SII-SWORD/CoKE huggingface dataset:
Semaphorin-3A, sema domain (Sema3A_sema)
Type: Domain

This entry represents the sema domain of Semaphorin-3A .

Sema3A has been reported to inhibit the growth of certain experimental tumours and to regulate endothelial cell migration and apoptosis in vitro, as well as arteriogenesis in the muscle, skin vessel permeability, and tumor angiogenesis in vivo . The function of Sema3A is mediated through receptors neuropilin-1 (NP1) and plexins, although little is known about the requirement of specific plexins in its receptor complex . It is known however that Plexin-A4 is the receptor for Sema3A in the Toll-like receptor- and sepsis-induced cytokine storm during immune response . Sema3A is a member of the Class 3 semaphorin family of secreted proteins .

Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module .
Semaphorin-5A, sema domain (Sema5A_sema)
Type: Domain

In mice, Sema5A has been identified as a protein that induces inhibitory responses during optic nerve development . It also has been identified as a candidate gene for causing idiopathic autism in humans . Plexin B3 functions as a binding partner and receptor for Sema5A . Sema5A is highly expressed in human pancreatic cancer cells and is associated with tumor growth, invasion and metastasis . Sema5A belongs to class 5 semaphorin family of proteins, which are transmembrane glycoproteins characterised by unique thrombospondin specific repeats in the extracellular region of the protein .

Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module .
Membrane Guanylate Cyclase receptor GC-C, pseudokinase domain (GC-C_PK)
Type: Domain

This entry represents the pseudokinase domain found in membrane Guanylate Cyclase receptor guanylyl cyclase C (GC-C, also known as heat-stable enterotoxin receptor). This domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding.

GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt .

Membrane (or particulate) guanylate cyclases (GCs) consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyses the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins .
E3 ubiquitin-protein ligase Dma1/Dma2, RING finger, H2 subclass (Dma1/Dma2_RING-H2)
Type: Domain

Proteins containing this domain include one Schizosaccharomyces pombe protein Dma1 (SpDma1p), two Saccharomyces cerevisiae proteins, Dma1 (ScDma1p) and Dma2 (ScDma2p), and their homologues from fungi . They are related to the mammalian CHFR/RNF8 family of ubiquitin ligases. SpDma1p functions to prevent mitotic exit and cytokinesis during spindle checkpoint arrest by inhibiting septation initiation network (SIN) signalling . ScDma1p and ScDma2p, also known as checkpoint forkhead associated with RING domains-containing protein 1 and 2 respectively, seem to be functionally redundant. They are involved in proper septin ring positioning and cytokinesis .
Semaphorin-7A, sema domain (Sema7A_sema)
Type: Domain

Semaphorin-7A (Sema7A) plays regulatory roles in both immune and nervous systems. Unlike other semaphorins, which act as repulsive guidance cues, Sema7A enhances central and peripheral axon growth and is required for proper axon tract formation during embryonic development . Sema7A also plays a critical role in the negative regulation of T cell activation and function . Sema7A is a membrane-anchored member of the semaphorin family of proteins.

Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module .
PLK2, catalytic domain (PLK2_STKc)
Type: Domain

PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication . Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint .

STKs (serine/threonine-protein kinases) catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs (polo-like kinases) play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes .
Plexin-A2, sema domain (Plexin-A2_sema)
Type: Domain

Plexin A2 serves as a receptor for class 6 semaphorins. Interactions between Plexin A2, A4 and semaphorins 6A and 6B control the lamina-restricted projection of hippocampal mossy fibres. Sema6B also repels the growth of mossy fibres in a Plexin A4 dependent manner . Plexin A2 does not suppress Sema6B function. In addition, studies have shown that Plexin A2 may be related to anxiety and other psychiatric disorders .

Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module .
PLEKHM1, PH domain (PLEKHM1_PH)
Type: Domain

This entry represents the Pleckstrin homology (PH) domain of PLEKHM1 and similar proteins from vertebrates.

Pleckstrin homology domain-containing family M member 1 (PLEKHM1) is a ubiquitously expressed protein involved in the regulation of osteoclast function and bone resorption . It may function as an adaptor protein that acts as a central hub to integrate endocytic and autophagic pathways at the lysosome . PLEKHM1 contains an N-terminal RUN domain (RPIP8/RaP2 interacting protein 8, UNC-14 and NESCA/new molecule containing SH3 at the carboxyl-terminus), followed by a PH domain, and either a C1 domain or a DUF4206 domain at its C terminus. The RUN domain is thought to be involved in Rab-mediated membrane trafficking, possibly as a Rab-binding site.

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner . They share little sequence conservation, but all have a common fold, which is electrostatically polarised. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity . PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane . A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signalling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
TRIM41, PRY/SPRY domain (TRIM41_SPRY_PRY)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyses the ubiquitin-mediated degradation of protein kinase C .
3-keto-steroid reductase (HSD17B7/Erg27)
Type: Family

This entry includes a group of 3-keto-steroid reductases, including 17beta-HSD7 (or HSD17B7) from animals and Erg27 from fungi. 3-keto steroid reductase (in concert with other enzymes) catalyzes NADP-dependent sterol C-4 demethylation, as part of steroid biosynthesis. 3-keto reductase is a classical short-chain dehydrogenase/reductase (SDR), with a well conserved canonical active site tetrad and fairly well conserved characteristic NAD-binding motif .

HSD17B7 is the orthologue of the yeast steroid-3-ketoreductase (Erg27), an enzyme of ergosterol biosynthesis . HSD17B7 catalyses the conversion of estrone (a 17beta-hydroxysteroid) to the biologically active estradiol . Similar to Erg27, it also acts as a 3-ketosteroid reductase .

In humans, predominant expression of 17beta-HSD7 is found not only in reproductive tissues (breast, ovary, placenta) but also in liver and developing brain, principal sites of cholesterol synthesis in keeping with the bifunctional nature of this enzyme .
Large ribosomal subunit protein mL40, fungi (Ribosomal_mL40_fung)
Type: Family

This entryrepresents the large ribosomal subunit protein mL40 (previously known as 54S ribosomal protein L28 (YmL28)/Mrpl28) from fungi.
PHLDA family (PHLA1/2/3)
Type: Family

PHLDA family members include PHLDA1, 2, and 3. They are phosphatidylinositol (PIP) binding proteins and function as repressors of Akt. They are involved in p53/TP53-dependent apoptosis .
BTB/POZ domain-containing protein 16 (BTBD16)
Type: Family

The function of BTB/POZ domain-containing protein 16 (BTBD16) is not clear.
Armadillo repeat-containing protein 12 (Armc12)
Type: Family

The function of Armadillo repeat-containing protein 12 (Armc12) is not clear.
Pleckstrin homology domain-containing family N member 1 (PLEKHN1)
Type: Family

Pleckstrin homology domain-containing family N member 1 (PLEKHN1), also known as CLPABP, is a cardiolipin phosphatidic acid binding protein that associates with microtubules and accumulates in RNA granules, which contain cytochrome-c mRNA . It binds to Bid (a pro-apoptotic protein), removes Bid from transient Bid-Bax complexes, and promotes apoptosis .
Sialic acid-binding Ig-like lectin 15 (SIG15)
Type: Family

Sialic acid-binding Ig-like lectin 15 (SIG15) is a cell-surface receptor that recognize sialylated glycans. It may play a regulatory role in the immune system of vertebrates .
Pentraxin-related protein PTX3 (PTX3)
Type: Family

Pentraxin-related protein PTX3 is a long pentraxin that provides defence against infectious agents and plays several functions in tissue repair and regulation of cancer-related inflammation .

Pentraxins are a family of evolutionarily conserved molecules with regulatory role in inflammation. They share the "pentraxin signature" (His-x-Cys-x-Ser/Thr-Trp-x-Ser, where x is any amino acid) and can be divided into a short and a long arm based on their structural organization. Short pentraxins, feature a peculiar quaternary structure with five or ten identical protomer subunits arranged into symmetric pentamers, such as CRP and SAP, are secreted proteins produced by hepatocytes in response to IL-6. Long pentraxins, on the other end, display an unrelated amino-terminal region coupled to a C-terminal pentraxin domain. PTX3 is the prototype of the long pentraxin subfamily produced by myeloid and stromal cells, but not by hepatocytes, in response to primary pro-inflammatory cytokines or microbial moieties .
Uncharacterized protein KIAA1958 (KIAA1958)
Type: Family

The function of KIAA1958 is not clear.
Forkhead box protein M1 (FOXM1)
Type: Family

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 .
Lamin tail domain-containing protein 1 (LMNTD1)
Type: Family

The function of Lamin tail domain-containing protein 1 (LMNTD1) is not clear.
Splicing factor, arginine/serine-rich 19 (SCAF1)
Type: Family

SCAF1, also known as SRA1, is a member of the human SR (Ser/Arg-rich) superfamily of pre-mRNA splicing factors. It interacts with the CTD domain of the RNA polymerase II polypeptide A and is involved in pre-mRNA splicing . It has been linked to cancers .
CD226 antigen (CD226)
Type: Family

CD226, also known as DNAM-1, is a nectin receptor that contains two extracellular Ig-like domains (CD226-D1 and CD226-D2), and is widely expressed in monocytes, platelets, T cells, and most of the resting NK cells. The interactions between CD226 and its nectin/Necl family ligands, CD155 (also known as Necl-5) and CD112 (nectin-2), play important roles in modulating NK cell adhesion and cytotoxicity, facilitating immunological synapse formation and promoting cytokine secretion during inflammation .
DTX3L, RING-HC finger (TX3L_RING-HC)
Type: Domain

DTX3L is a RING-domain E3 ubiquitin-protein ligase that regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes . It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism . DTX3L has a unique N terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a DTC domain. DTX3L can associate with DTX1 through its unique N terminus and further enhance self-ubiquitination .
Proto-oncogene c-Rel, RHD, N-terminal subdomain (RHD-n_c-Rel)
Type: Domain

NF-kappa B proteins are part of a protein complex that acts as a transcription factor, which is responsible for regulating a host of cellular responses to a variety of stimuli. This complex tightly regulates the expression of a large number of genes, and is involved in processes such as adaptive and innate immunity, stress response, inflammation, cell adhesion, proliferation and apoptosis. The cytosolic NF-kappa B complex is activated via phosphorylation of the ankyrin-repeat containing inhibitory protein I-kappa B, which dissociates from the complex and exposes the nuclear localization signal of the heterodimer (NF-kappa B and Rel) . c-Rel plays an important role in B cell proliferation and survival .

Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains. This entry represents the N-terminal RHD sub-domain of the c-Rel family of transcription factors, categorized as a class II member of the NF-kappa B family. In class II NF-kappa Bs, the RHD domain co-occurs with a C-terminal transactivation domain (TAD) .
BTB/POZ domain-containing protein 19 (BTBD19)
Type: Family

The function of BTB/POZ domain-containing protein 19 (BTBD19) is not clear.
EF-hand calcium-binding domain-containing protein 12 (EFC12)
Type: Family

The function of EF-hand calcium-binding domain-containing protein 12 (EFC12) is not clear.
Ribonuclease P protein subunit Rpp38 (Rpp38)
Type: Family

Ribonuclease P (Rnp) is a ubiquitous ribozyme that catalyzes a Mg2 -dependent hydrolysis to remove the 5'-leader sequence of precursor tRNA (pre-tRNA) in all three domains of life . In bacteria, the catalytic RNA (typically ~120kDa) is aided by a small protein cofactor (~14kDa) . Archaeal and eukaryote RNase P consist of a single RNA and archaeal RNase P has four or five proteins, while eukaryotic RNase P consists of 9 or 10 proteins. Eukaryotic and archaeal RNase P RNAs cooperatively function with protein subunits in catalysis .

Eukaryotic nuclear RNase P shares most of its protein components with another essential RNP enzyme, nucleolar RNase MRP . RNase MRP (mitochondrial RNA processing) is an rRNA processing enzyme that cleaves various RNAs, including ribosomal, messenger, and mitochondrial RNAs. It can cleave a specific site within precursor rRNA to generate the mature 5'-end of 5.8S rRNA . Despite its name, the vast majority of RNase MRP is localized in the nucleolus . RNase MRP has been shown to cleave primers for mitochondrial DNA replication and CLB2 mRNA. In yeast, RNase MRP possesses one putatively catalytic RNA and at least 9 protein subunits (Pop1, Pop3-Pop8, Rpp1, Snm1 and Rmp1) . Human RNase MRP complex consists of 267 nucleotides and supports the interaction with and among at least seven protein components: hPop1, hPop5, Rpp20, Rpp25, Rpp30, Rpp38, and Rpp40) and three additional proteins, hPop4, Rpp21 and Rpp14, have been reported to be associated with at least a subset of RNase MRP complexes .

This entry includes animal Rpp38, which is a component of the Rnp and the MRP ribonuclease complexes .
Rho guanine nucleotide exchange factor 33 (ARHGEF33)
Type: Family

The function of Rho guanine nucleotide exchange factor 33 (ARHGEF33) is not clear. It contains the Dbl homology (DH) domain and may act as a guanine-nucleotide releasing factor.
v-SNARE, coiled-coil homology domain (V_SNARE_CC)
Type: Domain

The entry represents the entire v-SNARE coiled-coil homology domain.

