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O00468 (AGRIN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Agrin
Gene names
Name:AGRN
Synonyms:AGRIN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2067 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 formsa bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain. Ref.11 Ref.13

Isoform 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. Ref.11 Ref.13

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. Ref.11 Ref.13

Isoform 3 and isoform 6:lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation. Ref.11 Ref.13

Agrin N-terminal 110 kDa subunit: 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. Ref.11 Ref.13

Agrin C-terminal 22 kDa fragment: 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. Ref.11 Ref.13

Subunit structure

Monomer By similarity. Interacts (N-terminal subunit) with TGF-beta family members, BMP2 AND BMP4; the interactions inhibit the activity of these growth factors. Interacts with TGFB1; the interaction enhances the activity of TGFB1 By similarity. Component of the AGRN-LRP4 complex that consists of a tetramer of two AGRN-LRP4 heterodimers. Interacts (via the laminin G-like 3 domain) directly with LRP4; the interaction is required for activation of MUSK and clustering of AChR and requires the 'z8' insert present in the z(+8) isoforms. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by alternative splicing of AGRN. Ref.4 Ref.11 Ref.15

Subcellular location

Isoform 1: Secretedextracellular spaceextracellular matrix. Note: Synaptic basal lamina at the neuromuscular junction By similarity. Ref.10

Isoform 2: Cell junctionsynapse. Cell membrane; Single-pass type II membrane protein Ref.10.

Tissue specificity

Expressed in basement membranes of lung and kidney. Muscle- and neuron-specific isoforms are found. Isoforms (y+) with the 4 AA insert and (z+8) isoforms with the 8 AA insert are all neuron-specific. Isoforms (z+11) are found in both neuronal and non-neuronal tissues. Ref.1 Ref.7 Ref.10

Domain

The NtA domain, absent in TM-agrin, is required for binding laminin and connecting to basal lamina.

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.

Post-translational modification

Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, are required for induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains heparan sulfate (HS) chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains. Heparin and heparin sulfate binding in the G3 domain is independent of calcium ions. Binds heparin with a stoichiometry of 2:1. Binds sialic acid with a stoichiometry of 1:1 and binding requires calcium ions By similarity.

At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site produces the agrin N-terminal 110-kDa subunit and the agrin C-terminal 110-kDa subunit. Further cleavage of agrin C-terminal 110-kDa subunit at the beta site produces the C-terminal fragments, agrin C-terminal 90 kDa fragment and agrin C-terminal 22 kDa fragment. Excessive cleavage at the beta-site releases large amounts of the agrin C-terminal 22 kDa fragment leading to destabilization at the neuromuscular junction (NMJ).

Involvement in disease

Myasthenia, limb-girdle, familial (LGM) [MIM:254300]: A congenital myasthenic syndrome characterized by a typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.15

Miscellaneous

Cleaved C-terminal fragments may be used as a biomarker for sarcopenia, age-related progressive loss of skeletal muscle (Ref.12).

Sequence similarities

Contains 4 EGF-like domains.

Contains 9 Kazal-like domains.

Contains 2 laminin EGF-like domains.

Contains 3 laminin G-like domains.

Contains 1 NtA (N-terminal agrin) domain.

Contains 1 SEA domain.

Caution

The unknown residue 'x' in the transmembrane isoform isprobably a proline residue by similarity to mouse and rat sequences.

Ontologies

Keywords
   Biological processDifferentiation
   Cellular componentCell junction
Cell membrane
Extracellular matrix
Membrane
Secreted
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCongenital myasthenic syndrome
Disease mutation
   DomainEGF-like domain
Laminin EGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Heparan sulfate
Proteoglycan
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled acetylcholine receptor signaling pathway

Traceable author statement PubMed 9405491. Source: UniProtKB

axon guidance

Traceable author statement. Source: Reactome

carbohydrate metabolic process

Traceable author statement. Source: Reactome

chondroitin sulfate metabolic process

Traceable author statement. Source: Reactome

clustering of voltage-gated sodium channels

Traceable author statement PubMed 9405491. Source: UniProtKB

extracellular matrix organization

Traceable author statement. Source: Reactome

glycosaminoglycan biosynthetic process

Traceable author statement. Source: Reactome

glycosaminoglycan catabolic process

Traceable author statement. Source: Reactome

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

neuromuscular junction development

Inferred from electronic annotation. Source: Ensembl

neurotransmitter receptor metabolic process

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

plasma membrane organization

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rho GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of filopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of synaptic growth at neuromuscular junction

