The EGF-like domain is an evolutionary conserved
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...
, which derives its name from the
epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins.
Most occurrences of the EGF-like domain are found in the extracellular domain of
membrane-bound proteins or in proteins known to be
secreted 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
. An exception to this is the
prostaglandin-endoperoxide synthase. The EGF-like domain includes 6
cysteine residues which in the epidermal growth factor have been shown to form 3
disulfide bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s. The structures of 4-disulfide EGF-domains have been solved from the
laminin
Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
and
integrin
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle ...
proteins. The main structure of EGF-like domains is a two-stranded
β-sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets.
EGF-like domains frequently occur in numerous tandem copies in proteins: these repeats typically
fold together to form a single, linear
solenoid domain block as a functional unit.
Subtypes
Despite the similarities of EGF-like domains, distinct domain subtypes have been identified.
The two main proposed types of EGF-like domains are the human EGF-like (hEGF) domain and the complement C1r-like (cEGF) domain,
which was first identified in the human complement protease C1r.
C1r is a highly specific
serine protease
Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site.
They are found ubiquitously in both eukaryotes and prokaryotes. Seri ...
initiating the classical pathway of
complement activation
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a ...
during immune response.
Both the hEGF- and cEGF-like domains contain three disulfides and derive from a common ancestor that carried four disulfides of which one was lost during evolution. Furthermore, cEGF-like domains can be divided in two subtypes (1 and 2) whereas all hEGF-like domains belong to one subtype.
The differentiation of cEGF-like and hEGF-like domains and their subtypes is based on structural features and the connectivity of their disulfide bonds. cEGF- and hEGF-like domains have a distinct shape and orientation of the minor sheet and one C-terminal half-cystine has a different position. The lost cysteines of the common ancestor differ between cEGF- and hEGF-like domains and hence these types differ in their disulfide linkages. The differentiation of cEGF into subtype 1 and 2, which probably occurred after its split from hEGF, is based on different residue numbers between the distinct half-cystines. An N-terminal located calcium binding motif can be found in hEGF- as well as in cEGF-like domains and is therefore not suitable to tell them apart.
hEGF- and cEGF-like domains also contain
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
s, which are often unusual and differ between hEGF- and cEGF-like domains. These post-translational modifications include O-glycosylations, mostly O-fucose modifications, and β-hydroxylation of aspartate and asparagine residues. O-fucose modifications have only been detected in hEGF-like domains and they are important for the proper folding of the hEGF-like domain. β-Hydroxylation appears in hEGF- and cEGF-like domains, the former is hydroxylated on an aspartic acid while the latter is hydroxylated on an asparagine residue. The biological role of this post-translational modification is unclear,
but mice with a knockout of the aspartyl-β-hydroxylation enzyme show developmental defects.
Proteins containing EGF-like domains are widespread and can be exclusively hEGF- or cEGF-like, or contain a mix of both. In many mitogenic and developmental proteins such as
Notch and Delta the EGF-like domains are only of the hEGF type. Other proteins contain only cEGF such as
thrombomodulin
Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoag ...
and the
LDL-receptor. In mixed EGF-proteins the hEGF- and cEGF-like domains are grouped together with the hEGFs always being N-terminal of the cEGFs. Such proteins are involved in blood coagulation or are components of the extracellular matrix like
fibrillin
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.
Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, whic ...
and LTBP-1 (Latent-transforming growth factor beta-binding protein 1). In addition to the aforementioned three disulfide hEGF- and cEGF-like types, there are proteins carrying a four-disulfide EGF-like domain like laminin and integrin.
The two main EGF-like domain subtypes hEGF and cEGF are not just distinct in their structure and conformation but also have different functions. This hypothesis is substantiated by research on LTBP-1. LTBP-1 anchors the transforming growth factor β (TGF-β) to the extracellular matrix. hEGF-like domains play a role in targeting the LTBP-1/TGF-β assembly to the extracellular matrix. Once attached to the extracellular matrix, TGF-β dissociates from hEGF subunits to allow its subsequent activation. cEGF-like domains seem to play an unspecific role in this activation by promoting the cleavage of LTBP-1 from TGF-β by various proteases.
