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0AGRN_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameAGRN
DescriptionAgrin precursor.
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0005605 basal lamina (IDA)
0043236 laminin binding (TAS)
0005200 structural constituent of cytoskeleton (TAS)
0007213 acetylcholine receptor signaling, muscarini... (TAS)
0045162 clustering of voltage-gated sodium channels (TAS)
0043113 receptor clustering (IDA)
0007165 signal transduction (TAS)
0050808 synapse organization and biogenesis (TAS)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains assigned to SynO:
Agrin is a multidomain heparan sulphate proteoglycan.hat is a key organizer for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain . This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The NtA domain forms the most N-terminal part.ollowed by 9 Kazal-like domains and 2 LE domains. The C-terminal part consists of a SEA domain. EGF-like domains and 3 Laminin G domains.esponsible for the clustering of acetylcholine receptors . Tertiairy structures show that the NtA domain folds as a beta-barrel core flanked by N- and C-terminal helical regions. The core of the domain consists of 5 beta-strands that form 2 beta-sheets. The structure belongs to the OB fold family and shows similarity with the protease inhibition domain of TIMP-1.uggesting alternative functions for agrin in addition to synaptogenic activity . Residues Leu 117 and Val 124 in helix 3 of the NtA domain are essential for binding to the laminin gamma1 chain .
  IPR004850:Agrin NtA
Laminins are large heterotrimeric glycoproteins involved in basement membrane function . The laminin globular (G) domain can be found in one to several copies in various laminin family members.ncluding a large number of extracellular proteins. The C-terminus of the laminin alpha chain contains a tandem repeat of five laminin G domains.hich are critical for heparin-binding and cell attachment activity . Laminin alpha4 is distributed in a variety of tissues including peripheral nerves.orsal root ganglion.keletal muscle and capillaries; in the neuromuscular junction.t is required for synaptic specialisation . The structure of the laminin-G domain has been predicted to resemble that of pentraxin .Laminin G domains can vary in their function.nd a variety of binding functions have been ascribed to different LamG modules. For example.he laminin alpha1 and alpha2 chains each have five C-teminal laminin G domains.here only domains LG4 and LG5 contain binding sites for heparin.ulphatides and the cell surface receptor dystroglycan . Laminin G-containing proteins appear to have a wide variety of roles in cell adhesion.ignalling.igration.ssembly and differentiation. Proteins with laminin-G domains include:Laminin.Merosin.Agrin.Neurexins.Vitamin K dependent protein S.Sex steroid binding protein SBP/SHBG.Drosophila proteins Slit.rumbs.at.several proteoglycan precursors.
  IPR001791:Laminin G
InterPro domains unassigned to SynO:
Laminins are large heterotrimeric glycoproteins involved in basement membrane function . The laminin globular (G) domain can be found in one to several copies in various laminin family members.ncluding a large number of extracellular proteins. The C-terminus of the laminin alpha chain contains a tandem repeat of five laminin G domains.hich are critical for heparin-binding and cell attachment activity . Laminin alpha4 is distributed in a variety of tissues including peripheral nerves.orsal root ganglion.keletal muscle and capillaries; in the neuromuscular junction.t is required for synaptic specialisation . The structure of the laminin-G domain has been predicted to resemble that of pentraxin . Laminin G domains can vary in their function.nd a variety of binding functions have been ascribed to different LamG modules. For example.he laminin alpha1 and alpha2 chains each have five C-teminal laminin G domains.here only domains LG4 and LG5 contain binding sites for heparin.ulphatides and the cell surface receptor dystroglycan . Laminin G-containing proteins appear to have a wide variety of roles in cell adhesion.ignalling.igration.ssembly and differentiation. This entry represents one subtype of laminin G domains.hich is sometimes found in association with thrombospondin-type laminin G domains ().
  IPR012680:Laminin G, subdomain 2
SEA is an extracellular domain associated with O-glycosylation .Proteins found to contain SEA-modules include.grin.nterokinase.3 kDa sea urchin (Strongylocentrotus purpuratus) sperm protein.erlecan (heparan sulphate proteoglycan core.ucin 1 and the cell surface antigen.14/A10.nd two functionally uncharacterised.robably extracellular.aenorhabditis elegans proteins. Despite the functional diversity of these adhesive proteins. common denominator seems to be their existence in heavily glycosylated environments. In addition.he better characterised proteins all contain O-glycosidic-linked carbohydrates such as heparan sulphate that contribute considerably to their molecular masses. The common module might regulate or assist binding to neighbouring carbohydrate moieties.Enterokinase.he initiator of intestinal digestion.s a mosaic protease composed of a distinctive assortment of domains .
  IPR000082:SEA
Laminins are the major noncollagenous components of basement membranesthat mediate cell adhesion.rowth migration.nd differentiation. They arecomposed of distinct but related alpha.eta and gamma chains. The threechains form a cross-shaped molecule that consist of a long arm and three shortglobular arms. The long arm consist of a coiled coil structure contributed byall three chains and cross-linked by interchain disulphide bonds.Beside different types of globular domains each subunit contains.n its firsthalf.onsecutive repeats of about 60 amino acids in length that include eightconserved cysteines . The tertiary structure .f this domain isremotely similar in its N-terminal to that of the EGF-like module (see ). It is known as a LE or laminin-type EGF-like domain. Thenumber of copies of the LE domain in the different forms of laminins is highlyvariable; from 3 up to 22 copies have been found.A schematic representation of the topology of the four disulphide bonds inthe LE domain is shown below.In mouse laminin gamma-1 chain.he seventh LE domain has been shown to be theonly one that binds with a high affinity to nidogen . The binding-sites arelocated on the surface within the loops C1-C3 and C5-C6 . Longconsecutive arrays of LE domains in laminins form rod-like elements of limitedflexibility .hich determine the spacing in the formation of lamininnetworks of basement membranes .
  IPR002049:EGF-like, laminin
Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors.espectively. In many cases they are synthesised as part of a larger precursor protein.ither as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. This family of Kazal inhibitors.elongs to MEROPS inhibitor family I1.lan IA. They inhibit serine peptidases of the S1 family () . The members are primarily metazoan.ut includes exceptions in the alveolata (apicomplexa).tramenopiles.igher plants and bacteria.Kazal inhibitors.hich inhibit a number of serine proteases (such astrypsin and elastase).elong to family of proteins that includespancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor;and elastase inhibitor. These proteins contain between 1 and 7 Kazal-typeinhibitor repeats . The structure of the Kazal repeat includes a large quantity of extended chain. short alpha-helices and a 3-stranded anti-parallel beta sheet .The inhibitor makes 11 contacts with its enzyme substrate: unusually. of these important residues are hypervariable . Altering the enzyme-contact residues.nd especially that of the active site bond.ffects the the strength of inhibition and specificity of the inhibitor for particular serine proteases . The presence of this Pfam domain is usually indicative of serine protease inhibitors.owever.azal-like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors.
  IPR002350:Proteinase inhibitor I1, Kazal
A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF)has been shown to be present.n a moreor less conserved form.n a large number of other.ostly animal proteins. The list of proteins currently known tocontain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains inwhat appear to be unrelated proteins is not yet clear. However. common feature is that these repeats are found inthe extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandinG/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphidebonds. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet.Subdomains between the conserved cysteines vary in length.
  IPR006209:EGF-like
This EGF-like domain resembles the follistatin-N-terminal domain.nd is distinct from the kazal-like sequence. Follistatin binds to activin and is a specific inhibotor of the biosynthesis and secretion of pituitary follicle stimulating hormone. This domain is also found in prespore vesicle protein and agrin.
  IPR003645:Follistatin-like, N-terminal
Epidermal growth factors and transforming growth factors belong to a general class of proteins that share a repeat pattern involving a number of conserved Cys residues. Growth factors are involved in cell recognition and division . The repeating pattern.specially of cysteines (the so-called EGF repeat).s thought to be important to the 3D structure of the proteins.nd hence its recognition by receptors and other molecules. The type 1 EGF signature includes six conserved cysteines believed to be involved in disulphide bond formation. The EGF motif is found frequently in nature.articularly in extracellular proteins.
  IPR006210:EGF
Lectins and glucanases exhibit the common property of reversibly binding to specific complex carbohydrates. The lectins/glucanases are a diverse group of proteins found in a wide range of species from prokaryotes to humans. The different family members all contain a concanavalin A-like domain.hich consists of a sandwich of 12-14 beta strands in two sheets with a complex topology. Members of this family are diverse.nd include the lectins: legume lectins.ereal lectins.iral lectins.nd animal lectins. Plant lectins function in the storage and transport of carbohydrates in seeds.he binding of nitrogen-fixing bacteria to root hairs.he inhibition of fungal growth or insect feeding.nd in hormonally regulated plant growth . Protein members include concanavalin A (Con A).avin.solectin I.ectin IV.oybean agglutinin and lentil lectin. Animal lectins include the galectins.hich are S-type lactose-binding and IgE-binding proteins such as S-lectin.LC protein.alectin1.alectin2.alectin3 CRD.nd Congerin I . Other members with a Con A-like domain include the glucanases and xylanases. Bacterial and fungal beta-glucanases.uch as Bacillus 1-3.-4-beta-glucanse.arry out the acid catalysis of beta-glucans found in microorganisms and plants . Similarly.appa-Carrageenase degrades kappa-carrageenans from marine red algae cell walls . Xylanase and cellobiohydrolase I degrade hemicellulose and cellulose.espectively . There are many Con A-like domains found in proteins involved in cell recognition and adhesion. For example.everal viral and bacterial toxins carry Con A-like domains. Examples include the Clostridium neurotoxins responsible for the neuroparalytic effects of botulism and tetanus . The Pseudomonas exotoxin A. virulence factor which is highly toxic to eukaryotic cells.ausing the arrest of protein synthesis.ontains a Con A-like domain involved in receptor binding . Cholerae neuraminidase can bind to cell surfaces.ossibly through their Con A-like domains.here they function as part of a mucinase complex to degrade the mucin layer of the gastrointestinal tract . The rotaviral outer capsid protein.P4.as a Con A-like sialic acid binding domain.hich functions in cell attachment and membrane penetration . Con A-like domains also play a role in cell recognition in eukaryotes. Proteins containing a Con A-like domain include the sex hormone-binding globulins which transport sex steroids in blood and regulate their access to target tissues .aminins which are large heterotrimeric glycoproteins involved in basement membrane architecture and function .eurexins which are expressed in hundreds of isoforms on the neuronal cell surface.here they may function as cell recognition molecules and sialidases that are found in both microorganisms and animals.nd function in cell adhesion and signal transduction . Other proteins containing a Con A-like domain include pentraxins and calnexins. The pentraxin PTX3 is a TNFalpha-induced.ecreted protein of adipose cells produced during inflammation . The calnexin family of molecular chaperones is conserved among plants.ungi.nd animals. Family members include Calnexin. type-I integral membrane protein in the endoplasmic reticulum which coordinates the processing of newly synthesized N-linked glycoproteins with their productive folding.almegin. type-I membrane protein expressed mainly in the spermatids of the testis.nd calreticulin. soluble ER lumenal paralog .
  IPR008985:Concanavalin A-like lectin/glucanase
Tissue inhibitors of metalloproteinases (TIMP) are a family of proteins that can form complexes with extracellular matrix metalloproteinases (such as collagenases) and irreversibly inactivate them . TIMP and related proteins contains a five-stranded antiparallel beta-sheet that is rolled over on itself to form a closed beta-barrel.nd two short helices.hich pack close to one another on the same barrel face. A comparison of the delta TIMP-2 structure with other known protein folds reveals that the beta-barrel topology is homologous to that seen in proteins of the oligosaccharide/oligonucleotide binding (OB) fold family. five-stranded beta-sheet coiled to form a closed beta-barrel capped by an alpha-helix located between the third and fourth strands .The SSF signature in this entry is currently under review. Please be aware that some of the protein hits may be false positives.
  IPR008993:TIMP-like OB-fold
Lectins and glucanases exhibit the common property of reversibly binding to specific complex carbohydrates. The lectins/glucanases are a diverse group of proteins found in a wide range of species from prokaryotes to humans. The different family members all contain a concanavalin A-like domain.hich consists of a sandwich of 12-14 beta strands in two sheets with a complex topology. Members of this family are diverse.nd include the lectins: legume lectins.ereal lectins.iral lectins.nd animal lectins. Plant lectins function in the storage and transport of carbohydrates in seeds.he binding of nitrogen-fixing bacteria to root hairs.he inhibition of fungal growth or insect feeding.nd in hormonally regulated plant growth . Protein members include concanavalin A (Con A).avin.solectin I.ectin IV.oybean agglutinin and lentil lectin. Animal lectins include the galectins.hich are S-type lactose-binding and IgE-binding proteins such as S-lectin.LC protein.alectin1.alectin2.alectin3 CRD.nd Congerin I . Other members with a Con A-like domain include the glucanases. Bacterial and fungal beta-glucanases.uch as Bacillus 1-3.-4-beta-glucanse.arry out the acid catalysis of beta-glucans found in microorganisms and plants . Similarly.appa-Carrageenase degrades kappa-carrageenans from marine red algae cell walls . This entry differs from () by omitting the xylanases and glycosyl hydrolases.
  IPR013320:Concanavalin A-like lectin/glucanase, subgroup
IPR004850:NtA 
Evalue:-111.823905944824 
Location:30-157IPR012680:Laminin_G_2 
Evalue:-45.8239097595215 
Location:1400-1528IPR001791:LamG 
Evalue:-38.7212463990472 
Location:1889-2025IPR012680:Laminin_G_2 
Evalue:-37.4685211181641 
Location:1668-1796IPR000082:SEA 
Evalue:-33.3565473235138 
Location:1130-1252IPR002049:Laminin_EGF 
Evalue:-21.8538722991943 
Location:793-844IPR002350:KAZAL 
Evalue:-19.4814860601221 
Location:489-534IPR002350:Kazal_1 
Evalue:-18.6989707946777 
Location:555-599IPR002350:Kazal_1 
Evalue:-18.1366767883301 
Location:923-969IPR002350:Kazal_1 
Evalue:-18 
Location:197-242IPR002350:Kazal_1 
Evalue:-17.6989707946777 
Location:620-664IPR002350:KAZAL 
Evalue:-17 
Location:704-750IPR002350:Kazal_1 
Evalue:-16.2518119812012 
Location:416-461IPR002350:Kazal_1 
Evalue:-13.1487417221069 
Location:272-317IPR002049:Laminin_EGF 
Evalue:-12.7695512771606 
Location:847-891IPR002350:Kazal_1 
Evalue:-12.2757244110107 
Location:342-389IPR006209:EGF 
Evalue:-8.38721656799316 
Location:1818-1852IPR006209:EGF 
Evalue:-7.85387182235718 
Location:1553-1585IPR006209:EGF 
Evalue:-7.29242992401123 
Location:1333-1366IPR006209:EGF 
Evalue:-6.0915150642395 
Location:1592-1624IPR003645:FOLN 
Evalue:-5.18045606445813 
Location:900-922IPR003645:FOLN 
Evalue:-5.0087739243075 
Location:247-271IPR003645:FOLN 
Evalue:-4.85387196432176 
Location:171-196
SequencesProtein: AGRN_HUMAN (2045 aa)
mRNA: NM_198576
Local Annotation
Synapse Ontology
A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface.
sdb:0024 neuromuscular junction  (Evidence:keywords,domains)
Any process that stops, prevents or reduces the rate, frequency or extent of synaptic growth at neuromuscular junction.
sdb:0046 long-term strengthening of neuromuscular junction  (Evidence:keywords,domains)
Any process that activates or increases the rate, frequency or extent of synaptic growth at neuromuscular junction.
sdb:0047 positive regulation of synaptic growth at neuromuscular junction  (Evidence:keywords,domains)
Na channel plays an important role in the course of action potential.
sdb:0287 Na channel  (Evidence:keywords,domains)
KO assignmentK06254
  Level 3 annotation:
    agrin
  Level 2 annotation:
    Proteoglycans
    ECM-receptor interaction
    CAM ligands
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 84 residues, 945365-945616Exon2: 89 residues, 947443-947705Exon3: 18 residues, 960519-960567Exon4: 74 residues, 965907-966123Exon5: 77 residues, 966415-966640Exon6: 77 residues, 966720-966945Exon7: 71 residues, 967198-967405Exon8: 75 residues, 968481-968700Exon9: 67 residues, 968780-968975Exon10: 69 residues, 969065-969266Exon11: 51 residues, 969351-969500Exon12: 37 residues, 969576-969682Exon13: 41 residues, 970403-970520Exon14: 57 residues, 970601-970766Exon15: 50 residues, 970975-971119Exon16: 43 residues, 971206-971331Exon17: 37 residues, 971402-971508Exon18: 115 residues, 971639-971978Exon19: 48 residues, 972062-972200Exon20: 44 residues, 972569-972697Exon21: 40 residues, 972815-972930Exon22: 42 residues, 973018-973138Exon23: 120 residues, 973254-973608Exon24: 66 residues, 974109-974302Exon25: 74 residues, 974478-974694Exon26: 78 residues, 974808-975038Exon27: 47 residues, 975145-975280Exon28: 34 residues, 975475-975572Exon29: 57 residues, 975669-975834Exon30: 39 residues, 975968-976080Exon31: 41 residues, 976495-976612Exon32: 66 residues, 976695-976888Exon33: 31 residues, 976970-977058Exon34: 77 residues, 978995-979220Exon35: 36 residues, 979690-979794Exon36: 431 residues, 980066-981355Exon37: 2 residues, -Jump to AGRN_HUMAN  
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Loci Cluster (Details)Loci: 2469 938741-939776 ~-1K 23(G1P2)(+)Loci: 2470 945365-981355 ~-36K 24(AGRN)(+)Loci: 2471 1207438-1217272 ~-10K 59(SCNN1D)(+)Loci: 2472 1540746-1555847 ~-15K 98(MIB2)(+)Loci: 2473 1940702-1952050 ~-11K 141(GABRD)(+)Loci: 2474 1971768-2106692 ~-135K 142(PRKCZ)(+)Loci: 2468 885829-890958 ~-5K 15(KLHL17)(+)Link out to UCSC