SII-SWORD/CoKE huggingface dataset:
SH3PXD2, PX domain (SH3PXD2_PX)
Type: Domain

This entry represents the PX domain of SH3PXD2A and SH3PXD2B. The PX domain is involved in targeting of proteins to phosphoinositide-enriched membranes, and may also be involved in protein-protein interaction .

SH3PXD2A, also known as Fish or Tks5, is a scaffold protein with five SH3 domains and one PX domain. It is required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells . SH3PXD2A binding partners include ADAM-family metalloproteases and Nck adaptor proteins .

SH3 and PX domain-containing protein 2B (SH3PXD2B, also known as Fad49 or Tks4) is an adaptor protein required for functional podosome formation . It binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides . It regulates epidermal growth factor-dependent cell migration and has been linked to cancer . Mutations in the SH3PXD2B gene cause Frank-ter Haar syndrome, a rare disease characterised by abnormalities that affect bone, heart, and eye development . It contains an N-terminal Phox homology (PX) domain and four SH3 domains.
Neuralized (Neuralized)
Type: Family

Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase. In Drosophila, Neur is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system . Notch signaling, which is crucial to metazoan development, requires endocytosis of Notch ligands. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis . In mammals there are two homologues of Neur, Neur1 (NEURL1) and Neur2 (NEURL1B), that can interact with Notch ligands Delta-like1 and Jagged1 . Neuralized homologues in flies and mammals have two NHR domains. Neuralized-like protein 2 (NEURL2), 3 (NEURL3) and 4 (NEURL4) are also included in this family. NEURL4 is a HERC2-interacting protein with six neuralized domains, whereas NEURL2 and NEURL3 have one neuralized domain only.
Apoptotic Protease-Activating Factor 1, CARD domain (APAF1_CARD_dom)
Type: Domain

Apoptotic protease activating factor-1 (Apaf-1) is a component protein of the apoptosome . During apoptosis, cytochrome c is released from mitochondria to the cytosol and binds Apaf-1. Binding of cytochrome c to Apaf-1 allows the recruitment and activation of caspase-9 within the apoptosome .

This entry represents the CARD domain of Apaf-1. CARDs are death domains (DDs) found associated with caspases. They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms .
Brd8, Bromo domain (Brd8_Bromo_dom)
Type: Domain

In mammals, brd8 (bromodomain containing 8) interacts with the thyroid hormone receptor in a ligand-dependent fashion and enhances thyroid hormone-dependent activation from thyroid response elements. Brd8 is thought to be a nuclear receptor coactivator . Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine .
ZMYND8, Bromo domain (ZMYND8_Bromo_dom)
Type: Domain

MYND-type zinc finger-containing chromatin reader ZMYND8 (also called human protein kinase C-binding protein (PRKCBP1) and RACK7) was identified as a potential tumour suppressor gene. It shares domain architecture with BS69/ZMYND11; both have been implicated in the regulation of cellular proliferation . ZMYND8 is a chromatin reader that recognises dual histone modifications . It acts as a transcriptional corepressor for KDM5D and EZH2 . ZMYND8 recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination . ZMYND8 also plays a role in neuronal development . This protein suppresses breast cancer, and prostate cancer cell invasion and metastasis. It has been proposed as a suitable epigenetic tool that can re-sensitize the chemo-refractory breast carcinoma .

This entry represents the bromodomain of ZMYND8. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine .
Protein polybromo-1, Bromodomain 5 (PBRM1_BD5)
Type: Domain

The human protein polybromo-1 (PBRM1, also known as BAF180) is part of a SWI/SNF chromatin-remodeling complex . It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine .
IRAK4, Death domain (IRAK4_Death)
Type: Domain

IRAK4 is a serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens . It is required for the efficient recruitment of IRAK1 to the interleukin-1 (IL-1) receptor complex following IL-1 engagement, triggering intracellular signalling cascades leading to transcriptional up-regulation and mRNA stabilisation . IRAK4 phosphorylates IRAK1. Pellino-2 may be a substrate for both IRAK1 and IRAK4 .

