SII-SWORD/CoKE huggingface dataset:
UNC5C, death domain (Death_UNC5C)
Type: Domain

This entry represents the death domain (DD) found in Uncoordinated-5C (UNC5C), which is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. It belongs to the UNC-5 family. UNC5C plays a critical role in the development of spinal accessory motor neurons . Methylation of the UNC5C gene is associated with early stages of colorectal carcinogenesis .

UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
UNC5A, death domain (Death_UNC5A)
Type: Domain

This entry represents the death domain (DD) found in Uncoordinated-5A (UNC5A), which is a receptor for the secreted netrin-1 and plays a critical role in neuronal development and differentiation, as well as axon-guidance . It also plays a role in regulating apoptosis in non-neuronal cells as a downstream target of p53 . It belongs to the UNC-5 family.

UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
UNC5B, death domain (Death_UNC5B)
Type: Domain

This entry represents the death domain (DD) found in Uncoordinated-5B (UNC5B), which is a receptor for the secreted netrin-1 and plays a role in axonal guidance, angiogenesis, and apoptosis. UNC5B signaling is involved in the netrin-1-induced proliferation and migration of renal proximal tubular cells . It is also required for vascular patterning during embryonic development, and its activation inhibits sprouting angiogenesis . It belongs to the UNC-5 family.

UNC5 proteins are transmembrane proteins with an extracellular domain consisting of two immunoglobulin repeats, two thrombospondin type-I modules and an intracellular region containing a ZU-5 domain, UPA domain and a DD .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Hydroxyacid-oxoacid transhydrogenase (HOT)
Type: Family

Hydroxyacid-oxoacid transhydrogenase (HOT or ADHFe1), also known as D-2-hydroxyglutarate transhydrogenase, catalyzes the conversion of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA), coupled to the stoichiometric conversion of alpha-ketoglutarate to D-2-hydroxyglutarate in gamma-Hydroxybutyrate catabolism . Unlike many other alcohols, which are oxidized by NAD-linked dehydrogenases, gamma-hydroxybutyrate is metabolized to succinate semialdehyde by hydroxyacid-oxoacid transhydrogenase which does not require free NAD or NADP, but instead using alpha-ketoglutarate as an acceptor, converting it to d-2-hydroxyglutarate. Alpha-ketoglutarate serves as an intermediate acceptor to regenerate NAD(P) required for the oxidation of GHB. HOT also catalyzes the reversible oxidation of a hydroxyacid obligatorily coupled to the reduction of an oxoacid, and requires no cofactor. In mammals, the HOT enzyme is located in mitochondria, and is expressed with an N-terminal mitochondrial targeting sequence. HOT enzyme is member of the metal-containing alcohol dehydrogenase family. They typically contain an iron although other metal ions may be used .
PI-PLC X domain-containing protein 1/2/3 (PLCXD1/2/3)
Type: Family

This entry includes phosphatidylinositol-specific phospholipase C X domain containing 1 (PI-PLCXD1), 2 (PI-PLCXD2) and 3 (PI-PLCXD3), which are bacterial phosphatidylinositol-specific phospholipase C (PI-PLC,

) sequence homologs found in animals. The typical eukaryotic phosphoinositide-specific phospholipase C (PI-PLC,

) has a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, members in this group contain a single TIM-barrel type catalytic domain, X domain, and are more closely related to bacterial PI-PLCs, which participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may distinct from that of typical eukaryotic PI-PLCs .
Class IV homeodomain-leucine zipper (HD-Zip_IV)
Type: Family

This entry represents a group of plant proteins that belong to transcription factors of the class IV homeodomain-leucine zipper (HD-Zip IV) protein family. This entry includes GLABRA2, ANTHOCYANINLESS2 (ANL2), ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1), PROTODERMAL FACTOR2 (PDF2), ROC1-9, HDG1-12 from Arabidopsis.

