SII-SWORD/CoKE huggingface dataset:
Unconventional myosin-IXb, Rho-GAP domain (RhoGAP_myosin_IXB)
Type: Domain

Unconventional myosin-IXb (MYO9B) belongs to class IX myosin that contains an extra Rho-specific GAP (GTPase-activating protein) domain in the tail region . MYO9B plays an important part in spatially coordinated cell shape changes and motility . In humans, there are two proteins in class IX, MYO9A and MYO9B. Class IX myosins may carry its own Rho-GAP tail using its motor head domain to sites that require down-regulation of Rho-dependent signalling .

Myosin constitutes a large superfamily of actin-dependent molecular motors. Myosin binds to actins and moves along actin filaments by using the energy from ATP hydrolysis. Myosin is involved in muscular contraction, cytokinesis, membrane trafficking and signal transduction . Myosins are typically composed of three functional domains:

Motor head domain whose core sequence is highly conserved in all the myosin classes. This domain binds to actin and uses ATP hydrolysis to generate force to move along actin filaments.

Neck domain composed of a long helix of variable length depending on the number of IQ motifs (has a consensus sequence of IQXXXRGXXXR) . This domain acts as a linker and as a lever arm. The neck domain also serves as a binding site for moysin light chains, which are calmodulin-like proteins that have regulatory functions.

Tail domain is the most diverse domain and vary in length and in sequence. Many myosin tails form coiled-coil structure that allow the molecules to dimerise and produce two-headed molecules. This domain mediates interaction with cargo molecules and/or other myosin subunits.
Unconventional myosin-IXa, Ras-associating domain (RA_Myosin-IXa)
Type: Domain

Unconventional myosin-IXa (MYO9A) belongs to class IX myosin and contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and an extra Rho GTPase activating domain (RhoGAP) in the tail region . In mice, MYO9A homologue, Myr7 regulates Rho by stimulating its GTPase activity in neurons and has a role in the regulation of neuronal morphology and function . In humans, there are two proteins in class IX, MYO9A and MYO9B. Class IX myosins may carry its own Rho-GAP tail using its motor head domain to sites that require down-regulation of Rho-dependent signalling .

Myosin-IXa binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit, and plays a key role in controlling the molecular structure and function of hippocampal synapses [

. Moreover, Myosin-IXa functions in epithelial cell morphology and differentiation such that its knockout mice develop hydrocephalus and kidney dysfunction . Myosin-IXa regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Myosin-IXa negatively regulates Rho GTPase signaling, and functions as a regulator of kidney tubule function .

This entry represents the RA domain of MYO9A, which is located at its head domain and has the β-grasp ubiquitin-like fold with unknown function.
tRNA methyltransferase TRM10-type domain (MT_TRM10-typ)
Type: Domain

This entry represents a domain found in class IV SAM-dependent methyltransferases TRM10-type . Methyltransferases classified as class IV (SPOUT) are homodimers and methylate only RNA. The common core of the SPOUT fold contains a five-stranded β-sheet, flanked by two layers of α-helices. The core can be divided into two subdomains, both displaying an α/β architecture: (1) the N-terminal strands exhibit a Rossmanoidal α/β fold while (2) an important part of the C-terminal (~ 30 residues) is tucked back into the structure forming a conserved topological trefoil knot where SAM binding occurs. The active site, located at the interface of the two subunits, is
formed by amino acids from both monomers .

TRM10-type methyltransferases include tRNA (guanine(9)-N(1))-methyltransferase, tRNA (adenine(9)-N(1))-methyltransferase and RNA (guanine-9-)-methyltransferase domain-containing protein. TRM10 homologues are widely found in eukaryotes and archaea, but not in bacteria.
Mu homology domain (MHD)
Type: Domain

The mu homology domain (MHD) is an ~280 residue protein-protein interaction module, which is found in endocytotic proteins involved in clathrin-mediated endocytosis :

Mu subunits of adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4.

Proteins of the stonin family.

Proteins of the muniscin family: Syp1, FCHO1/2 and SGIP1.

The MHD domain has an elongated, banana-shaped, all β-sheet structure. It can be considered as two β-sandwich subdomains (A and B), with subdomain B inserted between strands 6 and 15 of subdomain A, and joined edge to edge such that the convex surface is a continuous nine-stranded mixed β-sheet that runs the whole length of the molecule. The tyrosine based signal binds to a site on the surface of two parallel β-sheet strands (β1 and β16) in subdomain A .
Kalirin/Triple functional domain protein, SH3 domain 1 (Kalirin_TRIO_SH3_1)
Type: Domain

This entry includes a group of RhoGEFs, including Kalirin and Triple functional domain protein (TRIO) from mammals. Kalirin and TRIO are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and TRIO share the same complex multidomain structure and display several splice variants. They are implicated in secretory granule (SG) maturation and exocytosis . The longest Kalirin and TRIO proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyses exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and TRIO are closely related to p63RhoGEF and have PH domains of similar function. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner .

TRIO contains a protein kinase domain and two guanine nucleotide exchange factor (GEF) domains . These functional domains suggest that it may play a role in signalling pathways controlling cell proliferation . TRIO may form a complex with LAR transmembrane protein tyrosine phosphatase (PT-Pase), which localises to the ends of focal adhesions and plays an important part in coordinating cell-matrix and cytoskeletal rearrangements necessary for cell migration . Its expression is associated with invasive tumour growth and rapid tumour cell proliferation in urinary bladder cancer .

Kalirin (

) promotes the exchange of GDP by GTP and stimulates the activity of specific Rho GTPases . There are several Kalirin isoforms in humans and mice. Each Kalirin isoform is composed of a unique collection of domains and may have different functions . In rat, isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth, while isoform 6 is required for dendritic spine formation . In humans, the major isoform of Kalirin in the adult brain is Kalirin-7, which plays a critical role in spine formation/synaptic plasticity. Kalirin-7 has been linked to neuropsychiatric and neurological diseases such as Alzheimer's, Huntingtin's, ischemic stroke, schizophrenia, depression, and cocaine addiction .

This entry represents the first SH3 domain present in Kalirin and TRIO.
Putative thymidine phosphorylase (Thym_Pase_Put)
Type: Family

This entry consists of bacteria proteins that belong to the thymidine/pyrimidine-nucleoside phosphorylase family. They are annotated as putative thymidine phosphorylases
Deoxyribose-phosphate aldolase type I (DeoC_typeI)
Type: Family

Deoxyribose-phosphate aldolase is a widely distributed enzyme, which catalyses the following reversible reaction:

2-deoxy-D-ribose 5-phosphate = D-glyceraldehyde 3-phosphate + acetaldehyde

While the physiological role of this enzyme remains unknown in eukaryotes, in prokaroytes it is thought to function in the catabolism of deoxyribonucleotides .

In all studied structures, the deoxyribose-phophate aldolase subunits adopt the classical eight-bladed TIM barrel fold . The oligomerisation state of the enzyme appears to depend on the living temperature of the organism - the Escherichia coli enzyme (

) is a homodimer, while the enzymes from the thermophilic microorganisms Thermus thermophilus and Aeropyrum pernix (

) are homotetramers. The degree of oligomerisation does not, however, appear to affect catalysis.

Deoxyribose-phosphate aldolase type I is found in Bacteria, Archaea and fungi, while type II (

) is found in Proteobacteria.
Adenylate kinase isoenzyme 1 (AK1)
Type: Family

Adenylate kinases (AKs) are nucleoside monophosphate kinases, which catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors.
4-O-beta-D-mannosyl-D-glucose phosphorylase (Man_Glc_phosphorylase)
Type: Family

4-O-beta-D-mannosyl-D-glucose phosphorylase converts 4-O-beta-D-mannopyranosyl-D-glucopyranose (Man-Glc) to mannose 1-phosphate (Man1P) and glucose. It is involved in a mannan catabolic pathway which feeds into glycolysis .
Cellobiose 2-epimerase (Cellobiose_2_epim)
Type: Family

Cellobiose 2-epimerase catalyses the reversible epimerization of cellobiose to 4-O-beta-D-glucopyranosyl-D-mannose (Glc-Man). It can also epimerize cellotriose to Glc-Glc-Man, cellotetraose to Glc-Glc-Glc-Man, lactose to epilactose, and mannobiose to 4-O-beta-D-mannopyranosyl-D-glucopyranose (Man-Glc). It may function as a mannobiose 2-epimerase in vivo and be involved in a mannan catabolic pathway which feeds into glycolysis .
Adenylate kinase 4, mitochondrial (AK4_mitochondrial)
Type: Family

Adenylate kinases (AKs) are nucleoside monophosphate kinases, which catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors.

In humans, nine different AK isoenzymes have been identified (AK1-9) . This entry represents AK4 (also known as adenylate kinase 3-like). Despite its homology with other AKs, AK4 shows no enzymatic activity in vitro . AK4 is expressed predominantly in kidney and weakly in liver, heart and brain . It is localised in the mitochondrial matrix . It contains an unusual feature of an N-terminal mitochondrial import sequence that remains uncleaved after import into the mitochondria .
Adenylate kinase 3/4, mitochondrial (AK3/Ak4_mitochondrial)
Type: Family

Adenylate kinases (AKs) are nucleoside monophosphate kinases, which catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors.

In humans, nine different AK isoenzymes have been identified (AK1-9). This entry represents AK3/4. Both AK3 and AK4 are localised in the mitochondrial matrix. AK3 is expressed in liver, heart and skeletal muscle, while AK4 is expressed predominantly in kidney . Despite its homology with AK3, AK4 shows no enzymatic activity in vitro . AK4 contains an unusual feature of an N-terminal mitochondrial import sequence that remains uncleaved after import into the mitochondria .

This entry also includes yeast mitochondrial adenylate kinase, Adk2. Its 3' sequence varies with strain background .
Adenylate kinase 2 (AK2)
Type: Family

This entry represents the adenylate kinase 2 (AK2) subfamily of the adenylate kinases (AKs), which are nucleoside monophosphate kinases that catalyse the phosphorylation of AMP by using ATP or GTP as phosphate donors. Proteins in this entry include AK2 from humans, Adk1 from budding yeasts.
Thiol:disulfide interchange protein DsbL (DsbL)
Type: Family

DsbL is involved in disulfide-bond formation. It acts by transferring its disulfide bond to other proteins. DsbL, along with DsbI, form part of a redox system that mediates formation of an essential disulfide bond in ASST (uropathogen-specific arylsulfate sulfotransferase). DsbL and DsbI represent a second specific redox couple that guarantees biological activity of ASST .
AdoMet-dependent rRNA methyltransferase SPB1-like (SPB1-like)
Type: Family

SPB1 is an adoMet-dependent rRNA methyltransferase required for proper assembly of pre-ribosomal particles during the biogenesis of the 60S ribosomal subunit . In Saccharomyces cerevisiae, it specifically methylates the guanosine in position 2922 of the 25S rRNA at the stage of 27S pre-rRNA maturation . It interacts with the snoRNA-associated proteins Nop1 and Nop58 .
tRNA (cytidine(32)/guanosine(34)-2-O)-methyltransferase TRM7 (RNA_methyltr_E_TRM7)
Type: Family

This entry represents the tRNA (cytidine(32)/guanosine(34)-2'-O)-methyltransferases, including Trm7 from Saccharomyces cerevisiae. Trm7 methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of tRNA(Phe), tRNA(Trp) and tRNA(Leu(UAA)) . It requires Trm732 for methylation of the cytidine at position 32 and Rtt10/Trm734 for methylation of the nucleotides at position 34 in substrate tRNAs .

This entry also includes FTSJ1 from human. FTSJ1 is a homologue of yeast Trm7 and may play a role in the regulation of translation. Mutations in FTSJ1 cause the mental retardation, X-linked 44 (MRX44), which is a disorder characterised by significantly below average general intellectual functioning associated with impairments in adaptive behaviour and manifested during the developmental period .
DIS3-like exonuclease 2 (DIS3L2)
Type: Family

DIS3-like exonuclease 2 (DIS3L2) is a 3'-5'-exoribonuclease that specifically recognises RNAs polyuridylated at their 3' end and mediates their degradation. It plays an important role in the mRNA degradation pathway alternative to degradation by Xrn1 and the exosome . This entry also includes DIS3L2 plant homologue, SUPPRESSOR OF VARICOSE (SOV) (At1g77680), which functions in cytoplasmic mRNA decay and suppresses Arabidopsis decapping mutant phenotypes .
Queuine tRNA-ribosyltransferase accessory subunit QTRTD1 (QTRTD1)
Type: Family

Queuine tRNA-ribosyltransferase accessory subunit 2 (Qtrt2 or QTRTD1) interacts with QTRT1 to form an active queuine tRNA-ribosyltransferase. It exchanges queuine for the guanine at the wobble position of tRNAs with GUN anticodons (tRNA-Asp, -Asn, -His and -Tyr), thereby forming the hypermodified nucleoside queuosine (Q) (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) .
Protein Spindly, chordates (SPDLY_chordates)
Type: Family

Protein Spindly is required for the localisation of dynein and dynactin to the mitotic kintochore . It is required for silencing the spindle assembly checkpoint . It localises to microtubule plus ends in interphase and to kinetochores during mitosis . The localisation of human Spindly (hSpindly) to kinetochore-microtubules is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B .
Katanin p60 subunit A-like 1, chordates (Katnal1_chordates)
Type: Family

