SII-SWORD/CoKE huggingface dataset:
PKHA4-7, PH domain (PKHA4-7_PH)
Type: Domain

This entry represents pleckstrin homology (PH) domain found in the Pleckstrin homology domain-containing family A members 4-7 (PKHA4-7) from humans. This domain is involved in targeting these proteins to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. Some PH domains are responsible for the protein binding to phosphoinositide phosphates (PIPs) with high affinity and specificity, others display strong specificity in lipid binding. Its specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. Proteins included in this entry are predominantly found in chordates. Some members also contain WW (also known as WWP) domains, also occurring in proteins involved in signal transduction processes .
Three-prime repair exonuclease 1/2 (TREX1/2)
Type: Family

Three prime repair exonuclease (TREX)1 and TREX2 are closely related DEDDh-type DnaQ-like 3'-5' exonucleases. They contain three conserved sequence motifs known as ExoI, II, and III, with a specific Hx(4)D conserved pattern at ExoIII. These motifs contain four conserved acidic residues that participate in coordination of divalent metal ions required for catalysis. Both proteins play a role in the metabolism and clearance of DNA .
F-box only protein 25/32 (FBX25/32)
Type: Family

This entry includes a group of animal F-box containing proteins, including FBX25 and FBX32. FBXO32 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 . FBX25 is strongly expressed in human brain .
Tetratricopeptide repeat protein 19 (TTC19)
Type: Family

TTC19 is involved in complex III biogenesis and the clearance of UQCRFS1 N-terminal fragments . Mutations in the TTC19 gene cause mitochondrial complex III deficiency and neurological impairment in humans and flies .
Polyadenylate-binding protein-interacting protein 2-like (PAIP2-like)
Type: Family

This entry includes Paip2 (also known as Paip2A) and related proteins, such as Paip2B. Paip2 is a transcription repressor that inhibits translation by interdicting PABP (poly(A) binding protein) function . Paip2B acts in a manner similar to Paip2. However, they are expressed in different tissues and cell lines. Also, Paip2 is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome .
Suppressor of white apricot (SWAP)
Type: Family

Suppressor of white apricot, also known as SWAP, is an alternative splicing regulator. SWAP was originally identified in Drosophila as a suppressor of the transposon-induced white-apricot mutation. It regulates splicing of several genes, including Swap itself . Human SWAP has been shown to regulate alternative mRNA splicing of CD45 exon 4 and fibronectin IIICS .

This entry also includes CLK4-associating serine/arginine rich protein (CLASRP, also known as SWAP2). The function of SWAP2 is not clear.
CCR4-NOT transcription complex subunit 1 (Not1)
Type: Family

Not1 is the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels. This entry includes Not1 (also known as Cdc39) and its homologues, such as LET-711 from Caenorhabditis elegans . De novo variants in CNOT1 have been shown to cause neurodevelopmental delay .

The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 . The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress . Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex . Pop2, a component of the Ccr4-Not complex, functions as a deadenylase .
Transmembrane protein 35A/B (TMEM35A/B)
Type: Family

Shedding of transmembrane protein 35 (TMEM35) produces a soluble peptide that may modulate neurite outgrowth in the adrenal zona glomerulosa after sodium depletion . TMEM35 could be required for normal activity of the hypothalamic-pituitary-adrenal axis and limbic circuitry .

TMEM35A, also known as NACHO, acts as a acetylcholine receptor chaperone that mediates the proper assembly and functional expression of the nicotinic acetylcholine receptors (nAChRs) throughout the brain .
BAG family molecular chaperone regulator 5/6/7/8 (BAG5/6/7/8)
Type: Family

This entry represents a group of plant BAG domain containing proteins, including BAG5/6/7/8 from Arabidopsis. The plant BAG domain containing proteins are multifunctional proteins that regulate cytoprotective processes from pathogen attack to abiotic stress and development. AtBAG6 appears to play a role within basal defense pathways, while AtBAG7 is involved in the maintenance of the unfolded protein response in ER .
Coiled-coil domain-containing protein 162 (CCDC162)
Type: Family

The function of CCDC162 is not clear.
DNA-directed RNA polymerase IV/V subunit 1, C-terminal (NRPD1_C)
Type: Domain

Higher plants have five multi-subunit nuclear RNA polymerases: RNAP I, RNAP II and RNAP III, which are essential for viability; plus the non-essential polymerases IVa and V (IVb), which specialize in small RNA-mediated gene silencing pathways. RNAP IVa and/or RNAP IVb might be involved in RNA-directed DNA methylation of endogenous repetitive elements, silencing of transgenes, regulation of flowering-time genes, inducible regulation of adjacent gene pairs, and spreading of mobile silencing signals .

NRPD1a is the largest subunit of RNAP IVa, whereas NRPD1b is the largest subunit of RNAP V/IVb. The full subunit compositions of RNAP IVa and RNAP V/IVb are not known, nor are their templates or enzymatic products. However, it has been shown that RNAP IVa and, to a lesser extent, RNAP V/IVb are crucial for several RNA-mediated gene silencing phenomena .

This entry represents the C-terminal domain found in NRPD1a and NRPD1b.
DNA-directed RNA polymerase IV/V subunit 1, N-terminal (NRPD1_N)
Type: Domain

Higher plants have five multi-subunit nuclear RNA polymerases: RNAP I, RNAP II and RNAP III, which are essential for viability; plus the non-essential polymerases IVa and V (IVb), which specialize in small RNA-mediated gene silencing pathways. RNAP IVa and/or RNAP IVb might be involved in RNA-directed DNA methylation of endogenous repetitive elements, silencing of transgenes, regulation of flowering-time genes, inducible regulation of adjacent gene pairs, and spreading of mobile silencing signals .

NRPD1a is the largest subunit of RNAP IVa, whereas NRPD1b is the largest subunit of RNAP V/IVb. The full subunit compositions of RNAP IVa and RNAP V/IVb are not known, nor are their templates or enzymatic products. However, it has been shown that RNAP IVa and, to a lesser extent, RNAP V/IVb are crucial for several RNA-mediated gene silencing phenomena .

This entry represents the N-terminal domain found in NRPD1a and NRPD1b.
Phylloplanin-like (Phylloplanin-like)
Type: Family

Phylloplanin has been characterised in Nicotiana tabacum, where it inhibits spore germination and leaf infection by fungal pathogen Peronospora tabacina .
Uncharacterized protein DDB_G0275255-like (DDB_G0275255-like)
Type: Family

This is a family of unknown function. No member has yet been characterised.
Phytochelatin synthase (PCS-like)
Type: Family

Phytochelatins are well known as the heavy metal-detoxifying peptides in higher plants, eukaryotic algae, fungi, nematode and cyanobacteria. Phytochelatin synthase (PCS, also known as glutathione gamma-glutamylcysteinyltransferase;

) is involved in the synthesis of phytochelatins (PC) and homophytochelatins (hPC). This enzyme is required for detoxification of heavy metals such as cadmium and arsenate. The N-terminal region of phytochelatin synthase contains the active site, as well as four highly conserved cysteine residues that appear to play an important role in heavy-metal-induced phytochelatin catalysis. The C-terminal region is rich in cysteines, and may act as a metal sensor, whereby the Cys residues bind cadmium ions to bring them into closer proximity and transferring them to the activation site in the N-terminal catalytic domain . The C-terminal region displays homology to the functional domains of metallothionein and metallochaperone.
UPF0658 Golgi apparatus membrane protein (UPF0658_Golgi)
Type: Family

This uncharacterised family consists of Golgi apparatus membrane proteins from fungi.
Uncharacterized protein At5g23160-like (At5g23160-like)
Type: Family

This family of uncharacterised plant proteins includes Arabidopsis thaliana At5g23160.
Uncharacterized protein At1g65710-like (At1g65710-like)
Type: Family

At1g65710 is the representative of this family of uncharacterised plant proteins.
PAM2-containing protein CID1/CID2 (CID1/CID2)
Type: Family

PAM2-containing protein CID1, also known as protein EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15) or polyadenylate-binding protein-interacting protein 1, is a negative regulator of abscisic acid (ABA) responses . ABA plays an important role in plant germination and development, and accumulates in response to different stresses. ERD15 is involved in stress tolerance in plants, including resistance to drought .

This family also includes related protein CID2, whose function is not known.
SET domain-containing protein 9 (SETD9)
Type: Family

The function of SETD9 is not clear. Sequence and structure-based models suggest it could be a methyltransferase .
Transmembrane protein 181 (TMEM181)
Type: Family

TMEM181 mutants are resistant to CDT bacterial toxins. TMEM181 is a cell-surface protein, and CDT may bind to it to enter the cell through endocytosis . This protein is homologous to GPR180, TMEM145, and Wntless (WLS), which have been described as GOST proteins (for GOLD domain seven-transmembrane helix proteins) together with TMEM87A/B, GPR107, and GPR108, given they share the same domain topology consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain .
Glycine-rich cell wall structural protein 1/2 (GRP1/2)
Type: Family

This entry represents a group of plant proteins, including glycine-rich cell wall structural protein 1/2 (GRP1/2) from rice. Their function is not clear.
Protein crowded nuclei (CRWN)
Type: Family

CROWDED NUCLEI (CRWN) proteins, also known as LITTLE NUCLEI, are important architectural components of plant nuclei and are thought to play diverse roles in heterochromatin organization and the control of nuclear morphology . CRWN proteins regulate ABA-controlled seed germination by modulating the degradation of protein ABI5. CRWN3 has been shown to colocalize with ABI5 in nuclear bodies, where it might participate in its degradation .

Proteins in this entry also includes NMCP1A/B from rice. NMCP1B, also known as OsNMCP1, regulates drought resistance and root growth through chromatin accessibility .
DUF5568 family (DUF5568)
Type: Family

The function of this family, which includes human protein C5orf24, is not known.
Uncharacterized protein At1g76660-like (At1g76660-like)
Type: Family

At1g76660 is the representative of this family of uncharacterised proteins from plants.
Phosphoethanolamine transferase (PEA_transferase)
Type: Family

The enzyme EptA (also known as LptA,

) promotes phosphoethanolamine (PEA) decoration of lipid A, which promotes resistance to innate defence systems . In addition to lipid A PEA transferases, many Gram-negative bacteria have modifications on different sites of LPS that are catalysed by different PEA transferases . EptB and EptC (CptA) can modify 3-deoxy-d-manno-oct-2-ulosonate (Kdo II) of the inner core and O-6 of L-glycero-D-manoheptose I of LPS, respectively . Some phosphatidylethanolamine transferases, such as Mcr-1, are plasmid-encoded .
SMN complex subunit Smn1 (Smn1)
Type: Family

This entry includes human Survival motor neuron protein (SMN), its orthologue from Schizosaccharomyces pombe and similar proteins from eukaryotes. It is part of the SMN complex, which catalyses the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs . Interestingly, Smn is not present in Saccharomyces cerevisiae. Orthologues of this gene in fungi seem to be present predominately in filamentous fungi .
Uncharacterized protein C20orf141-like (C20orf141-like)
Type: Family

This family of uncharacterised proteins is present in mammals.
Uncharacterized protein C05B5.4-like (C05B5.4-like)
Type: Family

This family of uncharacterised proteins from nematodes includes C05B5.4 and R10E12.2 from Caenorhabditis elegans.
Fl(2)d-associated complex component (Flacc)
Type: Family

Flacc, also known as Zc3h13 (zinc finger CCCH domain-containing protein 13) or Xiong, is a component of the N6-methyladenosine (m6A) methyltransferase complex. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila .
Uncharacterised protein C11orf97-like (C11orf97-like)
Type: Family

The function of this family of uncharacterised proteins is not known.
Putative transcriptional regulator CudA-like (CudA-like)
Type: Family

This is a family of putative transcription factors found mainly in slime molds. CudA from Dictyostelium directly activates expL7 gene expression in prestalk cells in the anterior region of the migrating slug .
Cation channel sperm-associated auxiliary subunit TMEM262 (TM262)
Type: Family

This family represents the auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation .
Spermatid nuclear transition protein (Spermatid_TP)
Type: Family

Transition nuclear proteins (TNPs), major proteins found in the chromatin of condensing spermatids, have been implicated in spermatogenesis and male fertility . This entry includes TNP3 and TNP4. Ram TNP3 and boar TP4 belong to the same group and probably play similar functions in chromatin remodelling during spermiogenesis . TNP4 stimulates the DNA-relaxing activity of topoisomerase I . This entry also includes human uncharacterised protein CXorf51.
tRNA selenocysteine 1-associated protein 1 (TSAP1)
Type: Family

Selenocysteine tRNA 1 associated proteins (also known as TRNAU1AP) is involved in the early steps of selenocysteine biosynthesis and tRNA(Sec) charging to the later steps resulting in the cotranslational incorporation of selenocysteine into selenoproteins. Selenium deficiency results in a variety of diseases, including cardiac disease . TRNAU1AP contains RNA recognition motifs (RRM) and a Tyr-rich region found in the C-terminal. The Tyr-rich region (amino acids 185-225) is conserved among several mammals, including human, chimp, dog, cattle, mouse and rat. Furthermore, constitutive deletion of exons corresponding to the Tyr-rich region in mouse resulted in embryonic lethality .

This entry also includes uncharacterised protein C6orf52 from humans.
Putative G-protein coupled receptor, Chromadorea (Put_GPCR_Chromadorea)
Type: Family

This entry includes a group of putative G-protein coupled receptors from Chromadorea.
Protein disconnected-like (Disconnected-like)
Type: Family

Proteins in this family contain C2H2-type zinc fingers. Proteins include:

Protein disconnected (disco) from the fruit fly (Drosophila melanogaster), which is required for the formation of stable connections between larval optic nerve cells (also known as Bolwig's nerves) and cells in the brain .

Zinc finger protein basonuclin-1 (BNC1), which has three pairs of zinc fingers and a nuclear localization signal and expression of the gene is confined to keratinocytes of stratified squamous epithelia and hair follicles. It is probably a transcriptional activator, preventing terminal differentiation of keratinocytes . It is involved in the positive regulation of oocyte maturation through the regulation of AKT signalling cascade .

Zinc finger protein basonuclin-2 (BNC2), which also has three pairs of zinc fingers and a nuclear localization signal, with the gene expressed in the ovary, testis, kidney and skin. It is also located in the nucleus and probably a transcriptional activator, involved in the differentiation of spermatozoa and oocytes. It may also play an important role in early urinary-tract development .
Uncharacterized protein F10E9.3-like (F10E9.3-like)
Type: Family

This small family consists of uncharacterised proteins from Caenorhabditis.
Protein HIDE1 (HIDE1)
Type: Family

The function of the proteins in this family is not known. They are known as HIDE1 for highly expressed in immature dendritic cell transcript 1.
Protein FAM237 (FAM237A/B)
Type: Family

FAM237 proteins constitute an uncharacterised family from vertebrates.
Cilia- and flagella-associated protein 20/CFAP20DC (CFA20/CFAP20DC)
Type: Family

This entry includes cilia- and flagella-associated protein 20 (CFA20) and CFAP20DC, also known as C3orf67. CFA20 is a cilium- and flagellum-specific protein that plays a role in axonemal structure organisation and motility . In Chlamydomonas reinhardtii, it stabilises outer doublet microtubules (DMTs) of the axoneme and may work as a scaffold for intratubular proteins, such as tektin and PACRG, to produce the beak structures in DMT1 .
Pyruvate kinase-like domain superfamily (Pyrv_kinase-like_dom_sf)
Type: Homologous_superfamily

Pyruvate kinase controls the exit from the glysolysis pathway, catalysing the transfer of phosphate from phosphooenolpyruvate (PEP) to ADP. Mammalian pyruvate kinase is a homotetramer, where each polypeptide subunit consists of four domains: N-terminal, A domain, B domain and C-terminal. Activation of the enzyme is believed to occur via the clamping down of the B domain onto the A domain to dehydrate the active site cleft. The N- and C-terminal domains are situated at inter-subunit contact sites, and could be involved in assembly and communication within the complex. The N-terminal domain has a TIM β/α-barrel structure .
PH_15 domain (PH_15)
Type: Domain

This entry contains a PH domain.
PCNA-associated factor (PCNA-AF)
Type: Family

PCNA-associated factor or p15PAF is a nuclear protein first identified as a proliferating-cell-nuclear-antigen (PCNA)-binding protein . As a direct transcriptional target of activating transcription factor 3 (ATF3) it is involved in maintaining genomic integrity after UV exposure . It is also a direct transcriptional target of the Rb/E2F pathway, playing an essential role in DNA synthesis and cell cycle progression . p15PAF/KIAA0101 is overexpressed in multiple types of human cancer .
Potassium channel, inwardly rectifying, transmembrane domain (Kir_TM)
Type: Domain

Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release . To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x .

Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. The two 'transmembrane passes' place the C-terminal tail on the cytoplasmic side of the membrane . It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric .
Ribosomal RNA-processing protein 7 (RRP7)
Type: Family

Ribosomal RNA-processing protein 7 (RRP7) is an essential protein in yeast that is involved in pre-rRNA processing and ribosome assembly . It is speculated to be required for correct assembly of rpS27 into the pre-ribosomal particle .
Rrp7, RRM-like N-terminal domain (RRM_Rrp7)
Type: Domain

Ribosomal RNA-processing protein 7 (RRP7) is an essential protein in yeast that is involved in pre-rRNA processing and ribosome assembly . It is speculated to be required for correct assembly of rpS27 into the pre-ribosomal particle .

This domain corresponds to the N-terminal RNA-binding domain found in the Rrp7 protein. It has an RRM-like fold with a circular permutation .
PanZ, acetyltransferase (GNAT) domain (PanZ_GNAT)
Type: Domain

This entry represents the GNAT domain found in PanZ.

PanD is a l-aspartate alpha-decarboxylase involved in the biosynthesis of pantothenate, the precursor of coenzyme A (CoA). PanD is synthesised as pro-PanD, which undergoes auto-proteolytic cleavage to generate active PanD. PanM binds to and activates PanD by stabilising pro-PanD in an autocleavage-prone conformation . PanM acts as an acetyl-CoA sensor that can trigger the maturation of pro-PanD, but lacks acetyltransferase activity . The regulation of PanD by PanZ allows enterobacterial species to closely regulate production of beta-alanine and hence pantothenate in response to metabolic demand . Structure and function studies show that direct interaction of PanD with the PanZ Arg43-Leu46 loop promotes PanD to adopt a reactive conformation, which leads to activation .
LD-carboxypeptidase, N-terminal (Peptidase_S66_N)
Type: Domain

This entry includes proteins belonging to the MEROPS peptidase family S66, such as muramoyl-tetrapeptide carboxypeptidase and the microcin c7 self-immunity protein

.

The structure of Pseudomonas aeruginosa LD-carboxypeptidase showed that the enzyme consists of an N-terminal β-sheet and a C-terminal β-barrel domain . This entry represents the N-terminal domain.
TFIIF beta subunit, HTH domain (TFIIF_beta_HTH)
Type: Domain

Accurate transcription
in vivo
requires at least six general transcription initiation factors, in addition to RNA polymerase II. Transcription initiation factor IIF (TFIIF) is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30) . The beta subunit of TFIIF is required for recruitment of RNA polymerase II onto the promoter.
Glycosyl hydrolase family 81, N-terminal (GH81_N)
Type: Domain

The glycosyl hydrolase family 81 comprises beta-1,3-glucanases which includes Eng1/Eng2 from fission yeast. Proteins in this entry hydrolyse linear beta-1,3-glucan chains . Eng1 is required for the degradation of the primary septum after completion of cytokinesis . Eng2 plays a role in coupling the endocytic coat to the actin cytoskeleton and, independently of this activity, it is required to establish bipolar cell growth by promoting localization of the scaffold protein scd2 to cell poles and thereby, the activation of cdc42 . The endo-beta-1,3-glucanase activity is essential for efficient spore release .

This entry represents the N-terminal β-sandwich domain.
Sugar fermentation stimulation protein, C-terminal (SfsA_C)
Type: Domain

Sugar fermentation stimulation protein is probably a regulatory factor involved in maltose metabolism. SfsA has been shown to bind DNA and it contains a helix-turn-helix motif that probably binds DNA at its C terminus.
Mnd1, HTH domain (Mnd1_HTH)
Type: Domain

This HTH domain is found in Mnd1 from S. cerevisiae. The Mnd1 protein forms a complex with Hop2 to promote homologous chromosome pairing and meiotic double-strand break repair .