyme, sirohaem synthase .

Sirohaem and cobalamin are related macrocyclic structures derived from uroporphyrinogen III by C-methylation of the tetrapyrrole framework. All biologically important modified tetrapyrroles (including also haem and chlorophyll) share a common biosynthetic pathway up to the synthesis of the first macrocyclic intermediate, uroporphyrinogen III . Then, SUMT (corresponding to the C-terminal (CysGA) domain of CysG () catalyses C-methylation of uroporphyrinogen III (

). It transfers two methyl groups from S-adenosyl-L-methionine to the C-2 and C-7 atoms of uroporphyrinogen III to yield precorrin-2 via the intermediate formation of precorrin-1. SUMT is the first enzyme committed to the biosynthesis of either sirohaem or cobalamin rather than haem, and precorrin-2 is the last common intermediate in the biosynthesis of corrinoids such as cobalamin, sirohaem and coenzyme F430 . SUMT belongs to the domain superfamily of tetrapyrrole (corrin/porphyrin) methylases (

), which includes methylases that use S-AdoMet in the methylation of diverse substrates.

In sirohaem biosynthesis, the next two steps are beta-NAD(
+
)-dependent dehydrogenation of precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield sirohaem . Both of these steps are performed by precorrin-2 oxidase/ferrochelatase. In sirohaem synthase CysG, it corresponds to the N-terminal (CysGB) domain . Ferrochelation can also be performed by CbiK (

) or by SirB or CbiX .

In the anaerobic cobalamin biosynthesis (e.g., in Salmonella typhimurium), a cobaltochelatase produces cobalt-precorrin-2. This cobaltochelation can be performed by CbiK or by CbiX , but also by CysGB homologues , even though this is not their primary function . Therefore, CysGB can essentially duplicate the function of an unrelated chelatase, CbiK . Note that in the aerobic cobalamin biosynthesis, cobalt insertion occurs in a later, different step (see

).

Precorrin-2 oxidase/chelatases are not similar in sequence or structural fold to any other known chelatases or oxidases . Analysis of mutant proteins suggests that both catalytic activities share a single active site cleft formed between the N-terminal NAD-binding subdomain and the central subdomain . Therefore, they can be considered as the third class of cobalt chelatases, in addition to class I (ATP-dependent, aerobic pathway

) and class II (ATP-independent, anaerobic pathway

) . As with the class II chelatases, they do not require ATP for activity. However, they are not structurally similar to class II chelatases, and it is likely that they have arisen by the acquisition of a chelatase function within a dehydrogenase catalytic framework .
Nucleoside-diphosphate kinase-like NDK-H5 (NDK_H5)
Type: Family

This family contains homologues of nucleoside diphosphate kinases (NDPKs). They are designated NDP kinase homologue 5 (NDK-H5), and differ from other NDPKs by having a C-terminal Dpy-30 motif. Despite considerable sequence similarity to other NDPKs, and conservation of seven out of nine known functionally important residues , human NDK-H5 (nm23-H5) seems to lack NDP kinase activity . The nature of the sequence features specific to the NDK-H5 as compared to other NDPKs suggests that it may be unable to form hexamers and instead have a dimeric structure, which may affect its catalytic activity.

NDK-H5 is thought to be involved in early stages of spermatogenesis . Heterologous expression of murine NDK-H5 (nm23-M5) in yeast cells confers protection from cell death induced by Bax, which is due to the generation of reactive oxygen species, and over-expression of nm23-M5 in fibroblasts alters cellular levels of several antioxidant enzymes including Gpx5 . Therefore, nm23-M5 may play a role in late spermatogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species .
BA14k family (BA14K)
Type: Family

BA14K is strongly immunoreactive; it induces both humoral and cellular responses in hosts throughout the infective process . It has lectin-like properties, and may play a role in the synthesis of smooth lipopolysaccharide .
BDS potassium channel toxin (BDS_K_chnl_tox)
Type: Family

This entry represents the sea anemone type 3 (BDS) potassium channel toxins. Family members include toxin APETx1 and 2 , and the antihypertensive and antiviral proteins BDS-I (

) [[cite~:22442564]] and BDS-II (

) expressed by Anemonia sulcata. BDS-I is organised into a triple-stranded antiparallel β-sheet, with an additional small antiparallel β-sheet at the N terminus . The proteins are known to specifically block the Kv3.4 potassium channel, and thus bring about a decrease in blood pressure . Moreover, they inhibit the cytopathic effects of mouse hepatitis virus strain MHV-A59 on mouse liver cells, by an unknown mechanism . This entry also includes the BDS-like antimicrobial peptide known as Crassicorin-I, a peptide with both antimicrobial and neurotoxin activities that may act by impairing sodium or potassium channels in the prey .
CALMODULIN-BINDING PROTEIN60 (CBP60)
Type: Family