The process of vesicular membrane fusion in eukaryotic cells depends on a conserved fusion machinery called SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors). In the process of vesicle docking, proteins present on the vesicle (v-SNARE) have to bind to their counterpart on the target membrane (t-SNARE) to form a core complex that can then recruit the soluble proteins NSF and SNAP. This so called fusion complex can then disassemble after ATP hydrolysis mediated by the ATPase NSF in a process that leads to membrane fusion and the release of the vesicle contents. v-SNAREs include proteins homologous to synaptobrevin .

Structurally the SNARE complex is generally a four-helix bundle comprised of three coiled-coil-forming domains from t-SNAREs and one from
v-SNARE. Although sequence similarity in the t- and v-SNARE coiled-coil homology domains are low there is a striking conservation of the
so-called heptad repeat that is of central importance in forming a coiled-coil structure. In a coiled-coil motif, seven residues constitute a canonical
heptad and are designated 'a' through 'g', with 'a' and 'd' being occupied by hydrophobic residues. The association of the four α-helices in the SNARE fusion complex structure produces highly conserved layers of interacting amino acid side chains in the centre of the four-helix bundle. The centre of the bundle is made up of 15 hydrophobic layers from the 'a' and 'd' positions of the heptad repeats of the coiled-coil-forming domains, whereas the central 'ionic' layer is highly conserved and polar in nature, containing a glutamine residue in the three t-SNAREs and an arginine in the v-SNARE, hence the classification of v- and t-SNAREs as R- and Q-SNAREs, respectively. The v-SNARE coiled-coil homology domain is around 60 amino acids in length .
Radial spoke protein 14 (RSP14)
Type: Family

Radial spoke protein 14 (RSP14) functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia . In humans, it has been related to multiple diseases, such as duodenal adenocarcinoma and meningiomas. In non-small cell lung cancer cells it has been shown to regulate the proliferation, cell cycle progression, and apoptosis .
Transmembrane protein 266 (TMEM266)
Type: Family

Transmembrane protein 266 (TMEM266), also known as HVRP1 (Hv1 related protein 1), is a voltage sensor regulated by extracellular Zn2 . It may have an important function in the nervous system .
DnaJ homolog subfamily C member 8 (DNAJC8)
Type: Family

DnaJ homolog subfamily C member 8 (DNAJC8) suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells .
Nucleolar protein 11 (NOL11)
Type: Family

NOL11 is a nucleolar protein and a component of the human ribosomal small subunit (SSU) processome. It is required for the early stages of ribosome biogenesis in humans . It interacts with the C-terminal region of the known t-UTP/UTPA subcomplex member, hUTP4/Cirhin, the protein mutated in North American Indian childhood cirrhosis (NAIC) . In Xenopus, it is required for optimal rDNA transcription and craniofacial development .
MICOS complex subunit MIC25 (MIC25)
Type: Family

MIC25, also known as CHCHD6, is a component of the MICOS complex, a large protein complex of the mitochondrial inner membrane crucial for the formation and maintenance of cristae structure . The deletion of CHCHD6 does not affect cristae morphology or stability of other components .
Testis-expressed protein 11 (TEX11)
Type: Family

Testis-expressed protein 11 (TEX11), also known as ZIP4H, is a regulator of crossing-over during meiosis. It is involved in initiation and/or maintenance of chromosome synapsis and formation of crossovers . Mutations in the TEX11 gene cause Spermatogenic failure, X-linked, 2 (SPGFX2), an infertility disorder caused by spermatogenesis defects .
RING finger protein 32 (RNF32)
Type: Family

RING finger protein 32 (RNF32) is specifically expressed in testis and ovary. It may play a role in sperm formation .
Protein kish-B (Kish-B)
Type: Family

The function of kish-B is not clear. In general, protein kish is involved in the early part of the secretory pathway .
Transmembrane protein 25 (TMEM25)
Type: Family

The function of Transmembrane protein 25 (TMEM25) is not clear. It contains a C-2 type immunoglobulin domain homologous to Hemicentin (Fibulin-6, FIBL6), Titin (TTN), Sialoadhesin (SN) and Nephrin (NEPHS1) .
Aspartate-rich protein 1-like (DRICH1-like)
Type: Family

This entry includes aspartate-rich protein 1 (DRICH1) and uncharacterised protein C22orf42 from humans. Their function is not clear.
Sushi domain-containing protein 6 (SUSD6)
Type: Family

The expression of Sushi domain-containing protein 6 (SUSD6), also known as DRAGO or KIAA0247, is regulated by p53 and may cooperate with p53 as oncosuppressor . It has been shown to inhibit growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway and work as a tumor suppressor in glioma .
Phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIP/PHYHIPL)
Type: Family

This entry includes PHYHIP and PHYHIPL from humans. PHYHIP interacts with DYRK1A and may contribute to new cellular functions of DYRK1A .