SII-SWORD/CoKE huggingface dataset:
IMD/I-BAR domain (I-BAR_dom)
Type: Domain

The I-BAR domain (also known as IMD domain, IRSp53 and MIM homology domain) is a BAR-like domain of approximately 250 amino acids found at the N-terminal in the IRSp53 (insulin receptor tyrosine kinase substrate p53) and in the evolutionarily related IRSp53/MIM family. The BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. The BAR domain containing proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature . The I-BAR domain containing proteins include:

Vertebrate MIM (missing in metastasis, also known as Protein MTSS 1), an actin-binding scaffold protein that may be involved in cancer metastasis.

Vertebrate ABBA, a MIM-related protein (also known as Protein MTSS 2).

Vertebrate insulin receptor tyrosine kinase substrate p53 (IRSp53, also known as BAR/IMD domain-containing adapter protein 2), a multifunctional adaptor protein that links Rac1 with a Wiskott-Aldrich syndrome family verprolin-homologous protein 2 (WAVE2) to induce lamellipodia or Cdc42 with Mena to induce filopodia .

Vertebrate IRTKS (also known as BAR/IMD domain-containing adapter protein 2-like 1), which plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection .

Vertebrate Pinkbar (also known as BAR/IMD domain-containing adapter protein 2-like 2), which induces the formation of planar or gently curved membrane structures .

Caenorhabditis elegans M04F3.5 protein.

The vertebrate I-BAR family is divided into two major groups: the IRSp53/IRTKS/Pinkbar subfamily and the MIM/ABBA subfamily. The putative invertebrate homologues are positioned between them. The IRSp53/IRTKS/Pinkbar subfamily members contain a SH3 domain, and the MIM/ABBA subfamily proteins contain a WH2 (WASP-homology 2) domain. The vertebrate SH3-containing subfamily is further divided into three groups according to the presence or absence of the WWB and the half-CRIB motif . The BAR domain binds phosphoinositide-rich vesicles with high affinity and does not display strong actin filament binding/bundling activity .
Phospholipase A2-like domain (Phospholipase_A2-like)
Type: Domain

This entry represents a domain that is likely to be a phospholipase A2-like enzyme. It is found in a variety of contexts across the tree of life. This domain can be found in the N-terminal region of the Parvovirus VP1 coat protein ; its function is not known.

Parvoviruses are some of the smallest viruses containing linear, non-segmented single-stranded DNA genomes, with an average genome size of 5000 nucleotides. Parvoviruses have been described that infect a wide range of invertebrates and vertebrates and are well known for causing enteric disease in mammals. Genomes contain two large ORFs: NS1 and VP1; other ORFs are found in some sub-types and different gene products can arise from splice variants and the use of different start codons .
VWA N-terminal (VWA_N)
Type: Domain

This domain is found at the N terminus of proteins containing von Willebrand factor type A (VWA,

) and Cache (

) domains. It has been found in vertebrates, Drosophila melanogaster (Fruit fly) and Caenorhabditis elegans but has not yet been identified in other eukaryotes. It is probably involved in the function of some voltage-dependent calcium channel subunits .
Lambda-like tail fibre protein, N-terminal (Stf-like_N)
Type: Domain

This domain is found at the N terminus of Lambda-like phage and prophage tail fibre proteins.
N-terminal domain of anti-restriction factor ArdC (ArdC_N)
Type: Domain

This is the α-helical ssDNA binding domain of anti-restriction factor ArdC deployed by plasmids and phages in polyvalent proteins related to the BHD domains of XPC/Rad4 and the Tc-38 domain found in kinetoplastid minicircle binding proteins . The structure of this domain is composed of three α-helices and a three-stranded β-sheet that supports a long and protuberant β-hairpin . This domain is also found in the N-terminal region of the RP4 TraC1 primase, together with the Toprim domain (

) .
Transport-associated OB, type 2 (Transp-assoc_OB_typ2)
Type: Domain

The TOBE domain (Transport-associated OB) always occurs as a dimer as the C-terminal strand of each domain is supplied by the partner. Probably involved in the recognition of small ligands such as molybdenum (e.g.

