SII-SWORD/CoKE huggingface dataset:
F-box only protein 11, F-box domain (F-box_FBXO11)
Type: Domain

This entry represents the F-box domain of UBR11 and similar animal proteins. This domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

F-box only protein 11 (FBXO11, also called UBR6 and VIT-1) is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumour initiation and progression. FBXO11 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. FBXO11 does not bind N-terminal signals . In humans, the gene encoding this protein has been associated to intellectual developmental disorders .
E3 ubiquitin-protein ligase UBR7-like, UBR-box (UBR7-like_UBR-box)
Type: Domain

This entry represents the UBR-box of UBR7 and similar eukaryotic proteins.

Proteins in this entry include the putative E3 ubiquitin-protein ligase UBR7, which is found in mammalian spermatozoa, particularly the acrosomal cap and sperm acrosome . UBR7 is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. It may play an important role in spermiogenesis and fertilisation. Homologues are found in plants and fungi, including the uncharacterised protein Mlo2 from fission yeasts. Both UBR7 and Mlo2 contain both a PHD-type and an UBR-type zinc finger.
E3 ubiquitin-protein ligase UBR1, UBR-box (UBR-box_UBR1)
Type: Domain

This entry represents the UBR-box of human UBR1 and similar proteins found in vertebrates .

E3 ubiquitin-protein ligase UBR1 (

), also called ubiquitin-protein ligase E3-alpha-I (E3alpha-I), or N-recognin-1, is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognises and binds to proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their ubiquitination and subsequent degradation . Deficiency of UBR1 causes Johanson-Blizzard syndrome .
E3 ubiquitin-protein ligase UBR2, UBR-box (UBR-box_UBR2)
Type: Domain

This entry represents the UBR-box of human UBR2 and similar proteins found in vertebrates .

E3 ubiquitin-protein ligase UBR2 (

), also called ubiquitin-protein ligase E3-alpha-II (E3alpha-II), or N-recognin-2, is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognises and binds to proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their ubiquitination and subsequent degradation . UBR2 is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells . It plays an important role in spermatogenesis .
E3 ubiquitin-protein ligase UBR4-like, UBR-box (UBR4-like_UBR-box)
Type: Domain

This entry represents the UBR-box of human UBR4 and similar proteins predominantly found in vertebrates and arthropods.

E3 ubiquitin-protein ligase UBR4 (

), also called N-recognin-4, retinoblastoma-associated factor of 600 kDa, is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognises and binds to proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR4 acts as a multifunctional protein with roles in anoikis, viral transformation, and protein degradation, as well as in neurogenesis, neuronal migration, neuronal signalling, and survival .

The homologue from Drosophila melanogaster protein purity of essence is also included in this group of proteins .
Forkhead box protein H1, forkhead domain (FH_FOXH1)
Type: Domain

This entry represents the forkhead (FH) domain of FOXH1 and similar proteins from vertebrates. The FH domain is a winged helix DNA-binding domain.

This group of proteins includes a winged-helix transcription factor, FOXH1, which is also called Forkhead activin signal transducer 1 (Fast-1), or Forkhead activin signal transducer 2 (Fast-2). FOXH1 acts as a transcriptional activator that recognises and binds to the DNA sequence 5'-TGT[GT]][GT]]ATT-3'. It is required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signalling. FOXH1 forms a transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site on the GSC promoter called TARE (TGF-beta/activin response element). FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3' .
Forkhead box protein J1, forkhead domain (FH_FOXJ1)
Type: Domain

This entry represents the forkhead (FH) domain of FOXJ1 and similar proteins from animals. The FH domain is a winged helix DNA-binding domain.

Forkhead box protein J1 (FOXJ1), also called Forkhead-related protein FKHL13 or HFH-4, acts as a transcription factor specifically required for the formation of motile cilia . It acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. FOXJ1 binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T). It activates the transcription of a variety of ciliary proteins in the developing brain and lung . In humans, FOXJ1 is associated with mucosal inflammation caused by allergen exposure and a form of primary ciliary dyskinesia characterised by chronic inflammation and bronchiectasis due to defects in the respiratory cilia .
Forkhead box protein J1 (FOXJ1)
Type: Family

Forkhead box protein J1 (FOXJ1), also called Forkhead-related protein FKHL13 or HFH-4, acts as a transcription factor specifically required for the formation of motile cilia . It acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. FOXJ1 binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T). It activates the transcription of a variety of ciliary proteins in the developing brain and lung . In humans, FOXJ1 is associated with mucosal inflammation caused by allergen exposure and a form of primary ciliary dyskinesia characterised by chronic inflammation and bronchiectasis due to defects in the respiratory cilia .
Forkhead box protein L1, forkhead domain (FH_FOXL1)
Type: Domain

This entry represents the forkhead (FH) domain of FOXL1 and similar proteins from animals. The FH domain is a winged helix DNA-binding domain.

