SII-SWORD/CoKE huggingface dataset:
Peptide/nickel binding protein, MppA-type (Peptide/Ni-bd)
Type: Family

Solute-binding protein family 5 consists of peptide and nickel-binding proteins . MppA, a member of this family, is essential for import of the bacterial cell wall peptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate . GsiB (YliB) is a glutathione-binding protein . XP55 from Streptomyces lividans is one additional protein of unknown function that belongs to this group .

Proteins in this entry include:

Periplasmic oligopeptide-binding proteins (OppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (OppA, OmiA or AppA)

Periplasmic dipeptide-binding proteins of Escherichia coli (DppA) and Bacillus subtilis (DppE)

Periplasmic murein peptide-binding protein of E. coli (MppA)

Periplasmic peptide-binding proteins SapA of E. coli, Salmonella typhimurium and Haemophilus influenzae

Periplasmic nickel-binding protein (NikA) of E. coli

Haem-binding lipoprotein (HbpA or DppA) from H. influenzae

Lipoprotein xP55 from Streptomyces lividans

Metal-staphylopine-binding protein CntA from Staphylococcus aureus

Hypothetical protein from H. influenzae (HI0213)
ABC-type amino acid transport system, ATPase component, HisP-type (ABC_ATPase_HisP-typ)
Type: Family

The HisP sub-family of transporters essentially consists of cytoplasmic proteins which couple energy to the import of small substrates . HisP is part of the histidine permease ABC transporter .
Bombyxin A (Bombyxin_A)
Type: Family

Bombyxin family can be classified into 7 families, A to G, according to their sequence similarity . This entry represents the bombyxin A subfamily, and includes bombyxin A1-A9.

Bombyxin is a brain peptide responsible for activation of prothoracic glands to produce ecdysone in insects . When cleaved, bombyxins produce both subunits of the biologically active heterodimer. Several molecular species of bombyxin have now been identified in Bombyx, Agrius and Samia moth species. Both bombyxin and insulin contain six cysteine residues with identical distributions and are predicted to have similar tertiary structures, especially in their core regions . They are not functionally equivalent. However, the similarity to insulin has prompted speculation that it may play a role in the regulation of growth, and it has been shown to act as a growth factor for wing imaginal discs and midgut stem cells in some lepidopteran species .
Cholesterol 7-alpha-monooxygenase (Cholesterol_7a_monooxygenase)
Type: Family

Cholesterol 7-alpha-monooxygenase, also known as cytochrome P450 7A1, catalyses a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. It is the key enzyme that commits cholesterol to the neutral bile acid biosynthesis pathway, and is highly regulated . Gene transcription of cholesterol 7alpha-hydroxylase is stimulated by glucose .
Protein phosphatase 1 regulatory subunit 3B (PP1_3B)
Type: Family

This entry represents glycogen-targeting PP1 (protein phosphatase 1) subunit GL (coded for by the PPP1R3B gene). It is primarily expressed in the liver where it promotes hepatic glycogen synthesis in response to insulin. It is also highly expressed in mammaian fetal lungs and human (but not rodent) muscle .
Protein phosphatase 1 regulatory subunit 3C (PP1_3C)
Type: Family

This entry represents protein phosphatase 1 regulatory subunit 3C
(PP1R3C), also known as PTG (protein targeting to glycogen). It acts as a glycogen-targeting subunits for PP1 (protein phosphatase 1) and regulates its activity. Overexpression of PTG causes large increases in glycogen storage in isolated hepatocytes or intact rat liver .
Lactotransferrin (Lactotransferrin)
Type: Family

Lactotransferrin or lactoferrin (Lf) is an iron binding glycoprotein that exists in body secretions as a line of natural defence and plays an important role in defence against pathogenic bacteria, fungi, protozoa and viruses. It has multiple activities ranging from the intestinal iron absorption, intestinal cell growth, regulation of myelopoiesis and immune responses . Bovine Lf also possesses potent anti-cancer activities .
Lf has been shown to be a serine peptidase and belongs to MEROPS family S60.
Serotransferrin, mammalian (Serotransferrin_mammal)
Type: Family

Serotransferrin, also known as siderophilin, is a bilobal protein that transports iron from sites of storage to regions of iron metabolism . It binds ferric ions in the bloodstream and transports this bound iron to cells where it is released by a process of receptor-mediated endocytosis .
Cytochrome P450 8B1 (Cytochrome_CYP8B1)
Type: Family

Cytochrome P450 8B1 (Cyp8b1) plays an important role in the production of cholic acid, a major bile acid . Loss of Cyp8b1 improves glucose homeostasis by increasing glucagon like peptide-1 (GLP-1) in mice .
Sterol O-acyltransferase, metazoa (Sterol_acyltranf_meta)
Type: Family

Sterol O-acyltransferase 1 (SOAT1; also known as ACAT1) and sterol O-acyltransferase 2 (SOAT2; also known as ACAT2) both play a role in the formation of fatty acid-cholesterol esters . Cholesterol esters are less soluble in membranes than cholesterol and accumulate in atherosclerotic lesions, making ACAT inhibitors a pharmacological target against atherosclerosis . SOAT1 is present in steroidogenic tissues, kidneys, sebaceous glands and macrophages. SOAT2 is expressed predominantly in the liver and small intestine .
Methyltransferase MtrA/MtxA (MeTrfase_MtrA/MtxA)
Type: Family

Tetrahydromethanopterin S-methyltransferase is a complex that catalyses the formation of methyl-coenzyme M and tetrahydromethanopterin from coenzyme M and methyl-tetrahydromethanopterin in methanogenic archaea . It is a membrane-associated enzyme complex that uses the methyl-transfer reaction to drive a sodium-ion pump . The complex is composed of eight different subunits, MtrA-H. Subunit A (MtrA) harbours a corrinoid as prosthetic group .

MtxA from Methanosarcina is a putative methyltransferase with sequence homology to MtrA. Both show a conserved histidine (His84) at the putative active site .
Cytochrome b (Cytochrome_b)
Type: Family

Cytochrome b is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) in the mitochondrion of eukaryotes and in aerobic prokaryotes . This complex is involved in electron transport that generates an electrochemical potential coupled to ATP synthesis. Cytochrome b is the central redox catalytic subunit of the complex. It is involved in the binding of the quinone substrate and is responsible for the transmembrane electron transfer by which redox energy is converted into a protonmotive force .
Band 4.1-like protein 3, FERM domain, F1 sub-domain (Band4.1-L3_FERM_F1)
Type: Domain

Band 4.1-like protein 3, also known as 4.1B or DAL-1, belongs to the protein 4.1
family. Members of the 4.1 family contain a 4.1/ezrin/adixin/moesin (FERM) domain, which is involved in the linkage of cytoplasmic proteins to the membrane .

Protein 4.1B has been described to be a growth suppressor . It localises to the cell membrane to sites of cell-cell contact, and functions as an adapter protein, linking the plasma membrane to the cytoskeleton . It is involved in cytoskeleton-associated processes, such as cell motility and adhesion, and also plays a role in the regulation of cell growth, differentiation, and the establishment of epithelial-like cell structures .

The FERM domain of Band4.1-L3 is made up of three sub-domains, F1, F2, and F3. This entry represents the N-terminal F1 subdomain.
Band 4.1-like protein 4A, FERM domain, F1 sub-domain (Band4.1-like4A_FERM_F1)
Type: Domain

Band 4.1-like protein 4A (also named NBL4) belongs to the protein 4.1 family. Members of the 4.1 family contain a FERM (4.1/Ezrin/radixin/moesin) domain, which is involved in the linkage of cytoplasmic proteins to the membrane . NBL4 is an important component of the Wnt/beta-catenin pathway and may be involved in the cell polarity determination or proliferation . It might have a role in embryogenesis .

The FERM domain of NBL4 is made up of three sub-domains, F1, F2, and F3. This entry represents the N-terminal F1 subdomain.
Ras-related protein Rab29/Rab38/Rab32 (Rab29/Rab38/Rab32)
Type: Family

This entry represents the Rab29/Rab38/Rab32 subfamily. They are members of the Rab family of small GTPases. Human Rab32 was first identified in platelets but it is expressed in a variety of cell types, where it functions as an A-kinase anchoring protein (AKAP) . Rab32 and closely related Rab38 are functionally redundant regulators of melanosomal protein trafficking and melanocyte pigmentation .

