SII-SWORD/CoKE huggingface dataset:
Haemagglutinin stalk, influenza C (Hemagglutn_stalk_influenz-C)
Type: Domain

Haemagglutinin (HA) is one of two main surface fusion glycoproteins embedded in the envelope of influenza viruses, the other being neuraminidase (NA). There are sixteen known HA subtypes (H1-H16) and nine NA subtypes (N1-N9), which together are used to classify influenza viruses (e.g. H5N1). The antigenic variations in HA and NA enable the virus to evade host antibodies made to previous influenza strains, accounting for recurrent influenza epidemics . The HA glycoprotein is present in the viral membrane as a single polypeptide (HA0), which must be cleaved by the host's trypsin-like proteases to produce two peptides (HA1 and HA2) in order for the virus to be infectious. Once HA0 is cleaved, the newly exposed N-terminal of the HA2 peptide then acts to fuse the viral envelope to the cellular membrane of the host cell, which allows the viral negative-stranded RNA to infect the host cell. The type of host protease can influence the infectivity and pathogenicity of the virus.

The haemagglutinin glycoprotein is a trimer containing three structurally distinct regions: a globular head consisting of anti-parallel β-sheets that form a β-sandwich with a jelly-roll fold (contains the receptor binding site and the HA1/HA2 cleavage site); a triple-stranded, coiled-coil, α-helical stalk; and a globular foot composed of anti-parallel β-sheets . Each monomer consists of an intact HA0 polypeptide with the HA1 and HA2 regions linked by disulphide bonds. The N terminus of HA1 provides the central strand in the 5-stranded globular foot, while the rest of the HA1 chain makes its way to the 8-stranded globular head. HA2 provides two α helices, which form part of the triple-stranded coiled-coil that stabilises the trimer, its C terminus providing the remaining strands of the 5-stranded globular foot.

This entry represents the stalk segment of haemagglutinin in influenza C virus. It forms a coiled coil structure .
TnsA endonuclease C-terminal (TnsA_C)
Type: Domain

The Tn7 transposase is composed of proteins TnsA and TnsB. DNA breakage at the 5'-end of the transposon is carried out by TnsA, and breakage and joining at the 3'-end is carried out by TnsB. The C-terminal domain of TnsA binds DNA.
TnsA endonuclease, N-terminal (TnsA_N)
Type: Domain

The Tn7 transposase is composed of proteins TnsA and TnsB. DNA breakage at the 5' end of the transposon is carried out by TnsA, and breakage and joining at the 3' end is carried out by TnsB. The N-terminal domain of TnsA is catalytic . This domain is also found in Bacteriophage T4 gp4-like head completion protein (also known as Gp50) whose nuclease activity is required for packaging . This domain contains the catalytic triad of one basic and two acidic residues that form a restriction endonuclease-like active site and conserved between TnsA with gp4 proteins .
Gag protein p15 (Gag_p15)
Type: Domain

Gag p15 is a viral membrane-binding matrix protein which is α helical in structure.
NS1 nuclease, NS1-Nuc domain, parvovirinae (NS1-Nuc)
Type: Domain

This entry represents the NS1-Nuc domain found mainly in the Parvovirinae subfamily of viruses in the family Parvoviridae.

Adeno-associated virus (AAV) Replication (Rep) protein is essential for viral replication and integration. The catalytic domain has DNA binding and endonuclease activity.

The family Parvoviridae is a group of small (18-26nm diameter), non-enveloped, and autonomously replicating icosahedral viruses containing a single-stranded linear DNA genome ranging from 4-6 kb in length, with terminal hairpins [E1]. The parvoviral single-stranded DNA genome contains two open reading frames (ORFs), one encoding nonstructural (NS) proteins, the other capsid proteins. All parvoviruses encode a nonstructural protein NS1 (termed Rep in adeno-associated virus [AAV]) that is essential for viral DNA replication and packaging of viral DNA into capsid. It may play other versatile roles, for example, in the transactivation of viral and cellular gene expression, DNA damage response, cell cycle arrest, apoptosis, and/or the modulation of innate immunity.

The N terminus of the parvoviral NS1 protein contains an origin of replication binding (OBD) domain, also known as a DNA-specific binding domain or nuclease (NS1-Nuc) domain. Its central region contains a helicase domain, which includes an NTP-binding site, and its C terminus includes a transactivation domain (TAD). The PV NS1-Nuc domain plays an important role in the "rolling hairpin" replication of the single-stranded parvoviral DNA genome: after cellular enzymes have converted the viral genome into double-stranded DNA, it recognizes origin of replication sequences and cleaves (i.e., nicks) one strand DNA at a nearby site known as the terminal resolution site (trs). Since the DNA encountered by NS1 is double-stranded, it is assumed that binding of NS1 to its target sequences induces strand separation, allowing for the endonuclease activity of NS1 to cleave at the trs
site . A homologue of parvoviral NS1, U94, is found in human herpesvirus 6 variants A and B (HHV-6A and HHV-6B, respectively) which do not replicate by "rolling hairpin" mecanism. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation .
Integrin beta subunit, cytoplasmic domain (Integrin_bsu_cyt_dom)
Type: Domain

This entry represents the cytoplasmic domain of integrin beta subunits .

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
EF-hand, Ca insensitive (EF-hand_Ca_insen)
Type: Domain

EF hands are helix-loop-helix binding motifs involved in the regulation of many cellular processes. EF hands usually bind to Ca2+ ions, which cause a major conformational change that allows the protein to interact with its designated targets. This protein corresponds to an EF hand which has partially or entirely lost its calcium-binding properties. The calcium insensitive EF hand is still able to mediate protein-protein recognition .
Poliovirus 3A protein-like (P3A)
Type: Domain

The 3A protein is found in positive-strand RNA viruses. It is a critical component of the poliovirus replication complex, and is also an inhibitor of host cell ER to Golgi transport.
Ribonucleotide reductase, transcriptional regulator Crt10 (Crt10)
Type: Family

Crt10 is a transcriptional regulator of ribonucleotide reductase (RNR) genes . RNR catalyses the rate limiting step in dNTP synthesis. Mutations in CRT10 have been shown to enhance hydroxyurea resistance .
Hpc2-related domain (HRD)
Type: Domain

HPC2 (Histone promoter control 2) is required for cell-cycle regulation of histone transcription . It regulates transcription of the histone genes during the S-phase of the cell cycle by repressing transcription at other cell cycle stages. HPC2 mutants display synthetic interactions with FACT complex which allows RNA Pol II to elongate through nucleosomes .
Rad33 (Rad33)
Type: Family

Rad33 is involved in nucleotide excision repair (NER). NER is the main pathway for repairing DNA lesions induced by UV. Cells deleted for RAD33 display intermediate UV sensitivity that is epistatic with NER .
Iron-regulated transcriptional activator AFT (AFT)
Type: Family

AFT (activator of iron transcription) is an iron regulated transcriptional activator that regulates the expression of genes involved in iron homeostasis. This entry includes the paralogous pair of transcription factors AFT1 and AFT2 .
Protein Him1/Fmp52 (Him1/Fmp52)
Type: Family

Him1 (high induction of mutagenesis protein 1) plays a role in the control of spontaneous and induced mutagenesis . It is thought to participate in the control of processing of mutational intermediates appearing during error-prone bypass of DNA damage. This entry also includes mitochondrial protein Fmp52, whose function is not clear.
PalH/RIM21 (PalH)
Type: Family

PalH (also known as RIM21) is a transmembrane protein required for proteolytic cleavage of Rim101/PacC transcription factors which are activated by C-terminal proteolytic processing. Rim101/PacC family proteins play a key role in pH-dependent responses and PalH has been implicated as a pH sensor .
Protein GYD/TTHA1554 (GYD/TTHA1554)
Type: Family

The function of these proteins is not clear. A member of this family from T. thermophilus, TTHA1554, has been shown to bind to glutamine synthetase and cystathionine beta-lyase .
Protein of unknown function DUF1786, putative pyruvate format-lyase activating enzyme (DUF1786_pyruvate_format-lyase)
Type: Family

This family is annotated as pyruvate formate-lyase activating enzyme (

) in UniProt. Pyruvate formate-lyase (PFL) catalyses the non-oxidative dissimilation of pyruvate to formate and acetyl-CoA using a radical-chemical mechanism .
FERM adjacent (FA)
Type: Domain

This region is found adjacent to Band 4.1 / FERM domains (

) in a group of animal FERM containing proteins. The region has been hypothesised to play a role in regulatory adaptation, based on similarity to other protein kinase substrates .
Reduced growth phenotype protein 1 (Rgp1)
Type: Family

Rgp1 forms heterodimer with Ric1 (

) which associates with Golgi membranes and functions as a guanyl-nucleotide exchange factor .
EKC/KEOPS complex, subunit Gon7 (EKC/KEOPS_Gon7)
Type: Family

In Saccharomyces cerevisiae Gon7 is a member of the EKC/KEOPS protein complex. The complex proposed to be involved in transcription and promoting telomere uncapping and telomere elongation and is required for efficient recruitment of transcriptional coactivators .
BCS1, N-terminal (BCS1_N)
Type: Domain

This domain is found at the N-terminal of the mitochondrial ATPase BSC1. This domain is responsible for the import and intramitochondrial sorting .
Uncharacterised protein YwhD (YwhD)
Type: Family

The members of this entry are currently uncharacterised. They are around 170 amino acids in length.
VWF/SSPO/Zonadhesin-like, cysteine-rich domain (VWF/SSPO/ZAN-like_Cys-rich_dom)
Type: Domain

The proteins in this entry contained a domain rich in positionally conserved cysteine residues. Most proteins contains 7 or 8 cysteine residues. The domain is found in disease-related proteins including von Willebrand factor, Alpha tectorin, Zonadhesin and Mucin. It is often found on proteins containing

and

.
Non-structural maintenance of chromosome element 4, C-terminal (Nse4_C)
Type: Domain

Nse4 is the kleisin component of the Smc5/6 DNA repair complex. It bridges the heads of Smc5 and Smc6 . This entry represents the highly conserved C-terminal domain which interacts with the head domain of Smc5 .
Plant transcription factor NOZZLE (NOZZLE)
Type: Family

NOZZLE (also known as SPOROCYTELESS) is a transcription factor that plays a role in patterning the proximal-distal and adaxial-abaxial axes . It is an essential factor for ovule development and functions as an adaptor-like transcriptional repressor, recruiting TPL/TPR co-repressors to inhibit TCP transcription factors .
RNA-free ribonuclease P (RNA_free_RNase_P)
Type: Family

RNase P catalyzes the removal of the 5'-leader sequence from pre-tRNA to produce the mature 5'-terminus. The ancient form of RNase P is a ribonucleoprotein consisting of a catalytic RNA and one or more protein subunits. This entry represents a type of protein-only RNase P found in the hyperthermophilic bacterium Aquifex aeolicus and close relatives. It comprises a metallonuclease domain and has RNase P activity .
Non-structural maintenance of chromosomes element 1, RING C4HC3-type (Nse1_RING_C4HC3-type)
Type: Domain

This entry represents the C3HC4-type RING finger domain, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, found at the C-terminal of Nse1. This domain may play an important role in Rad52-dependent post-replication repair of UV-damaged DNA in Saccharomyces cerevisiae.

