SII-SWORD/CoKE huggingface dataset:
Multiple myeloma tumor-associated protein 2-like, N-terminal (MMTA2_N)
Type: Domain

This entry represents a glycine-rich domain found in MMTA2 (multiple myeloma tumor-associated protein 2). The region may contain nuclear localisation signals, so it might act as a signal molecule in the nucleus .
G8 domain (G8_domain)
Type: Domain

This entry represents a domain found in disease proteins PKHD1 and CEMIP2 (also known as KIAA1199) and is named G8 after its 8 conserved glycines. It is predicted to contain 10 β-strands and an α-helix . CEMIP2 is an inactive cell surface hyaluronidase that, unlike its mouse orthologue, has no catalytic hyaluronic acid-degrading activity, but acts as a regulator of hyaluronan (HA) metabolism through regulation of expression of CEMIP and HAS2, two enzymes involved in HA depolymerization and HA synthesis, respectively .
Membrane protein BRI3 (BRI3)
Type: Family

This is a highly conserved set of proteins which contains three pairs of cysteine residues within a length of 42 amino acids and is rich in proline residues towards the N terminus. It includes a membrane protein that has been found to be highly expressed in the mouse brain and consequently, several members have been assigned as BRI3 or brain protein i3 . Their function is unknown but they appear to play a role in TNF-induced cell death . They may be a target of Wnt/beta-catenin signalling in the liver .
Guanine nucleotide exchange factor, Ric8 (Gua_nucleotide_exch_fac_Ric8)
Type: Family

Ric8 (also known as Synembryn) is a chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity . It is involved in the regulation of the microtubule pulling forces during the mitotic movement of chromosomes and in the EGL-30 neurotransmitter signalling pathway . It is also a guanine nucleotide exchange factor that regulates neurotransmitter secretion.
Plasminogen receptor (KT) (Plg-R(KT))
Type: Family

Plg-R(KT) is a receptor for plasminogen and is involved in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response . It is essential for mammary lobuloalveolar development and lactation .
BLOC-1-related complex subunit 8 (BORCS8)
Type: Family

BORC is a multisubunit complex that regulates the positioning of lysosomes at the cell periphery, and consequently affects cell migration. BORC associates with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a series of interactions that promote the microtubule-guided transport of lysosomes toward the cell periphery .

The BORC complex consists of 8 subunits. This family represents subunit 8.
Nucleoporin Nup88 (Nucleoporin_Nup88)
Type: Family

Nup88 can be divided into two structural domains; the N-terminal two-thirds of the protein have no obvious structural motifs. It is, however, where it binds to Nup98; one of the components of the nuclear pore. The C-terminal end is a predicted coiled-coil domain . Nup88 is over expressed in tumour cells . This protein family includes human Nup88 and similar eukaryotic proteins, including its fission yeast orthologue Nup82.
Mitochondrial import inner membrane translocase subunit Tim29 (TIMM29)
Type: Family

This entry includes mitochondrial import inner membrane translocase subunit Tim29 (TIMM29), which is a component of the TIM22 complex. The TIM22 complex imports and inserts multi-pass transmembrane proteins into the mitochondrial inner membrane by formation of a twin-pore translocase with components in the outer and inner membranes. TIM29 is integrated into the inner member with the C terminus exposed to the intermembrane space and able to contact the translocase of the outer membrane. It is required for complex stability and for the addition of the TIMM22 protein to the complex .
Active zone protein ELKS (ELKS/CAST)
Type: Family

The active zone is the presynaptic region in the nerve terminals that mediates neurotransmitter release and is composed a dense collection of proteins called the cytomatrix at the active zone (CAZ). The CAZ proteins are thought to mediate synapse formation and regulate neurotransmitter release .

This entry represents the ELKS family, which are thought to be involved in the organisation of CAZ. Vertebrate ELKS proteins are produced by two genes, ERC1 and ERC2. Caenorhabditis elegans expresses a homologue of ELKS that acts downstream of syd2/liprin-alpha during active zone assembly . Drosophila melanogaster expresses a related protein termed bruchpilot (brp) that consists of a conserved N terminus and a C-terminal half with no homologous sequences in vertebrates. Brp is required for structural integrity and function of synaptic active zones . Vertebrate ELKS proteins are enriched at presynaptic active zones and support Ca2+ influx at nerve terminals of inhibitory hippocampal neurons . They have a C-terminal PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). These proteins also contain four coiled-coil domains .
M-phase phosphoprotein 6 (MPP6)
Type: Family

This entry describes M-phase phosphoprotein 6 (MPP6), which is involved in generation of the 3' end of the 5.8S rRNA precursor . MPP6 is required for the integrity maintenance of the rRNA processing complex as it mediates the interaction between MTR4 (RNA helicase) and RRP6 (an 3'-5' exonuclease), and the recruitment of Nuclear VCP-like 2 (NVL2) to the nuclear exosome .
NEDD4/Bsd2 (NEDD4/Bsd2)
Type: Family

Proteins in this entry include the human NEDD4 family-interacting protein 1/2 (Ndfip1 and Ndfip2) and the yeast Bsd2 metal homeostasis proteins.

Ndfip1 and Ndfip2 are endosomal membrane proteins that bind to and activate members of the Nedd4 family of E3 ubiquitin ligases . Ndfip1 plays a role in regulating metal transport in human neurons .
Protein NDNF (NDNF)
Type: Family

NDNF (neuron-derived neurotrophic factor) is a glycosylated, disulfide-bonded secretory protein that contains fibronectin type III domains and two predicted N-linked glycosylation sites . It is expressed in brain and spinal cord that promotes migration and neurite growth. It acts as a modulator that promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms .
WKF domain (WKF)
Type: Domain

This entry represents a domain found in a family of proteins found from fungi and animals. The domain is named WKF after a conserved sequence motif. This domain has been shown to bind RNA .
Phosphatidylinositol N-acetylglucosaminyltransferase subunit H, conserved domain (PIGH-H_dom)
Type: Domain

This entry represents a conserved domain found in PIG-H proteins. This entry also includes the PIG-H homologues from S. cerevisiae and S. pombe Gpi15 .

Phosphatidylinositol N-acetylglucosaminyltransferase subunit H (PIG-H, also known as Phosphatidylinositol-glycan biosynthesis class H protein) is part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis .
NADH:ubiquinone oxidoreductase, ESSS subunit (NADH_UbQ_OxRdtase_ESSS_su)
Type: Family

Mitochondrial complex I, which is located in the inner mitochondrial membrane, is the largest multimeric respiratory enzyme in the mitochondria, consisting of more than 45 subunits, one FMN co-factor and eight FeS clusters . The assembly of mitochondrial complex I is an intricate process that requires the cooperation of the nuclear and mitochondrial genomes .

This entry represents the ESSS subunit from mitochondrial NADH:ubiquinone oxidoreductase (complex I). It carries mitochondrial import sequences .
LRP chaperone MESD (MESD)
Type: Family

LRP chaperone MESD (also known as mesoderm development candidate 2) represents a set of highly conserved proteins found from nematodes to humans.
It is a chaperone that specifically assists with the folding of β-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). It also acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway and is essential for specification of embryonic polarity and mesoderm induction . The Drosophila homologue, known as boca, is an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members .

The final C-terminal residues, KEDL, are the endoplasmic reticulum retention sequence as it is an ER protein specifically required for the intracellular trafficking of members of the low-density lipoprotein family of receptors (LDLRs) . The N- and C-terminal sequences are predicted to adopt a random coil conformation, with the exception of an isolated predicted helix within the N-terminal region, The central folded domain flanked by natively unstructured regions is the necessary structure for facilitating maturation of LRP6 (Low-Density Lipoprotein Receptor-Related Protein 6 Maturation) .
FAM192A/Fyv6, N-terminal (FAM192A/Fyv6_N)
Type: Domain

This entry represents the N-terminal domain of the mammalian PIP30/FAM192A protein and the fungal Fyv6 protein.

PIP30/FAM192A acts as a regulator of PA28-gamma, a nuclear activator of the 20S proteasome. PIP30 favours PA28-gamma interaction with the 20S proteasome while inhibiting its association with coilin, a central component of nuclear Cajal bodies .

Fyv6 is a splicing factor that acts during exon ligation and promotes usage of consensus, branch point distal 3' splice sites . It is involved in telomere length regulation and required for survival upon exposure to K1 killer toxin . It promotes fully efficient non-homologous end-joining (NHEJ) by a mechanism activated in postdiauxic/stationary phase .
Organic solute carrier protein 1 (OSCP1)
Type: Family

Organic solute carrier protein 1, or Oscp1, is a family of proteins conserved from plants to humans. It is called organic solute transport protein or oxido-red-nitro domain-containing protein 1, however no reference could be find to confirm the function of the protein.
Integrator complex subunit 3, N-terminal (INTS3_N)
Type: Domain

This entry represents the N-terminal domain of the Integrator complex subunit 3 (Ints3). The Integrator complex is involved in small nuclear RNA (snRNA) U1 and U2 transcription, and in their 3'-box-dependent processing. This complex associates with the C-terminal domain of RNA polymerase II largest subunit and is recruited to the U1 and U2 snRNAs genes .