This entry represents the Death domain of IRAK4.

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Ankyrin-3, death domain (Ank3_Death)
Type: Domain

ANK-3, also called anykyrin-G (for general or giant), is found in neurons and at least one splice variant has been shown to be essential for propagation of action potentials as a binding partner to neurofascin and voltage-gated sodium channels . It is required for maintaining axo-dendritic polarity , and may be a genetic risk factor associated with bipolar disorder .

DDs (Death domains) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
RepB, N-terminal (RepB_N)
Type: Domain

RepB, found on plasmids and secondary chromosomes, works along with repA in directing plasmid segregation, and has been shown in Rhizobium etli to require the parS centromere-like sequence for full transcriptional repression of the repABC operon, inducing plasmid incompatibility . RepA is a Walker-type ATPase that complexes with RepB to form DNA-protein complexes in the presence of ATP/ADP. RepC is an initiator protein for the plasmid . repA and repB are homologous to the parA and parB genes of the parABS partitioning system found on primary chromosomes .
BICC1, SAM domain (BICC1_SAM_dom)
Type: Domain

Bicaudal-C (BICC, BICC1 in vertebrates) is an RNA-binding protein with translational repression function . It is involved in the regulation of embryonic differentiation and plays a role in the regulation of Dvl (Dishevelled) signaling, particularly in the correct cilia orientation and nodal flow generation . In Drosophila, disruption of BICC can disturb the normal migration direction of the anterior follicle cell of oocytes . In mammals, mutations in this gene are associated with polycystic kidney disease and it was suggested that the BICC1 protein can indirectly interact with ANKS6 protein (ANKS6 is also associated with polycystic kidney disease) through some protein and RNA intermediates .

BICC1 contains N-terminal K homology RNA-binding vigilin-like repeats and a C-terminal SAM domain. This entry represents the SAM (sterile alpha motif) domain, which is a protein-protein interaction domain .
Class XI myosin, cargo binding domain (MyosinXI_CBD)
Type: Domain

Class XI myosins are a plant specific group, homologous to class V myosins . They have roles in cell expansion, organelle motility and F-actin organization . The C-terminal domain of Arabidopsis myosin XI has been shown to be homologous to the cargo-binding domain (CBD) of yeast myosin V myo2p, which targets myosin to vacuole- and mitochondria, as well as secretory vesicle .
HERC2, APC10 domain (HERC2_APC10)
Type: Domain

This entry represents the APC10/DOC1 domain of HERC2 (HECT domain and RLD2). This domain is similar to the anaphase-promoting complex subunit APC10 and the DOC1 domain present in E3 ubiquitin ligases which mediate substrate ubiquitination (or ubiquitylation) . HERC2 may be involved in protein trafficking and degradation pathways. Mutations in HERC2 lead to neuromuscular secretory vesicle and sperm acrosome defects, other developmental abnormalities, and juvenile lethality of jdf2 mice . It has been shown that the HERC2-RNF8 protein complex coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes .
Afadin, cargo binding domain (CBD_Afadin)
Type: Domain

Afadin is an actin filament (F-actin) and Rap1 small G protein-binding protein, found in cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. It interacts with cell adhesion molecules and signaling molecules and plays a role in the formation of cell junctions, cell polarization, migration, survival, proliferation, and differentiation . Afadin is a multi domain protein, that contains beside a myosin5-like CBD, two Ras-associated domains, a forkhead-associated domain, a PDZ domain, three proline-rich domains, and an F-actin-binding domain .

The myosin5-like cargo binding domain (CBD) includes two helical lobules and C-terminal extension. The second lobule is also known as dilute domain .
TDRD7, third LOTUS domain (TDRD7_LOTUS_3)
Type: Domain

This entry represents the third LOTUS domain of TDRD7 and similar proteins from vertebrates.

