SII-SWORD/CoKE huggingface dataset:
Chorismatase, FkbO/Hyg5 family (Chori_FkbO_Hyg5)
Type: Family

Members of this family include two chemically distinct enzymes that cleave pyruvate from chorismate. FkbO and RapK convert chorismate to pyruvate and (4R,5R)-4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid (DCDC). HygB and Bra8 convert chorismate to pyruvate, water, and 3-hydroxybenzoate. These two enzymes are closely related, and lack homology to chorismate lyase,

, which converts chorismate to pyruvate plus 4-hydroxybenzoate .
Coenzyme gamma-F420-2:alpha-L-glutamate ligase (F420_CofF)
Type: Family

Members of this family are CofF, a RimK-related glutamate ligase that caps the gamma-glutamyl tail of the archaeal form of coenzyme F420, a hydride carrier. This enzyme does not appear in bacterial species, such as Mycobacterium tuberculosis, that make F420 with a different type of tail .
Conserved hypothetical protein CHP04442 (CHP04442)
Type: Family

Members of this family occur exclusively in certain Deltaproteobacteria, including Geobacter and Pelobacter. The function is unknown.
LA_1612 putative O-antigen biosynthesis protein (Lept_O_ant_chp1)
Type: Family

Members of this protein family occur only in a subset of Leptospira species, and in those species occur only in O-antigen biosynthesis regions. Members average about 375 amino acids in length. The function is unknown.
Glycosyltransferase domain (Glyco_TIGR04440)
Type: Domain

This entry represents a putative glycotransferase domain related to the glycosyltransferase 2-like domain (

).
Putative histamine N-monooxygenase (Histamin_N_OH)
Type: Family

Members of this family are involved in synthesising N-hydroxyhistamine as a precursor to acinetobactin, a siderophore found in Acinetobacter baumannii. Assuming histidine is first decarboxylated to histamine, then hydroxylated, members of this family are histamine N-monooxygenase. The putative histidine decarboxylase is found in the same biosynthetic cluster .
Small Trp-rich protein (Small_Trp_rich)
Type: Family

Members of this bacterial protein family average 80 residues in length, and average nearly 6 Trp residues (two of which are invariant) in the first 45, which are strongly hydrophobic. Past this region, the protein is highly charged, with large numbers of Lys, Arg, Asp, and Glu residues. Members usually are divergently transcribed from a gene encoding a c-type cytochrome.
Carnosine synthase 1 (CARNS1)
Type: Family

Carnosine synthase 1 (CARNS1, also known as ATPGD1) catalyses the synthesis of carnosine and homocarnosine, which are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates .
DNA helicase INO80, DEAQ-box helicase domain (DEXQc_INO80)
Type: Domain

Ino80 is evolutionarily conserved from yeast to human . It is an ATPase subunit of the INO80 complex . The Ino80 complex displays 3'-5' DNA helicase activity and is involved in transcription, DNA replication and repair, and chromatin remodelling . INO80 removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1 . INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status . INO80 is a member of the DEAD-like helicase superfamily.

This domain contains the ATP-binding region of INO80 from fungi and animals.
FHY3/FAR1 family (FHY3/FAR1)
Type: Family

This entry represents a group of plant and fungal proteins, including a number of Arbidopsis FHY3/FAR1-related proteins .
Chromodomain-helicase-DNA-binding protein 1-like (ALC1)
Type: Family

Chromodomain-helicase-DNA-binding protein 1-like (also known as amplified in liver cancer 1, ALC1) is a SNF2 family ATPase and a chromatin-remodeling enzyme that interacts with poly(ADP-ribose) and catalyses PARP1-stimulated nucleosome sliding . ALC1 is involved in DNA repair and in controlling the expression of several genes implicated in tumorigenesis and metastasis in mammals .

