Gene name: AGRN

Uniprot entry:

O00468

Protein names:

Agrin [Cleaved into: Agrin N-terminal 110 kDa subunit; Agrin C-terminal 110 kDa subunit; Agrin C-terminal 90 kDa fragment (C90); Agrin C-terminal 22 kDa fragment (C22)]

Protein sequence:

1_MAGRS 6_ HPGPL 11_ RPLLP 16_ LLVVA 21_ ACVLP 26_ GAGGT 31_ CPERA 36_ LERRE 41_ EEANV 46_ VLTGT 51_ VEEIL 56_ NVDPV 61_ QHTYS 66_ CKVRV 71_ WRYLK 76_ GKDLV 81_ ARESL 86_ LDGGN 91_ KVVIS 96_ GFGDP 101_ LICDN 106_ QVSTG 111_ DTRIF 116_ FVNPA 121_ PPYLW 126_ PAHKN 131_ ELMLN 136_ SSLMR 141_ ITLRN 146_ LEEVE 151_ FCVED 156_ KPGTH 161_ FTPVP 166_ PTPPD 171_ ACRGM 176_ LCGFG 181_ AVCEP 186_ NAEGP 191_ GRASC 196_ VCKKS 201_ PCPSV 206_ VAPVC 211_ GSDAS 216_ TYSNE 221_ CELQR 226_ AQCSQ 231_ QRRIR 236_ LLSRG 241_ PCGSR 246_ DPCSN 251_ VTCSF 256_ GSTCA 261_ RSADG 266_ LTASC 271_ LCPAT 276_ CRGAP 281_ EGTVC 286_ GSDGA 291_ DYPGE 296_ CQLLR 301_ RACAR 306_ QENVF 311_ KKFDG 316_ PCDPC 321_ QGALP 326_ DPSRS 331_ CRVNP 336_ RTRRP 341_ EMLLR 346_ PESCP 351_ ARQAP 356_ VCGDD 361_ GVTYE 366_ NDCVM 371_ GRSGA 376_ ARGLL 381_ LQKVR 386_ SGQCQ 391_ GRDQC 396_ PEPCR 401_ FNAVC 406_ LSRRG 411_ RPRCS 416_ CDRVT 421_ CDGAY 426_ RPVCA 431_ QDGRT 436_ YDSDC 441_ WRQQA 446_ ECRQQ 451_ RAIPS 456_ KHQGP 461_ CDQAP 466_ SPCLG 471_ VQCAF 476_ GATCA 481_ VKNGQ 486_ AACEC 491_ LQACS 496_ SLYDP 501_ VCGSD 506_ GVTYG 511_ SACEL 516_ EATAC 521_ TLGRE 526_ IQVAR 531_ KGPCD 536_ RCGQC 541_ RFGAL 546_ CEAET 551_ GRCVC 556_ PSECV 561_ ALAQP 566_ VCGSD 571_ GHTYP 576_ SECML 581_ HVHAC 586_ THQIS 591_ LHVAS 596_ AGPCE 601_ TCGDA 606_ VCAFG 611_ AVCSA 616_ GQCVC 621_ PRCEH 626_ PPPGP 631_ VCGSD 636_ GVTYG 641_ SACEL 646_ REAAC 651_ LQQTQ 656_ IEEAR 661_ AGPCE 666_ QAECG 671_ SGGSG 676_ SGEDG 681_ DCEQE 686_ LCRQR 691_ GGIWD 696_ EDSED 701_ GPCVC 706_ DFSCQ 711_ SVPGS 716_ PVCGS 721_ DGVTY 726_ STECE 731_ LKKAR 736_ CESQR 741_ GLYVA 746_ AQGAC 751_ RGPTF 756_ APLPP 761_ VAPLH 766_ CAQTP 771_ YGCCQ 776_ DNITA 781_ ARGVG 786_ LAGCP 791_ SACQC 796_ NPHGS 801_ YGGTC 806_ DPATG 811_ QCSCR 816_ PGVGG 821_ LRCDR 826_ CEPGF 831_ WNFRG 836_ IVTDG 841_ RSGCT 846_ PCSCD 851_ PQGAV 856_ RDDCE 861_ QMTGL 866_ CSCKP 871_ GVAGP 876_ KCGQC 881_ PDGRA 886_ LGPAG 891_ CEADA 896_ SAPAT 901_ CAEMR 906_ CEFGA 911_ RCVEE 916_ SGSAH 921_ CVCPM 926_ LTCPE 931_ ANATK 936_ VCGSD 941_ GVTYG 946_ NECQL 951_ KTIAC 956_ RQGLQ 961_ ISIQS 966_ LGPCQ 971_ EAVAP 976_ STHPT 981_ SASVT 986_ VTTPG 991_ LLLSQ 996_ ALPAP 1001_ PGALP 1006_ LAPSS 1011_ TAHSQ 1016_ TTPPP 1021_ SSRPR 1026_ TTASV 1031_ PRTTV 1036_ WPVLT 1041_ VPPTA 1046_ PSPAP 1051_ SLVAS 1056_ AFGES 1061_ GSTDG 1066_ SSDEE 1071_ LSGDQ 1076_ EASGG 1081_ GSGGL 1086_ EPLEG 1091_ SSVAT 1096_ PGPPV 1101_ ERASC 1106_ YNSAL 1111_ GCCSD 1116_ GKTPS 1121_ LDAEG 1126_ SNCPA 1131_ TKVFQ 1136_ GVLEL 1141_ EGVEG 1146_ QELFY 1151_ TPEMA 1156_ DPKSE 1161_ LFGET 1166_ ARSIE 1171_ STLDD 1176_ LFRNS 1181_ DVKKD 1186_ FRSVR 1191_ LRDLG 1196_ PGKSV 1201_ RAIVD 1206_ VHFDP 1211_ TTAFR 1216_ APDVA 1221_ RALLR 1226_ QIQVS 1231_ RRRSL 1236_ GVRRP 1241_ LQEHV 1246_ RFMDF 1251_ DWFPA 1256_ FITGA 1261_ TSGAI 1266_ AAGAT 1271_ ARATT 1276_ ASRLP 1281_ SSAVT 1286_ PRAPH 1291_ PSHTS 1296_ QPVAK 1301_ TTAAP 1306_ TTRRP 1311_ PTTAP 1316_ SRVPG 1321_ RRPPA 1326_ PQQPP 1331_ KPCDS 1336_ QPCFH 1341_ GGTCQ 1346_ DWALG 1351_ GGFTC 1356_ SCPAG 1361_ RGGAV 1366_ CEKVL 1371_ GAPVP 1376_ AFEGR 1381_ SFLAF 1386_ PTLRA 1391_ YHTLR 1396_ LALEF 1401_ RALEP 1406_ QGLLL 1411_ YNGNA 1416_ RGKDF 1421_ LALAL 1426_ LDGRV 1431_ QLRFD 1436_ TGSGP 1441_ AVLTS 1446_ AVPVE 1451_ PGQWH 1456_ RLELS 1461_ RHWRR 1466_ GTLSV 1471_ DGETP 1476_ VLGES 1481_ PSGTD 1486_ GLNLD 1491_ TDLFV 1496_ GGVPE 1501_ DQAAV 1506_ ALERT 1511_ FVGAG 1516_ LRGCI 1521_ RLLDV 1526_ NNQRL 1531_ ELGIG 1536_ PGAAT 1541_ RGSGV 1546_ GECGD 1551_ HPCLP 1556_ NPCHG 1561_ GAPCQ 1566_ NLEAG 1571_ RFHCQ 1576_ CPPGR 1581_ VGPTC 1586_ ADEKS 1591_ PCQPN 1596_ PCHGA 1601_ APCRV 1606_ LPEGG 1611_ AQCEC 1616_ PLGRE 1621_ GTFCQ 1626_ TASGQ 1631_ DGSGP 1636_ FLADF 1641_ NGFSH 1646_ LELRG 1651_ LHTFA 1656_ RDLGE 1661_ KMALE 1666_ VVFLA 1671_ RGPSG 1676_ LLLYN 1681_ GQKTD 1686_ GKGDF 1691_ VSLAL 1696_ RDRRL 1701_ EFRYD 1706_ LGKGA 1711_ AVIRS 1716_ REPVT 1721_ LGAWT 1726_ RVSLE 1731_ RNGRK 1736_ GALRV 1741_ GDGPR 1746_ VLGES 1751_ PKSRK 1756_ VPHTV 1761_ LNLKE 1766_ PLYVG 1771_ GAPDF 1776_ SKLAR 1781_ AAAVS 1786_ SGFDG 1791_ AIQLV 1796_ SLGGR 1801_ QLLTP 1806_ EHVLR 1811_ QVDVT 1816_ SFAGH 1821_ PCTRA 1826_ SGHPC 1831_ LNGAS 1836_ CVPRE 1841_ AAYVC 1846_ LCPGG 1851_ FSGPH 1856_ CEKGL 1861_ VEKSA 1866_ GDVDT 1871_ LAFDG 1876_ RTFVE 1881_ YLNAV 1886_ TESEL 1891_ ANEIP 1896_ VPETL 1901_ DSGAL 1906_ HSEKA 1911_ LQSNH 1916_ FELSL 1921_ RTEAT 1926_ QGLVL 1931_ WSGKA 1936_ TERAD 1941_ YVALA 1946_ IVDGH 1951_ LQLSY 1956_ NLGSQ 1961_ PVVLR 1966_ STVPV 1971_ NTNRW 1976_ LRVVA 1981_ HREQR 1986_ EGSLQ 1991_ VGNEA 1996_ PVTGS 2001_ SPLGA 2006_ TQLDT 2011_ DGALW 2016_ LGGLP 2021_ ELPVG 2026_ PALPK 2031_ AYGTG 2036_ FVGCL 2041_ RDVVV 2046_ GRHPL 2051_ HLLED 2056_ AVTKP 2061_ELRPC

Protein annotations

Protein functions:

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. 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 secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain

2: Transmembrane form that is 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

3: Isoform 1, isoform 4 and isoform 5: 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

4: Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation

5: 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)

6: 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