This entry represents Katanin p60 subunit A-like 1 (Katnal1) from chordates. Katnal1 regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility. It colocalizes with microtubules throughout the basal and adluminal compartments of Sertoli cells. It severs microtubules in an ATP-dependent manner, promoting rapid reorganisation of cellular microtubule arrays .
Methionine aminopeptidase, archaeal (MetAP_archaeal)
Type: Family

Methionine aminopeptidase (

) (MAP) catalyses the hydrolytic cleavage of the N-terminal methionine from newly synthesised polypeptides if the penultimate amino acid is small, with different tolerance to Val and Thr at this position . All MAP studied to date are monomeric proteins that require cobalt ions for activity. Two subfamilies of MAP enzymes are known to exist . While being evolutionary related, they only share a limited amount of sequence similarity mostly clustered around the residues shown, in the Escherichia coli MAP , to be involved in cobalt-binding. The first family consists of enzymes from prokaryotes as well as eukaryotic MAP-1 (

), while the second group is made up of archaeal MAP and eukaryotic MAP-2 and includes proteins which do not seem to be MAP, but that are clearly evolutionary related such as mouse proliferation-associated protein1 and fission yeast curved DNA-binding protein.
Katanin p60 subunit A1 (KATNA1)
Type: Family

Katanin is an ATP-dependent microtubule severing protein composed of 60kDa (katanin-p60) and 80kDa (katanin-p80) subunits encoded by KATNA1 and KATNB1 genes, respectively . Katanin-p60 has the enzymatic activity for microtubule severing, while katanin-p80 possesses multiple functions such as targeting katanin-p60 to the centrosome, augmenting microtubule severing by katanin-p60, and even suppressing microtubule severing .
Leucine zipper putative tumour suppressor 2 (LZTS2)
Type: Family

Leucine zipper putative tumor suppressor 2 (LZTS2, also known as LAPSER1) interacts with p80 katanin and regulates katanin-mediated microtubule severing . It is localised to the centrosome and the midbody in mitotic cells. During prophase, LAPSER1/LZTS2 inhibits centrosomal gamma-tubulin accumulation, which results in retardation of mitotic entry. During interphase, LAPSER1/LZTS2 inhibits katanin, which results in prevention of cell motility . LAPSER1/LZTS2 also modulates beta-catenin signaling and localisation .
WD repeat BOP1/Erb1 (BOP1/Erb1)
Type: Family

This entry represents the WD repeat BOP1/Erb1 family. Members of this family are ribosome biogenesis proteins.

In humans and mice, BOP1 is a component of the PeBoW complex (composed of BOP1, PES1 and WDR12), which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome .
WD repeat WDR12/Ytm1 (WDR12/Ytm1)
Type: Family

This entry represents the WD repeat WDR12/Ytm1 family. Members of this familiy are ribosome biogenesis proteins.
Cytosolic Fe-S cluster assembly factor NUBP2/Cfd1, eukaryotes (NUBP2/Cfd1_eukaryotes)
Type: Family

This entry represents the cytosolic Fe-S cluster assembly factor NUBP2/Cfd1 from eukaryotes.
Cytosolic Fe-S cluster assembly factor NUBP1/Nbp35 (NUBP1/Nbp35)
Type: Family

This entry represents the cytosolic Fe-S cluster assembly factor NUBP1/Nbp35 from eukaryotes. Members in this family are P loop NTPases that are involved in cytosolic iron-sulfur cluster assembly .
Protein argonaute-2 (AGO2)
Type: Family

Argonaute proteins are involved in RNA interference (RNAi) and microRNA (miRNA) pathways. They can be classified into three paralogous groups: Argonaute-like proteins, which are similar to Arabidopsis thaliana AGO1; Piwi-like proteins, which are closely related to D. melanogaster PIWI (P-element induced wimpy testis); and the Caenorhabditis elegans-specific group 3 Argonautes .

Protein argonaute-2 (AGO2) belongs to the first group (Argonaute-like proteins). It is a component of the RNA-induced silencing complex (RISC) that functions in RNA-mediated gene silencing (RNAi) . AGO2 is the catalytic engine that drives mRNA cleavage in the RNAi pathway . AGO2 suffers a phosphorylation cycle that is triggered by target engagement and negatively regulates target association, which is essential to maintain the global efficiency of miRNA-mediated silencing . It is also the primary AGO variant involved in modulating expression of progesterone receptor by antigene RNAs . AGO1 and AGO2 reside in three complexes with distinct Dicer and RNA-induced silencing complex activities . The structure of AGO2 has been solved .
Protein argonaute-3 (AGO3)
Type: Family

Argonaute proteins are involved in RNA interference (RNAi) and microRNA (miRNA) pathways. They can be classified into three paralogous groups: Argonaute-like proteins, which are similar to Arabidopsis thaliana AGO1; Piwi-like proteins, which are closely related to D. melanogaster PIWI (P-element induced wimpy testis); and the Caenorhabditis elegans-specific group 3 Argonautes .

Protein argonaute-3 (AGO3) belongs to the first group (Argonaute-like proteins) . It lacks endonuclease activity and does not appear to cleave target mRNAs . During human stem cells proliferation, AGO3 is involved in accumulation of processed DR2 Alu transcripts and subsequent recruitment of AGO3-associated decapping complexes to the target mRNA .
Protein argonaute-4 (AGO4)
Type: Family

Argonaute proteins are involved in RNA interference (RNAi) and microRNA (miRNA) pathways. They can be classified into three paralogous groups: Argonaute-like proteins, which are similar to Arabidopsis thaliana AGO1; Piwi-like proteins, which are closely related to D. melanogaster PIWI (P-element induced wimpy testis); and the Caenorhabditis elegans-specific group 3 Argonautes .

Protein argonaute-4 (AGO4) belongs to the first group (Argonaute-like proteins) . It is required for RNA-directed transcription and replication of the human hapatitis delta virus (HDV) .
RISC-loading complex subunit TRBP2 (TRBP2)
Type: Family

TRBP2 was first identified as a HIV-1 TAR RNA-binding protein . TRBP2 is a component of the RISC loading complex (RLC), which functions in RNA-mediated gene silencing (RNAi). It is a double-stranded RNA (dsRNA)-binding protein that associates with endonuclease Dicer, which cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs) in RNAi pathway . Together with another dsRNA-binding protein, PACT, they function as key regulators of miRNA and siRNA biogenesis by Dicer in substrate recognition, binding, processing and RISC loading .
Clp1 (Clp1)
Type: Family

Polyribonucleotide 5-hydroxyl-kinase Clp1 is a component of the cleavage factor IA (CF IA) complex, which is involved in the endonucleolytic cleavage during polyadenylation-dependent pre-mRNA 3'-end formation . It is involved in both the endonucleolyitc cleavage and polyadenylation steps of mRNA 3'-end maturation . Human Clp1 can also function as a tRNA splicing enzyme . In human, mutations in Clp1 affect tRNA biogenesis and lead to impairment of both peripheral and central nervous system function, causing severe motor-sensory defects, cortical dysgenesis and microcephaly . Clp1 contains three domains, a small N-terminal β sandwich domain involved in DNA binding , a C-terminal domain containing a novel α/β-fold and a central domain that binds ATP .
2-deoxynucleoside 5-phosphate N-hydrolase 1, DNPH1 (DNPH1)
Type: Family

DNPH1 (also known as Rcl) is an enzyme involved in nucleotide metabolism. It catalyses the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base . Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases. This enzyme is over-expressed in several cancers , which may be a potential molecular target for cancer treatment .
Probable cytosolic iron-sulfur protein assembly protein, CIAO1/Cia1 (CIAO1/Cia1)
Type: Family

Proteins in this entry are probable cytosolic iron-sulfur (FeS) protein assembly proteins from eukaryotes, including Cia1 from Saccharomyces cerevisiae and CIAO1 from humans. CIA1 from Arabidopsis is an essential component of the cytosolic iron-sulfur [FeS] protein assembly (CIA) machinery; it is required for the maturation of extramitochondrial Fe/S proteins . [Fe-S] clusters are ubiquitous and evolutionary ancient prosthetic groups that are required to sustain fundamental life processes . They can be used as part of catalytic centres for chemical sensing, stabilise protein structure and determine protein function .
Alanine dehydrogenase, archaeal-type (AlaDH_arch-typ)
Type: Family

Alanine dehydrogenase (AlaDH) catalyses the NAD+-dependent oxidative deamination of L-alanine to pyruvate, and the reverse reaction, the reductive amination of pyruvate. This entry represents the alanine dehydrogenase from archaea and some bacteria, which shows no significant amino acid sequence homology with previously known bacterial AlaDHs, but instead belongs to the ornithine cyclodeaminase-mu-crystallin family of enzymes .
Arylsulfate sulfotransferase AssT, Enterobacteria (AssT_Enterobac)
Type: Family

Arylsulfate sulfotransferase AssT catalyses the transfer of sulfuryl groups between phenolic compounds. AssT genes are present in different organisms, including mammals and a wide spectrum of microbial genomes .

This entry represents AssT from Enterobacteria.