In conclusion, although distinct EGF-like domains are grouped, subtypes can be clearly separated by their sequence, conformation and, most importantly, their function.
Role in the immune system and apoptosis
Selectins
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
, a group of proteins that are involved in
leukocyte rolling towards a source of inflammation, contain an EGF-like domain along with a lectin domain and short consensus repeats (SCRs).
The functions of the EGF-like domain vary between different selectin types. Kansas and co-workers were able to show that the EGF-like domain is not required for maximal cellular adhesion in L-selectin (expressed on lymphocytes). However, it is involved in both ligand recognition and adhesion in P-selectin (expressed on platelets) and may also be involved in protein-protein interactions. It has been suggested that the interactions between lectin domains and carbohydrate ligands might be calcium-dependent.
Immature human
dendritic cells
Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
appear to require interactions with the EGF-like domains of selectins during their maturation process. Blocking of this interaction with monoclonal anti-EGF-like domain antibodies prevents dendritic cell maturation. The immature cells fail to activate T-cells and produce less interleukin 12 than wild-type dendritic cells.
Phan ''et al.'' could show that the artificial insertion of an
N-glycosylation site into the EGF-like domains in P- and L-selectins increased the affinities of selectins to their ligands and led to slower rolling.
Therefore, EGF-like domains seem to play a crucial role in leukocyte movements towards inflammatory stimuli.
The EGF-like domain is also part of laminins, an important group of extracellular proteins. The EGF-like domains are usually masked in intact membranes, but become exposed when the membrane is destroyed, e.g. during inflammation, thereby stimulating membrane growth and restoring damaged membrane parts.
Moreover, the EGF-like domain repeats of the stabilin-2 domain have been shown to specifically recognize and bind apoptotic cells, probably by recognizing
phosphatidylserine
Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via ap ...
, an apoptotic cell marker (“eat me-signal”).
Park ''et al.'' further demonstrated that the domains are able to competitively impair recognition of apoptotic cells by macrophages.
In conclusion, the EGF-like domain appears to play a vital role in immune responses as well as in eliminating dead cells in the organism.
Calcium-binding
Calcium-binding EGF-like domains (cbEGF-like domains) play a seminal role in diseases such as the
Marfan syndrome or the X-chromosome linked hemorrhagic disorder
hemophilia B
Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII defi ...
and are among the most abundant extracellular calcium-binding domains.
Importantly, cbEGF- like domains impart specific functions to a variety of proteins in the blood clotting cascade. Examples include the coagulation factors
VII VII or vii may refer to: the Roman numeral 7
Art and entertainment
* The Vii, a video game console
* vii, leading-tone triad, see diminished triad
* ''VII'' (Blitzen Trapper album)
* ''VII'' (Just-Ice album)
* ''VII'' (Teyana Taylor album)
* ...
,
IX and
X, protein C and its cofactor protein S.
Calcium-binding EGF-like domains are typically composed of 45 amino acids, arranged as two antiparallel beta sheets.
Several cysteine residues within this sequence form disulfide bridges.
cbEGF-like domains show no significant structural deviations from EGF-like domains; however, as the name suggests, cbEGF-like domains bind a single
calcium ion
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
. The binding affinity to calcium varies widely and often depends on adjacent domains.
The consensus motif for calcium binding is Asp-Leu/Ile-Asp-Gln-Cys. Coordination of calcium strongly correlates with an unusual posttranslational modification of cbEGF-like domains: either an asparagine or aspartate is beta-hydroxylated giving rise to erythro-beta-hydroxyasparagine (Hyn) or erythro-beta-hydroxyaspartic acid (Hya), respectively. Hya can be found in the N-terminal cbEGF module (see below) of factors IX, X, and protein C. The Hyn modification appears to be more prevalent than Hya and has been shown to occur in fibrillin-1, an extracellular matrix protein.
Both modifications are catalyzed by the dioxygenase Asp/Asn-beta-hydroxylase,
and are unique to EGF domains in eukaryotes.
Further posttranslational modifications have been reported. Glycosylation in the form of O-linked di- or trisaccharides may occur at a serine residue between the first two cysteines of blood coagulation factors VII and IX.
Factor VII exhibits an O-linked fucose at Ser60.
Multiple cbEGF domains are often connected by one or two amino acids to form larger, repetitive arrays, here referred to as 'cbEGF modules'. In the blood-clotting cascade, coagulation factors VII, IX and X and protein C contain a tandem of two cbEGF modules, whereas protein S has four. Impressively, in fibrillin-1 and fibrillin-2, 43 cbEGF modules have been found.
The modularity of these proteins adds complexity to protein-protein but also module-module interaction. In factors VII, IX and X, the two cbEGF modules are preceded by an N-terminal gamma-carboxyglutamic acid (Gla) containing module (the
Gla module).
In vitro studies on the Gla-cbEGF tandem isolated from factor X revealed a K
d-value of 0.1 mM for calcium binding
with the free calcium blood plasma concentrations being approximately 1.2 mM. Surprisingly, in the absence of the Gla module, the cbEGF module exhibits a K
d-value of 2.2 mM for calcium.
Thus, the presence of the Gla module increases calcium affinity 20-fold. Similarly, the activity of Gla and serine protease modules are modified by the cbEGF modules. In the absence of calcium, the Gla and cbEGF modules are highly mobile. As the cbEGF module associates with calcium, however, movement of the Gla module is significantly restricted because the cbEGF module now adopts a conformation that locks the neighboring Gla module in a fixed position.
Therefore, calcium coordination induces conformational changes which, in turn, might modulate enzymatic activity.
Impaired coordination of calcium can result in serious disorders. Defective calcium binding to coagulation factor IX contributes to the development of hemophilia B. Individuals with this hereditary disease tend to develop hemorrhages, potentially leading to life-threatening conditions. The cause of hemophilia B is decreased activity or deficiency of blood coagulation factor IX. Point mutations resulting in decreased affinity of factor IX to calcium are thought to be implicated in this bleeding disorder.
On a molecular basis, it appears that hemophilia B can be the result of an impaired ability to localize the Gla module efficiently, as it usually occurs after calcium coordination by the cbEGF module in fully functional factor IX.
This defect is thought to impair the biological function of factor IX. A similar problem occurs in patients with hemophilia B and carrying a mutation (Glu78Lys) in factor IX that prevents interaction of the two cbEGF modules with one another.
Conversely, in healthy individuals, Glu78 in the first cbEGF-module contacts Arg94 in the second cbEGF module and thereby aligns both modules.
Thus, domain-domain interactions (partially facilitated by calcium coordination) are crucial for the catalytic activity of proteins involved in the blood-clotting cascade.
Proteins containing this domain
Below is a list of human proteins containing the EGF-like domain:
*
AGC1;
AGRIN
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. ...
;
AREG;
ATRN
Attractin is a protein that in humans is encoded by the ''ATRN'' gene.
Attractin is a Group XI C-type lectin
A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement ...
;
ATRNL1;
*
BCAN;
BMP1;
BTC;
*
C1S
Complement component 1s (, '' C1 esterase'', ''activated complement C1s'', ''complement C overbar 1r'', ''C1s'') is a protein involved in the complement system. C1s is part of the C1 complex. In humans, it is encoded by the ''C1S'' gene.
C1s cle ...
;
CASPR4;
CD248
Endosialin is a protein that in humans is encoded by the ''CD248'' gene.
Endosialin is a member of the “ Group XIV”, a novel family of C-type lectin transmembrane receptors which play a role not only in cell–cell adhesion processes but also ...
;
CD93
CD93 (Cluster of Differentiation 93) is a protein that in humans is encoded by the ''CD93'' gene. CD93 is a C-type lectin transmembrane receptor which plays a role not only in cell–cell adhesion processes but also in host defense.
Family
CD ...
;
CELSR1
Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the ''CELSR1'' gene.
