SII-SWORD/CoKE huggingface dataset:
Vitellogenin, N-terminal (Vitellogenin_N)
Type: Domain

This entry represents a conserved region found in several lipid transport proteins, including vitellogenin, microsomal triglyceride transfer protein and apolipoprotein B-100 .

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved. In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: lipovitellin-1, phosvitin, lipovitellin-2, and a von Willebrand factor type D domain (YGP40) .

Microsomal triglyceride transfer protein (MTTP) is an endoplasmic reticulum lipid transfer protein involved in the biosynthesis and lipid loading of apolipoprotein B. MTTP is also involved in the late stage of CD1d trafficking in the lysosomal compartment, CD1d being the MHC I-like lipid antigen presenting molecule .

Apolipoprotein B can exist in two forms: B-100 and B-48. Apoliporotein B-100 is present on several lipoproteins, including very low-density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and can assemble VLDL particles in the liver . Apolipoprotein B-100 has been linked to the development of atherosclerosis.
Pre-mRNA-splicing factor BUD31 (BUD31)
Type: Family

This family includes the pre-mRNA-splicing factor BUD31, also known as G10 protein, and its homologues. BUD31 is involved in the pre-mRNA splicing process and it is highly conserved in a wide range of eukaryotic species. Human BUD31 may play a role as regulator of androgen receptor (AR) transcriptional activity, probably, increasing the AR transcriptional activity .
GPCR, family 2, gastric inhibitory polypeptide receptor (GPCR_2_GIP_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The secretin-like GPCRs include secretin , calcitonin , parathyroid hormone/parathyroid hormone-related peptides and vasoactive intestinal peptide , all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products.

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells . The human GIP-receptor encodes a 7TM protein that is similar to the human glucagon-like peptide 1(GLP-1) receptor. It is hoped that an understanding of GIP-receptor regulation and signal transduction will shed light on the hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.
NADH:quinone oxidoreductase/Mrp antiporter, transmembrane domain (ND/Mrp_TM)
Type: Domain

This entry represents the transmembrane segments of subunits NuoL/ND5, NuoM/ND4, and NuoN/ND2 of the NADH:quinone oxidoreductase (complex I), Mrp antiporters subunits A and D, and in membrane subunits of hydrogenase complexes, such as hydrogenase-4 and F420H2 dehydrogenase.

Mrp-type antiporters comprise the cation/proton antiporter family 3 (CPA3), commonly referred to as Mrp. They are the products of operons that carry either six or seven genes (mrpA-G), and form complexes containing all subunits . They have Na(+)/H(+) antiporter activity . Two of the Mrp proteins, MrpA and MrpD, resemble NuoL/ND5, NuoM/ND4, NuoN/ND2, the homologous subunits that constitute the membrane-embedded, proton-translocating core of complex I . They also resemble subunits of membrane-bound hydrogenases, such as HyfB, HyfD and HyfF from E.coli and F420H2 dehydrogenasa (FPO complex) subunits L, N and M .
S100/Calcium binding protein 7/8-like, conserved site (S100/CaBP7/8-like_CS)
Type: Conserved_site

The calcium-binding domain found in S100, CaBP7/8 and similar proteins mainly from animals. It is a subfamily of the EF-hand calcium-binding domain . S100s are small dimeric acidic calcium and zinc-binding proteins abundant in the brain, with S100B playing an important role in modulating the proliferation and differentiation of neurons and glia cells . S100 proteins have two different types of calcium-binding sites: a low affinity one with a special structure, and a 'normal' EF-hand type high-affinity site.

Protein S100-G from humans (formerly known as Calbindin-D9k) also belong to this family of proteins, but it does not form dimers. CaBP-9k is a cytosolic protein expressed in a variety of tissues. Although its precise function is unknown, it appears to be under the control of the steroid hormones oestrogen and progesterone in the female reproductive system . In the intestine, this protein may be involved in calcium absorption by mediating intracellular diffusion .

Calcium-binding protein 8 from Rattus norvegicus (Rat) regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity. It may play a role in the physiology of neurons and is potentially important in memory and learning .
Enoyl-CoA hydratase/isomerase (Enoyl-CoA_hydra/iso)
Type: Family

This family contains a diverse set of enzymes from cellular organisms, including: fatty acid oxidation complex subunit alpha, enoyl-CoA hydratase, 1,4-dihydroxy-2-naphthoyl-CoA synthase (napthoate synthase), carnitinyl-CoA dehydratase (carnitine racemase), 3-hydroxybutyryl-CoA dehydratase and enoyl-CoA delta isomerase (dodecanoyl-CoA delta-isomerase).
Orotidine 5'-phosphate decarboxylase domain (OMPdeCOase_dom)
Type: Domain

Orotidine 5'-phosphate decarboxylase (OMPdecase) catalyses the last step in the
de novo
biosynthesis of pyrimidines, the decarboxylation of OMP into UMP. In higher eukaryotes OMPdecase is part, with orotate phosphoribosyltransferase, of a bifunctional enzyme, while the prokaryotic and fungal OMPdecases are monofunctional protein.