CALMODULIN-BINDING PROTEIN60 (CBP60) family from plants have been known to be involved in both biotic and abiotic stress responses . Some members (for example,

), are known to be involved in the induction of plant defence responses . In Arabidopsis, CBP60s have eight members, including CBP60g and SARD1, which encode positive regulators of plant immunity that promote production of salicylic acid (SA) and affect expression of SA-dependent and SA-independent defense genes .
Calmodulin-binding domain, plant (CaM-bd_dom_pln)
Type: Domain

This domain is found repeated in a number of plant calmodulin-binding proteins (such as

,

and

). It is thought to represent a calmodulin-binding domain . Binding of the proteins to calmodulin depends on the presence of calcium ions . Proteins containing this domain are thought to be involved in various processes, such as plant defence responses and stolonisation or tuberization .
CAP160 (CAP160)
Type: Repeat

This region featured in this family is repeated in spinach cold acclimation protein CAP160 (

) CAP160 is induced during periods of drought stress; its precise function is unknown but it has been implicated in the stabilisation of membranes, cytoskeletal elements, and ribosomes. By acting as a compatible solute, it may reduce the toxic effects of cellular solutes that accumulate at high concentration . Other members of this family are also induced by water stress, abscisic acid, and/or low temperature, such as desiccation-responsive protein 29B (

) and CDet11-24 protein (

).
Cas1p, 10 TM acyl transferase domain (Cas1_AcylTrans_dom)
Type: Domain

Cas1p protein of Cryptococcus neoformans is required for the synthesis of O-acetylated glucuronoxylomannans, a consitutent of the capsule, and is critical for its virulence . This entry represents the multi TM domain of the Cas1p, which was unified with the 10 TM Sugar Acyltransferase superfamily . This superfamily is comprised of members from the OatA, MdoC, OpgC, NolL and GumG families in addition to the Cas1p family . The Cas1p protein has a N-terminal PC-esterase domain with the opposing acyl esterase activity .
Cbp4 (Cbp4)
Type: Family

In Saccharomyces cerevisiae, Cbp4 is a mitochondrial protein required for assembly of cytochrome bc1 complex .
WisP, C-terminal (WisP_C)
Type: Domain

This entry represents the C-terminal domain found in the Tropheryma whipplei WisP family of proteins .
Cytochrome c oxidase, subunit IV, bacterial aa3 type (Cyt_c_oxidase_su4_bac-aa3)
Type: Domain

Bacterial cytochrome c oxidase is found bound to the to the cell membrane, where it is involved in the generation of the transmembrane proton electrochemical gradient. It is composed of four subunits. Subunit IV consists of one transmembrane helix that does not interact directly with the other subunits, but maintains its position by indirect contacts via phospholipid molecules found in the structure. The function of subunit IV is as yet unknown .
Chromatin modification-related protein Eaf7/MRGBP (Eaf7/MRGBP)
Type: Family

This entry includes fungal chromatin modification-related protein Eaf7 and its mammalian homologue, MRG/MORF4L-binding protein (MRGBP). Eaf7/MRGBP is a component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A .
Conjugative transposon, TraJ, C-terminal (Conjugative_transposon_TraJ_C)
Type: Domain

Proteins in this entry are designated TraJ and are found in a proposed transfer region of a class of conjugative transposon found primarily in the Bacteroides lineage. They are related to conjugation system proteins in the Proteobacteria, including TrbL of Agrobacterium Ti plasmids and VirB6.

This entry represents the C-terminal domain of these proteins.
DmpG-like communication (DmpG_comm)
Type: Domain

This domain is found towards the C-terminal region of various aldolase enzymes. It consists of five α-helices, four of which form an antiparallel helical bundle that plugs the C terminus of the N-terminal TIM barrel domain . The communication domain is thought to play an important role in the heterodimerisation of the enzyme .
Cell division protein SepF, archaea (SepF_arc)
Type: Family

This protein family represents the Cell division protein SepF and similar uncharacterised archaeal protein. Proteins in this family show sequence similarity to the bacterial SepF protein, which accumulates at the cell division site in an FtsZ-dependent manner and is required for proper septum formation . SepF from the halofilic archaea Haloferax volcanii co-localizes with the homologues FtsZ1 and FtsZ2 and is essential for cell division .
Protein of unknown function DUF1622 (DUF1622)
Type: Family

This is a family of highly conserved sequences, from hypothetical proteins expressed by both bacterial and archaeal species.
Autographa californica nuclear polyhedrosis virus (AcMNPV), Orf117 (AcMNPV_Orf117)
Type: Family

This entry is represented by Autographa californica nuclear polyhedrosis virus (AcMNPV), Orf117; it is a family of uncharacterised viral proteins.
Heparan-alpha-glucosaminide N-acetyltransferase, catalytic domain (HGSNAT_cat)
Type: Domain

Heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase (HGSNAT) catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required for its further catabolism. Mutations of the HGSNAT gene cause the neurodegenerative disease mucopolysaccharidosis IIIC (MPS IIIC) .