GLABRA2 regulates the frequency of trichome initiation and determines trichome spacing . ANL2 is involved in anthocyanin distribution and root development . PDF2 and ATML1 are involved in shoot epidermal cell differentiation. ATML1 and PDF2 function redundantly as positive regulators of shoot epidermal cell differentiation, and at least one copy of these genes is essential for embryo development . HDG5 is involved, together with PDF2, in the regulation of flower organ development by promoting the expression of APETALA 3 (AP3) in the epidermis and internal cell layers of developing flowers . ROC1 may be involved in protoderm differentiation and radial pattern formation during early embryogenesis .
Tetratricopeptide repeat protein 34 (TTC34)
Type: Family

The function of TTC34 is not clear.
Chaperone protein DnaJ 13 (AtJ13)
Type: Family

This entry represents a group of J-domain proteins from plants, including AtJ13 (also known as OWL1, At2g35720) from Arabidopsis. It is involved in perception of very low light fluences .
PHD finger protein 12 (PHF12)
Type: Family

PHF12, also known as Pf1, is a PHD zinc finger protein that binds TLE (transducin-like enhancer) in an mSin3A-independent manner and recruits functional TLE complexes to repress transcription .
Solute carrier family 25 member 44 (SLC25A44)
Type: Family

SLC25A44 belongs to the the solute carrier family 25 (SLC25) . Members of SLC25 are known to transport molecules across the mitochondrial membrane. In brown adipose tissue (BAT), SLC25A44 has been shown to transport branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria and to be required for BCAA catabolism .
Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1)
Type: Family

Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1) regulates phospholipid biosynthesis . In mammals, it is a mitochondrial phosphatidylglycerophosphate (PGP) phosphatase that regulates cardiolipin biosynthesis .
Vesicle-associated membrane protein 5 (Vamp5)
Type: Family

Vesicle-associated membrane protein 5 (Vamp5) is part of the Vamp family of SNAREs (soluble NSF attachment protein receptor), whose members are proteins responsible for the last stage of docking and subsequent fusion in diverse intracellular membrane transport events .
Serine protease inhibitor Kazal-type 2 (SPINK2)
Type: Family

SPINK2 is a serine proteinase inhibitor . It inhibits acrosin, which is a protease released from the acrosome of spermatozoa as a consequence of the acrosome reaction .
Purkinje cell protein 2 (Pcp2)
Type: Family

Pcp2, also known as Purkinje cell-specific protein L7, is a member of the GoLoco protein family with highly cell-specific expression, being restricted to cerebellar Purkinje cells and retinal bipolar neurons in various species. It may function as guanine nucleotide dissociation inhibitor, or a guanine nucleotide exchange factor .
NKG2-D type II integral membrane protein (NKG2D)
Type: Family

NKG2D is an activating receptor for triggering the NK cell cytotoxic activity . It binds to a variety of cell surface glycoproteins distantly related to MHC class I molecules, termed NKG2D ligands (NKG2DL). The expression of a certain ligand or a particular allelic variant is essential to drive a proper immune response . The NKG2D/NKG2DL axis has been shown to be the potential therapeutic candidate for anticancer immunotherapy .
Acyl-CoA thioesterase, double hotdog domain (Acyl-CoA_hotdog)
Type: Homologous_superfamily

This superfamily includes TE4 thioesterases that contain a hotdog domain. Studies on TesB from Y. pestis provide insights into the TE4 thioesterase family. It is organised in an octameric arrangement of hotdog domains (a tetramer of double-hotdog protomers) which is not present in any other thioesterase family .
Adenosylhomocysteinase-like superfamily (Adenosylhomocyst_ase-like_sf)
Type: Homologous_superfamily

Structural domains found in this superfamily share the structure of the enzyme adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase, AdoHcyase), which is formed in methylation and catalyses the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. This enzyme is ubiquitous, highly conserved, and a key regulator of the intracellular concentration of adenosylhomocysteine. In addition, this enzyme is a potent inhibitor of S-adenosyl-L-methionine dependent methyltransferases, and thus plays a critical role in the modulation of their activity .
Ribonuclease J, domain 2 (RNase_J_2)
Type: Homologous_superfamily

This superfamily contains proteins of about 50 to 77kDa. The central region is well conserved and contains three conserved histidines. Most of these proteins are related at the N-terminal region to the beta-lactamase family. Ribonuclease J cleaves the 5'-leader sequence of certain mRNAs and may play a role in the maturation and stability of specific mRNAs . It is also required for the maturation of the 16S rRNA acting preferentially on 16S rRNA precursors after association of the 30S and 50S ribosomal subunits .

This superfamily represents the domain 2 found in ribonuclease J.
DNA-binding RecF, domain 2 (RecF_2)
Type: Homologous_superfamily

This superfamily represents the second domain found in structural maintenance of chromosomes (SMC) proteins, which function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression . The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics . This domain is also found in the RecF protein (recombination mediator), which is involved in DNA metabolism and recombination.
Cell/Rod shape-determining protein MreC, domain 2 (Cell/Rod_MreC_2)
Type: Homologous_superfamily

This superfamily corresponds to the structure of the second of the two 6-stranded β barrels which comprise MreC, a rod shape-determining protein in E.coli. More generally, it is involved in cell shape determination of bacteria even when they are not rod shaped.
Pantoate-beta-alanine ligase, C-terminal domain (Pantoate_ligase_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of a pantoate-beta-alanine ligase (also known as pantoate-beta-alanine synthase) which catalyses the formation of pantothenate from pantoate and alanine in the pantothenate biosynthesis pathway. Its C-terminal domain partially covers the active site cavity in the N-terminal domain and it has been proposed that a hinged movement of this domains is responsible for the opening and closing of the active site .
Cell/Rod shape-determining protein MreC, domain 1 (Cell/Rod_1)
Type: Homologous_superfamily

This superfamily corresponds to the structure of the first of the two 6-stranded β barrels which comprise MreC, a rod shape-determining protein in E.coli. More generally, it is involved in cell shape determination of bacteria even when they are not rod shaped.
Serpin superfamily, domain 1 (Serpin_sf_1)
Type: Homologous_superfamily

Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are indeed serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins . Others, such as ovalbumin, are incapable of protease inhibition and serve other functions .

This superfamily represents the first domain found in Serpin proteins.
Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal domain superfamily (KGD_C_sf)
Type: Homologous_superfamily

The 2-oxoglutarate dehydrogenase (OGDH) multienzyme complex is rate-limiting in the TCA cycle in many species, and is an essential nexus in the utilization of sugar and amino acids, funnelled via 2-oxoglutarate and oxidized to succinyl-CoA, process which releases CO2 and results in the reduction of NAD to NADH . An alternative name for this complex is alpha-ketoglutarate dehydrogenase (KGD).

This superfamily represents the C-terminal domain of the multifunctional 2-oxoglutarate metabolism enzyme KGD and related proteins including human DHTKD1 .
MmgE/PrpD superfamily, domain 1 (MmgE/PrpD_sf_1)
Type: Homologous_superfamily

MmgE/PrpD superfamily members include 2-methylcitrate dehydratase (PrpD;

) and citrate/2-methylcitrate dehydratase MmgE. PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle . This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha beta domain . Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus .

This superfamily represents the large domain found in PrpD.
YqeY/Aim41, N-terminal domain (YqeY/Aim41_N)
Type: Homologous_superfamily

This superfamily represents the N terminus of a group of uncharacterised proteins from bacteria, such as YqeY from Bacillus subtilis, and Aim41/YOR215C from yeast.
Serpin superfamily, domain 2 (Serpin_sf_2)
Type: Homologous_superfamily

Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are indeed serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins . Others, such as ovalbumin, are incapable of protease inhibition and serve other functions .

This superfamily represents the second domain found in Serpin proteins.
Outer membrane usher protein FimD, plug domain (FimD_plug_dom)
Type: Homologous_superfamily

This superfamily represents the plug domain, which consists of 6 β strands, found in FimD. In apo-FimD this domain sits within the translocation channel of FimD. When FimC-FimH interacts with FimD, this domain is displaced and exposes a circular channel within the translocation channel .
Flagellin, C-terminal domain, subdomain 2 (Flagellin_C_sub2)
Type: Homologous_superfamily

Bacterial flagella are responsible for motility and chemotaxis . They comprise a basal body, a hook and a filament, the latter accounting for 98% of the mass . Flagellin is the subunit protein that polymerises to form the flagella , the subunits being transported through the centre of the filament to the tip, where they then polymerise . Both the N- and C- termini of the subunit protein, which are α-helical in structure , are required to mediate polymerisation. Although no export or assembly, consensus sequences have been identified: Ala, Val, Leu, Ile, Gly, Ser, Thr, Asn, Gln and Asp tend to make up around 90% of the sequence, Cys and Trp being absent .

Flagellin plays a role in the activation of innate and adaptive immunity. It is an specific ligand for Toll-like receptor 5 (TLR5) in the host, which has lead to great interest to use it as adjuvant for vaccines . The protein is also recognised by the intracellular NAIP5/NLRC4 inflammasome receptor .

This superfamily represents the subdomain 2 found at the C terminus of flagellin proteins.
MmgE/PrpD superfamily, domain 2 (MmgE/PrpD_sf_2)
Type: Homologous_superfamily

MmgE/PrpD superfamily members include 2-methylcitrate dehydratase (PrpD;

) and citrate/2-methylcitrate dehydratase MmgE. PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle . This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha beta domain . Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus .

This superfamily represents the small domain found in PrpD.
Sigma-70 factor, region 1.1 superfamily (RNA_pol_sigma_70_r1_1_sf)
Type: Homologous_superfamily

Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions.

This superfamily represents Region 1.1 which modulates DNA binding by region 2 and 4 when sigma is unbound by the core RNA polymerase . Region 1.1 is also involved in promoter binding, it contains a basic patch on its surface which suggests to play an important role in DNA interaction to facilitate open promoter complex formation .
Killer cell lectin-like receptor subfamily G member 1 (KLRG1)
Type: Family

Killer cell lectin-like receptor subfamily G member 1 (KLRG1) is a co-inhibitory receptor inhibiting the activity of T and NK cells . Its ligands include E-cadherin and N-cadherin. Binding of E-cadherin to KLRG1 has been shown to inhibits effector T-cell function .
GS homeobox 1/2 (GSH1/2)
Type: Family

This family represents the Gsx factors Gsx1 and Gsx2, also known as GSH1/2. These closely related proteins are among the earliest transcription factors expressed in neuronal progenitors of the lateral ganglionic eminence (LGE) in the ventral telencephalon . Both Gsx1 and Gsx2 are expressed in the developing MGE (medial ganglionic eminence) and diencephalon , Gsx2 is expressed at a high level in progenitors of the dorsal LGE (dLGE), whereas Gsx1 is expressed mainly in the MGE and ventral LGE. Gsx1 and Gsx2 control the choice between excitatory and inhibitory cell fates of the interneurons in the developing spinal cord . It has been shown that these factors are essential for striatal and olfactory bulb neurogenesis . Gsx1 also activates the transcription of the GHRH gene and also plays an important role in pituitary development .
Glycophorin-C (Glycophorin-C)
Type: Family

Antigens of the Gerbich blood group system are expressed on glycophorin C (GPC) and glycophorin D (GPD), which are both encoded by a single gene, GYPC. They stabilize red blood cell membranes through their intracellular interaction with protein 4.1 and p55 . Gebrich antigens can act as receptors for the malarial parasite Plasmodium falciparum . Gerbich antibodies usually do not cause serious hemolytic transfusion reactions (HTR); autoantibodies of anti-Ge2- or anti-Ge3 specificity can cause autoimmune hemolytic anemia (AIHA) .
FHIPEP, domain 3 (FHIPEP_3)
Type: Homologous_superfamily

The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus . This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.

This superfamily represents the domain 3 found in FHIPEP protein.
FHIPEP, domain 1 (FHIPEP_1)
Type: Homologous_superfamily

The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus . This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.

This superfamily represents the domain 1 found in FHIPEP protein.
ArgJ beta chain, C-terminal domain (ArgJ_beta_C)
Type: Homologous_superfamily

ArgJ (also known as Ornithine acetyltransferase/OAT) is a bifunctional protein that catalyses the first

and fifth steps

in arginine biosynthesis , coupling acetylation of glutamate with deacetylation of N-acetylornithine, which allows recycling of the acetyl group in the arginine biosynthetic pathway. The structure has been determined for glutamate N-acetyltransferase 2 (ornithine acetyltransferase;

), an ArgJ-like protein from Streptomyces clavuligerus .

When active, ArgJ is a heterotetramer of two alpha and two beta chains, where the alpha and beta chains are the result of autocatalytic cleavage.

This superfamily represents the C-terminal domain found in ArgJ beta chain.
FHIPEP, domain 4 (FHIPEP_4)
Type: Homologous_superfamily

The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus . This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.

This superfamily represents the domain 4 found in FHIPEP protein.
Apoptotic protease-activating factors, helical domain (Apaf_helical)
Type: Homologous_superfamily

This superfamily represents helical domains that are present in apoptotic protease-activating factors (apaf) proteins. On a higher level these proteins are associated with disease resistance in plants {

].