SII-SWORD/CoKE huggingface dataset:
Stomatal closure-related actin-binding protein, actin-binding domain (SCAB-ABD)
Type: Domain

This entry represents the actin-binding domain (ABD) of plant-specific actin-binding proteins or SCABs. SCAB proteins bind, bundle and stabilise actin filaments and regulate stomatal movement. The Ig-PH fusion domain is at the C terminus. The ABD is structurally independent from the first coiled-coil, CC1, domain which is also involved in binding; the CC1 is likely to function as a dimerisation module ,
Domain of unknown function DUF4795 (DUF4795)
Type: Domain

This domain is found in a group of animal proteins that is functionally uncharacterised.
Vibrio phage CTXphi pIII, N-terminal N1 domain (CTXphi_pIII-N1)
Type: Domain

This entry represents the N-terminal domain, N1, of the pIII protein of the CTXphi bacteriophage of Vibrio cholerae. CTXphi is a ssDNA Inovirus. pIII is a minor coat protein. This domain interacts directly with the C terminus of TolA, a periplasmic protein of Vibrio cholerae itself as part of the infection mechanism .
Stomatal closure-related actin-binding protein, Ig domain (SCAB-Ig)
Type: Domain

This entry represents an Ig-like domain found in plant-specific actin-binding proteins or SCABs. SCAB proteins bind, bundle and stabilise actin filaments and regulate stomatal movement. The Ig-PH fusion domain is at the C terminus. This domain is an Ig β-sandwich fold consisting of two antiparallel β-sheets built from strands β1 and β2 and strands β3-β6, respectively .
MKRN2 opposite strand protein-like (MKRN2OS-like)
Type: Family

This entry represents human MKRN2 opposite strand protein (MKRN2OS) and similar animal proteins of unknown function.
FAM76 protein (FAM76)
Type: Family

This family of proteins is known as FAM76 and it is functionally uncharacterised. It is found in eukaryotes. Proteins in this family are typically between 233 and 341 amino acids in length.
Putative lipoprotein, pathogenic bacteria (LppA/LppB/LprP)
Type: Family

This entry includes LppA, which is a lipoprotein found in pathogenic mycobacteria. These pathogenic lipoproteins may play a role in host-pathogen interactions. Lipoproteins localised to the cell-envelope of pathogenic bacteria are major determinants of virulence. The proteins are localised to the cell-surface via an N-terminal lipidation carried out by a transferase - pro-lipoprotein diacylglyceryl transferase Lgt - which attaches a diacylglyceride molecule to a sulfur atom from a crucial cysteine, and a consecutively acting lipoprotein signal peptidase LspA that cleaves the signal peptide just before the modified cysteine. When the peptidase is inactivated the pathogen has difficulty in replicating inside macrophages .
Frog antimicrobial peptide, ranacyclin-type, Ranidae (Frog_antimicrobial_Ranidae)
Type: Family

This domain contains about 17 amino acid residues with two cysteines forming a disulfide bridge. It can be found in the antimicrobial peptides from Ranidae (riparian frogs), such as Nigroain-A antimicrobial peptide, Ranacyclin-T/E, Odorranain-B1 and Odorranain-B-RA1, which are secreted from frog skin .
CAG pathogenicity island protein 13 (CagS)
Type: Family

This entry represents CAG pathogenicity island protein 13 (CagS), which is a family of proteins from the pathogenicity island of Helicobacter pylori. The gene lies just downstream of the cluster whose protein-products resemble those of the Vibrio proteins that form the structural core of T4SS. The exact function of CagS is not known .
Frog antimicrobial peptide, caerin-type, Litoria (Frog_Litoria)
Type: Family

This family includes antimicrobial peptides such as Aurein-5 and Caerin-2 which are secreted from Litoria (tree frog) skin .
KRIT, N-terminal NPxY motif-rich region (NUDIX)
Type: Domain

This domain is found in higher eukaryotes at the N terminus of KRIT1 or Krev interaction trapped proteins. KRIT1 is a 736 amino acid protein that contains three regions, an N-terminal NPxY motif-rich region, an ankyrin repeat domain (ARD) and a band four-point-one, ezrin, radixin, moesin (FERM) domain. The N-terminal region of KRIT1 contains three NPxY-like motifs and can bind ICAP1 (integrin cytoplasmic-associated protein 1 (ICAP1). In the absence of KRIT1, ICAP1 binds via its C-terminal PH/PTB fold domain to the integrin beta-1 cytoplasmic tail. Binding of KRIT1 to ICAP1 via this domain out-competes the binding of ICAP1 to integrin cytoplasmic tails such that ICAP1 is sequestered in the nucleus. Integrin activation is thus prevented. KRIT1 does not include the canonical "Nudix box" motif or other Nudix motifs but does, however, very clearly adopt a Nudix fold with a central β-sheet flanked by two α-helices .
GCC2, Rab binding domain (GCC2_Rab_bind)
Type: Domain

