SII-SWORD/CoKE huggingface dataset:
Transcription factor SRY (SRY)
Type: Family

This entry represents the testis-determining factor Sry (Sex-determining Region Y). Sry is a transcriptional activator that regulates a genetic switch in male development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells . Sry is involved in different aspects of gene regulation including promoter activation or repression and contains a high-mobility-group (HMG) box that recognises DNA by partial intercalation in the minor groove . It binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. Sry also facilitates DNA bending and is involved in pre-mRNA splicing. It is also involved in maintenance of motor functions of dopaminergic neurons in the male adult brain. Sry interacts with a number of partners, including CALM, EP300 (modulates Sry DNA-binding activity), HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1 (impaired Sry DNA-binding activity), SLC9A3R2 and WT1. The C-terminal nuclear localization signal in Sry HMG-box domain mediates nuclear import through importin beta 1 .

Defects in Sry can cause gonadal dysgenesis XY female type (GDXY) , which is also known as 'XY females' or Swyer syndrome . Patients suffer rapid and early degeneration of their gonads, which prevents the development secondary sexual characteristics at puberty. Defects in Sry are also found Turner's Syndrome, a disease characterised by gonadal dysgenesis in a 45,X female type . Defects in Sry can also cause true hermaphroditism , genetically heterogeneous condition where patients have both mature ovarian and mature testicular tissue (46,XX, 46,XY or a mosaic of 46,XX/46,XY) .
Lipoprotein, LppL (Lipoprotein_LppL)
Type: Family

This group represents a lipoprotein, LppL type.
Acetyltransferase, GNAT, predicted (AcTrfase_GNAT_prd)
Type: Family

This group represents a predicted acetyltransferase, GNAT family type.

Bacillus subtilis has a putative posttranslational modification system of the acuABC genes. Posttranslational modification is an efficient mechanism for controlling the activity of structural proteins, gene expression regulators and enzymes in response to rapidly changing physiological conditions .

The AcuA protein is a member of the Gcn5-related N-acetltransferase (GNAT) superfamily and the AcuC protein is a class I histone deacetylase. The role of the AcuB protein remains unknown. AcuA controls the activity of acetyl-CoA synthetase (

) by acetylating residue Lys549 .
Methane monooxygenase component D (MmoD)
Type: Family

Biological oxidation of methane to methanol by aerobic bacteria is catalysed by two different enzymes, the soluble methane monooxygenase (sMMO) and the membrane-bound or particulate methane monooxygenase (pMMO). This entry represents MmoD, a component and a regulator of the sMMO . sMMO is only expressed at very low copper:biomass ratios, while pMMO expression increases as this ratio increases. The copper switch that controlling the expression of these two MMOs is regulated by MmoD and methanobactin .
Spore germination protein GerPD, predicted (Spore_germination_GerPD_prd)
Type: Family

This entry represents a predicted spore germination protein GerPD. They are required for the formation of functionally normal spores. They could be involved in the establishment of normal spore coat structure and/or permeability, which allows the access of germinants to their receptor .
Chloroquine resistance transporter (Transprt_Chloroquine)
Type: Family

This family consists of the chloroquine resistance transporter (CRT) from apicomplexan parasites, including the malaria parasite Plasmodium falciparum, and homologues from Dictyostelium discoideum . Mutations in this transporter are responsible for resistance to the antimalarial drug chloroquine .
Uncharacterised conserved protein UCP037672 (UCP037672)
Type: Family

This group represents an uncharacterised conserved protein.
Uncharacterised conserved protein UCP037673 (UCP037673)
Type: Family

This entry represents a group of uncharacterised conserved proteins, including the uncharacterised protein ycf91 from Pyropia yezoensis (Red alga).
DNA mismatch repair protein MutS/MSH (DNA_mismatch_repair_MutS/MSH)
Type: Family

This family of DNA mismatch repair proteins includes MutS and Msh.

Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication . MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base . MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch . MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level . Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA.
Aegyptin-like (Aegyptin-like)
Type: Family

This entry represents a group of proteins from mosquitoes, including Aegyptin from Aedes aegypti (Yellowfever mosquito) and Aegyptin-like protein (AAPP) from Anopheles stephensi (Indo-Pakistan malaria mosquito). Both proteins modulate blood feeding of female mosquitoes on vertebrate hosts . Aegyptin, also known as salivary gland allergen Aed3, influences cytokine production and populations of circulating leukocytes . This protein is secreted by the adult female salivary gland and can cause allergic reactions in human . AAPP inhibits collagen-induced platelet aggregation in the host .
Uncharacterised conserved protein UCP037692 (UCP037692)
Type: Family

This group represents an uncharacterised conserved protein.
Small ribosomal subunit protein mS37, fungal-type (Ribosomal_mS37_fun)
Type: Family

This group represents a the small ribosomal subunit protein mS37, also known as mitochondrial ribosomal protein 10, which is involved in mitochondrial genome encoded proteins translation .
rRNA-processing protein Fyv7, fungi (Fyv7_fungi)
Type: Family

This entry represents Fyv7 (Function required for yeast viability protein 7) from fungi. These proteins are involved in the processing of 20S pre-rRNA during the maturation of SSU-rRNA from tricistronic RNA transcripts (SSU-rRNA, 5.8S rRNA, LSU-rRNA). The SSU (small subunit) processome is required for production of the small ribosomal subunit RNA, the 18S rRNA . Fyv7 may also be required for survival upon K1 Killer toxin exposure.
Cyclin-dependent kinase 2-associated protein 1/2 (DOC_1/2)
Type: Family

This group represents the cyclin-dependent kinase 2-associated protein 1/2 (DOC-1/1R). DOC-1 is a specific inhibitor of the cell-cycle kinase CDK2 . DOC-1R associates with CDK2 and inhibits CDK2 activation by obstructing its association with cyclin E and A .
Cytochrome c oxidase subunit VIIa-related, mitochondrial (Cyt_c_oxidase_su7a-rel_mt)
Type: Family

This group represents a cytochrome c oxidase subunit VIIa-related protein, mitochondrial type (also known as Cytochrome c oxidase subunit 7A2-like, mitochondrial) .
Tax1-binding protein 3 (Tax1-binding_p3)
Type: Family

This entry represents Tax1-binding protein 3, also known as TIP-1, which is a PDZ domain-containing protein that functions in a wide variety of biological events through selective interaction with different proteins. It interacts with the RhoA effector protein rhotekin . It also associates with glutaminase L , potassium channel Kir2.3 and NMDA receptors . In humans, Tax1-binding protein 3 has been shown to be involved in the activation of Cdc42 by the viral protein HPV16 E6 . TIP-1 can have both an oncogenic function or act as a tumor suppressor, probably by modulating the transcriptional activity of beta-catenin .
Biopolymer transport ExbB-like protein 1 (Biopolymer_transpt_ExbB-like_1)
Type: Family

This group represents the biopolymer transport exbB-like protein 1.
Putative MotA/TolQ/ExbB family protein (MotA/TolQ/ExbB-rel)
Type: Family

This entry represents uncharacterised proteins related to TolQ and other members of the MotA/TolQ/ExbB family. TolQ and TolR have structural and functional homologies not only to ExbB and ExbD of the TonB system, but also with MotA and MotB of the flagellar motor. These three systems are thought to function as ion potential-driven molecular motors .
Transcription regulator HTH, MJ1545, predicted (Tscrpt_reg_HTH_MJ1545_prd)
Type: Family

This group represents a predicted HTH transcriptional regulator, MJ1545 type.
Probable cell wall amidase LytH (LytH)
Type: Family

This group represents a predicted cell-wall amidase, LytH type. LytH (YunA) has been identified as a sporulation-specific part of the cortex structure. The lytH gene is only expressed during sporulation and is controlled by the mother cell-specific sigma factor sigma(K). lytH encodes an L-Ala-D-Glu peptidase involved in production of single L-alanine side chains from tetrapeptides in the spore cortex . Deficiency in the lytH gene causes an elevation of methicillin resistance in Staphylococcus aureus, strain SR17238, a strain of S. aureus with a low level of resistance to methicillin .
Putative N-acetyltransferase YlbP (YlbP)
Type: Family

This group represents a predicted N-acetyltransferase, YlbP type.
Transcription factor FapR (Transcription_factor_FapR)
Type: Family

This entry represents the transcription factor FapR, which is involved in the regulation of membrane lipid biosynthesis by repressing genes involved in fatty acid and phospholipid metabolism . FapR controls the expression of many genes involved in fatty acid and phospholipid metabolism (the fap regulon) .
Synthesis of cytochrome c oxidase, Sco1/Sco2 (Synth_of_cyt-c-oxidase_Sco1/2)
Type: Family

This entry represents cytochrome c oxidase assembly factors Sco1 and Sco2 (Synthesis of Cytochrome c Oxidase, factors 1 and 2), mitochondrial inner membrane-tethered metallochaperones that have regulatory roles in the maintenance of cellular copper homeostasis. These proteins are essential for the assembly of the catalytic core of cytochrome c oxidase (COX or complex IV), as well as other roles in copper homeostasis such as mitochondrial redox signalling . Both Sco1 and Sco2 contain highly conserved CXXXC motifs thought to be required for copper binidng.

COX is the terminal enzyme of the energy transducing respiratory chain in eukaryotes and certain prokaryotes. It catalyses the transfer of electrons from cytochrome c to molecular oxygen and pumps protons across the mitochondrial inner membrane to establish a proton gradient for ATP synthesis. It consists of 12-13 protein subunits, with 3 subunits (Cox1-Cox3) forming the enzyme core. COX uses haem and copper as cofactors: Cox1 contains a 1-copper centre (CuB) that interacts with the haem moiety and Cox2 contains a 2-copper centre (CuA). Sco1 and Sco2 act as copper chaperones, transporting copper to the CuA site in Cox2, and are thought to have cooperative functions in COX assembly . In addition, human Sco2 is also the downstream mediator of the balance between the utilization of respiratory and glycolytic pathways and both Sco1 and Sco2 may have regulatory roles in regulating cellular copper levels (homeostasis) . Sco2 may have a copper-level-detection signalling role, acting upstream and in conjunction with Sco1.

Defects in Sco1 are a cause of cytochrome c oxidase deficiency (COX deficiency) , a clinically heterogeneous disorder with features ranging from isolated myopathy to severe multisystem disease, and onset from infancy to adulthood. Defects in Sco2 are the cause of fatal infantile cardioencephalomyopathy with cytochrome c oxidase deficiency (FIC) , which is characterised by hypertrophic cardiomyopathy, lactic acidosis, and gliosis.
Putative antitoxin VapB45-like (VapB45-like)
Type: Family

This entry includes the putative antitoxin VapB45 from Mycobacterium tuberculosis. It is possibly the antitoxin component of a type II toxin-antitoxin (TA) module. Its cognate toxin is VapC45 .
TIR domain-containing adapter molecule 1 (TICAM1)
Type: Family

TIR domain-containing adapter molecule 1 (TICAM1) is involved in innate immunity against invading pathogens. It is an adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis .
Toll-interleukin 1 receptor domain-containing adaptor protein, Tirap (Tol-interleuk_rcpt_adapt_Tirap)
Type: Family

This group represents a toll-interleukin 1 receptor domain-containing adaptor protein, Tirap type.
Myeloid differentiation primary response protein MyD88 (Myelin_different_resp_MyD88)
Type: Family

Myeloid differentiation primary response protein MyD88 is an intracellular adaptor protein that has an essential role in innate immune signalling. It is vital for the proper responses of interleukin-1 and interleukin-18 and nearly all toll-like receptors (except TLR3) in the activation of transcription factors NF-kappa B and AP-1 followed by the induction of pro-inflammatory genes .
Histone deposition protein Asf1 (Hist_deposition_Asf1)
Type: Family

Asf1 is a histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly .
Protein/nucleic acid deglycase HchA (HchA)
Type: Family

Escherichia coli Hsp31, the hchA gene product, has been reported to function as a chaperone that plays an important role in protecting cells from severe heat shock and starvation, as well as in acid resistance of stationary-phase cells . It has also been reported to function as a glutathione-independent glyoxalase and to display an aminopeptidase activity specific against peptide substrates with alanine or basic amino acids (lysine, arginine) at N terminus . More recent studies suggest that Hsp31 is likely to function as a protein deglycase that repairs proteins and nucleic acids from glycation by methylglyoxal and glyoxal .
Tautomerase PptA (Tautomerase_PptA)
Type: Family

This entry represents tautomerase PptA (

), a 4-oxalocrotonate tautomerase homologue found in bacteria such as Escherichia coli (in which it is also known as YdcE) . It functions as a homodimer. Tautomerase PptA can use enol isomers of phenylpyruvate, 2-hydroxy-2,4-pentadienoate and (p-hydroxyphenyl)pyruvate as substrates. It is inhibited by (E)-2-fluoro-p-hydroxycinnamate .
Cyclin, herpesvirus (Cyclin_herpesvir)
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 a viral cyclin.
Retinal rod rhodopsin-sensitive cGMP 3', 5'-cyclic phosphodiesterase, delta subunit (Rhodop-sen_GMP-Pdiesterase_dsu)
Type: Family

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase (

) is an oligomer composed of two catalytic chains (alpha and beta), an inhibitory chain (gamma) and a delta chain. This protein interacts with RPGR (retinitis pigmentosa GTPase regulator) , ARL2 (Arf-like-2) and ARL3. This entry represents the delta subunit , which is thought to act as a prenyl-binding protein and participates in the transport of PDE6 catalytic alpha/beta subunits .
Bcl-2-like protein 11 (Bcl-2-like_11)
Type: Family

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.

This group represents the Bcl-2-like protein 11 which can induce apoptosis.
SH2 protein 1A (SH2_prot_1A)
Type: Family

SH2 domain-containing protein 1A (SH2D1A) is an adaptor protein that appears to regulate B-cell differentiation via switching of SLAM (CD150)-mediated signalling pathways . The SLAM receptor is expressed on activated T and B lymphocytes. SH2D1A inhibits SLAM self-association. SH2D1A acts by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region .

Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) , which is also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease . XLP is a rare immunodeficiency characterised by extreme susceptibility to infection with Epstein-Barr virus (EBV) (HHV-4) (Human herpesvirus 4). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.
Ribonuclease H, Bacteroides-type (RNase_H_bac)
Type: Family

This entry represents ribonuclease H (RNase H) from bacteria, especially from Bacteroides. RNase H is an endonuclease that specifically degrades the RNA of RNA-DNA hybrids .
Sulfofructosephosphate aldolase, YihT (SFP_aldolase_YihT)
Type: Family

This entry represents sulfofructosephosphate aldolase from Enterobacteriaceae. It cleaves 6-deoxy-6-sulfo-D-fructose 1-phosphate (SFP) to form dihydroxyacetone phosphate (DHAP) and 3-sulfolactaldehyde (SLA) .
Peptidase S8A, Vpr (Peptidase_S8A_Vpr)
Type: Family

This entry contains serine peptidases belonging to MEROPS peptidase family S8A (subtilisin family, clan SB). These Vpr proteases are involved in the maturation of the peptide antibiotic (lantibiotic) subtilin in Bacillus spp .
N-acetylmuramoyl-L-alanine amidase, YrvJ, predicted (N-acetylmuramoyl-L-ala_amidase)
Type: Family

This group represents a predicted N-acetylmuramoyl-L-alanine amidase, YrvJ type.
Peptidase S8A, subtilisin-related protease, kinetoplastidia (Subtilisin-like_kinetoplast)
Type: Family

Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes . The subtilisin-serine protease (SRSP) family hormone and pro-protein convertases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7/7/LPC) act within the secretory pathway to cleave polypeptide precursors at specific basic sites, generating their biologically active forms. Serum proteins, pro-hormones, receptors, zymogens, viral surface glycoproteins, bacterial toxins, amongst others, are activated by this route . The SRSPs share the same domain structure, including a signal peptide, the pro-peptide, the catalytic domain, the P/middle or homo B domain, and the C terminus.

This entry contains putative subtilisin-related proteases from Kinetoplastida (Trypanosomatid protozoa).
Peptidase S8A, subtilisin-related, cyanobacteria-1 (Pept_S8A_subtilisin_cyanobac-1)
Type: Family

Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes . The subtilisin-serine protease (SRSP) family hormone and pro-protein convertases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7/7/LPC) act within the secretory pathway to cleave polypeptide precursors at specific basic sites, generating their biologically active forms. Serum proteins, pro-hormones, receptors, zymogens, viral surface glycoproteins, bacterial toxins, amongst others, are activated by this route . The SRSPs share the same domain structure, including a signal peptide, the pro-peptide, the catalytic domain, the P/middle or homo B domain, and the C terminus.

This entry contains predicted subtilisin-related peptidases, predominantly found in cyanobacterial species. The peptides belong to MEROPS peptidase family S8A (subtilisin family, clan SB), and are unassigned.
Peptidase S8A, SAM-P45 (Peptidase_S8A_SAM-P45)
Type: Family

This entry contains serine peptidases belonging to MEROPS peptidase family S8A (subtilisin family, clan SB). They represent novel peptidases of the subtilisin family from Streptomyces spp .