Tag |
Content |
dbPAF ID |
dbPAF-0000101 |
Uniprot Accession |
O00468; AGRIN_HUMAN; Q5SVA1; Q5SVA2; Q60FE1; Q7KYS8; Q8N4J5; Q96IC1; Q9BTD4; |
Genbank Protein ID |
NP_940978.2; XP_005244806.1; |
Genbank Nucleotide ID |
NM_198576.3; XM_005244749.2; |
Protein Name |
Agrin |
Protein Synonyms/Alias |
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Gene Name |
AGRN |
Gene Synonyms/Alias |
AGRIN; |
Organism |
Homo sapiens(Human) |
NCBI Taxa ID |
9606 |
Functional Description (View all) |
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. 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.Functional Description
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. 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.
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Phosphorylation Sites
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dbPAF PTMs: 19 |
Sequence (Fasta) | MAGRSHPGPL RPLLPLLVVA ACVLPGAGGT CPERALERRE EEANVVLTGT VEEILNVDPV 60 QHTYSCKVRV WRYLKGKDLV ARESLLDGGN KVVISGFGDP LICDNQVSTG DTRIFFVNPA 120 PPYLWPAHKN ELMLNSSLMR ITLRNLEEVE FCVEDKPGTH FTPVPPTPPD ACRGMLCGFG 180 AVCEPNAEGP GRASCVCKKS PCPSVVAPVC GSDASTYSNE CELQRAQCSQ QRRIRLLSRG 240 PCGSRDPCSN VTCSFGSTCA RSADGLTASC LCPATCRGAP EGTVCGSDGA DYPGECQLLR 300 RACARQENVF KKFDGPCDPC QGALPDPSRS CRVNPRTRRP EMLLRPESCP ARQAPVCGDD 360 GVTYENDCVM GRSGAARGLL LQKVRSGQCQ GRDQCPEPCR FNAVCLSRRG RPRCSCDRVT 420 CDGAYRPVCA QDGRTYDSDC WRQQAECRQQ RAIPSKHQGP CDQAPSPCLG VQCAFGATCA 480 VKNGQAACEC LQACSSLYDP VCGSDGVTYG SACELEATAC TLGREIQVAR KGPCDRCGQC 540 RFGALCEAET GRCVCPSECV ALAQPVCGSD GHTYPSECML HVHACTHQIS LHVASAGPCE 600 TCGDAVCAFG AVCSAGQCVC PRCEHPPPGP VCGSDGVTYG SACELREAAC LQQTQIEEAR 660 AGPCEQAECG SGGSGSGEDG DCEQELCRQR GGIWDEDSED GPCVCDFSCQ SVPGSPVCGS 720 DGVTYSTECE LKKARCESQR GLYVAAQGAC RGPTFAPLPP VAPLHCAQTP YGCCQDNITA 780 ARGVGLAGCP SACQCNPHGS YGGTCDPATG QCSCRPGVGG LRCDRCEPGF WNFRGIVTDG 840 RSGCTPCSCD PQGAVRDDCE QMTGLCSCKP GVAGPKCGQC PDGRALGPAG CEADASAPAT 900 CAEMRCEFGA RCVEESGSAH CVCPMLTCPE ANATKVCGSD GVTYGNECQL KTIACRQGLQ 960 ISIQSLGPCQ EAVAPSTHPT SASVTVTTPG LLLSQALPAP PGALPLAPSS TAHSQTTPPP 1020 SSRPRTTASV PRTTVWPVLT VPPTAPSPAP SLVASAFGES GSTDGSSDEE LSGDQEASGG 1080 GSGGLEPLEG SSVATPGPPV ERASCYNSAL GCCSDGKTPS LDAEGSNCPA TKVFQGVLEL 1140 EGVEGQELFY TPEMADPKSE LFGETARSIE STLDDLFRNS DVKKDFRSVR LRDLGPGKSV 1200 RAIVDVHFDP TTAFRAPDVA RALLRQIQVS RRRSLGVRRP LQEHVRFMDF DWFPAFITGA 1260 TSGAIAAGAT ARATTASRLP SSAVTPRAPH PSHTSQPVAK TTAAPTTRRP PTTAPSRVPG 1320 RRPPAPQQPP KPCDSQPCFH GGTCQDWALG GGFTCSCPAG RGGAVCEKVL GAPVPAFEGR 1380 SFLAFPTLRA YHTLRLALEF RALEPQGLLL YNGNARGKDF LALALLDGRV QLRFDTGSGP 1440 AVLTSAVPVE PGQWHRLELS RHWRRGTLSV DGETPVLGES PSGTDGLNLD TDLFVGGVPE 1500 DQAAVALERT FVGAGLRGCI RLLDVNNQRL ELGIGPGAAT RGSGVGECGD HPCLPNPCHG 1560 GAPCQNLEAG RFHCQCPPGR VGPTCADEKS PCQPNPCHGA APCRVLPEGG AQCECPLGRE 1620 GTFCQTASGQ DGSGPFLADF NGFSHLELRG LHTFARDLGE KMALEVVFLA RGPSGLLLYN 1680 GQKTDGKGDF VSLALRDRRL EFRYDLGKGA AVIRSREPVT LGAWTRVSLE RNGRKGALRV 1740 GDGPRVLGES PKSRKVPHTV LNLKEPLYVG GAPDFSKLAR AAAVSSGFDG AIQLVSLGGR 1800 QLLTPEHVLR QVDVTSFAGH PCTRASGHPC LNGASCVPRE AAYVCLCPGG FSGPHCEKGL 1860 VEKSAGDVDT LAFDGRTFVE YLNAVTESEL ANEIPVPETL DSGALHEKAL QSNHFELSLR 1920 TEATQGLVLW SGKATERADY VALAIVDGHL QLSYNLGSQP VVLRSTVPVN TNRWLRVVAH 1980 REQREGSLQV GNEAPVTGSS PLGATQLDTD GALWLGGLPE LPVGPALPKA YGTGFVGCLR 2040 DVVVGRHPLH LLEDAVTKPE LRPCPTP
2068Fasta Sequence
>O00468|AGRN|Homo sapiens(Human) MAGRSHPGPLRPLLPLLVVAACVLPGAGGTCPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTGDTRIFFVNPAPPYLWPAHKNELMLNSSLMRITLRNLEEVEFCVEDKPGTHFTPVPPTPPDACRGMLCGFGAVCEPNAEGPGRASCVCKKSPCPSVVAPVCGSDASTYSNECELQRAQCSQQRRIRLLSRGPCGSRDPCSNVTCSFGSTCARSADGLTASCLCPATCRGAPEGTVCGSDGADYPGECQLLRRACARQENVFKKFDGPCDPCQGALPDPSRSCRVNPRTRRPEMLLRPESCPARQAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQCQGRDQCPEPCRFNAVCLSRRGRPRCSCDRVTCDGAYRPVCAQDGRTYDSDCWRQQAECRQQRAIPSKHQGPCDQAPSPCLGVQCAFGATCAVKNGQAACECLQACSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPCDRCGQCRFGALCEAETGRCVCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASAGPCETCGDAVCAFGAVCSAGQCVCPRCEHPPPGPVCGSDGVTYGSACELREAACLQQTQIEEARAGPCEQAECGSGGSGSGEDGDCEQELCRQRGGIWDEDSEDGPCVCDFSCQSVPGSPVCGSDGVTYSTECELKKARCESQRGLYVAAQGACRGPTFAPLPPVAPLHCAQTPYGCCQDNITAARGVGLAGCPSACQCNPHGSYGGTCDPATGQCSCRPGVGGLRCDRCEPGFWNFRGIVTDGRSGCTPCSCDPQGAVRDDCEQMTGLCSCKPGVAGPKCGQCPDGRALGPAGCEADASAPATCAEMRCEFGARCVEESGSAHCVCPMLTCPEANATKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPCQEAVAPSTHPTSASVTVTTPGLLLSQALPAPPGALPLAPSSTAHSQTTPPPSSRPRTTASVPRTTVWPVLTVPPTAPSPAPSLVASAFGESGSTDGSSDEELSGDQEASGGGSGGLEPLEGSSVATPGPPVERASCYNSALGCCSDGKTPSLDAEGSNCPATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFDPTTAFRAPDVARALLRQIQVSRRRSLGVRRPLQEHVRFMDFDWFPAFITGATSGAIAAGATARATTASRLPSSAVTPRAPHPSHTSQPVAKTTAAPTTRRPPTTAPSRVPGRRPPAPQQPPKPCDSQPCFHGGTCQDWALGGGFTCSCPAGRGGAVCEKVLGAPVPAFEGRSFLAFPTLRAYHTLRLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGQWHRLELSRHWRRGTLSVDGETPVLGESPSGTDGLNLDTDLFVGGVPEDQAAVALERTFVGAGLRGCIRLLDVNNQRLELGIGPGAATRGSGVGECGDHPCLPNPCHGGAPCQNLEAGRFHCQCPPGRVGPTCADEKSPCQPNPCHGAAPCRVLPEGGAQCECPLGREGTFCQTASGQDGSGPFLADFNGFSHLELRGLHTFARDLGEKMALEVVFLARGPSGLLLYNGQKTDGKGDFVSLALRDRRLEFRYDLGKGAAVIRSREPVTLGAWTRVSLERNGRKGALRVGDGPRVLGESPKSRKVPHTVLNLKEPLYVGGAPDFSKLARAAAVSSGFDGAIQLVSLGGRQLLTPEHVLRQVDVTSFAGHPCTRASGHPCLNGASCVPREAAYVCLCPGGFSGPHCEKGLVEKSAGDVDTLAFDGRTFVEYLNAVTESELANEIPVPETLDSGALHEKALQSNHFELSLRTEATQGLVLWSGKATERADYVALAIVDGHLQLSYNLGSQPVVLRSTVPVNTNRWLRVVAHREQREGSLQVGNEAPVTGSSPLGATQLDTDGALWLGGLPELPVGPALPKAYGTGFVGCLRDVVVGRHPLHLLEDAVTKPELRPCPTP
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Keyword |
KW-0025--Alternative splicing KW-0106--Calcium KW-0965--Cell junction KW-1003--Cell membrane KW-0181--Complete proteome KW-1004--Congenital myasthenic syndrome KW-0217--Developmental protein KW-0221--Differentiation KW-0225--Disease mutation KW-1015--Disulfide bond KW-0245--EGF-like domain KW-0272--Extracellular matrix KW-0325--Glycoprotein KW-0357--Heparan sulfate KW-0424--Laminin EGF-like domain KW-0472--Membrane KW-0597--Phosphoprotein KW-0621--Polymorphism KW-0654--Proteoglycan KW-1185--Reference proteome KW-0677--Repeat KW-0964--Secreted KW-0732--Signal KW-0770--Synapse KW-0812--Transmembrane KW-1133--Transmembrane helix
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Interpro |
IPR013320--ConA-like_dom IPR013032--EGF-like_CS IPR000742--EGF-like_dom IPR003645--Fol_N IPR002350--Kazal_dom IPR002049--Laminin_EGF IPR001791--Laminin_G IPR004850--NtA_dom IPR000082--SEA_dom IPR008993--TIMP-like_OB-fold
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PROSITE |
PS00022--EGF_1 PS01186--EGF_2 PS50026--EGF_3 PS01248--EGF_LAM_1 PS50027--EGF_LAM_2 PS51465--KAZAL_2 PS50025--LAM_G_DOMAIN PS51121--NTA PS50024--SEA
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Pfam |
PF00008--EGF PF00050--Kazal_1 PF07648--Kazal_2 PF00053--Laminin_EGF PF00054--Laminin_G_1 PF03146--NtA PF01390--SEA
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Gene Ontology |
GO:0005605--C:basal lamina GO:0030054--C:cell junction GO:0009986--C:cell surface GO:0005737--C:cytoplasm GO:0070062--C:extracellular exosome GO:0031012--C:extracellular matrix GO:0005576--C:extracellular region GO:0005615--C:extracellular space GO:0005796--C:Golgi lumen GO:0016021--C:integral component of membrane GO:0043202--C:lysosomal lumen GO:0005886--C:plasma membrane GO:0045202--C:synapse GO:0030548--F:acetylcholine receptor regulator activity GO:0005509--F:calcium ion binding GO:0035374--F:chondroitin sulfate binding GO:0002162--F:dystroglycan binding GO:0043395--F:heparan sulfate proteoglycan binding GO:0043236--F:laminin binding GO:0033691--F:sialic acid binding GO:0005200--F:structural constituent of cytoskeleton GO:0007411--P:axon guidance GO:0005975--P:carbohydrate metabolic process GO:0030204--P:chondroitin sulfate metabolic process GO:0045162--P:clustering of voltage-gated sodium channels GO:0030198--P:extracellular matrix organization GO:0007213--P:G-protein coupled acetylcholine receptor signaling pathway GO:0006024--P:glycosaminoglycan biosynthetic process GO:0006027--P:glycosaminoglycan catabolic process GO:0030203--P:glycosaminoglycan metabolic process GO:0007528--P:neuromuscular junction development GO:0045213--P:neurotransmitter receptor metabolic process GO:0007603--P:phototransduction, visible light GO:0007009--P:plasma membrane organization GO:0051491--P:positive regulation of filopodium assembly GO:0043547--P:positive regulation of GTPase activity GO:0043525--P:positive regulation of neuron apoptotic process GO:0045887--P:positive regulation of synaptic growth at neuromuscular junction GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter GO:0043113--P:receptor clustering GO:0001523--P:retinoid metabolic process GO:0007165--P:signal transduction GO:0044281--P:small molecule metabolic process GO:0050808--P:synapse organization GO:0007268--P:synaptic transmission
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