SII-SWORD/CoKE huggingface dataset:
Helicase Helix-turn-helix domain (Helicase_HTH)
Type: Domain

This presumed domain is found at the C terminus of a large number of helicases, including human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN, a multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates and also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang . Its depletion leads to chromosomal breaks and genome instability .
Domain of unknown function DUF4435 (DUF4435)
Type: Domain

This presumed domain is functionally uncharacterised. This domain is sometimes associated with AAA domains.
ATP-dependent RecD2 DNA helicase-like, helix-hairpin-helix domain (RecD2-like_HHH)
Type: Domain

This presumed domain contains at least one helix-hairpin-helix motif. This domain is found in ATP-dependent RecD2 DNA helicase from Bacillus subtilis and similar bacterial sequences. RecD2 may favor replication restart by preventing RecA from binding to blocked replication forks, avoiding unnecessary recombination during replication restart. It acts as a negative modulator of the RecA-ssDNA filament, and it may disassemble RecA threads. It can act as both a positive and negative regulator of strand exchange .
ssDNA thymidine ADP-ribosyltransferase, DarT (DarT)
Type: Domain

Proteins containing this domain can be found in bacteria, archaea and eukaryotes. Proteins containing this domain are distantly similar to (

). Studies in search for novel ADP-ribosylation systems in bacterial genomes have identified an operon that encodes a conserved protein containing a distinct type of macrodomain associated with this domain. This led to the identification of a toxin-antitoxin (TA) system, with DarT acting as the toxin. It is an enzyme that specifically modifies thymidines on single-stranded DNA in a sequence-specific manner by a nucleotide-type modification called ADP-ribosylation. This modification in turn can be removed by DarG, the antitoxin macrodomain protein. In addition, it was illustrated that substitution of the single completely conserved glutamate residue resulted in attenuation of function where DarT was non-toxic .
NACHT-associated domain (NACHT-assoc)
Type: Domain

This domain is frequently found associated with the NACHT domain (

) in fish and other vertebrates . Proteins containing this domain include NACHT, LRR and PYD domains-containing protein 3/12 (NLRP3/12). In humans, NLRP3 (also known as PYPAF1) may function as an inducer of apoptosis . NLRP12 is a non-inflammasome NLR (nucleotide-binding domain and leucine-rich repeat-containing receptors) that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-kappaB activation .
Type 4 fimbrial biogenesis protein PilY2 (Fimbrial_PilY2)
Type: Family

Members of this family were experimentally shown to be involved in fimbrial biogenesis, but its exact role is not clear . The structure of a member from Pseudomonas aeruginosa was determined (

) that adopts a β-barrel with an OB-fold topology.
Prion-inhibition and propagation, HeLo domain (HeLo_dom)
Type: Domain

This N-terminal domain, HeLo, has a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation . The domain is found exclusively in the fungal kingdom. Its structure, as it occurs in the heterokaryon incompatibility proteins HET-s and HET-S proteins, consists of two bundles of α-helices that pack into a single globular domain . The domain boundary determined from its structure and from protease-resistance experiments overlaps with the C-terminal prion-forming domain of HET-s

. The HeLo domains of HET-s and HET-S are very similar and their few differences (and not the prion-forming domains) determine the compatibility-phenotype of the fungi in which the proteins are expressed.

The mechanism of the HeLo domain-function in heterokaryon-incompatibility is still under investigation, however the HeLo domain is found in similar protein architectures as other cell death and apoptosis-inducing domains. The only other HeLo protein to which a function has been associated is LopB from Leptosphaeria maculans . Although its specific role in L. maculans is unknown, LopB- mutants have impaired ability to form lesions on oilseed rape. The HeLo domain is not related to the HET domain (

) which is another domain involved in heterokaryon incompatibility.
Corrinoid adenosyltransferase, PduO-type (PduO-typ)
Type: Family

ATP:cob(I)alamin (or ATP:corrinoid) adenosyltransferases (

), catalyse the conversion of cobalamin (vitamin B12) into its coenzyme form, adenosylcobalamin (AdoCbl)or coenzyme B12 . AdoCbl contains an adenosyl moiety liganded to the cobalt ion of cobalamin via a covalent Co-C bond. AdoCbl is required as a cofactor for the activity of certain enzymes.

ATP:cob(I)alamin adenosyltransferases are classed into three groups: CobA-type , EutT-type and PduO-type . Each of the three enzyme types appears to be specialised for particular AdoCbl-dependent enzymes or for the de novo synthesis AdoCbl. PduO and EutT are distantly related, sharing short conserved motifs, while CobA is evolutionarily unrelated and is an example of convergent evolution.

This entry represents the Corrinoid adenosyltransferase family corresponding to the N-terminal half of Salmonella PduO, a 1,2-propanediol utilization protein that probably is bifunctional . The PduO-type adenosyltransferase is the most widely distributed ATP:cobalamin adenosyltransferase . the mammalian ortholog (MmaB), also included in this family, is associated with mitochondrial B12 metabolism . Mutations in the human gene can result in the metabolic disorder known as methylmalonic aciduria (MMA) .
NADPH-dependent 7-cyano-7-deazaguanine reductase QueF (QueF)
Type: Family

This protein is involved in the biosynthesis of queuosine (Q), a modified nucleoside present in certain tRNAs. It catalyses the reduction of 7-cyano-7-deazaguanine (preQ0) to the corresponding amine 7-amino-methyl-7-deazaguanine (preQ1). QueF family members fall into two structural subfamilies . The YkvM (Bacillus subtilis QueF) subfamily is comprised of 160-amino-acid unimodular proteins, whereas the YqcD (E. coli QueF) subfamily is characterised by 280-amino-acid bimodular proteins. YkvM enzymes function as homododecamers, while the YqcD enzymes are homodimers .
Bacterial EndoU nuclease (EndoU_bac)
Type: Domain

This EndoU nuclease domain is a bacterial version eukaryotic EndoU nuclease. It is found at the C-terminal region of polymorphic toxin proteins . Nucleases are widely used as toxins for defense, offense or addiction of selfish elements.
Ribosomally synthesized peptide (Ribosomal_synth)
Type: Family

This is a family of ribosomally synthesized peptides prototyped by Frankia Franean 1_4349 (

) and linked to cyclases in chloroflexi. They may have a link to cyclic nucleotide signalling .
Phosphotransferase system EIIB component, mannitol-specific (PTS_EIIB_mannitol)
Type: Domain

The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII). IIB (

) is is phosphorylated by phospho-IIA, before the phosphoryl group is transferred to the sugar substrate.

Several PTS permease families are currently recognised, namely, the (i) glucose (including glucoside), (ii) fructose (including mannitol), (iii) lactose (including N,N-diacetylchitobiose), (iv) galactitol, (v) glucitol, (vi) mannose, and (vii) l-ascorbate families .

The IIA, IIB, and IIC domains are expressed from the mtlA gene as a single protein, also known as the mannitol PTS permease, the mtl transporter, or MtlA. MtlA is only functional as a dimer with the dimer contacts occuring between the IIC domains . MtlA takes up exogenous mannitol releasing the phosphate ester into the cytoplasm in preparation for oxidation to fructose-6-phosphate by the NAD-dependent mannitol-P dehydrogenase (MtlD) . The IIB domain fold includes a central four-stranded parallel open twisted β-sheet flanked by α-helices on both sides . This entry represents the component EIIB of mannitol-specific PTS systems.
Microcephalin, mammal (Microcephalin_mammal)
Type: Family

Microcephalin is implicated in chromosome condensation and DNA damage induced cellular responses . It may play a role in neurogenesis and regulation of the size of the cerebral cortex in animals. It is a protein, which if expressed homozygously, causes the organism to have the condition microcephaly - a drastically reduced brain mass and volume . Microcephalin is predicted to contain three BRCA1 C-terminal domains, the first of which is the probable microcephaly mutation site.
Aldehyde dehydrogenase, glutamic acid active site (Ald_DH_CS_GLU)
Type: Conserved_site

Aldehyde dehydrogenases (

and

) are enzymes that oxidize a wide variety of aliphatic and aromatic aldehydes using NADP as a cofactor. In mammals at least four different forms of the enzyme are known : class-1 (or Ald C) a tetrameric cytosolic enzyme, class-2 (or Ald M) a tetrameric mitochondrial enzyme, class- 3 (or Ald D) a dimeric cytosolic enzyme, and class IV a microsomal enzyme. Aldehyde dehydrogenases have also been sequenced from fungal and bacterial species. A number of enzymes are known to be evolutionary related to aldehyde dehydrogenases. A glutamic acid and a cysteine residue have been implicated in the catalytic activity of mammalian aldehyde dehydrogenase. These residues are conserved in all the enzymes of this family. This entry represents the glutamic acid active site.
Coiled-coil domain-containing protein 154 (CCDC154)
Type: Family

CCDC154 is an osteopetrosis-related protein that suppresses cell proliferation by inducing G2/M arrest .
Liprin (Liprin)
Type: Family

This entry represents liprin family from vertebrates and invertebrates.

Liprin was originally identified as binding partners of the receptor protein tyrosine phosphatase LAR (leukocyte common antigen-related), which functions in axon guidance and mammary gland development . In vertebrates, there are two families of liprins, liprin-alpha and liprin-beta, which have four (alpha1-4) and two (beta1-2) members. In C. elegans and Drosophila, there are only one liprin-alpha (known as Syd-2 and Dliprin-alpha) and one liprin-beta. Another liprin family member, liprin-gamma, has also been identified in Drosophila . Liprins contain an N-terminal coiled-coil domain and a C-terminal liprin homology (LH) region comprised of three sterile alpha motif (SAM) domains . The N-terminal coiled coils of liprin-alpha mediate interactions with adapter proteins at the presynaptic active zone, while the SAM repeats bind proteins such as LAR receptor tyrosine phosphatase .
Nucleoredoxin-like protein 2 (RdCVF2)
Type: Family

Nucleoredoxin-like protein 2 (Nxnl2, also known as RdCVF2) is a trophic factor with therapeutic potential that are involved in cone photoreceptor survival . It may be involved in the maintenance of both the function and the viability of sensory neurons, including photoreceptors and olfactory neurons .
Nucleoredoxin-like protein 1 (RdCVF)
Type: Family

Nucleoredoxin-like protein 1 (Nxnl1, also known as RdCVF) is a trophic factor with therapeutic potential that is involved in cone photoreceptor survival . It may slow down cone degeneration and play an important role in photoreceptor maintenance and resistance to retinal oxidative stress .
INO80 complex, subunit Ies2 (INO80B/Ies2)
Type: Family

This entry represents INO80 complex subunit 2 (Ies2), also known as INO80 complex subunit B (INO80B). INO80 is involved in transcriptional regulation, DNA replication and probably DNA repair . Ies2 functions as a molecular switch that potently activates INO80 DNA-dependent ATPase activity .
INO80 complex, subunit Ies6 (INO80C/Ies6)
Type: Family

This entry represents INO80 complex subunit Ies6 (also known as INO80 complex subunit C, INO80C). INO80 is involved in transcriptional regulation, DNA replication and probably DNA repair . Together with Arp5, Ies6 promotes binding of the INO80 complex to nucleosomes to help initiate the remodeling reaction . The homologue from Arabidopsis ENN mediates a regulatory mechanism that monitors the expression of the essential multifunctional plant stress regulator EIN2 via H3K27me3 repressive histone demethylation and histone variant H2A.Z eviction, thus modulating responses to ethylene (ET), especially during embryogenesis .
PiggyBac transposable element-derived protein (PGBD)
Type: Domain

This entry represents a domain found in the human PiggyBac transposable element-derived proteins (PGBDs) and some uncharacterised proteins. Its function is not clear.
Calpain-3, penta-EF-hand (CAPN3_PEF)
Type: Domain

This entry represents the Ca2 -binding penta-EF-hand (PEF) domain of CAPN3.

Calpain-3 (CAPN3) belongs to the calpain family, which consists of a group of Ca2+ dependent cysteine proteases that regulate functions of substrates by proteolysis . Calpain-3 is a calcium-dependent cysteine protease mainly expressed in skeletal muscle. It is involved in sarcomere maintenance and remodelling . It interacts with myospryn, which is a muscle-specific protein that functions in vesicular trafficking and protein kinase A signalling .
Serine/arginine-rich splicing factor 1, RNA recognition motif 2 (SRSF1_RRM2)
Type: Domain

Serine/arginine-rich (SR) proteins constitute a conserved family of RNA-binding proteins with roles in both constitutive and alternative splicing . Typically, SR proteins contain an N-terminal RNA-binding domain and a C-terminal RS domain that acts to promote protein-protein interactions .

This entry represents the second RNA recognition motif (RRM2) of serine/arginine-rich splicing factor 1 (SRSF1 or SF2/ASF). SF2/ASF regulates constitutive and alternative splicing . It has also been shown to regulate diverse aspects of gene regulation, including mRNA stability , translation , and transcription . SF2/ASF is upregulated in several human tumours, including lung, colon, kidney, liver, pancreas and breast tumours .
Astrocytic phosphoprotein PEA-15, death effector domain (PEA15_DED)
Type: Domain

Astrocytic phosphoprotein PEA-15 is a multifunctional protein that is involved in different biological processes and regulates several signalling pathways . It contains N-terminal death effector domain (DED) and a C-terminal tail with irregular structure . Expression of PEA-15 oscillates throughout the cell cycle, and the loss of PEA15 accelerates cell cycle progression .

PEA-15 blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade . It inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis . It also functions as a tumour suppressor by triggering the DNA damage-induced G2/M checkpoint and inhibiting RAS-mediated transformation . In humans PEA-15 is regarded as an important target for type 2 diabetes. PEA-15 overexpression impairs insulin regulation of glucose transport, and this is mediated by its interaction with the C-terminal D4 domain of phospholipase D1 (PLD1) and the consequent increase of protein kinase C-alpha activity .

This entry represents the Death Effector Domain (DED) of PEA15.
Retinoic acid receptor responder protein 2 (Chemerin)
Type: Family

Retinoic acid receptor responder protein 2 (also known as chemerin or TIG2) is an immunomodulating protein secreted predominantly by adipose tissue and skin. It is secreted in an inactive form and further processed to an active form through cleavage of its carboxyl terminus . It regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1) . It also binds to G protein-coupled receptor 1 (GPR1) and C-C chemokine receptor-like 2 (CCRL2) . Chemerin has been linked to obesity and inflammation. It also possesses antimicrobiological functions and may serve as a tumorsuppressor in skin .
Calcium homeostasis modulator family (CALHM)
Type: Family

This entry represents a group of voltage-gated ion channel proteins, including calcium homeostasis modulator protein 1/2/3/4/5/6 . This family is also known as FAM26 proteins.
Thyroid peroxidase (TPO)
Type: Family

Thyroid peroxidase (TPO) is a membrane-bound glycoprotein that serves as the key enzyme in the biosynthesis of thyroid hormones . TPO oxidizes iodide via hydrogen peroxide to form active iodine, which is then, for example, incorporated into the tyrosine residues of thyroglobulin to yield mono- and di-iodotyrosines .
Transient receptor potential cation channel subfamily M member 6, alpha-kinase domain (TRPM6_a-kinase_dom)
Type: Domain

The TRPM subfamily of TRP channels includes TRPM6, which is a bifunctional protein comprising a TRP cation channel segment ion channel fused to a kinase domain with homology to the family of atypical alpha kinases . The TRPM6 channel kinase plays a central role in systemic Mg(2+) homeostasis, and loss-of-function mutations in the human TRPM6 gene give rise to hypomagnesemia with secondary hypocalcemia (HSH) . TRPM6 may have a role in neural tube closure during development, since mice with TRPM6 gene defects show neural tube defects and embryonic mortality .

This entry represents the alpha-kinase domain of TRMP6.
Intraflagellar transport protein 81 (IFT81)
Type: Family

Intraflagellar transport of ciliary precursors such as tubulin from the cytoplasm to the ciliary tip is required for ciliogenesis . Intraflagellar transport protein 81 (IFT81) is a component of the intraflagellar transport (IFT) complex B, which contains at least 20 different protein subunits. Together with IFT74 forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium .
Transient receptor potential cation channel subfamily M member 7, alpha-kinase domain (TRPM7_a-kinase_dom)
Type: Domain

The TRPM subfamily of mammalian TRP channels includes TRPM7, which is a bifunctional molecule consisting of a TRP ion channel fused to a serine/threonine-protein kinase domain. It conducts Zn(2+), Mg(2+), and Ca(2+) as well as monovalent cations . The kinase domain is proteolytically cleaved from the channel domain in a cell-type-specific manner, with the cleaved kinase fragments translocating to the nucleus and binding multiple components of chromatin-remodeling complexes . TRPM7 plays a prominent role in cellular and systemic magnesium homeostasis, and is a key player in embryonic development, global ischemia, cardiovascular disease, and cancer .

This entry represents the alpha-kinase domain of TRMP7.
Intraflagellar transport protein 74 (IFT74)
Type: Family

Intraflagellar transport of ciliary precursors such as tubulin from the cytoplasm to the ciliary tip is required for ciliogenesis . Intraflagellar transport protein 74 (IFT74) is a component of the intraflagellar transport (IFT) complex B, which contains at least 20 different protein subunits. Together with IFT81, it forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium . In humans, it was reported to be essential for flagellogenesis during spermatogenesis .
Chromatin remodeling regulator CECR2 (CECR2)
Type: Family

Chromatin remodeling regulator CECR2 is part of the CERF (CECR2-containing-remodeling factor) complex, which is a chromatin remodelling complex that plays important roles in embryogenesis and neurulation . It may also contribute to spermatogenesis and form complexes with SNF2H in the testis .

CECR2 gene is a candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2 .
Lid2 complex component Snt2 (Snt2)
Type: Family

In fission yeasts, Snt2 is a component of the Lid2 complex, a complex that may be involved in regulation of chromatin remodelling . S. cerevisiae Snt2 is an E3 ubiquitin ligase that regulate histone protein levels .
Coiled-coil domain-containing protein 172 (CCDC172)
Type: Family

Proteins in this entry belong to the CCDC172 family and are functionally uncharacterised.
Protein FAM81 (FAM81)
Type: Family

This group of uncharacterised proteins is known as family FAM81.
Protein FAM169 (FAM169)
Type: Family

This is a family of uncharacterised proteins.
Serine-rich coiled-coil domain-containing protein (CCSER)
Type: Family

Proteins in this group belong to the CCSER family which consists of uncharacterised serine-rich coiled-coil domain-containing proteins.
Calbindin, six-EF hands domain (Calbindin_six-EFh_dom)
Type: Domain

Calbindin (also known as calbindin D28) is a major calcium-binding and buffering protein that is associated with Alzheimer's disease . It plays an important role in preventing a neuronal death as well as maintaining calcium homeostasis .

This protein contains six EF-hand motifs in a single globular domain (this entry), where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity .
Protein Csf1 (Csf1)
Type: Family

Cold sensitive for fermentation protein 1 (Csf1, also known as Bridge-like lipid transfer protein family member 1) is a fungal membrane protein required for fermentation at low temperature . It has been identified as a tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum .
Protein FAM78 (FAM78)
Type: Family

This is a family of uncharacterised proteins.
Anaphase-promoting complex subunit 16 (APC16)
Type: Family

The anaphase promoting complex/cyclosome (APC/C) is a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C consists of thirteen different subunits and, in somatic cells, has two co-activators: Cdc20 and Cdh1 (also known as Fzr1), which associate with the APC/C core at defined stages of the cell cycle. APC/C is only active between metaphase and the end of the next G1 phase. During this time, APC/CCdc20 initiates anaphase and mitotic exit, while APC/CCdh1 contributes to mitotic exit and establishment of a stable G1 state .

This entry represents the APC/C subunit 16 .
Calretinin (CALB2)
Type: Family

Calretinin (CR) is a calcium-binding protein that contains the EF-hand domains. It is expressed in a variety of normal and tumorigenic tissues . CR is a multi-functional protein associated with development, cell proliferation, differentiation, and cell death . It may be used as a marker in the differential diagnosis of ameloblastoma and keratocystic odontogenic tumour (KCOT) .
Arginine/serine-rich protein 1 (RSRP1)
Type: Family

This is a family of arginine/serine-rich proteins from Metazoa. The function of the proteins in this family is not known.
Proline-rich membrane anchor 1 (PRIMA1)
Type: Family

Proline-rich membrane anchor 1 (PRiMA) is required to organise acetylcholinesterase (ACHE) into tetramers and to anchor them to the basal lamina of the neuromuscular junction and to the membrane of neuronal synapses in brain . ACHE hydrolyses acetylcholine, thereby regulating cholinergic stimulation. The MAP kinase signalling pathway is one of the transcriptional regulators controlling PRiMA gene expression during neuronal differentiation .
Transmembrane protein 98 (TMEM98)
Type: Family

This entry represents a family of transmembrane proteins, which function as a negative regulator of MYRF in oligodendrocyte differentiation and myelination. Interacts with the C-terminal of MYRF inhibiting MYRF self-cleavage and N-fragment nuclear translocation . The secreted TMEM98 form promotes differentiation of T helper 1 cells (Th1) .