Saccharomyces cerevisiae Nse1 (

) forms part of a complex with SMC5-SMC6. This non-structural maintenance of chromosomes (SMC) complex plays an essential role in genomic stability, being involved in DNA repair and DNA metabolism . It is conserved in eukaryotes from yeast to human. Nse1 acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair and in repair of ionizing radiation damage. It also functions in homologous recombination repair of DNA double strand breaks and in recovery of stalled replication forks .
BREX protein BrxB (BrxB)
Type: Family

This family includes BREX protein BrxB from Bacillus cereus, which is part of a type 1 BREX (bacteriophage exclusion) system, a system that provides immunity against bacteriophage, which allows phage adsorption but prevents phage DNA replication, without degradation of the phage DNA . The exact function of BrxB is not clear.
Phage tail assembly chaperone (Phage_TAC_4)
Type: Family

This is a family of phage tail assembly chaperone proteins largely from phage T1 Gp40 .
CNP1-like, uncharacterised domain (CNP1-like_dom)
Type: Domain

This entry represents an uncharacterised domain in Cryptic neisserial protein 1 (CNP1) from Neisseria gonorrhoeae and similar bacterial proteins. The function of this protein remains to be characterised. CNP1 (cryptic neisserial protein) has been expressed in E. coli and shown to be localised periplasmicly . This domain contains an α/β fold.
TrwC relaxase (TrwC)
Type: Domain

Relaxases are DNA strand transferases which function during the conjugative cell to cell DNA transfer. TrwC binds to the origin of transfer (oriT) and melts the double helix.
Transcription factor, NikR, nickel binding C-terminal (TF_NikR_Ni-bd_C)
Type: Domain

NikR is a transcription factor that regulates nickel uptake. It consists of two dimeric DNA binding domains separated by a tetrameric regulatory domain that binds nickel. This protein corresponds to the C-terminal regulatory domain which contains four nickel binding sites at the tetramer interface .
YfkB-like domain (YfkB)
Type: Domain

YfkB is adjacent to YfkA in Bacillus subtilis. In other bacterial species, it is fused to this protein. As YfkA contains a Radical SAM domain it suggests this domain is interacts with them.
Spore coat protein CotH/Invasin CotH2/3/7 (Spore_coat_CotH_CotH2/3/7)
Type: Family

Members of this family include the Bacillus subtilis spore coat protein H (CotH). Assembly of CotH requires both CotE and GerE and is required for the correct assembly of both inner and outer layers of the coat. CotH appears to be a structural component of the coat being localised at the interface of the 2 coat layers . Furthermore, CotH has been shown to be an atypical protein kinase. CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores .

This entry also includes CotH2/3/7 from Rhizopus delemar (mucormycosis agent), which promote invasion of host epithelial cells by adhering to receptors on the host cell surface to facilitate endocytosis of the pathogen into host cells .
Cadherin prodomain (Cadherin_pro_dom)
Type: Domain

Cadherins are a group of proteins that mediate calcium dependent cell-cell adhesion. They are activated through cleavage of a prosequence in the late Golgi. The folded part of the prosequence (termed the prodomain) shows structural resemblance to cadherin adhesive domains, but lacks all the features known to be important for cadherin-cadherin interactions .

This entry represents the caderin prodomain.
Glycosyltransferase GT-D fold (GT-D)
Type: Domain

This domain is found at the C terminus of proteins such as the probable glycosyltransferase Gly (

) that also contain the glycosyl transferase domain at the N terminus. It is also found N-terminal in numerous putative glycosyltransferases such as GalT1. GalT1 has been shown to catalyze the third step of Fap1 glycosylation . This domain is structurally distinct from all known GT folds of glycosyltransferases and contains a metal binding site. This new glycosyltransferase fold has been named GT-D .
dUTPase/dCTP pyrophosphatase (dUTPase/dCTP_pyrophosphatase)
Type: Family

This entry represents dimeric deoxyuridine triphosphate nucleotidohydrolase (dUTPase) (

) and phage T4 dCTP pyrophosphatase (

). dUTPase catalyses the hydrolysis of dUTP to dUMP and pyrophosphate. There are several classes of dUTPases: trimeric dUTPases found in most organisms and homologous monomeric dUTPases, found in mammalian herpesviruses. The dUTPases in this entry belong to a third class of dUTPases that form a dimer in solution and are able to hydrolyse both dUTP and dUDP . It contains a novel all-α fold that is unrelated to the all-β fold found in dUTPases of the majority of organisms .
Dicistrovirus, capsid-polyprotein, C-terminal (Dicistrovirus_capsid-polyPr_C)
Type: Domain

This domain is found in Picornaviruses that include Cripavirus capsid proteins, (which are positive stranded ssRNA viruses) such as Cricket paralysis virus (CRPV). It forms an all β sheet structure .
Voltage-dependent calcium channel, alpha-1 subunit, IQ domain (VDCC_a1su_IQ)
Type: Domain

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins . The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.

Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.

The voltage-gated calcium channel alpha 1 subunit contains an IQ domain, named for its isoleucine-glutamine (IQ) motif, which interacts with hydrophobic pockets of Ca2+/calmodulin . The interaction regulates two self-regulatory calcium dependent feedback mechanisms, calcium dependent inactivation (CDI), and calcium-dependent facilitation (CDF).
Staphylocoagulase, N-terminal, subdomain 1 (Staphylocoagulase_N)
Type: Domain

This entry represents the N-terminal domain of staphylocoagulase. The C terminus contains a tandem repeat (

) which does not seem to be required for the procoagulant activity.

Staphylococcus aureus secretes a cofactor called staphylocoagulase. Staphylocoagulase is an extracellular protein that forms a complex with human prothrombin, and activates it without the usual proteolytic cleavages . The resulting complex directly initiates blood clotting.
Mor transcription activator (Mor_transcription_activator)
Type: Domain

Mor (Middle operon regulator) is a sequence specific DNA binding protein. It mediates transcription activation through its interactions with the C-terminal domains of the alpha and sigma subunits of bacterial RNA polymerase. The N-terminal region of Mor is the dimerisation region, and the C-terminal contains a helix-turn-helix motif which binds DNA .
DEK, C-terminal (DEK_C)
Type: Domain

DEK is a chromatin associated protein that is linked with cancers and autoimmune disease. This domain is found at the C-terminal of human DEK and is of clinical importance since it can reverse the characteristic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients . This domain folds into a three helical bundle that is topologically similar to the DNA/RNA-binding bundles. The DEK CTD structure revealed homology to the E2F/DP transcription factor family . This domain is also found in fungal chitin synthase proteins, including Chitin synthase 5 from Gibberella zeae , in protein phosphatases such human Protein phosphatase Slingshot homolog 1 (SSH1, ) and in plant proteins like DEK domain-containing chromatin-associated protein 3 from Arabidopsis thaliana (DEKP3, ).
Exportin-1, C-terminal (XPO1_C_dom)
Type: Domain

CRM1 (also known as exportin1) mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES). CRM1 forms a complex with the NES containing protein and the small GTPase Ran.

This entry represents the C-terminal domain of CRM1. It forms an α helical structure formed by six helical hairpin motifs that are structurally similar to the HEAT repeat, but share little sequence similarity to the HEAT repeat .
THAP4-like, heme-binding domain (THAP4-like_heme-bd)
Type: Domain

Nitrobindins (Nbs), constituting a heme-protein family spanning from bacteria to Homo sapiens, display an all-β-barrel structural organization. Proteins containing this domain are putatively related to fatty acid-binding proteins (FABPs) .

This domain can be found in THAP4 from mammals and At1g79260 from Arabidopsis. THAP4 catalyses the heme-based conversion of peroxynitrite into nitrate/NO3- in vitro . At1g79260 is a nitrophorin-like heme-binding protein that may reversibly bind nitric oxide (NO) and be involved in NO transport . This entry also includes the β-barrel domain of Caenorhabditis elegans protein male abnormal 7 (Mab-7) which plays an important role in determining body shape and sensory ray morphology .