AGRIN_CHICK
ID AGRIN_CHICK Reviewed; 2081 AA.
AC P31696; Q90609; Q90685;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 3.
DT 03-AUG-2022, entry version 195.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), AND FUNCTION.
RX PubMed=7860635; DOI=10.1083/jcb.128.4.625;
RA Gesemann M., Denzer A.J., Ruegg M.A.;
RT "Acetylcholine receptor-aggregating activity of agrin isoforms and mapping
RT of the active site.";
RL J. Cell Biol. 128:625-636(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-221 (ISOFORMS 1 AND 9), GLYCOSYLATION,
RP INTERACTION WITH LAMININ, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Spinal cord;
RX PubMed=8522611; DOI=10.1083/jcb.131.6.1547;
RA Denzer A.J., Gesemann M., Schumacher B., Rueegg M.A.;
RT "An amino-terminal extension is required for the secretion of chick agrin
RT and its binding to extracellular matrix.";
RL J. Cell Biol. 131:1547-1560(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 94-2073 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=1314620; DOI=10.1016/0896-6273(92)90089-v;
RA Tsim K.W.K., Rueegg M.A., Escher G., Kroeger S., McMahan U.J.;
RT "cDNA that encodes active agrin.";
RL Neuron 8:677-689(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1901-1921 (ISOFORM 1).
RC STRAIN=White leghorn;
RX PubMed=8393816; DOI=10.1006/dbio.1993.1210;
RA Thomas W.S., O'Dowd D.K., Smith M.A.;
RT "Developmental expression and alternative splicing of chick agrin RNA.";
RL Dev. Biol. 158:523-535(1993).
RN [5]
RP ALTERNATIVE SPLICING.
RX PubMed=1314621; DOI=10.1016/0896-6273(92)90090-z;
RA Rueegg M.A., Tsim K.W.K., Horton S.E., Kroeger S., Escher G., Gensch E.M.,
RA McMahan U.J.;
RT "The agrin gene codes for a family of basal lamina proteins that differ in
RT function and distribution.";
RL Neuron 8:691-699(1992).
RN [6]
RP ALTERNATIVE SPLICING, INTERACTION WITH DAG1, AND HEPARIN BINDING.
RX PubMed=8607994; DOI=10.1016/s0896-6273(00)80096-3;
RA Gesemann M., Cavalli V., Denzer A.J., Brancaccio A., Schumacher B.,
RA Ruegg M.A.;
RT "Alternative splicing of agrin alters its binding to heparin, dystroglycan,
RT and the putative agrin receptor.";
RL Neuron 16:755-767(1996).
RN [7]
RP LAMININ BINDING.
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 [8]
RP FUNCTION.
RX PubMed=11425874; DOI=10.1083/jcb.153.7.1441;
RA Bezakova G., Helm J.P., Francolini M., Lomo T.;
RT "Effects of purified recombinant neural and muscle agrin on skeletal muscle
RT fibers in vivo.";
RL J. Cell Biol. 153:1441-1452(2001).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 9), 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 [10]
RP HEPARAN SULFATE BINDING, AND CHONDROITIN SULFATE BINDING.
RX PubMed=12773545; DOI=10.1074/jbc.m212676200;
RA Winzen U., Cole G.J., Halfter W.;
RT "Agrin is a chimeric proteoglycan with the attachment sites for heparan
RT sulfate/chondroitin sulfate located in two multiple serine-glycine
RT clusters.";
RL J. Biol. Chem. 278:30106-30114(2003).
RN [11]
RP HEPARAN SULFATE BINDING, CHONDROITIN SULFATE BINDING, AND FUNCTION.
RX PubMed=15198666; DOI=10.1111/j.1471-4159.2004.02454.x;
RA Baerwald-de la Torre K., Winzen U., Halfter W., Bixby J.L.;
RT "Glycosaminoglycan-dependent and -independent inhibition of neurite
RT outgrowth by agrin.";
RL J. Neurochem. 90:50-61(2004).
