Agrn
entrez
25592
canonical
uniprot
P25304
canonical
ensembl
ENSRNOG00000020205
resolver
ensp
ENSRNOP00000040828
resolver
ensp
ENSRNOP00000050623
resolver
ensp
ENSRNOP00000105718
resolver
ensp
ENSRNOP00000108828
resolver
enst
ENSRNOT00000045678
resolver
enst
ENSRNOT00000047854
resolver
enst
ENSRNOT00000150948
resolver
genesymbol
Agrn
resolver
genesymbol_syn
Agrin
resolver
uniprot
A0ABK0L6P8
resolver
uniprot
D4A2F1
resolver
uniprot
F1LPF2
resolver
uniprot
Q63034
resolver
uniprot_entry
A0ABK0L6P8_RAT
resolver
uniprot_entry
AGRIN_RAT
resolver
uniprot_entry
D4A2F1_RAT
resolver
uniprot_entry
F1LPF2_RAT
resolver
uniprot_sec
Q63034
resolver
amino_acid_sequence
MPPLPLEHRPRQEPGASMLVRYFMIPCNICLILLATSTLGFAVLLFLSNYKPGIHFTPAPPTPPDVCRGMLCGFGAVCEPSVEDPGRASCVCKKNACPATVAPVCGSDASTYSNECELQRAQCNQQRRIRLLRQGPCGSRDPCANVTCSFGSTCVPSADGQTASCLCPTTCFGAPDGTVCGSDGVDYPSECQLLSHACASQEHIFKKFNGPCDPCQGSMSDLNHICRVNPRTRHPEMLLRPENCPAQHTPICGDDGVTYENDCVMSRIGATRGLLLQKVRSGQCQTRDQCPETCQFNSVCLSRRGRPHCSCDRVTCDGSYRPVCAQDGHTYNNDCWRQQAECRQQRAIPPKHQGPCDQTPSPCHGVQCAFGAVCTVKNGKAECECQRVCSGIYDPVCGSDGVTYGSVCELESMACTLGREIQVARRGPCDPCGQCRFGSLCEVETGRCVCPSECVESAQPVCGSDGHTYASECELHVHACTHQISLYVASAGHCQTCGEKVCTFGAVCSAGQCVCPRCEHPPPGPVCGSDGVTYLSACELREAACQQQVQIEEAHAGPCEPAECGSGGSGSGEDDECEQELCRQRGGIWDEDSEDGPCVCDFSCQSVPRSPVCGSDGVTYGTECDLKKARCESQQELYVAAQGACRGPTLAPLLPVAFPHCAQTPYGCCQDNFTAAQGVGLAGCPSTCHCNPHGSYSGTCDPATGQCSCRPGVGGLRCDRCEPGFWNFRGIVTDGHSGCTPCSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDGQVLGHLGCEADPMTPVTCVEIHCEFGASCVEKAGFAQCICPTLTCPEANSTKVCGSDGVTYGNECQLKAIACRQRLDISTQSLGPCQESVTPGASPTSASMTTPRHILSKTLPFPHNSLPLSPGSTTHDWPTPLPISPHTTVSIPRSTAWPVLTVPPTAAASDVTSLATSIFSESGSANGSGDEELSGDEEASGGGSGGLEPPVGSIVVTHGPPIERASCYNSPLGCCSDGKTPSLDSEGSNCPATKAFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFWSVRLRELGPGKLVRAIVDVHFDPTTAFQASDVGQALLRQIQVSRPWALAVRRPLQEHVRFLDFDWFPTFFTGAATGTTAAMATARATTVSRLPASSVTPRVYPSHTSRPVGRTTAPPTTRRPPTTATNMDRPRTPGHQQPSKSCDSQPCLHGGTCQDQDSGKGFTCSCTAGRGGSVCEKVQPPSMPAFKGHSFLAFPTLRAYHTLRLALEFRALETEGLLLYNGNARGKDFLALALLDGRVQFRFDTGSGPAVLTSLVPVEPGRWHRLELSRHWRQGTLSVDGETPVVGESPSGTDGLNLDTNLYVGGIPEEQVAMVLDRTSVGVGLKGCIRMLDINNQQLELSDWQRAAVQSSGVGECGDHPCLPNPCHGGALCQALEAGMFLCQCPPGRFGPTCADEKSPCQPNPCHGAAPCRVLSSGGAKCECPLGRSGTFCQTVLETAGSRPFLADFNGFSYLELKGLHTFERDLGEKMALEMVFLARGPSGLLLYNGQKTDGKGDFVSLALHNRHLEFCYDLGKGAAVIRSKEPIALGTWVRVFLERNGRKGALQVGDGPRVLGESPKSRKVPHTMLNLKEPLYIGGAPDFSKLARGAAVSSGFSGVIQLVSLRGHQLLTQEHVLRAVDVSPFADHPCTQALGNPCLNGGSCVPREATYECLCPGGFSGLHCEKGLVEKSVGDLETLAFDGRTYIEYLNAVIESELTNEIPAPETLDSRALFSEKALQSNHFELSLRTEATQGLVLWIGKAAERADYMALAIVDGHLQLSYDLGSQPVVLRSTVKVNTNRWLRIRAHREHREGSLQVGNEAPVTGSSPLGATQLDTDGALWLGGLQKLPVGQALPKAYGTGFVGCLRDVVVGHRQLHLLEDAVTKPELRPCPTP
uniprot
proteins
function
FUNCTION: Depending on alternative splicing and post-translational modifications, it has a role in different processes, including formation and maintenance of the neuromuscular junction, regulation of neurite outgrowth, and positive regulation of cartilage formation through alpha-dystroglycan binding and up-regulation of SOX9. {ECO:0000250|UniProtKB:A2ASQ1, ECO:0000250|UniProtKB:O00468}.; 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.; FUNCTION: 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.; FUNCTION: [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). {ECO:0000250, ECO:0000269|PubMed:18775496, ECO:0000269|PubMed:19524020, ECO:0000269|PubMed:20471381, ECO:0000269|PubMed:20505824, ECO:0000269|PubMed:20566625, ECO:0000269|PubMed:8398142, ECO:0000269|PubMed:8653787, ECO:0000269|PubMed:8693000}.; FUNCTION: [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.
uniprot
proteins
mass_dalton
208646
uniprot
proteins
mutagenesis
MUTAGEN 566..571; /note="SGGSGS->AGGAGA: Abolishes heparan sulfate (HS) binding, greatly reduced branched retraction fiber (BRF) formation, filopodia formation reduced by about 50% and lowered RAC1 and CDK1 activation. No chondroitin sulfate (CS) nor heparan sulfate attachment, almost no branched retraction fiber (BRF) formation, filopodia formation reduced by about 60% and lowered RAC1 and CDK1 activation; when associated with 953-AGA-955."; MUTAGEN 953..955; /note="SGS->AGA: Abolishes chondroitin sulfate (CS) binding, greatly reduced branched retraction fiber (BRF) formation, filopodia formation reduced by about 50% and lowered RAC1 and CDK1 activation. No chondroitin sulfate (CS) nor heparan sulfate (HS) binding almost no retraction fiber (BRF) formation, filopodia formation reduced by about 60% lowered RAC1 and CDK1 activation; when associated with 566-AGGAGA-571."; MUTAGEN 991; /note="P->A: About 13% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 992; /note="P->A: About 64% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 993; /note="I->A: About 60% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 994; /note="E->A: Almost completely abolishes cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 995; /note="R->A: Completely abolishes cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 995; /note="R->K: About 30% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1726; /note="S->A: Abolishes fucosylation of muscle agrin. Stimulates MUSK phosphorylation and increases AChR clustering."; /evidence="ECO:0000269|PubMed:18775496"; MUTAGEN 1751; /note="L->A: About 23% reduction in cleavage by neurotrypsin. Reduces cleavage by neurotrypsin by about 90%; when associated with A-1752. Completely abolishes cleavage by neurotrypsin; when associated with A-1753."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1752; /note="V->A: About 41% reduction in cleavage by neurotrypsin. Reduces cleavage by neurotrypsin by about 90%; when associated with A-1751. Completely abolishes cleavage by neurotrypsin; when associated with A-1753."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1753; /note="E->A,K: Almost completely abolishes cleavage by neurotrypsin. Completely abolishes cleavage by neurotrypsin; when associated with A-1751 or A-1752."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1753; /note="E->D,L,Q: About 20% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1754; /note="K->A: Completely abolishes cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1754; /note="K->R: About 55% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1755; /note="S->A: About 62% reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1756; /note="V->A: Slight reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1757; /note="G->A: Slight reduction in cleavage by neurotrypsin."; /evidence="ECO:0000269|PubMed:17586728"; MUTAGEN 1780; /note="E->A: Slight reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1781; /note="L->A: Slight reduction in AChR clustering ability. Slight reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1782; /note="T->A: Slight reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1783; /note="N->A: Abolishes formation of AGRN-LRP4 complex and MUSK activation. No AChR clustering activity."; /evidence="ECO:0000269|PubMed:20566625, ECO:0000269|PubMed:22302937"; MUTAGEN 1784; /note="E->A: Significant reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1785; /note="I->A: Significant reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625, ECO:0000269|PubMed:22302937"; MUTAGEN 1785; /note="I->S: Abolishes formation of AGRN-LRP4 complex and MUSK activation."; /evidence="ECO:0000269|PubMed:20566625, ECO:0000269|PubMed:22302937"; MUTAGEN 1786; /note="P->A: Significant reduction in AChR clustering ability."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1806; /note="H->L: No effect on formation of AGRN-LRP4 complex nor on MUSK activation."; /evidence="ECO:0000269|PubMed:22302937"; MUTAGEN 1831; /note="D->A: Abolishes calcium binding, lowering of binding to myotubes and some loss of AChR clustering activity; when associated with A-1900."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1876; /note="R->E: No effect formation of AGRN-LRP4 complex nor on MUSK activation."; /evidence="ECO:0000269|PubMed:22302937"; MUTAGEN 1900; /note="D->A: Abolishes calcium binding, lowering of binding to myotubes and some loss of AChR clustering activity; when associated with A-1831."; /evidence="ECO:0000269|PubMed:20566625"; MUTAGEN 1938; /note="H->L: No effect formation of AGRN-LRP4 complex nor on MUSK activation."; /evidence="ECO:0000269|PubMed:22302937
uniprot
proteins
post_translational_modification
PTM: Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. Glycosaminoglycans (GAGs), present in the agrin N-terminal 110 kDa fragment, are required for induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains. Heparin and heparin sulfate binding in the G3 doamin is independent of calcium ions. Binds heparin with a stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and binding requires calcium ions. {ECO:0000269|PubMed:18775496, ECO:0000269|PubMed:8398142}.; PTM: At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site produces the agrin N-terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. Further cleavage of agrin C-terminal 110-kDa subunit at the beta site produces the C-terminal fragments, agrin C-terminal 90 kDa fragment and agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site releases large amounts of the agrin C-terminal 22 kDa fragment leading to destabilization at the neuromuscular junction (NMJ). {ECO:0000269|PubMed:17586728, ECO:0000269|PubMed:20980386}.
uniprot
proteins
pubmed
11161480
uniprot
proteins
pubmed
1326608
uniprot
proteins
pubmed
17586728
uniprot
proteins
pubmed
1851019
uniprot
proteins
pubmed
18775496
uniprot
proteins
pubmed
19524020
uniprot
proteins
pubmed
20471381
uniprot
proteins
pubmed
20505824
uniprot
proteins
pubmed
20566625
uniprot
proteins
pubmed
20980386
uniprot
proteins
pubmed
22302937
uniprot
proteins
pubmed
7472435
uniprot
proteins
pubmed
8398142
uniprot
proteins
pubmed
8653787
uniprot
proteins
pubmed
8693000
uniprot
proteins
sequence_length
1959
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:8653787}. Cell membrane {ECO:0000269|PubMed:11161480}; Single-pass type II membrane protein {ECO:0000269|PubMed:11161480}.
uniprot
proteins
transmembrane_region
TRANSMEM 27..47; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins