SII-SWORD/CoKE huggingface dataset:
Piezo, TM25-28 (Piezo_TM25-28)
Type: Domain

This entry represents TM25-28, found in the central region of these proteins, associated with

at the C-terminal. Members of this entry are found in animals.

Piezo is a family of proteins that form mechanosensitive non-specific cation channels whose conductance is higher for Li+, intermediate for Na+ and lowest for Li+. Divalent ions except for Mn2+ permeate the channel but more slowly than monovalent ions and can reduce K+ currents. Members play key roles in cell adhesion, blood vessel formation and vascular structure in both development and adult physiology . These channels have a homotrimeric three-blade propeller-shaped structure that use a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways . Each protomer consists of 38 TM helices (referred to THUs) that form unusual non-planar blades, and an extracellular cap-like structure (

).
Domain of unknown function DUF4744 (DUF4744)
Type: Domain

This domain from Drosophila is functionally uncharacterised. Proteins with this domain are typically between 81 and 415 amino acids in length.
HicB-like antitoxin of toxin-antitoxin system (HicB-like)
Type: Domain

This entry includes HicB-like antitoxins of bacterial and archaeal toxin-antitoxin systems . The HicAB module is a novel toxin-antitoxin system that functions via RNA-binding and, possibly, cleavage .
JMY/WHAMM, N-terminal (JMY/WHAMM_N)
Type: Domain

This is the N-terminal domain of WHAMM (WASP homologue-associated protein with actin, membranes and microtubules) and JMY (junction-mediating and -regulatory protein), two nucleation-promoting factors (NPFs) with similar domain architecture . The function of this conserved region is not known; there are two highly conserved tryptophan residues.
Coiled-coil domain-containing protein 158 (CCDC158)
Type: Family

CCDC158 (coiled-coil domain-containing protein 158) is a family of proteins found in eukaryotes. The function is not known.
YjeJ-like (YjeJ-like)
Type: Family

YjeJ is a family of bacterial proteins. The function is not yet known. All proteins are from Gammaproteobacteria.
AlgX/AlgJ, SGNH hydrolase-like domain (ALGX/ALGJ_SGNH-like)
Type: Domain

This entry represents a domain found in alginate biosynthesis protein AlgX, probable alginate O-acetylase AlgJ, and related proteins. This domain demonstrates catalytic activity similar to that of the SGNH hydrolase-like domain, with the typical Ser-His-Asp triad found in this enzyme. Alginate is an exopolysaccharide that contributes to biofilm formation. AlgX is secreted into the biofilm and is responsible for the acetylation of biofilm polymers that help protect them from host destruction .
Protein C (C_Hendra)
Type: Family

This is a family of C proteins from a number of Paramyxoviridae species. They may counteract the cellular interferon antiviral system .
Domain of unknown function DUF4745 (DUF4745)
Type: Domain

This presumed domain is functionally uncharacterised. It is found in eukaryotes.
ALG11 mannosyltransferase, N-terminal (ALG11_N)
Type: Domain

GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11) is involved in N-linked oligosaccharide synthesis . It is highly conserved, with homologues in fission yeast, worms, flies, and plants . It catalyses the sequential transfer of two alpha1,2-linked mannose residues from GDP-mannose to Man3GlcNAc2-PP-Dol forming the Man5GlcNAc2-PP-Dol intermediate at the cytosolic side of the ER before flipping to the luminal side. Alg11 contains three hydrophobic transmembrane-spanning helices found in the N-terminal domain .
Protein of unknown function DUF5074 (DUF5074)
Type: Family

This family of proteins from Bacteroidetes has a PKD domain at the N terminus. Several members are annotated as putative quinonprotein alcohol dehydrogenase-like proteins but this could not be confirmed.
Protein of unknown function DUF5073 (DUF5073)
Type: Family

This family of unknown function consists of membrane proteins from Mycobacterium .
DotD protein (DotD)
Type: Family

The DotD protein is a component of the Dot/Icm type IVB secretion system (T4BSS). The T4BSS core complex spans the inner and outer membranes. It is thought to be comprised of at least five proteins: DotC, DotD, DotF, DotG and DotH, with the latter being the outer membrane protein. DotD, together with DotC, is thought to be involved in the targeting of DotH .
Protein Hri1 (Hri1)
Type: Family

Hri1 interacts with Sec72 and Hrr25. It's function is not known .
Read-through domain (Read-through_dom)
Type: Domain