Forkhead box protein L1 (FOXL1), also called Forkhead-related protein FKHL11 or Forkhead-related transcription factor 7 (FREAC-7), acts as a transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium . In zebrafish has been proposed as a regulator of neural development . It may play a critical role in suppressing tumorigenesis .
Forkhead box protein L2, forkhead domain (FH_FOXL2)
Type: Domain

This entry represents the forkhead (FH) domain of human FOXL2 and similar sequences from animals. The FH domain is a winged helix DNA-binding domain.

Forkhead box protein L2 (FOXL2) is a transcriptional regulator that is essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination . Mutations in the FOXL2 gene cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I, a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II, the eyelid defect occurs as an isolated entity .

This group of proteins also includes the homologue Forkhead transcription factor fkh-6 from Caenorhabditis elegans, which is involved in male germ-line sex determination and male gonad development .
Forkhead box protein M1, forkhead domain (FH_FOXM1)
Type: Domain

This entry represents the forkhead (FH) domain of human FOXM1 and similar sequences mainly found in vertebrates. The FH domain is a winged helix DNA-binding domain .

Forkhead box protein M1 (FOXM1) is a forkhead transcription factor that regulates expression of cell cycle genes essential for DNA replication and mitosis during organ repair and cancer progression . It is also involved in DNA break repair, participating in the DNA damage checkpoint response . It is regulated by the mitotic kinase Polo-like kinase 1 (Plk1) . It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence . FOXM1 promotes transcription of PHB2 .
Forkhead box protein Q1, forkhead domain (FH_FOXQ1)
Type: Domain

This entry represents the forkhead (FH) domain of human FOXQ1 and similar sequences mainly found in vertebrates. The FH domain is a winged helix DNA-binding domain.

Forkhead box protein Q1 (FOXQ1), also called HNF-3/Forkhead-like protein 1 (HFH-1), or hepatocyte nuclear factor 3 Forkhead homolog 1, plays a role in hair follicle differentiation. It has also been reported to promote epithelial differentiation, inhibit smooth muscle differentiation, activate T cells and autoimmunity, and control mucin gene expression and granule content in stomach surface mucous cells . FOXQ1 is significantly associated with the pathogenesis of various tumour types including gastric, breast, colorectal, pancreatic, bladder and ovarian cancer, and glioma .
Forkhead box protein Q2-like, forkhead domain (FH_FOXQ2-like)
Type: Domain

This entry represents the forkhead (FH) domain of human FOXQ2 and similar sequences from animals. The FH domain is a winged helix DNA-binding domain.

Forkhead box protein (FOXQ2) is the neurogenic ectoderm specification transcription factor that controls aboral development in cnidarians and anterior identity in bilaterians. It plays essential roles in epidermal development and central brain patterning. The foxQ2 gene is absent in placental mammals .
DNA repair endonuclease XPF, nuclease domain (XPF_nuclease)
Type: Domain

This entry represents the nuclease domain of XPF and similar proteins found in eukaryotes. This domain has the GDX(n)ERKX(3)D motif, which is required for metal-dependent endonuclease activity but not for DNA junction binding .

This entry includes XPF from animals and its fungal orthologues Rad1 from budding yeasts and Rad16 from fission yeasts. Human XPF is a catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. It is involved in homologous recombination that assists in removing interstrand cross-link . This protein is associated with several types of the Xeroderma pigmentosum disorder , XFE progeroid syndrome and a form of Fanconi anemia . Budding yeast Rad1 and Rad10 form an endonuclease that specifically degrades single-stranded DNA .

The plant homologue DNA repair endonuclease UVH1 from Arabidopsis thaliana, alternatively known as RAD1, is also included in this entry .
Crossover junction endonuclease EME1, XPF-like nuclease domain, ascomycetes (XPF_nuclease_EME1_ascomycetes)
Type: Domain

This entry represents the XPF-like nuclease domain of crossover junction endonuclease EME1 and similar proteins from ascomycetes. This domain lacks the catalytic motif.

Crossover junction endonuclease EME1, also known as Mms4 in fission yeast, is a putative transcriptional (co)activator that protects cells from endogenous and environmental DNA damage. It interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks with regressed leading strands and nicked Holliday junctions .
Crossover junction endonuclease EME1, XPF-like nuclease domain, vertebrates (XPF_nuclease_EME1_vertebrates)
Type: Domain

This entry represents the XPF-like nuclease domain of crossover junction endonuclease EME1 and similar proteins from vertebrates. This domain is a nuclease-like domain which is involved in targeting the MUS81-EME1 heterodimer complex to DNA .

Crossover junction endonuclease EME1, also called MMS4 homologue (hMMS4), interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Its typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. EME1 may be required in mitosis for the processing of stalled or collapsed replication forks .
Crossover junction endonuclease EME2, XPF-like nuclease domain (XPF_nuclease_EME2)
Type: Domain

This entry represents the XPF-like nuclease domain of Crossover junction endonuclease EME2 and similar proteins from vertebrates. This domain is a nuclease-like domain which is involved in targeting the MUS81-EME2 heterodimer complex to DNA.

Crossover junction endonuclease EME2 interacts with MUS81 to form a DNA structure-specific endonuclease which cleaves substrates such as 3'-flap structures. MUS81-EME2 is responsible for fork cleavage and restart in human cells . The MUS81-EME2 protein, whose actions are restricted to S phase, is also responsible for telomere maintenance in telomerase-negative ALT (Alternative Lengthening of Telomeres) cells .
Crossover junction endonuclease EME1, XPF-like nuclease domain, plants/arthropods (XPF_nuclease_EME1_plant/arthr)
Type: Domain

This entry represents the XPF-like nuclease domain of crossover junction endonuclease EME1 and similar proteins from plants and arthropods. This domain is a nuclease-like domain which is involved in targeting the MUS81-EME1 heterodimer complex to DNA.

The Mus81-EME1 complex is a structure-selective endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks, nicked Holliday junctions and also intact Holliday junctions with a reduced efficiency. It may be required in mitosis for the processing of stalled or collapsed replication fork intermediates. It plays a role in DNA repair and in genotoxic stress-induced homologous recombination (HR) in somatic cells and mediates a subset of meiotic recombination events that are insensitive to crossover interference .
DNA transformation protein TfoX-like (TfoX-like)
Type: Family

This entry represents TfoX/Sxy-type transcriptional regulators, which may play a key role in the development of genetic competence by regulating the expression of late competence-specific genes .

TfoX from Haemophilus influenzae positively regulates genes required for DNA transformation (late competence-specific genes) in association with CRP .

Protein Sxy from Escherichia coli, also known as TfoX induces low levels of natural DNA uptake by inducing transcription of the competence genes (the CRP-S regulon) required for DNA transformation .
Tumor necrosis factor receptor superfamily member 19/27/EDAR (TNR19/27/EDAR)
Type: Family

This entry represents a group of tumour necrosis factor receptors predominantly found in chordates, including human tumor necrosis factor receptor superfamily member 19/27/EDAR (TNR19/27/EDAR), which can mediate activation of JNK and NF-kappa-B and may promote caspase-independent cell death.

TNR19, also known as TAJ and TROY , activates the RhoA and inhibits neurite outgrowth . It is involved in the development of the epidermis in human and mice .

TNR27 is a receptor for EDA isoform A2, but not for EDA isoform A1 . On the contrary, EDAR is a receptor for EDA isoform A1, but not for EDA isoform A2. Mutations in the gene encoding for this protein are associated with certain forms of of ectodermal dysplasia .

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain - a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .
Histone-lysine N-methyltransferase NSD3, fifth PHD finger (PHD5_NSD3)
Type: Domain

This entry represents the fifth PHD finger found in NSD3 and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 3 (NSD3), also called histone-lysine N-methyltransferase NSD3 or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1L1) , is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines . Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukaemia . NSD3 contributes to tumourigenesis by interacting with bromodomain-containing protein 4 (BRD4), the bromodomain and extraterminal (BET) protein, which is a potential therapeutic target in acute myeloid leukaemia . NSD3 contains a SET, two PWWP domains, five plant-homeodomain (PHD) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions .
STAM1, VHS domain (VHS_STAM1)
Type: Domain

This entry represents the VHS domain of STAM1 and similar proteins from vertebrates, which is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM repeats.

