SII-SWORD/CoKE huggingface dataset:
Family of unknown function DUF5525 (DUF5525)
Type: Family

This is a group of animal proteins with no known function, including C15orf39 from humans.
RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMC1)
Type: Family

RAB7A-interacting MON1-CCZ1 complex subunit 1 (RIMC1, previously known as UPF0600 protein C5orf51) plays an important role in the removal of damaged mitochondria via mitophagy by controlling the stability and localization of RAB7A. It is required for the recruitment of RAB7A and ATG9A vesicles to damaged mitochondria and promotes the stability of RAB7A by inhibiting its proteasomal degradation during mitophagy .
Voltage-dependent calcium channel beta subunit-associated regulatory protein (CBARP)
Type: Family

CBARP is a voltage-gated calcium channel (VGCC) beta-anchoring and -regulatory protein. It interacts via two cytosolic domains (I and II) with all Cavbeta subunit isoforms, affecting their subcellular localization and suppressing VGCC activity .
Small integral membrane protein 7 (SMIM7)
Type: Family

The function of SMIM7 is not clear.
Coiled-coil domain-containing protein 51 (CCDC51)
Type: Family

This family contains the coiled-coil domain-containing protein 51 (CCDC51), also known as mitochondrial potassium channel (MITOK). In complex with ABCB8/MITOSUR it forms a protein complex localised in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane .
Transmembrane protein 196 (TMEM196)
Type: Family

The function of TMEM196 is not clear. It acts as a functional tumour suppressor in lung cancer .
Cilia- and flagella-associated protein 68/107 (CFAP68/107)
Type: Family

This entry includes Cilia- and flagella-associated proteins 107 (CFAP107 or C1orf158) and 68 (CFAP68, also known as UPF0686 protein C11orf1), that are microtubule inner proteins (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating .
Modulator of smoothened protein (Mosmo)
Type: Family

MOSMO, also known as Atthog (attenuator of hedgehog) in mouse, acts as a negative regulator of hedgehog (Hh) signaling, probably by promoting internalization and subsequent degradation of Smoothened (SMO). SMO is an oncoprotein that transduces the Hh signal across the membrane. In the absence of Atthog, SMO was stabilized at the cell surface and concentrated in the ciliary membrane .
BldD, C-terminal (BldD_C)
Type: Domain

The Streptomyces transcription factor BldD represses the transcription of ~170 sporulation genes during vegetative growth. It binds and is regulated by the second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) .

This entry represents the C-terminal domain of BldD from Streptomyces venezuelae (

) and similar proteins found in Actinobacteria. This domain shows two β-α-α repeats and a short C-terminal helix. It is responsible for the binding of the protein to the second messenger 3',5'-cyclic diguanylic acid (c-di-GMP) .
Nucleoporin peptidase S59-like (Nucleoporin_S59-like)
Type: Family

This entry represents nucleoporins, of which the precursors of some undergo autolytic processing. Some nucleoporins are synthesized as precursors, and each of these processes itself to release two large fragments that are both nucleoporins. Cleavage is dependent upon a His/Ser catalytic dyad, and cleavage occurs at the N-terminal side of the catalytic Ser. This means that the nucleoporin precursors are N-terminal nucleophile (NTN) hydrolases, but are structurally unrelated to other NTN hydrolases which are also peptidases, such as proteosome components. Autoprocessing nucleoporin precursors are members of peptidase family S59. The precursor Nup98-Nup96 (also known as nucleoporin 145 in Saccharomyces cerevisiae and Nup189 in Schizosaccharomyces pombe) processes itself to release Nup98 and Nup96 . Nucleoporins Nup98 and Nup96 are components of the nuclear pore complex (NPC), which is the only means by which macromolecules enter and exit the nucleus. Other nucleoporins in family S59 are not synthesized as precursors and do not undergo autoprocessing, such as Nup100 (from Saccharomyces cerevisiae). Nup100 is also a component of the NPC and binds the karyopherin transport factor Kap95 at its repetitive tetrapeptide glycine-leucine-phenylalanine-glycine (GLFG) motifs .
Coiled-coil domain-containing protein 43 (CCDC43)
Type: Family

The function of CCDC43 is not clear.
Protein FMC1 homologue (FMC1_homologue)
Type: Family

This entry includes FMC1 homologues from animals. The budding yeast Fmc1 (not included in this entry) is a nuclear protein required for the assembly/stability of yeast mitochondrial F(1)-ATPase in heat stress conditions .
Sperm-associated microtubule inner protein 3 (SPMIP3)
Type: Family

