SII-SWORD/CoKE huggingface dataset:
CUE domain-containing protein 1, CUE domain (CUE_CUED1)
Type: Domain

The entry represents the CUE domain from a group of uncharacterised CUE domain-containing protein termed CUED1.
Fido domain-containing protein (Fido_containing)
Type: Family

Proteins in this entry contain a fido domain. The domain is named after the Fic and Doc proteins where it is found. Included in this entry are adenosine monophosphate-protein transferase Fic and FICD. Both Fic and FICD add adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), or remove the same modification from target proteins (de-AMPylation), depending on whether cells are in a resting state or stressed . Both bind divalent cations, preferring Mn
2+
over Mg
2+
. The adenosine monophosphate-protein transferase SoFic from Shewanella oneidensis is known only to add AMP to target proteins, either at Tyr or Thr residues .
FAS1 domain-containing protein Mug57-like (Mug57-like)
Type: Family

This entry represents a group of FAS1 domain-containing proteins, including Mug57 from S. pombe and YDR262W from S. cerevisiae. Mug57 is a meiotically upregulated gene (mug) that may have a role in sporulation .
Protein Mrg3-like (Mrg3-like)
Type: Family

This entry includes Mrg3 and Mrg3-like proteins mostly from fungi. Mrg3 is part of the mitochondrial inner membrane i-AAA protease supercomplex, which degrades misfolded mitochondrial proteins .
Nucleus export protein Brl1/Brr6 (Brl1/Brr6)
Type: Family

This entry represents a group of integral membrane proteins of the nuclear envelope (NE), including Brl1 and Brr6 from budding yeasts . Brl1 and Brr6 form a complex with Apq12. This complex plays an important role in membrane homeostasis regulation and nuclear pore complex biogenesis .
DNA replication regulator Sld2 (Sld2)
Type: Family

This entry includes Sld2 from budding yeasts and Drc1 from fission yeasts. Sld2 is required for the initiation of DNA replication. Its association with DNA is required for the assembly of the Cdc45-Mcm2-7-GINS (CMG) replicative helicase complex in S phase . Sld2 can be regulated by S-Cdk-dependent phosphorylation . Similarly, Drc1 is regulated by Cdk phosphorylation and is required for DNA replication . Drc1 interacts with Cut5 and plays a role in the loading of Cut5 onto origins of replication .
E3 ubiquitin-protein ligase UBR7 (UBR7)
Type: Family

Proteins in this entry include the putative E3 ubiquitin-protein ligase UBR7, which is found in mammalian spermatozoa, particularly the acrosomal cap and sperm acrosome . UBR7 is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. It may play an important role in spermiogenesis and fertilisation. Homologues are found in plants and fungi, including the uncharacterised protein Mlo2 from fission yeasts. Both UBR7 and Mlo2 contain both a PHD-type and an UBR-type zinc finger.
HIN-200 family (HIN-200)
Type: Family

Proteins in the HIN-200 family are induced by type I and II interferons (IFN), and they are involved in inflammation and immune responses . In addition to this role in interferon biology, they function as regulators of cell proliferation and differentiation . This family includes human IFI16, myeloid cell nuclear differentiation antigen, absent in melanoma 2 (AIM2), pyrin and HIN domain-containing protein 1 (IFIX), and murine proteins Ifi202, Ifi203, Ifi204, Ifi205 and Ifi206. All HIN-200 proteins, with the exception of p202, have an N-terminal α-helical PAAD/DAPIN/Pyrin domain .
Protein Zds1/2 (Zds1/2)
Type: Family

In budding yeasts, Zds1 and Zds2 interact with Cdc55 and are required for the completion of mitotic exit and cytokinesis. They are involved in activation of the Cdc14 phosphatase at anaphase onset . Fisson yeast Zds1 has been shown to control sexual differentiation, cell wall integrity and cell morphology .
Cep85/Cep85L (Cep85/Cep85L)
Type: Family

This entry includes Cep85 and Cep85L from animals.

Cep85 is a centrosomal protein of 85kDa . It is a centriole duplication factor that directly interacts with STIL. It is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly .

Centrosomal protein of 85kDa-like (CEP85L) may localise to the centrosome . It is also known as breast cancer antigen NY-BR-15 . A chromosomal aberration involving CEP85L was found in a patient with T-lymphoblastic lymphoma and associated myeloproliferative neoplasm .
Small EDRK-rich factor 1/2-like (SERF1/2-like)
Type: Family

This entry includes SERF1, SERF2 and related proteins. They are short proteins rich in aspartate, glutamate, lysine and arginine. These proteins are positive regulators of amyloid protein aggregation and proteotoxicity. They induce conformational changes in amyloid proteins, driving them into compact formations preceding the formation of aggregates .
GIR2-like (GIR2-like)
Type: Family

RWD domain containing 1 (RWDD1) and Gir2 from S. cerevisiae have a similar amino acid composition . RWDD1 has been shown to interact with the androgen receptor and functions as a coactivator of androgen-dependent transcription . Gir2 and its interacting partner, Rbg1, associate with ribosomes .
Uncharacterized bromodomain-containing protein 10 (BRD10)
Type: Family

This entry represents a group of uncharacterised proteins from animals, including Uncharacterized bromodomain-containing protein 10 (BRD10, also known as KIAA2026) from humans.
Cytotoxic T-lymphocyte protein 4/CD28 (CTLA4/CD28)
Type: Family

T cell-dependent immune processes require cell-surface interactions that mediate the initiation, modulation and the ultimate course of the response. The specificity of T cell recognition is determined by the engagement of the T cell receptor (TCR) on T cells with cognate peptide-MHC complexes presented by antigen presenting cells (APCs). Additional signals are required to sustain and enhance T cell activity, the most important of which is provided by the engagement of CD28 on T cells with its ligands B7-1 (CD80) and B7-2 (CD86). By contrast, the interaction of B7 isoforms with cytotoxic T lymphocyte-associated molecule-4 CTLA-4, a CD28 homologue receptor on T cells (31% identity), provides inhibitory signals required for down-regulation of the response, while it may also prevent T cell activation by weak TCR signals .

Sequence comparison between human CTLA-4 and CD28 proteins suggests they are homologous, with the highest of degree of similarity being in the juxta- membrane and cytoplasmic regions. In addition, the cytoplasmic domains of human and murine CTLA-4 are identical, suggesting that this region has important functional properties .
ACT domain-containing protein ACR1-12 (ACR1-12)
Type: Family

This entry represents a group of ACT domain-containing proteins mostly from plants, including ACR1-12 from Arabidopsis. The ACT domains s a regulatory domain that serve as amino acid-binding sites in some feedback-regulated amino acid metabolic enzymes. Plant ACR domain-containing proteins may function as novel regulatory or sensor proteins .
Probable RNA polymerase II nuclear localization protein SLC7A6OS (SLC7A6OS)
Type: Family

SLC7A6OS share protein sequence similarity with budding yeast Iwr1, which binds RNA pol II and regulates the transcription of specific genes. Danio rerio SLC7A6OS plays a role in defined areas of the developing central nervous system .
Uncharacterized protein KIAA1143-like (KIAA1143-like)
Type: Family

This entry includes human KIAA1143 and related proteins. Their function is not clear.
Protein down-regulated in DIF1 11 (DD11)
Type: Family

This entry represents a group of plant proteins, including DD11 from Arabidopsis . Their function is not clear.
CDCA7/CDA7L (CDCA7/CDA7L)
Type: Family

This entry includes CDCA7 and CDA7L.

Cell division cycle-associated protein 7 (CDCA7/JPO1) is a transcription regulator whose expression is activated by c-Myc and by E2F1 . CDCA7 can associate with Myc in a phosphorylation-dependent manner. CDCA7 phosphorylation by AKT leads to loss of its association with Myc . This interaction affects Myc-dependent apoptosis and transformation . CDCA7 has also been identified as a Notch target involved in hematopoietic stem cell emergence .

Cell division cycle-associated 7-like protein (CDCA7L/JPO2/R1) is closely related to CDCA7/JPO1; and like CDCA7, it plays a role in transcriptional regulation and interacts with c-Myc . JPO2 overexpression induces metastasis in medulloblastoma . JPO2 can interact directly and dynamically with chromatin, the dynamics of JPO2 chromatin binding being decelerated upon interaction with LEDGF/p75, which binds and tethers JPO2 to chromatin .

JPO2 inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter . JPO2 and MAOA act upstream of cyclin D1 and E2F1, and are involved in apoptotic signalling pathways .
ALOG family (ALOG)
Type: Family

This entry represents a group of ALOG (Arabidopsis LSH1 and Oryza G1) domain containing proteins, including LSH1-10 from Arabidopsis and G1/G1L1-8 from rice. G1 may be involved in transcriptional regulation and specifies sterile lemma identity in the rice spikelet . LSH1 is involved in phytochrome-mediated light signaling and in shoot meristem identity . The expression of LSH3 and LSH4 can be regulated by CUC1, which may suppress organ differentiation in the boundary region .