RN [12]
RP FUNCTION, ALTERNATIVE SPLICING, INTERACTION WITH DAG1, HEPARIN BINDING, AND
RP MUTAGENESIS OF ASN-1905; GLU-1906; ILE-1907; 1905-ASN--ILE-1907 AND
RP 1902-HIS--PRO-1908.
RX PubMed=17012237; DOI=10.1074/jbc.m607887200;
RA Scotton P., Bleckmann D., Stebler M., Sciandra F., Brancaccio A., Meier T.,
RA Stetefeld J., Ruegg M.A.;
RT "Activation of muscle-specific receptor tyrosine kinase and binding to
RT dystroglycan are regulated by alternative mRNA splicing of agrin.";
RL J. Biol. Chem. 281:36835-36845(2006).
RN [13]
RP INTERACTION WITH DAG1, STRUCTURE OF CARBOHYDRATES, AND FUNCTION.
RX PubMed=17649979; DOI=10.1021/bi7006383;
RA Sallum C.O., Kammerer R.A., Alexandrescu A.T.;
RT "Thermodynamic and structural studies of carbohydrate binding by the agrin-
RT G3 domain.";
RL Biochemistry 46:9541-9550(2007).
RN [14]
RP INTERDOMAIN DISULFIDE BOND.
RX PubMed=19845005; DOI=10.1002/pro.276;
RA McFarlane A.A., Stetefeld J.;
RT "An interdomain disulfide bridge links the NtA and first FS domain in
RT agrin.";
RL Protein Sci. 18:2421-2428(2009).
RN [15]
RP FUNCTION OF ISOFORM 9.
RX PubMed=19940118; DOI=10.1074/jbc.m109.039420;
RA Porten E., Seliger B., Schneider V.A., Woll S., Stangel D., Ramseger R.,
RA Kroger S.;
RT "The process-inducing activity of transmembrane agrin requires follistatin-
RT like domains.";
RL J. Biol. Chem. 285:3114-3125(2010).
RN [16]
RP PROTEOLYTIC PROCESSING BY MMPS, AND FUNCTION.
RX PubMed=22984437; DOI=10.1371/journal.pone.0043669;
RA Patel T.R., Butler G., McFarlane A., Xie I., Overall C.M., Stetefeld J.;
RT "Site specific cleavage mediated by MMPs regulates function of agrin.";
RL PLoS ONE 7:E43669-E43669(2012).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-156 IN COMPLEX WITH LAMININ,
RP AND DISULFIDE BOND.
RX PubMed=11473262; DOI=10.1038/90422;
RA Stetefeld J., Jenny M., Schulthess T., Landwehr R., Schumacher B.,
RA Frank S., Rueegg M.A., Engel J., Kammerer R.A.;
RT "The laminin-binding domain of agrin is structurally related to N-TIMP-1.";
RL Nat. Struct. Biol. 8:705-709(2001).
RN [18]
RP STRUCTURE BY NMR OF 1870-2081 IN COMPLEX WITH CALCIUM IONS, X-RAY
RP CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 1870-2081 IN COMPLEX WITH CALCIUM IONS,
RP AND DISULFIDE BOND.
RX PubMed=15016366; DOI=10.1016/j.str.2004.02.001;
RA Stetefeld J., Alexandrescu A.T., Maciejewski M.W., Jenny M.,
RA Rathgeb-Szabo K., Schulthess T., Landwehr R., Frank S., Rueegg M.A.,
RA Kammerer R.A.;
RT "Modulation of agrin function by alternative splicing and Ca2+ binding.";
RL Structure 12:503-515(2004).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 26-156, INTERACTION WITH LAMININ,
RP AND DISULFIDE BOND.
RX PubMed=15694127; DOI=10.1016/j.matbio.2004.11.003;
RA Mascarenhas J.B., Rueegg M.A., Sasaki T., Eble J.A., Engel J.,
RA Stetefeld J.;
RT "Structure and laminin-binding specificity of the NtA domain expressed in
RT eukaryotic cells.";
RL Matrix Biol. 23:507-513(2005).