Ints3 (also known as SOSSA) is also a component of the sensor of single-stranded DNA complex (SOSS), which associates with single-stranded DNA, important for DNA repair and efficient homologous recombination . This subunit serves as a central adaptor for SOSS complex assembly and stability, and facilitates the accumulation of the complex to the sites of DNA damage. This region acts as a scaffold for SOSSB1 and SOSSC interaction and it is not essential for ssDNA binding .
Transmembrane protein 170 (Transmembrane_pr_170)
Type: Family

This entry represents a group of putative transmembrane proteins. The protein is only approximately 130 amino acids in length. The function is unknown.
Conserved oligomeric Golgi complex subunit 7 (COG7)
Type: Family

The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in membrane trafficking and glycoconjugate synthesis . COG7 is required for normal Golgi morphology and trafficking. Defects in COG7 are the cause of congenital disorder of glycosylation type 2E (CDG2E). CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation .
GPR180/TMEM145, transmembrane domain (GPR180/TMEM145_TM)
Type: Domain

This entry represents the seven transmembrane α-helical domain of GPR180 (also known as intimal thickness-related receptor, ITR) and TMEM145 . In vivo analyses of this gene revealed that expression of GPR180 protein increased with intimal thickening induced by cuff placement around murine femoral artery. Furthermore, GPR180-knockout mice were found to be resistant to this experimental intimal thickening . GPR180 was first thought to be an orphan Rhodopsin-like GPCR (G protein-coupled receptor) given structural similarities to GPCR transmembrane region, however, it was then confirmed not to signal as a GPCR . This protein is associated with TGF-beta signaling as it regulates the activity of the TGF-beta receptor complex through SMAD3 phosphorylation. Furthermore, GPR180 is also required for the action of Collagen triple helix repeat containing 1 (CTHRC1) to regulate brown and beige adipocyte activity and glucose homeostasis .

Proteins in this entry are homologous to TMEM181 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 architecture consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain .
Telomere length regulation protein, conserved domain (Telomere_length_regulation_dom)
Type: Domain

This entry represents a conserved domain found in a group of proteins called telomere-length regulation TEL2, or clock abnormal protein-2, which are conserved from plants to humans. These proteins regulate telomere length and contribute to silencing of sub-telomeric regions . Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling . In vitro the protein binds to telomeric DNA repeats.
Large ribosomal subunit protein bL35m (Ribosomal_bL35m)
Type: Family

This entry represents the large ribosomal subunit protein bL35m from metazoa, which is conserved from nematodes to humans and was previously known as L35 .

This entry represents the large ribosomal subunit protein bL35, previously known as L35, a basic protein of 60 to 70 amino-acid residues . Like many basic polypeptides, it completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes . This family of ribosomal proteins includes proteins from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
CBF1-interacting co-repressor CIR, N-terminal domain (CIR_N_dom)
Type: Domain

This entry represents a 45 residue conserved domain found at the N-terminal end CIR protein (CBF1-interacting co-repressor, also known as corepressor interacting with RBPJ 1). This domain can be found in the fungal CWC25 family members and mammlian LENG1 (leukocyte receptor cluster member 1) protein.

CBF1 (centromere-binding factor 1) acts as a transcription factor that causes repression by binding specifically to GTGGGAA motifs in responsive promoters, and it requires CIR as a co-repressor. CIR binds to histone deacetylase and to SAP30 and serves as a linker between CBF1 and the histone deacetylase complex . CIR also plays a role in alternative splicing .
Histone acetyltransferases subunit 3 (Histone_AcTrfase_su3)
Type: Family

This entry is found in Ada3 and homologous proteins which function as part of histone acetyltransferase complexes . Ada3 is an essential component of the Ada transcriptional coactivator (alteration/deficiency in activation) complex. It plays a key role in linking histone acetyltransferase-containing complexes to p53 (tumour suppressor protein) thereby regulating p53 acetylation, stability and transcriptional activation following DNA damage .
Alpha/gamma-adaptin-binding protein p34 (Alpha/Gamma-adaptin-bd_p34)
Type: Family

Alpha- and gamma-adaptin-binding protein p34 is a protein involved in membrane trafficking. It is known to interact with both alpha and gamma adaptin . It has been speculated that p34 may play a chaperone role such as preventing the soluble adaptors from co-assembling with soluble clathrin, or helping to remove the adaptors from the coated vesicle. It may also aid in the recruitment of soluble adaptors onto the membrane .
NADH:ubiquinone oxidoreductase, iron-sulphur subunit 5 (NADH_UbQ_OxRdtase_FeS-su5)
Type: Family

Proteins in this entry form part of the NADH:ubiquinone oxidoreductase complex I. Complex I is the first multisubunit inner membrane protein complex of the mitochondrial electron transport chain and it transfers two electrons from NADH to ubiquinone. The mammalian complex I is composed of 45 different subunits. The proteins in this entry represent a component of the iron-sulphur (IP) fragment of the enzyme, that is not involved in catalysis. These proteins carry four highly conserved cysteine residues, but these do not appear to be in a configuration which would favour metal binding, so the exact function of the protein is uncertain .
Protein phosphatase 1 regulatory subunit 21, N-terminal (PPP1R21_N)
Type: Domain

This entry represents a N-terminal 100 residues long domain found in Protein phosphatase 1 regulatory subunit 21, which contains a conserved KLRAQ motif. This domain is found in a family of coiled-coil domain-containing proteins that are conserved from nematodes to humans. These proteins also contain a C-terminal TTKRSYEDQ motif domain (

). Protein phosphatase 1 regulatory subunit 21 is likely a regulator of protein phosphatase 1 (PP1) activity . It may play a role in the endosomal sorting process or in endosome maturation pathway .
Mitochondrial F1-F0 ATP synthase subunit F, predicted (F1F0-ATPsyn_F_prd)
Type: Family

This entry represents small proteins of approximately 110 amino acids, which are highly conserved from nematodes to humans. Some have been annotated in Swiss-Prot as being the f subunit of mitochondrial F1F0-ATP synthase but this could not be confirmed. The sequence has a well-conserved WRW motif. The exact function of the protein is not known.
ARMET, C-terminal (ARMET_C)
Type: Domain

This entry represents the C-terminal domain of ARMET.

ARMET, also known as mesencephalic astrocyte-derived neurotrophic factor (MANF) or arginine-rich protein, is a small protein of approximately 170 residues which contains four di-sulphide bridges that are highly conserved from nematodes to humans. It is a soluble protein resident in the endoplasmic reticulum and induced by ER stress. It appears to be involved with dealing with mis-folded proteins in the ER, thus in quality control of ER stress . ARMET from Rattus norvegicus (Rat) selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. It modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra, and enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons .

Proteins containing this domain includes the related neurotrophic factor CDNF (cerebral dopamine neurotrophic factor) .
Large ribosomal subunit protein mL42 (Ribosomal_mL42)
Type: Family

This entry represents a family of short proteins; each approximately 100 amino acid residues in length. They are identified as the large ribosomal subunit protein mL42, also known as mitochondrial 39S ribosomal protein L42.
Axonemal dynein light chain (Axonemal_dynein_light_chain)
Type: Family

Axonemal dynein light chain proteins play a dynamic role in flagellar and cilial motility. Eukaryotic cilia and flagella are complex organelles consisting of a core structure, the axoneme, which is composed of nine microtubule doublets forming a cylinder that surrounds a pair of central singlet microtubules. This ultra-structural arrangement seems to be one of the most stable micro-tubular assemblies known and is responsible for the flagellar and ciliary movement of a large number of organisms ranging from protozoan to mammals. This light chain interacts directly with the N-terminal half of the heavy chains .
Protein phosphatase 1 regulatory subunit 21, six-helix bundle (PPP1R21_six_helix)
Type: Domain

This entry represents a middle domain found between the N- and C-terminal coiled-coil regions of PPP1R21. According to structure predictions, it appears to form a six-helix bundle, which contains a conserved TTKRSYEDQ motif.

Protein phosphatase 1 regulatory subunit 21 (PPP1R21) belong to a family of coiled-coil domain-containing proteins that are conserved from nematodes to humans. PPP1R21 is a regulator of protein phosphatase 1 (PP1) activity and may play a role in the endosomal sorting process or in endosome maturation pathway . These proteins also contain an N-terminal domain with a KLRAQ motif (

). Protein phosphatase 1 regulatory subunit 21 is likely a regulator of protein phosphatase 1 (PP1) activity . It may play a role in the endosomal sorting process or in endosome maturation pathway