Function
The protein encoded by this gene is a member of the flamingo su ...
;
CELSR2;
CELSR3
Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the ''CELSR3'' gene.
The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consist ...
;
CLEC14A;
CNTNAP1
CASPR also known as Contactin associated protein 1, Paranodin and CASPR1 is a protein that in humans is encoded by the CNTNAP1 gene.
CASPR is a part of the neurexin family of proteins, hence its another name "Neurexin IV". CASPR is a membrane pr ...
;
CNTNAP2
Contactin-associated protein-like 2 is a protein that in humans is encoded by the ''CNTNAP2'' gene. Since the most recent reference human genome GRCh38, CNTNAP2 is the longest gene in the human genome
This gene encodes a member of the neurexin fa ...
;
CNTNAP3;
CNTNAP4;
CNTNAP5;
COMP
Comp, COMP or Comps may refer to:
Places
In England:
* Comp, Kent
In France:
* Comps, Drôme
* Comps, Gard
* Comps, Gironde
* Comps-la-Grand-Ville
* Comps-sur-Artuby
Arts, entertainment, and media
;Music
*Accompaniment, especially in jazz ...
;
COX-2
Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
;
CRB1
Crumbs homolog 1 is a protein that in humans is encoded by the ''CRB1'' gene.
This gene encodes a protein which is similar to the Drosophila ''crumbs'' protein and localizes to the inner segment of mammalian photoreceptors. In Drosophila, crumbs ...
;
CRB2;
CSPG3;
CUBN
Cubilin is a protein that in humans is encoded by the ''CUBN'' gene.
Function
Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a re ...
;
*
DLK1;
DLL1
Delta-like protein 1 is a protein that in humans is encoded by the ''DLL1'' gene.
Function
DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions d ...
;
DLL3;
DLL4
Delta-like 4 is a protein that in humans is encoded by the ''DLL4'' gene.
This gene is a homolog
In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologou ...
;
DNER;
*
EDIL3;
EGF;
EGFL11;
EGFL8;
EGFL9;
EGFLAM
Pikachurin, also known as AGRINL (AGRINL) and EGF-like, fibronectin type-III and laminin G-like domain-containing protein (EGFLAM), is a protein that in humans is encoded by the ''EGFLAM'' gene.
Pikachurin is a dystroglycan-interacting protein ...
;
EPGN;
EREG;
*
F7;
F9;
F10;
F12;
FAT
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple est ...
;
FAT2
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers spec ...
;
FAT4;
FBN1
Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfib ...
;
FBN2
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.
Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, whi ...
;
FBN3;
*
GAS6
Growth arrest – specific 6, also known as GAS6, is a human gene coding for the GAS6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth a ...
;
*
HABP2;
HBEGF;
HEG1;
HGFAC
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.
The protein encoded by this gene belongs to peptidase family S1. It is first synthesized as an inactive single-chain precursor before being activated to ...
;
HMCN1
Hemicentin-1 is a protein that in humans is encoded by the ''HMCN1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' o ...
;
HSPG2
Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the ''HSPG2'' gene. The HSPG2 gene codes for a 4,391 amin ...
;
*
ITGB5;
*
JAG1
Jagged1 (''JAG1'') is one of five cell surface proteins (ligands) that interact with four receptors in the mammalian Notch signaling pathway. The Notch Signaling Pathway is a highly conserved pathway that functions to establish and regulate cell fa ...
;
JAG2
Jagged-2 is a protein that in humans is encoded by the ''JAG2'' gene.
Function
The Notch signaling pathway is an intercellular signaling mechanism that is essential for proper embryonic development. Members of the Notch gene family encode tran ...
;
*
LDLR;
LRP1
Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membr ...
;
LRP10
Low-density lipoprotein receptor-related protein 10 is a protein that in humans is encoded by the ''LRP10'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." ...
;
LRP1B;
LRP2
Low density lipoprotein receptor-related protein 2 also known as LRP-2 or megalin is a protein which in humans is encoded by the ''LRP2'' gene.