This entry also includes the probable helicase CHR10 from Arabidopsis.
High mobility group protein HMGB, plant (HMGB_plant)
Type: Family

The plant high mobility group (HMG) proteins can be grouped into two families: HMGB (HMG 1/2) and HMGA (HMG I/Y). This entry represents a subset of the HMGB family from plants, including Arabidopsis HMGB1-5. HMGB proteins bind to chromosomal DNA via their DNA binding motif, a HMG box, and induce structural changes of chromatin .
Basic helix-loop-helix (bHLH) transcription factors ALC-like, plant (bHLH_ALC-like_plant)
Type: Family

This entry represents a group of plant helix-loop-helix (bHLH) transcription factors, including ALC, UNE10, PIFs (phy-interacting factors) and SPATULA from Arabidopsis . ALC enables cell separation in fruit dehiscence, the processes in which the fruit opens and releases the seed . PIF1 regulates chlorophyll biosynthesis to optimise the greening process . SPATULA plays a role in floral organogenesis . UNE10 is required during the fertilisation of ovules by pollen .
Crustacean CHH/MIH/GIH neurohormone family (Crust_neurohorm)
Type: Family

Arthropod express a family of neuropeptides which so far consist of the following types of neurohormones:

Crustacean hyperglycemic hormone (CHH). CHH is primarily involved in blood sugar regulation, but also plays a role in the control of molting and reproduction.

Molt-inhibiting hormone (MIH). MIH inhibits Y-organs where molting hormone (ecdysteroid) is secreted. A molting cycle is initiated when MIH secretion diminishes or stops.

Gonad-inhibiting hormone (GIH), also known as vitellogenesis-inhibiting hormone (VIH) because of its role in inhibiting vitellogenesis in female animals.

Mandibular organ-inhibiting hormone (MOIH). MOIH represses the synthesis of methyl farnesoate, the precursor of insect juvenile hormone III in the mandibular organ.

Ion transport peptide (ITP) from locust. ITP stimulates salt and water reabsorption and inhibits acid secretion in the ileum of the locust.

These neurohormones are peptides of 70 to 80 residues which are processed from larger size precursors. They contain six conserved cysteines that are involved in disulphide bonds, as shown in the following schematic representation.

Alpha-latrotoxin associated low molecular weight proteins (LMWPs) are a family of uncharacterised venom peptides associated with alpha-latrotoxin, a black widow spider neurotoxin, which are probably also expressed in the venoms of other Latrodectus and Steatoda species .

This entry also includes proteins from Nematoda, such as Caenorhabditis elegans hypothetical protein ZC168.2.
BRCA1-associated (BRCA1-associated)
Type: Family

This entry includes animal BRCA1 (BREAST CANCER SUSCEPTIBILITY 1) proteins and their homologues from plants .

The animal BRCA1 protein is a E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage . It contains an N-terminal zinc-finger domain. It also contains a BRCT C-terminal domain, an approximately 100 amino acid tandem repeat, which appears to act as a phospho-protein binding domain .
LOG family (LOG_fam)
Type: Family

The members of this family share a highly conserved motif PGGXGTXXE that is probably functionally important. This family includes cytokinin riboside 5'-monophosphate phosphoribohydrolase LOG and pyrimidine/purine nucleotide 5'-monophosphate nucleosidase ygdH. LOG converts inactive cytokinin nucleotides to the biologically active free-base forms . YgdH may catalyse the hydrolysis of the N-glycosidic bond of diverse pyrimidine and purine nucleotide 5'-monophosphates, to form ribose 5-phosphate and the corresponding free base .
RNA polymerase-associated protein Ctr9 (Ctr9)
Type: Family

This entry includes budding yeast RNA polymerase-associated protein Ctr9 and its homologues from other yeasts, animals and plants. The homologue in fission yeast is known as tetratricopeptide repeat protein 1 (Tpr1) .

Budding yeast Ctr9 is part of the Paf1 complex, an RNA polymerase II-associated protein complex containing Paf1, Cdc73, Ctr9, Rtf1 and Leo1 . Paf1 complex is involved in histone modifications, transcription elongation and other gene expression processes that include transcript site selection . Human Paf1 complex (Paf1C) consists of Paf1, Cdc73, Ctr9, Rtf1, Leo1 and Wdr61 (Ski8). As in yeast, the human Paf1C has a central role in co-transcriptional histone modifications .

Arabidopsis Paf1C related proteins such as VIP4 (Leo1), VIP5 (Rtf1), ELF7 (Paf1), ELF8 (Ctr9) and ATXR7 (Set1) are required for the induction of seed dormancy. They control both germination and flowering time .
Telomere repeat-binding protein, plant (TRP_plant)
Type: Family

This entry represents a group of plant telomere repeat-binding proteins, including AtTRP1-6 from Arabidopsis and RTBP1 from Oryza sativa subsp. japonica.

