SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF4530 (DUF4530)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically around 140 amino acids in length. The human member of this family is C19orf69.
Tektin bundle-interacting protein 1 (TKTI1)
Type: Family

This family includes Tektin bundle-interacting protein 1 (TKTI1) which has been recently characterised as a microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. It is located at the centre of the tektin bundle where may function to recruit tektins or stabilize the bundle .
CB1 cannabinoid receptor-interacting protein 1 (CNRIP1)
Type: Family

This family of proteins interacts with cannabinoid receptor 1 (CNR1). In humans, there are two isoforms, CRIP1a and CRIP1b. CRIP1a, but not CRIP1b, suppresses cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels .
Aftiphilin, clathrin-binding box (Clathrin-bd)
Type: Domain

Aftiphilin forms a stable complex with p200 and gamma-synergin . It may play a role in membrane trafficking. Aftiphilin contains a clathrin box, with two identified clathrin-binding motifs .
Protein of unknown function DUF4532 (DUF4532)
Type: Family

This family includes testis-expressed protein 52, which is functionally uncharacterised. This family of proteins is found in metazoa.
FAM198 family (FAM198)
Type: Family

This family of proteins is found in eukaryotes. The function of this family is unknown. Murine FAM198B is downregulated by FGFR signalling .
Cytochrome c oxidase assembly protein COX14 (COX14)
Type: Family

COX14 plays an essential role in cytochrome oxidase assembly. The COX14 product is a low-molecular weight membrane protein of mitochondria, but it is not a subunit of cytochrome oxidase . Orthology-prediction methods have identified the vertebrate C12orf62 orthologues to be orthologues of the yeast COX14 .
DML1/Misato, tubulin domain (DML1/Misato_tubulin)
Type: Domain

Misato from Drosophila and DML1p from fungi are descendants of an ancestral tubulin-like protein, and exhibit regions with similarity to members of a GTPase family that includes eukaryotic tubulin and prokaryotic FtsZ . DML1p and Misato have been co-opted into a role in mtDNA inheritance in yeast, and into a cell division-related mechanism in flies, respectively. DML1p might additionally function in the partitioning of the mitochondrial organelle itself, or in the segregation of chromosomes, thereby explaining its essential requirement. This domain subject to extensive post-translational modifications.
Plasmodium falciparum erythrocyte membrane protein-1, N-terminal segment (PfEMP1_NTS)
Type: Domain

NTS, the N-terminal segment, is the most variable part of the variant surface antigen family of Plasmodium falciparum, the erythrocyte membrane protein-1 (PfEMP1) proteins. PfEMP1 is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors . A structural and functional study of the N-terminal domain of PfEMP1 from the VarO variant comprising the N-terminal segment (NTS) and the first DBL domain, shows this region is directly implicated in rosetting. NTS, previously thought to be a structurally independent component of PfEMP1, forms an integral part of the DBL1 domain that is found to be the important heparin-binding site . This domain is closely associated with PFEMP DBL domain (

), and Duffy-antigen binding (

).
Plasmodium falciparum erythrocyte membrane protein 1, acidic terminal segment (PfEMP1_ATS)
Type: Domain

ATS is the intracellular and relatively conserved acidic terminal segment of the Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) . This domain appears to be present in all variants of the highly polymorphic PfEMP1 proteins.
Rho guanine nucleotide exchange factor 5/35, N-terminal (ARHGEF5/35_N)
Type: Domain

This entry represents the N-terminal domain of Rho guanine nucleotide exchange factor 5 (also known as Ephexin3 or TIM) and Rho guanine nucleotide exchange factor 5-like (also known as Rho guanine nucleotide exchange factor 35).
Cell-cell fusogen EFF/AFF (Fusogen_EFF/AFF)
Type: Family

Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally . AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans .

The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity . C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle .
Cilia- and flagella-associated protein 144 (CFAP144)
Type: Family

This family includes Cilia- and flagella-associated protein 144 (CFAP144, also known as FAM183A) from human and its homologues. This is a microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating . this entry also includes CFAP144P1 (known as FAM183B) that could be a product of a pseudogene.
High mobility group box domain 5 (HMG_box_5)
Type: Domain

Nucleolar transcription factor/upstream binding factor contains six HMG box domains. This is the fifth HMG box domain in these proteins. This domain has lost DNA-binding ability .
Phytoplasma antigenic membrane protein (Phyto-Amp)
Type: Family

This entry represents the antigenic membrane protein (also known as Phyto-Amp) from Candidatus Phytoplasma . The bacteria are limited to the phloem and pose a major threat to agriculture worldwide. They are transmitted in a persistent, propagative manner by phloem-sucking Hemipteran insects. Phytoplasma membrane proteins are in direct contact with hosts and are assumed to be involved in determining vector specificity. Phyto-Amp is thought to be one family of proteins that mediates such specificity. The proteins appear to be encoded by circular extrachromosomal elements, at least one of which is a plasmid .
Sporulation-specific protein 71, N-terminal domain (Spo7_2_N)
Type: Domain

This entry represents the N-terminal domain of the sporulation-specific protein 71 (Spo71) from fungi. In many members this domain is associated with a Pleckstrin-homology (PH) domain. Spo71 is required for spore wall formation during sporulation .
Penicillin-binding protein Tp47, domain C (PBP-Tp47_dom_C)
Type: Domain

Domain C is the largest domain in this unusual penicillin-binding protein (PBP), Tp47. This domain is mainly characterised by an immunoglobulin fold with two opposing β-sheets that form the typical barrel-like structure. In contrast to the classical immunoglobulin fold, however, this has an additional β-strand inserted after strand 3. Also, the strands are connected by rather large loops. Helices are inserted between strands 2 and 3 and between strands 4 and 5. Domain C interacts with domain B via a surface that has a slightly concave, goblet-like shape in addition to interacting tightly with domain A and weakly with domain D. Tp47 is unusual in that it displays beta-lactamase activity, so it does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP .
UNC119-binding protein (UNC119-bd)
Type: Family

UNC119-binding protein family include human Macrophage immunometabolism regulator (also known as C5orf30) and its homologues from eukaryotes. C5orf30 may play a role in trafficking of proteins via its interaction with UNC119 and UNC119B cargo adapters. It may also play a role in ciliary membrane localisation .
Penicillin-binding protein Tp47, domain D (BP-Tp47_dom_D)
Type: Homologous_superfamily

The crystal structure of the unusual penicillin-binding protein (PBP) Tp47 from Treponema pallidum revealed a unique structure different to any other known PBP, and thus it appears to represent an entirely new class of PBP. Tp47 consists of four distinct domains (A-D) arranged to give the molecule a crab-like appearance. Domain D, like domain C, features an immunoglobulin fold. In contrast to domain C it contains only the characteristic seven-stranded barrel and short loops. As in domain C, a single α-helical turn is inserted between strands 2 and 3 . Domain D is rather isolated as it only interacts with domain C via an ionic interaction between Arg-330 and Glu-404 in the linker region. This explains the large degree of motion observed for this domain.

The abundance of hydrophobic residues and the immunoglobulin fold of domain D suggests that it mediates protein-protein interactions. In addition its location, flexibility, and relative disposition indicate a function other that PBP and beta-lactamase activities . It is thought to have an haemagglutination activity.
Penicillin-binding protein Tp47 domain A (PBP-Tp47_A)
Type: Domain

This is the first domain in Tp47, an unusual penicillin-binding protein (PBP) from Treponema pallidum. It is mainly composed of β-strands and is sequentially non-contiguous. The first three domains in Tp47 interact with each other through intimate domain-domain interfaces. Domain A contacts domain B through its N-terminal segment. Domain A also interacts tightly with domain C. Tp47 is unusual in that it displays beta-lactamase activity, and thus it does not fit the classical structural and mechanistic paradigms for PBPs. Tp47 appears to represent a new class of PBP .
VCF1/2-like (VCF1/2-like)
Type: Family

This entry represents a family of proteins mainly found in vertebrates, including human Protein VCF1/2 (also known as FAM104A/B). These proteins contain a conserved SLQ sequence motif.
Pilus-assembly complex, chaperone PapJ (PapJ)
Type: Family

PapJ and PrsJ are part of the Pap pilus assembly complex that plays an auxiliary role by ensuring the proper integration of PapA into the fimbrial shaft . PapA is the major shaft protein of the pilus.
Nse4/EID protein, Nse3/MAGE-binding domain (Nse4_Nse3-bd)
Type: Domain

This entry represents the Nse3/MAGE (

) binding domain found in NSE4/EID family proteins .

Proteins in the NSE4/EID (Non-structural maintenance of chromosomes element 4/EP300-interacting inhibitor of differentiation 3) family are components of the Smc5/6 complex that is involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components . In human, it acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. It may function as a coinhibitor of other CREBBP/EP300-dependent transcription factors .

Interestingly, there is a single NSE4 gene in most eukaryotes up to non-placental mammals while there are several NSE4/EID copies in placental mammals . In humans, there are two NSE4 proteins, NSE4a and NSE4b/EID3. They contain both N and C-terminal kleisin domains. Their N-terminal domain binds to SMC6 neck and bridges it to the SMC5 head and to the Nse3 (another SMC5-6 complex subunit) pocket , which seems to increased the stability of the ATP-free SMC5/6 complex.
Ecp2 effector protein-like (Ecp2-like)
Type: Domain

This domain corresponds to the mature part of the Ecp2 effector protein from the tomato pathogen Cladopsorium fulvum (also known as Passalora fulva). Effectors are low molecular weight proteins that are secreted by bacteria, oomycetes and fungi to manipulate their hosts and adapt to their environment. Ecp2 is a 165 amino acid secreted protein that was originally identified as a virulence factor in C. fulvum, since disruption reduces virulence of the fungus on tomato plants. It has been recently determined that Ecp2 is a member of a novel, widely distributed and highly diversified within the fungal kingdom, multigene superfamily which have been designated Hce2, for Homologs of C. fulvum Ecp2 effector .

This domain is also found in secreted chitanases LysM15 and LysM18 which may be involved in the degradation of chitin, a component of the cell walls of fungi and exoskeletal elements of some animals, and they might be involved in manipulation of host defenses for successful infection .
Plant antimicrobial peptide (Plant_Antimicrobial)
Type: Domain

This domain includes plant antimicrobial peptides . They adopt an α-helical hairpin fold stabilised by two disulphide bonds .
Alkyl sulfatase dimerisation domain (Alkyl_sulf_dimr)
Type: Domain

This domain is found in alkyl sulfatases such as the Pseudomonas aeruginosa SDS hydrolase SdsA1 (

), where it acts as a dimerisation domain .
Alkyl sulfatase, C-terminal (Alkyl_sulf_C)
Type: Domain

This domain is found at the C terminus of alkyl sulfatases. Together with the N-terminal catalytic domain, this domain forms a hydrophobic chute and may recruit hydrophobic substrates .
Macin (Macin)
Type: Family

The macin family consists of theromacin, neuromacin and hydramacin-1. All of the macins exert antimicrobial activity , but neuromacin also possesses nerve repair activity . Structurally, they form a disulphide-stabilised α-β motif .
Fimbrillin-like (Mfa-like_2)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are typically between 348 and 360 amino acids in length. Analysis of structural comparisons shows this family to be part of the FimbA (CL0450) superfamily of adhesin components or fimbrillins.
Ciliary microtubule inner protein 4 (CIMIP4)
Type: Family

This entry represents homologues of Ciliary microtubule inner protein 4 (CIMIP4, also known as C22orf33, EAN57, TEX33). CIMIP4 is an axoneme microtubule inner protein (MIP) that binds to protofilament B07 .
Factor associated with metabolism and energy (FAME)
Type: Family

This entry represents the metazoan family of proteins called FAME. Proteins in this family are typically between 128 and 299 amino acids in length. Knockout experiments link FAME to altered body weight and energy expenditure. FAME is a kidney-enriched, membrane-bound protein, influencing albumin levels in urine and ferritin in blood .
Protein of unknown function DUF4618 (DUF4618)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 238 and 363 amino acids in length. There are two conserved sequence motifs: EYP and KCTPD.
Long chain scorpion toxin, cysteine-stabilized alpha/beta domain (Long_scorpion_toxin_alpha/beta)
Type: Domain

This entry consists of long chain scorpion potassium channel toxins and scorpine-like peptides . Scorpine-like peptides include scorpine, opiscorpine1-4, HgeScplp1, HgeScplp2 and heteroscorpine 1. They exhibit strong antimicrobial effects as well as cytolytic activity against eukaryotic cells .

This is the cysteine-stabilized alpha/beta (CS-α/β) domain, which is more closely related to invertebrate defensins, than to the classical scorpion toxins. Its structure shows an α-helix along with one β-sheet stabilized by three disulfide bridges, folding into a CS-α/β motif (see

) .
Shadow of prion protein (Shadoo)
Type: Family

This family of prion-like proteins has a neuroprotective function, similar to PrP(C)-like . Shadoo is mainly expressed in the brain, and highly expressed in the hippocampus, the area of the brain which co-ordinates memory as well as spatial memory and navigation. This protein may also alter the biological actions of normal and abnormal prion protein (PrP) which lead to lethal neurodegenerative diseases . This family of proteins is found in eukaryotes. Proteins in this family are approximately 150 amino acids in length, of which the first 90 are alanine rich.
Cilia- and flagella-associated protein 418 (CFAP418)
Type: Family

C8orf37 encodes a ciliary protein known as CFAP418. In humans, mutations in C8orf37 cause two types of retinal dystrophies: cone-rod dystrophy type 16 (CORD16) and retinitis pigmentosa type 64 (RP64). CORD16 affects the cone receptors which detect red, green or blue wavelengths of light, and RP64 affects the cone receptors first and then the rod receptors. Both of these affect the photo-receptors in the eye leading to colour blindness or blindness respectively .
MMS19, N-terminal (MMS19_N)
Type: Domain

This entry represents the N-terminal domain of MMS19. 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 .
Testis-specific gene 13 protein (TSGA13)
Type: Family

This family of uncharacterised proteins are found in chordates. In humans this gene is found to be expressed specifically in the testes.
Protein melan-A (MLANA)
Type: Family

Melan-A, also known as melanoma antigen recognised by T-cells 1, or MART-1, is a protein that in humans is encoded by the MLANA gene. It is required for the function of the melanosomal matrix protein PMEL17/GP100 and thus plays an important role in regulating mammalian pigmentation . Melan-A is a member of the MAGE gene family and is a tumour associated antigen. Clinically, the protein may serve as an anti-cancer vaccine .
Lantibiotic alpha component (Lantibiotic_alpha)
Type: Family

Lantibiotics are lanthionine-containing peptide antibiotics produced by and active on Gram-positive bacteria. Lanthionine is an unusual amino acid composed of two alanine residues crosslinked by a thioether linkage. Many lantibiotics also possess other modified residues.

This family represents the alpha peptide of a group of two-component system lantibiotics, and includes lichenicidin A1 and lacticin A1 peptides .
FAM69, N-terminal (FAM69_N)
Type: Domain

The FAM69 family of cysteine-rich type II transmembrane proteins localise to the endoplasmic reticulum (ER) in cultured cells, probably via N-terminal di-arginine motifs. These proteins carry at least 14 luminal cysteines which are conserved in all FAM69s. There are currently few indications of the involvement of FAM69 members in human diseases . It would appear that FAM69 proteins are predicted to be have a protein kinase structure and function. Analysis of three-dimensional structure models and conservation of the classic catalytic motifs of protein kinases in four of human FAM69 proteins suggests they might have retained catalytic phosphotransferase activity. An EF-hand Ca2+-binding domain, inserted within the structure of the kinase domain, suggests they function as Ca2+-dependent kinases .
Protein of unknown function DUF4528 (DUF4528)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 95 and 154 amino acids in length. This family includes human C15orf61.
Protein TALPID3 (TALPID3)
Type: Family

TALPID3 is the name of a classical chicken mutant with abnormal limb patterning and malformations in other regions of the embryo. It was so called because their paddle-shaped limbs resemble those of the mole (Talpa) . Besides the limbs, there is a set of malformations including face, skeleton, and vascular defects . TALPID3 gene was then identified and found to be a target for Hedgehog signalling . In chickens, TALPID3 protein is a centrosomal protein required for the function of both Gli repressor and activator in the intracellular Hedgehog pathway . Similar to the chicken TALPID3 mutants, the mouse mutants also lack primary cilia and have face and neural tube defects. Moreover, it has defects in left/right asymmetry .
FAM168A/MANI (FAM168A/MANI)
Type: Family

The FAM168 family consists of FAM168A and FAM168B. The function of FAM168A is unknown, but FAM168B has been renamed as myelin-associated neurite-outgrowth inhibitor (MANI), as it is an inhibitor of neuronal axonal outgrowth . MANI interacts with cell division cycle protein 27 (Cdc27) .
Transmembrane protein 107 (TMEM107)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 138 and 164 amino acids in length. They have two completely conserved residues (H and E) that may be functionally important and four transmembrane helices.
Rotatin, N-terminal (Rotatin_N)
Type: Domain

Rotatin and its homologues such as Ana3 in Drosophila are found to be essential for centriole function . A deficiency of rotatin in mice leads to randomised heart tube looping, defects in embryonic turning , and abnormal expression of HNF3beta, lefty, and nodal. Thus it is required for left-right and axial patterning. Ana3 - the Drosophila homologue - is present in centrioles and basal bodies, is required for the structural integrity of both centrioles and basal bodies and for centriole cohesion. Rotatin also localises to centrioles and basal bodies and appears to be essential for cilia function . This entry represents the N-terminal domain.
Exosomal polycystin-1-interacting protein (ECPIP)
Type: Family

This family includes the exosomal polycystin-1-interacting protein (also known as C21orf62 or CU062 in human), which is a small glycoprotein that can oligomerize with itself and interact with PC1 protein polycystin-1 (PC1). It may have a role in the identification of senescent mitochondria and their extrusion in extracellular vesicles .
Fanconi anemia-associated protein of 100kDa (Faap100)
Type: Family

Fanconi anemia-associated protein of 100kDa (FAAP100) is component of the Fanconi anemia (FA) core complex, which plays a central role in FA-associated DNA damage response. FAAP100 is essential for the stability and function of the complex .

Fanconi anemia (FA) is a human disorder characterised by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 .
Regulator of cell cycle RGCC (RGCC)
Type: Family

RGCC (also known as RGC32) modulates the activity of cell cycle-specific kinases and may play a role in cell cycle activation . This family of proteins is found in eukaryotes and has a conserved KLGDT sequence motif.
Cytokine-like protein 1 (CYTL1)
Type: Family

Cytokine-like protein 1 (CYTL1) was identified as a secretory protein expressed in CD34+ haemopoietic cells . CYTL1 seems to regulate chondrogenesis and is required for the maintenance of cartilage homeostasis . It may also work as a regulatory factor in embryo implantation .
MORF4 family-associated protein 1 (MRFAP1)
Type: Family

MRFAP1 (MORF4 family-associated protein 1) and its interaction partner MORF4L1 (or MRG15) are target proteins of the NEDD8-cullin pathway, which plays an important role in the degradation of cell cycle regulators and transcriptional control networks. It has been suggest that MRFAP1 competes with MRGBP for binding to MORF4L1, thereby regulating MORF4L1 function in chromatin modification .