Function
LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman neph ...
;
LRP4;
LRP5
Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the ''LRP5'' gene. LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway. Mutations in LRP5 can le ...
;
LRP6
Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the ''LRP6'' gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.
Structure
LRP6 is a t ...
;
LRP8;
LTBP1;
LTBP2
Latent-transforming growth factor beta-binding protein 2 is a protein that in humans is encoded by the ''LTBP2'' gene.
The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), ...
;
LTBP3;
LTBP4;
*
MATN1
Matrilin 1, cartilage matrix protein, also known as MATN1, is a matrilin protein which in humans is encoded by the ''MATN1'' gene.
Function
This gene encodes a member of von Willebrand factor A domain containing protein family. This family of ...
;
MATN2
Matrilin-2 is a matrilin protein that in humans is encoded by the ''MATN2'' gene.
This gene encodes a member of the von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of fi ...
;
MATN3
Matrilin-3 is a matrilin protein that in humans is encoded by the ''MATN3'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bi ...
;
MATN4;
MEGF12;
MEGF6
Multiple EGF like domains 6 is a protein that in humans is encoded by the MEGF6 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...
;
MEP1A;
MEP1B;
MFGE8
Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein that in humans is encoded by the ''MFGE8'' gene.
Species distribution
Mfge8 is a secreted protein found in vertebrates, including mammals as well as birds.
...
;
MMRN1;
MMRN1;
MUC4;
*
NAGPA
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase is an enzyme that in humans is encoded by the ''NAGPA'' gene.
Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. T ...
;
NID1
Nidogen-1 (NID-1), formerly known as entactin, is a protein that in humans is encoded by the ''NID1'' gene. Both nidogen-1 and nidogen-2 are essential components of the basement membrane alongside other components such as type IV collagen, proteog ...
;
NID2
Nidogen-2, also known as osteonidogen, is a basal lamina protein of the nidogen family. It was the second nidogen to be described after nidogen-1 (entactin). Both play key roles during late embryonic development. In humans it is encoded by the ' ...
;
NOTCH1
Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor.
Function
This gene encodes a member of the Notch family. Members of this Type 1 transm ...
;
NOTCH2
Neurogenic locus notch homolog protein 2 (Notch 2) is a protein that in humans is encoded by the ''NOTCH2'' gene.
NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome.
Function
Notch 2 is a member of the notch family. Membe ...
;
NOTCH2NL;
NOTCH3
Neurogenic locus notch homolog protein 3 (Notch 3) is a protein that in humans is encoded by the ''NOTCH3'' gene.
Function
This gene encodes the third discovered human homologue of the ''Drosophila melanogaster'' type I membrane protein notch ...
;
NOTCH4;
NRG1
Neuregulin 1, or NRG1, is a gene of the epidermal growth factor family that in humans is encoded by the ''NRG1'' gene. NRG1 is one of four proteins in the neuregulin family that act on the EGFR family of receptors. Neuregulin 1 is produced in num ...
;
NRG2
Neuregulin 2, also known as NRG2, is a protein which in humans is encoded by the ''NRG2'' gene.
Function
Neuregulin 2 (NRG2) is a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ErbB f ...
;
NRG3
Neuregulin 3, also known as NRG3, is a neural-enriched member of the neuregulin protein family which in humans is encoded by the ''NRG3'' gene. The NRGs are a group of signaling proteins part of the superfamily of epidermal growth factor, EGF ...
;
NRG4
Neuregulin 4 also known as NRG4 is a member of the neuregulin protein family which in humans is encoded by the ''NRG4'' gene.
Function
The neuregulins, including NRG4, activate erb-b2 receptor tyrosine kinase 4 (ERBB4) to initiating cell signal ...
;
NRXN1
Neurexin-1-alpha is a protein that in humans is encoded by the ''NRXN1'' gene.
Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes ...
;
NRXN2
Neurexin-2-alpha is a protein that in humans is encoded by the ''NRXN2'' gene.
Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes ...
;
NRXN3
Neurexin-3-alpha is a protein that in humans is encoded by the ''NRXN3'' gene.
Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes o ...
;
NTNG2
Netrin-G2 is a protein that in humans is encoded by the ''NTNG2'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ' ...
;
*
ODZ1;
ODZ2;
OIT3;
*
PLAT
In the United States, a plat ( or ) (plan) is a cadastral map, drawn to scale, showing the divisions of a piece of land. United States General Land Office surveyors drafted township plats of Public Lands Surveys to show the distance and bea ...
;
PP187;
PROC;
PROS1
Protein S (also known as PROS) is a vitamin K-dependent plasma glycoprotein synthesized in the liver. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In hum ...
;
PROZ;
PTGS1;
PTGS2
Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...
;
*
RAMP
An inclined plane, also known as a ramp, is a flat supporting surface tilted at an angle from the vertical direction, with one end higher than the other, used as an aid for raising or lowering a load. The inclined plane is one of the six clas ...
;
*
SCUBE1
Signal peptide, CUB domain and EGF like domain containing 1 is a protein that in humans is encoded by the SCUBE1 gene.
Function
This gene encodes a cell surface glycoprotein that is a member of the SCUBE ( signal peptide, CUB domain, EGF ( e ...
;
SCUBE2;
SCUBE3;
SEL-OB;
SELE;
SELL;
SELP;
SLIT1
Slit homolog 1 protein is a protein that in humans is encoded by the ''SLIT1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ' ...
;
SLIT2;
SLIT3
Slit homolog 3 protein is a protein that in humans is encoded by the ''SLIT3'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ' ...
;
SNED1;
STAB1;
STAB2;
SVEP1;
*
TECTA
Alpha-tectorin is a protein that in humans is encoded by the ''TECTA'' gene.
The tectorial membrane is an apical extracellular matrix (aECM) of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces ...
;
TGFA;
THBD;
THBS1
Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the ''THBS1'' gene.
Thrombospondin 1 is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and ...
;
THBS2
Thrombospondin-2 is a protein that in humans is encoded by the ''THBS2'' gene.
The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix ...
;
THBS4
Thrombospondin-4 is a protein that in humans is encoded by the ''THBS4'' gene.
The protein encoded by this gene belongs to the thrombospondin
Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to th ...
;
TIE1
Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 also known as TIE1 is an angiopoietin receptor which in humans is encoded by the ''TIE1'' gene.
Function
TIE1 is a cell surface protein expressed exclusively in endothelial cells, ...
;
TLL1
Tolloid-like protein 1 is a protein that in humans is encoded by the ''TLL1'' gene.
This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. A similar protein in mice is required during ...
;
TLL2
Tolloid-like protein 2 is a protein that in humans is encoded by the ''TLL2'' gene.
This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein ...
;
TMEFF1;
TMEFF2;
TNC;
TNXB;
*
UMOD
Uromodulin (UMOD), also known as Tamm–Horsfall protein (THP), is a Zona pellucida-like domain-containing glycoprotein that in humans is encoded by the ''UMOD'' gene. Uromodulin is the most abundant protein excreted in ordinary urine.
Gene
T ...
;
*
VASN;
VCAN;
VLDLR
The very-low-density-lipoprotein receptor (VLDLR) is a transmembrane lipoprotein receptor of the low-density-lipoprotein (LDL) receptor family. VLDLR shows considerable homology with the members of this lineage. Discovered in 1992 by T. Yamamoto, ...
;
VWA2;
*
WIF1
Wnt inhibitory factor 1 is a protein that in humans is encoded by the ''WIF1'' gene. WIF1 is a lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D ...
;
*
ZAN
Zan or ZAN, may refer to:
Geography
* Zhan, Kurdistan, Iran, also known as Zān
* Zhan, Lorestan, Iran, also known as Žān
* Zan, Tehran, a village in Tehran Province, Iran
Ethnicity and language
* Zans, the Zan People, people who speak the Za ...
;
See also
*
Epidermal growth factor
References
{{Reflist, 2
Protein domains
Single-pass transmembrane proteins