SII-SWORD/CoKE huggingface dataset:
Ceroid-lipofuscinosis neuronal protein 6 (CLN6)
Type: Family

Mutations in CLN6 (ceroid-lipofuscinosis neuronal protein 6) cause variant late-onset neuronal ceroid lipofuscinosis (vLINCL), a childhood neurodegenerative disorder (CLN6). Alterations in neurite maturation resulting from a loss of CLN6 interaction with protein CRMP2, which has been implicated in controlling axon number and outgrowth, may contribute to this neuronal pathology . A link between CLN6 expression and biometal homeostasis has been suggested .
Helicase-associated putative binding domain (Heliccase-ass-bd)
Type: Domain

The function of this short, serine-rich region is not known. However, as it is frequently found at the C terminus of P-loop containing nucleoside triphosphate hydrolases. It might be a binding domain.
Rab3GAP regulatory subunit, C-terminal (RAB3GAP2_C)
Type: Domain

This entry represents the C terminus of the Rab3 GTPase-activating protein non-catalytic subunit.

Small G proteins of the Rab family are regulators of intracellular vesicle traffic. Their rate of GTP hydrolysis is enhanced by specific GTPase-activating proteins (GAPs) that switch G proteins to their inactive form . Rab3GAP1 (catalytic subunit) has been shown to form a heterodimeric complex with Rab3GAP2 (the regulatory subunit), and this complex acts as a guanosine nucleotide exchange factor for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3GAP complex may participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters . It also activates Rab18 and promotes autolysosome maturation through the Vps34 Complex I .

Mutations in the Rab3GAP1/2 gene cause Warburg micro syndrome (WMS), a hereditary autosomal neuromuscular disorder .
Rapamycin-insensitive companion of mTOR, phosphorylation-site (RICTOR_phospho)
Type: PTM

The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that forms two functionally distinct complexes, mTORC1 and mTORC2, important for nutrient- and growth-factor signalling . Rictor (rapamycin-insensitive companion of mTOR) is an essential component of the complex mTORC2 . It appears to serve as a scaffolding protein important for maintaining mTORC2 integrity. Rictor interacts with 14-3-3 in a Thr1135-dependent manner . Rictor can be inhibited by short-term rapamycin treatment, showing that Thr1135 is an mTORC1-regulated site .

This short region is the phoshorylation site of Rictor.
Dual specificity/tyrosine protein phosphatase, N-terminal (DSPn)
Type: Domain

The active core of the dual specificity protein phosphatase is made up of two globular domains both with the DSP-like fold. These domains are arranged in tandem, and are associated via an extensive interface to form a single globular whole.

The conserved PTP signature motif (Cys-[X]5-Arg) that defines the catalytic centre of all PTP-family members is located within the C-terminal domain, DSPc (

). Although the centre of the catalytic site is formed from DSPc, two loops from the N-terminal domain, DSPn, also contribute to the catalytic site, facilitating peptide substrate specificity .

This domain represents the N-terminal half of the core (DSPn).
Transposase IS204/IS1001/IS1096/IS1165, zinc-finger (Transposase_Znf)
Type: Domain

This entry represents a zinc-finger domain found in transposases for insertion sequence IS204, IS1001, IS1096 and IS1165.
DNA-directed RNA polymerase, N-terminal (RPOL_N)
Type: Domain

This is the N-terminal domain of DNA-directed RNA polymerase. This domain has a role in interaction with regions of upstream promoter DNA and the nascent RNA chain, leading to the processivity of the enzyme . In order to make mRNA transcripts the RNA polymerase undergoes a transition from the initiation phase (which only makes short fragments of RNA) to an elongation phase. This domain undergoes a structural change in the transition from initiation to elongation phase. The structural change results in abolition of the promoter binding site, creation of a channel accommodating the heteroduplex in the active site, and formation of an exit tunnel which the RNA transcript passes through after peeling off the heteroduplex .
Respiratory nitrate reductase beta, C-terminal (Nitr_red_bet_C)
Type: Domain

This domain occurs near the C terminus of the respiratory nitrate reductase beta chain. The nitrate reductase complex is a dimer of heterotrimers each consisting of an alpha, beta and gamma chain. This domain plays a role in the interactions between subunits and shielding of the Fe-S clusters .
ARF7 effector protein, C-terminal (ARF7EP_C)
Type: Domain

This domain represents the C terminus of the ARF7 effector protein (ARF7EP), also known as ARL14 effector protein. ARF7EP interacts with actin based motor protein myosin 1E (MYO1E) and may be involved in connecting MHC class II-containing cytoplasmic vesicles to the actin network in dendritic cells . It contains a conserved CXCXXXXCXXCXXXCXXCXXXXCXXXCXC motif in its C-terminal half.
Transmembrane protein 51 (TMEM51)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 233 and 253 amino acids in length.
FAM217 family (FAM217)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 329-507 amino acids in length and contain a conserved YPDFLP sequence motif.
FAM212 domain (FAM212)
Type: Domain

This entry represents a domain found in the Inka proteins, including Inka1 and Inka2. They are inhibitors of PAK4, a metazoan-specific kinase acting downstream of Cdc42 . Danio rerio (Zebrafish) Inka1 is required for the proper migration of neural crest cells during embryonic development .
Small muscular protein Chisel (Chisel)
Type: Family

Chisel protein plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. The X-linked gene Chisel (Csl/Smpx) was first found expressed selectively in human cardiac and skeletal muscle cells . It is expressed in embryos in sub-regions of the developing heart corresponding to the future chamber myocardium and in developing skeletal muscles . It is a potential target of the cardiac homeodomain transcription factor Nkx2-5 . It localises to the costameric cytoskeleton of muscle cells through its association with focal adhesion proteins, where it may participate in regulating the dynamics of actin through the Rac1/p38 kinase pathway .
Putative treble-clef, zinc-finger domain (Zf-tcix)
Type: Domain

This entry represents a domain found in eukaryotic proteins. It resembles the zinc-binding domain of prokaryotic topoisomerases,

.
Limb expression 1 (LIX1)
Type: Family

This entry represents the limb expression 1 (LIX1) family. LIX1 was identified in a screen for genes transiently expressed during early chicken limb development . It has homologues in human, mouse and Drosophila.
Psoriasis susceptibility 1 candidate gene 2 protein (SPR1)
Type: Family

This entry represents SPR1, which is the psoriasis susceptibility locus 2 protein . Its function is not clear.
Coiled-coil domain-containing protein 7 (CCDC7)
Type: Family

This entry represents the coiled-coil domain-containing protein 7 (also known as BioT2), which is a testis-specific protein found abundantly in five types of murine cancer cell lines. It may play a role in testis development and tumourigenesis .
Cdc42 effector-like (Cdc42_effect-like)
Type: Domain

The Rho-type GTPase Cdc42 regulates cell morphology and signal transduction in eukaryotic cells. The Cdc42 effector (CEP) or binder of Rho GTPase (BORG) proteins are involved in the organisation of the actin cytoskeleton . They may function as negative regulators of Rho GTPase signaling .

This entry consists of Cdc42 effector proteins, including CEP1-5 from humans.
Protein of unknown function DUF4615 (DUF4615)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 161 and 229 amino acids in length. There is a single completely conserved residue F that may be functionally important.
Trimeric autotransporter adhesin, putative GIN domain (HiaBD2_put_GIN_domain)
Type: Domain

This represent the GIN (Gly-Ile-Asn) domain of the Head region of TAAs - trimeric autotransporter adhesins. Not all TAAs carry this domain; however, in those that do, the GIN in combination with the Trp-ring domain is necessary for adhesion to fibronectin in the host cell .
Plasminogen-binding protein PgbA, N-terminal (PgbA_N)
Type: Domain

This entry represents the N-terminal domain of the bacterial proteins (PgbA) that bind plasminogen. This activity was identified in In Helicobacter pylori where it is thought to contribute to the virulence of this bacterium. Both PgbA and PgbB are surface-exposed proteins that mediate binding to plasminogen such that it can be converted into plasmin in the presence of a Pg activator .
Single domain Von Willebrand factor type C domain (SVWC_dom)
Type: Domain

This entry represents the von Willebrand factor type C (SVWC) domain. The canonical pattern of most von Willebrand factor type C (VWC) domains is of ten cysteines, however proteins in this entry, largely but not exclusively of arthropod proteins, contains only eight. SVWC domain containing proteins respond to environmental challenges, such as bacterial infection and nutritional status. They also are involved in anti-viral immunity, and all of these functions seem linked to SVWC expression being induced by Dicer2 .
Immunity protein 26 (Imm26)
Type: Family

This entry represents a predicted immunity protein with mostly all-β fold and several conserved hydrophobic residues. They are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, usually containing a domain of the Tox-URI1 or Tox-HNH family . The protein is also found heterogeneous polyimmunity loci.
FLYWCH-type zinc finger-containing protein, N-terminal (FLYWCH_N)
Type: Domain