Some parts of the sequence of OMPdecase are well conserved across species. The best conserved region is located in the N-terminal half of OMPdecases and is centred around a lysine residue which is essential for the catalytic function of the enzyme.

This entry also includes enzymes such as 3-hexulose-6-phosphate synthase

and 3-keto-L-gulonate-6-phosphate decarboxylase

.
P-type ATPase (P_typ_ATPase)
Type: Family

This entry represents the P-type ATPases. These P-ATPases are found in both prokaryotes and eukaryotes.

P-ATPases (also known as E1-E2 ATPases) (

) are found in bacteria and in a number of eukaryotic plasma membranes and organelles . P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H
+
, Na
+
, K
+
, Mg
2+
, Ca
2+
, Ag
+
and Ag
2+
, Zn
2+
, Co
2+
, Pb
2+
, Ni
2+
, Cd
2+
, Cu
+
and Cu
2+
. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
Prostanoid EP4 receptor (Prost_EP4_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide variety of actions and play important physiological roles in the cardiovascular and immune systems, and in pain sensation in peripheral systems. PGI2 and TXA2 have opposing actions, involving regulation of the interaction of platelets with the vascular endothelium, while PGE2, PGI2 and PGD2 are powerful vasodilators and potentiate the action of various autocoids to induce plasma extravasation and pain sensation. To date, evidence for at least 5 classes of prostanoid receptor has been obtained. However, identification of subtypes and their distribution is hampered by expression of more than one receptor within a tissue, coupled with poor selectivity of available agonists and antagonists.

EP4 receptors are found in high levels in the intestine, and in lower levels in the lung, kidney, thymus, uterus and brain; they are not found in the liver, heart, retina or in skeletal muscle. The receptors activate adenylate cyclase.
Pentraxin-related (Pentraxin-related)
Type: Family

This entry represents Pentaxins and its related proteins such as CRP (C-reactive protein) and SAP (serum amyloid P component protein) . This entry also includes adhesion G-protein coupled receptors D2 and G6 from humans.

Pentraxins (or pentaxins) are a family of proteins which show, under electron microscopy, a discoid arrangement of five noncovalently bound subunits. Proteins of the pentraxin family are involved in acute immunological responses . Three of the principal members of the pentraxin family are serum proteins and Ca
2
dependent: namely, C-reactive protein (CRP) , serum amyloid P component protein (SAP) , and female protein (FP) . CRP binds to ligands containing phosphocholine, SAP binds to amyloid fibrils, DNA, chromatin, fibronectin, C4-binding proteins and glycosaminoglycans.

CRP is expressed during acute phase response to tissue injury or inflammation in mammals. The protein resembles antibody and performs several functions associated with host defence: it promotes agglutination, bacterial capsular swelling and phagocytosis, and activates the classical complement pathway through its calcium-dependent binding to phosphocholine. CRPs have also been sequenced in an invertebrate, Limulus polyphemus (Atlantic horseshoe crab), where they are a normal constituent of the hemolymph .

SAP is a vertebrate protein that is a precursor of amyloid component P. It is found in all types of amyloid deposits, in glomerular basement menbrane and in elastic fibres in blood vessels. SAP binds to various lipoprotein ligands in a calcium-dependent manner, and it has been suggested that, in mammals, this may have important implications in atherosclerosis and amyloidosis .

FP is a SAP homologue found in Mesocricetus auratus (golden hamster). The concentration of this plasma protein is altered by sex steroids and stimuli that elicit an acute phase response.

"Long" pentraxins have N-terminal extensions to the common pentraxin domain ; one group, the neuronal pentraxins, may be involved in synapse formation and remodeling, and they may also be able to form heteromultimers . Pentraxin proteins expressed in the nervous system are neural pentraxin I (NPI) and II (NPII) . NPI and NPII are homologous and can exist within one species. It is suggested that both proteins mediate the uptake of synaptic macromolecules and play a role in synaptic plasticity. Apexin, a sperm acrosomal protein, is a homologue of NPII found in Cavia porcellus (Guinea pig) .

PTX3 is a long pentraxin that provides defence against infectious agents and plays several functions in tissue repair and regulation of cancer-related inflammation .
Opsin (Opsin)
Type: Family

Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to the chromophore cis-retinal. Vision is effected through the absorption of a photon by cis-retinal which is isomerised to trans-retinal. This isomerisation leads to a change of conformation of the protein. Opsins are integral membrane proteins with seven transmembrane regions that belong to family 1 of G-protein coupled receptors.

In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for colour vision and contain three or more colour pigments (for example, in mammals: red, blue and green).

By contrast with vertebrate rhodopsin, which is found in rod cells, insect photoreceptors are found in the ommatidia that comprise the compound eyes. Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8 are inner cells. Opsins RH3 and RH4 are sensitive to UV light . In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.