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

receptor clustering

Inferred from direct assay PubMed 15340048. Source: UniProtKB

retinoid metabolic process

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement Ref.1. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

synapse organization

Traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

basal lamina

Inferred from direct assay PubMed 9405491. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

extracellular matrix

Inferred from direct assay PubMed 17628813. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708PubMed 20458337. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosomal lumen

Traceable author statement. Source: Reactome

plasma membrane

Inferred from direct assay. Source: HPA

synapse

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionacetylcholine receptor regulator activity

Inferred from electronic annotation. Source: Ensembl

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

chondroitin sulfate binding

Inferred from sequence or structural similarity. Source: UniProtKB

dystroglycan binding

Inferred from sequence or structural similarity. Source: UniProtKB

heparan sulfate proteoglycan binding

Inferred from sequence or structural similarity. Source: UniProtKB

laminin binding

Traceable author statement Ref.1. Source: UniProtKB

sialic acid binding

Inferred from sequence or structural similarity. Source: UniProtKB

structural constituent of cytoskeleton

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATXN7O152652EBI-947482,EBI-708350

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: 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. Isoforms differ in their acetylcholine receptor clustering activity and tissue specificity.
Isoform 1 (identifier: O00468-1)

Also known as: Secreted agrin; LN-agrin;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O00468-2)

Also known as: Transmembrane agrin; TM-agrin;

The sequence of this isoform differs from the canonical sequence as follows:
     1-104: Missing.
     105-154: NQVSTGDTRI...NLEEVEFCVE → MPXLAVARDT...FAVLLFLNNY
Note: Produced by usage of an alternative first exon.
Isoform 3 (identifier: O00468-3)

Also known as: Agrin z(0);

The sequence of this isoform differs from the canonical sequence as follows:
     1889-1906: Missing.
Isoform 4 (identifier: O00468-4)

Also known as: Agrin z(+11);

The sequence of this isoform differs from the canonical sequence as follows:
     1889-1896: Missing.
Isoform 5 (identifier: O00468-5)

Also known as: Agrin z(+8);

The sequence of this isoform differs from the canonical sequence as follows:
     1897-1906: Missing.
Isoform 6 (identifier: O00468-6)

Also known as: Agrin y(0)z(0);

The sequence of this isoform differs from the canonical sequence as follows:
     1752-1755: Missing.
     1889-1906: Missing.
Isoform 7 (identifier: O00468-7)

Also known as: y(0);

The sequence of this isoform differs from the canonical sequence as follows:
     1752-1755: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Chain30 – 20672038Agrin
PRO_0000007471
Chain30 – 11021073Agrin N-terminal 110 kDa subunit By similarity
PRO_0000421613
Chain1103 – 2067965Agrin C-terminal 110 kDa subunit By similarity
PRO_0000421614
Chain1103 – 1863761Agrin C-terminal 90 kDa fragment By similarity
PRO_0000421615
Chain1864 – 2067204Agrin C-terminal 22 kDa fragment By similarity
PRO_0000421616

Regions

Domain30 – 157128NtA
Domain191 – 24454Kazal-like 1
Domain264 – 31956Kazal-like 2
Domain337 – 39155Kazal-like 3
Domain408 – 46356Kazal-like 4
Domain484 – 53653Kazal-like 5
Domain540 – 60162Kazal-like 6
Domain607 – 66660Kazal-like 7
Domain699 – 75254Kazal-like 8
Domain793 – 84654Laminin EGF-like 1
Domain847 – 89347Laminin EGF-like 2
Domain917 – 97155Kazal-like 9
Domain1130 – 1252123SEA
Domain1329 – 136739EGF-like 1
Domain1372 – 1548177Laminin G-like 1
Domain1549 – 158638EGF-like 2
Domain1588 – 162538EGF-like 3
Domain1635 – 1822188Laminin G-like 2
Domain1818 – 185740EGF-like 4
Domain1868 – 2064197Laminin G-like 3
Calcium binding1940 – 200869 By similarity
Compositional bias671 – 6777Gly/Ser-rich
Compositional bias974 – 1099126Ser/Thr-rich
Compositional bias1058 – 109740Gly/Ser-rich
Compositional bias1254 – 132471Ser/Thr-rich

