SII-SWORD/CoKE huggingface dataset:
Alphavirus E2 glycoprotein, domain C (Alphavir_E2_C)
Type: Homologous_superfamily

Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses . Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 (

) that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. The proteolytic maturation of P62 into E2 and E3 (

) causes a change in the viral surface. Together the E1, E2, and sometimes E3 glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike . Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together . This entry represents the alphaviral E2 glycoprotein. The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor.

The E2 glycoproteins interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor. This is an all beta protein belonging to the immunoglobulin superfamily, with three immunoglobulin domains labelled A, B and C in amino- to carboxy-terminal order.

This superfamily represents the C-terminal domain, known as domain C, of the alphavirus E2 glycoprotein.
Reeler domain superfamily (Reeler_sf)
Type: Homologous_superfamily

The reeler or reelin domain is a ~170 amino acid module, which has been identified in the amino terminus of the extracellular matrix proteins reelin and F-spondin (renamed Spon1) . The reelin domain is found in association with other modules, such as the thrombospondin type I repeat (TSP1), the spondin domain, the fibronectin type III domain or the Kunitz trypsin protease inhibitor domain. Its function is not yet known .

Extracellular matrix (ECM) proteins play an important role in early cortical development, specifically in the formation of neural connections and in controlling the cyto-architecture of the central nervous system. The product of the reeler gene in mouse is reelin,a large extracellular protein secreted by pioneer neurons that coordinates cell positioning during neurodevelopment . F-spondin and mindin are a family of matrix-attached adhesion molecules that share structural similarities and overlapping domains of expression. Both F-spondin and mindin promote adhesion and outgrowth of hippocampal embryonic neurons and bind to a putative receptor(s) expressed on both hippocampal and sensory neurons .

Structurally, the reeler domain of F-spondin is composed of four-stranded and five-stranded antiparallel β-sheets that are arranged in a β-sandwich fold .
Helper-component proteinase (HC-Pro) cysteine protease (CPD) domain superfamily (HC_PRO_CPD_sf)
Type: Homologous_superfamily

Potyviruses form one of the most numerous groups of plant viruses and are a major cause of crop loss worldwide. The helper-component proteinase (HC-Pro) is an indispensable, multifunctional protein of members of the genus Potyvirus and other viruses of the family Potyviridae. It is directly involved in diverse steps of viral infection, such as aphid plant-to-plant transmission, polyprotein processing, and suppression of host antiviral RNA silencing. HC-Pro is generally divided into three functional domains: a N-terminal domain, a central region, and a cysteine protease domain (CPD) in the C-terminal region. The HC-Pro CPD domain has a protease activity that autocatalytically cleaves a Gly-Gly dipeptide at its own C terminus to release HC-Pro from the rest of the viral polyprotein. Cysteine and histidine residues form the catalytic dyad at the active site. The HC-Pro CPD domain constitutes the peptidase family C6 of the CA clan .

The HC-Pro CPD domain adopts a compact oval-shaped α/β fold. The secondary structure elements include four α-helices (alpha1-alpha4) and two short β-strands (beta1 and beta2) arranged in the order alpha1-alpha2-alpha3-beta1-beta2-alpha4. In addition, two 3(10) helices are located between alpha3 and beta1 and downstream of alpha4. The four helices form a helix bundle packed against one face of a short β-hairpin formed by strands beta1 and beta2. The catalytic residue Cys is located at the N terminus of helix alpha1, and the other catalytic residue His is located on strand beta2. The substrate binding cleft is lined by the loop connecting helices alpha2 and alpha3 and the N-terminal region of helix alpha1 on one side and by strand beta2 on the other side .

This superfamily represents the CPD domain of the HC-Pro protein.
Pestivirus envelope glycoprotein E2, domain A (Pestivirus_E2_A)
Type: Homologous_superfamily

Pestiviruses have an outer lipid envelope bearing two glycoproteins, E1 and E2, required for cell entry. E2 is an elongated molecule which consists of four domains (DA, DB, DC, DD), arranged linearly from N to C terminus. Domains DA and DB are the most distal from the viral membrane and are likely to be the most exposed on the virus surface. Both domains possess Ig-like folds, consistent with a cell-receptor binding function .

This superfamily represents the domain A (DA) of the Pestivirus envelope glycoprotein E2.
Pestivirus envelope glycoprotein E2, domain B (Pestivirus_E2_B)
Type: Homologous_superfamily

Pestiviruses have an outer lipid envelope bearing two glycoproteins, E1 and E2, required for cell entry. E2 is an elongated molecule which consists of four domains (DA, DB, DC, DD), arranged linearly from N to C terminus. Domains DA and DB are the most distal from the viral membrane and are likely to be the most exposed on the virus surface. Both domains possess Ig-like folds, consistent with a cell-receptor binding function .

This superfamily represents the domain B (DB) of the Pestivirus envelope glycoprotein E2. It is thought to play a role in the receptor interactions. Structurally, it consists of 7 β strands and 1 small α helix.
Pestivirus envelope glycoprotein E2, domain D (Pestivirus_E2_D)
Type: Homologous_superfamily

Pestiviruses have an outer lipid envelope bearing two glycoproteins, E1 and E2, required for cell entry. E2 is an elongated molecule which consists of four domains (DA, DB, DC, DD), arranged linearly from N to C terminus. Domains DA and DB are the most distal from the viral membrane and are likely to be the most exposed on the virus surface. Both domains possess Ig-like folds, consistent with a cell-receptor binding function .

This superfamily represents the domain D (DD) found at the C terminus of the Pestivirus envelope glycoprotein E2.
Uncharacterized protein F26C11.3-like (F26C11.3-like)
Type: Family

This entry represents a group of proteins from Nematoda, including F26C11.3 from C. elegans. Their function is not clear.
RELT-like protein 2 (RELL2)
Type: Family

RELT-like protein 2 (RELL2) belongs to the RELT family. Overexpression of RELL2 induces activation of MAPK14/p38 cascade .

RELT (receptor expressed in lymphoid tissues) is a member of the TNFR superfamily. The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and selectively binds tumor necrosis factor receptor-associated factor 1 . RELT like proteins 1 and 2 (RELL1 and RELL2) are two RELT homologues that bind to RELT. The expression of RELL1 at the mRNA level is ubiquitous, whereas expression of RELL2 mRNA is more restricted to particular tissues .
Transmembrane protein 121 (TMEM121)
Type: Family

The function of Transmembrane protein 121 (TMEM121) is not clear. It may play a role in MAPK signaling .
RELT-like protein 1 (RELL1)
Type: Family

RELT-like protein 1 (RELL1) belongs to the RELT family. Its overexpression induces activation of MAPK14/p38 cascade .

RELT (receptor expressed in lymphoid tissues) is a member of the TNFR superfamily. The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and selectively binds tumor necrosis factor receptor-associated factor 1 . RELT like proteins 1 and 2 (RELL1 and RELL2) are two RELT homologues that bind to RELT. The expression of RELL1 at the mRNA level is ubiquitous, whereas expression of RELL2 mRNA is more restricted to particular tissues .
IRK-interacting protein-like (IRKI-like)
Type: Family

This entry represents a group of plant proteins, including IRKI (At5g12900) from Arabidopsis .
F-box protein she-1-like (She-1-like)
Type: Family

This entry represents a group of proteins from Nematoda, including She-1 from Caenorhabditis briggsae. She-1 is a sex-determining factor which regulates hermaphrodite development .
Consortin (Consortin)
Type: Family

Consortin is a trans-Golgi network cargo receptor involved in targeting connexins to the plasma membrane .
Glycoprotein integral membrane protein 1 (GINM1)
Type: Family

The function of Glycoprotein integral membrane protein 1 (GINM1) is not clear.
Protein MMS22-like (MMS22-like)
Type: Family

Methyl methanesulfonate-sensitivity protein 22-like (MMS22L) is a component of the MMS22L-TONSL complex, a complex that stimulates the recombination-dependent repair of stalled or collapsed replication forks . The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication by promoting homologous recombination-mediated repair of replication fork-associated double-strand breaks . It may act by mediating the assembly of RAD51 filaments on ssDNA .
Integral inner nuclear membrane protein ima1 (Ima1)
Type: Family

This entry represents a group of proteins from fungi. Ima1 couples centromeres to the nuclear envelope, thus contributing to their association with the microtubule organizing centre attachment site and to the positioning of the nucleus at the cell centre by microtubules .
Protein Pbn1 (Pbn1)
Type: Family

This entry represents a group of fungal proteins, including Pbn1. It is a component of glycosylphosphatidylinositol-mannosyltransferase I that probably acts by stabilising the mannosyltransferase GPI14 (the catalytic component). Pbn1 is an essential endoplasmic reticulum membrane protein required for protein processing in the endoplasmic reticulum .
CTD kinase subunit gamma (Ctk3)
Type: Family

This entry represents Ctk3 from fungi.

CTDK-I complex is a three-subunit complex comprised of Ctk1, Ctk2, and Ctk3, that plays a key role in regulation of transcription and translation and in coordinating these two processes. Both Ctk2 and Ctk3 are regulated at the level of protein turnover, and are unstable proteins processed through a ubiquitin-proteasome pathway. Their physical interaction is required to protect both subunits from degradation, and both Ctk2 and Ctk3 are required for Ctk1 CTD kinase activation .
DASH complex subunit Hsk3 (Hsk3)
Type: Family

Hsk3 is a subunit of the DASH complex, a microtubule-binding complex that is transferred to the kinetochore prior to mitosis . In Saccharomyces cerevisiae DASH forms both rings and spiral structures on microtubules in vitro .
LRAD2/Mig-13-like (LRAD2/Mig-13-like)
Type: Family

The his entry includes Low-density lipoprotein receptor class A domain-containing protein 2 from human (LDLRAD2), whose function is unknown and Mig-13 (also known as abnormal cell migration protein 13) from C. elegans. Mig-13 is probably a receptor that acts as an upstream signalling protein to promote the guidance, migration and positioning of the right Q neuroblast (QR) and its descendants along the anteroposterior body axis, and also the anterior migration of BDU interneurons during larval development . It is involved in cytoskeleton dynamics regulating the organisation of the actin cytoskeleton at the leading edge of migrating cells to ensure correct Q cell polarity and promote migration .
Ankyrin repeat domain-containing protein 31 (ANKRD31)
Type: Family

This family includes Ankyrin repeat domain-containing protein 31 (ANKRD31) from mouse, similar sequences from eukaryotes and some uncharacterised proteins from bacteria. ANKRD31 is required for DNA double-strand breaks (DSBs) formation during meiotic recombination. It regulates the spatial and temporal patterns of pre-DSB recombinosome assembly and recombination activity by acting as a scaffold that anchors REC114 and other factors to specific genomic locations, thereby regulating DSB formation. This protein plays a key role in recombination in the pseudoautosomal regions of sex chromosomes .
Ankyrin repeat domain-containing protein 53 (ANKRD53)
Type: Family

Ankyrin repeat domain-containing protein 53 (ANKRD53) is recruited to the mitotic spindle by DDA3 and acts as a regulator of spindle dynamics and cytokinesis .
Golgi integral membrane protein 4 (GOLIM4)
Type: Family

GOLIM4 (Golgi integral membrane protein 4), also known as GPP130, is a cycling Golgi membrane protein . It serves as an endosome-to-Golgi trafficking receptor for the toxin .
Genetic suppressor element 1 (GSE1)
Type: Family

The function of Genetic suppressor element 1 (GSE1) is not clear.
Tumor necrosis factor ligand superfamily member 4 (TNFSF4)
Type: Family

TNFSF4 (also known as OX40L) is a cytokine that binds to its unique receptor, TNFRSF4 .

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
Lymphocyte antigen 6D (Ly6D)
Type: Family

Lymphocyte antigen 6D (Ly6D) can serve as a specification marker at earliest stage specification of lymphocytes between B- and T-cell development .
High affinity immunoglobulin epsilon receptor subunit gamma (FCER1G)
Type: Family

The high affinity immunoglobulin epsilon receptor (IgE Fc receptor) subunit gamma associates with a variety of FcR alpha chains to form a functional signaling complex. The gamma subunit has a critical role in allowing the IgE Fc receptor to reach the cell surface and regulates several aspects of the immune response . It has significant structural homology to CD3 zeta and the related CD3 eta subunit and can facilitate T cell receptor expression and signaling in the absence of CD3 zeta and CD3 eta .
B-lymphocyte antigen CD19 (CD19)
Type: Family

CD19 is a component of a cell surface receptor complex that play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival .

Mutations in the CD19 gene cause immunodeficiency, common variable, 3 (CVID3), a primary immunodeficiency characterised by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen .
Tetratricopeptide repeat protein 22 (TTC22)
Type: Family

The function of Tetratricopeptide repeat protein 22 (TTC22) is not clear.
Protein BANP (BANP)
Type: Family

BANP, also known as SMAR1, is a scaffold/matrix attachment region-binding protein that regulates gene expression by binding to various promoter elements . It has been shown to recruit a repressor complex to the cyclin D1 promoter that results in deacetylation of chromatin at that locus . It has also been shown to regulate alternative splicing via HDAC6-mediated deacetylation of Sam68 .
Zinc finger CCHC domain-containing protein 14 (ZCCHC14)
Type: Family

The function of Zinc finger CCHC domain-containing protein 14 (ZCCHC14) is not clear.
BTB/POZ domain-containing protein 7 (Btbd7)
Type: Family

BTB/POZ domain-containing protein 7 (BTBD7) is a crucial regulator that is essential for region-specific epithelial cell dynamics and branching morphogenesis, especially for branching of embryonic mammalian salivary glands and lungs . It has been implicated in various cancers . BTBD7 contains two BTB domains and a BACK domain.
Uncharacterized protein C9orf40-like (C9orf40-like)
Type: Family

This entry represents a group of vertebrate proteins, including C9orf40 from humans. Their function is not clear.
All-trans retinoic acid-induced differentiation factor (ATRAID)
Type: Family

ATRAID (All-trans retinoic acid-induced differentiation factor), also known as APR3, is a membrane protein that functions as a proliferation suppressor. It plays a role in inducing the cell cycle arrest via inhibiting CCND1 expression in all-trans-retinoic acid (ATRA) signal pathway .
Uncharacterized protein C3orf18-like (C3orf18-like)
Type: Family

This entry represents a group of animal proteins, including C3orf18 from humans. Their function is not clear.
EF-hand calcium-binding domain-containing protein 14 (EFCAB14)
Type: Family

The function of EF-hand calcium-binding domain-containing protein 14 (EFCAB14) is not clear.
Probable G-protein coupled receptor 160 (GPR160)
Type: Family

Probable G-protein coupled receptor 160 (GPR160) is an orphan receptor from G-protein coupled receptors (GPCRs) family. The function of GPR160 is not clear. It has been linked to apoptosis and cell cycle arrest of prostate cancer cells .
F-box only protein 38 (FBX38)
Type: Family

F-box only protein 38 (FBX38) is an E3 ubiquitin ligase that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation of PD-1, an immune checkpoint mediator and negative regulator of T cell-mediated immunity .
IGF-like family receptor 1 (IGFLR1)
Type: Family

IGF-like family receptor 1 (IGFLR1), previously known as TMEM149, is a cell membrane receptor for the IGF-like family proteins, such as IGFL1 and IGFL3 .
Claudin domain-containing protein 1 (CLDN1)
Type: Family

The function of Claudin domain-containing protein 1 (CLDN1) is not clear. It belongs to the claudin family, which comprises four-pass transmembrane proteins involved in the formation of tight junctions (TJs) .
WAP four-disulfide core domain protein 1 (WFDC1)
Type: Family

WAP four-disulfide core domain protein 1 (WFDC1), also known as ps20, has been implicated in epithelial cell behaviour and angiogenesis . It has been linked to prostate cancer .
Filensin (BFSP1)
Type: Family

Filensin (also known as BFSP1) is a lens-specific cytoskeletal protein that interacts with aquaporin-0 (AQP0). It plays an important role during lens development . Mutations of the Filensin gene cause Cataract 33, multiple types (CTRCT33), an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness .
Telomere repeats-binding bouquet formation protein 1 (TERB1)
Type: Family

Telomere repeats-binding bouquet formation protein 1 (TERB1) is a TRF1-binding protein that promotes chromosome movement and telomere rigidity in meiosis . Disruption of the TRF1-TERB1 interaction has been shown to result in failure of spermatogenesis . The structure of TERB1 has been revealed .
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2)
Type: Family

Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2), also known as multisynthase complex auxiliary component p38, is required for assembly and stability of the multi-tRNA synthetase complex (MSC complex) . MSC is a macromolecular protein complex consisting of nine different ARSs and three ARS-interacting multifunctional proteins (AIMPs) .
Z-DNA-binding protein 1 (ZBP1)
Type: Family

Z-DNA-binding protein 1 (ZBP1), also known as DAI (DNA-dependent activator of IFN regulatory factors), is a cytosolic DNA sensor that activates the innate immune system .
Z-binding domain (Z_dom)
Type: Domain

Double-stranded (ds) DNA typically adopts the so-called B-conformation, while dsRNA is usually in the A-conformation. Both DNA and RNA can also adopt a Z-form double helix that is characterised by a left-handed helical arrangement, a zigzag pattern of the phosphodiester backbone and the absence of major grooves. Z-DNA is believed to play a role in transcription by relieving torsional strain induced within the DNA template by the movement of RNA polymerases, and Z-DNA may also promote genetic instability. Physiological functions of Z-RNA remain unknown. This entry represents the Z-binding domain (ZBD), also referred to as Zalpha or Zbeta, which is a 78-amino-acid protein fold that specifically binds to Z-DNA as well as to Z-RNA but not to B-DNA. ZBDs have been identified in four proteins: ADAR1, ZBP1, E3L and PKZ. ADAR1 and ZBP1 are mammalian proteins implicated in antiviral innate immune responses. E3L is a poxvirus protein known to antagonise this host response. Lastly, PKZ is a fish protein related to mammalian PKR, also involved in antiviral immunity. This suggests an important role of ZBDs in innate antiviral immune responses and may imply that Z-DNA and/or Z-RNA trigger such a host defense response .

The Z-binding domain displays an α/β architecture with three α-helices packed against three antiparallel β-strands (

). It belongs to the winged helix-turn-helix (wHTH) domain superfamily. The three helices form the core of the domain, with helices 2 and 3 forming the helix-turn-helix unit. Helix 1 is joined to helix 2 by a β-strand, beta1. C-terminal to helix 3 is the 'wing', formed by two antiparallel β-strands (β2 and β3), which hydrogen bond to each other and to beta1, forming a three-stranded β-sheet .
Interleukin-15 receptor subunit alpha (IL15RA)
Type: Family

IL-15 receptor (IL-15R) composed of IL-15Ralpha, IL-2/15Rbeta (CD122), and gamma(c) (CD132) subunits . IL-15 is a cytokine that plays an important role in innate and adaptive immunity . Syk kinase interacts with IL-15Ralpha and may play a key role in mediating IL-15-induced signal transduction .
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)
Type: Family

TNFSF9, also known as 4-1BBL, is a member of the tumor necrosis factor (TNF) superfamily and is the ligand for the TNFR superfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells. Human h4-1BB has been targeted with agonists in cancer immunotherapy. The structure of 4-1BBL has be revealed .
CD70 antigen (CD70)
Type: Family

CD70 is a ligand of CD27 and is a TNF related transmembrane protein induced upon activation on T and B cells . The CD27/CD70 interaction plays a key role in T dependent B cell responses and is responsible for plasma cell differentiation . The CD27/CD70 pathway has been shown to contribute to the pathophysiology of autoimmunity .
A-kinase anchor protein 5 (AKAP5)
Type: Family

A-kinase anchor protein 5 (AKAP5), also known as AKAP79, is a PKA anchoring protein that binds to adenylyl cyclase type 8 (AC8) and to regulate its responsiveness to store-operated Ca(2) entry (SOCE) . The AKAP79 and AC8 interaction may occur in lipid raft domains of the plasma membrane, with palmitoylation of AKAP79 plays an important role in targeting the AKAP to the cholesterol- and sphingolipid-rich regions of the plasma membrane where it can impact on local Ca2 -stimulated AC8 activity .
Mediator of RNA polymerase II transcription subunit 26 (MED26)
Type: Family

MED26 is a subunit of Mediator, a complex involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. MED26 plays a role in the switch between the initiation and elongation phases of RNA Polymerase II-mediated transcription process .