This entry represents the homologs of Sperm-associated microtubule inner protein 3 (SPMIP3 also known as C1orf100). SPMIP3 is a mammalian sperm specific microtubule-associate protein .
Uncharacterized protein C11orf87 (C11orf87)
Type: Family

The function of human C11orf87 is not known. Homologues are found in vertebrates.
GPI ethanolamine phosphate transferase 1, N-terminal (PIGN_N)
Type: Domain

GPI ethanolamine phosphate transferase 1 (also known as PIGN) is an ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. It catalyzes the transfer of ethanolamine phosphate to the first alpha-1,4-linked mannose of the glycosylphosphatidylinositol precursor of GPI-anchor. It may act as suppressor of replication stress and chromosome missegregation .

This entry represents the N-terminal domain of PIGN.
Large-conductance mechanosensitive channel/anditomin synthesis protein L (MSC/AndL)
Type: Family

Mechanosensitive ion channels (MscL) play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. MscL is a protein which forms a channel organised as a homopentamer, with each subunit containing two transmembrane regions . Prokaryotes harbor a large-conductance mechanosensitive channel (gene mscL) that opens in response to stretch forces in the membrane lipid bilayer and participate in the regulation of osmotic pressure changes within the cell . MscL has a conserved domain architecture which comprises an amphipathic α-helix (S1) that lies along the cytoplasmic membrane, a highly conserved first transmembrane domain (TM1) that forms the pore constriction, a periplasmic loop, a second transmembrane domain (TM2) that faces the lipid membrane, and a linker that leads to a cytoplasmic α-helical bundle .

This family also includes anditomin synthesis protein L (AndL), which is part of the gene cluster that mediates the biosynthesis of anditomin. Its role of in this pathway is not known .
GPI ethanolamine phosphate transferase 2, N-terminal (PIG-G_N)
Type: Domain

Many eukaryotic cell surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). GPI ethanolamine phosphate transferase 2 (also known as PIG-G) is an ethanolamine phosphate transferase involved in GPI-anchor biosynthesis. It catalyzes the transfer of ethanolamine phosphate to the GPI second mannose .
GPI ethanolamine phosphate transferase 3, N-terminal (PIG-O_N)
Type: Domain

GPI ethanolamine phosphate transferase 3 (also known as PIG-O) is an ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. It catalyzes the transfer of ethanolamine phosphate to the GPI third mannose which links the GPI-anchor to the C terminus of the proteins by an amide bond .
CD80, IgC-like domain (CD80_IgC)
Type: Domain

Glycoproteins B7-1 (CD80) and B7-2 (CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (CD152) on T cells. Signalling through CD28 augments the T-cell response, whereas CTLA-4 signalling attenuates it . CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors .

Members of the Ig family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and Major Histocompatibility Complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions .

This entry represents the immunoglobulin constant (IgC)-like domain of CD80.
CD86, IgV domain (CD86_IgV)
Type: Domain

Glycoproteins B7-1 (CD80) and B7-2 (CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (CD152) on T cells. Signalling through CD28 augments the T-cell response, whereas CTLA-4 signalling attenuates it . The CTLA-4 and B7-2 monomers are both two-layer β-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively .

Members of the IgV family are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain . Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding .
Anaphase-promoting complex subunit 5 (Apc5)
Type: Family

Apc5 is a subunit of the eukaryotic anaphase-promoting complex/cyclosome (APC/C) which is a multi-subunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G1. Although Apc5 does not contain a classical RNA binding domain, it binds the poly(A) binding protein (PABP), which directly binds the internal ribosome entry site (IRES) of growth factor 2 mRNA .

This entry also includes two Apc5 paralogues from C. elegans: such-1 and gfi-3. They are coexpressed in the germline but have nonoverlapping expression patterns in other tissues. They have a redundant function during the meiotic divisions .
Protein RMD5 homologue A, degenerated RING finger (RMD5A_dRING)
Type: Domain

RMD5A is one of the vertebrate homologus of yeast Rmd5. The biological function of RMD5A remains unclear. Like Rmd5/Gid2, RMD5A contains a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterised by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers .
Protein RMD5 homologue B, degenerated RING finger (RMD5B_dRING)
Type: Domain

RMD5B is one of the vertebrate homologus of yeast Rmd5. The biological function of RMD5B remains unclear. RMD5B contains a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterised by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers .
TonB, C-terminal (TonB_C)
Type: Domain

TonB is bound to an inner membrane-bound protein ExbB via a globular domain and has a flexible middle region that is likely to help in positioning the C-terminal domain into the iron-transporter barrel in the outer membrane .

This entry represents the C-terminal domain of TonB. TonB_C interacts with the N-terminal TonB box of the outer membrane transporter that binds the Fe3+-siderophore complex. The barrel of the transporter, consisting of 22 β-sheets and an inside plug, binds the iron complex in the barrel entrance .
Rmd5, degenerated RING (dRING) finger (Rmd5_dRing)
Type: Domain

Rmd5 (also known as Gid2) is an E3 ubiquitin ligase containing a Lissencephaly type-1-like homology motif (LisH), a C-terminal to LisH motif (CTLH) domain, and a degenerated RING finger that is characterised by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers . It forms the heterodimeric E3 ligase unit of the glucose induced degradation deficient (GID) complex with Gid9 (also known as Fyv10), which has a degenerated RING finger as well .

The GID complex triggers polyubiquitylation and subsequent proteasomal degradation of the gluconeogenic enzymes fructose-1, 6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), and cytoplasmic malate dehydrogenase (c-MDH). Moreover, Rmd5p can form the GID complex with the other six Gid proteins, including Gid1/Vid30, Gid4/Vid24, Gid5/Vid28, Gid7, Gid8, and Gid9/Fyv10. The GID complex in which the seven Gid proteins reside functions as a novel ubiquitin ligase (E3) involved in the regulation of carbohydrate metabolism .
Guanylate-binding protein, C-terminal (GBP_C)
Type: Domain

Guanylate-binding protein (GBP) is a cytokine-induced GTPase that hydrolyzes guanosine triphosphate (GTP) to both guanosine diphosphate (GDP) and GMP. It has the properties of nucleotide-dependent oligomerization and concentration-dependent GTPase activity .
RNA polymerase RBP11 (RBP11)
Type: Family

The eukaryotic RPB11 subunit of RNA polymerase (RNAP) II is involved in the assembly of RNAP subunits. RNAP is a large multi-subunit complex responsible for the synthesis of RNA. It is the principal enzyme of the transcription process, and is a final target in many regulatory pathways that control gene expression in all living cells . At least three distinct RNAP complexes are found in eukaryotic nuclei: RNAP I, RNAP II, and RNAP III. RNAP II is responsible for the synthesis of mRNA precursor . The RPB11 subunit heterodimerizes with the RPB3 subunit, and together with RPB10 and RPB12, anchors the two largest subunits, RPB1 and RPB2, and stabilizes their association .
Zinc finger B-box domain-containing protein (ZBBX)
Type: Family

The function of this family of zinc finger B-box domain-containing proteins is not known.
BAG family molecular chaperone regulator 2 (BAG2)
Type: Family

This entry represents the BAG2 protein, which belongs to the BAG family. BAG2 acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release .

BAG-family proteins contain a single BAG domain, except for human BAG-5 which has four BAG repeats. The BAG domain is a conserved region located at the C terminus of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. BAG family proteins regulate chaperone protein activities through their interaction with Hsc70/Hsp70 .
Protein FAM204A (FAM204A)
Type: Family

The function of FAM204A is not clear.
Uncharacterized protein C11orf98 (C11orf98)
Type: Family

The function of C11orf98 is not clear. It has been shown to interact with nucleolar proteins nucleophosmin and nucleolin .
Centrosomal protein of 70kDa (CEP70)
Type: Family

CEP70 localizes to the centrosome throughout the cell cycle and binds to the key centrosomal component, gamma-tubulin . It plays an important role in the regulation of microtubule dynamics, mitotic spindle formation, cell migration, and ciliogenesis . It has been shown to regulate cancer growth and metastasis .
Coiled-coil domain-containing protein 15 (CCDC15)
Type: Family

The function of CCDC15 is not known.
Mitochondrial nucleoid-associated protein 1 (MTNAP1)
Type: Family

Mitochondrial nucleoid-associated protein 1 (MTNAP1, previously known as C17orf80) has been identified as is a mitochondrial membrane-associated protein that interacts with nucleoids . It is a critical regulator of mitochondrial DNA (mtDNA) abundance . It binds dsDNA throughout the mitochondrial genome without sequence specificity and controls mtDNA copy number by promoting its replication . MTNAP1 also plays important roles in mitochondrial metabolism and cell proliferation .
IQ motif and ubiquitin-like domain-containing protein (IQUB)
Type: Family

IQ motif and ubiquitin-like domain-containing protein (IQUB) is an adapter protein that anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes . The triple radial spokes (RS1, RS2 and RS3) are required to modulate the beating of the sperm flagellum . IQUB may also play a role in inhibiting signalling via MAPK1/ERK2 and MAPK3/ERK1 . It may play roles in cilia formation and/or maintenance . Defects in this protein may lead to spermatogenic failure with radial spoke defects. The ubiquitin domain in IQUB is represented by

.
Coiled-coil domain-containing protein 77 (CCDC77)
Type: Family

The function of CCDC77 is not clear.
Ubiquinol-cytochrome-c reductase complex assembly factor 2 (UQCC2)
Type: Family

Complex III (cytochrome bc1) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. UQCC1 and UQCC2 are complex III assembly factors participating in cytochrome b biogenesis .
Uncharacterized protein At5g65660-like (At5g65660-like)
Type: Family

This family from plants includes Arabidopsis At5g65660 protein. Its function is not known.
Nucleoporin NUP88/NUP82 (NUP88/NUP82)
Type: Family

This entry include a nucleoporin known as NUP88 in animals and NUP82 in fission and budding yeasts. NUP88 is a component of the nuclear pore complex (NPC), which is the only means by which macromolecules enter and exit the nucleus . NUP82 is also a component of the NPC subcomplex (with NUP159 and NSP1) which tethers nucleoporins to the nuclear membrane .
Nucleoporin Pom152 (Pom152)
Type: Family

This entry includes nucleoporin Pom152, which is a component of the nuclear pore complex (NPC) . Pom152 is a glycoprotein subunit of transmembrane ring of NPC and is important for the assembly of the NPC .
Phosphatidylinositol 3-kinase beta, catalytic domain (PI3-kinase_beta_cat)
Type: Domain

This entry represents the catalytic domain of PI3Kbeta (also known as p110beta), which is a Class IA phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). It has been shown to regulate chromosome segregation in mitosis .

Phosphatidylinositol 3-kinase (PI3-kinases) can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3-kinases are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (p110alpha, beta, gamma or delta) and one of several regulatory subunits (p85alpha, beta or gamma). They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3-kinase homology domain of unknown function, and a C-terminal ATP-binding catalytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors .
Phosphatidylinositol 3-kinase delta, catalytic domain (PI3-kinase_delta_cat)
Type: Domain

This entry represents the catalytic domain of PI3Kdelta (also known as p110delta), which is a Class IA phosphoinositide-3-kinase (PI3K) that that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells .

Phosphatidylinositol 3-kinase (PI3-kinases) can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3-kinases are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (p110alpha, beta, gamma or delta) and one of several regulatory subunits (p85alpha, beta or gamma). They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3-kinase homology domain of unknown function, and a C-terminal ATP-binding catalytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors .
Phosphatidylinositol 3-kinase alpha, catalytic domain (PI3-kinase_alpha_cat)
Type: Domain

This entry represents the catalytic domain of PI3Kalpha (also known as p110alpha), which is a Class IA phosphoinositide-3-kinase (PI3K) that that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PI3Kalpha plays an important role in insulin signaling . It also mediates cardiac growth induced by exercise training . Mutations in the PI3Kalpha gene have been linked to various cancers .

Phosphatidylinositol 3-kinase (PI3-kinases) can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3-kinases are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (p110alpha, beta, gamma or delta) and one of several regulatory subunits (p85alpha, beta or gamma). They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3-kinase homology domain of unknown function, and a C-terminal ATP-binding catalytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors .
Phosphatidylinositol 3-kinase C2-alpha, catalytic domain (PI3-kinase_C2-alpha_cat)
Type: Domain

This entry represents the catalytic domain of PI3K-C2-alpha, which is a Class II phosphoinositide-3-kinase (PI3K) that generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). It plays key roles in clathrin assembly and clathrin-mediated membrane trafficking , insulin signaling , and vascular smooth muscle contraction .

Phosphatidylinositol 3-kinase (PI3-kinases) can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3-kinases are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (p110alpha, beta, gamma or delta) and one of several regulatory subunits (p85alpha, beta or gamma). They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3-kinase homology domain of unknown function, and a C-terminal ATP-binding catalytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors .