CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000082
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Agrin 
Protein Synonyms/Alias
 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 
Gene Name
 AGRN 
Gene Synonyms/Alias
 AGRIN 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
1418YNGNARGKDFLALALubiquitination[1]
Reference
 [1] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
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 homestasis 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. 
Sequence Annotation
 DOMAIN 30 157 NtA.
 DOMAIN 191 244 Kazal-like 1.
 DOMAIN 264 319 Kazal-like 2.
 DOMAIN 337 391 Kazal-like 3.
 DOMAIN 408 463 Kazal-like 4.
 DOMAIN 484 536 Kazal-like 5.
 DOMAIN 540 601 Kazal-like 6.
 DOMAIN 607 666 Kazal-like 7.
 DOMAIN 699 752 Kazal-like 8.
 DOMAIN 793 846 Laminin EGF-like 1.
 DOMAIN 847 893 Laminin EGF-like 2.
 DOMAIN 917 971 Kazal-like 9.
 DOMAIN 1130 1252 SEA.
 DOMAIN 1329 1367 EGF-like 1.
 DOMAIN 1372 1548 Laminin G-like 1.
 DOMAIN 1549 1586 EGF-like 2.
 DOMAIN 1588 1625 EGF-like 3.
 DOMAIN 1635 1822 Laminin G-like 2.
 DOMAIN 1818 1857 EGF-like 4.
 DOMAIN 1868 2064 Laminin G-like 3.
 CARBOHYD 135 135 N-linked (GlcNAc...).
 CARBOHYD 250 250 N-linked (GlcNAc...) (Potential).
 CARBOHYD 777 777 N-linked (GlcNAc...) (Potential).
 CARBOHYD 932 932 N-linked (GlcNAc...) (Potential).
 CARBOHYD 1835 1835 O-linked (Fuc...) (By similarity).
 DISULFID 31 103 By similarity.
 DISULFID 152 177 Or C-152 with C-183 (By similarity).
 DISULFID 793 805 By similarity.
 DISULFID 795 812 By similarity.
 DISULFID 814 823 By similarity.
 DISULFID 826 844 By similarity.
 DISULFID 847 859 By similarity.
 DISULFID 849 866 By similarity.
 DISULFID 868 877 By similarity.
 DISULFID 880 891 By similarity.
 DISULFID 1333 1344 By similarity.
 DISULFID 1338 1355 By similarity.
 DISULFID 1357 1366 By similarity.
 DISULFID 1519 1548 By similarity.
 DISULFID 1553 1564 By similarity.
 DISULFID 1558 1574 By similarity.
 DISULFID 1576 1585 By similarity.
 DISULFID 1592 1603 By similarity.
 DISULFID 1597 1613 By similarity.
 DISULFID 1615 1624 By similarity.
 DISULFID 1822 1836 By similarity.
 DISULFID 1830 1845 By similarity.
 DISULFID 1847 1856 By similarity.
 DISULFID 2038 2064 By similarity.  
Keyword
 Alternative splicing; Calcium; Cell junction; Cell membrane; Complete proteome; Congenital myasthenic syndrome; Developmental protein; Differentiation; Disease mutation; Disulfide bond; EGF-like domain; Extracellular matrix; Glycoprotein; Heparan sulfate; Laminin EGF-like domain; Membrane; Polymorphism; Proteoglycan; Reference proteome; Repeat; Secreted; Signal; Synapse; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2067 AA 
Protein Sequence
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 2067 
Gene Ontology
 GO:0005605; C:basal lamina; IDA:UniProtKB.
 GO:0030054; C:cell junction; IEA:UniProtKB-KW.
 GO:0005796; C:Golgi lumen; TAS:Reactome.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0043202; C:lysosomal lumen; TAS:Reactome.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0045202; C:synapse; ISS:UniProtKB.
 GO:0005509; F:calcium ion binding; ISS:UniProtKB.
 GO:0035374; F:chondroitin sulfate binding; ISS:UniProtKB.
 GO:0002162; F:dystroglycan binding; ISS:UniProtKB.
 GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
 GO:0043236; F:laminin binding; TAS:UniProtKB.
 GO:0033691; F:sialic acid binding; ISS:UniProtKB.
 GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
 GO:0030204; P:chondroitin sulfate metabolic process; TAS:Reactome.
 GO:0045162; P:clustering of voltage-gated sodium channels; TAS:UniProtKB.
 GO:0007213; P:G-protein coupled acetylcholine receptor signaling pathway; TAS:UniProtKB.
 GO:0006024; P:glycosaminoglycan biosynthetic process; TAS:Reactome.
 GO:0006027; P:glycosaminoglycan catabolic process; TAS:Reactome.
 GO:0007603; P:phototransduction, visible light; TAS:Reactome.
 GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB.
 GO:0032321; P:positive regulation of Rho GTPase activity; ISS:UniProtKB.
 GO:0045887; P:positive regulation of synaptic growth at neuromuscular junction; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0043113; P:receptor clustering; IDA:UniProtKB.
 GO:0001523; P:retinoid metabolic process; TAS:Reactome.
 GO:0050808; P:synapse organization; TAS:UniProtKB. 
Interpro
 IPR004850; Agrin_NtA.
 IPR008985; ConA-like_lec_gl_sf.
 IPR013320; ConA-like_subgrp.
 IPR000742; EG-like_dom.
 IPR013032; EGF-like_CS.
 IPR002049; EGF_laminin.
 IPR003645; Fol_N.
 IPR002350; Kazal_dom.
 IPR001791; Laminin_G.
 IPR000082; SEA_dom.
 IPR008993; TIMP-like_OB-fold. 
Pfam
 PF00008; EGF
 PF00050; Kazal_1
 PF07648; Kazal_2
 PF00053; Laminin_EGF
 PF00054; Laminin_G_1
 PF03146; NtA
 PF01390; SEA 
SMART
 SM00181; EGF
 SM00180; EGF_Lam
 SM00274; FOLN
 SM00280; KAZAL
 SM00282; LamG
 SM00200; SEA 
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 
PRINTS