Signal transducing adapter molecule 1 (STAM1) is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome . It may also be involved in the regulation of IL2 and GM-CSF mediated signalling, and has been implicated in neural cell survival . STAM1, together with another GAT domain-containing protein Hrs, forms a Hrs/STAM1 core complex that consists of two intertwined GAT domains, each consisting of two helices from one subunit, and one from the other subunit. The two GAT domains are connected by a two-stranded coiled-coil. The Hrs/STAM1 complex, an intertwined GAT heterodimer, is a scaffold for binding of ubiquitinated cargo proteins and coordinating ubiquitination and deubiquitination reactions that regulate sorting . It plays an important role in Dengue virus entry .

STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation . They function in cytokine signalling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases , Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS, ubiquitin interacting (UIM), and SH3 domains .
E3 ubiquitin-protein ligase ORTHRUS 1-5, second RING finger, HC subclass (RING-HC_ORTHRUS_rpt2)
Type: Domain

This entry represents the second RING finger, HC subclass, found in ORTH1-5 from Arabidopsis thaliana and similar sequences from brassicales.

E3 ubiquitin-protein ligase ORTHRUS 1-5 from Arabidopsis thaliana (ORTH1-5) may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing . ORTH1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologues (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTH2 and ORTH5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTH1 and ORTH2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this group of proteins contain two typical C3HC4-type RING-HC fingers .
RNA-dependent RNA polymerase, flavivirus (Flavi_RdRp)
Type: Domain

This entry represents RNA-directed RNA polymerase (RdRp) from flaviviruses . These are arthropod-borne viruses, with distinct groups infecting mosquitoes or ticks. Mammals and birds are the usual primary hosts, in which infections range from asymptomatic to severe or fatal haemorrhagic fever or neurological disease. Important human pathogens include yellow fever virus, dengue virus, Japanese encephalitis virus, West Nile virus and tick-borne encephalitis virus. Other members cause economically important diseases in domestic or wild animals. The viral genome of Flavivirus is a positive strand RNA that encodes a single polyprotein precursor containing three structural proteins found in the mature virion (C, prM, and E) and seven "non-structural" proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), which is processed into mature proteins by the host signal peptidase and NS3 serine protease, which requires NS2B as a cofactor .
Sex comb on midleg-like, SAM domain (SAM_Scm-like)
Type: Domain

This entry represents the SAM (sterile alpha motif) domain of Polycomb-group proteins from the Scm (Sex comb on midleg) subfamily, including Scm from Drosophila melanogaster and human SCML1/2/4. It is a protein-protein interaction domain. Members of this group are found mainly in vertebrates and arthropods.

The Scm (Sex comb on midleg) subfamily of Polycomb group includes transcriptional repressors associated with PRC1 complex. Originally the Scm protein was described in Drosophila as a regulator required for proper spatial expression of homeotic genes . It plays a major role during early embryogenesis. SAM domains of Scm proteins can interact with each other, forming homooligomers, as well as with SAM domains of other proteins, in particular with SAM domains of Ph (polyhomeotic) proteins, forming heterooligomers. Homooligomers are similar to the ones formed by SAM Pointed domains of the TEL proteins. Such SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Mammalian Scmh1 protein is known be indispensable member of PRC1 complex; it plays a regulatory role for the complex during meiotic prophase of male sperm cells, and is particularly involved in regulation of chromatin modification at the XY chromatin domain of the pachytene spermatocytes .
Peroxisomal biogenesis factor 6, second ATPase domain (RecA-like_PEX6_r2)
Type: Domain

This entry represents the second of two ATPase domains of Peroxisomal biogenesis factor 6 (PEX6) and similar proteins from eukaryotes.

PEX6 and PEX1 form a heterohexameric Type-2 AAA-ATPase complex and are essential for peroxisome biogenesis as they are required for the import of folded proteins into the peroxisomal matrix. This group of proteins belongs to the RecA-like NTPase family .