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A2ASQ1 (AGRIN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Agrin
Gene names
Name:Agrn
Synonyms:Agrin
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1950 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. This neuron-specific (z+) isoform isa 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 transmembrane agrin (TM-agrin) isoform, 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.3 Ref.6 Ref.7 Ref.9 Ref.11 Ref.13 Ref.15

Isoform 2 and isoform 3:these isoforms lacking the 'z' insert (z0) are muscle-specific, have no AChR clustering ability and may be involved in nervous system endothelial cell differentiation. Ref.3 Ref.6 Ref.7 Ref.9 Ref.11 Ref.13 Ref.15

Agrin N-terminal 110 kDa subunit: 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.3 Ref.6 Ref.7 Ref.9 Ref.11 Ref.13 Ref.15

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.3 Ref.6 Ref.7 Ref.9 Ref.11 Ref.13 Ref.15

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. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by alternative splicing of AGRN 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. Ref.3

Subcellular location

Cell junctionsynapse. Cell membrane; Single-pass type II membrane protein Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12.

Tissue specificity

Expressed in central nervous system (CNS) synapses such as in the cerebral cortex and hippocampus. Localizes to basal lamina of hippocampal blood vessels. Both (z+) and (z-) isoforms found in kidney, heart and cerebral vasculature. Ref.6 Ref.7 Ref.11 Ref.12

Developmental stage

All (z+), (z-), (y+) and (y-) isoforms present throughout muscle fiber basal laminae in neonatal animals.

Domain

Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding By similarity. Ref.17

Post-translational modification

Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. 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. 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.

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). Cleavage is developmentally regulated. In developing brain, neurotrypsin-mediated cleavage occurs mainly during late fetal days and in the first postnatal week. Ref.12 Ref.13 Ref.15

Disruption phenotype

Z-/z- mice lacking the 'z' insert are stillborn or die immediately after birth. They did not inflate their lungs and were never seen to move spontaneously. An intramuscular nerve is formed and axons leave the nerve and branch but do not stop and arborize. AChR clusters were fewer in number, about 30% smaller in size and lower in density. Transgenic null (Tg/Agrn -/-) mice, exhibit atrophied muscle due to denervation and are smaller than normal littermates. There is impairment of locomotory behavior and half the mice die after 50 days. There is a greatly reduced number of synapses and about 30% loss of postsynaptic spines and a decrease in the length of dendrites in cortical neurons. Ref.6 Ref.11

Miscellaneous

Mice that have excessive neurotrypsin-mediated agrin cleavage, exhibit pathological symptoms characteristic of precocious sarcopenia, with fragmentation and disassembly of the neuromuscular junction (NMJ) (Ref.15).

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 SEA domain.

Sequence caution

The sequence CAM14888.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processDifferentiation
   Cellular componentCell junction
Cell membrane
Membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainEGF-like domain
Laminin EGF-like domain
Repeat
Signal-anchor
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Heparan sulfate
Proteoglycan
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

neuromuscular junction development

Inferred from genetic interaction PubMed 12165471. Source: MGI

neurotransmitter receptor metabolic process

Inferred from direct assay PubMed 14622576. Source: MGI

plasma membrane organization

Inferred from mutant phenotype PubMed 8653788. Source: MGI

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 mutant phenotype PubMed 11312299. Source: MGI

positive regulation of protein binding

Inferred from direct assay PubMed 21969364. Source: UniProt

positive regulation of protein geranylgeranylation

Inferred from mutant phenotype PubMed 14622576. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 14622576. Source: UniProtKB

positive regulation of synaptic growth at neuromuscular junction

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 9422725. Source: MGI

receptor clustering

Inferred from direct assay Ref.7PubMed 17119023. Source: MGI

regulation of Rac GTPase activity

Inferred from direct assay PubMed 14622576. Source: UniProtKB

regulation of receptor activity

Inferred from direct assay PubMed 14622576. Source: GOC

regulation of synaptic growth at neuromuscular junction

Inferred from mutant phenotype Ref.7. Source: MGI

synaptic transmission

Inferred from direct assay PubMed 8653788. Source: MGI

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

basal lamina

Inferred from direct assay Ref.7PubMed 7670489. Source: MGI

basement membrane

Inferred from direct assay PubMed 18757743. Source: MGI

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface

Inferred from direct assay Ref.7. Source: MGI

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 12165471PubMed 9422725. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synapse

Inferred from direct assay Ref.12. Source: MGI

   Molecular_functionacetylcholine receptor regulator activity

Inferred from direct assay PubMed 14622576. Source: MGI

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

chondroitin sulfate binding

Inferred from direct assay PubMed 12773545. Source: UniProtKB

dystroglycan binding

Inferred from sequence or structural similarity. Source: UniProtKB

heparan sulfate proteoglycan binding

Inferred from direct assay PubMed 12773545. Source: UniProtKB

sialic acid binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Many isoforms exist depending on the occurrence and length of inserts at the x, y or z splice site. There are 4 'z' isoforms produced with inserts of 0, 8, 11 or 19 AA. Isoforms differ in their acetylcholine receptor clustering activity and tissue specificity. In addition, a secreted isoform is produced by alternative usage of the first exon.
Isoform 1 (identifier: A2ASQ1-1)

Also known as: Transmembrane agrin; TM-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: A2ASQ1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1634-1637: Missing.
     1771-1788: Missing.
Isoform 3 (identifier: A2ASQ1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
     1634-1637: Missing.
     1771-1788: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19501950Agrin
PRO_0000356178
Chain48 – 986939Agrin N-terminal 110 kDa subunit
PRO_0000421617
Chain987 – 1950964Agrin C-terminal 110 kDa subunit
PRO_0000421618
Chain987 – 1745759Agrin C-terminal 90 kDa fragment
PRO_0000421619
Chain1746 – 1950205Agrin C-terminal 22 kDa fragment
PRO_0000421620

Regions

Topological domain1 – 2626Cytoplasmic Potential
Transmembrane27 – 4721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain48 – 19501903Extracellular Potential
Domain86 – 13954Kazal-like 1
Domain159 – 21456Kazal-like 2
Domain232 – 28655Kazal-like 3
Domain303 – 35856Kazal-like 4
Domain379 – 43153Kazal-like 5
Domain442 – 49655Kazal-like 6
Domain502 – 56160Kazal-like 7
Domain594 – 64754Kazal-like 8
Domain688 – 74154Laminin EGF-like 1
Domain742 – 78847Laminin EGF-like 2
Domain812 – 86655Kazal-like 9
Domain1014 – 1136123SEA
Domain1211 – 124939EGF-like 1
Domain1254 – 1430177Laminin G-like 1
Domain1431 – 146838EGF-like 2
Domain1470 – 150738EGF-like 3
Domain1517 – 1699183Laminin G-like 2
Domain1700 – 173940EGF-like 4
Domain1775 – 1947173Laminin G-like 3
Calcium binding1811 – 188070 By similarity
Calcium binding1822 – 189170 By similarity
Compositional bias565 – 5728Gly/Ser-rich
Compositional bias900 – 95051Ser/Thr-rich
Compositional bias962 – 9687Gly/Ser-rich
Compositional bias1138 – 120669Ser/Thr-rich

Sites

Site986 – 9872Cleavage, alpha site; by neurotrypsin By similarity
Site11341Alternative splice site to produce 'x' isoforms
Site16331Alternative splice site to produce 'y' isoforms
Site17441Critical for cleavage by neurotrypsin By similarity
Site1745 – 17462Cleavage, beta site; by neurotrypsin By similarity
Site17701Alternative splice site to produce 'z' isoforms
Site17741Highly important for the agrin receptor complex activity of the 'z' insert By similarity

Amino acid modifications

Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation6721N-linked (GlcNAc...) Potential
Glycosylation8271N-linked (GlcNAc...) Potential
Glycosylation9481N-linked (GlcNAc...) Potential
Disulfide bond97 ↔ 116 By similarity
Disulfide bond105 ↔ 137 By similarity
Disulfide bond171 ↔ 191 By similarity
Disulfide bond180 ↔ 212 By similarity
Disulfide bond244 ↔ 263 By similarity
Disulfide bond252 ↔ 284 By similarity
Disulfide bond316 ↔ 335 By similarity
Disulfide bond324 ↔ 356 By similarity
Disulfide bond389 ↔ 408 By similarity
Disulfide bond397 ↔ 429 By similarity
Disulfide bond454 ↔ 473 By similarity
Disulfide bond462 ↔ 494 By similarity
Disulfide bond518 ↔ 538 By similarity
Disulfide bond527 ↔ 559 By similarity
Disulfide bond604 ↔ 624 By similarity
Disulfide bond613 ↔ 645 By similarity
Disulfide bond688 ↔ 700 By similarity
Disulfide bond690 ↔ 707 By similarity
Disulfide bond709 ↔ 718 By similarity
Disulfide bond721 ↔ 739 By similarity
Disulfide bond742 ↔ 754 By similarity
Disulfide bond744 ↔ 761 By similarity
Disulfide bond763 ↔ 772 By similarity
Disulfide bond775 ↔ 786 By similarity
Disulfide bond823 ↔ 843 By similarity
Disulfide bond832 ↔ 864 By similarity
Disulfide bond1215 ↔ 1226 By similarity
Disulfide bond1220 ↔ 1237 By similarity
Disulfide bond1239 ↔ 1248 By similarity
Disulfide bond1401 ↔ 1430 By similarity
Disulfide bond1435 ↔ 1446 By similarity
Disulfide bond1440 ↔ 1456 By similarity
Disulfide bond1458 ↔ 1467 By similarity
Disulfide bond1474 ↔ 1485 By similarity
Disulfide bond1479 ↔ 1495 By similarity
Disulfide bond1497 ↔ 1506 By similarity
Disulfide bond1704 ↔ 1718 By similarity
Disulfide bond1712 ↔ 1727 By similarity
Disulfide bond1729 ↔ 1738 By similarity
Disulfide bond1921 ↔ 1947 By similarity

Natural variations

Alternative sequence1 – 6161Missing in isoform 3.
VSP_035995
Alternative sequence1634 – 16374Missing in isoform 2 and isoform 3.
VSP_035996
Alternative sequence1771 – 178818Missing in isoform 2 and isoform 3.
VSP_035997
Natural variant10611F → S in a mutant strain; shows symptoms similar to the motor neuron disease, agrin-associated congenital myasthenic syndrome (CMS) with progressive degradation of the neuromuscular junction, decreased acetylcholine receptor (AChR) density and increased subsynaptic reticulum. Synapses eventually denervate and muscles atrophy. There is decreased glycosylation and proteolytic processing is altered due to changes in sensitivity to neurotrypsin. Ref.16

Experimental info

Sequence conflict12121P → T in AAI50704. Ref.2

Secondary structure

.................................. 1950
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Transmembrane agrin) (TM-agrin) [UniParc].

Last modified February 20, 2007. Version 1.
Checksum: 0679A3F6D8BD1286

FASTA1,950207,539
        10         20         30         40         50         60 
MPPLPLEHRP RQQPGASVLV RYFMIPCNIC LILLATSTLG FAVLLFLSNY KPGIHFTAAP 

        70         80         90        100        110        120 
SMPPDVCRGM LCGFGAVCEP SVEDPGRASC VCKKNVCPAM VAPVCGSDAS TYSNECELQR 

       130        140        150        160        170        180 
AQCNQQRRIR LLRQGPCGSR DPCANVTCSF GSTCVPSADG QTASCLCPTT CFGAPDGTVC 

       190        200        210        220        230        240 
GSDGVDYPSE CQLLRHACAN QEHIFKKFDG PCDPCQGSMS DLNHICRVNP RTRHPEMLLR 

       250        260        270        280        290        300 
PENCPAQHTP ICGDDGVTYE NDCVMSRIGA ARGLLLQKVR SGQCQTRDQC PETCQFNSVC 

       310        320        330        340        350        360 
LSRRGRPHCS CDRVTCDGAY RPVCAQDGHT YDNDCWRQQA ECRQQQTIPP KHQGPCDQTP 

       370        380        390        400        410        420 
SPCRGAQCAF GATCTVKNGK AVCECQRVCS GGYDPVCGSD GVTYGSVCEL ESMACTLGRE 

       430        440        450        460        470        480 
IRVARRGPCD RCGQCRFGSL CEVETGRCVC PSECVESAQP VCGSDGHTYA SECELHVHAC 

       490        500        510        520        530        540 
THQISLYVAS AGHCQTCGET VCTFGAVCSA GQCVCPRCEH PPPGPVCGSD GVTYLSACEL 

       550        560        570        580        590        600 
REAACQQQVQ IEEARAGPCE PAECGSGGSG SGEDNACEQE LCRQHGGVWD EDSEDGPCVC 

       610        620        630        640        650        660 
DFSCQSVLKS PVCGSDGVTY STECHLKKAR CEARQELYVA AQGACRGPTL APLLPMASPH 

       670        680        690        700        710        720 
CAQTPYGCCQ DNVTAAQGVG LAGCPSTCHC NPHGSYSGTC DPVTGQCSCR PGVGGLRCDR 

       730        740        750        760        770        780 
CEPGFWNFRG IVTDGHSGCT PCSCDPRGAV RDDCEQMTGL CSCRPGVAGP KCGQCPDGQA 

       790        800        810        820        830        840 
LGHLGCEADP TTPVTCVEMH CEFGASCVEE AGFAQCVCPT LTCPEANSTK VCGSDGVTYG 

       850        860        870        880        890        900 
NECQLKTIAC RQRLDISIQS LGPCRESVAP GVSPTSASMT TPRHILSRTL ASPHSSLPLS 

       910        920        930        940        950        960 
PSTTAHDWPT PLPTSPQTVV GTPRSTAATP SDVASLATAI FRESGSTNGS GDEELSGDEE 

       970        980        990       1000       1010       1020 
ASGGGSGGLE PPVGSVVVTH GPPIERASCY NSPLGCCSDG KTPSLDSEGS NCPATKAFQG 

      1030       1040       1050       1060       1070       1080 
VLELEGVEGQ ELFYTPEMAD PKSELFGETA RSIESTLDDL FRNSDVKKDF WSIRLRELGP 

      1090       1100       1110       1120       1130       1140 
GKLVRAIVDV HFDPTTAFQA PDVGQALLQQ IQVSRPWALA VRRPLREHVR FLDFDWFPTF 

      1150       1160       1170       1180       1190       1200 
FTGAATGTTA AVATARATTV SRLSASSVTP RVYPSYTSRP VGRTTAPLTT RRPPTTTASI 

      1210       1220       1230       1240       1250       1260 
DRPRTPGPQR PPKSCDSQPC LHGGTCQDLD SGKGFSCSCT AGRAGTVCEK VQLPSVPAFK 

      1270       1280       1290       1300       1310       1320 
GHSFLAFPTL RAYHTLRLAL EFRALETEGL LLYNGNARGK DFLALALLDG HVQFRFDTGS 

      1330       1340       1350       1360       1370       1380 
GPAVLTSLVP VEPGRWHRLE LSRHWRQGTL SVDGEAPVVG ESPSGTDGLN LDTKLYVGGL 

      1390       1400       1410       1420       1430       1440 
PEEQVATVLD RTSVGIGLKG CIRMLDINNQ QLELSDWQRA VVQSSGVGEC GDHPCSPNPC 

      1450       1460       1470       1480       1490       1500 
HGGALCQALE AGVFLCQCPP GRFGPTCADE KNPCQPNPCH GSAPCHVLSR GGAKCACPLG 

      1510       1520       1530       1540       1550       1560 
RSGSFCETVL ENAGSRPFLA DFNGFSYLEL KGLHTFERDL GEKMALEMVF LARGPSGLLL 

      1570       1580       1590       1600       1610       1620 
YNGQKTDGKG DFVSLALHNR HLEFRYDLGK GAAIIRSKEP IALGTWVRVF LERNGRKGAL 

      1630       1640       1650       1660       1670       1680 
QVGDGPRVLG ESPKSRKVPH TMLNLKEPLY VGGAPDFSKL ARGAAVASGF DGAIQLVSLR 

      1690       1700       1710       1720       1730       1740 
GHQLLTQEHV LRAVDVAPFA GHPCTQAVDN PCLNGGSCIP REATYECLCP GGFSGLHCEK 

      1750       1760       1770       1780       1790       1800 
GIVEKSVGDL ETLAFDGRTY IEYLNAVTES ELTNEIPAPE TLDSRALFSE KALQSNHFEL 

      1810       1820       1830       1840       1850       1860 
SLRTEATQGL VLWIGKVGER ADYMALAIVD GHLQLSYDLG SQPVVLRSTV KVNTNRWLRV 

      1870       1880       1890       1900       1910       1920 
RAHREHREGS LQVGNEAPVT GSSPLGATQL DTDGALWLGG LQKLPVGQAL PKAYGTGFVG 

      1930       1940       1950 
CLRDVVVGHR QLHLLEDAVT KPELRPCPTL 

« Hide

Isoform 2 [UniParc].

Checksum: 8D720587D8FCA978
Show »

FASTA1,928205,041
Isoform 3 [UniParc].

Checksum: D3CCD34419F1FE14
Show »

FASTA1,867198,336

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[2]"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] (ISOFORM 3).
Tissue: Brain.
[3]"Agrin acts via a MuSK receptor complex."
Glass D.J., Bowen D.C., Stitt T.N., Radziejewski C., Bruno J., Ryan T.E., Gies D.R., Shah S., Mattsson K., Burden S.J., DiStefano P.S., Valenzuela D.M., DeChiara T.M., Yancopoulos G.D.
Cell 85:513-523(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEUROMUSCULAR JUNCTION DEVELOPMENT, SUBCELLULAR LOCATION, FUNCTION IN PHOSPHORYLATION OF MUSK, INTERACTION WITH LRP4.
[4]"Selective regulation of agrin mRNA induction and alternative splicing in PC12 cells by Ras-dependent actions of nerve growth factor."
Smith M.A., Fanger G.R., O'Connor L.T., Bridle P., Maue R.A.
J. Biol. Chem. 272:15675-15681(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION OF ALTERNATIVE SPLICING.
[5]"Interaction of agrin with laminin requires a coiled-coil conformation of the agrin-binding site within the laminin gamma1 chain."
Kammerer R.A., Schulthess T., Landwehr R., Schumacher B., Lustig A., Yurchenco P.D., Ruegg M.A., Engel J., Denzer A.J.
EMBO J. 18:6762-6770(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: LAMININ BINDING.
[6]"Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction."
Burgess R.W., Nguyen Q.T., Son Y.J., Lichtman J.W., Sanes J.R.
Neuron 23:33-44(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION.
[7]"Agrin isoforms with distinct amino termini: differential expression, localization, and function."
Burgess R.W., Skarnes W.C., Sanes J.R.
J. Cell Biol. 151:41-52(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
[8]"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: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION.
[9]"The COOH-terminal domain of agrin signals via a synaptic receptor in central nervous system neurons."
Hoover C.L., Hilgenberg L.G., Smith M.A.
J. Cell Biol. 161:923-932(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF AGRIN C-TERMINAL 22 KDA FRAGMENT, SUBCELLULAR LOCATION.
[10]"Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[11]"Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death."
Ksiazek I., Burkhardt C., Lin S., Seddik R., Maj M., Bezakova G., Jucker M., Arber S., Caroni P., Sanes J.R., Bettler B., Ruegg M.A.
J. Neurosci. 27:7183-7195(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION.
[12]"Neurotrypsin cleaves agrin locally at the synapse."
Stephan A., Mateos J.M., Kozlov S.V., Cinelli P., Kistler A.D., Hettwer S., Rulicke T., Streit P., Kunz B., Sonderegger P.
FASEB J. 22:1861-1873(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, IDENTIFICATION OF PROTEOLYTICALLY CLEAVED FRAGMENTS BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]"Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage."
Matsumoto-Miyai K., Sokolowska E., Zurlinden A., Gee C.E., Luscher D., Hettwer S., Wolfel J., Ladner A.P., Ster J., Gerber U., Rulicke T., Kunz B., Sonderegger P.
Cell 136:1161-1171(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, FUNCTION.
[14]"Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing."
Ruggiu M., Herbst R., Kim N., Jevsek M., Fak J.J., Mann M.A., Fischbach G., Burden S.J., Darnell R.B.
Proc. Natl. Acad. Sci. U.S.A. 106:3513-3518(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION OF ALTERNATIVE SPLICING AT THE Z SITE.
[15]"Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia."
Butikofer L., Zurlinden A., Bolliger M.F., Kunz B., Sonderegger P.
FASEB J. 25:4378-4393(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, FUNCTION, MOUSE MODEL OF PRECOCIOUS SARCOPENIA.
[16]"A valid mouse model of AGRIN-associated congenital myasthenic syndrome."
Bogdanik L.P., Burgess R.W.
Hum. Mol. Genet. 20:4617-4633(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT A MUTANT STRAIN SER-1061, CHARACTERIZATION OF A MOUSE MODEL OF AGRIN-ASSOCIATED CONGENITAL MYASTHENIC SYNDROME.
[17]"Structural and biophysical characterisation of agrin laminin G3 domain constructs."
Tidow H., Mattle D., Nissen P.
Protein Eng. Des. Sel. 24:219-224(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURAL CHARACTERISTICS OF LAMININ G3 DOMAIN.
[18]"Crystal structure of the g2 domain of agrin from Mus musculus."
New York structural genomix research consortium (NYSGXRC)
Submitted (JAN-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1510-1701.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL928667 Genomic DNA. Translation: CAM14888.1. Sequence problems.
AL928667 Genomic DNA. Translation: CAM14889.1.
AL928667 Genomic DNA. Translation: CAM14890.1.
BC150703 mRNA. Translation: AAI50704.1.
UniGeneMm.273098.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3PVEX-ray1.40A/B1510-1701[»]
ProteinModelPortalA2ASQ1.
SMRA2ASQ1. Positions 65-646, 688-865, 1207-1949.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PaxDbA2ASQ1.
PRIDEA2ASQ1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000105575; ENSMUSP00000101200; ENSMUSG00000041936. [A2ASQ1-1]
UCSCuc008wgf.2. mouse. [A2ASQ1-2]
uc008wgg.1. mouse. [A2ASQ1-1]

Organism-specific databases

MGIMGI:87961. Agrn.

Phylogenomic databases

eggNOGNOG312635.
GeneTreeENSGT00530000063501.
HOGENOMHOG000033860.
HOVERGENHBG080471.
InParanoidA2ASQ1.
OrthoDBEOG7BGHJZ.
PhylomeDBA2ASQ1.
TreeFamTF326548.

Enzyme and pathway databases

ReactomeREACT_188937. Metabolism.
REACT_189085. Disease.
REACT_194409. Developmental Biology.

Gene expression databases

ArrayExpressA2ASQ1.
BgeeA2ASQ1.
GenevestigatorA2ASQ1.

Family and domain databases

Gene3D2.60.120.200. 4 hits.
3.30.70.960. 1 hit.
InterProIPR008985. 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.
[Graphical view]
PfamPF00008. EGF. 3 hits.
PF00050. Kazal_1. 4 hits.
PF07648. Kazal_2. 5 hits.
PF00053. Laminin_EGF. 2 hits.
PF00054. Laminin_G_1. 3 hits.
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. 3 hits.
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.
PS50024. SEA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAGRN. mouse.
EvolutionaryTraceA2ASQ1.
PROA2ASQ1.
SOURCESearch...

Entry information

Entry nameAGRIN_MOUSE
AccessionPrimary (citable) accession number: A2ASQ1
Secondary accession number(s): A2ASP9, A2ASQ0, B2RWU1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 69 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot