SII-SWORD/CoKE huggingface dataset:
Zinc finger protein 414 (ZN414)
Type: Family

The function of zinc finger protein 414 (ZN414) is not known. ZN414 contains a C2H2-type zinc ribbon. Homologues are known only from vertebrates.
Fcf2/DNTTIP2 (Fcf2/DNTTIP2)
Type: Family

This entry includes Fcf2 from budding yeasts and DNTTIP2 from animals. Fcf2 is involved in pre-rRNA processing . DNTTIP2 regulates the transcriptional activity of DNTT and ESR1 .
Coiled-coil domain-containing protein R3HC1/R3HCL (R3HC1/R3HCL)
Type: Family

The functions of R3HC1 and R3HCL are not known.
BTBD10/KCTD20, BTB/POZ domain (BTBD10/KCTD20_BTB/POZ)
Type: Domain

This entry represents the BTB/POZ domain found in BTBD10 and KCTD20 proteins.

BTBD10 acts as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated . KCTD20 is also a positive regulator of Akt .
BTBD10/KCTD20 (BTBD10/KCTD20)
Type: Family

BTBD10 acts as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated . KCTD20 is also a positive regulator of Akt .
IQ domain-containing protein F (IQCF)
Type: Family

This entry includes IQ domain-containing proteins F1, F2, F3, F5, and F6 from vertebrates. In mice, IQCF1 is a acrosomal protein involved in sperm capacitation and the acrosome reaction .
Protein melted-like (Melted-like)
Type: Family

This entry includes protein melted from fruit flies and its homologues. They contain a single C-terminal PH domain that is required for membrane targeting. Melted interacts with both Tsc1 and FOXO and can recruit them to the cell membrane . In vertebrates the melted protein homologue, veph, is expressed in the developing central nervous system . The human homologue VEPH1 (ventricular zone-expressed PH domain-containing protein homologue 1) has been shown to inhibit TGF-beta signaling by impeding the release of activated SMAD2 from TbetaRI .
Coiled-coil domain-containing protein 33 (CCD33)
Type: Family

The function of coiled-coil domain-containing protein 33 (CCD33) is not known.
von Willebrand factor A domain-containing protein 8 (VWA8)
Type: Family

The function of von Willebrand factor A domain-containing protein 8 (VWA8) is not known. The VWA8 short isoform has in vitro ATPase activity .
Protein Spa2/Sph1 (Spa2/Sph1)
Type: Family

This entry includes Spa2 and Sph1 from budding yeasts. They function in cell polarity and cell morphogenesis. Sph1- and Spa2-deleted cells possess defects in mating projection morphology and pseudohyphal growth . Spa2 has been shown to interact with actomyosin ring components during cytokinesis .
Centrosomal protein of 120kDa-like (CEP120-like)
Type: Family

CEP120 is a centrosomal protein required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner . It has been shown to interact with SPICE1 and CPAP . This entry also includes CEP120-like proteins from plants and fungi, which do not have centrosomes.

Mutations of the CEP120 gene cause short-rib thoracic dysplasia 13 with or without polydactyly (SRTD13) and Joubert syndrome 31 (JBTS31) .
tRNA pseudouridine synthase Pus10-like (Pus10-like)
Type: Family

Archaeal Pus10 is responsible for the synthesis of pseudouridine from uracil-54 and uracil-55 in the psi GC loop of transfer RNAs . This entry also includes Pus10 homologues from eukaryotes. Human Pus10 homologue is a modulator of TRAIL-induced cell death and is required for the progression of the apoptotic signal through intrinsic mitochondrial cell death . Although eukaryotic Pus10 shares a conserved catalytic domain with archaeal Pus10 genes, their biological roles are not resolved .
Protein cordon-bleu-like (COBL-like)
Type: Family

This entry includes protein cordon-bleu (COBL) and COBLL1. Single WH2 domains can sequester G-actin. COBL contains three G-actin-binding WH2 domains and act as a dynamizer of actin assembly. COBL has profilin-like filament nucleating and severing activities . It is a CaM-controlled component important for early neuronal morphogenesis .
Protein Red-like (Red-like)
Type: Family

Protein RED (also known as IK) is found in the nucleus and is a component of the spliceosome . It is also associated with the spindle pole where it co-localizes with and interacts with the spindle assembly checkpoint protein MAD1 during metaphase and anaphase. Depletion of RED shortens the mitotic cycle and MAD1 is incorrectly localized .