The 125-residue ALOG (Arabidopsis LSH1 and oryza G1) domain is rich in basic amino acids, especially arginine, and is highly conserved among land plants. Members of the ALOG family of proteins function as key developmental regulators. It has been proposed that the ALOG domain originated from the N- terminal DNA-binding domains of integrases belonging to the tyrosine recombinase superfamily encoded by a distinct type of DIRS1-like LTR retrotransposon found in several eukaryotes. Secondary structure predictions revealed an all-α helical domain with four conserved helices .
PAR basic leucine zipper protein (PAR_bZIP)
Type: Family

PAR basic leucine zipper (bZIP) factors constitute a group of circadian transcription factors that have conserved basic regions flanked by proline- and acidic-amino-aci-rich (PAR) domains and functionally compatible leucine zipper dimerization domains . PARbZip proteins are transcriptionally controlled by the circadian molecular oscillator, and in turn control expression of transcription factors and enzymes involved in metabolism and xenobiotic detoxification .

This entry includes vertebrates PARbZip proteins thyrotroph embryonic factor TEF/VBP, D site-binding protein (DBP), and hepatic leukemia factor (HLF), and Drosophila giant bZIP factor. Giant regulates the expression of the Krüppel and knirps segmentation gap genes .
RAD52 motif-containing protein 1 (RDM1)
Type: Family

RAD52 motif-containing protein 1 (RDM1) is involved in DNA damage repair pathway and the cell response to the anti-cancer drug cisplatin . RDM1 contains a small RD motif that is shared with the recombination and repair protein RAD52, and an RNA recognition motif (RRM). The RD motif is responsible for the acidic pH-dependent DNA-binding properties of RDM1. It interacts with ss- and dsDNA, and may act as a DNA-damage recognition factor by recognizing the distortions of the double helix caused by cisplatin-DNA adducts in vitro. In addition, due to the presence of RRM, RDM1 can bind to RNA as well as DNA .
Protein gravitropic in the light 1-like (GIL1-like)
Type: Family

This entry represents a group of plant proteins including, protein GRAVITROPIC IN THE LIGHT 1 (GIL1) from Arabidopsis. GIL1 is essential for light-dependent randomization of hypocotyl growth orientation .
THH1/TOM1/TOM3 (THH1/TOM1/TOM3)
Type: Family

This entry represents a group of plant proteins, including THH1/TOM1/TOM3 from Arabidopsis. TOM1 and TOM3 are transmembrane proteins necessary for the efficient multiplication of tobamoviruses . THH1 supports tobamovirus multiplication, but to a lesser extent than TOM1 and TOM3 . Proteins in this family belong to the GPCR superfamily and are also involved in stress tolerance .
Nibrin-related (Nibrin-rel)
Type: Family

Nibrin (also known as Nbs1 or p95) plays an important role in the DNA damage response (DDR) and DNA repair. It is part of the nuclear MRN complex, which consists of Mre11, Rad50, and Nbs1, and is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis . Mutations in the NBN gene coding for nibrin cause the Nijmegen Breakage Syndrome (NBS), a rare autosomal recessive disorder characterised by genomic instability and increased risk of haematopoietic malignancies .

NBS1 homologues from plants are also involved in DNA repair and recombination . In S. pombe, Nbs1 is required for DNA damage repair and S-phase DNA damage checkpoint .
Uncharacterized membrane protein At3g27390-like (At3g27390-like)
Type: Family

This entry includes At3g27390 and related proteins. Their function is not clear.
Protease TIKI1/2-like (TIKI1/2-like)
Type: Family

TIKI1/2 are membrane-associated proteases that inhibit Wnt via the cleavage of its amino terminus, diminishing Wnt's binding to receptors .

This entry also matches TraB-like proteins from bacteria .
Protein Kreg-1 (Kreg-1)
Type: Family

This entry represents Kreg-1 from Caenorhabditis spp. Kreg-1 is required for the defense against heavy metal stress .
CCD97-like, C-terminal (CCD97-like_C)
Type: Domain

This domain is found at the C-terminal of Coiled-coil domain-containing protein 97 (CCD97). In some proteins, this domain is found as two conserved domains separated by a region of low complexity, spanning some 200 residues. The function is unknown.
Glutaminyl-peptide cyclotransferase-like (QC/QCL)
Type: Family

This entry represents glutaminyl cyclases (QC), which are a subfamily of the peptidase M28 family. Glutaminyl cyclase (QC, QPCT, glutaminyl-peptide cyclotransferase) and iso-glutaminyl cyclase (QPCTL, isoQC) catalyze the formation of an N-terminal pyroglutamate (pGlu) residue from a glutaminyl or glutamyl residue. QC and isoQC are closely related single-zinc metalloenzymes that exhibit nearly identical substrate specificity in vitro . The major difference refers to subcellular localization: QC is secreted from expressing cells; isoQC is a resident enzyme of the Golgi complex . In humans, QCs are involved in several pathological conditions, such as Alzheimer disease .