) and sulphate (

). Found in ABC transporters immediately after the ATPase domain. A strong RPE motif is found at the presumed N terminus of the domain.
Amino acid permease, N-terminal (AA_permease_N)
Type: Domain

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related . These proteins appear to contain up to 12 transmembrane segments. The best conserved region in this family is located in the second transmembrane segment. This domain is found to the N terminus of the amino acid permease domain (

) in metazoan Na-K-Cl cotransporters.
Baculoviridae p74 N-terminal (Baculo_p74_N)
Type: Domain

This domain is found at the N terminus of P74 occlusion-derived virus (ODV) envelope proteins which are required for oral infectivity. The envelope proteins are found in baculoviruses which are insect pathogens. The C terminus of P74 is anchored to the membrane whereas the N terminus is exposed to the virion surface. Furthermore P74 is unusual for a virus envelope protein as it lacks an N-terminal localisation signal sequence . Also see

.
Viral polyprotein, Caliciviridae N-terminal (Viral_PP_Calicivir_N)
Type: Domain

This domain is found at the N terminus of non-structural viral polyproteins of the Caliciviridae subfamily.
CbbQ/NirQ/NorQ, C-terminal (CbbQ_C)
Type: Domain

This domain is found at the C terminus of proteins of the CbbQ/NirQ/NorQ family of proteins which play a role in the post-translational activation of Rubisco . It is also found in the Thauera aromaticaTutH protein which is similar to the CbbQ/NirQ/NorQ family , as well as in putative chaperones. The ATPase domain associated with various cellular activities (AAA)

is found in the same bacterial and archaeal proteins as the domain described here.
Chitin synthase N-terminal (Chitin_synth_N)
Type: Domain

This is the N-terminal domain of Chitin synthase.
DNA-directed DNA polymerase, family B, viral insert domain (DNA-dir_DNA_pol_B_vir_insert)
Type: Domain

This viral domain is found between the exonuclease domain of the DNA polymerase family B (

) and the

domain, connecting the two.
Protein O-mannosyl-transferase TMTC, DUF1736 (TMTC_DUF1736)
Type: Domain

This domain of unknown function is found in O-mannosyl-transferases TMTC1-4, and constitutes a loop between TM7 and TM8 located in the ER lumen that contains a small hydrophobic, but not membrane-embedded helix. This loop is critical for catalysis and binding of ligands, especially the lipid-linked sugar moiety .

TMTCs transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases acting primarily on the cadherin superfamily; each member has distinct roles in decorating the cadherin domains with O-linked mannose glycans at specific regions. These proteins also act as O-mannosyl-transferase on other proteins such as PDIA3 .
Domain of unknown function DUF1737 (DUF1737)
Type: Domain

This domain of unknown function is found at the N terminus of bacterial and viral hypothetical proteins.
Exodeoxyribonuclease I, C-terminal (Exonuc_1_C)
Type: Domain

This bacterial domain is found at the C terminus of exodeoxyribonuclease I/Exonuclease I (

), which is a single-strand specific DNA nuclease affecting recombination and expression pathways. The exonuclease I protein in Escherichia coli is associated with DNA deoxyribophosphodiesterase (dRPase) .
Ion transport N-terminal (Ion_trans_N)
Type: Domain

This domain is found to the N terminus of

in voltage- and cyclic nucleotide-gated K/Na ion channels.
NADPH oxidase Respiratory burst (NADPH_Ox)
Type: Domain

This domain is found in plant proteins such as respiratory burst NADPH oxidase proteins which produce reactive oxygen species as a defence mechanism. It tends to occur to the N terminus of an EF-hand (

), which suggests a direct regulatory effect of Ca2+ on the activity of the NADPH oxidase in plants .
Tensin/EPS8 phosphotyrosine-binding domain (PTB)
Type: Domain

The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) of tensin tends to be found at the C terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (

) domain and a region similar to the tumour suppressor PTEN . The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif . The PTB domain is also found in the epidermal growth factor receptor kinase substrate 8 (EPS8).

PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules . This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether . In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine . PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains .
Pheophorbide a oxygenase (PaO)
Type: Domain

This domain is found in bacterial and plant proteins to the C terminus of a Rieske 2Fe-2S domain (

). One of the proteins the domain is found in is Pheophorbide a oxygenase (PaO) which seems to be a key regulator of chlorophyll catabolism. Arabidopsis PaO (AtPaO) is a Rieske-type 2Fe-2S enzyme that is identical to Arabidopsis accelerated cell death 1 and homologous to lethal leaf spot 1 (LLS1) of maize , in which the domain described here is also found.
DNA polymerase alpha, subunit B, N-terminal (Pol_alpha_B_N)
Type: Domain

This entry represents the N-terminal domain of subunit B of DNA polymerase alpha-primase, an enzyme which is essential for DNA replication in higher eukaryotes as it initiates synthesis on both leading and lagging strand single-stranded DNA templates. It consists of a primase heterodimer that synthesises RNA primers, a DNA polymerase that extends them, and a fourth subunit, p68 (also termed B-subunit), which is believed to regulate the whole complex. This domain docks on the SV40 helicase and activates the viral primosome . This domain adopts an α-helical fold .
Methyltransferase putative zinc binding domain (Methyltransf_Zn-bd_dom_put)
Type: Domain

This domain is found at the N terminus of bacterial methyltransferases and contains four conserved cysteines suggesting a potential role in zinc binding.
DNA recombination and repair protein Rad51-like, C-terminal (DNA_recomb/repair_Rad51_C)
Type: Domain

This domain is found at the C terminus of DNA repair and recombination protein Rad51, and eukaryotic and archaeal Rad51-like proteins. It is critical for DNA binding . Rad51 is a homologue of the bacterial RecA protein. Rad51 and RecA share a core ATPase domain.

Unlike eubacteria, several archaeal species have two recA/RAD51-like genes, called RadA and RadB. Among eukaryotes, yeast contain four RAD51-like genes (RAD51, DMC1, RAD55/rhp55, and RAD57/rhp57). In vertebrate animals and plants, there are different RAD51-like genes: RAD51, RAD51B, RAD51C, RAD51D, DMC1, XRCC2, and XRCC3 .
siRNA-mediated silencing protein NRDE-2 (NRDE-2)
Type: Family

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that regulate heterochromatin formation, developmental timing, defence against parasitic nucleic acids, and genome rearrangement. Many small regulatory RNAs are thought to function in nuclei, and in plants and fungi small interfering RNAs (siRNAs) associate with nascent transcripts and direct chromatin and/or DNA modifications. NRDE-2, is required for siRNA-mediated silencing in nuclei. NRDE-2 associates with the Argonaute protein NRDE-3 within nuclei and is recruited by NRDE-3/siRNA complexes to nascent transcripts that have been targeted by RNA interference, RNAi, the process whereby double-stranded RNA directs the sequence-specific degradation of mRNA .
Protein Ice2 (Ice2)
Type: Family

Ice2 is a fungal ER protein which has been shown to play an important role in forming/maintaining the cortical ER . It has also been identified as a protein which is necessary for nuclear inner membrane targeting .
Armadillo-like helical domain-containing protein 3, C-terminal (ARMH3_C)
Type: Domain

This is the C-terminal domain of Armadillo-like helical domain-containing protein 3 (ARMH3), the previously uncharacterised peripheral Golgi protein C10orf76. ARMH3 interacts with and is involved in GBF1 recruitment, Golgi maintenance and protein secretion . C10orf76 associates with the lipid kinase PI4KB that increases phosphatidylinositol 4-phosphate (PI4P) levels at the Golgi, being essential for the viral replication of specific enteroviruses . The function of this domain is unknown.
Lysine-specific demethylase-like domain (Lys_sp_deMease-like_dom)
Type: Domain

This domain is found in the central region of lysine-specific demethylases, which are nuclear proteins that may have a role in DNA-binding and transcription, and are associated with malignant cancer phenotypes . The domain is also found in various other Jumonji/ARID domain-containing proteins (see

,

).
Fork-head N-terminal (Fork-head_N)
Type: Domain

The region described in this entry is found towards the N terminus of various eukaryotic fork head/HNF-3-related transcription factors (which contain the

domain). These proteins play key roles in embryogenesis, maintenance of differentiated cell states, and tumorigenesis .
VPS4-associated protein 1 (Vfa1)
Type: Family