This coiled-coil domain, found in GRIP and coiled-coil domain-containing protein 2 (GCC2), has been shown to bind to Rab GTPase .
Protein of unknown function DUF5064 (DUF5064)
Type: Family

Members of this family are found in Pseudomonas species. Several are annotated as being acetyl-CoA carboxylase alpha subunit, but this could not be confirmed.
Protein of unknown function DUF5063 (DUF5063)
Type: Family

The function of DUF5063 is not clear.
Adenylate cyclase regulatory domain (Ad_Cy_reg)
Type: Domain

This domain regulates the activity of Actinobacterial adenylate cyclase in a pH-dependent manner, allowing activation at acidic pH .
Synphilin-1, alpha-Synuclein-binding domain (SNCAIP_SNCA-bd)
Type: Domain

This coiled-coil domain found in Synphilin-1 is responsible for binding to alpha-Synuclein .
Cleavage stimulation factor subunit 1, dimerisation domain (CSTF1_dimer)
Type: Domain

This entry represents the dimerisation domain found at the N terminus of cleavage stimulation factor subunit 1 (CSTF1) from eukaryotes. This domain allows for homodimerisation such that the functional state of CSTF1 is a heterohexamer. The Cleavage stimulation Factor (CstF) complex is composed of three subunits and is essential for pre-mRNA 3'-end processing. CstF recognises U and G/U-rich cis-acting RNA sequence elements and helps to stabilise the Cleavage and Polyadenylation Specificity Factor (CPSF) at the polyadenylation site as required for productive RNA cleavage .
ADAM17, membrane-proximal domain (ADAM17_MPD)
Type: Domain

This entry represents the membrane-proximal domain (MPD) of disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) from animals. ADAM17 is a major sheddase responsible for the regulation of a wide range of biological processes, such as cellular differentiation, regeneration, and cancer progression.
YscD, cytoplasmic domain (YscD_cytoplasmic_dom)
Type: Domain

This entry represents the cytoplasmic domain of YscD from Yersinia enterocolitica and similar proteins from bacteria. This domain consists of a forkhead-associated (FHA) fold. The FHA domain is a small phosphopeptide recognition module. Due to the lack of the conserved residues that are required for binding phosphothreonine, the cytoplasmic domain of YscD protein is therefore unlikely to function as a true FHA domain.

YscD is a single-pass inner membrane protein required for the export process of the Yop proteins. It is an essential component of the type III secretion system. YscD contains an N-terminal cytoplasmic domain (

), a transmembrane linker and a large periplasmic region formed by the three BON domains (

), (

) and (

). YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus .
Zinc finger FYVE domain-containing protein 21, C-terminal (ZFYVE21_C)
Type: Domain

Zinc finger FYVE domain-containing protein 21 (ZF21) regulates focal adhesions and cell migration binds by binding multiple factors that promote disassembly of focal adhesions (FAs) such as FAK, beta-tubulin, m-calpain, and SHP-2 .

This is the C-terminal domain of ZF21. It has a PH-like fold and is required for the regulation of focal adhesions and in cell migration .
Type VI secretion system (T6SS), amidase immunity protein (Tai4)
Type: Family

Tai4 is a new form of autoimmunity protein for a type VI secretion system, T6SS. T6SS has roles in interspecies interactions, as well as higher order host-infection, by injecting effector proteins into the periplasmic compartment of the recipient cells of closely related species. Pseudomonas aeruginosa produces at least three effector proteins to other cells and thus has three specific cognate immunity proteins to protect itself. Tae4, or type VI amidase effector 4, in Enterobacter cloacae has a cognate Tai4 or type VI amidase immunity 4 protein . The effector is Tae4 (

).
Cytochrome P460 (Cytochrome_P460)
Type: Domain

This entry includes cytochrome P460 from Nitrosomonas europea. It is a monoheme c-type cytochrome. Its structure has been revealed .
YscD-like, Bon-like domain 1 (YscD_ppl_1st)
Type: Domain

This entry represents the first of three periplasmic BON domains of YscD from Proteobacteria.

YscD is a single-pass inner membrane protein required for the export process of the Yop proteins. It is an essential component of the type III secretion system. YscD contains an N-terminal cytoplasmic domain (

), a transmembrane linker and a large periplasmic region formed by the three BON domains (

), (

) and (

). YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus .
Folliculin, DENN domain (Folliculin_DENN)
Type: Domain

Folliculin (FLCN) is a tumor suppressor that enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) Activating Protein (GAP) activity. It belong to the DENN module family of proteins and contains a divergent DENN module comprised of a N-terminal longin domain (also known as upstream DENN domain, u-DENN), followed by a DENN domain. It forms a complex with its partners, FNIP1 or FNIP2 (Folliculin interacting protein 1 or 2), which directly contacts the Rag GTPases RagC/D to stimulate GTP hydrolysis and thus promote the conversion to the GDP-bound state. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. They contain longin domains that heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, and C-terminal DENN domains which interact at the distal end of the structure .

This is the DENN domain found at the C-terminal of folliculin. This domain shares structural similarity with DENN domain of DENN1B (a Rab GEF). It mediates contact with the longin domain in the heterodimers to ensure a strong intersubunit interaction .
Protein of unknown function DUF5062 (DUF5062)
Type: Family

The function of DUF5062 is not known.
Methylmalonic aciduria and homocystinuria type C family (MMACHC)
Type: Family

MMACHC, also known as Cyanocobalamin reductase / alkylcobalamin dealkylase, is involved in the intracellular processing of vitamin B12 by catalyzing two reactions: the reductive decyanation of cyanocobalamin in the presence of a flavoprotein oxidoreductase and the dealkylation of alkylcobalamins through the nucleophilic displacement of the alkyl group by glutathione . Mutations in the MMACHC gene have been linked to a disease known as Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), the most common inborn error of vitamin B(12) (cobalamin) metabolism. The C-terminal region of this protein folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake .

The structure of MMACHC reveals it to be the most divergent member of the NADPH-dependent flavin reductase family that can use FMN or FAD to catalyze reductive decyanation; it is also the first enzyme with glutathione transferase (GST) activity that is unrelated to the GST superfamily in structure and sequence .
Adenomatous polyposis coli, N-terminal dimerisation domain (APC_N)
Type: Domain

This entry represents the N-terminal, coiled-coil dimerisation domain of the adenomatosis polyposis coli (APC) tumour-repressor proteins. It plays a key role in the regulation of cellular levels of the oncogene product beta-catenin. Coiled-coil regions are binding repeats that in this case bind to the armadillo repeat region of beta-catenin .
Alphacoronavirus nsp1 (A-CoV_nsp1)
Type: Domain

This entry represents the N-terminal region of the alphacoronovirus polyprotein, which contains non-structural protein 1 (Nsp1). Nsp1 from alphacoronavirus transmissible gastroenteritis virus (TGEV) folds into a six-stranded β-barrel fold with a long α helix on the rim of the barrel. This fold is shared with betacoronavirus SARS-CoV nsp1 .
ELYS, beta-propeller domain (ELYS-bb)
Type: Domain

This entry represents the N-terminal seven-bladed β-propeller domain of ELYS nucleoporins in higher eukaryotes. It is required for anchorage of the nucleoporin to the nuclear envelope during cell-division .
Paf1 complex subunit Cdc73, N-terminal domain (Cdc73_N)
Type: Domain

This is the N-terminal region of Cdc73 (cell division cycle 73). Cdc73 forms part of the Paf1 post-initiation complex . As part of the Paf1 complex, Cdc73 associates with RNA-polymerase II and is involved in several transcriptional and posttranscriptional events. In vertebrates, the protein encoded by HRPT2/CCdc73 is known as Parafibromin, and acts as a tumour suppressor .
Protection of telomeres protein 1, ssDNA-binding domain (POT1PC)
Type: Domain

This entry represents the ssDNA-binding domain found in telomere protection protein 1 (Pot1). This domain is able to accommodate heterogeneous ssDNA ligands. Pot1 is responsible for binding to and protecting the 3' single-stranded DNA (ssDNA) overhang at most eukaryotic telomeres .
E3 ubiquitin-protein ligase Msl2, zinc RING finger (Msl2_Znf-RING)
Type: Domain

MSL2, also known as RING finger protein 184 (RNF184), is a putative DNA-binding protein required for X chromosome dosage compensation in Drosophila males. Its expression is sex specifically regulated by Sex-lethal. Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3 are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation). MSL2 plays a critical role in translation and/or stability of MSL1 in males. In complex with MSL1, it acts as an E3 ubiquitin ligase that promotes ubiquitination of histone H2B. MSL2 contains a C3HC4-type RING-HC finger and a metallothionein-like domain with eight conserved and two non-conserved cysteines, as well as a positively and a negatively charged amino acid residue cluster and a coiled coil domain that may be involved in protein-protein interactions .

This entry represents the N-terminal domain of the E3 ubiquitin-protein ligase Msl2 and its homologues. This domain binds Msl1 and exhibits ubiquitin E3 ligase activity towards H2B K34 .
Telomere resolvase ResT/TelK, catalytic domain (ResT/TelK_cat)
Type: Domain

Telomere resolvase ResT (protelomerase) catalyses the conversion of linear double-stranded DNA into hairpin telomeres . This entry represents the catalytic domain of ResT and TelK .
Transglutaminase elicitor (TGase_elicitor)
Type: Family

This entry represents a family of largely oomycete sequences from plant pathogens that elicit transglutaminase/acyltransferase activity. The enzyme classification is (

). From the presence of sequences from Vibrio spp one can propose a lateral gene transfer event having occurred between bacteria and oomycetes to the probable selective advantage of the pathogen .
E3 ubiquitin-protein ligase Msl2, CXC domain (Msl2-CXC)
Type: Domain

This entry represents an autonomously folded domain that binds three zinc ions. This domain can be found in E3 ubiquitin-protein ligase Msl2 from eukaryotes. The CXC domain critically contributes to the DNA-binding activity of Msl2 . It carries 9 invariant cysteines within about a 50 residue region.
Domain of unknown function DUF4797 (DUF4797)
Type: Domain

This presumed domain is functionally uncharacterised. It is found in insect proteins, and is approximately 40 amino acids in length. There is a conserved SGLPT sequence motif. There are two completely conserved residues (P and G) that may be functionally important.
CD3 gamma/delta subunit, Ig-like domain (Ig_4)
Type: Domain

This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 gamma/delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex .
Small ribosomal subunit protein mS34 (Ribosomal_mS34)
Type: Family

This entry represents ribosomal protein S34 from the mitochondrial 28S subunit .
DNA replication factor Cdt1, C-terminal (Cdt1_C)
Type: Domain

In eukaryotic replication licensing, Cdt1 plays a key role by recruiting the MCM2-7 complex onto the origin of chromosome. This entry represents the C-terminal domain of Cdt1 which is the most conserved region of Cdt1, essential for licensing and directly interacts with the MCM2-7 complex . This region contains a WHD (winged helix domain), a typical DNA recognition motif . The winged-helix fold is conserved throughout several other licensing factors, suggesting that they evolved from a common ancestor. In mouse Cdt1, the main role of the WH motif is to interact with MCM2-7 rather than with the DNA, as other winged-helix domains.
Transmembrane protein 72 (TMEM72)
Type: Family

This family of eukaryotic proteins is functionally uncharacterised. Proteins in this family are typically between 145 and 275 amino acids in length.
Protein of unknown function DUF4798 (DUF4798)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically found in insects and are between 80 and 365 amino acids in length. There is a single completely conserved residue H that may be functionally important.
Protein of unknown function DUF4799 (DUF4799)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically found in insects and are between 362 and 1493 amino acids in length.
Mucin-like domain (Mucin-like)
Type: Domain

This domain is found repeated at the C terminus (C-tail) of bile salt-activated lipase, where it is O-glycosylated .
MGA, conserved domain (MGA_dom)
Type: Domain

This domain can be found in the MAX gene-associated protein (Mga), which is a dual-specificity transcription factor that contains both a bHLHZip domain and a T-box domain and is able to bind to and regulate transcriptional targets through both E-box sites as well as T-box-binding elements (TBEs) .

MAX gene-associated protein (MGA) is a dual-specificity transcription factor, acting as a repressor or an activator and binding to 5'-AATTTCACACCTAGGTGTGAAATT-3'. MGA regulates genes targeted by MYC-MAX, suppressing transcriptional activation by MYC and inhibiting MYC-dependent cell transformation. MGA binds DNA via a T-Box . MGA is a component of the MLL1 complex .
Domain of unknown function DUF4802 (DUF4802)
Type: Domain

This presumed domain is functionally uncharacterised. It is approximately 70 amino acids in length. There are two conserved sequence motifs: CRC and YFDC.
Protein of unknown function DUF4803 (DUF4803)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in arthropods. Proteins in this family are typically between 351 and 686 amino acids in length. There is a conserved RRY sequence motif.
ADP-ribosylhydrolase MavL-like (MavL-like)
Type: Family

This entry represents a class of MavL-like macrodomain enzymes whose representative members show unique selectivity for mono-ADP-ribosylated arginine residue in synthetic substrates, including ADP-ribosylarginine hydrolase CG2909

and ADP-ribosylarginine hydrolase CG3568

from Drosophila melanogaster, which are distantly related to MavL from Legionella pneumophila . They are (ADP-ribosyl)hydrolases that share a mode of ADP-ribose interaction distinct from previously characterised macrodomains .
Protein of unknown function DUF4805 (DUF4805)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically found in insects and they are between 244 and 363 amino acids in length. There is a conserved WEL sequence motif.
E3 ubiquitin-protein ligase RNF31, UBA-like domain (RNF31-UBA)
Type: Domain

This entry represents a binding domain found in E3 ubiquitin-protein ligase RNF31 and similar animal proteins. RNF31 is also known as HOIL-1L binding partner (HOIP). The interaction of HOIL-1L and HOIP is via the UBL-UBA interaction. This interaction is important in E3 complex formation and the subsequent activation of NF-kappaB .
DNA-packaging protein gp3 (GP3_package)
Type: Family

DNA-packaging protein gp3 (terminase small subunit) is involved in DNA packing in bacteriophage. It contains a channel where DNA is bound and passed to DNA-packaging protein gp2 (terminase large subunit) .
FOXO protein, transactivation domain (FOXO-TAD)
Type: Domain

TAD is a promiscuous binding domain that mediates the association of the transcription factor FOXO with the coactivator CBP/p300. Both this domain and the KIX-binding domain bind simultaneously the KIX domain of CBP/p300. Coactivator CBP/p300 is recruited by FOXO3 though binding to these two regions. The promiscuity of the TAD is further evidenced by that the finding that they also bind the TAZ1 and TAZ2 domains of CBP/p300 .
FOXO protein, KIX-binding domain (FOXO_KIX-bd)
Type: Domain

This entry represents a domain found in the transcription factor forkhead box O (FOXO) that binds to the KIX domain of CREB-binding proteins. Coactivator CBP/p300 is recruited by FOXO3 via the binding of this domain as well as the simultaneous binding of the C-terminal TAD domain .
Ubiquitin carboxyl-terminal hydrolase 37, pleckstrin homology-like domain (USP37-like_PH)
Type: Domain

This entry represents a pleckstrin homology (PH)-like domain found at the N terminus of some ubiquitin carboxyl-terminal hydrolases, including USP26, USP29 and USP37. USP37 antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), resulting in promoting S phase entry . USP26 is a regulator of androgen receptor (AR) signaling . Both USP26 and USP37 are critical for double-strand breaks repair by homologous recombination . USP29 plays a role in apoptosis and oxidative stress .

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 . They share little sequence conservation, but all have a common fold, which is electrostatically polarized.
TNF receptor-associated factor, BIRC3 binding domain (TRAF_BIRC3-bd)
Type: Domain

This domain is found in TNF receptor-associated factor 1 and 2 (TRAF1 and TRAF2), where it binds to Baculoviral IAP repeat-containing protein 3 (BIRC3) (cIAP2) .
Domain of unknown function DUF4806 (DUF4806)
Type: Domain

This presumed domain is functionally uncharacterised. This domain is found in eukaryotes, and is approximately 80 amino acids in length.
Protein of unknown function DUF4807 (DUF4807)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically between 171 and 270 amino acids in length. There is a conserved STLGG sequence motif.
Fibronectin type III domain-containing protein 5, C-terminal domain (FNDC5_C)
Type: Domain

This domain is found in fibronectin type III domain-containing protein 5 (FNDC5). FNDC5 is cleaved into Irisin, a putative myokin that stimulates white-to-brown fat conversion in mice , though this role is disputed in humans . This domain is found C-terminal to the irisin domain .