AtTRP1 binds specifically to the plant telomeric double-stranded DNA sequences 5'-GGTTTAG-3' . It interacts with the ethylene receptor ERS1 and modulates development in Arabidopsis . AtTRP4, also known as AtTBP1 (AT5G13820), is required for telomere length homeostasis and its Myb-extension domain stabilises plant telomeric DNA binding .
CCAAT/enhancer-binding protein C/EBP (C/EBP)
Type: Family

This entry includes a group of basic-leucine zipper domain containing proteins, including CCAAT/enhancer-binding protein (C/EBP) from animals and BZIP23 (AT2G16770,

) and BZIP19 (At4g35040,

) from Arabidopsis. They are zipper transcription factors that bind to sequence-specific DNA.

Drosophila C/EBP may be required for the expression of gene products mediating border cell migration . Arabidopsis BZIP19 and BZIP23 regulate the adaptation to zinc deficiency .

Mammalian C/EBP consists of CEBPalpha/beta/delta/epsilon/gamma. C/EBP-alpha coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta . C/EBP-beta is important in the differentiation and maturation of adipocytes and is increased during ER stress and proinflammatory conditions .
Small heat shock protein (Small_HSP)
Type: Family

Prokaryotic and eukaryotic organisms respond to heat shock or other environmental stress by inducing the synthesis of proteins collectively known
as heat-shock proteins (hsp) . Amongst them is a family of proteins with an average molecular weight of 20 Kd, known as the hsp20 proteins . These seem to act as chaperones that can protect other proteins against heat-induced denaturation and aggregation. Hsp20 proteins seem to form large heterooligomeric aggregates.

Structurally, this family is characterised by the presence of a conserved C-terminal domain of about 100 residues.
WD repeat HIR1-like (HIR1-like)
Type: Family

This entry includes HIR1/HIR2 from yeasts and HIRA from animals. They are WD-repeat containing proteins required for regulation of histone gene transcription.
KH domain containing protein RIK/BLOM7 (RIK/BLOM7)
Type: Family

This entry represents a group of KH domain containing proteins from eukaryotes, including RIK (rough sheath 2-interacting KH domain) from plants and BLOM7 (also known as KH homology domain-containing protein 4, KHDC4) from animals. KHDC4 is an RNA-binding protein involved in pre-mRNA splicing. It interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. KHDC4 binds preferentially RNA with A/C rich sequences and poly-C stretches. KHDC4 contains two type I K homology (KH) RNA-binding domains .

RIK1 interacts with rough sheath2 (RS2), which is a myb domain protein required to repress knox genes during leaf development .
E3 ubiquitin ligase RBR family (E3_UB_ligase_RBR)
Type: Family

This family of E3 ligases has a distinctive organisation of RING fingers called 'RING-betweenRING-RING' (RBR), characterised by two RING fingers with a cysteine-rich region called the 'in-between-RING' domain that separates them . The domains in the RBR E3 ligases have been further named as RING1-BRcat-Rcat according to their structure and function: the C-terminal Rcat (required-for-catalysis) domain is essential for catalytic activity, whereas the central BRcat (benign-catalytic) domain adopts the same fold as the Rcat, but lacks a catalytic cysteine residue and ubiquitination activity . These ligases have a unique mechanism of elongating ubiquitin chains that distinguishes them from other E3 ligases .

On the basis of sequence conservation within the RBR segment, RBR proteins are assigned to 15 subfamilies (A-I, P, S, T, U, X, Z). There are two RBR proteins in the yeast Saccharomyces cerevisiae, six in Drosophila melanogaster, 10 in Caenorhabditis elegans, about 40 in Arabidopsis thaliana, around 23 in the zebrafish (Danio rerio), and about 15 in humans .
E3 ubiquitin-protein ligase RNF14, RING finger, HC subclass (RNF14_RING-HC_Zfn)
Type: Domain

This entry represents the C3HC4-type RING-HC finger of RNF14 and similar proteins predominantly found in animals. This domain is required for RBR (RING1-BRcat-Rcat)-mediated ubiquitination.

