Protein detail

AGRIN

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)]

Entry name AGRIN	UniProt ID O00468	EVMP confidence score 0.75
Supporting publications (n) 36	Transmembrane count	Protein classification Disease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted secreted proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information11

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 Class (7)

Disease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted secreted proteinsTransporters

Protein Function (6)

Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
Predicted intracellular proteins
Potential drug targets
Predicted secreted proteins
Transporters:Accessory Factors Involved in Transport
Disease related genes

Ensembl

ENSG00000188157

Entrez Gene Symbol

AGRN

Gene Synonym

AGRIN

Gene Description

Agrin

Chromosome

Position

1020120-1056118

Supporting publications (n)

EVMP confidence score

0.75

Function & Pathway8

Protein Function (6)

Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
Predicted intracellular proteins
Potential drug targets
Predicted secreted proteins
Transporters:Accessory Factors Involved in Transport
Disease related genes

Cellular Component (8)

Molecular Function (9)

Biological Process (3)

KEGG (2)

Reactome (35)

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Canonical Pathways (3)

M3468 Naba ecm regulators
M5885 Naba matrisome associated
M5889 Naba matrisome

Mediation Categories (4)

Clinical-translation mediationImmune mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence31

Ligand-Receptor Signaling (26)

26 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
ecm	ecm	GO_Intercell	Yes	No	Yes	No	No
ecm	ecm	Ramilowski_location	Yes	No	Yes	No	No
ecm	ecm	UniProt_location	Yes	No	Yes	No	No
proteoglycan	ecm	OmniPath	Yes	No	Yes	No	No
ecm	ecm	OmniPath	Yes	No	Yes	No	No
extracellular	extracellular	HPMR	No	No	Yes	No	No
extracellular	extracellular	LOCATE	No	No	Yes	No	No
extracellular	extracellular	OmniPath	No	No	Yes	No	No
intracellular	intracellular	ComPPI	No	No	Yes	No	No
intracellular	intracellular	GO_Intercell	No	No	Yes	No	No

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Regulatory Interaction Network (3)

3 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
AGRIN	O00468	MUSK	O15146	Yes	Yes	No	HPMRFantom5_LRdbCellTalkDBHPMR_LRdbiTALKHPMR_CellinkertalklrRamilowski2015Reactome_LRdbconnectomeDB2020HINTSignaLink3CellinkerLRdbHPMR_talklr	SignaLink3:18848351 HPMR:8653787 connectomeDB2020:8653787 Cellinker:8653787 LRdb:8653787 HINT:37252960 SignaLink3:23331499 CellTalkDB:8653787
AGRIN	O00468	LRP4	O75096	Yes	Yes	No	Fantom5_LRdbCellTalkDBiTALKtalklrSIGNORReactome_LRdbconnectomeDB2020HINTCellinkerLRdbRamilowski2015	SIGNOR:23458718 Cellinker:18848351 LRdb:18848351 HINT:37252960 Ramilowski2015:18848351 talklr:18848351 connectomeDB2020:18848351
AGRIN	O00468	ACHB3	Q05901	Yes	Yes	No	SIGNOR	SIGNOR:14502292

Protein Complex Composition (1)

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	AGRN APP COPG1 FOS	O00468 P01100 P05067 Q9Y678	1:1:1:1	NetworkBlastCompleat	Compleat:HC4016

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometryWestern blottingFlow cytometry	4	37862381 39290459 30550287 40098346

Sequence, Structure & Domains10

Sequences

Length

2,068

Mass

217,320

Sequence

MAGRSHPGPLRPLLPLLVVAACVLPGAGGTCPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTGDTRIFFVNPAPPYLWPAHKNELMLNSSLMRITLRNLEEVEFCVEDKPGTHFTPVPPTPPDACRGMLCGFGAVCEPNAEGPGRASCVCKKSPCPSVVAPVCGSDASTYSNECELQRAQCSQQRRIRLLSRGPCGSRDPCSNVTCSFGSTCARSADGLTASCLCPATCRGAPEGTVCGSDGADYPGECQLLRRACARQENVFKKFDGPCDPCQGALPDPSRSCRVNPRTRRPEMLLRPESCPARQAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQCQGRDQCPEPCRFNAVCLSRRGRPRCSCDRVTCDGAYRPVCAQDGRTYDSDCWRQQAECRQQRAIPSKHQGPCDQAPSPCLGVQCAFGATCAVKNGQAACECLQACSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPCDRCGQCRFGALCEAETGRCVCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASAGPCETCGDAVCAFGAVCSAGQCVCPRCEHPPPGPVCGSDGVTYGSACELREAACLQQTQIEEARAGPCEQAECGSGGSGSGEDGDCEQELCRQRGGIWDEDSEDGPCVCDFSCQSVPGSPVCGSDGVTYSTECELKKARCESQRGLYVAAQGACRGPTFAPLPPVAPLHCAQTPYGCCQDNITAARGVGLAGCPSACQCNPHGSYGGTCDPATGQCSCRPGVGGLRCDRCEPGFWNFRGIVTDGRSGCTPCSCDPQGAVRDDCEQMTGLCSCKPGVAGPKCGQCPDGRALGPAGCEADASAPATCAEMRCEFGARCVEESGSAHCVCPMLTCPEANATKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPCQEAVAPSTHPTSASVTVTTPGLLLSQALPAPPGALPLAPSSTAHSQTTPPPSSRPRTTASVPRTTVWPVLTVPPTAPSPAPSLVASAFGESGSTDGSSDEELSGDQEASGGGSGGLEPLEGSSVATPGPPVERASCYNSALGCCSDGKTPSLDAEGSNCPATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFDPTTAFRAPDVARALLRQIQVSRRRSLGVRRPLQEHVRFMDFDWFPAFITGATSGAIAAGATARATTASRLPSSAVTPRAPHPSHTSQPVAKTTAAPTTRRPPTTAPSRVPGRRPPAPQQPPKPCDSQPCFHGGTCQDWALGGGFTCSCPAGRGGAVCEKVLGAPVPAFEGRSFLAFPTLRAYHTLRLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGQWHRLELSRHWRRGTLSVDGETPVLGESPSGTDGLNLDTDLFVGGVPEDQAAVALERTFVGAGLRGCIRLLDVNNQRLELGIGPGAATRGSGVGECGDHPCLPNPCHGGAPCQNLEAGRFHCQCPPGRVGPTCADEKSPCQPNPCHGAAPCRVLPEGGAQCECPLGREGTFCQTASGQDGSGPFLADFNGFSHLELRGLHTFARDLGEKMALEVVFLARGPSGLLLYNGQKTDGKGDFVSLALRDRRLEFRYDLGKGAAVIRSREPVTLGAWTRVSLERNGRKGALRVGDGPRVLGESPKSRKVPHTVLNLKEPLYVGGAPDFSKLARAAAVSSGFDGAIQLVSLGGRQLLTPEHVLRQVDVTSFAGHPCTRASGHPCLNGASCVPREAAYVCLCPGGFSGPHCEKGLVEKSAGDVDTLAFDGRTFVEYLNAVTESELANEIPVPETLDSGALHSEKALQSNHFELSLRTEATQGLVLWSGKATERADYVALAIVDGHLQLSYNLGSQPVVLRSTVPVNTNRWLRVVAHREQREGSLQVGNEAPVTGSSPLGATQLDTDGALWLGGLPELPVGPALPKAYGTGFVGCLRDVVVGRHPLHLLEDAVTKPELRPCPTP

Alternative Products

Event=Alternative splicing; Named isoforms=7; Comment=Many isoforms may exist depending on the occurrence and length of inserts at the x, y or z splice site. Four 'z' isoforms can be produced with inserts of 0, 8, 11 or 19 AA. Isoform 3 and isoform 6 lack any 'z' insert. Isoforms differ in their acetylcholine receptor clustering activity and tissue specificity.; Name=1; Synonyms=Secreted agrin, LN-agrin; IsoId=O00468-1; Sequence=Displayed; Name=2; Synonyms=Transmembrane agrin, TM-agrin; IsoId=O00468-2; Sequence=VSP_045753, VSP_045754; Name=3; Synonyms=Agrin z(0); IsoId=O00468-3; Sequence=VSP_045756; Name=4; Synonyms=Agrin z(+11); IsoId=O00468-4; Sequence=VSP_045757; Name=5; Synonyms=Agrin z(+8); IsoId=O00468-5; Sequence=VSP_045758; Name=6; Synonyms=Agrin y(0)z(0); IsoId=O00468-6; Sequence=VSP_045755, VSP_045756; Name=7; Synonyms=y(0); IsoId=O00468-7; Sequence=VSP_045755

Alternative Sequence

1..104; Missing (in isoform 2); 105..154; NQVSTGDTRIFFVNPAPPYLWPAHKNELMLNSSLMRITLRNLEEVEFCVE -> MPXLAVARDTRQPAGASLLVRGFMVPCNACLILLATATLGFAVLLFLNNY (in isoform 2); 1752..1755; Missing (in isoform 6 and isoform 7); 1889..1907; Missing (in isoform 3 and isoform 6); 1889..1896; Missing (in isoform 4); 1897..1907; Missing (in isoform 5)

3D Structural Models

3D Structure

Electron microscopy (1)

Domain & Motif Annotations

Compositional Bias

1023..1042; Low complexity; 1050..1065; Low complexity; 1297..1318; Low complexity; 1321..1332; Pro residues

Domain (CC)

The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina.; DOMAIN: Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan/DAG1 binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding (By similarity).

Domain (FT)

31..157; NtA; 191..244; Kazal-like 1; 264..319; Kazal-like 2; 337..391; Kazal-like 3; 408..463; Kazal-like 4; 484..536; Kazal-like 5; 540..601; Kazal-like 6; 607..666; Kazal-like 7; 699..752; Kazal-like 8; 793..846; Laminin EGF-like 1; 847..893; Laminin EGF-like 2; 917..971; Kazal-like 9; 1130..1252; SEA; 1329..1367; EGF-like 1; 1372..1548; Laminin G-like 1; 1549..1586; EGF-like 2; 1588..1625; EGF-like 3; 1635..1822; Laminin G-like 2; 1818..1857; EGF-like 4; 1868..2065; Laminin G-like 3

Region

995..1096; Disordered; 1277..1334; Disordered

Clinical Relevance2

Disease Involvement (2)

Congenital myasthenic syndromeDisease variant

Antibody

HPA040090

Supporting Publications32

PMID	Title	Abstract
19837982	Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature.	A conspicuous finding of this comparative analysis was the presence of host cell-specific (LIM1215 exosome) proteins such as A33, cadherin-17, carcinoembryonic antigen, epithelial cell surface antigen (EpCAM), proliferating cell nuclear antigen, epidermal growth factor receptor, mucin 13, misshapen-like kinase 1, keratin 18, mitogen-activated protein kinase 4, claudins (1, 3, and 7), centrosomal protein 55 kDa, and ephrin-B1 and -B2. Here, we describe an immunoaffinity capture method using the colon epithelial cell-specific A33 antibody to purify colorectal cancer cell (LIM1215)-derived exosomes.
22740476	Restoration of full-length APC protein in SW480 colon cancer cells induces exosome-mediated secretion of DKK-4.	No abstract available
23161513	Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.	Exosomes from mutant KRAS cells contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases, and integrins.
27894104	Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers.	No abstract available
28986585	Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics.	No abstract available
29045505	Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients.	Proteomic analysis of the exosome 'surfaceome' revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers.
30379855	Harmonization of exosome isolation from culture supernatants for optimized proteomics analysis.	No abstract available
30585730	Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer.	No abstract available
30646616	Preferential Localization of MUC1 Glycoprotein in Exosomes Secreted by Non-Small Cell Lung Carcinoma Cells.	THBS1, ANXA6, HIST1H4A, COL18A1, MDK, SRGN, ENO1, TUBA4A, SLC3A2, GPI, MIF, MUC1, TALDO1, SLC7A5, ICAM1, HSP90AA1, G6PD, and LRP1 were found to be expressed in exosomes at more than 5-fold higher level as compared to total cellular membrane proteins.
30915084	Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton.	No abstract available

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