Ras-related protein Rab29 (also known as RAB7L) is related to Rab32 and Rab38. Rab29 regulates phagocytosis and traffic from the Golgi to the lysosome . It is associated with trans-Golgi network (TGN) and is essential for maintaining the integrity of the TGN. Together with LRRK2, it plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner .
Band 4.1-like protein 4B, FERM domain, F1 sub-domain (EHM2_FERM_F1)
Type: Domain

Band 4.1-like protein 4B (EHM2) belongs to the protein 4.1 family. Members of the 4.1 family contain a FERM (4.1/Ezrin/radixin/moesin) domain, which is involved in the linkage of cytoplasmic proteins to the membrane . EHM2 shows highest homology to band 4.1-like protein 4A (NBL4), which may be involved in the cell polarity determination or proliferation . EHM2 is expressed in high-metastatic K1735 murine melanoma cells .

The FERM domain of EHM2 is made up of three sub-domains, F1, F2, and F3. This entry represents the N-terminal F1 subdomain.
N-end rule aminoacyl transferase (N-end_Aminoacyl_Trfase)
Type: Family

This entry represents a family of aminoacyl-transferases that includes prokaryotic aspartate/glutamate leucyltransferase, and eukaryotic arginine-tRNA-protein transferase.

Arginine-tRNA-protein transferase catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N-end rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis . In Saccharomyces cerevisiae, Cys20, 23, 94 and/or 95 are thought to be important for activity . Of these, only Cys 94 appears to be completely conserved in this family.

Aspartate/glutamate leucyltransferase (also known as bacterial protein transferase or Bpt) functions in the N-end rule pathway of protein degradation where it conjugates Leu from its aminoacyl-tRNA to the N-termini of proteins containing an N-terminal aspartate or glutamate. This protein shows sequence similarity to the eukaryotic N-end rule pathway component arginyl-transferase Ate1 .
Ras-related protein Rab14 (Rab14)
Type: Family

Ras-related protein Rab14 is a small GTPase that mediates endocytic recycling and functions in phagosome maturation . Rab14 and its exchange factor FAM116 regulates the specific endocytic transport of ADAM10 and thereby N-cadherin shedding and cell motility . Rab14 regulates claudin-2 trafficking, which is required for epithelial morphogenesis . It regulates apical targeting in polarised epithelial cells . Rab14 also regulates the interaction of phagosomes with early endocytic compartments and the maturation of macrophage phagosomes containing the fungal pathogen Candida albicans . Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus aureus .
Dedicator of cytokinesis protein 5, DHR2 domain (DHR2_DOCK5)
Type: Domain

DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane . DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) . All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker).

DOCK5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It functions upstream of Rac1 to regulate osteoclast function . Along with DOCK1, DOCK5 mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on collagen IV .

This entry represents the DHR-2 domain of DOCK5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like DOCK5, are specific GEFs for Rac.
Extracellular cadherin domain superfamily (EC_dom_sf)
Type: Homologous_superfamily

Protocadherin-15 (Pcdh15) belongs to the epsilon subfamily of nonclustered protocadherins. It is a component of the tip-links, the extracellular filaments that connect the tips of stereocilia and gate hair cell mechano-electrical transduction channels in the inner ear . Pcdh15 interacts with transmembrane channel-like proteins TMC1 and TMC2, which have been implicated in mechanotransduction in mammalian hair cells . Mutations in genes coding for Pcdh15 cause deafness in both mice and humans . Pcdh15 plays an important role in hair-bundle morphogenesis .

This entry represents an extracellular cadherin (EC) domain which can be found at the N-terminal region of Pcdh15. Pcdh15 features exceptionally long extracellular domains containing 11 ECs . These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved calcium-binding sites that confer mechanical strength to them .
Ral guanine nucleotide dissociation stimulator-like 1, RA domain (RGL1_RA)
Type: Domain

RalGDS family members can act both as Ras effectors and as guanine nucleotide exchange factors (GEFs) for Ral. They act downstream of Ras and bind to the GTP-bound active form of Ras or Ras family members. They also promote the GDP to GTP exchange for Ral small GTPase, member of the Ras family . Due to their double action, the RalGDS proteins bridge Ras and Ral .

RGL1 (RalGDS-like 1) belongs to the Ral GDP dissociation stimulator (RalGDS) family . It is a binding partner for small G-proteins. The function of RGL1 is not clear.

This entry represents the RA domain found at the C-terminal end of RGL1. It has a β-grasp ubiquitin-like fold .
Ral guanine nucleotide dissociation stimulator-like 3, RA domain (RGL3_RA)
Type: Domain

RalGDS family members can act both as Ras effectors and as guanine nucleotide exchange factors (GEFs) for Ral. They act downstream of Ras and bind to the GTP-bound active form of Ras or Ras family members. They also promote the GDP to GTP exchange for Ral small GTPase, member of the Ras family . Due to their double action, the RalGDS proteins bridge Ras and Ral .

RGL3 (RalGDS-like 3) belongs to the Ral GDP dissociation stimulator (RalGDS) family . RGL3 functions as an exchange factor for Ral and may serve as a downstream effector for both Rit and Ras .

This entry represents the RA domain found at the C-terminal end of RGL3. It has a β-grasp ubiquitin-like fold.
Monocarboxylate transporter 7 (MCT7)
Type: Family

Monocarboxylate transporter 7 (MCT7), also known as SLC16A6, belongs to the MCT family. The function of MCT7 is not clear.

Monocarboxylate transporters (MCTs) catalyse the proton-linked transport of monocarboxylates such as L-lactate, pyruvate, and the ketone bodies across the plasma membrane . All of the MCT family (also known as SLC16 solute carrier family) members share conserved sequence motifs. They are are predicted to have 12-transmembrane helices (TMs) with intracellular C and N termini and a large cytosolic loop between TMs 6 and 7 .
Monocarboxylate transporter 9 (MCT9)
Type: Family

This entry represents a protein family that includes Monocarboxylate transporter 9 (MCT9), also known as SLC16A9, which belongs to the MCT family. The function of MCT9 is not clear. A variant in human MCT9 gene has been linked to renal overload gout .

Monocarboxylate transporters (MCTs) catalyse the proton-linked transport of monocarboxylates such as L-lactate, pyruvate, and the ketone bodies across the plasma membrane . All of the MCT family (also known as SLC16 solute carrier family) members share conserved sequence motifs. They are are predicted to have 12-transmembrane helices (TMs) with intracellular C and N termini and a large cytosolic loop between TMs 6 and 7 .
Histatin/statherin family (Histatin/statherin)
Type: Family

Histatins are small molecular weight proteins produced by the human salivary glands that exhibit antifungal and antibacterial activities . They are also components of the acquired enamel pellicle (AEP) . Histatins 1 and 3 are full-length peptides of 38 and 32 amino acid residues respectively; other characterised members of the histatin family are proteolytic products formed during secretion . The predominant histatins are histatin 1, 3, and 5; histatin 5 is a proteolytic product of histatin 3.

Statherin is a 43-residue peptide, secreted by parotid and submandibular glands. It is a multifunctional molecule that prevents calcium phosphate precipitation in saliva, thus maintaining a high calcium and phosphate levels . Moreover, statherin and its C-terminal fragments inhibit the growth of anaerobic bacteria from the oral cavity . Statherin and histatin 1 reduce Streptococcus mutans adhesion onto hydroxyapatite surfaces .
PSTPIP1, SH3 domain (PSTPIP1_SH3)
Type: Domain

This entry represents the SH3 domain of proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1).

Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) belongs to the PCH family. It interacts with Wiskott-Aldrich syndrome protein (WASP) and PTPN12, which are important regulators of the cytoskeleton and cell migration, suggesting that PSTPIP1 functions in these pathways . PSTPIP1 has been identified as a component of the leukocyte uropod that regulates endocytosis and cell migration . It also controls extracellular matrix degradation and filopodia formation in macrophages . It interacts with pyrin, a protein that associates with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis . Mutations in the PSTPIP1 gene have been linked to PAPA syndrome, an inflammatory disease .

Pombe Cdc15 homology (PCH) family proteins were initially identified as adaptor proteins involved in the regulation of cytokinesis and actin dynamics . They share a similar domain architecture, consisting of an N-terminal FCH domain followed by a coiled coil (CC) region and by one or two C-terminal SH3 domains. However, in some family members the SH3 domain is absent (FCHO1, FCHO2 and PSTPIP2) or there are tissue-specific alternatively spliced isoforms with and without an SH3 domain (CIP4b, CIP4c, CIP4V, Fbp17b). PCH family proteins interact with receptors, adaptors, enzymes and structural proteins to regulate their localisation and activity. Through these interactions, PCH proteins regulate cell morphology and motility, organelle integrity, protein trafficking and the organisation of the actin cytoskeleton .
Rotatin (Rotatin)
Type: Family

Rotatin (RTTN) is a centriolar protein that appears to be required for cilia function . Mouse RTTN is required for embryonic axial rotation, and left-right specification. It is essential for the correct expression of the key left-right specification genes nodal, lefty and Pitx2 . The Drosophila homologue of rotatin, Anastral spindle 3 (Ana3), is needed for structural integrity of centrioles and basal bodies and participates in the later stages of centriole assembly through the interaction with Rcd4 leading to the centriole to centrosome conversion . Rotatin colocalizes with the basal bodies at the primary cilium, and has a role in cilia structure and function . Mutations in RTTN have been identified in individuals with polymicrogyria, a malformation of the developing cerebral cortex .
Arfaptin family (Arfaptin_fam)
Type: Family

This family consists of Arfaptin-1, Arfaptin-2, and protein kinase C-binding protein 1 (PICK1). They all contain a Bin/amphiphysin/Rvs (BAR) domain . BAR-domain-containing proteins are key players in membrane dynamics as their crescent shape allows them to sense or generate curvature on lipid bilayers .

Arfaptin-1 and 2 have been shown to interact with Arf GTPases and Arf-like 1 (Arl1). They are recruited to trans-Golgi membranes through interaction with Arl1 .

In neurons, PICK1 forms homodimers and serves as one of the scaffolding proteins that interacts with AMPA receptors and regulates their trafficking in synaptic plasticity . In pancreatic beta cells, it forms heteromeric BAR-domain complexes with another cytosolic lipid-binding protein, ICA69. Together they are key regulators of the formation and maturation of insulin granules .
Lipid A Kdo2 1-phosphate O-methyltransferase (LmtA_Leptospira)
Type: Family

This entry represents LmtA from Leptospira. It methylates a phosphate on the Kdo2 sugar of lipid A. Members of this family belong to the broader family of phospholipid methyltransferase

, which includes a characterised yeast enzyme that acts on a range of unsaturated phospholipids .
Glutamate 2,3-aminomutase (Glu_2_3_NH3_mut)
Type: Family

Glutamate 2,3-aminomutase is a radical SAM enzyme with a pyridoxal phosphate group. It catalyses the interconversion of L-glutamate and L-beta-glutamate . It is closely related to lysine 2,3-aminomutase, but can be distinguished by architecture (longer N-terminal region, shorter C-terminal region) and replacement of key lysine-binding residues .
ABC transporter permease MalE (Permease_MalE)
Type: Family

Intermembrane phospholipid transport system permease protein MlaE is a permease which in E. coli is a component of the Mla pathway, an ABC transport system that functions to maintain the asymmetry of the outer membrane . In

it is involved in L-glutamate import into the cell . In

it is involved in lipid transfer within the cell . Many bacterial species have one or two members from this family. The Mycobacteria have large paralogous families included in this entry .
BBSome complex member BBS5/sex-determination protein fem-3 (BBS5/fem-3)
Type: Family

BBSome complex member BBS5 is part of the BBSome complex that may function as a coat complex required for sorting of specific membrane proteins to the primary cilia . Mutations in the BBS5 gene cause Bardet-Biedl syndrome 5, which is a syndrome characterised by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation .

Also included in this family is fem-3, required for male development in Caenorhabditis elegans. Together with fem-2, fem-3 associates with the CBC(fem-1) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of tra-1, a transcription factor that is the terminal effector of the sex-determination pathway .
Oxidoreductase-SelD-related fusion protein (Oxidorec-SedlD_fusion)
Type: Family

Some selenium donor proteins (selenide,water dikase, product of the selD gene,

) are fusion proteins with an N-terminal extension described by

. Members of this family have a C-terminal region similar to SelD, fused to an N-terminal region similar to, but outside the scope of

.
Putative sugar O-methyltransferase (Methyltran_NanM)
Type: Family

Members of this family appear to be SAM-dependent O-methyltransferases acting on sugars, based on iterated sequence searches and gene context. Members occur in Leptospira O-antigen regions, as well as NanM from the biosynthesis cluster for nanchangmycin, which produces 4-O-methyl-L-rhodinose as an intermediate .