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.
CC -!- FUNCTION: [Isoform 9]: Transmembrane agrin (TM-agrin), the predominant
CC form 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 2, isoform 4 and isoform 7: muscle agrin isoforms,
CC which lack the 8-amino acid insert at the 'B' site, but with the insert
CC at the'A' site have no AChr clustering activity nor MUSK activation but
CC bind heparin. Bind alpha-dystroglycan with lower affinity.
CC -!- FUNCTION: [Isoform 5]: Muscle agrin A0B0 lacking inserts at both 'A'
CC and 'B' sites has no heparin-binding nor AChR clustering activity but
CC binds strongly alpha-dystroglycan.
CC -!- FUNCTION: [Agrin N-terminal 110 kDa subunit]: Is involved in modulation
CC of growth factor signaling (By similarity). Involved also in the
CC regulation 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. {ECO:0000250,
CC ECO:0000269|PubMed:11425874, ECO:0000269|PubMed:15198666,
CC ECO:0000269|PubMed:17012237, ECO:0000269|PubMed:17649979,
CC ECO:0000269|PubMed:19940118, ECO:0000269|PubMed:22984437,
CC ECO:0000269|PubMed:7860635}.
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 'B' splice variants of this fragment
CC 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. Component of the AGRN-LRP4 complex that
CC consists of a tetramer of two AGRN-LRP4 heterodimers. Interacts (via
CC the laminin G-like 3 domain) directly with LRP4; the interaction is
CC required for activation of MUSK and clustering of AChR and requires the
CC 'B8' insert present in the B8 isoforms. Interacts with DAG1; the
CC interaction is influenced by cell surface glycosaminoglycans and by
CC alternative splicing of AGRN. {ECO:0000250,
CC ECO:0000269|PubMed:11473262, ECO:0000269|PubMed:15016366,
CC ECO:0000269|PubMed:15694127, ECO:0000269|PubMed:17012237,
CC ECO:0000269|PubMed:17649979, ECO:0000269|PubMed:8522611,
CC ECO:0000269|PubMed:8607994}.
CC -!- INTERACTION:
CC P31696; PRO_0000000093 [P05067]: APP; Xeno; NbExp=3; IntAct=EBI-457650, EBI-2431589;
CC P31696; P02469: Lamb1; Xeno; NbExp=2; IntAct=EBI-457650, EBI-6662997;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted, extracellular space,
CC extracellular matrix {ECO:0000269|PubMed:11161480,
CC ECO:0000269|PubMed:8522611}. Note=Synaptic basal lamina at the
CC neuromuscular junction. {ECO:0000269|PubMed:11161480}.
CC -!- SUBCELLULAR LOCATION: [Isoform 9]: Synapse
CC {ECO:0000269|PubMed:11161480}. Cell membrane
CC {ECO:0000269|PubMed:11161480}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:11161480}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Comment=Many isoforms exist including secreted and transmembrane
CC forms, isoforms with different length inserts produced at the 'B'
CC splice site, B0, B8, B11 and B19, with or without the 'A' splice site
CC insert.;
CC Name=1; Synonyms=LN-agrin, agrin A4B19;
CC IsoId=P31696-1; Sequence=Displayed;
CC Name=2; Synonyms=Agrin-related protein 1, agrin A4B0;
CC IsoId=P31696-2; Sequence=VSP_045774;
CC Name=3; Synonyms=Agrin-related protein 2, agrin A4B8;
CC IsoId=P31696-3; Sequence=VSP_045776;
CC Name=4; Synonyms=Agrin A4B11;
CC IsoId=P31696-4; Sequence=VSP_045775;
CC Name=5; Synonyms=Muscle agrin, agrin A0B0;
CC IsoId=P31696-5; Sequence=VSP_045773, VSP_045774;
CC Name=6; Synonyms=Agrin A0B8;
CC IsoId=P31696-6; Sequence=VSP_045773, VSP_045776;
CC Name=7; Synonyms=Muscle agrin, agrin A0B11;
CC IsoId=P31696-7; Sequence=VSP_045773, VSP_045775;
CC Name=8; Synonyms=Agrin A0B19;
CC IsoId=P31696-8; Sequence=VSP_045773;
CC Name=9; Synonyms=TM-agrin, SN-agrin;
CC IsoId=P31696-9; Sequence=VSP_045770, VSP_045771;
CC Name=10;
CC IsoId=P31696-10; Sequence=VSP_045772;
CC -!- TISSUE SPECIFICITY: Detected in embryonic brain, spinal cord, skeletal
CC muscle, vitreous humor and liver (at protein level).
CC {ECO:0000269|PubMed:8522611}.
CC -!- DOMAIN: The 4 amino acid insert at the 'A' site is required for
CC efficient binding of heparin.
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 binding. G3 domain is required for
CC C-terminal heparin, heparan sulfate and sialic acid binding.
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 (By similarity). C-terminal heparin and
CC heparin sulfate binding is independent of calcium ions. Binds heparin
CC with a stoichiometry of 2:1. Binds sialic acid with a stoichiometry of
CC 1:1 and binding requires calcium ions. Inserts at the 'B' site have no
CC effect on sialic acid binding. {ECO:0000250,
CC ECO:0000269|PubMed:8522611}.
CC -!- PTM: At synaptic junctions, cleaved at two conserved sites, alpha and
CC beta, by neurotrypsin. Cleavage at the alpha-site produces the N- and
CC C- terminal 110-kDa subunits. Further cleavage of the C-terminal at the
CC beta site produces C-terminal fragments, C22 and C90, of 90 kDa and 22
CC kDa respectively (By similarity). {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved in vitro in both the N-terminal and C-
CC terminal by several matrix metalloproteinases (MMPs).
CC {ECO:0000269|PubMed:22984437}.
CC -!- MISCELLANEOUS: [Isoform 9]: Transmembrane isoform produced by usage of
CC an alternative first exon. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA48585.1; Type=Frameshift; 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; U35613; AAC59740.1; -; mRNA.
DR EMBL; M94271; AAA48585.1; ALT_FRAME; mRNA.
DR EMBL; M97371; AAA48586.1; -; mRNA.
DR EMBL; M97372; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U07271; AAA16788.1; -; mRNA.
DR PIR; JH0591; AGCH.
DR PDB; 1JB3; X-ray; 1.60 A; A=26-156.
DR PDB; 1JC7; X-ray; 2.73 A; A=26-154.
DR PDB; 1PXU; X-ray; 2.20 A; A=25-155.
DR PDB; 1PZ7; X-ray; 1.42 A; A/B=1870-2081.
DR PDB; 1PZ8; X-ray; 2.35 A; A/B/C/D=1870-2081.
DR PDB; 1PZ9; X-ray; 2.80 A; A/B=1870-2081.
DR PDB; 1Q56; NMR; -; A=1870-2081.
DR PDB; 3I70; X-ray; 2.30 A; A=26-153.
DR PDBsum; 1JB3; -.
DR PDBsum; 1JC7; -.
DR PDBsum; 1PXU; -.
DR PDBsum; 1PZ7; -.
DR PDBsum; 1PZ8; -.
DR PDBsum; 1PZ9; -.
DR PDBsum; 1Q56; -.
DR PDBsum; 3I70; -.
DR AlphaFoldDB; P31696; -.
DR SMR; P31696; -.
DR BioGRID; 676782; 2.
DR IntAct; P31696; 5.
DR STRING; 9031.ENSGALP00000039379; -.
DR PaxDb; P31696; -.
DR PRIDE; P31696; -.
DR VEuPathDB; HostDB:geneid_396538; -.
DR eggNOG; KOG3509; Eukaryota.
DR InParanoid; P31696; -.
DR OrthoDB; 414294at2759; -.
DR EvolutionaryTrace; P31696; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:AgBase.
DR GO; GO:0045178; C:basal part of cell; IDA:AgBase.
DR GO; GO:0005604; C:basement membrane; IDA:AgBase.
DR GO; GO:0031012; C:extracellular matrix; TAS:AgBase.
DR GO; GO:0098965; C:extracellular matrix of synaptic cleft; IDA:SynGO.
DR GO; GO:0005576; C:extracellular region; IMP:AgBase.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA:AgBase.
DR GO; GO:0031594; C:neuromuscular junction; IDA:AgBase.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:AgBase.
DR GO; GO:0045202; C:synapse; IDA:AgBase.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0035374; F:chondroitin sulfate binding; IDA:UniProtKB.
DR GO; GO:0002162; F:dystroglycan binding; IDA:UniProtKB.
DR GO; GO:0050840; F:extracellular matrix binding; IMP:AgBase.
DR GO; GO:0005539; F:glycosaminoglycan binding; IMP:AgBase.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0043236; F:laminin binding; IDA:UniProtKB.
DR GO; GO:0043237; F:laminin-1 binding; IDA:AgBase.
DR GO; GO:0033691; F:sialic acid binding; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:AgBase.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; TAS:AgBase.
DR GO; GO:0007420; P:brain development; IMP:AgBase.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0046847; P:filopodium assembly; IDA:AgBase.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; IEA:InterPro.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:AgBase.
DR GO; GO:0007399; P:nervous system development; IDA:AgBase.
DR GO; GO:0007528; P:neuromuscular junction development; TAS:AgBase.
DR GO; GO:0007158; P:neuron cell-cell adhesion; TAS:AgBase.
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:0071340; P:skeletal muscle acetylcholine-gated channel clustering; IDA:AgBase.
DR CDD; cd00055; EGF_Lam; 2.
DR CDD; cd00110; LamG; 3.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 3.30.70.960; -; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
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 Pfam; PF00008; EGF; 4.
DR Pfam; PF00050; Kazal_1; 2.
DR Pfam; PF07648; Kazal_2; 7.
DR Pfam; PF00053; Laminin_EGF; 2.
DR Pfam; PF00054; Laminin_G_1; 3.
DR Pfam; PF03146; NtA; 1.
DR Pfam; PF01390; SEA; 1.
DR SMART; SM00181; EGF; 8.
DR SMART; SM00179; EGF_CA; 3.
DR SMART; SM00180; EGF_Lam; 2.
DR SMART; SM00057; FIMAC; 2.
DR SMART; SM00274; FOLN; 6.
DR SMART; SM00280; KAZAL; 9.
DR SMART; SM00282; LamG; 3.
DR SMART; SM00200; SEA; 1.
DR SUPFAM; SSF100895; SSF100895; 9.
DR SUPFAM; SSF49899; SSF49899; 3.
DR SUPFAM; SSF50242; SSF50242; 1.
