ID AGRIN_HUMAN Reviewed; 2068 AA. AC O00468; Q5SVA1; Q5SVA2; Q60FE1; Q7KYS8; Q8N4J5; Q96IC1; Q9BTD4; DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 12-SEP-2018, sequence version 6. DT 27-MAR-2024, entry version 212. DE RecName: Full=Agrin; DE Contains: DE RecName: Full=Agrin N-terminal 110 kDa subunit; DE Contains: DE RecName: Full=Agrin C-terminal 110 kDa subunit; DE Contains: DE RecName: Full=Agrin C-terminal 90 kDa fragment; DE Short=C90; DE Contains: DE RecName: Full=Agrin C-terminal 22 kDa fragment; DE Short=C22; DE Flags: Precursor; GN Name=AGRN; Synonyms=AGRIN; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6). RC TISSUE=Retinal pigment epithelium; RA Kato S.; RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-2068 (ISOFORM 6), AND TISSUE SPECIFICITY. RX PubMed=9652404; DOI=10.1046/j.1432-1327.1998.2540123.x; RA Groffen A.J.A., Buskens C.A.F., Van Kuppevelt T.H., Veerkamp J.H., RA Monnens L.A.H., Van den Heuvel L.P.W.J.; RT "Primary structure and high expression of human agrin in basement membranes RT of adult lung and kidney."; RL Eur. J. Biochem. 254:123-128(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-172 (ISOFORMS 1/3/4/5/6/7), AND RP INTERACTION WITH LAMININ. RX PubMed=9151673; DOI=10.1083/jcb.137.3.671; RA Denzer A.J., Brandenberger R., Gesemann M., Chiquet M., Ruegg M.A.; RT "Agrin binds to the nerve-muscle basal lamina via laminin."; RL J. Cell Biol. 137:671-683(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1558-2068 (ISOFORM 6), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1869-2068 (ISOFORM 3). RC TISSUE=Brain, Colon, and Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION OF TRANSMEMBRANE ISOFORM (ISOFORM 2). RX PubMed=11161480; DOI=10.1006/mcne.2000.0932; RA Neumann F.R., Bittcher G., Annies M., Schumacher B., Kroger S., Ruegg M.A.; RT "An alternative amino-terminus expressed in the central nervous system RT converts agrin to a type II transmembrane protein."; RL Mol. Cell. Neurosci. 17:208-225(2001). RN [7] RP IDENTIFICATION OF TRANSMEMBRANE ISOFORM (ISOFORM 2), ALTERNATIVE SPLICING, RP AND TISSUE SPECIFICITY. RX PubMed=16487930; DOI=10.1016/j.bbrc.2006.01.161; RA Kumar P., Ferns M.J., Meizel S.; RT "Identification of agrinSN isoform and muscle-specific receptor tyrosine RT kinase (MuSK) in sperm."; RL Biochem. Biophys. Res. Commun. 342:522-528(2006). RN [8] RP ERRATUM OF PUBMED:16487930. RA Kumar P., Ferns M.J., Meizel S.; RL Biochem. Biophys. Res. Commun. 344:453-453(2006). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RX PubMed=20551380; DOI=10.1074/mcp.m110.001693; RA Didangelos A., Yin X., Mandal K., Baumert M., Jahangiri M., Mayr M.; RT "Proteomics characterization of extracellular space components in the human RT aorta."; RL Mol. Cell. Proteomics 9:2048-2062(2010). RN [11] RP INTERACTION WITH LRP4, AND FUNCTION. RX PubMed=21969364; DOI=10.1074/jbc.m111.279307; RA Zhang W., Coldefy A.S., Hubbard S.R., Burden S.J.; RT "Agrin binds to the N-terminal region of Lrp4 protein and stimulates RT association between Lrp4 and the first immunoglobulin-like domain in RT muscle-specific kinase (MuSK)."; RL J. Biol. Chem. 286:40624-40630(2011). RN [12] RP POTENTIAL USAGE AS A BIOMARKER FOR SARCOPENIA. RX PubMed=22683512; DOI=10.1016/j.exger.2012.05.021; RA Drey M., Sieber C.C., Bauer J.M., Uter W., Dahinden P., Fariello R.G., RA Vrijbloed J.W.; RT "C-terminal Agrin Fragment as a potential marker for sarcopenia caused by RT degeneration of the neuromuscular junction."; RL Exp. Gerontol. 48:76-80(2013). RN [13] RP INVOLVEMENT IN CMS8, VARIANT CMS8 ARG-1709, VARIANTS LEU-23; ASN-58; RP ILE-105; MET-267; SER-375; VAL-728; ARG-852; MET-984; PHE-1088; LYS-1118; RP ARG-1135; LEU-1240; ARG-1341; LEU-1451; THR-1514; HIS-1565; ILE-1666; RP GLN-1671; PRO-1698; HIS-1734; ASN-1789 AND VAL-2046, FUNCTION, AND RP CHARACTERIZATION OF VARIANT CMS8 ARG-1709. RX PubMed=19631309; DOI=10.1016/j.ajhg.2009.06.015; RA Huze C., Bauche S., Richard P., Chevessier F., Goillot E., Gaudon K., RA Ben Ammar A., Chaboud A., Grosjean I., Lecuyer H.A., Bernard V., Rouche A., RA Alexandri N., Kuntzer T., Fardeau M., Fournier E., Brancaccio A., RA Ruegg M.A., Koenig J., Eymard B., Schaeffer L., Hantai D.; RT "Identification of an agrin mutation that causes congenital myasthenia and RT affects synapse function."; RL Am. J. Hum. Genet. 85:155-167(2009). RN [14] RP ERRATUM OF PUBMED:19631309. RA Huze C., Bauche S., Richard P., Chevessier F., Goillot E., Gaudon K., RA Ben Ammar A., Chaboud A., Grosjean I., Lecuyer H.A., Bernard V., Rouche A., RA Alexandri N., Kuntzer T., Fardeau M., Fournier E., Brancaccio A., RA Ruegg M.A., Koenig J., Eymard B., Schaeffer L., Hantai D.; RL Am. J. Hum. Genet. 85:536-536(2009). RN [15] RP VARIANT CMS8 PHE-1727, INTERACTION WITH DAG1, AND CHARACTERIZATION OF RP VARIANT CMS8 PHE-1727. RX PubMed=22205389; DOI=10.1007/s00439-011-1132-4; RA Maselli R.A., Fernandez J.M., Arredondo J., Navarro C., Ngo M., Beeson D., RA Cagney O., Williams D.C., Wollmann R.L., Yarov-Yarovoy V., Ferns M.J.; RT "LG2 agrin mutation causing severe congenital myasthenic syndrome mimics RT functional characteristics of non-neural (z-) agrin."; RL Hum. Genet. 131:1123-1135(2012). RN [16] RP VARIANT VAL-745, VARIANTS CMS8 SER-76; ILE-105 AND ARG-1875, AND RP CHARACTERIZATION OF VARIANTS CMS8 SER-76 AND ILE-105. RX PubMed=24951643; DOI=10.1093/brain/awu160; RA Nicole S., Chaouch A., Torbergsen T., Bauche S., de Bruyckere E., RA Fontenille M.J., Horn M.A., van Ghelue M., Loeseth S., Issop Y., Cox D., RA Mueller J.S., Evangelista T., Staalberg E., Ioos C., Barois A., RA Brochier G., Sternberg D., Fournier E., Hantai D., Abicht A., Dusl M., RA Laval S.H., Griffin H., Eymard B., Lochmueller H.; RT "Agrin mutations lead to a congenital myasthenic syndrome with distal RT muscle weakness and atrophy."; RL Brain 137:2429-2443(2014). CC -!- FUNCTION: [Isoform 1]: Heparan sulfate basal lamina glycoprotein that CC plays a central role in the formation and the maintenance of the CC neuromuscular junction (NMJ) and directs key events in postsynaptic CC differentiation. Component of the AGRN-LRP4 receptor complex that CC induces the phosphorylation and activation of MUSK. The activation of CC MUSK in myotubes induces the formation of NMJ by regulating different CC processes including the transcription of specific genes and the CC clustering of AChR in the postsynaptic membrane. Calcium ions are CC required for maximal AChR clustering. AGRN function in neurons is CC highly regulated by alternative splicing, glycan binding and CC proteolytic processing. Modulates calcium ion homeostasis in neurons, CC specifically by inducing an increase in cytoplasmic calcium ions. CC Functions differentially in the central nervous system (CNS) by CC inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking CC depolarization at CNS synapses. This secreted isoform forms a bridge, CC after release from motor neurons, to basal lamina through binding CC laminin via the NtA domain. CC -!- FUNCTION: [Isoform 2]: Transmembrane form that is the predominate form CC in neurons of the brain, induces dendritic filopodia and synapse CC formation in mature hippocampal neurons in large part due to the CC attached glycosaminoglycan chains and the action of Rho-family GTPases. CC -!- FUNCTION: Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) CC isoforms that contain C-terminal insertions of 8-19 AA are potent CC activators of AChR clustering. Isoform 5, agrin (z+8), containing the CC 8-AA insert, forms a receptor complex in myotubules containing the CC neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of CC the LDL receptor family. The splicing factors, NOVA1 and NOVA2, CC regulate AGRN splicing and production of the 'z' isoforms. CC -!- FUNCTION: Isoform 3 and isoform 6: lack any 'z' insert, are muscle- CC specific and may be involved in endothelial cell differentiation. CC -!- FUNCTION: [Agrin N-terminal 110 kDa subunit]: Is involved in regulation CC of neurite outgrowth probably due to the presence of the CC glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate CC attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in CC modulation of growth factor signaling (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:19631309, ECO:0000269|PubMed:21969364}. CC -!- FUNCTION: [Agrin C-terminal 22 kDa fragment]: This released fragment is CC important for agrin signaling and to exert a maximal dendritic CC filopodia-inducing effect. All 'z' splice variants (z+) of this CC fragment also show an increase in the number of filopodia. CC -!- SUBUNIT: Monomer (By similarity). Interacts (N-terminal subunit) with CC TGF-beta family members, BMP2 and BMP4; the interactions inhibit the CC activity of these growth factors. Interacts with TGFB1; the interaction CC enhances the activity of TGFB1 (By similarity). Component of the AGRN- CC LRP4 complex that consists of a tetramer of two AGRN-LRP4 heterodimers. CC Interacts (via the laminin G-like 3 domain) directly with LRP4; the CC interaction is required for activation of MUSK and clustering of AChR CC and requires the 'z8' insert present in the z(+8) isoforms. Interacts CC with DAG1; the interaction is influenced by cell surface CC glycosaminoglycans and by alternative splicing of AGRN. {ECO:0000250, CC ECO:0000269|PubMed:21969364, ECO:0000269|PubMed:22205389, CC ECO:0000269|PubMed:9151673}. CC -!- INTERACTION: CC O00468; O15265: ATXN7; NbExp=2; IntAct=EBI-947482, EBI-708350; CC O00468-6; Q8N9W6-4: BOLL; NbExp=3; IntAct=EBI-17740588, EBI-11983447; CC O00468-6; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-17740588, EBI-716006; CC O00468-6; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-17740588, EBI-11139477; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:20551380}. Note=Synaptic basal CC lamina at the neuromuscular junction. {ECO:0000250|UniProtKB:P31696}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Synapse CC {ECO:0000250|UniProtKB:A2ASQ1}. Cell membrane CC {ECO:0000250|UniProtKB:A2ASQ1}; Single-pass type II membrane protein CC {ECO:0000250|UniProtKB:A2ASQ1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=Many isoforms may exist depending on the occurrence and CC length of inserts at the x, y or z splice site. Four 'z' isoforms can CC be produced with inserts of 0, 8, 11 or 19 AA. Isoforms differ in CC their acetylcholine receptor clustering activity and tissue CC specificity.; CC Name=1; Synonyms=Secreted agrin, LN-agrin; CC IsoId=O00468-1; Sequence=Displayed; CC Name=2; Synonyms=Transmembrane agrin, TM-agrin; CC IsoId=O00468-2; Sequence=VSP_045753, VSP_045754; CC Name=3; Synonyms=Agrin z(0); CC IsoId=O00468-3; Sequence=VSP_045756; CC Name=4; Synonyms=Agrin z(+11); CC IsoId=O00468-4; Sequence=VSP_045757; CC Name=5; Synonyms=Agrin z(+8); CC IsoId=O00468-5; Sequence=VSP_045758; CC Name=6; Synonyms=Agrin y(0)z(0); CC IsoId=O00468-6; Sequence=VSP_045755, VSP_045756; CC Name=7; Synonyms=y(0); CC IsoId=O00468-7; Sequence=VSP_045755; CC -!- TISSUE SPECIFICITY: Expressed in basement membranes of lung and kidney. CC Muscle- and neuron-specific isoforms are found. Isoforms (y+) with the CC 4 AA insert and (z+8) isoforms with the 8 AA insert are all neuron- CC specific. Isoforms (z+11) are found in both neuronal and non-neuronal CC tissues. {ECO:0000269|PubMed:16487930, ECO:0000269|PubMed:20551380, CC ECO:0000269|PubMed:9652404}. CC -!- DOMAIN: The NtA domain, absent in TM-agrin, is required for binding CC laminin and connecting to basal lamina. CC -!- DOMAIN: Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains CC are required for alpha-dystroglycan/DAG1 binding. G3 domain is required CC for C-terminal heparin, heparan sulfate and sialic acid binding (By CC similarity). {ECO:0000250}. CC -!- PTM: Contains heparan and chondroitin sulfate chains and alpha- CC dystroglycan as well as N-linked and O-linked oligosaccharides. CC Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, CC are required for induction of filopodia in hippocampal neurons. The CC first cluster (Gly/Ser-rich) for GAG attachment contains heparan CC sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains CC chondroitin sulfate (CS) chains. Heparin and heparin sulfate binding in CC the G3 domain is independent of calcium ions. Binds heparin with a CC stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and CC binding requires calcium ions (By similarity). {ECO:0000250}. CC -!- PTM: At synaptic junctions, cleaved at two conserved sites, alpha and CC beta, by neurotrypsin. Cleavage at the alpha-site produces the agrin N- CC terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. CC Further cleavage of agrin C-terminal 110-kDa subunit at the beta site CC produces the C-terminal fragments, agrin C-terminal 90 kDa fragment and CC agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site CC releases large amounts of the agrin C-terminal 22 kDa fragment leading CC to destabilization at the neuromuscular junction (NMJ). CC -!- DISEASE: Myasthenic syndrome, congenital, 8 (CMS8) [MIM:615120]: A form CC of congenital myasthenic syndrome, a group of disorders characterized CC by failure of neuromuscular transmission, including pre-synaptic, CC synaptic, and post-synaptic disorders that are not of autoimmune CC origin. Clinical features are easy fatigability and muscle weakness. CC CMS8 is an autosomal recessive disease characterized by prominent CC defects of both the pre- and postsynaptic regions. Affected individuals CC have onset of muscle weakness in early childhood; the severity of the CC weakness and muscles affected is variable. CC {ECO:0000269|PubMed:19631309, ECO:0000269|PubMed:22205389, CC ECO:0000269|PubMed:24951643}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Cleaved C-terminal fragments may be used as a biomarker CC for sarcopenia, age-related progressive loss of skeletal muscle. CC {ECO:0000305|PubMed:22683512}. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by usage of an alternative first CC exon. {ECO:0000305}. CC -!- CAUTION: The unknown residue 'x' in the transmembrane isoform is CC probably a proline residue by similarity to mouse and rat sequences. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=The Leiden Muscular Dystrophy pages, Agrin (AGRN); CC Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/AGRN"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB191264; BAD52440.1; -; mRNA. DR EMBL; AL645608; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF016903; AAC39776.1; -; mRNA. DR EMBL; U84406; AAB52917.1; -; mRNA. DR EMBL; BC004220; AAH04220.2; -; mRNA. DR EMBL; BC007649; AAH07649.1; -; mRNA. DR EMBL; BC034009; AAH34009.1; -; mRNA. DR EMBL; BC063620; AAH63620.1; -; mRNA. DR CCDS; CCDS30551.1; -. [O00468-6] DR RefSeq; NP_001292204.1; NM_001305275.1. [O00468-1] DR RefSeq; NP_940978.2; NM_198576.3. [O00468-6] DR RefSeq; XP_005244806.1; XM_005244749.3. [O00468-3] DR PDB; 8S9P; EM; 3.80 A; A=1-2068. DR PDBsum; 8S9P; -. DR AlphaFoldDB; O00468; -. DR EMDB; EMD-40241; -. DR SMR; O00468; -. DR BioGRID; 132000; 288. DR IntAct; O00468; 27. DR MINT; O00468; -. DR STRING; 9606.ENSP00000368678; -. DR ChEMBL; CHEMBL4295648; -. DR TCDB; 8.A.74.1.3; the tm9 or phg1 targeting receptor (phg1) family. DR UniLectin; O00468; -. DR CarbonylDB; O00468; -. DR GlyConnect; 998; 17 N-Linked glycans (4 sites). DR GlyCosmos; O00468; 18 sites, 29 glycans. DR GlyGen; O00468; 50 sites, 17 N-linked glycans (4 sites), 13 O-linked glycans (45 sites). DR iPTMnet; O00468; -. DR PhosphoSitePlus; O00468; -. DR BioMuta; AGRN; -. DR EPD; O00468; -. DR jPOST; O00468; -. DR MassIVE; O00468; -. DR MaxQB; O00468; -. DR PaxDb; 9606-ENSP00000368678; -. DR PeptideAtlas; O00468; -. DR ProteomicsDB; 47914; -. [O00468-1] DR Pumba; O00468; -. DR Antibodypedia; 12009; 238 antibodies from 27 providers. DR DNASU; 375790; -. DR Ensembl; ENST00000379370.7; ENSP00000368678.2; ENSG00000188157.15. [O00468-6] DR GeneID; 375790; -. DR KEGG; hsa:375790; -. DR MANE-Select; ENST00000379370.7; ENSP00000368678.2; NM_198576.4; NP_940978.2. [O00468-6] DR UCSC; uc001ack.3; human. [O00468-1] DR AGR; HGNC:329; -. DR CTD; 375790; -. DR DisGeNET; 375790; -. DR GeneCards; AGRN; -. DR GeneReviews; AGRN; -. DR HGNC; HGNC:329; AGRN. DR HPA; ENSG00000188157; Low tissue specificity. DR MalaCards; AGRN; -. DR MIM; 103320; gene. DR MIM; 615120; phenotype. DR neXtProt; NX_O00468; -. DR OpenTargets; ENSG00000188157; -. DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes. DR Orphanet; 98914; Presynaptic congenital myasthenic syndromes. DR PharmGKB; PA24626; -. DR VEuPathDB; HostDB:ENSG00000188157; -. DR eggNOG; KOG3509; Eukaryota. DR GeneTree; ENSGT00940000158337; -. DR HOGENOM; CLU_001582_1_0_1; -. DR InParanoid; O00468; -. DR OMA; AMEISPF; -. DR OrthoDB; 2878505at2759; -. DR TreeFam; TF326548; -. DR PathwayCommons; O00468; -. DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis. DR Reactome; R-HSA-2022928; HS-GAG biosynthesis. DR Reactome; R-HSA-2024096; HS-GAG degradation. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type. DR Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD. DR Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2. DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS. DR Reactome; R-HSA-419037; NCAM1 interactions. DR Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1. DR Reactome; R-HSA-9694614; Attachment and Entry. DR Reactome; R-HSA-975634; Retinoid metabolism and transport. DR SignaLink; O00468; -. DR SIGNOR; O00468; -. DR BioGRID-ORCS; 375790; 11 hits in 1157 CRISPR screens. DR ChiTaRS; AGRN; human. DR GeneWiki; Agrin; -. DR GenomeRNAi; 375790; -. DR Pharos; O00468; Tbio. DR PRO; PR:O00468; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O00468; Protein. DR Bgee; ENSG00000188157; Expressed in right uterine tube and 188 other cell types or tissues. DR ExpressionAtlas; O00468; baseline and differential. DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB. DR GO; GO:0002162; F:dystroglycan binding; ISS:UniProtKB. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB. DR GO; GO:0043236; F:laminin binding; TAS:UniProtKB. DR GO; GO:0033691; F:sialic acid binding; ISS:UniProtKB. DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB. DR GO; GO:0045162; P:clustering of voltage-gated sodium channels; TAS:UniProtKB. DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0007528; P:neuromuscular junction development; IBA:GO_Central. DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB. DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0043113; P:receptor clustering; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB. DR GO; GO:0050808; P:synapse organization; TAS:UniProtKB. DR CDD; cd00054; EGF_CA; 3. DR CDD; cd00055; EGF_Lam; 2. DR CDD; cd00104; KAZAL_FS; 9. DR CDD; cd00110; LamG; 3. DR Gene3D; 2.40.50.120; -; 1. DR Gene3D; 2.60.120.200; -; 3. DR Gene3D; 3.30.60.30; -; 9. DR Gene3D; 2.10.25.10; Laminin; 5. DR Gene3D; 3.30.70.960; SEA domain; 1. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR003884; FacI_MAC. DR InterPro; IPR003645; Fol_N. DR InterPro; IPR002350; Kazal_dom. DR InterPro; IPR036058; Kazal_dom_sf. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR002049; LE_dom. DR InterPro; IPR004850; NtA_dom. DR InterPro; IPR000082; SEA_dom. DR InterPro; IPR036364; SEA_dom_sf. DR InterPro; IPR008993; TIMP-like_OB-fold. DR PANTHER; PTHR15036:SF83; AGRIN; 1. DR PANTHER; PTHR15036; PIKACHURIN-LIKE PROTEIN; 1. DR Pfam; PF00008; EGF; 2. DR Pfam; PF00050; Kazal_1; 1. DR Pfam; PF07648; Kazal_2; 8. DR Pfam; PF00053; Laminin_EGF; 2. DR Pfam; PF00054; Laminin_G_1; 3. DR Pfam; PF03146; NtA; 1. DR Pfam; PF01390; SEA; 1. DR PRINTS; PR00011; EGFLAMININ. DR SMART; SM00181; EGF; 7. DR SMART; SM00179; EGF_CA; 3. DR SMART; SM00180; EGF_Lam; 2. DR SMART; SM00057; FIMAC; 4. DR SMART; SM00274; FOLN; 5. DR SMART; SM00280; KAZAL; 9. DR SMART; SM00282; LamG; 3. DR SMART; SM00200; SEA; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 3. DR SUPFAM; SSF57196; EGF/Laminin; 3. DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 9. DR SUPFAM; SSF82671; SEA domain; 1. DR SUPFAM; SSF50242; TIMP-like; 1. DR PROSITE; PS00022; EGF_1; 6. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 4. DR PROSITE; PS01248; EGF_LAM_1; 1. DR PROSITE; PS50027; EGF_LAM_2; 2. DR PROSITE; PS51465; KAZAL_2; 9. DR PROSITE; PS50025; LAM_G_DOMAIN; 3. DR PROSITE; PS51121; NTA; 1. DR PROSITE; PS50024; SEA; 1. DR Genevisible; O00468; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Congenital myasthenic syndrome; Developmental protein; Differentiation; KW Disease variant; Disulfide bond; EGF-like domain; Extracellular matrix; KW Glycoprotein; Heparan sulfate; Laminin EGF-like domain; Membrane; KW Metal-binding; Phosphoprotein; Proteoglycan; Reference proteome; Repeat; KW Secreted; Signal; Synapse; Transmembrane; Transmembrane helix. FT SIGNAL 1..29 FT /evidence="ECO:0000255" FT CHAIN 30..2068 FT /note="Agrin" FT /id="PRO_0000007471" FT CHAIN 30..1102 FT /note="Agrin N-terminal 110 kDa subunit" FT /evidence="ECO:0000250" FT /id="PRO_0000421613" FT CHAIN 1103..2068 FT /note="Agrin C-terminal 110 kDa subunit" FT /evidence="ECO:0000250" FT /id="PRO_0000421614" FT CHAIN 1103..1863 FT /note="Agrin C-terminal 90 kDa fragment" FT /evidence="ECO:0000250" FT /id="PRO_0000421615" FT CHAIN 1864..2068 FT /note="Agrin C-terminal 22 kDa fragment" FT /evidence="ECO:0000250" FT /id="PRO_0000421616" FT DOMAIN 31..157 FT /note="NtA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00443" FT DOMAIN 191..244 FT /note="Kazal-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 264..319 FT /note="Kazal-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 337..391 FT /note="Kazal-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 408..463 FT /note="Kazal-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 484..536 FT /note="Kazal-like 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 540..601 FT /note="Kazal-like 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 607..666 FT /note="Kazal-like 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 699..752 FT /note="Kazal-like 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 793..846 FT /note="Laminin EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460" FT DOMAIN 847..893 FT /note="Laminin EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460" FT DOMAIN 917..971 FT /note="Kazal-like 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 1130..1252 FT /note="SEA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188" FT DOMAIN 1329..1367 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1372..1548 FT /note="Laminin G-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1549..1586 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1588..1625 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1635..1822 FT /note="Laminin G-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1818..1857 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1868..2065 FT /note="Laminin G-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT REGION 995..1096 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1277..1334 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1008..1034 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1277..1313 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1316..1333 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1940 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 1957 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 2007 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 2009 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT SITE 1102..1103 FT /note="Cleavage, alpha site; by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1250 FT /note="Alternative splice site to produce 'x' isoforms" FT /evidence="ECO:0000250" FT SITE 1751 FT /note="Alternative splice site to produce 'y' isoforms" FT /evidence="ECO:0000250" FT SITE 1862 FT /note="Critical for cleavage by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1863..1864 FT /note="Cleavage, beta site; by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1888 FT /note="Alternative splice site to produce 'z' isoforms" FT /evidence="ECO:0000250" FT SITE 1892 FT /note="Highly important for the agrin receptor complex FT activity of the 'z(8)' insert" FT /evidence="ECO:0000250" FT MOD_RES 674 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2ASQ1" FT MOD_RES 676 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2ASQ1" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 250 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 777 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 932 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1835 FT /note="O-linked (Fuc...) serine" FT /evidence="ECO:0000250|UniProtKB:P25304" FT DISULFID 31..103 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00443" FT DISULFID 152..177 FT /note="Or C-152 with C-183" FT DISULFID 197..228 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 202..221 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 210..242 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 270..303 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 276..296 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 285..317 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 349..368 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 357..389 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 414..447 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 421..440 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 429..461 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 490..520 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 494..513 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 502..534 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 546..585 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 555..578 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 567..599 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 613..650 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 623..643 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 632..664 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 705..736 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 709..729 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 718..750 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 793..805 FT /evidence="ECO:0000250" FT DISULFID 795..812 FT /evidence="ECO:0000250" FT DISULFID 814..823 FT /evidence="ECO:0000250" FT DISULFID 826..844 FT /evidence="ECO:0000250" FT DISULFID 847..859 FT /evidence="ECO:0000250" FT DISULFID 849..866 FT /evidence="ECO:0000250" FT DISULFID 868..877 FT /evidence="ECO:0000250" FT DISULFID 880..891 FT /evidence="ECO:0000250" FT DISULFID 923..955 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 928..948 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 937..969 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 1333..1344 FT /evidence="ECO:0000250" FT DISULFID 1338..1355 FT /evidence="ECO:0000250" FT DISULFID 1357..1366 FT /evidence="ECO:0000250" FT DISULFID 1519..1548 FT /evidence="ECO:0000250" FT DISULFID 1553..1564 FT /evidence="ECO:0000250" FT DISULFID 1558..1574 FT /evidence="ECO:0000250" FT DISULFID 1576..1585 FT /evidence="ECO:0000250" FT DISULFID 1592..1603 FT /evidence="ECO:0000250" FT DISULFID 1597..1613 FT /evidence="ECO:0000250" FT DISULFID 1615..1624 FT /evidence="ECO:0000250" FT DISULFID 1822..1836 FT /evidence="ECO:0000250" FT DISULFID 1830..1845 FT /evidence="ECO:0000250" FT DISULFID 1847..1856 FT /evidence="ECO:0000250" FT DISULFID 2039..2065 FT /evidence="ECO:0000250" FT VAR_SEQ 1..104 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_045753" FT VAR_SEQ 105..154 FT /note="NQVSTGDTRIFFVNPAPPYLWPAHKNELMLNSSLMRITLRNLEEVEFCVE FT -> MPXLAVARDTRQPAGASLLVRGFMVPCNACLILLATATLGFAVLLFLNNY (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_045754" FT VAR_SEQ 1752..1755 FT /note="Missing (in isoform 6 and isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_045755" FT VAR_SEQ 1889..1907 FT /note="Missing (in isoform 3 and isoform 6)" FT /evidence="ECO:0000303|PubMed:9652404, ECO:0000303|Ref.1" FT /id="VSP_045756" FT VAR_SEQ 1889..1896 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_045757" FT VAR_SEQ 1897..1907 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_045758" FT VARIANT 23 FT /note="V -> L" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068724" FT VARIANT 58 FT /note="D -> N" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068725" FT VARIANT 76 FT /note="G -> S (in CMS8; results in decreased AChR FT clustering)" FT /evidence="ECO:0000269|PubMed:24951643" FT /id="VAR_071367" FT VARIANT 105 FT /note="N -> I (in CMS8; results in decreased AChR FT clustering)" FT /evidence="ECO:0000269|PubMed:19631309, FT ECO:0000269|PubMed:24951643" FT /id="VAR_068726" FT VARIANT 267 FT /note="T -> M" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068727" FT VARIANT 375 FT /note="A -> S (in dbSNP:rs138031468)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068728" FT VARIANT 728 FT /note="E -> V (in dbSNP:rs113288277)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068729" FT VARIANT 745 FT /note="A -> V" FT /evidence="ECO:0000269|PubMed:24951643" FT /id="VAR_071368" FT VARIANT 852 FT /note="Q -> R (in dbSNP:rs9697293)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068730" FT VARIANT 984 FT /note="V -> M" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068731" FT VARIANT 1088 FT /note="L -> F (in dbSNP:rs150132566)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068732" FT VARIANT 1118 FT /note="T -> K (in dbSNP:rs149159118)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068733" FT VARIANT 1135 FT /note="Q -> R (in dbSNP:rs142416636)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068734" FT VARIANT 1240 FT /note="P -> L (in dbSNP:rs142620337)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068735" FT VARIANT 1341 FT /note="G -> R" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068736" FT VARIANT 1451 FT /note="P -> L" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068737" FT VARIANT 1514 FT /note="A -> T (in dbSNP:rs111818381)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068738" FT VARIANT 1565 FT /note="Q -> H (in dbSNP:rs199876002)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068739" FT VARIANT 1666 FT /note="V -> I (in dbSNP:rs17160775)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_048966" FT VARIANT 1671 FT /note="R -> Q" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068740" FT VARIANT 1698 FT /note="R -> P" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068741" FT VARIANT 1709 FT /note="G -> R (in CMS8; results in disruption of the FT neuromuscular junction architecture; does not affect FT phosphorylation of MUSK; does not affect AChR clustering)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068742" FT VARIANT 1727 FT /note="V -> F (in CMS8; decreased AGRN-induced clustering FT of AChR by >100-fold and decreased phosphorylation of the FT MUSK receptor and AChR beta subunit by about 10-fold. FT Increased binding to alpha-dystroglycan)" FT /evidence="ECO:0000269|PubMed:22205389" FT /id="VAR_069066" FT VARIANT 1734 FT /note="R -> H (in dbSNP:rs145444272)" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068743" FT VARIANT 1789 FT /note="D -> N" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068744" FT VARIANT 1875 FT /note="G -> R (in CMS8)" FT /evidence="ECO:0000269|PubMed:24951643" FT /id="VAR_071369" FT VARIANT 2046 FT /note="G -> V" FT /evidence="ECO:0000269|PubMed:19631309" FT /id="VAR_068745" FT CONFLICT 343 FT /note="L -> R (in Ref. 3; AAC39776)" FT /evidence="ECO:0000305" SQ SEQUENCE 2068 AA; 217320 MW; 8B3E3D0FF65517F0 CRC64; MAGRSHPGPL RPLLPLLVVA ACVLPGAGGT CPERALERRE EEANVVLTGT VEEILNVDPV QHTYSCKVRV WRYLKGKDLV ARESLLDGGN KVVISGFGDP LICDNQVSTG DTRIFFVNPA PPYLWPAHKN ELMLNSSLMR ITLRNLEEVE FCVEDKPGTH FTPVPPTPPD ACRGMLCGFG AVCEPNAEGP GRASCVCKKS PCPSVVAPVC GSDASTYSNE CELQRAQCSQ QRRIRLLSRG PCGSRDPCSN VTCSFGSTCA RSADGLTASC LCPATCRGAP EGTVCGSDGA DYPGECQLLR RACARQENVF KKFDGPCDPC QGALPDPSRS CRVNPRTRRP EMLLRPESCP ARQAPVCGDD GVTYENDCVM GRSGAARGLL LQKVRSGQCQ GRDQCPEPCR FNAVCLSRRG RPRCSCDRVT CDGAYRPVCA QDGRTYDSDC WRQQAECRQQ RAIPSKHQGP CDQAPSPCLG VQCAFGATCA VKNGQAACEC LQACSSLYDP VCGSDGVTYG SACELEATAC TLGREIQVAR KGPCDRCGQC RFGALCEAET GRCVCPSECV ALAQPVCGSD GHTYPSECML HVHACTHQIS LHVASAGPCE TCGDAVCAFG AVCSAGQCVC PRCEHPPPGP VCGSDGVTYG SACELREAAC LQQTQIEEAR AGPCEQAECG SGGSGSGEDG DCEQELCRQR GGIWDEDSED GPCVCDFSCQ SVPGSPVCGS DGVTYSTECE LKKARCESQR GLYVAAQGAC RGPTFAPLPP VAPLHCAQTP YGCCQDNITA ARGVGLAGCP SACQCNPHGS YGGTCDPATG QCSCRPGVGG LRCDRCEPGF WNFRGIVTDG RSGCTPCSCD PQGAVRDDCE QMTGLCSCKP GVAGPKCGQC PDGRALGPAG CEADASAPAT CAEMRCEFGA RCVEESGSAH CVCPMLTCPE ANATKVCGSD GVTYGNECQL KTIACRQGLQ ISIQSLGPCQ EAVAPSTHPT SASVTVTTPG LLLSQALPAP PGALPLAPSS TAHSQTTPPP SSRPRTTASV PRTTVWPVLT VPPTAPSPAP SLVASAFGES GSTDGSSDEE LSGDQEASGG GSGGLEPLEG SSVATPGPPV ERASCYNSAL GCCSDGKTPS LDAEGSNCPA TKVFQGVLEL EGVEGQELFY TPEMADPKSE LFGETARSIE STLDDLFRNS DVKKDFRSVR LRDLGPGKSV RAIVDVHFDP TTAFRAPDVA RALLRQIQVS RRRSLGVRRP LQEHVRFMDF DWFPAFITGA TSGAIAAGAT ARATTASRLP SSAVTPRAPH PSHTSQPVAK TTAAPTTRRP PTTAPSRVPG RRPPAPQQPP KPCDSQPCFH GGTCQDWALG GGFTCSCPAG RGGAVCEKVL GAPVPAFEGR SFLAFPTLRA YHTLRLALEF RALEPQGLLL YNGNARGKDF LALALLDGRV QLRFDTGSGP AVLTSAVPVE PGQWHRLELS RHWRRGTLSV DGETPVLGES PSGTDGLNLD TDLFVGGVPE DQAAVALERT FVGAGLRGCI RLLDVNNQRL ELGIGPGAAT RGSGVGECGD HPCLPNPCHG GAPCQNLEAG RFHCQCPPGR VGPTCADEKS PCQPNPCHGA APCRVLPEGG AQCECPLGRE GTFCQTASGQ DGSGPFLADF NGFSHLELRG LHTFARDLGE KMALEVVFLA RGPSGLLLYN GQKTDGKGDF VSLALRDRRL EFRYDLGKGA AVIRSREPVT LGAWTRVSLE RNGRKGALRV GDGPRVLGES PKSRKVPHTV LNLKEPLYVG GAPDFSKLAR AAAVSSGFDG AIQLVSLGGR QLLTPEHVLR QVDVTSFAGH PCTRASGHPC LNGASCVPRE AAYVCLCPGG FSGPHCEKGL VEKSAGDVDT LAFDGRTFVE YLNAVTESEL ANEIPVPETL DSGALHSEKA LQSNHFELSL RTEATQGLVL WSGKATERAD YVALAIVDGH LQLSYNLGSQ PVVLRSTVPV NTNRWLRVVA HREQREGSLQ VGNEAPVTGS SPLGATQLDT DGALWLGGLP ELPVGPALPK AYGTGFVGCL RDVVVGRHPL HLLEDAVTKP ELRPCPTP //