SII-SWORD/CoKE huggingface dataset:
Astrotactin (Astrotactin)
Type: Family

Astrotactin-1 and 2 (ASTN1/2) are integral membrane perforin-like, vertebrate-specific proteins that play critical roles in neurodevelopment . They consist of an N-terminal cytosolic domain suspended between two transmembrane α-helices with a large C-terminal domain, extracellular for ASTN1 and endosome luminal for ASTN2. ASTN1 acts as a neuronal receptor for granule neuron migration along astroglial fibres . ASTN2 forms a complex with ASTN1, which regulates the surface expression of ASTN1. It mediates ASTN1 recycling by promoting its internalisation and transport during endocytosis . ASTN2 is also involved in the planar cell polarity pathway in hair cells .
Calpastatin (Calpastatin)
Type: Family

Calpain inhibitor (calpastatin) is restricted to the metazoa and specifically inhibits calpain (calcium-dependent cysteine protease) . Calpastatin belongs to MEROPS inhibitor family I27, clan II. It plays a key role in post-mortem tenderisation of meat and may be involved in muscle protein degradation in living tissue.

The calpain system originally comprised three molecules: two Ca2+-dependent proteases, mu-calpain and m-calpain, and a third polypeptide, calpastatin, whose only known function is to inhibit the two calpains. Both mu-and m-calpain are heterodimers containing an identical 28kDa subunit and an 80kDa subunit that shares 55-65% sequence homology between the two proteases. The single calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17kDa to 85kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent.
Alpha-s1 casein (Alpha-s1_casein)
Type: Family

Alpha-S1-casein plays an important role in the capacity of milk to transport calcium phosphate . It is also required for efficient export of the other caseins from the endoplasmic reticulum and plays a key role in early steps of casein micelle biogenesis and casein transport in the secretory pathway .

Caseins are the major protein constituent of milk. In milk, caseins interact with calcium phosphate, forming large stable colloidal particles termed micelles. These micelles make it possible to maintain a supersaturated calcium phosphate concentration in milk, providing the newborn with sufficient calcium phosphate for the mineralisation of calcified tissues . Caseins can be classified into two families; the first consists of the kappa-caseins, and the second groups the alpha-s1, alpha-s2, and beta-caseins. The alpha/beta caseins are a rapidly diverging family of proteins . However two regions are conserved: a cluster of phosphorylated serine residues and the signal sequence.
O-mannosyl-transferase-like (PMT-like)
Type: Family

This entry represents protein-O-mannosyltransferases, including yeast Dolichyl-phosphate-mannose--protein mannosyltransferase 1 and similar enzymes from bacteria and eukaryotes.

Dolichyl-phosphate-mannose-protein mannosyltransferase proteins

belong to the glycosyltransferase family 39 (

) and are responsible for O-linked glycosylation of proteins. They catalyse the reaction:
Dolichyl phosphate D-mannose + protein ->dolichyl phosphate + O-D-mannosyl-protein.

The transfer of mannose to seryl and threonyl residues of secretory proteins is catalysed by a family of protein mannosyltransferases in Saccharomyces cerevisiae coded for by seven genes (PMT1-7). Protein O-glycosylation is essential for cell wall rigidity and cell integrity and this protein modification is vital for S. cerevisiae .

Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase proteins

belong to the glycosyltransferase family 83 (

). They catalyse the reaction:
4-amino-4-deoxy-alpha-L-arabinopyranosyl di-trans,octa-cis-undecaprenyl phosphate + lipid IV(A) = lipid II(A) + di-trans,octa-cis-undecaprenyl phosphate.
C2 DOCK-type domain (C2_DOCK-type_domain)
Type: Domain

Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with an adjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct and smaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DHR-2 domain (also termed the CZH2 or DOCKER domain), .

The ~200 residue DOCK-type C2 domain is located toward the N terminus. It adopts a C2-like architecture and interacts with phosphatidylinositol 3,4,5-trisphosphate to mediate signalling and membrane localization. The central core of the DOCK-type C2 domain domain adopts an antiparallel β-sandwich with the "type II" C2 domain fold (a circular permutation of the more common "type I" topology), in which two 4-stranded sheets with strand order 6-5-2-3 and 7-8-1-4 create convex- and concave-exposed faces, respectively .

Some DOCK proteins are listed below:

Mammalian Mammalian dedicator of cytokinesis 180 (DOCK180 or DOCK1), important for cell migration.

Mammalian DOCK2, important for lymphocyte development, homong, activation, adhesion, polarization and migration processes.

Mammalian DOCK3 (also known as MOCA), is expressed predominantly in neurons and resides in growth cones and membrane ruffles.

Mammalian DOCK4, possesses tumor suppressor properties.

Mammalian DOCK9 (zizimin1), plays an important role in dendrite growth in hippocampal neurons through activation of Cdc42.

Drosophila melanogaster Myoblast city.

Caenorhabditis elegans CED-5.
Teashirt family (Teashirt_fam)
Type: Family

The teashirt family of transcription factors consists of Drosophila teashirt (tsh), the tsh paralogue tiptop (tio), which despite being dispensable for Drosophila development is functionally equivalent to tsh , and the three teashirt homologues (tshz) identified in vertebrates . All of them show similarity in their three first and widely spaced Zn-finger domains, with vertebrate members having additional Zn-fingers and a vertebrate-specific homeodomain . Teashirt is known to play a major role during the development of Drosophila, but the expression and function of other members of the family is only partially known .
Enkurin domain (Enkurin_dom)
Type: Domain

The transient receptor potential-canonical (TRPC) family of cation channel has been implicated in receptor- or phospholipase C (PLC)-mediated Ca(2+) entry into animal cells. Enkurin (derived from the Greek verb enkuros: to trip or to stumble upon) interacts with several TRPC proteins and colocalises with these channels in sperm. Three protein-protein interaction domains were identified in enkurin: a C-terminal region is essential for channel interaction; an IQ motif binds the Ca(2+) sensor, calmodulin, in a Ca(2+) dependent manner; and a proline-rich N-terminal region contains predicted ligand sequences for SH3 domain proteins, including the SH3 domain of the p95 regulatory subunit of 1-phosphatidylinositol-3-kinase. Enkurin then has the anticipated chraracteristics of a scaffold protein that tethers cargo, such as SH3 domain proteins, to a subset of TRPC channels .
Uncharacterised protein with YceI domain (UCP029811)
Type: Family

This entry represents an uncharacterised family of bacterial proteins that have a YceI domain.
Uncharacterised peptidase with NlpC/P60 domain, YkfC type (P60_peptidase_YkfC)
Type: Family

This entry represents a predicted uncharacterised peptidase with NlpC/P60 domain, YkfC type.
Hemolysin E (Hemolysin_E)
Type: Family

This family consists of bacterial haemolysin E (HlyE) proteins. HlyE is a toxin, which has some hemolytic activity towards mammalian cells. It acts by forming a pore-like structure upon contact with mammalian cells .
HlyE is unrelated to the well characterised pore-forming E. coli haemolysins of the RTX family, haemolysin A (HlyA), and the enterohaemolysin encoded by the plasmid borne ehxA gene of E. coli 0157. However, it is evident that expression of HlyE in the absence of the RTX toxins is sufficient to give a haemolytic phenotype in E. coli. HlyE is a protein of 34kDa that is expressed during anaerobic growth of E. coli. Anaerobic expression is controlled by the transcription factor, FNR, such that, upon ingestion and entry into the anaerobic mammalian intestine, HlyE is produced and may then contribute to the colonisation of the host .
Protein YnjB (YnjB)
Type: Family

This family includes uncharacterised protein YnjB from Escherichia coli.
Cyclic di-GMP binding protein, PA4608 type (C-di-GMP_BP_PA4608)
Type: Family

This entry represents a family of proteins with a PilZ domain, indicating their involvement in cyclic di-GMP binding.
ABC transporter permease protein, BceB-type (ABC_permease_BceB-typ)
Type: Family

This family represents the permease component of ABC-type antimicrobial peptide transport systems. BceB is part of the ABC transporter complex BceAB involved in bacitracin export . Another member of this family, YxdM, is the permease component of the ABC transporter complex yxdLM, also involved in peptide resistance .
Putative lipopolysaccharide kinase InaA (Put_LipoPS_kinase_InaA)
Type: Family

InaA may be an environmental sensor responsive to several stimuli, including internal pH, proton motive force, temperature, and possibly other unknown factors .
ABC-type uncharacterised transport system, substrate-binding component, TM0202 type (UCP027386_ABC_sbc_TM0202)
Type: Family

This entry represents a family of ABC-type uncharacterised transport system, substrate-binding components.
GOSR2/Membrin/Bos1 (GOSR2/Membrin/Bos1)
Type: Family

This entry consists of a group of SNAREs (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors), including Golgi SNAP receptor complex member 2 (GOSR2), vesicle transport through interaction with t-SNAREs homologue 1 (VTI1) and the related proteins membrin (Memb11 and Memb12) in plants and Bos1 in yeasts. Bos1 is necessary for vesicular transport from the ER to the Golgi . GOSR2 is involved in protein transport through the Golgi apparatus . In Arabidopsis, Memb11 is a v-SNARE involved in anterograde protein trafficking at the ER-Golgi interface .

SNARE proteins are a family of membrane-associated proteins characterised by an α-helical coiled-coil domain called the SNARE motif . These proteins are classified as v-SNAREs and t-SNAREs based on their localisation on vesicle or target membrane; another classification scheme defines R-, Qa-, Qb- and Qc-SNAREs according to sequence similarities . SNAREs are localised to distinct membrane compartments of the secretory and endocytic trafficking pathways, and contribute to the specificity of intracellular membrane fusion processes.
Glycyl-tRNA synthetase/DNA polymerase subunit gamma-2 (Gly-tRNA_synthase/POLG2)
Type: Family

This family includes both Glycyl-tRNA synthetases and mitochondrial DNA polymerase subunit gamma-2 (POLG2).
Twinkle-like protein (Twinkle-like)
Type: Family

Twinkle protein (T7-like mitochondrial DNA helicase) is a DNA helicase needed for mitochondrial DNA replication . It catalyses the ATP-dependent unwinding of a DNA duplex with 5' to 3' directionality, and it needs a single-stranded 5'-DNA and a short 3'-tail to initiate unwinding . In humans, mutations in TWINKLE cause autosomal dominant progressive external ophthalmoplegia, a human disorder associated with multiple deletions in the mitochondrial DNA . Arabidopsis encodes a homologue to phage T7 gp4/Twinkle proteins that has both DNA primase and DNA helicase activities .
Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (Cnh)
Type: Family

This entry includes a group of cytidine monophosphate-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase catalyses the conversion of CMP-N-acetylneuraminic acid (CMP-Neu5Ac) into its hydroxylated derivative CMP-N-glycolylneuraminic acid (CMP-Neu5Gc), a sialic acid abundantly expressed at the surface of many cells, except in brain . However, the human homologue of CMP-NeuAc hydroxylase in this entry is inactive because it lacks an N-terminal domain essential for enzyme activity . Instead, it may play a role in Wnt signalling .
Ran GTPase-activating protein (RanGap)
Type: Family

Ran GTPase-activating protein (RanGap) is a GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state . RanGap is an antagonist of RCC1, a nuclear protein that converts RanGDP to RanGTP and keep Ran in an active state. Together, they control Ran dependent transport between the nucleus and cytoplasm . In human, RanGap is regulated by sumoylation and phosphorylation through the cell cycle .
Cartilage acidic protein 1 (Crtac1)
Type: Family

Proteins in this family have unknown function. In humans, cartilage acidic protein 1 is expressed in the interterritorial matrix of articular deep zone cartilage .
26S proteasome non-ATPase regulatory subunit 4 (PSMD4)
Type: Family

The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively .

This family consists of the RC subunit S5A or non-ATPase regulatory subunit 4 (PSMD4, also known as Rpn10). Rpn10 binds and presumably selects ubiquitin-conjugates for destruction .
XdhC Rossmann domain (XdhC_Rossmann_dom)
Type: Domain

This entry represents the rossmann domain found in the Xanthine dehydrogenase accessory protein.
Mannosyltransferase ALG2 (ALG2)
Type: Family

ALG2 mannosylates Man2GlcNAc(2)-dolichol diphosphate and Man1GlcNAc(2)-dolichol diphosphate to form Man3GlcNAc(2)-dolichol diphosphate .

Defects in ALG2 are the cause of congenital disorder of glycosylation type 1I (CDG1I). CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterised by under-glycosylated serum proteins .
Gluconate 2-dehydrogenase subunit 3 (Gluconate_2DH_su3)
Type: Family

This family corresponds to subunit 3 of the Gluconate 2-dehydrogenase enzyme that catalyses the conversion of gluconate to 2-dehydro-D-gluconate . In Caulobacter crescentus an homologous subunit has been named as LacC, and is part, together with two other subunits, of a membrane-bound dehydrogenase that oxidises lactose, salicin, and trehalose .
CAAX prenyl protease 1 (CAXX_Prtase_1)
Type: Family

Following prenylation, proteins are subject to prenyl-dependent modifications at their C-terminal end, which are required for their subcellular targeting. The three C-terminal residues of the CAAX box prenylation signaling motif are removed before methylation of the free carboxyl group of the prenyl cysteine moiety.

CAAX prenyl protease 1 (also known as Ste24p) removes the C-terminal three residues of CAAX . It also acts to cleave the N-terminal extension of the farnesylated A-factor mating pheromone in Saccharomyces cerevisiae .
Coatomer delta subunit (Coatomer_dsu)
Type: Family

This entry represents the delta subunit of the coatomer complex, which is involved in the regulation of intracellular protein trafficking between the endoplasmic reticulum and the Golgi complex .

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .
Lon protease (Lon_Prtase)
Type: Family

Lon protease belongs to the S16 peptidase family and is an ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins, as well as certain short-lived regulatory proteins. It is required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress . In pathogenic bacteria, it is required for the expression of virulence genes that promote cell infection .

Lon (La) protease was the first ATP-dependent protease to be purified from
E. coli . The enzyme is a homotetramer of 87kDa subunits, with one proteolytic and one ATP-binding site per monomer, making it structurally less complex than other known ATP-dependent proteases . Despite this relative structural simplicity, Lon recognises its substrates directly, without delegating the task of substrate recognition to other enzymes .
5'-3' exoribonuclease (5_3_exoribonuclease)
Type: Family

This entry includes 5'-3'exoribonuclease type 1 and type 2. Putative viral exonucleases 059L and 012L, plant Xrn3 and Xrn4 also belong to this family. 5'-3'-exoribonucleases are enzymes that degrade RNA by removing terminal nucleotides from the 5' end. An exosome and a 5'-3'-exoribonuclease are important in the degradation of very unstable transcripts .
Integrator complex subunit 9 (Integrator_9su)
Type: Family

This family represents subunit 9 of the integrator complex (INTS9). The integrator complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription, and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes .
Cleavage and polyadenylation specificity factor subunit 2 (CPSF2)
Type: Family

Cleavage and polyadenylation specificity factor (CPSF) plays a key role in pre-mRNA 3'-end formation, recognising the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition .
Small nuclear ribonucleoprotein E (snRNP-E)
Type: Family

Small nuclear ribonucleoprotein E (SME1) is involved in pre-mRNA splicing. It is required for pre-mRNA splicing, cap modification and for the stability of snRNA U1, U2, U4 and U5 .

The eukaryotic Sm proteins (B/B', D1, D2, D3, E, F and G) assemble into a hetero-heptameric ring around the Sm site of the 2,2,7-trimethyl guanosine (m3G) capped U1, U2, U4 and U5 snRNAs (Sm snRNAs) forming the core of the snRNP particle. The snRNP particle, in turn, assembles with other components onto the pre-mRNA to form the spliceosome which is responsible for the excision of introns and the ligation of exons . Members of this family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet . Sm subunit E binds subunits F and G to form a trimer which then assembles onto snRNA along with the D1/D2 and D3/B heterodimers forming a seven-membered ring structure .
TFIIH subunit Tfb1/GTF2H1 (Tfb1/GTF2H1)
Type: Family

TFIIH is a eukaryotic complex composed of two subcomplexes, the CAK (Cdk activating kinase) and the core-TFIIH. This entry represents Tfb1/GTF2H1, a component of the core-TFIIH basal transcription factor, which consists of seven subunits known as XPB, XPD, GTF2H1 (p62), p52, p44, p34, and p8 in humans and Ssl2, Rad3, Tfb1, Tfb2, Ssl1, Tfb4 and Tfb5 in yeast . TFIIH is involved in nucleotide excision repair (NER) of DNA and RNA transcription by RNA polymerase II and I .
Protein Unc-13 (Unc-13)
Type: Family

Unc-13 is a phorbol ester/diacylglycerol-binding protein that plays a role in vesicle maturation during exocytosis . Unc-13 disruption causes diverse defects in the nervous system of the nematode Caenorhabditis elegans . This family also includes mammalian homologues A, B and C . Unc13 homologue C is cerebellum-specific and regulates cerebellar synaptic transmission . Homologues A and B are involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion . They are essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses .
CyclinH/Ccl1 (CyclinH/Ccl1)
Type: Family

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs).

This entry includes cyclin-H from vertebrates, mcs2 from fission yeast and Ccl1 from budding yeasts. They are cyclins that play a role in cell cycle. They are also subunits forming the core-TFIIH basal transcription factor. Human cyclin-H regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex . mcs2 posseses kinase activity that can be detected when myelin basic protein (MBP) is provided as an exogenous substrate . Ccl1 is a regulatory component of the TFIIK complex, which is the protein kinase component of transcription factor IIH (TFIIH). TFIIH is essential for both basal and activated transcription and is involved in nucleotide excision repair (NER) of damaged DNA and in polymerase II transcription .
Protein kinase Mps1 family, catalytic domain (Mps1_cat)
Type: Domain

This entry represents the catalytic domain of Mps1, which is in the C-terminal region .

The Mps1 family of protein kinases is a critical regulator
of genetic stability . In yeast, Mps1 is required for the spindle checkpoint and SPB
duplication . Human Mps1, also known as TTK, is required for proper chromosome alignment on the metaphase plate and for the fidelity of chromosome segregation, and might also have a role at centrosomes . It is associated with cell proliferation and involved in mitotic cell cycle checkpoint control . In late mitosis, Mps1 is ubiquitinated by the APC/C and subsequently degraded .
EAF family (EAF_fam)
Type: Family

This entry represents the ELL-associated factor (Eaf) family of proteins. They interact with ELL and ELL2, which are RNA polymerase II elongation factors. Eaf proteins form a stable heterodimer complex with ELL proteins to facilitate the binding of RNA polymerase II to activate transcription elongation . ELL and EAF1 are components of Cajal bodies, which have a role in leukemogenesis .