This entry represents the catalytic domain of HGSNAT which contains the conserved histidine in the active site (His269), thought to hold the acetyl group during the transfer across the membrane and required for its enzymatic activity .
Transmembrane protein 43 family (TMEM43_fam)
Type: Family

This entry represents the transmembrane protein 43 family of proteins, which may function as tetraspanin-like membrane organisers .
PD-(D/E)XK nuclease (PDDEXK_10)
Type: Family

This family is found to carry modified motifs characteristic of PD-(D/E)XK endonuclease superfamily. These are the conserved Glu of motif I, the Asp surreounded by hydrophobics of motif II, EIKS of motif III, and the lysine of mmotif IV has migrated to an α-helix following the third core β-strand. The conserved patch of positively charged lysine and arginine residues in the motif IV apha-helix might be involved in substrate-binding or be contributing to active site formation . Members with an additional N-terminal coi9led-coil domain, are annotated as tropomyosin, coiled-coil or microtubule binding proteins .
Protein of unknown function DUF1627 (DUF1627)
Type: Family

This is a group of hypothetical proteins predicted to be expressed in a number of bacterial species.
Immunity MXAN_0049 protein (Imm11)
Type: Domain

This entry, previously known as DUF1629, represents a domain found in a group of bacterial proteins, including MXAN_0049 from Myxococcus xanthus (

), which adopts an α-β structure (

). This domain covers the whole length of the protein in most members and is found associated with (

) in others. Some members were identified as immunity proteins .
Protein of unknown function DUF1631 (DUF1631)
Type: Family

The members of this family are sequences derived from a group of hypothetical proteins expressed by certain bacterial species. The region concerned is approximately 440 amino acid residues in length.
TMEM144 (TMEM144)
Type: Family

Members of this family fall in to the drug/metabolite transporter (dmt) superfamily. They carry 10xTM domains arranged as 5+5. Although these two sets may originally have arisen by gene-duplication the divergence now is such that the similarity between the two halves is no longer detectable by sequence.
Protein of unknown function DUF1633 (DUF1633)
Type: Family

This family contains sequences derived from a group of hypothetical proteins expressed by Arabidopsis thaliana (Mouse-ear cress). These sequences are highly similar and the region concerned is about 100 residues long.
Domain of unknown function DUF1638 (DUF1638)
Type: Domain

This entry contains sequences covering an approximately 270 amino acid stretch of a group of hypothetical proteins and are confined to Bacteria and Archaea. DUF1638 domain-containing protein, such as PGA1_c13340 from Phaeobacter inhibens, is suggested to be involved in the synthesis of vitamin B12 .
Protein of unknown function DUF1639 (DUF1639)
Type: Family

This approximately 50-residue region is found in a number of sequences derived from hypothetical plant proteins. This region features a highly basic 5 amino-acid stretch towards its centre.
Protein of unknown function DUF1641 (DUF1641)
Type: Family

Archaeal and bacterial hypothetical proteins are found in this family, with the region in question being approximately 40 residues long.
Protein of unknown function DUF1643 (DUF1643)
Type: Family

This entry includes Bacteriophage D3, Orf41.6. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

The members of this family are all sequences found within hypothetical proteins expressed by various bacteria, archaea and phage. The region concerned is approximately 150 residues long.
Protein of unknown function DUF1645, plant (DUF1645_plant)
Type: Family

These sequences are derived from a number of hypothetical plant proteins. The region in question is approximately 270 amino acids long. Some members of this family are annotated as yeast pheromone receptor proteins AR781 but no literature was found to support this.
Protein of unknown function DUF1646 (DUF1646)
Type: Family

Some of the members of this family are hypothetical bacterial and archaeal proteins, but others are annotated as being cation transporters expressed by the archaeon Methanosarcina mazei (Methanosarcina frisia) (

,

and

).
Protein of unknown function DUF1647 (DUF1647)
Type: Family

This entry consists of hypothetical proteins of unknown function.
Autophagy-related protein 101 (ATG101)
Type: Family

Atg101 is a critical autophagy factor that functions together with ULK, Atg13 and FIP200 . In fission yeasts, it has a role in meiosis and sporulation .
Calcium release-activated calcium channel protein (CRAC_channel)
Type: Family

This entry includes Drosophila Orai and human Orai1, Orai2 and Orai3. ORAI-1 green fluorescent protein (GFP) reporters are co-expressed with STIM-1 (ER CA(2+) sensors) in the gonad and intestine. The protein has four predicted transmembrane domains with a highly conserved region between TM2 ad TM3. This conserved domain is thought to function in channel regulation. ORAI1-related proteins are required for the production of the calcium channel, CRAC, along with STIM1-related proteins .
Protein of unknown function DUF1651 (DUF1651)
Type: Family

The proteins in this entry have not been characterised.