Human Gene AGRN (ENST00000379370.7_4) from GENCODE V47lift37
  Description: agrin, transcript variant 2 (from RefSeq NM_198576.4)
Gencode Transcript: ENST00000379370.7_4
Gencode Gene: ENSG00000188157.16_10
Transcript (Including UTRs)
   Position: hg19 chr1:955,500-991,496 Size: 35,997 Total Exon Count: 36 Strand: +
Coding Region
   Position: hg19 chr1:955,553-990,361 Size: 34,809 Coding Exon Count: 36 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:955,500-991,496)mRNA (may differ from genome)Protein (2045 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: AGRIN_HUMAN
DESCRIPTION: RecName: Full=Agrin; Flags: Precursor;
FUNCTION: Plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Ligand of the MUSK signaling complex that directly binds LRP4 in this complex and induces the phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane.
SUBUNIT: Interacts with LRP4; the interaction is direct and recruits AGRIN to the MUSK signaling complex composed at least of MUSK and LRP4 (By similarity). Binds to laminin.
INTERACTION: O15265:ATXN7; NbExp=2; IntAct=EBI-947482, EBI-708350;
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. Note=Synaptic basal lamina at the neuromuscular junction (By similarity).
PTM: Contains heparan sulfate chains as well as N-linked and O- linked oligosaccharides (By similarity).
DISEASE: Defects in AGRN are a cause of myasthenia, limb-girdle, familial (LGM) [MIM:254300]. A congenital myasthenic syndrome characterized by a typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function.
SIMILARITY: Contains 4 EGF-like domains.
SIMILARITY: Contains 9 Kazal-like domains.
SIMILARITY: Contains 2 laminin EGF-like domains.
SIMILARITY: Contains 3 laminin G-like domains.
SIMILARITY: Contains 1 NtA (N-terminal agrin) domain.
SIMILARITY: Contains 1 SEA domain.
WEB RESOURCE: Name=The Leiden Muscular Dystrophy pages, Agrin (AGRN); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/AGRN";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: AGRN
Diseases sorted by gene-association score: myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects* (1200), congenital myasthenic syndrome* (182), postsynaptic congenital myasthenic syndromes* (124), presynaptic congenital myasthenic syndromes* (111), agrn-related congenital myasthenic syndrome* (100), myasthenia gravis (10), muscular dystrophy, congenital merosin-deficient (9), sclerosteosis 2 (7), neuromuscular junction disease (7), cenani-lenz syndactyly syndrome (7), diffuse mesangial sclerosis (6), muscular dystrophy-dystroglycanopathy , type b, 6 (5), muscular dystrophy-dystroglycanopathy , type b, 5 (4), walker-warburg syndrome (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 52.39 RPKM in Kidney - Cortex
Total median expression: 656.24 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -18.9053-0.357 Picture PostScript Text
3' UTR -474.901135-0.418 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004850 - Agrin_NtA
IPR008985 - ConA-like_lec_gl_sf
IPR013320 - ConA-like_subgrp
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS
IPR002049 - EGF_laminin
IPR003645 - Fol_N
IPR011497 - Kazal-type_dom
IPR001791 - Laminin_G
IPR002350 - Prot_inh_Kazal
IPR000082 - SEA
IPR008993 - TIMP-like_OB-fold

Pfam Domains:
PF00008 - EGF-like domain
PF00050 - Kazal-type serine protease inhibitor domain
PF00053 - Laminin EGF domain
PF00054 - Laminin G domain
PF01390 - SEA domain
PF02210 - Laminin G domain
PF03146 - Agrin NtA domain
PF07648 - Kazal-type serine protease inhibitor domain

SCOP Domains:
49899 - Concanavalin A-like lectins/glucanases
50242 - TIMP-like
82671 - SEA domain
57196 - EGF/Laminin
57184 - Growth factor receptor domain
100895 - Kazal-type serine protease inhibitors

ModBase Predicted Comparative 3D Structure on O00468
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
    Protein Sequence 
    Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002162 dystroglycan binding
GO:0005200 structural constituent of cytoskeleton
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0033691 sialic acid binding
GO:0035374 chondroitin sulfate binding
GO:0043236 laminin binding
GO:0043395 heparan sulfate proteoglycan binding

Biological Process:
GO:0001523 retinoid metabolic process
GO:0006024 glycosaminoglycan biosynthetic process
GO:0006027 glycosaminoglycan catabolic process
GO:0007010 cytoskeleton organization
GO:0007165 signal transduction
GO:0007213 G-protein coupled acetylcholine receptor signaling pathway
GO:0007275 multicellular organism development
GO:0030154 cell differentiation
GO:0030198 extracellular matrix organization
GO:0043113 receptor clustering
GO:0043547 positive regulation of GTPase activity
GO:0045162 clustering of voltage-gated sodium channels
GO:0045887 positive regulation of synaptic growth at neuromuscular junction
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050808 synapse organization
GO:0051491 positive regulation of filopodium assembly

Cellular Component:
GO:0005576 extracellular region
GO:0005605 basal lamina
GO:0005796 Golgi lumen
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0031012 extracellular matrix
GO:0043202 lysosomal lumen
GO:0045202 synapse
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AB191264 - Homo sapiens AGRN mRNA for agrin, complete cds.
AB385240 - Synthetic construct DNA, clone: pF1KB9484, Homo sapiens AGRN gene for agrin precursor, complete cds, without stop codon, in Flexi system.
JD476218 - Sequence 457242 from Patent EP1572962.
JD476220 - Sequence 457244 from Patent EP1572962.
JD140864 - Sequence 121888 from Patent EP1572962.
U84406 - Human agrin mRNA, partial cds.
AF016903 - Homo sapiens agrin precursor mRNA, partial cds.
JD246360 - Sequence 227384 from Patent EP1572962.
JD214086 - Sequence 195110 from Patent EP1572962.
JD426074 - Sequence 407098 from Patent EP1572962.
JD169861 - Sequence 150885 from Patent EP1572962.
JD061907 - Sequence 42931 from Patent EP1572962.
AK021586 - Homo sapiens cDNA FLJ11524 fis, clone HEMBA1002547, highly similar to Agrin precursor.
BC084578 - Homo sapiens agrin, mRNA (cDNA clone IMAGE:5727776), partial cds.
DQ595896 - Homo sapiens piRNA piR-62008, complete sequence.
S44195 - AGRN=agrin {alternatively spliced} [human, mRNA, 188 nt].
BC007649 - Homo sapiens agrin, mRNA (cDNA clone IMAGE:3544662), partial cds.
BC063620 - Homo sapiens agrin, mRNA (cDNA clone IMAGE:4179742), partial cds.
BC034009 - Homo sapiens agrin, mRNA (cDNA clone IMAGE:3850833), partial cds.
AK128761 - Homo sapiens cDNA FLJ45064 fis, clone BRAWH3024242.
AK125197 - Homo sapiens cDNA FLJ43207 fis, clone FEBRA2010719.
BC004220 - Homo sapiens agrin, mRNA (cDNA clone IMAGE:3506210), partial cds.
JD295231 - Sequence 276255 from Patent EP1572962.
JD159296 - Sequence 140320 from Patent EP1572962.
JD329520 - Sequence 310544 from Patent EP1572962.
JD147471 - Sequence 128495 from Patent EP1572962.
JD382436 - Sequence 363460 from Patent EP1572962.
JD564658 - Sequence 545682 from Patent EP1572962.
JD564659 - Sequence 545683 from Patent EP1572962.
JD233413 - Sequence 214437 from Patent EP1572962.
JD362977 - Sequence 344001 from Patent EP1572962.
JD250773 - Sequence 231797 from Patent EP1572962.
JD514618 - Sequence 495642 from Patent EP1572962.
JD514619 - Sequence 495643 from Patent EP1572962.
JD400434 - Sequence 381458 from Patent EP1572962.
JD419286 - Sequence 400310 from Patent EP1572962.
JD485018 - Sequence 466042 from Patent EP1572962.
JD217906 - Sequence 198930 from Patent EP1572962.
JD065187 - Sequence 46211 from Patent EP1572962.
JD439231 - Sequence 420255 from Patent EP1572962.
JD108965 - Sequence 89989 from Patent EP1572962.
JD264189 - Sequence 245213 from Patent EP1572962.
JD045633 - Sequence 26657 from Patent EP1572962.
JD484491 - Sequence 465515 from Patent EP1572962.
JD449854 - Sequence 430878 from Patent EP1572962.
JD334576 - Sequence 315600 from Patent EP1572962.
JD085924 - Sequence 66948 from Patent EP1572962.
JD122539 - Sequence 103563 from Patent EP1572962.
JD383450 - Sequence 364474 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_agrPathway - Agrin in Postsynaptic Differentiation

Reactome (by CSHL, EBI, and GO)

Protein O00468 (Reactome details) participates in the following event(s):

R-HSA-375155 Interaction of NCAM1 with agrin
R-HSA-2396124 AGRN binds Laminins with gamma-1 subunit
R-NUL-2467431 Agrin binds Integrin alphaVbeta1 (alpha1beta1)
R-HSA-2467436 AGRN binds Integrins alphaVbeta1 (Other beta1-containing integrins)
R-HSA-2467633 AGRN binds LRP4:MUSK
R-HSA-2467659 AGRN binds NCAM1, PTPRS
R-HSA-2467665 AGRN binds Beta amyloid fibril via GAG chains
R-HSA-2467716 AGRN binds Alpha-dystroglycan
R-HSA-2396113 Dystroglycan binds AGRN and HSPG2
R-HSA-1878002 XYLTs transfer Xyl to core protein
R-HSA-1889955 B3GATs transfer GlcA to tetrasaccharide linker
R-HSA-1889978 B3GALT6 transfers Gal to the tetrasaccharide linker
R-HSA-1889981 B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker
R-HSA-2022919 EXT1:EXT2 transfers GlcNAc to the terminal GlcA residue
R-HSA-2022860 NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)
R-HSA-2022887 NDST1-4 N-deacetylates GlcNAc residues in heparan
R-HSA-2076392 EXT1:EXT2 transfers GlcA to heparan
R-HSA-2022851 EXT1:EXT2 transfer GlcNAc to the heparan chain
R-HSA-2022856 EXT1:EXT2 transfers GlcNAc to heparan
R-HSA-2076371 GLCE epimerises more GlcA to IdoA as sulfate content rises
R-HSA-2076383 HS3ST1 sulfates GlcN at C3 in heparan sulfate
R-HSA-2076611 HS3STs sulfate GlcN at C3 in heparan sulfate
R-HSA-2024100 GLCE epimerises GlcA to IdoA
R-HSA-2076508 HS2ST1 sulfates IdoA at C2 in heparan sulfate
R-HSA-2076419 HS6STs sulfate GlcN at C6 in heparan sulfate/heparin
R-HSA-1678694 Heparanase 2 (HPSE2) cleaves heparan sulfate from its proteoglycan (plasma membrane)
R-HSA-1667005 Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)
R-HSA-2423785 CR:atREs binds apoE and HSPG
R-HSA-2429643 NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
R-HSA-2404131 LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
R-HSA-419037 NCAM1 interactions
R-HSA-3000178 ECM proteoglycans
R-HSA-216083 Integrin cell surface interactions
R-HSA-3000171 Non-integrin membrane-ECM interactions
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-1474244 Extracellular matrix organization
R-HSA-1971475 A tetrasaccharide linker sequence is required for GAG synthesis
R-HSA-3560801 Defective B3GAT3 causes JDSSDHD
R-HSA-4420332 Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-2022928 HS-GAG biosynthesis
R-HSA-3656253 Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-3656237 Defective EXT2 causes exostoses 2
R-HSA-3560783 Defective B4GALT7 causes EDS, progeroid type
R-HSA-2024096 HS-GAG degradation
R-HSA-422475 Axon guidance
R-HSA-1638091 Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1793185 Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-3560782 Diseases associated with glycosaminoglycan metabolism
R-HSA-975634 Retinoid metabolism and transport
R-HSA-1266738 Developmental Biology
R-HSA-1630316 Glycosaminoglycan metabolism
R-HSA-3781865 Diseases of glycosylation
R-HSA-2187338 Visual phototransduction
R-HSA-6806667 Metabolism of fat-soluble vitamins
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1643685 Disease
R-HSA-418594 G alpha (i) signalling events
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-1430728 Metabolism
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: AGRIN, AGRIN_HUMAN, ENST00000379370.1, ENST00000379370.2, ENST00000379370.3, ENST00000379370.4, ENST00000379370.5, ENST00000379370.6, NM_198576, O00468, Q5SVA1, Q5SVA2, Q60FE1, Q7KYS8, Q8N4J5, Q96IC1, Q9BTD4, uc318oxu.1, uc318oxu.2
UCSC ID: ENST00000379370.7_4
RefSeq Accession: NM_198576.4
Protein: O00468 (aka AGRIN_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene AGRN:
cms (Congenital Myasthenic Syndromes Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.