This entry represents the N terminus of some FLYWCH-zinc-finger proteins, found in eukaryotes. The family is found in association with

. There are two conserved sequence motifs: EQE and QEPS.
Leukemia NUP98 fusion partner 1 (LNP1)
Type: Family

This family of proteins includes leukemia NUP98 fusion partner 1, the gene encoding this protein is involved in a chromosomal translocation with the NUP98 locus in a form of T-cell acute lymphoblastic leukemia .
FAM194, C-terminal (FAM194_C)
Type: Domain

This domain can be found in a group of uncharacterised proteins, including FAM194A, FAM194B and C3orf20. They are approximately 210 amino acids in length and have a conserved YPSG sequence motif. The function of this domain is unknown.
Equatorin (Eqtn/Afaf)
Type: Family

Equatorin (also known as Afaf) is an acrosomal membrane-anchored protein involved in membrane trafficking during acrosome formation and participate in fertilisation . In mice, it is localised in the inner and outer membrane of forming acrosomes (Acrs), and declined in the maturing Acrs .
Calcium-dependent cell adhesion molecule 1, membrane-binding domain (Membrane-bd)
Type: Domain

This domain is found at the C terminus of Dictyostelium discoideum Calcium-dependent cell adhesion molecule, which has an immunoglobulin-like fold . It tethers the protein to the cell membrane. Calcium-dependent cell adhesion molecule 1 mediates calcium-dependent cell-cell adhesion during the early stage of development .
p53-regulated apoptosis-inducing protein 1 (TP53AIP1)
Type: Family

The expression of the TP53AIP1 (p53-regulated apoptosis-inducing protein 1) protein is induced by wild-type p53. Ectopically expressed TP53AIP1, which is localised within mitochondria, leads to apoptotic cell death through dissipation of mitochondrial A(psi)m. Phosphorylation of p53 Ser-46 regulates the transcriptional activation of TP53AIP1, thereby mediating p53-dependent apoptosis .
CagY type 1 repeat (CagY_I)
Type: Repeat

This repeat is found at the N terminus of the CagY proteins - part of the CAG pathogenicity island - and involved in delivery of the protein CagA into host cells .
Aurora kinase A- and ninein interacting protein (AUNIP)
Type: Family

Aurora kinase A- and ninein-interacting protein (also known as AIBp or AUNIP) is a family of eukaryotic proteins necessary for the adequate functioning of Aurora-A, a protein involved in chromosome alignment, centrosome maturation, mitotic spindle assembly and aspects of tumourigenesis. AIBp is likely to act as a regulator of Aurora-A activity . It interacts with with AURKA via its C terminus and interacts with NIN via its N terminus .
Retinoic acid early-inducible protein 1 (RAE-1)
Type: Domain

Members of this group are known as retinoic acid early inducible proteins (RAE-1) . They are ligands for the activating immunoreceptor NKG2D, which is widely expressed on natural killer cells, T cells, and macrophages . There is a considerable diversity of NKG2D ligands. In mice, the ligands include, among others, five members of the retinoic acid early inducible gene 1 (RAE-1; α-ε) .

RAE-1 proteins are distant major histocompatibility complex (MHC) class I homologues, comprising isolated alpha1-alpha2 platform domains .
Protein of unknown function DUF4607 (DUF4607)
Type: Family

This entry represents a group of a eukaryotic proteins that are typically between 207 and 359 amino acids in length.
Coordinator of PRMT5 and differentiation stimulator (COPR5)
Type: Family

Coordinator of PRMT5 and differentiation stimulator (also known as COPRS or COPR5) is a histone-binding protein required for histone H4 methyltransferase activity of PRMT5, which targets nuclear and cytoplasmic proteins. COPR5 is specifically required for histone H4 'Arg-3' methylation mediated by PRMT5, but not histone H3 'Arg-8' methylation, suggesting that it modulates the substrate specificity of nuclear PRMT5-containing complexes, at least towards histones. Recombinant COPR5 binds to the N-terminal of histone H4 and is required to recruit PRMT5 to reconstituted nucleosomes in vitro .
TP53-target gene 5 protein (TP53TG5)
Type: Family

The tumour suppressor TP53 gene (encoding cellular tumour antigen p53 or p53) is the most frequently altered gene in human tumours. TP53-target gene 5 protein (also known as cellular tumour antigen p53-inducible 5) suppresses cell growth and may play a significant role in p53/TP53-mediating signalling pathway. Its intracellular location and expression change in a cell-cycle-dependent manner .
DNA binding protein Tfx, C-terminal (Tfx_C)
Type: Domain