Ring Finger Protein 14 (RNF14, ARA54, Triad2) belongs to the ring between ring fingers (RBR) family. It is an E3 ubiquitin ligase that acts on unknown substrates and has autoubiquitination activity . It is an enhancer of the Wnt-dependent transcriptional outputs acting at the level of the TCF/LEF-beta-catenin complex , crucial for colon cancer cell survival. Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It may also participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. It may function as an AR (androgen receptor) coactivators to induce AR target gene expression . RNF14 may play a regulatory role in mitochondrial and immune gene expression .

RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)]] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.
Growth-regulating factor (GRF)
Type: Family

Growth-regulating factors (GRFs) are transcription factors that play a regulatory role in growth and development of leaves and cotyledons . Typical GRFs contain QLQ and WRC domains. The QLQ domain is involved in protein-protein interactions, while the WRC domain contains a nuclear localisation signal and a DNA-binding motif . Arabidopsis have 9 GRF members (AtGRF1-9): AtGRF1 and AtGRF2 act as transcriptional activators; AtGRF1 and AtGRF3 contribute to the regulation of various biological processes associated with defense response and disease resistance; AtGRF7 has been reported to function as transcriptional repressor of osmotic stress-responsive genes by binding to the cis-element TGTCAGG .
RPGRIP1 family (RPGRIP1_fam)
Type: Family

RPGR-interacting protein 1 (RPGRIP1) is mutated in the eye disease Leber congenital amaurosis (LCA) and its structural homologue, RPGRIP1-like (RPGRIP1L, also called NPHP8 or fantom), is mutated in many different ciliopathies . Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR) . Both consist of an N-terminal coiled coil domain, two C2 domains (C2N and C2C), and a C-terminal RPGR-interacting domain (RID). RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module .

Both RPGRIP1 and RPGRIP1L interact with the ciliary transition zone protein nephrocystin 4 (NPHP4) via their C2C domain . An hypothesis is that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability . The expression of RPGRIP1 seems to be limited to photoreceptors and amacrine cells in the retina , whereas RPGRIP1L is found in other tissues as well.
Protein indeterminate-domain 1-16 (IDD1-16)
Type: Family

This is a family of plant-specific transcription factors including protein indeterminate-domain 1-16 (IDD1-16) from Arabidopsis containing the conserved INDETERMINATE DOMAIN (IDD) with four zinc finger motifs. These proteins are involved in regulation of multiple developmental processes . IDD8/NUC, IDD3/MAGPIE (MAG), and IDD10/JACKDAW (JKD) regulate root development and patterning [. IDD8/NUTCRACKER (NUC) also regulates photoperiodic flowering by modulating sugar transport and metabolism . IDD15/SHOOT GRAVITROPISM 5 (SGR5) is involved in the gravitropic response of inflorescence stems. INDETERMINATE1 plays an important role in regulating the transition to flowering in maize . This family also includes similar proteins from rice, such as EHD2, which are transcription activators that act as a flowering master switches in both long and short days, independently of the circadian clock .
E3 SUMO-protein ligase SIZ1/2, SP-RING finger (SIZ1/2_SP-RING)
Type: Domain

SIZ1/2 are small ubiquitin-like modifier (SUMO) E3 ligase found in plants and fungi. In plants, SIZ1 regulates plant growth and responses to multiple environmental stimuli, such as phosphate starvation or low temperature . It is also required for salicylic acid and PAD4-mediated R gene signalling, which in turn confers innate immunity in Arabidopsis . It promotes FLC expression by repressing FLD activity through sumoylation and positively controls nitrogen assimilation by promoting sumoylation of nitrate reductases in Arabidopsis . In yeast, it acts as an E3 ligase mediating SUMO/Smt3 attachment to septins and PCNA and may be involved in chromosome maintenance .

