SII-SWORD/CoKE huggingface dataset:
Lysine-specific demethylase 4A, second Tudor domain (Tudor_KDM4A_rpt2)
Type: Domain

This is the second Tudor domain of KDM4A, which is a methyl-lysine reader domain .

Lysine-specific demethylase 4A (KDM4A), also known as JMJD2A or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyses the demethylation of di- and trimethylated histone H3, specifically at 'Lys-9' and 'Lys-36' positions (H3K9 and H3K36) . It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor corepressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER), and plays an essential role in growth of both ER-positive and -negative breast tumours . It is also involved in prostate, colon, and lung cancer progression . JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains .
Lysine-specific demethylase 4A, extended PHD finger (JMJD2A_ePHD)
Type: Domain

This entry represents the extended PHD (ePHD) finger of KDM4A.

Lysine-specific demethylase 4A (KDM4A), also known as JMJD2A or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyses the demethylation of di- and trimethylated histone H3, specifically at 'Lys-9' and 'Lys-36' positions (H3K9 and H3K36) . It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor corepressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER), and plays an essential role in growth of both ER-positive and -negative breast tumours . It is also involved in prostate, colon, and lung cancer progression . JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains .
Lysine-specific demethylase 4B, first Tudor domain (Tudor_KDM4B_rpt1)
Type: Domain

This entry represents the first Tudor domain of KDM4B, which is a methyl-lysine reader domain .

Lysine-specific demethylase 4B, also known as JMJD2B, or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the tri-methyl group from H3K9 in pericentric heterochromatin and reduces H3K36 methylation in mammalian cells . It plays an essential role in the growth regulation of cancer cells by modulating the G1-S transition and promotes cell-cycle progression through the regulation of cyclin-dependent kinase 6 (CDK6) . It interacts with heat shock protein 90 (Hsp90) and its stability can be regulated by Hsp90 . KDM4B also functions as a direct transcriptional target of p53, which induces its expression through promoter binding . Moreover, KDM4B expression can be controlled by hypoxia-inducible factor 1alpha (HIF1alpha) in colorectal cancer and estrogen receptor alpha (ERalpha) in breast cancer . It is also involved in bladder, lung, and gastric cancer. Members of this entry contains jmjN and jmjC domains in the N-terminal region, followed by a canonical plant homeodomain (PHD) domain, a noncanonical extended PHD domain, and tandem Tudor domains.
Diacylglycerol kinase zeta, second protein kinase C conserved region 1 (C1_DGKzeta_rpt2)
Type: Domain

This entry represents the second protein kinase C conserved region 1 (C1 domain) of DAG kinase zeta and similar proteins from vertebrates. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn2-binding sites.

Diacylglycerol (DAG) kinase (

) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase zeta, also called diglyceride kinase zeta (DGK-zeta), displays a strong preference for 1,2-diacylglycerols over 1,3-diacylglycerols, but lacks substrate specificity among molecular species of long chain diacylglycerols. It is classified as a type IV DAG kinase (DGK), containing myristoylated alanine-rich protein kinase C substrate (MARCKS), PDZ-binding, and ankyrin domains, in addition to C1 and catalytic domains that are present in all DGKs. The MARCKS domain regulates the nuclear localisations of type IV DGKs while the PDZ-binding and ankyrin domains regulate interactions with several proteins. DAG kinase zeta contains two copies of the C1 domain .
Diacylglycerol kinase zeta, first protein kinase C conserved region 1 (C1_DGKzeta_rpt1)
Type: Domain

This entry represents the first protein kinase C conserved region 1 (C1 domain) of DAG kinase zeta and similar proteins from vertebrates. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn2-binding sites.

Diacylglycerol (DAG) kinase (

) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase zeta, also called diglyceride kinase zeta (DGK-zeta), displays a strong preference for 1,2-diacylglycerols over 1,3-diacylglycerols, but lacks substrate specificity among molecular species of long chain diacylglycerols. It is classified as a type IV DAG kinase (DGK), containing myristoylated alanine-rich protein kinase C substrate (MARCKS), PDZ-binding, and ankyrin domains, in addition to C1 and catalytic domains that are present in all DGKs. The MARCKS domain regulates the nuclear localisations of type IV DGKs while the PDZ-binding and ankyrin domains regulate interactions with several proteins. DAG kinase zeta contains two copies of the C1 domain .
Diacylglycerol kinase iota, first protein kinase C conserved region 1 (C1_DGKiota_rpt1)
Type: Domain

This entry represents the first protein kinase C conserved region 1 (C1 domain) of DAG kinase iota and similar proteins from vertebrates. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn2-binding sites.

Diacylglycerol (DAG) kinase (

) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase iota, also called diglyceride kinase iota (DGK-iota), or DGKI, is a homologue of Drosophila DGK2, RdgA. It may have important cellular functions in the retina and brain. It is classified as a type IV DAG kinase (DGK), containing myristoylated alanine-rich protein kinase C substrate (MARCKS), PDZ-binding, and ankyrin domains, in addition to C1 and catalytic domains that are present in all DGKs. The MARCKS domain regulates the nuclear localizations of type IV DGKs while the PDZ-binding and ankyrin domains regulate interactions with several proteins. DAG kinase iota contains two copies of the C1 domain .
Diacylglycerol kinase iota, second protein kinase C conserved region 1 (C1_DGKiota_rpt2)
Type: Domain

This entry represents the second protein kinase C conserved region 1 (C1 domain) of DAG kinase iota and similar proteins from vertebrates. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn2-binding sites.

Diacylglycerol (DAG) kinase (

) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase iota, also called diglyceride kinase iota (DGK-iota), or DGKI, is a homologue of Drosophila DGK2, RdgA. It may have important cellular functions in the retina and brain. It is classified as a type IV DAG kinase (DGK), containing myristoylated alanine-rich protein kinase C substrate (MARCKS), PDZ-binding, and ankyrin domains, in addition to C1 and catalytic domains that are present in all DGKs. The MARCKS domain regulates the nuclear localizations of type IV DGKs while the PDZ-binding and ankyrin domains regulate interactions with several proteins. DAG kinase iota contains two copies of the C1 domain .
U2-associated protein SR140, cwf21 domain (SR140_cwf21)
Type: Domain

This entry represents the cwf21 domain of SR140 and similar animal proteins. This domain is involved in mRNA splicing. It binds directly to the spliceosomal protein Prp8.

SR140, also called U2 snRNP-associated SURP motif-containing protein, U2SURP, or 140 kDa Ser/Arg-rich domain protein, is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as a 17S U2 snRNP-associated protein, the molecular and physiological function of SR140 remains unclear .
Serine/arginine repetitive matrix protein 3, cwf21 domain (SRRM3_cwf21)
Type: Domain

This entry represents the cwf21 domain of SRRM3 and similar proteins mainly found in vertebrates. This domain is involved in mRNA splicing. It binds directly to the spliceosomal protein Prp8.

Serine/arginine repetitive matrix protein 3 (SRRM3) may play a role in regulating breast cancer cell invasiveness. It may also be involved in RYBP-mediated breast cancer progression. SRRM3 contains a cwf21 domain at the N-terminal .
Serine/arginine repetitive matrix protein 2, cwf21 domain (SRRM2_cwf21)
Type: Domain

This entry represents the cwf21 domain of SRRM2 and similar proteins from vertebrates. This domain is involved in mRNA splicing. It binds directly to the spliceosomal protein Prp8.

Serine/arginine repetitive matrix protein 2 (SRRM2) is also called 300 kDa nuclear matrix antigen, serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa, SR-related nuclear matrix protein of 300 kDa, or Tax-responsive enhancer element-binding protein 803 (TaxREB803). It is required for pre-mRNA splicing as component of the spliceosome. It contains a cwf21 domain at the N-terminal .
Protein RRC1-like, cwf21 domain (RRC1-like_cwf21)
Type: Domain

This entry represents the cwf21 domain of protein RRC1 from Arabidopsis thaliana and similar plant proteins. This domain is involved in mRNA splicing. It binds directly to the spliceosomal protein Prp8.

RRC1, also called reduced red-light responses in cry1cry2 background 1, is a SR-like splicing factor required for phytochrome B (phyB) signal transduction and involved in phyB-dependent alternative splicing. This group of sequences also includes protein RRC1-like, which may also function as a SR-like splicing factor. SR family splicing factors are characterised by the presence of a domain rich in arginine and serine dipeptides, called the RS domain .
STAM1, non-canonical GAT domain (GAT_STAM1)
Type: Domain

This entry represents the non-canonical GAT domain of STAM1 and similar proteins from vertebrates.

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 .
STAM2, VHS domain (VHS_STAM2)
Type: Domain

This entry represents the VHS domain of STAM2 and similar proteins from vertebrates. This domain is involved in cytokine-mediated intracellular signal transduction and has a superhelical structure similar to the structure of ARM repeats .

Signal transducing adapter molecule 2 (STAM2), a subunit of the ESCRT-0 complex, is an endosomal protein acting as a regulator of receptor signaling and trafficking. It contains an N-terminal VHS domain, UIM (ubiquitin-interacting motif), SH3, coiled-coil (CC), SSM (STAM-specific motif) and C-terminal ITAM (immunoreceptor tyrosine-based activation motif) domains. It may play a regulatory role in the endosomal sorting of ubiquitinated membrane proteins. It is highly expressed in neurons, where it is localized in the nucleus .

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 .
RNA-binding protein FXR1, first type I K homology domain (KH_I_FXR1_rpt1)
Type: Domain

FXR1 contains three K-homology (KH) RNA-binding domains, the first one is represented in this entry, which corresponds to a divergent KH domain that lacks the RNA-binding GXXG motif.

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins . These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs .
RNA-binding protein FXR1, second type I K homology domain (KH_I_FXR1_rpt2)
Type: Domain

FXR1 contains three K-homology (KH) RNA-binding domains, the second one is represented in this entry.

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins . These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs .
RNA-binding protein FXR2, third type I K homology domain (KH_I_FXR1_rpt3)
Type: Domain

FXR2 contains three K-homology (KH) RNA-binding domains, the third one is represented in this entry.

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins . These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs .
Protein LURE 1.1-1.6, defensin-like domain (DEFL_AtLURE1-like)
Type: Domain

This entry represents the defensin-like (DEFL) domain of AtLURE1.1-1.6 and similar sequences found in Arabidopsis. This domain adopts a typical structure characterised by cysteine-stabilized α/β scaffold .

LURE1.1-1.6 from Arabidopsis thaliana are pollen tube attractants guiding pollen tubes to the ovular micropyle . AtLURE1.2 attracts specifically pollen tubes from A. thaliana, but not those from A. lyrata . It triggers endocytosis of MDIS1 in the pollen tube tip .
E3 ubiquitin-protein ligase ORTHRUS 1/2-like, first RING finger, HC subclass (RING-HC_ORTHRUS_rpt1)
Type: Domain

This entry represents the first RING finger, HC subclass, found in ORTH1/2 from Arabidopsis thaliana and similar sequences from plants.

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 .
Adenylate kinase 7, dimerization/docking domain (DD_AK7)
Type: Domain

This entry represents the dimerization/docking (D/D) domain found at the C-terminal of human AK7 and similar proteins mainly found in animals. This domain shows high sequence similarity to the dimerization/docking (D/D) domain of protein DPY-30/SDC1.

Adenylate kinase (AK7,

/

), also called ATP-AMP transphosphorylase 7, is a nucleoside monophosphate (NMP) kinase that catalyses the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. It has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. It also displays broad nucleoside diphosphate kinase activity. AK7 is involved in maintaining ciliary structure and function .
Enolase 4, dimerization/docking domain (DD_ENO4)
Type: Domain

This entry represents the dimerization/docking (D/D) domain found at the N-terminal of human ENO4 and similar proteins predominantly found in vertebrates. This domain shows high sequence similarity to the dimerization/docking (D/D) domain of regulatory subunit of cAMP-dependent protein kinase (PKA) and protein DPY-30/SDC1.

Enolase (

), also known as phosphopyruvate hydratase, is a metalloenzyme responsible for the catalysing the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), the ninth and penultimate step of glycolysis. ENO4, also called 2-phospho-D-glycerate hydro-lyase, seems to be required for sperm motility and function .
Ciliogenesis-associated TTC17-interacting protein, dimerization/docking domain (DD_CATIP)
Type: Domain

This entry represents the dimerization/docking (D/D) domain found at the C-terminal of human CATIP and similar proteins predominantly found in animals. This domain shows high sequence similarity to the dimerization/docking (D/D) domain of regulatory subunit of cAMP-dependent protein kinase (PKA).

Ciliogenesis-associated TTC17-interacting protein (CATIP), also called C2orf62, plays a role in primary ciliogenesis by modulating actin polymerization. It interacts with TTC17. Mutations in CATIP contribute to oligoteratoasthenozoospermia through its involvement in actin polymerization and the actin cytoskeleton .
Tubulin polyglutamylase complex subunit 1, dimerization/docking domain (DD_TPGS1)
Type: Domain

This entry represents the dimerization/docking (D/D) domain found at the N-terminal of human TPGS1 and similar proteins predominantly found in vertebrates. This domain shows high sequence similarity to the dimerization/docking (D/D) domain of regulatory subunit of cAMP-dependent protein kinase (PKA).

Tubulin polyglutamylase complex subunit 1 (TPGS1) is part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1. It is required for the development of the spermatid flagellum .
E3 ubiquitin-protein ligase UBR5, UBR-box (UBR-box_UBR5)
Type: Domain

This entry represents the UBR-box of UBR5 and similar animal proteins.

E3 ubiquitin-protein ligase UBR5 (also known as E3 ligase identified by differential display, EDD), the ER ubiquitin ligase from the HECT ligases, acts as a key regulator of the ubiquitin proteasome system in both cancer and developmental biology. It is frequently overexpressed in breast and ovarian cancer. It is required for Wnt signal responses in Drosophila and human cell lines downstream of activated Armadillo/beta-catenin . It also plays a key role in ciliogenesis by regulating centriolar satellite stability and primary cilia . UBR5 contains an N-terminal ubiquitin-associated (UBA) domain which binds ubiquitin, a zinc-finger-like domain termed the ubiquitin-recognin (UBR) box, a MLLE (mademoiselle) domain, and a C-terminal catalytic HECT domain .
F-box only protein 11, UBR-box (FBXO11_UBR-box)
Type: Domain

This entry represents the UBR-box of UBR11, its homologue from C.elegans dre-1 and similar proteins from animals.

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 .