AGRN

Protein identityUniProt · HPA

UniProt accession

O00468

Gene

AGRN

Ensembl

ENSG00000188157

Chromosome

1

Canonical length

2068 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins, Transporters

Subcellular location

Plasma membrane,Cytosol

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

Canonical amino-acid sequenceUniProt

2068 residues, UniProt reviewed canonical sequence.

>O00468|AGRN
     1  MAGRSHPGPL RPLLPLLVVA ACVLPGAGGT CPERALERRE EEANVVLTGT VEEILNVDPV
    61  QHTYSCKVRV WRYLKGKDLV ARESLLDGGN KVVISGFGDP LICDNQVSTG DTRIFFVNPA
   121  PPYLWPAHKN ELMLNSSLMR ITLRNLEEVE FCVEDKPGTH FTPVPPTPPD ACRGMLCGFG
   181  AVCEPNAEGP GRASCVCKKS PCPSVVAPVC GSDASTYSNE CELQRAQCSQ QRRIRLLSRG
   241  PCGSRDPCSN VTCSFGSTCA RSADGLTASC LCPATCRGAP EGTVCGSDGA DYPGECQLLR
   301  RACARQENVF KKFDGPCDPC QGALPDPSRS CRVNPRTRRP EMLLRPESCP ARQAPVCGDD
   361  GVTYENDCVM GRSGAARGLL LQKVRSGQCQ GRDQCPEPCR FNAVCLSRRG RPRCSCDRVT
   421  CDGAYRPVCA QDGRTYDSDC WRQQAECRQQ RAIPSKHQGP CDQAPSPCLG VQCAFGATCA
   481  VKNGQAACEC LQACSSLYDP VCGSDGVTYG SACELEATAC TLGREIQVAR KGPCDRCGQC
   541  RFGALCEAET GRCVCPSECV ALAQPVCGSD GHTYPSECML HVHACTHQIS LHVASAGPCE
   601  TCGDAVCAFG AVCSAGQCVC PRCEHPPPGP VCGSDGVTYG SACELREAAC LQQTQIEEAR
   661  AGPCEQAECG SGGSGSGEDG DCEQELCRQR GGIWDEDSED GPCVCDFSCQ SVPGSPVCGS
   721  DGVTYSTECE LKKARCESQR GLYVAAQGAC RGPTFAPLPP VAPLHCAQTP YGCCQDNITA
   781  ARGVGLAGCP SACQCNPHGS YGGTCDPATG QCSCRPGVGG LRCDRCEPGF WNFRGIVTDG
   841  RSGCTPCSCD PQGAVRDDCE QMTGLCSCKP GVAGPKCGQC PDGRALGPAG CEADASAPAT
   901  CAEMRCEFGA RCVEESGSAH CVCPMLTCPE ANATKVCGSD GVTYGNECQL KTIACRQGLQ
   961  ISIQSLGPCQ EAVAPSTHPT SASVTVTTPG LLLSQALPAP PGALPLAPSS TAHSQTTPPP
  1021  SSRPRTTASV PRTTVWPVLT VPPTAPSPAP SLVASAFGES GSTDGSSDEE LSGDQEASGG
  1081  GSGGLEPLEG SSVATPGPPV ERASCYNSAL GCCSDGKTPS LDAEGSNCPA TKVFQGVLEL
  1141  EGVEGQELFY TPEMADPKSE LFGETARSIE STLDDLFRNS DVKKDFRSVR LRDLGPGKSV
  1201  RAIVDVHFDP TTAFRAPDVA RALLRQIQVS RRRSLGVRRP LQEHVRFMDF DWFPAFITGA
  1261  TSGAIAAGAT ARATTASRLP SSAVTPRAPH PSHTSQPVAK TTAAPTTRRP PTTAPSRVPG
  1321  RRPPAPQQPP KPCDSQPCFH GGTCQDWALG GGFTCSCPAG RGGAVCEKVL GAPVPAFEGR
  1381  SFLAFPTLRA YHTLRLALEF RALEPQGLLL YNGNARGKDF LALALLDGRV QLRFDTGSGP
  1441  AVLTSAVPVE PGQWHRLELS RHWRRGTLSV DGETPVLGES PSGTDGLNLD TDLFVGGVPE
  1501  DQAAVALERT FVGAGLRGCI RLLDVNNQRL ELGIGPGAAT RGSGVGECGD HPCLPNPCHG
  1561  GAPCQNLEAG RFHCQCPPGR VGPTCADEKS PCQPNPCHGA APCRVLPEGG AQCECPLGRE
  1621  GTFCQTASGQ DGSGPFLADF NGFSHLELRG LHTFARDLGE KMALEVVFLA RGPSGLLLYN
  1681  GQKTDGKGDF VSLALRDRRL EFRYDLGKGA AVIRSREPVT LGAWTRVSLE RNGRKGALRV
  1741  GDGPRVLGES PKSRKVPHTV LNLKEPLYVG GAPDFSKLAR AAAVSSGFDG AIQLVSLGGR
  1801  QLLTPEHVLR QVDVTSFAGH PCTRASGHPC LNGASCVPRE AAYVCLCPGG FSGPHCEKGL
  1861  VEKSAGDVDT LAFDGRTFVE YLNAVTESEL ANEIPVPETL DSGALHSEKA LQSNHFELSL
  1921  RTEATQGLVL WSGKATERAD YVALAIVDGH LQLSYNLGSQ PVVLRSTVPV NTNRWLRVVA
  1981  HREQREGSLQ VGNEAPVTGS SPLGATQLDT DGALWLGGLP ELPVGPALPK AYGTGFVGCL
  2041  RDVVVGRHPL HLLEDAVTKP ELRPCPTP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AGRN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

41 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AGRN.

Disease | AllUniProt

Conditions AGRN is implicated in, by any mechanism.

• Myasthenic syndrome, congenital, 8 (CMS8) MIM:615120

Disease | GeneticClinVar

66 pathogenic / likely-pathogenic of 2,567 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital myasthenic syndrome 8
• Congenital myasthenic syndrome
• Presynaptic congenital myasthenic syndrome
• Abnormality of the musculature
• Neurodevelopmental disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0

gnomAD missense Z

0.23

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• chondrocyte differentiation
• clustering of voltage-gated sodium channels
• filopodium assembly
• G protein-coupled acetylcholine receptor signaling pathway
• neuromuscular junction development
• positive regulation of transcription by RNA polymerase II
• receptor clustering
• signal transduction
• synapse organization
• positive regulation of synaptic assembly at neuromuscular junction

Molecular functions

• calcium ion binding
• chondroitin sulfate binding
• dystroglycan binding
• heparan sulfate proteoglycan binding
• laminin binding
• receptor ligand activity
• sialic acid binding
• structural constituent of cytoskeleton

Cellular components

• basement membrane
• extracellular exosome
• extracellular matrix
• extracellular region
• Golgi lumen
• lysosomal lumen
• plasma membrane
• synapse

Protein domainsUniProt · Pfam · InterPro

• SEA domain
• EGF-like domain
• Laminin G domain
• EGF-like calcium-binding domain
• Laminin-type EGF domain
• Kazal domain
• Follistatin-like, N-terminal
• Factor I / membrane attack complex
• Tissue inhibitor of metalloproteinases-like, OB-fold
• Concanavalin A-like lectin/glucanase domain superfamily
• Kazal domain superfamily
• SEA domain superfamily
• Neurexin-related cell adhesion and synaptic protein
• EGF-like domain
• Kazal-type serine protease inhibitor domain
• Laminin EGF domain
• Laminin G domain
• SEA domain
• Kazal-type serine protease inhibitor domain
• NtA (N-terminal agrin) domain
• Agrin NtA domain

KeywordsUniProt

• Calcium
• Cell membrane
• Congenital myasthenic syndrome
• Developmental protein
• Differentiation
• Disulfide bond
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Heparan sulfate
• Laminin EGF-like domain
• Membrane
• Metal-binding
• Phosphoprotein
• Proteoglycan
• Repeat
• Secreted
• Signal
• Synapse
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of AGRN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DAG1
• TGFB1