Tfx has an N-terminal basic domain with a helix-turn-helix motif for DNA binding and a C-terminal acidic domain possibly for transcriptional activation . This is the C-terminal region of Tfx-like DNA-binding proteins.
Methylated in normal thymocytes protein (MENT)
Type: Family

This entry represents protein MENT (methylated in normal thymocytes protein), which is involved in control of cellular proliferation. It is an onconcogenic modifier contributing to the tumour suppressor function of DNMT3B (DNA methyltransferase 3B) . This entry also includes the mouse Pmis1 protein that may regulate sperm transport into the oviducts and function in modulating sperm-zona binding .
Rad9, Rad1, Hus1-interacting nuclear orphan protein 1 (RHNO1)
Type: Family

This entry represents Rad9, Rad1, Hus1-interacting nuclear orphan protein 1 (RHINO or RHNO1), which plays a role in DNA damage response (DDR) signalling upon genotoxic stresses such as ionizing radiation (IR) during the S phase . RHNO1 is recruited to sites of DNA damage through interaction with the Rad9-Rad1-Hus1 (9-1-1) complex and ATR activator TopBP1. It plays a role in ATR-mediated activation of Chk1 driven by TopBP1 and 9-1-1 . It is involved in mammary carcinogenesis .
Helically-extended SH3 domain (hSH3)
Type: Domain

This domain corresponds to the 70 C-terminal residues of ADAP - Adhesion and de-granulation promoting adapter protein, also known as FYN-binding protein. This domain shows homology to SH3 domains; however, conserved residues of the fold are absent. It thus represents an altered SH3 domain fold. An N-terminal, amphipathic, helix makes extensive contacts to residues of the regular SH3 domain fold thereby creating a composite surface with unusual surface properties. The domain can no longer bind conventional proline-rich peptides . There are key phosphorylation sites within the two hSH3 domains and it would appear that binding at these sites does not materially affect the folding of these regions although the equilibrium towards the unfolded state may be slightly altered . Instead, the hSH3 domain functions as a novel lipid interaction domain and can bind acidic lipids such as phosphatidylserine, phosphatidylinositol, phosphatidic acid, and polyphosphoinositides .
Snf2, ATP coupling domain (SnAC)
Type: Domain

This domain lies within the catalytic subunit (Snf2) of the yeast SWI/SNF chromatin remodelling complex. It binds histones and is required for mobilising nucleosomes . This domain is conserved and can also be found in Snf2 homologues, such as Sth1 .
Putative Bcl-2 like protein of testis (Bcl-2-like_put)
Type: Family

This entry represents a group of mammalian proteins. This entry includes the human C20orf144 protein, which is a Bcl-2-like protein preferentially expressed in the testis.
Spermatogenesis-associated protein 32 (SPATA32)
Type: Family

Spermatogenesis-associated protein 32 (SPATA32, also known as VAD1-2) is expressed in testis and may be involved in acrosome formation during spermiogenesis . VAD1-2 can be detected in the acrosome region of the round and elongated spermatids of mouse, human, monkey and pig. Putative interacting partners syntaxin 1, beta-actin, and myosin heavy chain (MHC) protein were identified from the co-immunoprecipitation experiments .
RFX5, C-terminal (RFX5_C)
Type: Domain

Transcription of all the members of MHCII family of genes is controlled by a set of conserved transcription factors and promoter elements. One of these class II transactivators is the DNA-binding RFX complex, which consists of subunits RFX5 and its accessory proteins RFXAP and RFXANK .

This entry represents the C-terminal domain of RFX5. The C-terminal domain mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters .
ALMS motif (ALMS_motif)
Type: Domain

This domain is found at the C terminus of centrosome-associated protein ALMS1, centrosomal protein of 295 kDa (CEP295, also known as KIAA1731) and (E2-independent) E3 ubiquitin-conjugating enzyme FATS (also known as C10orf90) . These proteins play a role in centrosomal functions. ALMS1 is implicated in ciliary function, cell cycle control, and intracellular transport. It interacts with alpha-actinin and components of the endosomal recycling pathway . CEP295 is a centriole-enriched microtubule-binding protein involved in centriole biogenesis, essential for the generation of the distal portion of newborn centrioles and recruitment of centriolar proteins, such as POC1B, POC5 and CEP135 .