DR SUPFAM; SSF82671; SSF82671; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 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 Developmental protein; Differentiation; Disulfide bond; EGF-like domain;
KW Extracellular matrix; Glycoprotein; Heparan sulfate;
KW Laminin EGF-like domain; Membrane; Metal-binding; Proteoglycan;
KW Reference proteome; Repeat; Secreted; Signal; Synapse; Transmembrane.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..2081
FT /note="Agrin"
FT /id="PRO_0000055624"
FT CHAIN 25..1116
FT /note="Agrin N-terminal 110 kDa subunit"
FT /id="PRO_0000421629"
FT CHAIN 1117..2081
FT /note="Agrin C-terminal 110 kDa subunit"
FT /id="PRO_0000421630"
FT CHAIN 1117..1876
FT /note="Agrin C-terminal 90 kDa fragment"
FT /id="PRO_0000421631"
FT CHAIN 1877..2081
FT /note="Agrin C-terminal 22 kDa fragment"
FT /id="PRO_0000421632"
FT DOMAIN 25..159
FT /note="NtA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00443"
FT DOMAIN 193..246
FT /note="Kazal-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 268..321
FT /note="Kazal-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 339..393
FT /note="Kazal-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 409..464
FT /note="Kazal-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 486..538
FT /note="Kazal-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 551..603
FT /note="Kazal-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 616..668
FT /note="Kazal-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 700..753
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 1144..1266
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT DOMAIN 1347..1383
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1388..1563
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 1564..1601
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1603..1640
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1650..1831
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 1832..1870
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1894..2078
FT /note="Laminin G-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT REGION 1066..1114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1301..1357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1066..1094
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1319..1349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1953
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P25304"
FT BINDING 1970
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P25304"
FT BINDING 2020
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P25304"
FT BINDING 2022
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P25304"
FT SITE 140..141
FT /note="Cleavage; by MMP1"
FT SITE 153..154
FT /note="Cleavage; by MMP7"
FT SITE 161..162
FT /note="Cleavage; by MMP12"
FT SITE 1116..1117
FT /note="Cleavage, alpha site; by neurotrypsin"
FT /evidence="ECO:0000250"
FT SITE 1765
FT /note="Alternative splice site to produce 'A' isoform"
FT /evidence="ECO:0000250"
FT SITE 1821..1822
FT /note="Cleavage; by MMP1"
FT SITE 1830..1831
FT /note="Cleavage; by MMP7"
FT SITE 1875
FT /note="Critical for cleavage by neurotrypsin"
FT /evidence="ECO:0000250"
FT SITE 1876..1877
FT /note="Cleavage, beta site; by neurotrypsin"
FT /evidence="ECO:0000250"
FT SITE 1901
FT /note="Alternative splice site to produce 'B' isoforms"
FT /evidence="ECO:0000250"
FT SITE 1905
FT /note="Highly important for the agrin receptor complex
FT activity of the 'B8' insert"
FT /evidence="ECO:0000250"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 508
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 882
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 932
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..98
FT DISULFID 147..179
FT /note="Or C-147 with C-185"
FT DISULFID 199..230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 204..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 212..244
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 274..305
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 278..298
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 287..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 351..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 359..391
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 415..448
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 422..441
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 430..462
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 492..522
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 496..515
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 504..536
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 557..587
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 561..580
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 569..601
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 622..652
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 625..645
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 634..666
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 706..737
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 710..730
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 719..751
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 1351..1362
FT /evidence="ECO:0000250"
FT DISULFID 1356..1371
FT /evidence="ECO:0000250"
FT DISULFID 1373..1382
FT /evidence="ECO:0000250"
FT DISULFID 1568..1579
FT /evidence="ECO:0000250"
FT DISULFID 1573..1589
FT /evidence="ECO:0000250"
FT DISULFID 1591..1600
FT /evidence="ECO:0000250"
FT DISULFID 1607..1618
FT /evidence="ECO:0000250"
FT DISULFID 1612..1628
FT /evidence="ECO:0000250"
FT DISULFID 1630..1639
FT /evidence="ECO:0000250"
FT DISULFID 1836..1849
FT /evidence="ECO:0000250"
FT DISULFID 1843..1858
FT /evidence="ECO:0000250"
FT DISULFID 1860..1869
FT /evidence="ECO:0000250"
FT DISULFID 2052..2078
FT VAR_SEQ 1..60
FT /note="MGGSGAAATLALGLALGLALGGWANCPERELQRREEEANVVLTGTVEEIMNV
FT DPVHHTYS -> MTACQYPMAPGALERDRLYQHKVSLVVRYFMIPCNICLILLATSTLG
FT FAVLLFLNNY (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:8522611"
FT /id="VSP_045770"
FT VAR_SEQ 61..157
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:8522611"
FT /id="VSP_045771"
FT VAR_SEQ 150..156
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000305"
FT /id="VSP_045772"
FT VAR_SEQ 1766..1769
FT /note="Missing (in isoform 5, isoform 6, isoform 7 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:7860635"
FT /id="VSP_045773"
FT VAR_SEQ 1902..1920
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:7860635"
FT /id="VSP_045774"
FT VAR_SEQ 1902..1909
FT /note="Missing (in isoform 4 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:7860635"
FT /id="VSP_045775"
FT VAR_SEQ 1910..1920
FT /note="Missing (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:7860635"
FT /id="VSP_045776"
FT MUTAGEN 1902..1908
FT /note="HLSNEIP->AAANEIA: No reduction in AGRN-induced MUSK
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17012237"
FT MUTAGEN 1905..1907
FT /note="NEI->AAA,AES: Large reduction in AGRN-induced MUSK
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17012237"
FT MUTAGEN 1905..1906
FT /note="NE->AA: Some reduction in AGRN-induced MUSK
FT phosphorylation."
FT MUTAGEN 1905
FT /note="N->A: No effect on AGRN-induced MUSK
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17012237"
FT MUTAGEN 1906
FT /note="E->A: No effect on AGRN-induced MUSK
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17012237"
FT MUTAGEN 1907
FT /note="I->A: No effect on AGRN-induced MUSK
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:17012237"
FT CONFLICT 1247..1249
FT /note="RTI -> SIL (in Ref. 3; AAA48586)"
FT /evidence="ECO:0000305"
FT HELIX 31..36
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 39..53
FT /evidence="ECO:0007829|PDB:1JB3"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 58..70
FT /evidence="ECO:0007829|PDB:1JB3"
FT HELIX 72..78
FT /evidence="ECO:0007829|PDB:1JB3"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1PXU"
FT STRAND 107..114
FT /evidence="ECO:0007829|PDB:1JB3"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:1JB3"
FT TURN 120..125
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:1JB3"
FT HELIX 138..152
FT /evidence="ECO:0007829|PDB:1JB3"
FT STRAND 1879..1881
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1884..1889
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1892..1895
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1922..1935
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1938..1946
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1954..1960
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1963..1972
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1975..1982
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1985..1987
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1989..1996
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 1999..2004
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 2010..2013
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 2021..2023
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 2026..2031
FT /evidence="ECO:0007829|PDB:1PZ7"
FT TURN 2037..2040
FT /evidence="ECO:0007829|PDB:1PZ7"
FT HELIX 2043..2046
FT /evidence="ECO:0007829|PDB:1PZ7"
FT STRAND 2050..2058
FT /evidence="ECO:0007829|PDB:1PZ7"
FT TURN 2065..2067
FT /evidence="ECO:0007829|PDB:1PZ7"
SQ SEQUENCE 2081 AA; 224980 MW; 87FEFE1A11664F0E CRC64;
MGGSGAAATL ALGLALGLAL GGWANCPERE LQRREEEANV VLTGTVEEIM NVDPVHHTYS
CKVRVWRYLK GKDIVTHEIL LDGGNKVVIG GFGDPLICDN QVSTGDTRIF FVNPAPQYMW
PAHRNELMLN SSLMRITLRN LEEVEHCVEE HRKLLADKPN SYFTQTPPTP RDACRGMLCG
FGAVCERSPT DPSQASCVCK KTACPVVVAP VCGSDYSTYS NECELEKAQC NQQRRIKVIS
KGPCGSKDPC AEVTCSFGST CVRSADGQTA GCVCPASCSG VAESIVCGSD GKDYRSECDL
NKHACDKQEN VFKKFDGACD PCKGILNDMN RVCRVNPRTR RVELLSRPEN CPSKREPVCG
DDGVTYASEC VMGRTGAIRG LEIQKVRSGQ CQHQDKCKDE CKFNAVCLKR WHARCSCDRI
TCDGTYRPVC ARDSRTYSND CERQKAECHQ KAAIPVKHSG PCDLGTPSPC LSVECTFGAT
CVVKNREPVC ECQQVCQGRY DPVCGSDNRT YGNPCELNAM ACVLKREIRV KHKGPCDRCG
KCQFGAICEA ETGRCVCPTE CVPSSQPVCG TDGNTYGSEC ELHVRACTQQ KNILVAAQGD
CKSCGTTVCS FGSTCVGGQC VCPRCEQQPL AQVCGTDGLT YDNRCELRAA SCQQQKSIEV
AKMGPCEDEC GSGGSGSGDG SECEQDRCRH YGGWWDEDAE DDRCVCDFTC LAVPRSPVCG
SDDVTYANEC ELKKTRCEKR QNLYVTSQGA CRALTTTPPP LPVVHCSQTI YGCCPDNMTL
ALGVGAAGCP STCQCNPYGS YGGTCDPATG QCSCKPGVGG LKCDRCEPGF WNFRGIVTDS
KSGCTPCNCD PVGSVRDDCE QMTGLCSCKT GITGMKCNQC PNGSKMGMAG CEKDPSAPKS
CEEMSCEFGA TCVEVNGFAH CECPSPLCSE ANMTKVCGSD GVTYGDQCQL KTIACRQGQL
ITVKHVGQCH ESITHTSHTM PPTPLPTLPL DKLIVPPPLQ LTTQAPEPTE LATTSLLMEA
SPTTRSHPTT RRVTTTRPVT TPWMTHGVLK TTVRPLSTSP VVLATTQPPY AESGSAEGSG
DQEMSISGDQ ESSGAGSAGE EEVEESQVTP TPAIERATCY NTPLGCCSDG KTAAADAEGS
NCPATKVFQG VLILEEVEGQ ELFYTPEMAD PKSELFGETA RSIESALDEL FRNSDVKNDF
KSIRVRDLGQ SSAVRVIVES HFDPATSYTA ADVQAASLKQ IRASKKRTIL VKKPQQEHVK
FMDFDWIPRI FTTTITTTTA TTMAPATTRR HTTASAATTA HILRQDTVGH PSAKLAAPAS
TRRPTSTLPT TARRKPTRQP PSTTKKPSRP CDSHPCLHGG TCEDDGREFT CRCPAGKGGA
VCEKPIRYFI PSFGGKSYLA FKMMKAYHTV RIAMEFRATE LSGLLLYNGQ NRGKDFISLA
LVGGFVELRF NTGSGTGVIT SKVRVEPGKW HQLVVNRNRR SGMLAVDGEH VSGESPTGTD
GLNLDTDLFV GGAPEDQMAV VAERTAATVG LKGSIRLLDV NNQMYDLREK GSDVLYGSGV
GECGNDPCHP NPCHHGASCH VKEAEMFHCE CLHSYTGPTC ADERNPCDPT PCHISATCLV
LPEGGAMCAC PMGREGEFCE RVTEQDHTMP FLPEFNGFSY LELNGLQTLF LTCRQMSMEV
VFLAKSPSGM IFYNGQKTDG KGDFVSLALH DGYLEYRYDL GKGAAVLRSK EPVPLNTWIS
VLLERSGRKG VMRINNGERV MGESPKSRKV PHAFLNLKEP FYVGGAPDFS KLARAAAIST
SFYGAVQRIS IKGVPLLKEQ HIRSAVEIST FRAHPCTQKP NPCQNGGTCS PRLESYECAC
QRGFSGAHCE KVIIEKAAGD AEAIAFDGRT YMEYHNAVTK SHLSNEIPAP DALDYPAEPS
EKALQSNHFE LSIKTEATQG LILWSGKGLE RSDYIALAIV DGFVQMMYDL GSKPVVLRST
VPINTNHWTH IKAYRVQREG SLQVGNEAPI TGSSPLGATQ LDTDGALWLG GMERLSVAHK
LPKAYSTGFI GCIRDVIVDR QELHLVEDAL NNPTILHCSA K