Vps Four-Associated 1, Vfa1, in yeast, is an endosomal protein that interacts with the AAA-ATPase Vps4. It would seem to be involved in regulating the trafficking of other proteins to the endocytic vacuole . There is a CCCH zinc finger at the N terminus.
Protein KTI12/L-seryl-tRNA(Sec) kinase (KTI12/PSTK)
Type: Family

Kti12 associates with Elongator complex, a six-subunit histone acetytransferase complex that functions with the elongating form of RNA polymerase II during transcription . It is not a structural subunit but may play a regulatory role in Elongator function . It has been shown that Kti12 is associated with chromatin throughout the genome, even in non-transcribed regions and in the absence of Elongator . It is required for an early step in synthesis of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups present on uridines at the wobble position in tRNA .

L-seryl-tRNA(Sec) kinase (PSTK) specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis .
Calcium-activated chloride channel, N-terminal (CLCA_N)
Type: Domain

The CLCA family of calcium-activated chloride channels has been identified in many epithelial and endothelial cell types as well as in smooth muscle cells and has four or five putative transmembrane regions. Additionally to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors . This protein cleaves itself into an N-terminal portion and a C-terminal portion. The N terminus contains an HEXXHXXXGXXDE motif which is essential for proteolytic cleavage .
Calicivirus coat protein C-terminal (Calicivirus_coat_C)
Type: Domain

This is the calicivirus coat protein (

) C-terminal region.

Bovine calicivirus is a positive-stranded ssRNA viruses that cause gastroenteritis . The calicivirus genome contains two open reading frames, ORF1 and ORF2 . ORF1 encodes a non-structural polypeptide, which has RNA helicase, cysteine protease and RNA polymerase activity. The regions of the poly-protein in which these activities lie are similar to proteins produced by the picornaviruses . ORF2 encodes a structural protein . This signature finds ORF2, the structural coat protein. Two different families of caliciviruses can be distinguished on the basis of sequence similarity, namely those classified as small round structured viruses (SRSVs) and those classed as non-SRSVs.

Rabbit hemorrhagic disease virus (RHDV) which causes a highly contagious disease of wild and domestic rabbits belongs to the family Caliciviridae . The capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry. It is about 38nm in diameter and consists of 180 capsid proteins. The capsid encapsulates the genomic RNA and VP2 proteins and attaches the virion to target cells by binding histo-blood group antigens present on gastroduodenal epithelial cells. The Shell domain (S domain) contains elements essential for the formation of the icosahedron. The Protruding domain (P domain) is divided into sub-domains P1 and P2. An hypervariable region in P2 is thought to play an important role in receptor binding and immune reactivity.
1-deoxy-D-xylulose 5-phosphate reductoisomerase, C-terminal (DXP_reductoisomerase_C)
Type: Domain

This domain is found to the C terminus of

domains in bacterial and plant 1-deoxy-D-xylulose 5-phosphate reductoisomerases. This domain has been related to the dimer formation, for providing residues necessary for active site metal binding, and for positioning the substrate .

1-deoxy-D-xylulose 5-phosphate reductoisomerase synthesises 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate in a single step by intramolecular rearrangement and reduction and is responsible for terpenoid biosynthesis in some organisms . In Arabidopsis thaliana 1-deoxy-D-xylulose 5-phosphate reductoisomerase is the first committed enzyme of the non-mevalonate pathway for isoprenoid biosynthesis. The enzyme requires Mn2+, Co2+ or Mg2+ for activity, with the first being most effective.

The structure of this enzyme has been solved, showing the protein forms a dimeric assembly and contains a metal ion in the active site .
Glycosyl transferase, family 8, C-terminal (Glyco_transf_8N)
Type: Domain

This domain is found at the C terminus of bacterial glucosyltransferase and galactosyltransferase proteins.
Obg-like GTPase YGR210-like, G4 motif-containing domain (YGR210-like_G4)
Type: Domain

This domain is part of the G domain found at the C-terminal of

in archaeal and eukaryotic GTPases. Members of this entry form a subfamily within the Obg family of GTPases, and includes YGR210 from yeasts and its homologues from archaea . This domain contains the NKxD motif, known as the G4 motif .

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.

Within the translation factor-related (TRAFAC) class of P-loop GTPases, the OBG family comprises a group of high-molecular mass GTPases conserved from bacteria to eukaryotes. The OBG family consists of :

Obg from bacteria and eukaryotes .