Human pituitary glutaminyl cyclase shares a common fold and active site residues with and bacterial zinc aminopeptidase. In contrast to the aminopeptidase, however, QC does not appear to require zinc for enzymatic activity .

This entry also includes peptidase_M28 domain-containing proteins from bacteria.
Nicolin-1 (Nicolin-1)
Type: Family

The function of Nicolin-1 is not clear .
Transmembrane protein 198 (TMEM198)
Type: Family

TMEM198 is a membrane scaffold protein that promotes LRP6 phosphorylation and Wnt signaling activation .
Helix-loop-helix protein TAL-like (TAL-like)
Type: Family

This entry includes highly related proteins with a Myc-type, basic helix-loop-helix (bHLH) domain, including T-cell acute lymphocytic leukemia proteins 1 and 2 (TAL1 and TAL2), helix-loop-helix proteins 1 and 2 (NHLH1/HEN1 and NHLH2/HEN2), and protein lyl-1 (LYL1). The bHLH domain is required for protein dimerization and DNA binding . TAL1 may be a positive regulator of erythroid differentiation . The TAL1 and TAL2 genes are altered in T-cell acute lymphoblastic leukemia . The NHLH1 and NHLH2 genes are expressed in the developing nervous system, especially cell lines derived from neuroblastoma, PNET, and small cell lung cancer , and the proteins may have regulatory functions in the developing nervous system . LYL1 has a role in primitive erythropoiesis . A chromosomal aberration involving the LYL1 gene may be a cause of a form of T-cell acute lymphoblastic leukemia .
Beta-lactamase HcpB-like (HcpB-like)
Type: Family

Proteins in this entry have Sel1-like repeats, a subgroup of tetratricopeptide repeats, and include the following:

Beta-lactamase HcpB from Helicobacter pylori, which is a a cysteine-rich protein with a modular architecture consisting of four α/α-motifs that are cross-linked by disulfide bridges. HcpB is a penicillin-binding protein, binding and hydrolysing 6-amino penicillinic acid and 7-amino cephalosporanic acid derivatives .

Cytochrome c oxidase assembly factor 7 (COA7), which is required for the assembly of mitochondrial respiratory chain complexes I and IV .
Transcription initiation factor TFIID subunit 1 (TAF1)
Type: Family

Transcription initiation factor TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. The complex includes TATA binding protein (TBP) and various TBP-associated factors (TAFS). TFIID is a RNA polymerase II-specific TATA-binding protein-associated factor (TAF) that is essential for viability.

This group represents a transcription initiation factor TFIID subunit 1 (TAF1, also known as cell cycle gene 1 protein) . This is the largest subunit and the core scaffold of the complex, contains Ser/Thr kinase domains which can autophosphorylate or transphosphorylate other transcription factors including TP53, GTF2A1 and GTF2F1 , and has acetyltransferase activity towards histones H3 and H4 . It is essential for progression of the G1 phase of the cell cycle .
Transient receptor potential channel Flc/Pkd2-like (TRP_Flc/Pkd2-like)
Type: Family

This entry includes flavin carrier proteins Flc1-3 from budding yeasts and Pkd2 from fission yeasts. They are transient receptor potential channel-like proteins. Flc1 may be responsible for the transport of FAD into the endoplasmatic reticulum lumen, where it is required for oxidative protein folding . Pkd2 acts as a key signaling component in the regulation of cell shape and cell wall synthesis through interaction with GTPase Rho1 .
Tumor protein p63-regulated gene 1-like (TPRG1-like)
Type: Family

This entry includes TPRG1 and TPRG1L. TPRG1L, also known as protein Mover, is a presynaptic protein that is differentially expressed across brain areas and synapse types .
Steroid receptor RNA activator 1 (Steroid_recept_RNA_1)
Type: Family

The steroid receptor RNA activator gene (SRA1) produces both a functional RNA (SRA) and a protein (SRAP), both of which can modulate gene transcription . SRA-RNA coactivates steroid hormone receptor-mediated transcription as well as coactivating nuclear receptors, such as the androgen, estrogen, progesterone and glucocorticoid receptors . SRA/SRAP stimulate proliferation and apoptosis, and regulate cancer cell motility . It has been suggested that SRAP may prevent the transcriptional regulatory activity of SRA1 gene by binding a specific SRA stem-loop , though other studies have failed to detect any interaction between SRAP and SRA .
Protein enhanced disease resistance 4-like (EDR4-like)
Type: Family

