SII-SWORD/CoKE huggingface dataset:
Adenylate cyclase, conserved domain (Adcy_conserved_dom)
Type: Domain

Cyclic AMP (cAMP) is a ubiquitous signalling molecule which mediates many cellular processes by activating cAMP-dependent kinases and also inducing protein-protein interactions. This molecule is produced by the adenylate cyclase (AC) enzyme, using ATP as its substrate. Mammalian adenylate cyclase has nine closely related membrane-bound isoforms (AC1-9) showing significant sequence homology and sharing the same overall structure: two hydrophobic transmembrane domains, and two cytoplasmic domains that are responsible for the catalytic activity. These isoforms differ in both their tissue specificity and their regulation. Regulatory factors known to influence one or more of these isoforms include G proteins, protein kinases, calcium and calmodulin .

This entry represents a region of unknown function found in many of these isoforms. It is part of the N-terminal cytoplasmic domain but its presence is not necessary for catalytic activity .
TFIIH subunit TTDA/Tfb5 (TFIIH_TTDA/Tfb5)
Type: Family

This entry represents TTDA/Tfb5 subunit of TFIIH basal transcription factor complex. These proteins have a structural motif consisting of a 2-layer sandwich structure with an α/β plait topology. Nucleotide excision repair is a major pathway for repairing UV light-induced DNA damage in most organisms.

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair. The TFIIH multiprotein complex consists of a 7-subunit core (XPB, p62, p52, p44, p34, and TTDA) that is associated with a 3-subunit CDK-activating kinase module (MAT1, cyclin H and Cdk7) .

In humans, defects in TTDA cause the trichothiodystrophy photosensitive (TTDP), an autosomal recessive disease characterised by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect .
Mediator complex subunit Med13, C-terminal (Med13_C)
Type: Domain

This entry represents the C-terminal domain of Med13. This domain is also identified as an RNaseH domain of the medPIWI PIWI/Argonaute module. medPIWI is the core domain found in the Med13 protein. The medPIWI module in Med13 is predicted to bind double-stranded nucleic acids, triggering the experimentally-observed conformational switch in the CDK8 subcomplex which regulates the Mediator complex . Med13 is a component of the SRB8-11 complex. The SRB8-11 complex is a regulatory module of the Mediator complex, which may be involved in the transcriptional repression of a subset of genes regulated by Mediator. It acts by inhibiting the association of the Mediator complex with RNA polymerase II to form the holoenzyme complex .

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.
Orthopoxvirus A47 (Orthopox_A47)
Type: Family

This family consists of several Orthopoxvirus A47 proteins. The function of this family is unknown.
Protein of unknown function UPF0637 (UPF0637)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Coronavirus 5a (Corona_5a)
Type: Family

This family consists of several Coronavirus 5a proteins. The function of this family is unknown .
Vibrio cholerae toxin co-regulated pilus biosynthesis F (TcpF)
Type: Family

This family consists of several Vibrio cholerae toxin co-regulated pilus biosynthesis protein F (TcpF) sequences. TcpF is known to be a secreted virulence protein but its exact function is unknown .
Protein of unknown function DUF1056 (DUF1056)
Type: Family

This family consists of several proteins of unknown function from tailed bacteriophages and Firmicutes, including putative head-tail joining bacteriophage proteins.
Viral polyprotein, parechovirus P3B (VPP_parechovir_P3B)
Type: Domain

The viral polyprotein of parechoviruses contains: coat protein VP0 (P1AB); coat protein VP3 (P1C); coat protein VP1 (P1D); picornain 2A (

, core protein P2A); core protein P2B; core protein P2C; core protein P3A; genome-linked protein VPg (P3B); picornain 3C (

, MEROPS peptidase subfamily 3CF: parechovirus picornain 3C (P3C)) .

This entry consists of the genome-linked protein Vpg type P3B.
Protein of unknown function DUF1059 (DUF1059)
Type: Family

This entry consists of short hypothetical archaeal and bacterial proteins of unknown function.
Allene oxide cyclase (Allene_ox_cyc)
Type: Family

This family consists of several plant specific allene oxide cyclase proteins (

). The allene oxide cyclase (AOC)-catalysed step in jasmonate (JA) biosynthesis is important in the wound response of tomato .
Protein of unknown function DUF1062 (DUF1062)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Hemolysin, aegerolysin type (Aegerolysin-typ)
Type: Family

This family consists of several bacterial and eukaryotic Aegerolysin-like proteins. Aegerolysin and ostreolysin are expressed during formation of primordia and fruiting bodies, and these haemolysins may play an important role in initial phase of fungal fruiting. The bacterial members of this family are expressed during sporulation . Ostreolysin was found cytolytic to various erythrocytes and tumour cells . It forms transmembrane pores 4 nm in diameter. Its activity is inhibited by total membrane lipids, and modulated by lysophosphatides.
Protein of unknown function DUF1064 (DUF1064)
Type: Family

This entry includes Bacteriophage 92, Orf34. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several phage and bacterial proteins whose functions have not been experimentally determined. Computational analysis involving sequence, predicted structure and genomic context suggests that these proteins may be endonucleases which function in phage genome segregation, or the repair of double-stranded breaks introduced during either this process or DNA replication .
Omega-atracotoxin (Omega-atracotox)
Type: Family

This family consists of several Hadronyche versuta (Blue mountains funnel-web spider) specific omega-atracotoxin proteins. Omega-Atracotoxin-Hv1a is an insect-specific neurotoxin whose phylogenetic specificity derives from its ability to antagonise insect, but not vertebrate, voltage-gated calcium channels. Two spatially proximal residues, Asn(27) and Arg(35), form a contiguous molecular surface that is essential for toxin activity. It has been proposed that this surface of the β-hairpin is a key site for interaction of the toxin with insect calcium channels .
ESAT-6-like protein, Mycobacterium (ESAT-6-like_Myco)
Type: Family

This family consists of several Mycobacterium ESAT-6 like proteins. EsxO from Mycobacterium tuberculosis plays an important role in mycobacterial pathogenesis by inducing oxidative stress mediated genomic instability in infected macrophages . At least 23 ESAT-6 family proteins are encoded in the genome of M. tuberculosis; however, the function of many of them is still unknown.
Rice tungro bacilliform virus P12 (RTBV_P12)
Type: Family

This family consists of several Rice tungro bacilliform virus P12 proteins. The function of this family is unknown .
Protein of unknown function DUF1067 (DUF1067)
Type: Family

This family consists of several hypothetical Mycobacterium leprae specific proteins. The function of this family is unknown.
Viral polyprotein, parechovirus P3A (VPP_parechovir_P3A)
Type: Domain

The viral polyprotein of parechoviruses contains: coat protein VP0 (P1AB); coat protein VP3 (P1C); coat protein VP1 (P1D); picornain 2A (

, core protein P2A); core protein P2B; core protein P2C; core protein P3A; genome-linked protein VPg (P3B); picornain 3C (

, MEROPS peptidase subfamily 3CF: parechovirus picornain 3C (P3C)).

This entry consists of the parechovirus P3A protein. P3A has been identified as a genome-linked protein (VPg), which is involved in replication .
Flagellar protein FlhE (FlhE)
Type: Family

This family consists of several Enterobacterial FlhE flagellar proteins. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death. FlhE is a member of the flhBAE operon. FlhA and FlhB are established components of the flagellar type III secretion system. However, the function of FlhE is not clear .
Gem-associated protein 6 (Gemin6)
Type: Family

This family consists of several animal Gemin6 proteins. The exact function of Gemin6 is unknown but it has been found to form part of the Survival of motor neuron complex. The SMN complex plays a key role in the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and other ribonucleoprotein particles .
NADH dehydrogenase [ubiquinone] 1 subunit C2, NDUC2 (NDUC2)
Type: Family

This family consists of several NADH dehydrogenase [ubiquinone] 1 subunit C2 (NDUC2 or NDUFC2, also known as NADH-ubiquinone oxidoreductase subunit b14.5b) proteins. It is an accessory protein, not involved in catalysis .
Arabinogalactan protein 16/20/22/41 (AGP16/20/22/41)
Type: Family

This entry represents a group of arabinogalactan proteins (AGPs) from plants, and includes AGP16, AGP20, AGP22 and AGP41 . These proteoglycans have been implicated in various processes associated with plant growth and development, including embryogenesis and cell proliferatio
SSAP, RNA binding domain (DSRM_SSAP)
Type: Domain

This entry describes the RNA binding domain from the Sak Single-Strand Annealing Protein (SSAP) from Staphylococcal Bacteriophage 80alpha, which is part of the Rad52-like superfamily.

The Sak protein from phage 80alpha shares similarities with other SSAPs, such as Red-beta from phage lambda and RAD52 from eukaryotes. SSAPs like Sak play a crucial role in homologous recombination by promoting the annealing of complementary single-stranded DNA. Sak adopts a structure similar to other SSAPs and features a groove commonly observed in this protein group, which accommodates single-stranded DNA on the outer surface of the torus, known as the ssDNA binding groove or ssDBG . Mutations in Sak3 can reduce sensitivity to the antiviral abortive infection mechanism AbiK .
Barley yellow dwarf virus (BYDV), Gp6 (BYDV_Gp6)
Type: Family

This family consists of several Barley yellow dwarf virus proteins of unknown function.
Uncharacterised conserved protein UCP020357 (UCP020357)
Type: Family

This entry represents a protein family of unknown function found in Borrelia species.
Beta-catenin-interacting ICAT domain (ICAT_dom)
Type: Domain

This domain is characteristic of eukaryotic beta-catenin-interacting (ICAT) proteins. Beta-catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. Transcription mediated by the beta-catenin/Tcf complex is involved in embryological development and is upregulated in various cancers. ICAT selectively inhibits beta-catenin/Tcf binding
in vivo
, without disrupting beta-catenin/cadherin interactions .

Protein LZIC contains a leucine zipper domain and an ICAT homologous domain, with particular conservation of residues that are used by ICAT for beta-catenin-binding .
Baculovirus LEF-11 (Baculo_LEF-11)
Type: Family

This family consists of several Baculovirus LEF-11 proteins. The exact function of this family is unknown although it has been shown that LEF-11 is required for viral DNA replication during the infection cycle and plays a role in late/very late gene activation.
Gas vesicle protein L/F (GvpL/GvpF)
Type: Family

Gas vesicles provide cells with buoyancy, enabling them to remain at the water surface. These organelles are generally synthesised by halophilic archaea and cyanobacteria, as well as some other prokaryotes. A cluster of 12-14 gvp genes (gvpMLKJIHGFEDACNO) is responsible for gas vesicle synthesis in Halobacterium sp. . This family includes Gas vesicle proteins L and F (GvpL and GvpF), which are essential for gas vesicle formation and display sequence similarity to one another, both containing predicted coiled-coil domains that are often involved in self-oligomerisation. They are structural components of the vesicle .
Neuronal vesicle trafficking-associated protein (NSG)
Type: Family

This family includes the neuron-enriched endosomal proteins NSG1 (NEEP21), NSG2 (P19) and NSG3 (calcyon, Caly). They interact with distinct elements of the endosomal and synaptic scaffolding machinery . NSG1 and NSG2 may not be resident endosomal proteins, and are also known as neuronal vesicle trafficking-associated proteins 1 and 2 respectively . NSG1/NEEP21 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and beta-APP . The role of NSG2 is not known.

It was originally thought that the Neuron-specific vesicular protein calcyon (previously known as D1 dopamine receptor-interacting, calcyon), interacted directly with the D1 dopamine receptor (DRD1) to modulate neocortical and hippocampal neuronal excitability as well as cAMP-dependent signalling . However, this work was retracted, as it was shown that a direct interaction with the dopamine D1 receptor had been misinterpreted . However, it has been shown that calcyon induces D1DR to stimulate intracellular Ca2+ release, and this suggests a possible functional interaction between calcyon and D1DR, despite there being, as yet, no direct interaction between them. A recent study suggested that calcyon-containing vesicles might transport D1DR by associating calcyon with D1DR through their assembly to clathrin . However, as a single transmembrane protein, it is currently not clear how calcyon can regulate the internalization of D1DR from the plasma membrane to endocytic vesicles.

Calcyon is a brain-specific protein, mainly localized in the intracellular endosomal vesicles of dendritic spines in dopamine expressing pyramidal cells in the prefrontal cortex and hippocampus and dorsal striatum region . Neuron-specific vesicular protein calcyon has implicated in clathrin-mediated endocytosis. It is exclusively expressed in neurons, and localized in moving vesicles and it thought to play a role in brain plasticity . Defective calcyon proteins have been implicated in both attention-deficit/hyperactivity disorder (ADHD) and schizophrenia .
Protein of unknown function DUF1075 (DUF1075)
Type: Family

This family consists of several eukaryotic proteins of unknown function.
Filovirus membrane-associated VP24 (Filo_VP24)
Type: Family

This family consists of several membrane-associated protein VP24 sequences from a variety of Ebola viruses, as well as Lake Victoria marburgvirus. The VP24 protein of Ebola virus sp. is believed to be a secondary matrix protein and minor component of virions. VP24 possesses structural features commonly associated with viral matrix proteins and that VP24 may have a role in virus assembly and budding .
Neuroendocrine secretory protein 55 (NESP55)
Type: Family

The imprinted GNAS cluster, located on chromosome 2 in mice and chromosome 20 in humans, contains transcripts that are maternally, paternally, and/or biallelically expressed. Neuroendocrine secretory protein 55 (NESP55) is encoded by an upstream exon of the GNAS1 gene, which is expressed exclusively from the maternal allele . It is a neuroendocrine secretory granule protein originally identified by screening cDNA libraries from bovine chromaffin cells with antibody against secretogranin II . It belongs to the granin family, whose members are involved in endocrine and neuronal secretory pathways .

NESP55 has been shown to act as biomarkers for endocrine and neuroendocrine tumours and implicated in cell growth . It has been linked to pseudohypoparathyroidism type Ib (PHP-1b), an imprinted human disorder associated with methylation changes at one or several differentially methylated regions at the GNAS locus .
Type-1 angiotensin II receptor-associated protein (AGTRAP)
Type: Family

AGTRAP (type-1 angiotensin II receptor-associated protein) appears to be a negative regulator of type-1 angiotensin II receptor-mediated signalling by regulating receptor internalisation as well as mechanism of receptor desensitization such as phosphorylation . It plays an important role in cardiac hypertrophy .
Lamprin (Lamprin)
Type: Family

This family consists of several lamprin proteins from Petromyzon marinus (sea lamprey). Lamprin, an insoluble non-collagen, non-elastin protein, is the major connective tissue component of the fibrillar extracellular matrix of lamprey annular cartilage. Although not generally homologous to any other protein, soluble lamprins contain a tandemly repeated peptide sequence (GGLGY), which is present in both silkmoth chorion proteins and spider dragline silk. Strong homologies to this repeat sequence are also present in several mammalian and avian elastins. It is thought that these proteins share a structural motif which promotes self-aggregation and fibril formation in proteins through interdigitation of hydrophobic side chains in β-sheet/β-turn structures, a motif that has been preserved in recognisable form over several hundred million years of evolution .
Phytosulfokine (Phytosulfokine)
Type: Family

This family consists of several plant specific phytosulfokine precursor proteins. Phytosulfokines, are active as either a pentapeptide or a C-terminally truncated tetrapeptide. These compounds were first isolated because of their ability to stimulate cell division in somatic embryo cultures of Asparagus officinalis .
Red chlorophyll catabolite reductase (RCC_reductase)
Type: Family

This family consists of several red chlorophyll catabolite reductase (RCC reductase) proteins. Red chlorophyll catabolite (RCC) reductase (RCCR) and pheophorbide (Pheide) a oxygenase (PaO) catalyse the key reaction of chlorophyll catabolism, porphyrin macrocycle cleavage of Pheide a to a primary fluorescent catabolite (pFCC) . In rice, RCCR has been shown to play key role in senescence and is involved in wound responses .
Plasmid segregation protein ParM/StbA, N-terminal (ParM/StbA_N)
Type: Domain

This entry represents the N-terminal domain of bacterial plasmid segregation protein ParM, also known as StbA . ParM is involved in the control of plasmid partition and required for the accurate segregation of the plasmid, which forms filaments to drive partition.
P40 nucleoprotein, Borna disease virus (P40_nucleoprot_BD-vir)
Type: Family

This entry represents P40 nucleoproteins from several Borna disease virus (BDV) strains. BDV is an RNA virus that is a member of the Mononegavirales family, which includes such members as Measles virus and Ebola virus sp.. BDV causes an infection of the central nervous system in a wide range of vertebrates, which can progress to an often fatal immune-mediated disease. Viral nucleoproteins are central to transcription, replication, and packaging of the RNA genome. P40 nucleoprotein from BDV is multi-helical in structure and can be divided into two subdomains, each of which has an α-bundle topology . The nucleoprotein assembles into a planar homotetramer, with the RNA genome either wrapping around the outside of the tetramer or possibly fitting within the charged central channel of the tetramer .
Nuclear pore complex interacting protein (NPIP)
Type: Family

This family consists of a series of primate-specific nuclear pore complex-interacting protein (NPIP) sequences.

NPIP are not considered one of the core structural nucleoporins that form the main scaffold of the nuclear pore complex (NPC), but it is classified as a nucleoporin-associated protein. This family is well conserved from African apes to humans .

Nuclear pore complexes (NPCs) are composed of several copies of 30 different proteins called nucleoporins (Nups). NPCs penetrate the nuclear envelope (NE) and regulate the nucleocytoplasmic trafficking of macromolecules. Beyond this vital role, NPC components influence genome functions in a transport-independent manner. Nups play an evolutionarily conserved role in gene expression regulation that, in metazoans, extends into the nuclear interior. Additionally, in proliferative cells, Nups play a crucial role in genome integrity maintenance and mitotic progression .
Conjugal transfer, TraD, alpha-type (Conjugal_tfr_TraD_a-type)
Type: Family

This family consists of a group of TraD conjugal transfer proteins found primarily, though not exclusively, in the alphaproteobacteria .
ER membrane protein complex subunit 4 (TMEM85/Emc4)
Type: Family

This entry includes ER membrane protein complex subunit 4 (EMC4, also known as TMEM85 in mammals) from animals and its orthologue Emc4 from budding yeasts. They inhibit hydrogen peroxide mediated cell death in yeast . Emc4 is part of the ER membrane complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins .
Mitochondrial genome maintenance protein Mgm101 (Mgm101)
Type: Family

The Mgm101 is a Rad52-type single-stranded annealing protein (SSAP) required for mitochondrial DNA (mtDNA) repair and maintenance. Its C-terminal tail is required for single-stranded DNA binding . It may also play roles in the replication of the mitochondrial genome and the maintenance of its telomeres .
Phosphatidylinositol anchor biosynthesis protein PIGW/GWT1 (PIGW/GWT1)
Type: Family

Glycosylphosphatidylinositol (GPI) is a conserved post-translational modification to anchor cell surface proteins to plasma membrane in eukaryotes. PIGW and the yeast homologue GWT1 are involved in the addition of the acyl-chain to inositol in an early step of GPI biosynthesis . Mutations in PIGW are associated with West syndrome and hyperphosphatasia with mental retardation syndrome .
UDP-glucose:Glycoprotein Glucosyltransferase (UDP-g_GGtrans)
Type: Family

The N-terminal region of this group of proteins is required for correct folding of the ER UDP-Glc: glucosyltransferase. These proteins selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER. Unfolded, denatured glycoproteins are substantially better substrates for glucosylation by this enzyme than are the corresponding native proteins. This protein and transient glucosylation may be involved in monitoring and/or assisting the folding and assembly of newly made glycoproteins, in order to identify glycoproteins that need assistance in folding from chaperones
GDP/GTP exchange factor Sec2, N-terminal (Sec2_N)
Type: Domain

In Saccharomyces cerevisiae, Sec2 is a GDP/GTP exchange factor for Rab GTPase Sec4, which is required for vesicular transport at the post-Golgi stage of yeast secretion . It catalyses the dissociation of GDP from Sec4, also potently promoting binding of GTP. Activation of Sec4 by Sec2 is needed for the directed transport of vesicles to sites of exocytosis. Sec2 binds the Rab GTPase YPT32, but does not have exchange activity on YPT32 .