Centrosome-associated protein Alms1a, the Drosophila homologue of centrosome-associated protein ALMS1, plays critical role in ensuring centrosome duplication in asymmetrically dividing germline stem cells (GSCs), which is essential for the production of centrosomes and centrioles in all downstream germ cells . This domain directly interacts with Klp10, a microtubule-depolymerizing kinesin of kinesin-13 family, at GSC centrosome . Alms1a might recruit SAK for daughter centriole duplication .
CEP170, C-terminal (CEP170_C)
Type: Domain

This entry represents the C terminus of centrosomal protein of 170kDa (CEP170) .

Centrosomal protein of 170kDa (Cep170) plays a role in microtubule organisation . Human Cep170 is constantly expressed throughout the cell cycle, but phosphorylated during mitosis. Cep170 is a substrate of Polo-like kinase 1 (Plk1) . It is associated with the mature mother centriole. Cep170 is also required for Kif2b-induced microtubule depolymerisation .
Sperm acrosome-associated protein 7 (SPACA7)
Type: Family

Sperm acrosome associated 7 (SPACA7) is expressed only in testis. Its release from the acrosome accelerates the dispersal of cumulus cells surrounding the oocyte and facilitates fertilisation in mice .
Intraflagellar transport protein 43 (IFT43)
Type: Family

Intraflagellar transport protein 43 (IFT43) is a subunit of the IFT complex A (IFT-A), which is involved in retrograde ciliary transport along microtubules from the ciliary tip to the base .
Capsular polysaccharide assembling protein CapF, C-terminal domain (CapF_C)
Type: Domain

This domain is found at the C-terminal end of proteins homologous to Staphylococcus aureus CapF (also known as WbjC in Pseudomonas aeruginosa and FnlB in Escherichia coli). CapF is a bifunctional metalloenzyme produced by certain pathogenic bacteria and is essential in the biosynthetic path of capsular polysaccharide (CP), a mucous layer on the surface of bacterium that facilitates immune evasion and infection. CapF is an antibacterial/therapeutic target. In S. aureus, enzymes CapE, CapF and CapG catalyse the sequential transformation of UDP-D-GlcNAc in the CP precursor UDP-L-FucNAc via the intermediate compound UDP-N-acetyl-L-talosamine (UDP-L-TalNAc) . CapF consists of two domains; the C-terminal cupin-like domain catalyses the epimerisation of the compound produced by the upstream enzyme CapE, and the N-terminal short-chain dehydrogenase/reductase (SDR) domain catalyses the reduction of the compound afforded by the cupin domain, requiring one equivalent of NADPH. The cupin domain is crucial for catalysing the first chemical reaction, and also important for the stability of the enzyme . Similarly, in P. aeruginosa, WbjC, WbjB and WbjD enzymes synthesise UDP-N-acetyl-L-reexamine, a precursor of the lipopolysacharide component L-fucosamine . The N-terminal domain adopts a Rossmann fold and the cupin domain contains a typical "jelly roll-like" β-barrel fold .
A-kinase anchor protein 2, C-terminal domain (AKAP2_C)
Type: Domain

This domain is found at the C terminus of A-kinase anchor protein 2 (AKAP2). It includes the site where the regulatory subunits (RII) of protein kinase AII binds .

Besides AKAP2, proteins containing this domain include mitotic interactor and substrate of PLK1 (Misp) and uncharacterised protein LOC113230.
FANCI solenoid 1 cap (FANCI_S1-cap)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This entry represents the solenoid 1 cap (S1-cap) domain of the Fanconi anemia complementation group I protein (FANCI).
E3 ubiquitin-protein ligase Arkadia, N-terminal (RNF111_N)
Type: Domain

This domain is found at the N terminus of E3 ubiquitin-protein ligase Arkadia. Arkadia plays a role in embryonic development . Proteins containing this domain also include ARK2N (C18orf25) from humans, the closest homologue of Arkadia, a novel exercise-regulated AMPK substrate that lacks the entire RING domain, suggesting that it lacks ubiquitination activity .
INTS6/SAGE1/DDX26B/CT45, C-terminal (INT_SG_DDX_CT_C)
Type: Domain

This domain is found at the C terminus of integrator complex subunit 6 (INTS6) , sarcoma antigen 1 (SAGE1) , protein DDX26B and members of the cancer/testis antigen family 45 .
FANCI solenoid 1 domain (FANCI_S1)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the solenoid 1 (S1) domain of the Fanconi anemia group I protein (FANCI).