The following text describes a protein:
Function:
[Isoform 1]: Heparan sulfate basal lamina glycoprotein that plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ) and directs key events in postsynaptic differentiation. This neuron-specific (z+) isoform is a component of the AGRN-LRP4 receptor complex that induces the phosphorylation and activation of MUSK. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Calcium ions are required for maximal AChR clustering. AGRN function in neurons is highly regulated by alternative splicing, glycan binding and proteolytic processing. Modulates calcium ion homeostasis in neurons, specifically by inducing an increase in cytoplasmic calcium ions. Functions differentially in the central nervous system (CNS) by inhibiting the alpha(3)-subtype of Na+/K+-ATPase and evoking depolarization at CNS synapses. This transmembrane agrin (TM-agrin) isoform, the predominate form in neurons of the brain, induces dendritic filopodia and synapse formation in mature hippocampal neurons in large part due to the attached glycosaminoglycan chains and the action of Rho-family GTPases; Isoform 1, isoform 4, isoform 5 and isoform 6: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms; [Agrin N-terminal 110 kDa subunit]: Is involved in regulation of neurite outgrowth probably due to the presence of the glycosaminoglcan (GAG) side chains of heparan and chondroitin sulfate attached to the Ser/Thr- and Gly/Ser-rich regions. Also involved in modulation of growth factor signaling (By similarity); [Agrin C-terminal 22 kDa fragment]: This released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'z' splice variants (z+) of this fragment also show an increase in the number of filopodia.
Subcellular Localization:
Synapse. Cell membrane; Single-pass type II membrane protein.
Domain:
Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding.
Sequence:
MPPLPLEHRPRQEPGASMLVRYFMIPCNICLILLATSTLGFAVLLFLSNYKPGIHFTPAPPTPPDVCRGMLCGFGAVCEPSVEDPGRASCVCKKNACPATVAPVCGSDASTYSNECELQRAQCNQQRRIRLLRQGPCGSRDPCANVTCSFGSTCVPSADGQTASCLCPTTCFGAPDGTVCGSDGVDYPSECQLLSHACASQEHIFKKFNGPCDPCQGSMSDLNHICRVNPRTRHPEMLLRPENCPAQHTPICGDDGVTYENDCVMSRIGATRGLLLQKVRSGQCQTRDQCPETCQFNSVCLSRRGRPHCSCDRVTCDGSYRPVCAQDGHTYNNDCWRQQAECRQQRAIPPKHQGPCDQTPSPCHGVQCAFGAVCTVKNGKAECECQRVCSGIYDPVCGSDGVTYGSVCELESMACTLGREIQVARRGPCDPCGQCRFGSLCEVETGRCVCPSECVESAQPVCGSDGHTYASECELHVHACTHQISLYVASAGHCQTCGEKVCTFGAVCSAGQCVCPRCEHPPPGPVCGSDGVTYLSACELREAACQQQVQIEEAHAGPCEPAECGSGGSGSGEDDECEQELCRQRGGIWDEDSEDGPCVCDFSCQSVPRSPVCGSDGVTYGTECDLKKARCESQQELYVAAQGACRGPTLAPLLPVAFPHCAQTPYGCCQDNFTAAQGVGLAGCPSTCHCNPHGSYSGTCDPATGQCSCRPGVGGLRCDRCEPGFWNFRGIVTDGHSGCTPCSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDGQVLGHLGCEADPMTPVTCVEIHCEFGASCVEKAGFAQCICPTLTCPEANSTKVCGSDGVTYGNECQLKAIACRQRLDISTQSLGPCQESVTPGASPTSASMTTPRHILSKTLPFPHNSLPLSPGSTTHDWPTPLPISPHTTVSIPRSTAWPVLTVPPTAAASDVTSLATSIFSESGSANGSGDEELSGDEEASGGGSGGLEPPVGSIVVTHGPPIERASCYNSPLGCCSDGKTPSLDSEGSNCPATKAFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFWSVRLRELGPGKLVRAIVDVHFDPTTAFQASDVGQALLRQIQVSRPWALAVRRPLQEHVRFLDFDWFPTFFTGAATGTTAAMATARATTVSRLPASSVTPRVYPSHTSRPVGRTTAPPTTRRPPTTATNMDRPRTPGHQQPSKSCDSQPCLHGGTCQDQDSGKGFTCSCTAGRGGSVCEKVQPPSMPAFKGHSFLAFPTLRAYHTLRLALEFRALETEGLLLYNGNARGKDFLALALLDGRVQFRFDTGSGPAVLTSLVPVEPGRWHRLELSRHWRQGTLSVDGETPVVGESPSGTDGLNLDTNLYVGGIPEEQVAMVLDRTSVGVGLKGCIRMLDINNQQLELSDWQRAAVQSSGVGECGDHPCLPNPCHGGALCQALEAGMFLCQCPPGRFGPTCADEKSPCQPNPCHGAAPCRVLSSGGAKCECPLGRSGTFCQTVLETAGSRPFLADFNGFSYLELKGLHTFERDLGEKMALEMVFLARGPSGLLLYNGQKTDGKGDFVSLALHNRHLEFCYDLGKGAAVIRSKEPIALGTWVRVFLERNGRKGALQVGDGPRVLGESPKSRKVPHTMLNLKEPLYIGGAPDFSKLARGAAVSSGFSGVIQLVSLRGHQLLTQEHVLRAVDVSPFADHPCTQALGNPCLNGGSCVPREATYECLCPGGFSGLHCEKGLVEKSVGDLETLAFDGRTYIEYLNAVIESELTNEIPAPETLDSRALFSEKALQSNHFELSLRTEATQGLVLWIGKAAERADYMALAIVDGHLQLSYDLGSQPVVLRSTVKVNTNRWLRIRAHREHREGSLQVGNEAPVTGSSPLGATQLDTDGALWLGGLQKLPVGQALPKAYGTGFVGCLRDVVVGHRQLHLLEDAVTKPELRPCPTP