This entry represents a group of plant proteins, including protein ENHANCED DISEASE RESISTANCE 4 (EDR4) from Arabidopsis. EDR4 plays a negative role in resistance to powdery mildew. It localizes at the plasma membrane and endosomal compartments. It interacts with EDR1 and recruits EDR1 to the fungal penetration site, where it regulates defense responses. It also interacts with CLATHRIN HEAVY CHAIN2 (CHC2) and edr4 mutants show reduced endocytosis .
UPF0547 protein C16orf87-like (C16orf87-like)
Type: Family

This entry represents a group of uncharacterised proteins from animals, including C16orf87 from humans.
Protein of unknown function DUF5524 (DUF5524)
Type: Family

This is a family of unknown function found in Metazoa.
Ribosome-binding protein 1 (RRBP1)
Type: Family

Ribosome-binding protein 1 (RRBP1), also called ES/130 or p180, is an endoplasmic reticulum membrane protein that is critical for ribosome binding and for the the transportation and secretion of nascent proteins . RRBP1 plays a critical role in terminal differentiation of secretory cells and tissues . RRBP1 is highly expressed in several cancers .
Ricin B-like lectin EULS3-like (Ricin_B-like_lectin_EULS3-like)
Type: Family

This entry represents a group of plant proteins, including EULS3 from Arabidopsis and related proteins from rice. They are lectins which bind carbohydrates. Rice Euonymus-related lectins (EULs) are stress-related lectins composed of one or two EUL domains . Arabidopsis EULS3 is involved in stomatal closure .
Nucleobindin (Nucleobindin)
Type: Family

This family consists of nucleobindin-1 (NUCB1, also known as CALNUC or Nuc), nucleobindin-2 (NUCB2, also known as nesfatin or NEFA), and yeast homologues.

Nucb2 is a calcium-binding protein that may have a role in calcium homeostasis . It can be cleaved into an isoform named nesfatin-1, which is an anorexigenic peptide that seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner . Nucb1 is a major calcium-binding protein of the Golgi, which may have a role in calcium homeostasis . Nucb1/2 act as non-receptor guanine nucleotide exchange factors which bind to and activate alpha subunits of guanine nucleotide-binding proteins (G proteins) . Nucb1 is expressed in pancreatic islets and other endocrine tissues and may have a role in in Ca(2+) handling/sensing in secretory cells . Nucleobindin-1 encodes a nesfatin-1-like peptide that stimulates insulin secretion .
Protein transport protein SEC31-like (SEC31-like)
Type: Family

This entry contains proteins with WD40 repeats and includes protein transport protein SEC31, which is a component of the coat protein complex II (COPII). COPII promotes the formation of transport vesicles from the endoplasmic reticulum by deformating the endoplasmic reticulum membrane into vesicles and selectiing cargo molecules . In humans and other mammals, there are two SEC31 proteins known as SEC31A and SEC31B .
Protein Ecm3-like (Ecm3-like)
Type: Family

This entry represents a group of fungal proteins, including Ecm3 and uncharacterised transporters from budding yeasts. The function of Ecm3 is not clear.
Non-specific endonuclease (Non-specific_endonuclease)
Type: Family

A family of bacterial and eukaryotic endonucleases

share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. A histidine has been shown to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.

This entry also includes Salivary proteins Tsal1 and Tsal2A, both high affinity nucleic acid binding proteins with residual nuclease activity and with a preference for dsDNA in a broad pH range.
Uncharacterized protein At4g02000-like (At4g02000-like)
Type: Family

This entry represents a group of plant proteins, including At4g02000. Their function is not clear.
FACT complex subunit Spt16 (Spt16)
Type: Family

This entry represents a the FACT complex subunit SPT16 from diverse eukaryotes . FACT is a general chromatin factor that acts to reorganise nucleosomes .
Mesogenin/MesP (Mesogenin/MesP)
Type: Family

This class C basic helix-loop-helix (bHLH) family of transcription factors consists of mesogenin and orthologues MesP1 (mesoderm posterior protein 1) and MesP2. Mesogenin is involved in specifying the paraxial mesoderm, which gives rise to all future trunk and limb skeletal muscles in vertebrates . MesP1 is expressed in the posterior part of the embryonic mesoderm and is expressed in cardiac progenitors during embryogenesis and required for cardiovascular development . Mesp2 plays a critical role in establishing the rostro-caudal patterning of each somite, as well as somite boundary formation .