Sites

Site1102 – 11032Cleavage, alpha site; by neurotrypsin By similarity
Site12501Alternative splice site to produce 'x' isoforms By similarity
Site17511Alternative splice site to produce 'y' isoforms By similarity
Site18621Critical for cleavage by neurotrypsin By similarity
Site1863 – 18642Cleavage, beta site; by neurotrypsin By similarity
Site18881Alternative splice site to produce 'z' isoforms By similarity
Site18921Highly important for the agrin receptor complex activity of the 'z(8)' insert By similarity

Amino acid modifications

Glycosylation1351N-linked (GlcNAc...) Ref.9
Glycosylation2501N-linked (GlcNAc...) Potential
Glycosylation7771N-linked (GlcNAc...) Potential
Glycosylation9321N-linked (GlcNAc...) Potential
Glycosylation18351O-linked (Fuc...) By similarity
Disulfide bond31 ↔ 103 By similarity
Disulfide bond152 ↔ 177Or C-152 with C-183 By similarity
Disulfide bond793 ↔ 805 By similarity
Disulfide bond795 ↔ 812 By similarity
Disulfide bond814 ↔ 823 By similarity
Disulfide bond826 ↔ 844 By similarity
Disulfide bond847 ↔ 859 By similarity
Disulfide bond849 ↔ 866 By similarity
Disulfide bond868 ↔ 877 By similarity
Disulfide bond880 ↔ 891 By similarity
Disulfide bond1333 ↔ 1344 By similarity
Disulfide bond1338 ↔ 1355 By similarity
Disulfide bond1357 ↔ 1366 By similarity
Disulfide bond1519 ↔ 1548 By similarity
Disulfide bond1553 ↔ 1564 By similarity
Disulfide bond1558 ↔ 1574 By similarity
Disulfide bond1576 ↔ 1585 By similarity
Disulfide bond1592 ↔ 1603 By similarity
Disulfide bond1597 ↔ 1613 By similarity
Disulfide bond1615 ↔ 1624 By similarity
Disulfide bond1822 ↔ 1836 By similarity
Disulfide bond1830 ↔ 1845 By similarity
Disulfide bond1847 ↔ 1856 By similarity
Disulfide bond2038 ↔ 2064 By similarity

Natural variations

Alternative sequence1 – 104104Missing in isoform 2.
VSP_045753
Alternative sequence105 – 15450NQVST…EFCVE → MPXLAVARDTRQPAGASLLV RGFMVPCNACLILLATATLG FAVLLFLNNY in isoform 2.
VSP_045754
Alternative sequence1752 – 17554Missing in isoform 6 and isoform 7.
VSP_045755
Alternative sequence1889 – 190618Missing in isoform 3 and isoform 6.
VSP_045756
Alternative sequence1889 – 18968Missing in isoform 4.
VSP_045757
Alternative sequence1897 – 190610Missing in isoform 5.
VSP_045758
Natural variant231V → L. Ref.13
VAR_068724
Natural variant581D → N. Ref.13
VAR_068725
Natural variant1051N → I. Ref.13
VAR_068726
Natural variant2671T → M. Ref.13
VAR_068727
Natural variant3751A → S. Ref.13
Corresponds to variant rs138031468 [ dbSNP | Ensembl ].
VAR_068728
Natural variant7281E → V. Ref.13
Corresponds to variant rs113288277 [ dbSNP | Ensembl ].
VAR_068729
Natural variant8521Q → R. Ref.13
Corresponds to variant rs9697293 [ dbSNP | Ensembl ].
VAR_068730
Natural variant9841V → M. Ref.13
VAR_068731
Natural variant10881L → F. Ref.13
Corresponds to variant rs150132566 [ dbSNP | Ensembl ].
VAR_068732
Natural variant11181T → K. Ref.13
Corresponds to variant rs149159118 [ dbSNP | Ensembl ].
VAR_068733
Natural variant11351Q → R. Ref.13
Corresponds to variant rs142416636 [ dbSNP | Ensembl ].
VAR_068734
Natural variant12401P → L. Ref.13
Corresponds to variant rs142620337 [ dbSNP | Ensembl ].
VAR_068735
Natural variant13411G → R. Ref.13
VAR_068736
Natural variant14511P → L. Ref.13
VAR_068737
Natural variant15141A → T. Ref.13
Corresponds to variant rs111818381 [ dbSNP | Ensembl ].
VAR_068738
Natural variant15651Q → H. Ref.13
Corresponds to variant rs199876002 [ dbSNP | Ensembl ].
VAR_068739
Natural variant16661V → I. Ref.13
Corresponds to variant rs17160775 [ dbSNP | Ensembl ].
VAR_048966
Natural variant16711R → Q. Ref.13
VAR_068740
Natural variant16981R → P. Ref.13
VAR_068741
Natural variant17091G → R in LGM; results in disruption of the neuromuscular junction architecture; does not affect phosphorylation of MUSK; does not affect AChR clustering. Ref.13
VAR_068742
Natural variant17271V → F in LGM; decreased AGRN-induced clustering of AChR by >100-fold and decreased phosphorylation of the MUSK receptor and AChR beta subunit by about 10-fold. Increased binding to alpha-dystroglycan. Ref.15
VAR_069066
Natural variant17341R → H. Ref.13
Corresponds to variant rs145444272 [ dbSNP | Ensembl ].
VAR_068743
Natural variant17891D → N. Ref.13
VAR_068744
Natural variant20451G → V. Ref.13
VAR_068745

Experimental info

Sequence conflict3431L → R in AAB52917. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Secreted agrin) (LN-agrin) [UniParc].

Last modified March 6, 2013. Version 5.
Checksum: E7FAAB9AFB7B8039

FASTA2,067217,232
        10         20         30         40         50         60 
MAGRSHPGPL RPLLPLLVVA ACVLPGAGGT CPERALERRE EEANVVLTGT VEEILNVDPV 

        70         80         90        100        110        120 
QHTYSCKVRV WRYLKGKDLV ARESLLDGGN KVVISGFGDP LICDNQVSTG DTRIFFVNPA 

       130        140        150        160        170        180 
PPYLWPAHKN ELMLNSSLMR ITLRNLEEVE FCVEDKPGTH FTPVPPTPPD ACRGMLCGFG 

       190        200        210        220        230        240 
AVCEPNAEGP GRASCVCKKS PCPSVVAPVC GSDASTYSNE CELQRAQCSQ QRRIRLLSRG 

       250        260        270        280        290        300 
PCGSRDPCSN VTCSFGSTCA RSADGLTASC LCPATCRGAP EGTVCGSDGA DYPGECQLLR 

       310        320        330        340        350        360 
RACARQENVF KKFDGPCDPC QGALPDPSRS CRVNPRTRRP EMLLRPESCP ARQAPVCGDD 

       370        380        390        400        410        420 
GVTYENDCVM GRSGAARGLL LQKVRSGQCQ GRDQCPEPCR FNAVCLSRRG RPRCSCDRVT 

       430        440        450        460        470        480 
CDGAYRPVCA QDGRTYDSDC WRQQAECRQQ RAIPSKHQGP CDQAPSPCLG VQCAFGATCA 

       490        500        510        520        530        540 
VKNGQAACEC LQACSSLYDP VCGSDGVTYG SACELEATAC TLGREIQVAR KGPCDRCGQC 

       550        560        570        580        590        600 
RFGALCEAET GRCVCPSECV ALAQPVCGSD GHTYPSECML HVHACTHQIS LHVASAGPCE 

       610        620        630        640        650        660 
TCGDAVCAFG AVCSAGQCVC PRCEHPPPGP VCGSDGVTYG SACELREAAC LQQTQIEEAR 

       670        680        690        700        710        720 
AGPCEQAECG SGGSGSGEDG DCEQELCRQR GGIWDEDSED GPCVCDFSCQ SVPGSPVCGS 

       730        740        750        760        770        780 
DGVTYSTECE LKKARCESQR GLYVAAQGAC RGPTFAPLPP VAPLHCAQTP YGCCQDNITA 

       790        800        810        820        830        840 
ARGVGLAGCP SACQCNPHGS YGGTCDPATG QCSCRPGVGG LRCDRCEPGF WNFRGIVTDG 

       850        860        870        880        890        900 
RSGCTPCSCD PQGAVRDDCE QMTGLCSCKP GVAGPKCGQC PDGRALGPAG CEADASAPAT 

       910        920        930        940        950        960 
CAEMRCEFGA RCVEESGSAH CVCPMLTCPE ANATKVCGSD GVTYGNECQL KTIACRQGLQ 

       970        980        990       1000       1010       1020 
ISIQSLGPCQ EAVAPSTHPT SASVTVTTPG LLLSQALPAP PGALPLAPSS TAHSQTTPPP 

      1030       1040       1050       1060       1070       1080 
SSRPRTTASV PRTTVWPVLT VPPTAPSPAP SLVASAFGES GSTDGSSDEE LSGDQEASGG 

      1090       1100       1110       1120       1130       1140 
GSGGLEPLEG SSVATPGPPV ERASCYNSAL GCCSDGKTPS LDAEGSNCPA TKVFQGVLEL 

      1150       1160       1170       1180       1190       1200 
EGVEGQELFY TPEMADPKSE LFGETARSIE STLDDLFRNS DVKKDFRSVR LRDLGPGKSV 

      1210       1220       1230       1240       1250       1260 
RAIVDVHFDP TTAFRAPDVA RALLRQIQVS RRRSLGVRRP LQEHVRFMDF DWFPAFITGA 

      1270       1280       1290       1300       1310       1320 
TSGAIAAGAT ARATTASRLP SSAVTPRAPH PSHTSQPVAK TTAAPTTRRP PTTAPSRVPG 

      1330       1340       1350       1360       1370       1380 
RRPPAPQQPP KPCDSQPCFH GGTCQDWALG GGFTCSCPAG RGGAVCEKVL GAPVPAFEGR 

      1390       1400       1410       1420       1430       1440 
SFLAFPTLRA YHTLRLALEF RALEPQGLLL YNGNARGKDF LALALLDGRV QLRFDTGSGP 

      1450       1460       1470       1480       1490       1500 
AVLTSAVPVE PGQWHRLELS RHWRRGTLSV DGETPVLGES PSGTDGLNLD TDLFVGGVPE 

      1510       1520       1530       1540       1550       1560 
DQAAVALERT FVGAGLRGCI RLLDVNNQRL ELGIGPGAAT RGSGVGECGD HPCLPNPCHG 

      1570       1580       1590       1600       1610       1620 
GAPCQNLEAG RFHCQCPPGR VGPTCADEKS PCQPNPCHGA APCRVLPEGG AQCECPLGRE 

      1630       1640       1650       1660       1670       1680 
GTFCQTASGQ DGSGPFLADF NGFSHLELRG LHTFARDLGE KMALEVVFLA RGPSGLLLYN 

      1690       1700       1710       1720       1730       1740 
GQKTDGKGDF VSLALRDRRL EFRYDLGKGA AVIRSREPVT LGAWTRVSLE RNGRKGALRV 

      1750       1760       1770       1780       1790       1800 
GDGPRVLGES PKSRKVPHTV LNLKEPLYVG GAPDFSKLAR AAAVSSGFDG AIQLVSLGGR 

      1810       1820       1830       1840       1850       1860 
QLLTPEHVLR QVDVTSFAGH PCTRASGHPC LNGASCVPRE AAYVCLCPGG FSGPHCEKGL 

      1870       1880       1890       1900       1910       1920 
VEKSAGDVDT LAFDGRTFVE YLNAVTESEL ANEIPVPETL DSGALHEKAL QSNHFELSLR 

      1930       1940       1950       1960       1970       1980 
TEATQGLVLW SGKATERADY VALAIVDGHL QLSYNLGSQP VVLRSTVPVN TNRWLRVVAH 

      1990       2000       2010       2020       2030       2040 
REQREGSLQV GNEAPVTGSS PLGATQLDTD GALWLGGLPE LPVGPALPKA YGTGFVGCLR 

      2050       2060 
DVVVGRHPLH LLEDAVTKPE LRPCPTP 

« Hide

Isoform 2 (Transmembrane agrin) (TM-agrin) [UniParc].

Checksum: 8E904C7A584AE78F
Show »

FASTA1,963205,544
Isoform 3 (Agrin z(0)) [UniParc].

Checksum: C6CC67CA63060E92
Show »

FASTA2,049215,345
Isoform 4 (Agrin z(+11)) [UniParc].

Checksum: 45560978CFB636D3
Show »

FASTA2,059216,366
Isoform 5 (Agrin z(+8)) [UniParc].

Checksum: 099A9FB384BDE301
Show »

FASTA2,057216,211
Isoform 6 (Agrin y(0)z(0)) [UniParc].

Checksum: 108BDA7146ECB94D
Show »

FASTA2,045214,846
Isoform 7 (y(0)) [UniParc].

Checksum: 9E761313F0E53B1B
Show »

FASTA2,063216,733

References

« Hide 'large scale' references
[1]"Primary structure and high expression of human agrin in basement membranes of adult lung and kidney."
Groffen A.J.A., Buskens C.A.F., Van Kuppevelt T.H., Veerkamp J.H., Monnens L.A.H., Van den Heuvel L.P.W.J.
Eur. J. Biochem. 254:123-128(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[2]Kato S.
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Retinal pigment epithelium.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1703-1949 (ISOFORM 6).
[4]"Agrin binds to the nerve-muscle basal lamina via laminin."
Denzer A.J., Brandenberger R., Gesemann M., Chiquet M., Ruegg M.A.
J. Cell Biol. 137:671-683(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-172, INTERACTION WITH LAMININ.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1558-2045.
Tissue: Brain, Colon and Kidney.
[6]"An alternative amino-terminus expressed in the central nervous system converts agrin to a type II transmembrane protein."
Neumann F.R., Bittcher G., Annies M., Schumacher B., Kroger S., Ruegg M.A.
Mol. Cell. Neurosci. 17:208-225(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF TRANSMEMBRANE ISOFORM (ISOFORM 2).
[7]"Identification of agrinSN isoform and muscle-specific receptor tyrosine kinase (MuSK) in sperm."
Kumar P., Ferns M.J., Meizel S.
Biochem. Biophys. Res. Commun. 342:522-528(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF TRANSMEMBRANE ISOFORM (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[8]Erratum
Kumar P., Ferns M.J., Meizel S.
Biochem. Biophys. Res. Commun. 344:453-453(2006)
[9]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135.
Tissue: Liver.
[10]"Proteomics characterization of extracellular space components in the human aorta."
Didangelos A., Yin X., Mandal K., Baumert M., Jahangiri M., Mayr M.
Mol. Cell. Proteomics 9:2048-2062(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[11]"Agrin binds to the N-terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase (MuSK)."
Zhang W., Coldefy A.S., Hubbard S.R., Burden S.J.
J. Biol. Chem. 286:40624-40630(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRP4, FUNCTION.
[12]"C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction."
Drey M., Sieber C.C., Bauer J.M., Uter W., Dahinden P., Fariello R.G., Vrijbloed J.W.
Exp. Gerontol. 48:76-80(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: POTENTIAL USAGE AS A BIOMARKER FOR SARCOPENIA.
[13]"Identification of an agrin mutation that causes congenital myasthenia and affects synapse function."
Huze C., Bauche S., Richard P., Chevessier F., Goillot E., Gaudon K., Ben Ammar A., Chaboud A., Grosjean I., Lecuyer H.A., Bernard V., Rouche A., Alexandri N., Kuntzer T., Fardeau M., Fournier E., Brancaccio A., Ruegg M.A. expand/collapse author list , Koenig J., Eymard B., Schaeffer L., Hantai D.
Am. J. Hum. Genet. 85:155-167(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LGM ARG-1709, VARIANTS LEU-23; ASN-58; ILE-105; MET-267; SER-375; VAL-728; ARG-852; MET-984; PHE-1088; LYS-1118; ARG-1135; LEU-1240; ARG-1341; LEU-1451; THR-1514; HIS-1565; ILE-1666; GLN-1671; PRO-1698; HIS-1734; ASN-1789 AND VAL-2045, FUNCTION, CHARACTERIZATION OF VARIANT LGM ARG-1709.
[14]Erratum
Huze C., Bauche S., Richard P., Chevessier F., Goillot E., Gaudon K., Ben Ammar A., Chaboud A., Grosjean I., Lecuyer H.A., Bernard V., Rouche A., Alexandri N., Kuntzer T., Fardeau M., Fournier E., Brancaccio A., Ruegg M.A. expand/collapse author list , Koenig J., Eymard B., Schaeffer L., Hantai D.
Am. J. Hum. Genet. 85:536-536(2009)
[15]"LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin."
Maselli R.A., Fernandez J.M., Arredondo J., Navarro C., Ngo M., Beeson D., Cagney O., Williams D.C., Wollmann R.L., Yarov-Yarovoy V., Ferns M.J.
Hum. Genet. 131:1123-1135(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LGM PHE-1727, INTERACTION WITH DAG1, CHARACTERIZATION OF PHE-1727.
+Additional computationally mapped references.

Web resources

The Leiden Muscular Dystrophy pages, Agrin (AGRN)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U84406 mRNA. Translation: AAB52917.1.
AB191264 mRNA. Translation: BAD52440.1.
AL645608 Genomic DNA. Translation: CAI15575.2.
AL645608 Genomic DNA. Translation: CAI15576.1.
AF016903 mRNA. Translation: AAC39776.1.
BC004220 mRNA. Translation: AAH04220.2.
BC007649 mRNA. Translation: AAH07649.1.
BC034009 mRNA. Translation: AAH34009.1.
BC063620 mRNA. Translation: AAH63620.1.
RefSeqNP_940978.2. NM_198576.3.
XP_005244806.1. XM_005244749.1.
UniGeneHs.273330.
Hs.602356.

3D structure databases

ProteinModelPortalO00468.
SMRO00468. Positions 36-975, 1320-2067.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid132000. 8 interactions.
IntActO00468. 7 interactions.
MINTMINT-4053526.
STRING9606.ENSP00000368678.

PTM databases

PhosphoSiteO00468.

Proteomic databases

PaxDbO00468.
PRIDEO00468.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379370; ENSP00000368678; ENSG00000188157. [O00468-6]
GeneID375790.
KEGGhsa:375790.
UCSCuc001ack.2. human. [O00468-1]

Organism-specific databases

CTD375790.
GeneCardsGC01P000946.
HGNCHGNC:329. AGRN.
HPAHPA040090.
MIM103320. gene.
254300. phenotype.
neXtProtNX_O00468.
Orphanet98913. Postsynaptic congenital myasthenic syndromes.
PharmGKBPA24626.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG312635.
HOGENOMHOG000033860.
HOVERGENHBG080471.
InParanoidO00468.
KOK06254.
OMAPRCSCDR.
OrthoDBEOG7BGHJZ.
TreeFamTF326548.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_118779. Extracellular matrix organization.
REACT_196873. Extracellular matrix organization.
SignaLinkO00468.

Gene expression databases

ArrayExpressO00468.
BgeeO00468.
CleanExHS_AGRN.
GenevestigatorO00468.

Family and domain databases

Gene3D2.60.120.200. 3 hits.
3.30.70.960. 1 hit.
InterProIPR004850. 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.
[Graphical view]
PfamPF00008. EGF. 3 hits.
PF00050. Kazal_1. 3 hits.
PF07648. Kazal_2. 6 hits.
PF00053. Laminin_EGF. 2 hits.
PF00054. Laminin_G_1. 3 hits.
PF03146. NtA. 1 hit.
PF01390. SEA. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 4 hits.
SM00180. EGF_Lam. 2 hits.
SM00274. FOLN. 5 hits.
SM00280. KAZAL. 9 hits.
SM00282. LamG. 3 hits.
SM00200. SEA. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 4 hits.
SSF50242. SSF50242. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEPS00022. EGF_1. 6 hits.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 4 hits.
PS01248. EGF_LAM_1. 1 hit.
PS50027. EGF_LAM_2. 2 hits.
PS51465. KAZAL_2. 9 hits.
PS50025. LAM_G_DOMAIN. 3 hits.
PS51121. NTA. 1 hit.
PS50024. SEA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAgrin.
GenomeRNAi375790.
NextBio100617.
PROO00468.
SOURCESearch...

Entry information

Entry nameAGRIN_HUMAN
AccessionPrimary (citable) accession number: O00468
Secondary accession number(s): Q5SVA1 expand/collapse secondary AC list , Q5SVA2, Q60FE1, Q7KYS8, Q8N4J5, Q96IC1, Q9BTD4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2004
Last sequence update: March 6, 2013
Last modified: April 16, 2014
This is version 134 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM