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";
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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 Genevisible; O00468; HS.
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.
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
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