Proteins evolutionary related to opsins include:

Squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal.

Mammalian opsin 3 (Encephalopsin) that may play a role in encephalic photoreception.

Mammalian opsin 4 (Melanopsin) that may mediate regulation of circadian rhythms and acute suppression of pineal melatonin.

Mammalian retinal pigment epithelium (RPE) RGR , a protein that may also act in retinal isomerisation.
Periplasmic binding protein/LacI sugar binding domain (Peripla_BP/Lac1_sug-bd_dom)
Type: Domain

This entry represents periplasmic binding proteins, and the LacI family of transcriptional regulators sugar binding domain. The periplasmic binding proteins are the primary receptors for chemotaxis and transport of many sugar based solutes. The LacI family of proteins consist of transcriptional regulators related to the lac repressor. In this case, generally the sugar binding domain binds a sugar which changes the DNA binding activity of the repressor domain (lacI) .
Disintegrin domain (Disintegrin_dom)
Type: Domain

Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion . Integrin receptors are involved in cell-cell and cell-extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet-platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor-glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen . The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant .

Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin , schistatin , echistatin , elegantin, eristicophin, flavoridin , halysin, kistrin, tergeminin, salmosin and triflavin.

Disintegrin-like proteins are found in various species ranging from slime mold to humans. Some other proteins known to contain a disintegrin domain are:

Some snake venom zinc metalloproteinases consist of an N-terminal catalytic domain fused to a disintegrin domain. Such is the case for trimerelysin I (HR1B), atrolysin-e (Ht-e) and trigramin. It has been suggested that these proteinases are able to cleave themselves from the disintegrin domains and that the latter may arise from such a post-translational processing.

The beta-subunit of guinea pig sperm surface protein PH30 . PH30 is a protein involved in sperm-egg fusion. The beta subunit contains a disintegrin at the N-terminal extremity.

Mammalian epididymial apical protein 1 (EAP I) . EAP I is associated with the sperm membrane and may play a role in sperm maturation. Structurally, EAP I consists of an N-terminal domain, followed by a zinc metalloproteinase domain, a disintegrin domain, and a large C-terminal domain that contains a transmembrane region.
Glycoside hydrolase, family 3, N-terminal (Glyco_hydro_3_N)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 3

comprises enzymes with a number of known activities; beta-glucosidase (

); beta-xylosidase (

); N-acetyl beta-glucosaminidase (

); glucan beta-1,3-glucosidase (

); cellodextrinase (

); exo-1,3-1,4-glucanase (

).
These enzymes are two-domain globular proteins that are N-glycosylated at three sites . This domain is often N-terminal to the glycoside hydrolase family 3, C-terminal domain

.
Carbonic anhydrase (Carbonic_anhydrase)
Type: Family

Carbonic anhydrases (

) (CA) are zinc metalloenzymes which catalyze the reversible hydration of carbon dioxide.
In Escherichia coli, CA (gene cynT) is involved in recycling carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate by cyanase (gene cynS). By this action, it prevents the depletion of cellular bicarbonate . In photosynthetic bacteria and plant chloroplast, CA is essential to inorganic carbon fixation .
Prokaryotic and plant chloroplast CA are structurally and evolutionary related and form a family distinct from the one which groups the many different forms of eukaryotic CA's (see

).

This family also includes the carbonyl sulfide hydrolase from Thiobacillus thioparus which responsible for the degradation of carbonyl sulfide to hydrogen sulfide and CO2, the second step of SCN(-) assimilation , and a carbon disulfide hydrolase from acidothermophilic archaeon Acidianus, which has a typical carbonic anhydrase fold and active site but does not use CO2 as a substrate .
Fork head domain (Fork_head_dom)
Type: Domain

The fork head domain is a conserved DNA-binding domain (also known as a "winged helix") of about 100 amino-acid residues.

Drosophila melanogaster fork head protein is a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors . Instead, it contains a distinct type of DNA-binding region, containing around 100 amino acids, which has since been identified in a number of transcription factors (including D. melanogaster FD1-5, mammalian HNF-3, human HTLF, Saccharomyces cerevisiae HCM1, etc.). This is referred to as the fork head domain but is also known as a 'winged helix' .

The fork head domain binds B-DNA as a monomer , but shows no similarity to previously identified DNA-binding motifs. Although the domain is found in several different transcription factors, a common function is their involvement in early developmental decisions of cell fates during embryogenesis .
Hedgehog protein, Hint domain (Hedgehog_Hint)
Type: Domain

Hedgehog proteins are a family of secreted signal molecules required for embryonic cell differentiation. They are synthesised as inactive precursors with an N-terminal signalling domain linked to a C-terminal autoprocessing domain. The three-dimensional structure of the autolytic domain of the hedgehog protein of shows similarity with the β-strand core of intein splicing domains. It has hence been termed the hint (Hedgehog/Intein) domain .

This entry represents the Hint module in the Hedgehog proteins. It does not include any Inteins, which also possess the Hint domain.