ID AGRIN_MOUSE Reviewed; 1950 AA. AC A2ASQ1; A2ASP9; A2ASQ0; B2RWU1; DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 1. DT 02-SEP-2026, entry version 149. 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; GN Name=Agrn; Synonyms=Agrin; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; 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 [3] RP FUNCTION IN NEUROMUSCULAR JUNCTION DEVELOPMENT, SUBCELLULAR LOCATION, RP FUNCTION IN PHOSPHORYLATION OF MUSK, AND INTERACTION WITH LRP4. RX PubMed=8653787; DOI=10.1016/s0092-8674(00)81252-0; RA Glass D.J., Bowen D.C., Stitt T.N., Radziejewski C., Bruno J., Ryan T.E., RA Gies D.R., Shah S., Mattsson K., Burden S.J., DiStefano P.S., RA Valenzuela D.M., DeChiara T.M., Yancopoulos G.D.; RT "Agrin acts via a MuSK receptor complex."; RL Cell 85:513-523(1996). RN [4] RP REGULATION OF ALTERNATIVE SPLICING. RX PubMed=9188458; DOI=10.1074/jbc.272.25.15675; RA Smith M.A., Fanger G.R., O'Connor L.T., Bridle P., Maue R.A.; RT "Selective regulation of agrin mRNA induction and alternative splicing in RT PC12 cells by Ras-dependent actions of nerve growth factor."; RL J. Biol. Chem. 272:15675-15681(1997). RN [5] RP LAMININ BINDING. RX PubMed=10581249; DOI=10.1093/emboj/18.23.6762; RA Kammerer R.A., Schulthess T., Landwehr R., Schumacher B., Lustig A., RA Yurchenco P.D., Ruegg M.A., Engel J., Denzer A.J.; RT "Interaction of agrin with laminin requires a coiled-coil conformation of RT the agrin-binding site within the laminin gamma1 chain."; RL EMBO J. 18:6762-6770(1999). RN [6] RP ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE RP SPECIFICITY, AND FUNCTION. RX PubMed=10402191; DOI=10.1016/s0896-6273(00)80751-5; RA Burgess R.W., Nguyen Q.T., Son Y.J., Lichtman J.W., Sanes J.R.; RT "Alternatively spliced isoforms of nerve- and muscle-derived agrin: their RT roles at the neuromuscular junction."; RL Neuron 23:33-44(1999). RN [7] RP ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP FUNCTION. RX PubMed=11018052; DOI=10.1083/jcb.151.1.41; RA Burgess R.W., Skarnes W.C., Sanes J.R.; RT "Agrin isoforms with distinct amino termini: differential expression, RT localization, and function."; RL J. Cell Biol. 151:41-52(2000). RN [8] RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION. 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 [9] RP FUNCTION OF AGRIN C-TERMINAL 22 KDA FRAGMENT, AND SUBCELLULAR LOCATION. RX PubMed=12796478; DOI=10.1083/jcb.200301013; RA Hoover C.L., Hilgenberg L.G., Smith M.A.; RT "The COOH-terminal domain of agrin signals via a synaptic receptor in RT central nervous system neurons."; RL J. Cell Biol. 161:923-932(2003). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200; RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.; RT "Comprehensive identification of phosphorylation sites in postsynaptic RT density preparations."; RL Mol. Cell. Proteomics 5:914-922(2006). RN [11] RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND RP FUNCTION. RX PubMed=17611272; DOI=10.1523/jneurosci.1609-07.2007; RA Ksiazek I., Burkhardt C., Lin S., Seddik R., Maj M., Bezakova G., RA Jucker M., Arber S., Caroni P., Sanes J.R., Bettler B., Ruegg M.A.; RT "Synapse loss in cortex of agrin-deficient mice after genetic rescue of RT perinatal death."; RL J. Neurosci. 27:7183-7195(2007). RN [12] RP PROTEOLYTIC PROCESSING, IDENTIFICATION OF PROTEOLYTICALLY CLEAVED FRAGMENTS RP BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18230682; DOI=10.1096/fj.07-100008; RA Stephan A., Mateos J.M., Kozlov S.V., Cinelli P., Kistler A.D., Hettwer S., RA Rulicke T., Streit P., Kunz B., Sonderegger P.; RT "Neurotrypsin cleaves agrin locally at the synapse."; RL FASEB J. 22:1861-1873(2008). RN [13] RP PROTEOLYTIC PROCESSING, AND FUNCTION. RX PubMed=19303856; DOI=10.1016/j.cell.2009.02.034; RA Matsumoto-Miyai K., Sokolowska E., Zurlinden A., Gee C.E., Luscher D., RA Hettwer S., Wolfel J., Ladner A.P., Ster J., Gerber U., Rulicke T., RA Kunz B., Sonderegger P.; RT "Coincident pre- and postsynaptic activation induces dendritic filopodia RT via neurotrypsin-dependent agrin cleavage."; RL Cell 136:1161-1171(2009). RN [14] RP REGULATION OF ALTERNATIVE SPLICING AT THE Z SITE. RX PubMed=19221030; DOI=10.1073/pnas.0813112106; RA Ruggiu M., Herbst R., Kim N., Jevsek M., Fak J.J., Mann M.A., Fischbach G., RA Burden S.J., Darnell R.B.; RT "Rescuing Z+ agrin splicing in Nova null mice restores synapse formation RT and unmasks a physiologic defect in motor neuron firing."; RL Proc. Natl. Acad. Sci. U.S.A. 106:3513-3518(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569 AND SER-571, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and RC Pancreas; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP PROTEOLYTIC PROCESSING, FUNCTION, AND MOUSE MODEL OF PRECOCIOUS SARCOPENIA. RX PubMed=21885656; DOI=10.1096/fj.11-191262; RA Butikofer L., Zurlinden A., Bolliger M.F., Kunz B., Sonderegger P.; RT "Destabilization of the neuromuscular junction by proteolytic cleavage of RT agrin results in precocious sarcopenia."; RL FASEB J. 25:4378-4393(2011). RN [17] RP VARIANT A MUTANT STRAIN SER-1061, AND CHARACTERIZATION OF A MOUSE MODEL OF RP AGRIN-ASSOCIATED CONGENITAL MYASTHENIC SYNDROME. RX PubMed=21890498; DOI=10.1093/hmg/ddr396; RA Bogdanik L.P., Burgess R.W.; RT "A valid mouse model of AGRIN-associated congenital myasthenic syndrome."; RL Hum. Mol. Genet. 20:4617-4633(2011). RN [18] RP STRUCTURAL CHARACTERISTICS OF LAMININ G3 DOMAIN. RX PubMed=21037280; DOI=10.1093/protein/gzq082; RA Tidow H., Mattle D., Nissen P.; RT "Structural and biophysical characterisation of agrin laminin G3 domain RT constructs."; RL Protein Eng. Des. Sel. 24:219-224(2011). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1510-1701. RG New York structural genomix research consortium (NYSGXRC); RT "Crystal structure of the g2 domain of agrin from Mus musculus."; RL Submitted (JAN-2011) to the PDB data bank. CC -!- FUNCTION: Depending on alternative splicing and post-translational CC modifications, it has a role in different processes, including CC neuromuscular junction formation and maintenance, and regulation of CC neurite outgrowth (PubMed:10402191, PubMed:11018052, PubMed:12796478, CC PubMed:17611272, PubMed:19303856, PubMed:21885656, PubMed:8653787). CC Involved in the positive regulation of cartilage formation through CC alpha-dystroglycan binding and up-regulation of SOX9 (By similarity). CC {ECO:0000250|UniProtKB:O00468, ECO:0000269|PubMed:10402191, CC ECO:0000269|PubMed:11018052, ECO:0000269|PubMed:12796478, CC ECO:0000269|PubMed:17611272, ECO:0000269|PubMed:19303856, CC ECO:0000269|PubMed:21885656, ECO:0000269|PubMed:8653787}. 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 (PubMed:8653787, PubMed:10402191). This neuron-specific CC (z+) isoform is a 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 transmembrane agrin (TM-agrin) CC isoform, the predominate form in neurons of the brain, induces CC dendritic filopodia and synapse formation in mature hippocampal neurons CC in large part due to the attached glycosaminoglycan chains and the CC action of Rho-family GTPases (PubMed:17611272, PubMed:19303856). CC {ECO:0000269|PubMed:10402191, ECO:0000269|PubMed:17611272, CC ECO:0000269|PubMed:19303856, ECO:0000269|PubMed:8653787}. CC -!- FUNCTION: Isoform 2 and isoform 3: these isoforms lacking the 'z' CC insert (z0) are muscle-specific, have no AChR clustering ability and CC may be involved in nervous system endothelial cell differentiation. CC -!- FUNCTION: [Agrin N-terminal 110 kDa subunit]: Involved in regulation of CC neurite outgrowth probably due to the presence of the glycosaminoglcan CC (GAG) side chains of heparan and chondroitin sulfate attached to the CC Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of CC growth factor signaling (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:10402191, ECO:0000269|PubMed:11018052, CC ECO:0000269|PubMed:12796478, ECO:0000269|PubMed:17611272, CC ECO:0000269|PubMed:19303856, ECO:0000269|PubMed:21885656, CC ECO:0000269|PubMed:8653787}. 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 {ECO:0000269|PubMed:12796478}. 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. Interacts with DAG1; the interaction is CC influenced by cell surface glycosaminoglycans and by alternative CC splicing of AGRN, and is required for up-regulation of SOX9 and CC cartilage formation (By similarity). Component of the AGRN-LRP4 complex CC that consists of a tetramer of two AGRN-LRP4 heterodimers. Interacts CC (via the laminin G-like 3 domain) directly with LRP4; the interaction CC is required for activation of MUSK and clustering of AChR and requires CC the 'z8' insert present in the z(+8) isoforms. CC {ECO:0000250|UniProtKB:P25304, ECO:0000269|PubMed:8653787}. CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:10402191, CC ECO:0000269|PubMed:12796478, ECO:0000269|PubMed:17611272, CC ECO:0000269|PubMed:18230682, ECO:0000269|PubMed:8653787}. Cell membrane CC {ECO:0000269|PubMed:11018052, ECO:0000269|PubMed:11161480}; Single-pass CC type II membrane protein {ECO:0000269|PubMed:11018052, CC ECO:0000269|PubMed:11161480}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Many isoforms exist depending on the occurrence and length of CC inserts at the x, y or z splice site. There are 4 'z' isoforms CC produced with inserts of 0, 8, 11 or 19 AA. Isoforms differ in their CC acetylcholine receptor clustering activity and tissue specificity. In CC addition, a secreted isoform is produced by alternative usage of the CC first exon.; CC Name=1; Synonyms=Transmembrane agrin, TM-agrin; CC IsoId=A2ASQ1-1; Sequence=Displayed; CC Name=2; CC IsoId=A2ASQ1-2; Sequence=VSP_035996, VSP_035997; CC Name=3; CC IsoId=A2ASQ1-3; Sequence=VSP_035995, VSP_035996, VSP_035997; CC -!- TISSUE SPECIFICITY: Expressed in central nervous system (CNS) synapses CC such as in the cerebral cortex and hippocampus. Localizes to basal CC lamina of hippocampal blood vessels. Both (z+) and (z-) isoforms found CC in kidney, heart and cerebral vasculature. CC {ECO:0000269|PubMed:10402191, ECO:0000269|PubMed:11018052, CC ECO:0000269|PubMed:17611272, ECO:0000269|PubMed:18230682}. CC -!- DEVELOPMENTAL STAGE: All (z+), (z-), (y+) and (y-) isoforms present CC throughout muscle fiber basal laminae in neonatal animals. CC -!- DOMAIN: Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains CC are required for alpha-dystroglycan binding. G3 domain is required for CC 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. Heparin CC and heparin sulfate binding in the G3 domain is independent of calcium CC ions. Binds heparin with a stoichiometry of 2:1. Binds sialic acid with CC a stoichiometry of 1:1 and binding requires calcium ions (By CC similarity). Glycosaminoglycans (GAGs), present in the N-terminal 110 CC kDa fragment, are required for induction of filopodia in hippocampal CC neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains CC heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), CC contains chondroitin sulfate (CS) chains. {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). Cleavage is CC developmentally regulated. In developing brain, neurotrypsin-mediated CC cleavage occurs mainly during late fetal days and in the first CC postnatal week. {ECO:0000269|PubMed:18230682, CC ECO:0000269|PubMed:19303856, ECO:0000269|PubMed:21885656}. CC -!- DISRUPTION PHENOTYPE: Z(-)/z(-) mice lacking the 'z' insert are CC stillborn or die immediately after birth. They did not inflate their CC lungs and were never seen to move spontaneously. An intramuscular nerve CC is formed and axons leave the nerve and branch but do not stop and CC arborize. AChR clusters were fewer in number, about 30% smaller in size CC and lower in density. Transgenic null (Tg/Agrn -/-) mice, exhibit CC atrophied muscle due to denervation and are smaller than normal CC littermates. There is impairment of locomotory behavior and half the CC mice die after 50 days. There is a greatly reduced number of synapses CC and about 30% loss of postsynaptic spines and a decrease in the length CC of dendrites in cortical neurons. {ECO:0000269|PubMed:10402191, CC ECO:0000269|PubMed:17611272}. CC -!- MISCELLANEOUS: Mice that have excessive neurotrypsin-mediated agrin CC cleavage, exhibit pathological symptoms characteristic of precocious CC sarcopenia, with fragmentation and disassembly of the neuromuscular CC junction (NMJ). {ECO:0000305|PubMed:21885656}. CC -!- SEQUENCE CAUTION: CC Sequence=CAM14888.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; 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; AL928667; CAM14888.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL928667; CAM14889.1; -; Genomic_DNA. DR EMBL; AL928667; CAM14890.1; -; Genomic_DNA. DR EMBL; BC150703; AAI50704.1; -; mRNA. DR CCDS; CCDS89874.1; -. [A2ASQ1-1] DR RefSeq; NP_001355955.1; NM_001369026.2. [A2ASQ1-1] DR PDB; 3PVE; X-ray; 1.40 A; A/B=1510-1701. DR AlphaFoldDB; A2ASQ1; -. DR SMR; A2ASQ1; -. DR FunCoup; A2ASQ1; 181. DR IntAct; A2ASQ1; 2. DR STRING; 10090.ENSMUSP00000137931; -. DR GlyCosmos; A2ASQ1; 5 sites, No reported glycans. DR GlyGen; A2ASQ1; 8 sites, 1 O-linked glycan (1 site). DR iPTMnet; A2ASQ1; -. DR PhosphoSitePlus; A2ASQ1; -. DR SwissPalm; A2ASQ1; -. DR PaxDb; 10090-ENSMUSP00000137931; -. DR PeptideAtlas; A2ASQ1; -. DR ProteomicsDB; 296138; -. [A2ASQ1-1] DR ProteomicsDB; 296139; -. [A2ASQ1-2] DR ProteomicsDB; 296140; -. [A2ASQ1-3] DR Pumba; A2ASQ1; -. DR Antibodypedia; 12009; 212 antibodies from 28 providers. DR Ensembl; ENSMUST00000105575.9; ENSMUSP00000101200.3; ENSMUSG00000041936.19. [A2ASQ1-1] DR GeneID; 11603; -. DR KEGG; mmu:11603; -. DR UCSC; uc008wgg.1; mouse. [A2ASQ1-1] DR AGR; MGI:87961; -. DR CTD; 375790; -. DR MGI; MGI:87961; Agrn. DR VEuPathDB; HostDB:ENSMUSG00000041936; -. DR eggNOG; KOG3509; Eukaryota. DR GeneTree; ENSGT00940000158337; -. DR InParanoid; A2ASQ1; -. DR PhylomeDB; A2ASQ1; -. DR Reactome; R-MMU-1971475; Glycosaminoglycan-protein linkage region biosynthesis. DR Reactome; R-MMU-2022928; HS-GAG biosynthesis. DR Reactome; R-MMU-2024096; HS-GAG degradation. DR Reactome; R-MMU-3000178; ECM proteoglycans. DR Reactome; R-MMU-975634; Retinoid metabolism and transport. DR Reactome; R-MMU-9769735; Initiation of coagulation cascade. DR Reactome; R-MMU-9769739; Regulation of clotting cascade. DR Reactome; R-MMU-9913351; Formation of the dystrophin-glycoprotein complex (DGC). DR BioGRID-ORCS; 11603; 3 hits in 78 CRISPR screens. DR EvolutionaryTrace; A2ASQ1; -. DR PRO; PR:A2ASQ1; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; A2ASQ1; protein. DR Bgee; ENSMUSG00000041936; Expressed in metanephric proximal tubule and 264 other cell types or tissues. DR ExpressionAtlas; A2ASQ1; baseline and differential. DR GO; GO:0044295; C:axonal growth cone; ISO:GO_Central. DR GO; GO:0005604; C:basement membrane; IDA:MGI. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0140148; C:gel phase of basement membrane; TAS:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; ISO:GO_Central. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; EXP:UniProtKB. DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL. DR GO; GO:0045202; C:synapse; IDA:MGI. DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IDA:MGI. DR GO; GO:0042030; F:ATPase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0036122; F:BMP binding; ISO:GO_Central. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB. DR GO; GO:0002162; F:dystroglycan binding; ISS:UniProtKB. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI. DR GO; GO:0033691; F:sialic acid binding; ISS:UniProtKB. DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:GO_Central. DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IBA:GO_Central. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL. DR GO; GO:0141110; F:transporter inhibitor activity; IDA:BHF-UCL. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IDA:MGI. DR GO; GO:0002062; P:chondrocyte differentiation; ISO:GO_Central. DR GO; GO:0007623; P:circadian rhythm; IGI:MGI. DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; IDA:MGI. DR GO; GO:0046847; P:filopodium assembly; ISS:UniProtKB. DR GO; GO:1903277; P:negative regulation of sodium ion export across plasma membrane; IDA:BHF-UCL. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0007528; P:neuromuscular junction development; IGI:MGI. DR GO; GO:0007009; P:plasma membrane organization; IMP:MGI. DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISO:GO_Central. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:MGI. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:UniProtKB. DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IDA:MGI. DR GO; GO:1904395; P:positive regulation of skeletal muscle acetylcholine-gated channel clustering; IDA:UniProtKB. DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0015031; P:protein transport; IDA:MGI. DR GO; GO:0043113; P:receptor clustering; IDA:MGI. DR GO; GO:1902667; P:regulation of axon guidance; ISO:GO_Central. DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; IDA:BHF-UCL. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; IDA:BHF-UCL. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:GO_Central. DR GO; GO:0050807; P:regulation of synapse organization; ISO:GO_Central. DR GO; GO:0060025; P:regulation of synaptic activity; IDA:MGI. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; ISO:GO_Central. DR GO; GO:0007416; P:synapse assembly; ISO:GO_Central. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00055; EGF_Lam; 2. DR CDD; cd00104; KAZAL_FS; 9. DR CDD; cd00110; LamG; 3. DR FunFam; 3.30.60.30:FF:000013; Agrin; 1. DR FunFam; 3.30.60.30:FF:000016; Agrin; 1. DR FunFam; 3.30.60.30:FF:000075; Agrin; 1. DR FunFam; 3.30.60.30:FF:000039; Agrin isoform B; 1. DR FunFam; 2.10.25.10:FF:000228; agrin isoform X1; 1. DR FunFam; 3.30.60.30:FF:000041; agrin isoform X5; 1. DR FunFam; 2.10.25.10:FF:000095; Notch, isoform B; 1. DR FunFam; 2.60.120.200:FF:000031; NtA agrin; 1. DR FunFam; 3.30.60.30:FF:000019; NtA agrin; 1. DR FunFam; 3.30.70.960:FF:000001; NtA agrin; 1. DR FunFam; 2.10.25.10:FF:000134; Transmembrane agrin; 1. DR FunFam; 2.10.25.10:FF:000140; Transmembrane agrin; 1. DR FunFam; 2.60.120.200:FF:000027; Transmembrane agrin; 1. DR FunFam; 2.60.120.200:FF:000045; Transmembrane agrin; 1. DR FunFam; 3.30.60.30:FF:000008; Transmembrane agrin; 1. DR FunFam; 3.30.60.30:FF:000015; Transmembrane agrin; 1. DR FunFam; 3.30.60.30:FF:000022; Transmembrane agrin; 1. DR Gene3D; 2.60.120.200; -; 3. DR Gene3D; 3.30.60.30; -; 9. DR Gene3D; 2.10.25.10; Laminin; 6. DR Gene3D; 3.30.70.960; SEA domain; 1. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000742; EGF. DR InterPro; IPR001881; EGF-like_Ca-bd_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; IPR050372; Neurexin-related_CASP. DR InterPro; IPR000082; SEA_dom. DR InterPro; IPR036364; SEA_dom_sf. DR PANTHER; PTHR15036:SF83; AGRIN; 1. DR PANTHER; PTHR15036; PIKACHURIN-LIKE PROTEIN; 1. DR Pfam; PF00008; EGF; 3. DR Pfam; PF00053; EGF_laminin; 2. DR Pfam; PF00050; Kazal_1; 1. DR Pfam; PF07648; Kazal_2; 8. DR Pfam; PF00054; Laminin_G_1; 3. DR Pfam; PF01390; SEA; 1. DR PRINTS; PR00011; EGFLAMININ. DR SMART; SM00181; EGF; 6. DR SMART; SM00179; EGF_CA; 3. DR SMART; SM00180; EGF_Lam; 2. DR SMART; SM00057; FIMAC; 3. 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 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; PS50024; SEA; 1. DR PDBsum; 3PVE; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Developmental protein; Differentiation; Disulfide bond; EGF-like domain; KW Glycoprotein; Heparan sulfate; Laminin EGF-like domain; Membrane; KW Metal-binding; Phosphoprotein; Proteoglycan; Reference proteome; Repeat; KW Signal-anchor; Synapse; Transmembrane; Transmembrane helix. FT CHAIN 1..1950 FT /note="Agrin" FT /id="PRO_0000356178" FT CHAIN 48..986 FT /note="Agrin N-terminal 110 kDa subunit" FT /id="PRO_0000421617" FT CHAIN 987..1950 FT /note="Agrin C-terminal 110 kDa subunit" FT /id="PRO_0000421618" FT CHAIN 987..1745 FT /note="Agrin C-terminal 90 kDa fragment" FT /id="PRO_0000421619" FT CHAIN 1746..1950 FT /note="Agrin C-terminal 22 kDa fragment" FT /id="PRO_0000421620" FT TOPO_DOM 1..26 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 27..47 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 48..1950 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 86..139 FT /note="Kazal-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 159..214 FT /note="Kazal-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 232..286 FT /note="Kazal-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 303..358 FT /note="Kazal-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 379..431 FT /note="Kazal-like 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 442..496 FT /note="Kazal-like 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 502..561 FT /note="Kazal-like 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 594..647 FT /note="Kazal-like 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 688..741 FT /note="Laminin EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460" FT DOMAIN 742..788 FT /note="Laminin EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460" FT DOMAIN 812..866 FT /note="Kazal-like 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DOMAIN 1014..1136 FT /note="SEA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188" FT DOMAIN 1211..1249 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1254..1430 FT /note="Laminin G-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1431..1468 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1470..1507 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1517..1699 FT /note="Laminin G-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1700..1739 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1775..1947 FT /note="Laminin G-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT REGION 892..971 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1174..1217 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 892..906 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 915..929 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 951..961 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1183..1198 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1822 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 1839 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 1889 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT BINDING 1891 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P25304" FT SITE 986..987 FT /note="Cleavage, alpha site; by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1134 FT /note="Alternative splice site to produce 'x' isoforms" FT SITE 1633 FT /note="Alternative splice site to produce 'y' isoforms" FT SITE 1744 FT /note="Critical for cleavage by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1745..1746 FT /note="Cleavage, beta site; by neurotrypsin" FT /evidence="ECO:0000250" FT SITE 1770 FT /note="Alternative splice site to produce 'z' isoforms" FT SITE 1774 FT /note="Highly important for the agrin receptor complex FT activity of the 'z' insert" FT /evidence="ECO:0000250" FT MOD_RES 569 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 672 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 827 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 948 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1717 FT /note="O-linked (Fuc...) serine" FT /evidence="ECO:0000250|UniProtKB:P25304" FT DISULFID 92..123 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 97..116 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 105..137 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 165..198 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 171..191 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 180..212 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 244..263 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 252..284 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 309..342 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 316..335 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 324..356 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 385..415 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 389..408 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 397..429 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 448..480 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 454..473 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 462..494 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 508..545 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 518..538 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 527..559 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 600..631 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 604..624 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 613..645 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 688..700 FT /evidence="ECO:0000250" FT DISULFID 690..707 FT /evidence="ECO:0000250" FT DISULFID 709..718 FT /evidence="ECO:0000250" FT DISULFID 721..739 FT /evidence="ECO:0000250" FT DISULFID 742..754 FT /evidence="ECO:0000250" FT DISULFID 744..761 FT /evidence="ECO:0000250" FT DISULFID 763..772 FT /evidence="ECO:0000250" FT DISULFID 775..786 FT /evidence="ECO:0000250" FT DISULFID 818..850 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 823..843 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 832..864 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 1215..1226 FT /evidence="ECO:0000250" FT DISULFID 1220..1237 FT /evidence="ECO:0000250" FT DISULFID 1239..1248 FT /evidence="ECO:0000250" FT DISULFID 1401..1430 FT /evidence="ECO:0000250" FT DISULFID 1435..1446 FT /evidence="ECO:0000250" FT DISULFID 1440..1456 FT /evidence="ECO:0000250" FT DISULFID 1458..1467 FT /evidence="ECO:0000250" FT DISULFID 1474..1485 FT /evidence="ECO:0000250" FT DISULFID 1479..1495 FT /evidence="ECO:0000250" FT DISULFID 1497..1506 FT /evidence="ECO:0000250" FT DISULFID 1704..1718 FT /evidence="ECO:0000250" FT DISULFID 1712..1727 FT /evidence="ECO:0000250" FT DISULFID 1729..1738 FT /evidence="ECO:0000250" FT DISULFID 1921..1947 FT /evidence="ECO:0000250" FT VAR_SEQ 1..61 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_035995" FT VAR_SEQ 1634..1637 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_035996" FT VAR_SEQ 1771..1788 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_035997" FT VARIANT 1061 FT /note="F -> S (in a mutant strain; shows symptoms similar FT to the motor neuron disease, agrin-associated congenital FT myasthenic syndrome (CMS) with progressive degradation of FT the neuromuscular junction, decreased acetylcholine FT receptor (AChR) density and increased subsynaptic FT reticulum. Synapses eventually denervate and muscles FT atrophy. There is decreased glycosylation and proteolytic FT processing is altered due to changes in sensitivity to FT neurotrypsin)" FT /evidence="ECO:0000269|PubMed:21890498" FT CONFLICT 1212 FT /note="P -> T (in Ref. 2; AAI50704)" FT /evidence="ECO:0000305" FT STRAND 1520..1525 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1527..1530 FT /evidence="ECO:0007829|PDB:3PVE" FT HELIX 1533..1535 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1545..1555 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1557..1564 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1572..1578 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1581..1590 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1592..1596 FT /evidence="ECO:0007829|PDB:3PVE" FT HELIX 1600..1602 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1605..1614 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1617..1622 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1628..1631 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1649..1652 FT /evidence="ECO:0007829|PDB:3PVE" FT HELIX 1657..1659 FT /evidence="ECO:0007829|PDB:3PVE" FT HELIX 1662..1664 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1671..1679 FT /evidence="ECO:0007829|PDB:3PVE" FT HELIX 1687..1689 FT /evidence="ECO:0007829|PDB:3PVE" FT STRAND 1690..1695 FT /evidence="ECO:0007829|PDB:3PVE" SQ SEQUENCE 1950 AA; 207539 MW; 0679A3F6D8BD1286 CRC64; MPPLPLEHRP RQQPGASVLV RYFMIPCNIC LILLATSTLG FAVLLFLSNY KPGIHFTAAP SMPPDVCRGM LCGFGAVCEP SVEDPGRASC VCKKNVCPAM VAPVCGSDAS TYSNECELQR AQCNQQRRIR LLRQGPCGSR DPCANVTCSF GSTCVPSADG QTASCLCPTT CFGAPDGTVC GSDGVDYPSE CQLLRHACAN QEHIFKKFDG PCDPCQGSMS DLNHICRVNP RTRHPEMLLR PENCPAQHTP ICGDDGVTYE NDCVMSRIGA ARGLLLQKVR SGQCQTRDQC PETCQFNSVC LSRRGRPHCS CDRVTCDGAY RPVCAQDGHT YDNDCWRQQA ECRQQQTIPP KHQGPCDQTP SPCRGAQCAF GATCTVKNGK AVCECQRVCS GGYDPVCGSD GVTYGSVCEL ESMACTLGRE IRVARRGPCD RCGQCRFGSL CEVETGRCVC PSECVESAQP VCGSDGHTYA SECELHVHAC THQISLYVAS AGHCQTCGET VCTFGAVCSA GQCVCPRCEH PPPGPVCGSD GVTYLSACEL REAACQQQVQ IEEARAGPCE PAECGSGGSG SGEDNACEQE LCRQHGGVWD EDSEDGPCVC DFSCQSVLKS PVCGSDGVTY STECHLKKAR CEARQELYVA AQGACRGPTL APLLPMASPH CAQTPYGCCQ DNVTAAQGVG LAGCPSTCHC NPHGSYSGTC DPVTGQCSCR PGVGGLRCDR CEPGFWNFRG IVTDGHSGCT PCSCDPRGAV RDDCEQMTGL CSCRPGVAGP KCGQCPDGQA LGHLGCEADP TTPVTCVEMH CEFGASCVEE AGFAQCVCPT LTCPEANSTK VCGSDGVTYG NECQLKTIAC RQRLDISIQS LGPCRESVAP GVSPTSASMT TPRHILSRTL ASPHSSLPLS PSTTAHDWPT PLPTSPQTVV GTPRSTAATP SDVASLATAI FRESGSTNGS GDEELSGDEE ASGGGSGGLE PPVGSVVVTH GPPIERASCY NSPLGCCSDG KTPSLDSEGS NCPATKAFQG VLELEGVEGQ ELFYTPEMAD PKSELFGETA RSIESTLDDL FRNSDVKKDF WSIRLRELGP GKLVRAIVDV HFDPTTAFQA PDVGQALLQQ IQVSRPWALA VRRPLREHVR FLDFDWFPTF FTGAATGTTA AVATARATTV SRLSASSVTP RVYPSYTSRP VGRTTAPLTT RRPPTTTASI DRPRTPGPQR PPKSCDSQPC LHGGTCQDLD SGKGFSCSCT AGRAGTVCEK VQLPSVPAFK GHSFLAFPTL RAYHTLRLAL EFRALETEGL LLYNGNARGK DFLALALLDG HVQFRFDTGS GPAVLTSLVP VEPGRWHRLE LSRHWRQGTL SVDGEAPVVG ESPSGTDGLN LDTKLYVGGL PEEQVATVLD RTSVGIGLKG CIRMLDINNQ QLELSDWQRA VVQSSGVGEC GDHPCSPNPC HGGALCQALE AGVFLCQCPP GRFGPTCADE KNPCQPNPCH GSAPCHVLSR GGAKCACPLG RSGSFCETVL ENAGSRPFLA DFNGFSYLEL KGLHTFERDL GEKMALEMVF LARGPSGLLL YNGQKTDGKG DFVSLALHNR HLEFRYDLGK GAAIIRSKEP IALGTWVRVF LERNGRKGAL QVGDGPRVLG ESPKSRKVPH TMLNLKEPLY VGGAPDFSKL ARGAAVASGF DGAIQLVSLR GHQLLTQEHV LRAVDVAPFA GHPCTQAVDN PCLNGGSCIP REATYECLCP GGFSGLHCEK GIVEKSVGDL ETLAFDGRTY IEYLNAVTES ELTNEIPAPE TLDSRALFSE KALQSNHFEL SLRTEATQGL VLWIGKVGER ADYMALAIVD GHLQLSYDLG SQPVVLRSTV KVNTNRWLRV RAHREHREGS LQVGNEAPVT GSSPLGATQL DTDGALWLGG LQKLPVGQAL PKAYGTGFVG CLRDVVVGHR QLHLLEDAVT KPELRPCPTL //