TDRD7 (also called PCTAIRE2-binding protein, or Tudor repeat associator with PCTAIRE-2 (Trap)) belongs to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. It is a component of specific cytoplasmic RNA granules involved in post-transcriptional regulation of specific genes; it probably acts by binding to specific mRNAs and regulating their translation. It is required for lens transparency during lens development, by regulating translation of genes such as CRYBB3 and HSPB1 in the developing lens . It is also essential for dynamic ribonucleoprotein (RNP) remodelling of chromatoid bodies during spermatogenesis. In mice, TDRD7 together with TDRD1/MTR-1, TDRD5 and TDRD6 forms a ribonucleoprotein complex in the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs) involved in RNA processing for spermatogenesis . TDRD7 is functionally essential for the differentiation of germ cells .

TDRD7 contains three N-terminal LOTUS domains and three Tudor domains at the C-terminal. The LOTUS domain adopts the winged helix-turn-helix fold that may bind RNA .
TDRD5, second LOTUS domain (TDRD5_LOTUS_2)
Type: Domain

TDRD5 belongs to the evolutionary conserved Tudor domain-containing protein (TDRD) family involved in germ cell development. In mice, TDRD5 is a component of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis .

TDRD5 contains three N-terminal LOTUS domains and a C-terminal Tudor domain. This entry represents the second LOTUS domain of TDRD5. The LOTUS domain adopts the winged helix-turn-helix fold and may bind RNA .
Rasip1/Radil, cargo-binding domain (CBD_Rasip1/Radil)
Type: Domain

Ras-interacting protein 1 (Rasip1 or RAIN) is an effector of the small G protein Rap1 and plays an important role in endothelial junction stabilization . It plays an essential role in vascular development .

Radil is also a Rap1 effector. It regulates beta1 and beta2-integrin activation and controls neutrophil chemotaxis . Radil, like Rasip1, is a multi domain protein, that contains a myosin5-like cargo-binding domain (CBD).
SGIP1, mu-homology domain (SGIP1_MHD)
Type: Domain

SGIP1 is a member of the muniscin family. It is an endophilin-interacting protein that plays an obligatory role in the regulation of energy homeostasis , and is also involved in clathrin-mediated endocytosis by interacting with phospholipids and eps15 .

The muniscins are a family of endocytic adaptors that is conserved from yeast to humans. Their C-terminal domain is structurally similar to mu homology domains (MHDs), and is the region of the muniscin proteins involved in the interactions with the endocytic adaptor-scaffold proteins Ede1-eps15 .
Dilute domain-containing protein, fungi, CBD domain (Myo5p-like_CBD_DIL)
Type: Domain

This group of dilute domain-containing proteins from fungi contain a domain homologous to the cargo-binding domain of class V myosins. Their function is unknown.

The myosinV-like CBD includes two helical lobules and C-terminal extension. The second lobule is also known as dilute domain .
Myosin 5a, cargo-binding domain (Myo5a_CBD)
Type: Domain

Class V myosins are well studied unconventional myosins, represented by three paralogs (Myo5a,b,c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA. They interact with several adaptor proteins, in case of Myo5a-CBD, melanophilin (MLPH), Rab interacting lysosomal protein-like 2 (RILPL2), and granuphilin . Mutations in human Myo5a (many of which map to the cargo binding domain) lead to Griscelli syndrome, a severe neurological disease .
Myosin 5b, cargo-binding domain (Myo5b_CBD)
Type: Domain

Class V myosins are well studied unconventional myosins, represented by three paralogues (Myo5a, b, c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA . They interact with several adaptor proteins, in case of Myo5b-CBD, Rab11-family interacting protein 2 .
Myosin 5c, cargo-binding domain (Myo5c_CBD)
Type: Domain

Class V myosins are well studied unconventional myosins, represented by three paralogues (Myo5a,b,c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA. The Myo5-CBDs directly interact with several adaptor proteins . Myo5b and myo5c are primarily expressed in epithelial cells, and have been implicated as motors involved in recycling endosomes .
TRAPP complex, Trs33 subunit (TRAPPC6/Trs33)
Type: Family

Trs33 (corresponding to human homologues TRAPPC6A and TRAPPC6B) is a subunit of the trafficking protein particle complex (TRAPP). Transport protein particle (TRAPP) complexes are multimeric guanine nucleotide-exchange factors for the GTPase Ypt1. Trs33 is one of the core subunits of TRAPP complexes which play a key role in the regulation of ER-to-Golgi and intra-Golgi transport by tethering the vesicle membrane to the target membrane . In yeast, it is a core component of TRAPP complexes I, II and IV. Complex IV is thought to be involved in autophagy . In mammals, mutations in TRAPPC6a cause mosaic loss of coat pigment .
NDPK7, second NDPk domain (NDPk7B)
Type: Domain

The nm23-H7 nucleoside diphosphate kinase (also known as NDPk7 or NME7) consists of an N-terminal DM10 domain and two functional catalytic NDPk modules, NDPk7A and NDPk7B. The function of the DM10 domain, which also occurs in multiple copies in other proteins, is unknown. NDPk7 is predominantly expressed in testes, although appreciable amounts are also found in liver, heart, brain, ovary, small intestine and spleen . The nm23-H7 gene is located in or near the hereditary prostrate cancer susceptibility locus. Nm23-H7 may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner .

This entry represents the second NDPk domain (NDPk7B) of NDPk7.
Nucleoside diphosphate kinase 6 (NDPk6)
Type: Family

Nucleoside diphosphate kinase 6 (NDPk6, also known as NM23-H6) is expressed mainly in mitochondria, but also found at a lower level in most tissues . NDPk6 has all nine residues considered crucial for enzyme structure and activity, and has been found to have NDP kinase activity . It may play a role in cell growth and cell cycle progression. The nm23-H6 gene locus has been implicated in a variety of malignant tumours .
CTP-dependent diacylglycerol kinase 1-like (Dgk1-like)
Type: Family

Dgk1 is a diacylglycerol kinase that catalyzes the formation of phosphatidate from diacylglycerol. It uses CTP, instead of ATP, to generate phosphatidate. It counteracts the activity of phosphatidate phosphatase Pah1 at the nuclear envelope by controlling phosphatidate levels . Its activity can be regulated by casein kinase II phosphorylation .

This entry also includes uncharacterised bacterial and archaeal proteins.
Maternal protein exuperantia (Exu)
Type: Family

This entry represents a group of insect proteins that play a role in the establishment of the polarity of the oocyte. Proteins in this entry include exuperantia (Exu), which is a an RNA-binding pseudonuclease associated with bicoid mRNA and required for its localization. It interacts with its target RNA as a homodimer .
Alpha-2-macroglobulin RAP, domain 3 (RAP_D3)
Type: Domain

This entry is the C-terminal domain (D3) of receptor-associated protein, RAP, also known as alpha-2-macroglobulin receptor-associated protein. RAP is a three domain ER (endoplasmic reticulum)-resident protein that is a chaperone for the LRP (low-density lipoprotein receptor-related protein). RAP is an antagonist and a specialized chaperone that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands . D3 is required for folding and trafficking of low-density lipoprotein receptor-related protein (LRP) . In the mildly acidic pH of the Golgi, unfolding of RAP-D3 helical bundle facilitates dissociation of RAP from the LDL receptor type A (LA) repeats of LDLR family proteins . Also, RAP has 3 regions that interact weakly with heparin, two regions located in D3 and one in RAP domain 2 (D2) . The double module of complement type repeats, CR56, of LRP binds many ligands including alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease .
Alpha-2-macroglobulin RAP, domain 2 (RAP_D2)
Type: Domain

This entry is the domain 2 (D2) of receptor-associated protein, RAP, also known as alpha-2-macroglobulin receptor-associated protein. RAP is a three domain ER (endoplasmic reticulum)-resident protein that is a chaperone for the LRP (low-density lipoprotein receptor-related protein). RAP is an antagonist and a specialized chaperone that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands .

D2, along with RAP domain 1 (D1), is essential for blocking low-density lipoprotein receptor-related protein (LRP) from binding of certain ligands, such as alpha2-macroglobulin; D1 and D2 each bind LRP weakly but the tandem D1D2 binds much more tightly to the second and the fourth ligand-binding clusters present on LRP, suggesting the avidity effects arising from amino acid residues contributed from each domain . Also, RAP has regions that interact weakly with heparin, one located in D2 and two located in D3. The double module of complement type repeats, CR56, of LRP binds many ligands including alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease .
Alpha-2-macroglobulin receptor-associated protein (A2-macroglobuin_RAP)
Type: Family

The alpha-2-macroglobulin receptor-associated protein (RAP) is a intracellular glycoprotein that binds to the alpha-2-macroglobulin receptor (a2MR), also known as low-density lipoprotein receptor-related protein (LRP), and other members of the low density lipoprotein receptor family. The protein inhibits binding of all currently known ligands of these receptors .
Virus X resistance protein-like, coiled-coil domain (RX-like_CC)
Type: Domain

The potato virus X resistance protein (RX) confers resistance against potato virus X. It is a member of a family of resistance proteins with a domain architecture that includes an N-terminal coiled-coil domain (modeled here), a nucleotide-binding domain, and leucine-rich repeats (CC-NB-LRR). These intracellular resistance proteins recognize pathogen effector proteins and will subsequently trigger a response that may be as severe as localized cell death . The N-terminal coiled-coil domain of RX has been shown to interact with RanGAP2, which is a necessary co-factor in the resistance response .
Transcription factor COE, IPT domain (COE_IPT)
Type: Domain

This entry represents the IPT domain of the COE family members (Col/Olf-1/EBF), which are non-basic, helix-loop-helix (HLH)-containing transcription factors. COE family proteins are all transcription factors and play an important role in variety of developmental processes. Mouse EBF is involved in the regulation of the early stages of B-cell differentiation, Drosophila collier is a regulator of the head patterning, and a related protein in Xenopus is involved in primary neurogenesis. All COE family members have a well conserved DNA binding domain that contains an atypical Zn finger motif. The function of the IPT domain is unknown .
RBP-Jkappa, IPT domain (RBP-Jkappa_IPT)
Type: Domain

This entry represents the IPT domain of the recombination signal Jkappa binding protein (RBP-Jkappa, also known as RBP-J). RBP-J kappa, was initially considered to be involved in V(D)J recombination because of its DNA binding specificity and structural similarity to site-specific recombinases known as the integrase family. Further studies indicated that RBP-J kappa functions as a repressor of transcription, via destabilization of the general transcription factor IID and recruitment of histone deacetylase complexes. Later, its was found to be a transcriptional regulator downstream of Notch receptors .

IPT/TIG (immunoglobulin, plexin, transcription factor-like/transcription factor immunoglobulin) domains adopt an immunoglobulin-like fold and have been found in proteins involved in transcriptional regulation and signal transduction, and can also participate in protein-protein interactions .
Jag, KH domain (Jag_KH)
Type: Domain

This entry represents the KH domain found in proteins homologous to the Bacillus subtilis RNA-binding protein KhpB, also known as Jag and EloR, which is associated with SpoIIIJ and is necessary for the third stage of sporulation. It forms a complex with KhpA which binds to cellular RNA and controls its expression. It also plays a role in peptidoglycan (PG) homeostasis and cell length regulation . The KH domain is a β-α-α-β-β unit that folds into an α/β structure with a three stranded β-sheet interrupted by two contiguous helices. In general, the KH binds single-stranded RNA or DNA. It is found in a wide variety of proteins including ribosomal proteins, transcription factors and post-transcriptional modifiers of mRNA .