Proteins in this entry also include SPBC1539.02 from the fission yeast and smu-2 from C. elegans. SPBC1539.02 is required for chromosome segregation during meiosis . SMU-2 and SMU-1 bind to each other as components of the spliceosome and modulate splice site selection of many pre-mRNAs .

Protein RED and related proteins contain an arginine/glutamic acid/aspartic acid repetitive sequence. The region in question has several conserved NLS sequences and a putative trimeric coiled-coil region, indicative that these proteins are expressed in the nucleus .
BET1, SNARE domain (BET1_SNARE)
Type: Domain

This entry represents the SNARE domain of BET1-like protein.

BET1-like protein (also known as Golgi SNARE with a size of 15kDa, GS15 or
GOS-15) is a protein required for movement of vesicles with the Golgi. In one hypothesis of how proteins move through the Golgi, vesicles containing proteins are budded from one cisterna and then fuse with the next cisterna in the stack. The fusion of the vesicle to the cisterna membrane requires N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNAREs on a transport vesicle are known as v-SNAREs, and those on the target compartment are known as t-SNAREs; the v-SNARE and a t-SNARE form a trans-SNARE complex. GS15 is a v-SNARE protein found in the medial-cisternae of the Golgi apparatus and it forms a complex with three t-SNAREs (Syntaxin5, GS28, and Ykt6) to form a distinct GS15/Syn5/GS28/Ykt6 SNARE complex. This complex is required for endoplasmic reticulum to Golgi transport and intra-Golgi transport .
Pat1-like (Pat1-like)
Type: Family

This entry represents budding yeast Pat1 and its homologues.

Pat1 is involved in translational repression and enhanced mRNA decay. It is part of the Lsm1-7-Pat1 complex that plays a role in activation of deadenylation-dependent decapping in the 5' to 3' pathway and in the protection of mRNA 3' ends .

There are two Pat1 homologues in vertebrates, Pat1a and Pat1b, in contrast to the single protein in yeast and invertebrates. The maternally expressed Pat1a protein acts as a translational repressor, while Pat1b functions in mRNA decay in somatic cells. Pat1b is localised to P-body and is a nucleocytoplasmic shuttling protein that may perform various nuclear functions upstream of their multiple posttranscriptional regulatory roles in the cytoplasm .
3-deoxy-D-manno-octulosonic acid transferase (Kdotransferase)
Type: Family

The proteins in this family are found mainly in bacteria and plants. In bacteria, 3-deoxy-D-manno-octulosonic acid (Kdo) transferase is involved in lipopolysaccharide synthesis; it catalyses the transfer of two Kdo residues from CMP-Kdo to lipid IV(A), the precursor of lipid A . In plants it is though to be involved in the synthesis of a mitochondrial lipid A-like molecule .
Coiled-coil domain-containing protein CCDC148/CCDC112 (CCDC148/CCDC112)
Type: Family

The functions of coiled-coil domain-containing proteins CCDC148 and CCDC112 are not known.
E3 ubiquitin-protein ligase Zswim2 (Zswim2)
Type: Family

Zswim2, also known as MEX, is an E3 ubiquitin ligase that promotes death receptor-induced apoptosis .
TPR and ankyrin repeat-containing protein 1 (TRANK1)
Type: Family

The function of TPR and ankyrin repeat-containing protein 1 (TRANK1) is not known.
CD2 antigen cytoplasmic tail-binding protein 2/Lin1 (CD2BP2/Lin1)
Type: Family

CD2BP2, also known as U5-52K or LIN1, is a component of the U5 snRNP complex and acts as a splicing factor . It also may play a role in the immune response as CD2 receptor binding protein 2 (CD2BP2) . Lin1 from Saccharomyces cerevisiae is a non-essential component of U5 snRNP ; it may link together proteins involved in chromosome segregation, mRNA splicing and DNA replication .
RNA-binding protein NOB1 (NOB1)
Type: Family

RNA-binding protein NOB1 has a nuclear location and contains a PIN domain and binds a single zinc ion. Budding yeast Nob1 is involved in proteasomal and 40S ribosomal subunit biogenesis . It is also required for maturation of the small subunit ribosomal RNA by catalyzing cleavage at site D after export of the preribosomal subunit into the cytoplasm. Nob1 is also found in archaea, where it is manganese-dependent and also processes RNA-substrates . This entry also includes VapC1 and VapC3. VapC1 is a toxic component and a ribonuclease of a toxin-antitoxin (TA) module .
Protein sepa-1 (Sepa-1)
Type: Family

This entry includes protein sepa-1 from roundworms. Sepa-1 is a receptor protein that connects P-granules in somatic cells with the autophagic machinery . It directly binds to the P granule component PGL-3 and also to the autophagy protein LGG-1/Atg8 .
Surface antigen D15-like (D15-like)
Type: Family

This entry includes proteins with a domain similar to that of bacterial surface antigen (D15) from Haemophilus influenzae. Proteins include:

Outer membrane protein assembly factor BamA, which forms part of the outer membrane protein assembly complex involved in assembly and insertion of β-barrel proteins into the outer membrane in Gram-negative bacteria .

Sorting and assembly machinery component 50, which is required for the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes .

Translocation and assembly module subunit TamA, which is a component of the translocation and assembly module (TAM) autotransporter assembly complex which translocates autotransporters across the outer membrane .

Outer envelope protein 80, chloroplastic, for which knockout is embryonic lethal .

Outer envelope protein 39, chloroplastic .

Protein TOC75, chloroplastic (translocon at the outer envelope membrane of chloroplasts, 75 kD), which functions as a preprotein translocation channel during chloroplast import .
JNK-interacting protein 3/4 (JIP3/JIP4)
Type: Family

C-Jun-amino-terminal kinase (JNK)-interacting protein 3 (JIP3) and 4 (JIP4) are two highly related scaffolding proteins for MAP kinases. They are binding partners for molecular motors kinesin-1 and dynactin, as well as for the small G protein ARF6, which they bind through their leucine zipper II (LZII) region . ARF6, together with JIP3 and JIP4, regulates membrane-tethered membrane type 1-matrix metalloproteinase exocytosis in cancer invasion .

The function of JIP4 has been shown to be different from that of other JIP proteins. Although JIP4 binds JNK, it does not activate JNK signaling .
RNA polymerase II-associated protein RPAP1/Rba50 (RPAP1/Rba50)
Type: Family

This entry represents a group of RNA polymerase II-associated proteins, including RPAP1 from animals and Rba50 from yeasts.

In Saccharomyces cerevisiae (Bakers yeast), inhibition of RNA polymerase II-associated protein 1 (RPAP1) synthesis leads to global changes in gene expression that closely resemble those observed upon loss of the RNAPII subunit Rpb11 . RPAP1 forms an interface between the RNA polymerase II enzyme and chaperone or scaffolding proteins, suggesting its essential role in linking RNA polymerase II to regulators involved in protein complex formation. Furthermore, it is required for the interaction of the RNA polymerase II complex with acetylated histone H3, indicating a function in the coordination between transcription and chromatin modification.
Signal recognition particle SRP9-like (SRP9-like)
Type: Family

This entry represents proteins contain an SRP9 domain, such as human signal recognition particle 9kDa protein (SRP9), a component of the signal recognition particle (SRP) and its homologues, such as the Srp21 protein from budding yeasts .

The signal recognition particle (SRP) is a multimeric protein, which along with its conjugate receptor (SR), is involved in targeting secretory proteins to the rough endoplasmic reticulum (RER) membrane in eukaryotes, or to the plasma membrane in prokaryotes . SRP recognises the signal sequence of the nascent polypeptide on the ribosome. In eukaryotes this retards its elongation until SRP docks the ribosome-polypeptide complex to the RER membrane via the SR receptor . Eukaryotic SRP consists of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) and a single 300 nucleotide 7S RNA molecule. The RNA component catalyses the interaction of SRP with its SR receptor . In higher eukaryotes, the SRP complex consists of the Alu domain and the S domain linked by the SRP RNA. The Alu domain consists of a heterodimer of SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. This domain is necessary for retarding the elongation of the nascent polypeptide chain, which gives SRP time to dock the ribosome-polypeptide complex to the RER membrane. In archaea, the SRP complex contains 7S RNA like its eukaryotic counterpart, yet only includes two of the six protein subunits found in the eukaryotic complex: SRP19 and SRP54 .
TACC family (TACC)
Type: Family

The TACC protein family localises to the centrosome (the spindle pole body in fungi) and mitotic spindle, and plays a crucial role in bipolar spindle assembly . Furthermore, Alp7/TACC recruits kinesin-8-PP1 to the kinetochore to regulate timely mitotic progression and chromosome movement during anaphase A .

There is only one TACC protein in the nematode Caenorhabditis elegans (TAC-1), in Drosophila melanogaster (D-TACC), in Xenopus laevis (Maskin), and in fission yeast (Alp7 also known as Mia1p); by contrast, mammals have three TACC proteins (TACC1, TACC2 and TACC3) .
Exophilin-5 (EXPH5)
Type: Family

Exophilin-5 (EXPH5) has putative roles in intracellular vesicle trafficking. Mutations in the EXPH5 gene cause inherited skin fragility .
Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4)
Type: Family

PPP4R4 is a putative regulatory subunit of serine/threonine-protein phosphatase 4 .
Rho guanine nucleotide exchange factor 10/17 (ARHGEF10/ARHGEF17)
Type: Family

This entry includes Rho guanine nucleotide exchange factors 10 and 17.

ARHGEF10 is a Rho guanine nucleotide exchange factor that may play a role in developmental myelination of peripheral nerves . It was found to regulate mitotic spindle formation and play a role in the regulation of the cell division cycle .

ARHGEF17 is a guanine nucleotide exchange for for RhoA GTPases; it contains a Dbl homology (DH) domain but lacks the typical pleckstrin homology domain .
DNA repair/transcription protein MMS19 (MMS19)
Type: Family

MMS19 is a key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity . In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER), homologous recombination-mediated double-strand break DNA repair, DNA replication and RNA polymerase II (POL II) transcription .
Inscuteable (Inscuteable)
Type: Family

Inscuteable (Insc) is a key regulator of spindle orientation in asymmetric divisions in both Drosophila and mammals . Insc is a competitive interactor of LGN .
GDP-fucose protein O-fucosyltransferase 1 (POFUT1)
Type: Family

GDP-fucose protein O-fucosyltransferase 1 (POFUT1) transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins. It is essential for Notch signal transduction in mammals . Mutations in the POFUT1 gene cause Dowling-Degos disease 2 (DDD2), a type of rare autosomal-dominant genodermatosis characterised by reticular hyperpigmentation and hypopigmentation of the flexures . The structure of POFUT1 has been determined .
Protodermal factor 1 (Protodermal_1)
Type: Family

This family of plant proteins includes protodermal factor 1, a putative extracellular proline-rich protein that it is exclusively expressed in the L1 layer of vegetative, inflorescence and floral meristems and the protoderm of organ primordia .
Protein ICln/Lot5/Saf5 (ICln/Lot5/Saf5)
Type: Family

This entry includes ICln from animal and plants, and Lot5/Saf5 from fungi. The function of Lot5 (low temperature responsive 5) is not known .

ICln, known as methylosome subunit pICln or chloride conductance regulatory protein ICln, owes these different names to its function in multiple regulatory pathways as different as ion permeation, ribonucleoprotein biosynthesis and cytoskeletal organisation . ICln can be identified both in the cytosol and in the cellular membrane, where it functions as a chloride current regulator and is important in regulating volume decrease after cellular swelling .

pLCln also functions as a Sm chaperone in the stepwise snRNP assembly process . snRNPs is a RNA-protein complex esessential to the removal of introns from pre-mRNA . In humans, the core of snRNPs is composed of seven Sm proteins bound to snRNA. pLCln tethers the hetero-oligomers SmD1/D2 and SmE/F/G into a ring-shaped 6S complex, which subsequently docks onto the SMN complex. The SMN complex then removes pICln and enables the transfer of pre-assembled Sm proteins onto snRNA . Consistent with the role of human pICln, the orthologue from S. pombe is required for optimal production of the spliceosomal snRNPs and for efficient splicing .

In Schizosaccharomyces pombe, Saf5 serves as a chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs .
RNF37, RING-Ubox (RNF37_RING-Ubox)
Type: Domain

RNF37 is an E3 ubiquitin-protein ligase found exclusively in the nucleus as part of a nuclear dot-like structure. It interacts with the molecular chaperone VCP/p97 protein. RNF37 contains a U-box domain followed by a potential nuclear location signal (NLS), and a C-terminal C3HC4-type RING-HC finger. The U-box domain is a modified RING finger domain that lacks the hallmark metal-chelating cysteines and histidines of the latter, but is likely to adopt a RING finger-like conformation. The presence of the U-box, but not of the RING finger, is required for the E3 activity. The U-box domain can directly interact with several E2 enzymes, including UbcM2, UbcM3, UbcM4, UbcH5, and UbcH8, suggesting a similar function as the RING finger in the ubiquitination pathway .
Protein egg apparatus-1 (Egg_app_1)
Type: Family

This family of plant proteins includes EGG APPARATUS-1 (EA1), which is required for female fertility. It is a small protein involved in short-range signaling required for pollen tube attraction by the female gametophyte. It is exclusively expressed in the egg apparatus .
Large ribosomal subunit protein mL43 (Ribosomal_mL43)
Type: Family

This entry includes the large ribosomal subunit protein mL43, also known as 39S ribosomal protein L43 (MRPL43) in animals and 54S ribosomal protein L51 (MRPL51) in fungi. They are components of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins .
LNK family (LNK)
Type: Family

The LNK family consists of light and clock regulated morning genes from plants. These control both the pace of circadian rhythms and the photoperiodic regulation of flowering time by promoting the expression of a subset of clock and flowering time genes in the afternoon . The LCL domain of clock-related factor REVEILLE8 recruits LNKs to target promoters, while its MYB domain provides DNA binding specificity. In turn, LNKs interact with RNA Polymerase II and the transcript elongation FACT complex, resulting in rhythmic changes of gene expression .
Ral GTPase-activating protein subunit beta (RALGAPB)
Type: Family

Ral GTPase-activating protein subunit beta (RALGAPB) is a non-catalytic subunit of the heterodimeric RalGAP1 and RalGAP2 complexes which act as GTPase activators for the Ras-like small GTPases RALA and RALB .
EEIG1/2-like (EEIG1/2-like)
Type: Family

This entry includes human early estrogen-induced gene proteins 1 and 2 (EEIG1/2), also known as FAM102A and FAM102B, respectively, and some uncharacterised proteins from fungi. EEIG1 was first identified as early estrogen-inducible gene in breast cancer cell lines . More recently, EEIG1 has been described as a RANK ligand (RANKL)-inducible protein that controls RANK-mediated osteoclast formation, which constitutes a possible therapeutic target for pathological bone destruction .
Serine protease inhibitor Kazal-type 4-like (Spink4-like)
Type: Family

This entry includes a group of protease inhibitors from inhibitor family I1, including Spink4 from mammals and thrombin inhibitor rhodniin from a Triatomid bug .
Protein XRI1 (XRI1)
Type: Family

This family of plant proteins includes XRI1 (X-ray induced 1), which is essential for male and female meiosis. It could be required for meiotic DNA repair .
C2 domain-containing protein 2-like (C2CD2/C2CD2L)
Type: Family

This entry includes C2 domain-containing protein 2 (C2CD2) and C2CD2-like (C2CD2L) proteins. C2CD2L, also known as TMEM24, is an endoplasmic reticulum (ER)-anchored membrane protein that binds lipids and transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P2 hydrolyzed during signaling . The function of C2CD2 is not known.
Uncharacterized protein YML079W-like (YML079W-like)
Type: Family

The function of this family of proteins is not known. The crystal structure of the Saccharomyces cerevisiae member, YML079w, revealed a jelly-roll fold .
Sorting nexin SNX20/SNX21 (SNX20/SNX21)
Type: Family

This entry includes sorting nexins SNX20 and SNX21. They are sorting nexins (SNX) that orchestrate membrane trafficking and signaling events required for the proper distribution of proteins within the endosomal network. They contain an N-terminal PX domain and a C-terminal PX-associated B (PXB) domain. Their structures have been determined . SNX20 has been shown to direct subcellular distribution of PSGL-1, a mucin-like glycoprotein . SNX21 has been shown to serve as a scaffold for the endosomal recruitment of huntingtin .
Transcription factor Sp4-like (Sp4-like)
Type: Family

This family includes a group of zinc finger-containing proteins from human, including ZNF826/781 which may be involved in transcriptional regulation and Sp4, which binds to GT and GC boxes promoters elements and it is probable a transcriptional activator. It is required for normal male reproductive behavior.
V-set and immunoglobulin domain-containing protein 4 (VSIG4)
Type: Family

V-set and Ig domain-containing 4 (VSIG4) is a strong negative regulator of T cell proliferation and IL-2 production . It also negatively regulates macrophage activation by activating the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, reduction in mitochondrial reactive oxygen species secretion, and macrophage inhibition .
Tetratricopeptide repeat protein 30 (TT30)
Type: Family

This entry includes TT30A, TT30B (also known as intraflagellar transport protein 70A/B) and related proteins. They contain tetratricopeptide repeats. These proteins may be required for polyglutamylation of axonemal tubulin in sensory cilia and they may play a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.
Somatomedin-B and thrombospondin type-1 domain-containing protein (SBSPO)
Type: Family

The function of SBSPO is not known.