The Enterobacteria phage minor coat protein A1 is a C-terminal extended version of the coat protein formed when ribosomes read-through a leaky stop codon. This is the C-terminal read-through domain of A1 .
CRISPR-associated protein Csn2 subfamily St (Cas_St_Csn2)
Type: Family

This is a family of Csn2 CRISPR-associated (Cas) proteins found in Firmicutes, largely Streptococcus and Enterococcus. CRISPR-associated (Cas) proteins are the main executioners of the process whereby prokaryotes acquire immunity against foreign genetic material. Cas allow short segments of this DNA, called spacer, to become incorporated into chromosomal loci as clustered regularly interspaced short palindromic repeats or CRISPRs; the resulting encoded RNAs are then processed into small fragments that guide the silencing of the invading genetic elements. Thus Cas are involved in the acquisition of new spacers.

Proteins in this family are usually longer than the canonical Csn2 (

) through the addition of a large C-terminal domain. The central domain present in both families appears to be a channel that selectively interacts with dsDNA .
SOSS complex subunit C (SOSSC)
Type: Family

SOSS complex subunit C is a component of the SOSS complex, a single-stranded DNA binding complex involved in genomic stability, double-stranded break repair and ataxia telangiectasia-mutated-dependent signaling pathways .
Fiber protein 1, C-terminal (AdHead_fibreRBD)
Type: Domain

This entry represents a C-terminal part of the head domain of the dsDNA viruses, no RNA stage, Adenovirus. This is a globular head domain with an anti-parallel β-sandwich fold formed by two four-stranded β-sheets with the same overall topology as human adenovirus fibre heads. This C-terminal domain is the receptor-binding domain of the avian adenovirus long fibre .
TRAP transporter T-component (TatT)
Type: Family

Tripartite ATP-independent periplasmic (TRAP) transporters are bacterial transport systems implicated in the import of small molecules into the cytoplasm. Tetratricopeptide repeat-protein associated TRAP transporters (TPATs) constitute a subfamily of the TRAP transporters (TRAP-Ts). TPATs have four components. Three are common to both TRAP-Ts and TPATs: the P component, a ligand-binding protein, and a transmembrane symporter apparatus comprising the M and Q components (M and Q are sometimes fused to form a single polypeptide). TPATs are distinguished from TRAP-Ts by the presence of a unique protein called the T-component .

TatT (TRAP transporter T-component) consists of a 13-α-helical fold containing cryptic tetratricopeptide repeat motifs (cTPRs) and encompassing a pore, ie is a water-soluble trimer whose protomers are each perforated by a pore. It forms a complex with a P component, and a putative ligand-binding cleft of TatPT aligns with the pore of TatT .
E3 ubiquitin-protein ligase RNF220, middle domain (RNF220_mid)
Type: Domain

This entry represents the central region of the E3 ubiquitin-protein ligase RNF220 . RNF220 also interacts with beta-catenin independently of its E3 ligase activity; instead of ubiquitinating and destabilising it, RNF220 promotes beta-catenin stabilisation and canonical Wnt signaling . Proteins containing this domain also include Drosophila Tey protein and some uncharacterised fungal proteins. Tey (Teyrha-Meyhra) is a transcription factor that suppresses Toll expression .
RXLR phytopathogen effector protein (RXLR)
Type: Family

RXLR proteins constitute a family of phytopathogen avirulence or effector proteins. They are defined by a secretion signal peptide followed by a conserved N-terminal domain with the sequence motif RXLR (Arg-Xaa-Leu-Arg) consensus sequence. The RXLR part is required for translocation inside plant cells, although it appears to be dispensable for the biochemical activity of the effectors when expressed directly inside host cells. The effector activity resides in the C-terminal part of the family, which activate effector-triggered immunity in plants that carry a corresponding resistance (R) protein. The C-terminal region exhibits a fold appears to be able to evolve to outwit the host as the latter tries to acquire new immunity .
IC97/Casc1, N-terminal (IC97/Casc1_N)
Type: Domain

This domain is found in CASC1 (cancer susceptibility candidate gene 1 protein) from humans and IC97 from Chlamydomonas . There are two completely conserved residues (N and W) that may be functionally important.

Dynein-f, also known as dynein I1, is an inner-arm dynein complex comprising two different heavy chains together with a number of intermediate and light chains. In Chlamydomonas, IC97 is the intermediate chain of the Dynein-f complex. This entry includes IC97 (

) and its homologues, including CASC1 (also known as Dnai7) from humans .

The CAncer Susceptibility Candidate 1 (CASC1) gene is expressed in lung tissues, and is a strong candidate for the pulmonary adenoma susceptibility 1 (Pas1) locus, the major determinant of strain variation in lung tumour susceptibility . There appears to be a strong correlation between functional polymorphism of CASC1 and lung tumour suspectibility in mice .

Different mouse strains fall into two genotype groups (susceptible and intermediate) according to differences in the 60th codon of the CASC1 gene . The mouse CASC1 gene shares 81% similarity with the human equivalent; the role of CASC1 in human lung-cancer risk may nevertheless differ from that in mice .
Domain of unknown function DUF4746 (DUF4746)
Type: Domain

This presumed domain is functionally uncharacterised. This domain is found in eukaryotes, and is typically between 247 and 324 amino acids in length.
Myofilin (Myofilin)
Type: Family

Myofilin is an insect muscle protein found in thick muscle filaments .
Effector protein NleF (NleF)
Type: Family

NleF (Non-LEE-encoded type III effector F) is an effector protein that alters host cell physiology and promotes bacterial survival in host tissues. It binds to and inhibits caspase-9, caspase-8 and caspase-4, and therefore preventing caspase-induced apoptosis in the host cell .
Uncharacterised protein YdiH (YdiH)
Type: Family

YdiH is a family of proteins found in bacteria. Proteins in this family are typically between 62 and 80 amino acids in length. The function is not known.
cGMP-dependent protein kinase, N-terminal coiled-coil domain (PKcGMP_CC)
Type: Domain

This entry represents the N-terminal coiled-coil, dimerisation domain of cGMP-protein kinases .
Protein of unknown function DUF4747 (DUF4747)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are typically between 263 and 305 amino acids in length.
Protein of unknown function DUF4748 (DUF4748)
Type: Family

This family of proteins is functionally uncharacterised and is found in eukaryotes.
Antitoxin RnlB/LsoB (RnlB/LsoB_antitoxin)
Type: Family

RnlB antitoxin, formerly known as yfjO, has been found to be the antidote protein to RNase LS or RnlA in E. coli . Bacterial toxin-antitoxin systems consist of a stable toxin and an unstable antitoxin. In this case, a novel type II system, RnlA is the stable toxin that causes inhibition of cell growth and rapidly degrades T4 late mRNAs to prevent their expression, and this is neutralised by the activity of the unstable antitoxin RnlB . Antitoxin IsoB inhibits the endonuclease activity of cognate toxin LsoA, but not that of non-cognate toxin RnlA .
Antiactivator protein ExsD, N-terminal domain (ExsD_N)
Type: Domain

This entry represents the N-terminal domain of ExsD.

The antiactivator protein ExsD represses the transcriptional activator ExsA. ExsA activates expression of type III secretion system genes. ExsD inhibits the DNA-binding and self-association properties of ExsA . Repression of ExsA by ExsD is relieved by the secretion chaperone ExsC .
Late transcription coactivator (Trans_coact)
Type: Family

This family of proteins is found in Caudovirales. It is a late-transcription coactivator which interacts with the host RNA polymerase forming a part of the initiation complex . It activates transcription at late promoters when the sliding clamp is present . It is able to bind to both the host RNA polymerase (RNAP) and the upstream dsDNA .
Domain of unknown function DUF5071 (DUF5071)
Type: Domain

The function of DUF5071 is not known. This domain adopts a right-handed superhelix assembled from eight, repeated in tandem, α-helices

.
Fe-S cluster assembly protein Dre2, N-terminal (Dre2_N)
Type: Domain

This is the N-terminal domain of the fungal Fe-S cluster assembly protein Dre2. Yeast Dre2 has been implicated in cytosolic Fe-S protein biogenesis and in cell death regulation in response to oxidative stress .
Protein of unknown function DUF5070 (DUF5070)
Type: Family

This protein family is specific to Chlamydia. Members of this group had initially been related to a divalent cation transcription repressor . However, protein CT296 from Chlamydia trachomatis

, which show structural features typical of non-heme Fe(II) 2-oxoglutarate-dependent enzymes, contradicts this statement . The specific function of these proteins is not known.
Protein male-specific lethal-1, dimerisation domain (MSL1_dimer)
Type: Domain

This entry represents the short coiled dimerisation domain of higher eukaryotic MSL1, part of the MSL or Male-Specific Lethal complex. This complex regulates the dosage compensation of the male X chromosome in Drosophila and other eukaryotes. The structure of the MSL1/MSL2 core shows that two MSL2 subunits bind to a dimer formed by two molecules of MSL1. MSL1 is a substrate for MSL2 E3 ubiquitin ligase activity .
DL-endopeptidase inhibitor IseA (Endopep_inhib)
Type: Family

Bacillus subtilis DL-endopeptidases play essential roles in cell growth and separation. IseA inhibits DL-endopeptidases post-translationally and the overexpression of IseA causes significantly long chained cell morphology. The structure of IseA has been solved .
Yuri gagarin (Yuri_gagarin)
Type: Family

Drosophila yuri gagarin protein has multiple roles in the generation of elongate individualized sperm . It may mediate specialised actin- and microtubule-related activities in Drosophila tissues .
Voltage-gated hydrogen channel 1, C-terminal membrane-localisation domain (VGPC1_C)
Type: Domain

This entry represents the short C-terminal region of voltage-gated proton channel 1 proteins in higher eukaryotes. This domain is necessary for achieving the dimeric architecture, two monomers form a dimer via parallel α-helical coiled-coil interaction. This domain is also essential for localising the protein to an intracellular membrane .
Bacterial toxin, RNase RnlA/LsoA, N-terminal repeated domain (RnlA_toxin_NRD)
Type: Domain

Toxin/antitoxin (TA) systems are highly conserved among bacteria and archaea. They play a role in plasmid maintenance, biofilm formation, persister cell formation, general stress response, and phage defense and consist of a stable toxin and an unstable antitoxin. Toxins RnlA (RNase LS) and LsoA are type II TA systems that play a role in phage defence . RnlA and LsoA have endoribonuclease activity, activated after bacteriophage T4 infection. RnlA is the stable toxin that causes inhibition of cell growth and rapidly degrades T4 late mRNAs to prevent their expression, and this is neutralised by the activity of the unstable antitoxin RnlB .

The crystal structure of RnlA revealed that it consist of an N-terminal domain (NTD), an N-Repeated Domain (NRD) and a Dmd-Binding Domain (DBD), being this structure unique and different from all known toxin structures .

This entry represents the N-terminal repeated domain (NRD) of RnlA and LsoA bacterial toxins. NRD from RnlA interacts with RNAse HI and with RnlB. Although its function is unknown, it is required, together with RNase HI, for neutralisation of the RnlA toxicity by endogenous RnlB .
Voltage-gated hydrogen channel 1 (Hvcn1)
Type: Family

Voltage-gated hydrogen channel 1 (Hvcn1, also known as Hv1 or VSOP) mediates the voltage-dependent proton permeability of excitable membranes. It forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient . It is required for high-level superoxide production by phagocytes . It has also been shown to regulate human sperm motility through activating alkalization-activated calcium channels . The structure of Hvcn1 has been solved .
PDZ and LIM domain protein 1-4/Zasp-like, middle domain (PDLI1-4/Zasp-like_mid)
Type: Domain

This presumed domain is found in eukaryotes, and is typically between 121 and 170 amino acids in length, but is functionally uncharacterised. It is found in the middle region of Zasp-like proteins, including Zasp from Drosophila and its orthologue from human ZASP/LIM domain-binding protein 3, and it is usually found in association with

(PDZ) and

(LIM), and often contains the

Zasp-like motif. Zasp is a regulator of cell matrix adhesion having two related functions, one upstream of Actn organizing the Z line and the other downstream of integrins regulating assembly of integrin adhesion sites. It is also required for the formation of myotendinous junctions in muscles .
PrlF antitoxin (PrlF_antitoxin)
Type: Family

PrlF is a bacterial antitoxin that neutralises the toxin YhaV. PrlF is labile and forms a homodimer that then binds to the YhaV toxin thereby neutralising its ribonuclease activity. Alone, it can also act as a transcription factor. The YhaV/PrlF complex binds the prlF-yhaV operon, probably regulating its expression negatively. Over-expression of PrlF leads to increased doubling time .
Domain of unknown function DUF5069 (DUF5069)
Type: Domain

The function of DUF5069 is not known.
Fungal kinase associated-1 domain (Fungal_KA1_dom)
Type: Domain

This domain is found at the C terminus of yeast septin-associated kinases (Kcc4, Gin4 and Hsl1). It is a membrane association domain that binds acidic phospholipids. The structure of this domain has been revealed .
Protein of unknown function DUF4750 (DUF4750)
Type: Family

This family of uncharacterised proteins includes proteins described as small integral membrane protein 13. This family of proteins is found in eukaryotes. There are two completely conserved W residues that may be functionally important.
Spindle pole body-associated protein Vik1/Cik1, microtubule binding domain (Vik1/Cik1_MT-bd)
Type: Domain

This domain can be found in the C-terminal of the yeast spindle pole body-associated protein Vik1 and its paralogue, Cik1. This domain is a motor homology domain that retains microtubule binding properties but lacks a nucleotide binding site .
Putative antitoxin YmcE (YmcE_antitoxin)
Type: Family

YmcE is the putative antitoxin for the supposed bacterial toxin GnsA (

) .
Putative membrane protein FidL-like (FidL-like)
Type: Family

FidL-like is a family of bacterial proteins that are purported to be membrane proteins.
Protein of unknown function DUF4751 (DUF4751)
Type: Family

This family of uncharacterised proteins is found in bacteria.
Bacterial antitoxin YdaS-like (YdaS_toxin-like)
Type: Family

YdaS is a transcription factor found in the cryptic prophage Rac of E. coli K12 and represents a novel family within the HigA superfamily as it is distantly related to HigA antitoxins. YdaS can act as a toxin whose expression is regulated by RacR and behaves as a monomer in solution . Previously, it was thought to be an antitoxin that neutralises the toxin YdaT . This entry also includes some bacteriophage proteins, such as cro from Pseudomonas phage D3 and gene 30 protein from Enterobacteria phage phi80.
Integrase SSV1, C-terminal (Integrase_SSV1_C)
Type: Domain

This entry represent the C-terminal catalytic domain of an integrase, SSV1, from Sulfolobus shibatae. This domain is capable of DNA cleavage and ligation, but at efficiencies significantly lower than those of the full-length protein .
Protein of unknown function DUF4752 (DUF4752)
Type: Family

This family of proteins is found in bacteria and viruses. Proteins in this family are typically between 90 and 105 amino acids in length. There is a conserved GLA sequence motif.
Protein of unknown function DUF4754 (DUF4754)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are approximately 80 amino acids in length.
Phage tail base-plate attachment protein, N-terminal barrel domain (Caud_bapl16_1st)
Type: Domain

Caudo_bapla16 is a family of ORF16 tail-phage P2-like proteins that forms part of the base-plate at the tip of the phage tail. The whole base-plate complex is involved in host recognition and attachment, and consists of several proteins derived from consecutive open-reading-frames . This entry represents the N-terminal RIFT barrel domain.
Gap junction alpha-5 protein (Cx40), C-terminal (Cx40_C)
Type: Domain

This entry represents the C-terminal domain of connexin 40 (Cx40). It interacts with the C-terminal and cytoplasmic loop domains of connexin 43 and with the cytoplasmic loop of another connexin 40 .

Connexin 40 is a gap junction protein that has been linked to lone atrial fibrillation . Gap junctions is composed of two hemichannels, each constituted by the oligomerisation of six connexins (Cx). This junction allows direct exchange of ions and small molecules between apposing cells .
Protein of unknown function DUF4755 (DUF4755)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are approximately 160 amino acids in length.
Protein of unknown function DUF4756 (DUF4756)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are approximately 160 amino acids in length.
Domain of unknown function DUF4757 (DUF4757)
Type: Domain

This presumed domain is functionally uncharacterised. This domain family is found in eukaryotes. There are two completely conserved residues (W and L) that may be functionally important.
Domain of unknown function DUF4758 (DUF4758)
Type: Domain

This presumed domain is functionally uncharacterised. It is found in proteins from arthropods.
MiT/TFE transcription factors, N-terminal (MiT/TFE_N)
Type: Domain

This entry represents a domain found at the N terminus of the MiT/TFE family members, which include MITF (microphthalmia-associated transcription factor) and its related family members TFE3, TFEB and TFEC . They are basic helix-loop-helix leucine zipper transcription factors found in chordata. These transcription factors heterodimerize with each other and bind to the E-box core sequence (3'-CANNTG-5') .
Sliding-clamp-loader small subunit gp62 (Phage_clamp_gp62)
Type: Family

This is the gp62 subunit of bacteriophage DNA clamp loader required for loading of sliding clamps onto chromosomal DNA. These clamps are involved in processivity of DNA replication .
YscO-like protein (YscO-like)
Type: Family

This family of proteins is similar to the type III secretion protein YscO. The family includes Chlamydia trachomatis CT670 which is found in a type III secretion gene cluster. CT670 interacts with CT671, a putative YscP homologue and CT670 and CT671 may form a chaperone-effector pair .
ATF7-interacting protein , protein binding domain (ATF7IP_BD)
Type: Domain

This entry represents a short conserved region of activating transcription factor 7-interacting protein 1 found in higher eukaryotes. This domain appears to bind several key proteins such as TFIIE-alpha and TFIIE-beta as well the transcriptional regulator Sp1 which are part of the transcriptional machinery .