This entry represents the SP-RING finger of SIZ1, a specific variant of RING finger .
SPX domain-containing protein (SPX_prot)
Type: Family

This entry represents a group of plant SPX domain-containing proteins, including AtSPX1-6 from Arabidopsis. AtSPX1 (

) and AtSPX2 (

) have a cellular Pi-dependent inhibitory effect on Phosphate Starvation Response 1 (PHR1) . Their rice homologue, OsSPX1 (

), may play an important role in linking cold stress and Pi starvation signal transduction pathways .
Aquaporin-10, invertebrate (Invert_Aqp-10)
Type: Family

Aquaporin channels facilitate the transport of water, glycerol, and other small solutes across cell membranes. Eight canonical aquaporin-encoding genes (aqp) are present in the genome of Caenorhabditis elegans . This entry represents a putative aquaporin-10 protein from C. elegans and other invertebrates. It is orthologous to human aqp-11 and aqp-12.
Plexin family (Plexin)
Type: Family

Plexins are neuronal receptors for the axon guidance regulators Semaphorins. Semaphorin-plexin interactions play central roles in regulating processes such as neuronal axon guidance, angiogenesis and immune responses. Plexin is activated upon binding of semaphorin to the extracellular region. The GTPase Activating Protein (GAP) domain in the cytoplasmic region mediates intrantracellular signalling .

In mammals, nine plexins have been identified, which are grouped into four subfamilies: Plexin-A1-4, Plexin-B1-3, Plexin-C1, and Plexin-D1 .
Plexin domain-containing protein (PLXDC)
Type: Family

Plexin domain-containing protein 1 (TEM7) and plexin domain-containing protein 2 (TEM7R) were identified as tumour endothelial markers (TEMs) that displayed elevated expression during tumour angiogenesis . TEM7 encodes a type I transmembrane protein with a large extracellular domain, a hydrophobic transmembrane domain, and a short cytoplasmic tail. Its cell surface expression is essential during endothelial cell capillary morphogenesis .
Urea active transporter (DUR)
Type: Family

This entry represents a group of urea transporters, including Dur3 from budding yeast and its homologues from plants. Budding yeast Dur3 is a plasma membrane transporter for both urea and polyamines . In maize plants, ZmDUR3 functions as an active urea permease with physiological roles in effective urea uptake and nitrogen remobilisation . Arabidopsis AtDUR3 is the major transporter for high-affinity urea uptake in Arabidopsis roots .

This entry also includes the spermidine transporter DUR3 from C. albicans, the orthologue of plants and yeast DUR3 .
Tr-type G domain, conserved site (G_TR_CS)
Type: Conserved_site

The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

Translational GTPases (trGTPases) are a family of proteins in which GTPase activity is stimulated by the large ribosomal subunit. This family includes translation initiation, elongation, and release factors and contains four subfamilies that are widespread, if not ubiquitous, in all three superkingdoms :

Prokaryotic initiation factor 2 (IF2) and the related eukaryotic initiation factor 5B (eIF5B), catalyze ribosomal subunit joining to form elongation- competent ribosomes .

Bacterial SelB and eukaryotic/archaeal gamma subunit of initiation factor 2 (eIF-2gamma), specifically recognise noncanonical tRNAs. SelB specifically recognises selenocysteylated tRNA(Sec) and eIF-2gamma initiator tRNA (Met-tRNA(i)) .

Bacterial elongation factor Tu (EF-Tu) and its archaeal and eukaryotic counterpart elongation factor 1 (EF-1 alpha), bring the aminoacyl-tRNA into the A site of the ribosome .

Bacterial peptide elongation factor G (EF-G) and its counterpart in Eukarya and Archaea, EF-2, catalyse the translocation step of translation .

The basic topology of the tr-type G domain consists of a six-stranded central β-sheet surrounded by five α-helices. Helices alpha2, alpha3 and alpha4 are on one side of the sheet, whereas alpha1 and alpha5 are on the other . GTP is bound by the CTF-type G domain in a way common for G domains involving five conserved sequence motifs termed G1-G5. The base is in contact with the NKxD (G4) and SAx (G5) motifs, and the phosphates of the nucleotide are stabilised by main- and side-chain interactions with the P loop GxxxxGKT (G1). The most severe conformational changes are observed for the two switch regions which contain the xT/Sx (G2) and DxxG (G3) motifs that function as sensors for the presence of the gamma-phosphate. A Mg(2+) ion is coordinated by six oxygen ligands with octahedral coordination geometry; two of the ligands are water molecules, two come from the beta- and gamma-phosphates, and two are provided by the side chains of G1 and G2 threonines.

This entry represents a conserved site in the tr-type G domain. It is on a G2-containing region that has been shown to be involved in a conformational change mediated by the hydrolysis of GTP to GDP.