SII-SWORD/CoKE huggingface dataset:
RNA-dependent RNA polymerase, bromovirus (Bromoviridae_RdRp)
Type: Domain

This entry represents RNA-directed RNA polymerase 2a from RNA viruses belonging to the family Bromoviridae. The Bromoviridae family of plant viruses contains tri-segmented, (+)ssRNA viruses with a total genome size of about 8 kb . Bromoviridae virions are variable in morphology (spherical or bacilliform) and are transmitted mechanically, in/on the pollen and non-persistently by insect vectors. Members of the family cause major disease epidemics in fruit, vegetable and fodder crops such as tomato, cucurbits, bananas, and alfalfa

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]. The RdRp domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. This domain contains conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in its fidelity in processes of correct incorporation and reorganization of nucleotides .
RNA-dependent RNA polymerase, virgavirus (Virgaviridae_RdRp)
Type: Domain

This entry represents the RdRp of RNA viruses belonging to the family Virgaviridae, order Martellivirales. The Virgaviridae is a family of plant viruses with rod-shaped virions, a (+)ssRNA genome with a 3'-terminal tRNA-like structure and a replication protein similar to those of the alpha-like supergroup . This domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in the fidelity of processes such as correct incorporation and reorganization of nucleotides .
RNA-dependent RNA polymerase, togavirus (Togaviridae_RdRp)
Type: Domain

This entry represents the RNA-directed RNA polymerase of RNA viruses belonging to the family Togaviridae, which is cleaved from polyprotein P1234. Togaviridae is a family of small, enveloped viruses with (+)ssRNA genomes of 10-12 kb, and contains a single genus, Alphavirus . Alphavirus includes a large number of species that are mostly mosquito-borne and pathogenic in their vertebrate hosts. Many are important human and veterinary pathogens (e.g., chikungunya virus, eastern equine encephalitis virus). The genus Alphavirus mainly consists of mosquito-borne viruses although other hematophagous insects, including ticks, lice, and cliff swallow bugs, have been implicated in transmission . Vertebrate hosts include humans, non-human primates, equids, birds, amphibians, reptiles, rodents, and pigs. There are two aquatic alphaviruses, southern elephant seal virus and salmon pancreas disease virus, infecting sea mammals and fish respectively . Interestingly, Eilat virus (EILV) has been shown to only infect insect cells and is incapable of replicating in vertebrate cells. This domain displays a right hand with three functional subdomains, called fingers, palm, and thumb. All RdRps contain conserved polymerase motifs (A-G), located in the palm (A-E motifs) and finger (F-G) subdomains. All these motifs have been implicated in the fidelity of processes such as correct incorporation and reorganization of nucleotides .
Coatomer subunit alpha, WD Associated Region (Coatomer_alpha_WD-assoc_reg)
Type: Domain

This entry represents the WD-associated region of coatomer subunit alpha which consists of a β-propeller and an α-solenoid. .

This group represents coatomer subunit alpha, a component of the coatomer, which is a cytosolic protein complex involved in biosynthetic protein transport from the endoplasmic reticulum in eukaryotic cells. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunit. It is a heptameric complex that can polymerize into a cage to deform the membrane into a bud. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.

Structural studies show the homo-oligomerization of this protein plays a key role in the stability of the coat complex . It is composed of β-propellers and extended α-solenoids .

In humans, defects in its expression are related to primary immunodeficiencies that lead to immune dysregulation, arthritis and interstitial lung disease . This protein has also been related to Alzheimer's disease .
Survival motor neuron protein, C-terminal oligomerization domain (SMN_C)
Type: Domain

This entry represents the C-terminal oligomerization domain of SMN family proteins. This domain is also called the YG-box.

The survival motor neuron (SMN) protein family includes metazoan SMN and fungal SMN-like protein 1 (SMN1). SMN forms the oligomeric core of a multiprotein complex, called the SMN complex, that functions in the assembly and biogenesis of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. It is expressed in all tissues of metazoan organisms, but is particularly expressed at high levels in motor neurons. Schizosaccharomyces pombe SMN1 is essential for viability and has been shown to interact with human SMN and Sm proteins. Loss of function mutations in the SMN gene of humans cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. While most eukaryotes have a single copy of the SMN gene, humans have two; the telomeric SMN1 gene is deleted or mutated in SMA patients, whereas the centromeric SMN2 gene is unaffected and can be present in multiple copies. SMN has three highly conserved domains: a short N-terminal region that is responsible for binding with high affinity to Gemin2; a central Tudor domain that recognizes symmetric dimethylarginine (sDMA) modifications in arginine/glycine rich regions of a number of proteins involved in RNA processing, including the Sm proteins; and a C-terminal domain .
Protein kinase C zeta type, conserved region 1 (C1_aPKC_zeta)
Type: Domain

This entry represents the conserved domain 1 (C1 domain) found in aPKC isoform zeta. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. Ιt contains two separate Zn(2)-binding sites.

Protein kinases C (PKCs) are classified into three groups, classical, atypical (aPKCs), and novel, depending on their mode of activation and the structural characteristics of their regulatory domain . aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota . aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation . They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways . PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells . In addition, it affects actin remodelling in muscle cells .
Ski oncogene-like, Dachshund-homology domain (DHD_Ski)
Type: Domain

This entry represents the Dachshund-homology domain (DHD), also known as the N-terminal Ski/Sno/Dac domain, found in Ski oncogene protein from vertebrates and Transforming protein Ski from Avian erythroblastosis virus. This domain adopts a mixed α/β structure containing a helix-turn-helix motif, similar to features found in the forkhead/winged-helix family of DNA binding proteins. It contains a conserved CLPQ motif and can bind co-factors. Its structure suggests that it may also bind DNA .

Ski may play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. It functions as a repressor of transforming growth factor-beta (TGF-beta) signalling . In humans, mutations in this protein are associated with Shprintzen-Goldberg craniosynostosis syndrome (SGS) .
Mucolipin-1, extracytosolic/lumenal domain (ML1_ELD)
Type: Domain

This entry represents the extracytosolic/lumenal domain (ELD), a linker located between the first two transmembrane segments (S1 and S2), of ML1 and similar proteins found in vertebrates. It forms a tight tetramer that is crucial for full-length ML1 assembly and localisation .

Mucolipin-1 (ML1), also called transient receptor potential channel mucolipin 1 (TRPML1), is a Ca2-releasing cation channel that mediates the calcium signaling and homeostasis of lysosomes . Mutations in this protein in humans are associated with mucolipidosis type IV .
Mucolipin-3, extracytosolic/lumenal domain (MCOLN3_ELD)
Type: Domain

This entry represents the extracytosolic/lumenal domain (ELD), a linker located between the first two transmembrane segments (S1 and S2), of ML3 and similar proteins found in vertebrates. It forms a tight tetramer that is crucial for full-length ML3 assembly and localisation .

Mucolipin-3 (ML3), also called TRPML3, acts as Ca2-permeable cation channel with inwardly rectifying activity. It mediates release of Ca2 from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway . It is also involved in regulation of autophagy .
CD276 antigen-like, IgV domain (CD276_IgV)
Type: Domain

This entry represents the immunoglobulin variable (IgV) domain of CD276 antigen, also known as B7-H3, and similar proteins predominantly found in mammals.

CD276 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation . Although CD276 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe CD276 as a T-cell inhibitor that promotes tumour aggressiveness and proliferation . Moreover, this protein is highly overexpressed on a wide range of human solid cancers and promotes tumour growth, metastasis, and drug resistance . Thus, CD276 expression in tumours often correlates with both negative prognosis and poor clinical outcome in cancer patients. This protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail .
DDB1- and CUL4-associated factor 15, C-terminal domain (DCAF15_C)
Type: Domain

This entry represents the C-terminal domain of DCAF15 (DDB1- and CUL4-associated factor 15), the cullin RING ligase substrate receptor/adaptor that forms a complex with CUL4A or CUL4B, as part of the Rbx-Cul4-DDA1-DDB1-DCAF15 E3 ubiquitin ligase that is responsible for the proteasome degradation of certain proteins . Aryl sulfonamide anticancer agents such as indisulam, tasisulam, E7820, and chloroquinoxaline have been shown to recruit the essential mRNA-splicing factor RBM39 to DCAF15. These agents appear to promote binding of DCAF15 to the RNA-recognition motif (RRM) of RBM39, which suggests that derivatives of the aryl-sulfonamides may be used to target other RRM-containing proteins. Cell proliferation is inhibited by these aryl sulfonamides by causing degradation of RBM39, which leads to aberrant processing of pre-mRNA in hundreds of genes, primarily reflected by intron retention and exon skipping, thus collectively referred to as splicing inhibitor sulfonamides, or SPLAMs .
Cyclin-T1, second cyclin box (CYCLIN_CCNT1_rpt2)
Type: Domain

This entry represents the second cyclin box of CCNT1 and similar proteins found in vertebrates. It is a protein binding domain .

Cyclin-T1 (CCNT1) is a host factor essential for HIV-1 replication in CD4 T cells and macrophages . It is a regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the C-terminal domain of the large subunit of RNA polymerase II (RNA Pol II) . CCNT1 contains two cyclin boxes.
Cyclin-T2, first cyclin box (CYCLIN_CCNT2_rpt1)
Type: Domain

This entry represents the first cyclin box of CCNT2 and similar proteins found in vertebrates. It is a protein binding domain.

Cyclin-T2 (CCNT2) is a regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the C-terminal domain of the large subunit of RNA polymerase II (RNAP II) . CCNT2 contains two cyclin boxes.
Cyclin-T2, second cyclin box (CYCLIN_CCNT2_rpt2)
Type: Domain

This entry represents the second cyclin box of CCNT2 and similar proteins found in vertebrates. It is a protein binding domain.

Cyclin-T2 (CCNT2) is a regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the C-terminal domain of the large subunit of RNA polymerase II (RNAP II) . CCNT2 contains two cyclin boxes.
DNA repair protein RAD51 homolog 4, C-terminal (Rad51D_C)
Type: Domain

This entry represents the C-terminal region of Rad51D and similar eukaryotic proteins.

DNA repair protein RAD51 homolog 4 (RAD51D), a RAD51 paralogue, plays an important role in DNA repair by homologous recombination (HR). HR is an important error-free repair mechanism for chromosomal double-strand break (DSB) which otherwise leads to cell cycle arrest and death. RAD51D, together with the other RAD51 paralogues, RAD51B, RAD51C, XRCC3, and XRCC2, helps recruiting RAD51 to the break site .
Gamma carbonic anhydrase-like (LbH_gamma_CA-like)
Type: Family

This family includes of gamma carbonic anhydrases (CAs) and similar proteins. CAs are the most ubiquitous ancient zinc metalloenzymes known that catalyse the reversible hydration of carbon dioxide in a two-step mechanism, involving the nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide, followed by the regeneration of the active site by ionization of the zinc-bound water molecule and removal of a proton from the active site. They are involved in fundamental processes like photosynthesis, respiration, pH homeostasis and ion transport. Gamma CAs are trimeric enzymes with left-handed parallel β-helix (LbH) structural domain, widespread in prokaryotes with homologous proteins found in plants .

This entry also includes YrdA from E.coli, which is structurally similar to gamma CAs, however, its function is unknown as it does not show significant CA activity .
Cyclic nucleotide phosphodiesterase, catalytic domain (CNPase_cat)
Type: Domain

This entry represents the catalytic domain of CNP, which catalyses the hydrolysis of nucleoside 2',3'-cyclic monophosphates to nucleoside 2'-monophosphates .

This entry includes the eukaryotic protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) . CNPase is one of the earliest myelin-related proteins expressed in differentiating oligodendrocytes and Schwann cells. CNPase is abundant in the central nervous system and in oligodendrocytes . This protein is also found in mammalian photoreceptor cells, testis and lymphocytes. It may participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin . CNP selectively cleaves 2',3'-cyclic nucleotides to produce 2'-nucleotides. Although physiologically relevant substrates with 2',3'-cyclic termini are still unknown, numerous cyclic phosphate containing RNAs occur transiently within eukaryotic cells. Other known protein families capable of hydrolysing 2',3'-cyclic nucleotides include tRNA ligases and plant cyclic phosphodiesterases. The catalytic domains from all these proteins contain two tetra-peptide motifs H-X-T/S-X, where X is usually a hydrophobic residue. Mutation of either histidine in CNPase abolishes enzymatic activity .
PLEKHM1, RUN domain (RUN_PLEKHM1)
Type: Domain

This entry represents the RUN domain of PLEKHM1 and similar proteins from animals.

PH domain-containing family M member 1 (PLEKHM1), also called 162 kDa adapter protein (AP162), may act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways . In case of infection, this protein contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7 . In humans, mutations in the gene encoding for this protein are associated to osteopetrosis, a bone disorder characterised by increased skeletal mass due to defective osteoclast function .
PLEKHM2, RUN domain (RUN_PLEKHM2)
Type: Domain

This entry represents the RUN domain of PLEKHM2 and similar animal proteins.

Pleckstrin homology domain-containing family M member 2 (PLEKHM2), also called Salmonella-induced filaments A (SifA) and Kinesin-Interacting Protein (SKIP), is the lysosome, melanosome and lytic granule cargo adaptor that controls lysosome positioning using a composite kinesin-1 heavy and light chain-binding domain. In addition to kinesin-1, it also interacts with several Rabs to affect endosomal trafficking .
Sorting nexin-29, RUN domain (RUN_SNX29)
Type: Domain

This entry represents the RUN domain of SNX29 and similar animal proteins.

Sorting nexin-29 (SNX29) belongs to the sorting nexin family. Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain, a phospholipid-binding motif, or through protein-protein interactions with membrane-associated protein complexes. Some sorting nexin family members have been shown to facilitate protein sorting.
RUN and FYVE domain-containing protein 1, RUN domain (RUN_RUFY1)
Type: Domain

This entry represents the RUN domain of RUFY1 and similar proteins from vertebrates.

RUN and FYVE domain-containing protein 1 (RUFY1), also called Rab4-interacting protein (Rabip4), is an homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo . RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between .
RUN and FYVE domain-containing protein 1, FYVE domain (FYVE_RUFY1)
Type: Domain

This entry represents the FYVE domain of RUFY1 and similar proteins from vertebrates.

RUN and FYVE domain-containing protein 1 (RUFY1), also called Rab4-interacting protein (Rabip4), is an homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo . RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between .
RUN and FYVE domain-containing protein 2, RUN domain (RUN_RUFY2)
Type: Domain

This entry represents the RUN domain of RUFY2 and similar proteins from vertebrates.

RUN and FYVE domain-containing protein 2 (RUFY2) is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. It is a paralogue of RUFY1 .
RUN and FYVE domain-containing protein 2, FYVE domain (FYVE_RUFY2)
Type: Domain

This entry represents the FYVE domain of RUFY2 and similar proteins from vertebrates.

RUN and FYVE domain-containing protein 2 (RUFY2) is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. It is a paralogue of RUFY1 .
RUN and FYVE domain-containing protein 3, RUN domain (RUN_RUFY3)
Type: Domain

This entry represents the RUN domain of RUFY3 and similar proteins from vertebrates.

RUN and FYVE domain-containing protein 3 (RUFY3), also called Single axon-regulated protein (Singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5 . RUFY3 plays a role in the formation of F-actin-enriched protrusive structures at the cell periphery, in cytoskeletal organisation, and in the generation of neuronal polarity formation and axon growth . This protein promotes gastric cancer cell migration and invasion in a PAK1-dependent manner .
RUN and FYVE domain-containing protein 1-3 (RUFY1-3)
Type: Family

This entry represents a group of proteins from animals, including RUN and FYVE domain-containing protein 1-3 (RUNFY1-3) from mammals.

RUFY1, also called Rab4-interacting protein (Rabip4), is an homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between .

RUFY2 is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. It is a paralogue of RUFY1 .

RUFY3, also called Single axon-regulated protein (Singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5 . RUFY3 plays a role in the formation of F-actin-enriched protrusive structures at the cell periphery, in cytoskeletal organisation, and in the generation of neuronal polarity formation and axon growth . This protein promotes gastric cancer cell migration and invasion in a PAK1-dependent manner .
FYCO1, RUN domain (RUN_FYCO1)
Type: Domain

This entry represents the RUN domain of FYCO1 and similar proteins predominantly found in vertebrates.

FYVE and coiled-coil domain-containing protein 1 (FYCO1) is a multidomain autophagy adaptor protein that interacts with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7, and Phosphatidylinositol 3-phosphate (PI3P), to mediate microtubule plus-end-directed autophagosome transport . This protein is associated with congenital cataracts .