DRG from eukaryotes and archaea. DRG proteins may regulate fundamental cellular processes through RNA binding .

Nog1 from eukaryotes and archaea. It is involved in the assembly of the large ribosomal subunit.

Yyaf/YchF from bacteria and eukaryotes. It consists of a central G domain, flanked by a coiled-coil domain and a TGS (ThrRS, GTPase, SpoT) domain. Members of this subfamily bind and hydrolyse ATP more efficiently than GTP .

Ygr210 from archaea and fungi.

The OBG-type G domain has a mononucleotide binding fold typical for the P-loop NTPases. A six-stranded mostly parallel β-sheet is flanked by α-helices on both sides. The OBG-type G domain contains five characteristic sequence motifs, termed G1-G5, involved in nucleotide binding and hydrolysis. The G1/Walker A motif (GXXXXGK(S/T)), also referred to as P-loop, helps to position the triphosphate moiety of the bound nucleotide. The G2 (X(T/S)X) and G3/Walker B (hhhDXXG) motifs are involved in the coordination of a Mg(2)+ ion that is required for nucleotide binding and hydrolysis. Specificity in nucleotide binding is conferred by the G4 motif, which has a (N/T)KXD signature in guanine nucleotide binding P-loop NTPases. The G5 motif ((T/G)(C/S)A) supports guanine base recognition .
Oligopeptidase F, N-terminal domain (OligopepF_N_dom)
Type: Domain

This domain is found towards the N terminus of oligoendopeptidase F proteins. An example protein is Lactococcus lactis PepF,

. The function of this N-terminal domain is unknown.
Polyprotein, Potyviridae (PP_Potyviridae)
Type: Domain

This domain is found in polyproteins of the viral Potyviridae taxon.
Integrin alpha, first immunoglubulin-like domain (Integrin_alpha_Ig-like_1)
Type: Domain

This entry represents the first immunoglobulin-like domain of the three found in integrin alpha and integrin alpha precursors to the C terminus of a number of FG-GAP repeats (

) and to the N terminus of the cytoplasmic region

.
ATP-grasp fold, succinyl-CoA synthetase-type (ATP-grasp_succ-CoA_synth-type)
Type: Domain

The ATP-grasp superfamily currently includes 17 groups of enzymes, catalysing ATP-dependent ligation of a carboxylate containing molecule to an amino or thiol group-containing molecule . They contribute predominantly to macromolecular synthesis. ATP-hydrolysis is used to activate a substrate. For example, DD-ligase transfers phosphate from ATP to D-alanine on the first step of catalysis. On the second step the resulting acylphosphate is attacked by a second D-alanine to produce a DD dipeptide following phosphate elimination .

The ATP-grasp domain contains three conserved motifs, corresponding to the phosphate binding loop and the Mg(2+) binding site . The fold is characterised by two α-β subdomains that grasp the ATP molecule between them. Each subdomain provides a variable loop that forms a part of the active site, completed by region of other domains not conserved between the various ATP-grasp enzymes .

The ATP-grasp domain represented by this entry is found primarily in succinyl-CoA synthetases (

).
ATP-grasp fold, RimK-type (ATP-grasp_RimK-type)
Type: Domain

This ATP-grasp domain is found in the ribosomal S6 modification enzyme RimK . It has an unusual nucleotide-binding fold referred to as palmate, or ATP-grasp fold. This domain is found in a number of enzymes of known structure as well as in urea amidolyase, tubulin-tyrosine ligase, and three enzymes of purine biosynthesis.
Glycine N-acyltransferase, C-terminal (Glycine_N-acyltransferase_C)
Type: Domain

This entry represents mammalian-specific glycine N-acyltransferase (also called aralkyl acyl-CoA:amino acid N-acyltransferase;

). Mitochondrial acyltransferases catalyse the transfer of an acyl group from acyl-CoA to the N terminus of glycine to produce N-acylglycine. These enzymes can conjugate a multitude of substrates to form a variety of N-acylglycines. The CoA derivatives of a number of aliphatic and aromatic acids, but not phenylacetyl-CoA or (indol-3-yl)acetyl-CoA, can act as donor .