A2ASQ1 (AGRIN_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Agrin

Cleaved into the following 4 chains:

1. Agrin N-terminal 110 kDa subunit
2. Agrin C-terminal 110 kDa subunit
3. Agrin C-terminal 90 kDa fragment
   Short name=C90
4. Agrin C-terminal 22 kDa fragment
   Short name=C22

Gene names

Name:	Agrn
Synonyms:	Agrin

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1950 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 is a 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.10 Ref.12 Ref.14 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.10 Ref.12 Ref.14 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.10 Ref.12 Ref.14 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.10 Ref.12 Ref.14
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 junction › synapse. Cell membrane; Single-pass type II membrane protein Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11.
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.10 Ref.11
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.16
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.11 Ref.12 Ref.14
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.10
Miscellaneous	Mice that have excessive neurotrysin-mediated agrin cleavage, exhibit pathological symptoms characteristic of precocious sarcopenia, with fragmentation and disassembly of the neuromuscular junction (NMJ) (Ref.14).
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 process	Differentiation
Cellular component	Cell junction Cell membrane Membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Laminin EGF-like domain Repeat Signal-anchor Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Heparan sulfate Proteoglycan
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 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
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome basal lamina Inferred from direct assay Ref.7PubMed 7670489. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay Ref.7. Source: MGI extracellular space Inferred from direct assay PubMed 12165471PubMed 9422725. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from direct assay Ref.11. Source: MGI
Molecular_function	acetylcholine 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1950

1950

Agrin

PRO_0000356178

Chain

48 – 986

939

Agrin N-terminal 110 kDa subunit

PRO_0000421617

Chain

987 – 1950

964

Agrin C-terminal 110 kDa subunit

PRO_0000421618

Chain

987 – 1745

759

Agrin C-terminal 90 kDa fragment

PRO_0000421619

Chain

1746 – 1950

205

Agrin C-terminal 22 kDa fragment

PRO_0000421620

Regions

Topological domain

1 – 26

26

Cytoplasmic Potential

Transmembrane

27 – 47

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

48 – 1950

1903

Extracellular Potential

Domain

86 – 139

54

Kazal-like 1

Domain

159 – 214

56

Kazal-like 2

Domain

232 – 286

55

Kazal-like 3

Domain

303 – 358

56

Kazal-like 4

Domain

379 – 431

53

Kazal-like 5

Domain

442 – 496

55

Kazal-like 6

Domain

502 – 561

60

Kazal-like 7

Domain

594 – 647

54

Kazal-like 8

Domain

688 – 741

54

Laminin EGF-like 1

Domain

742 – 788

47

Laminin EGF-like 2

Domain

812 – 866

55

Kazal-like 9

Domain

1014 – 1136

123

SEA

Domain

1211 – 1249

39

EGF-like 1

Domain

1254 – 1430

177

Laminin G-like 1

Domain

1431 – 1468

38

EGF-like 2

Domain

1470 – 1507

38

EGF-like 3

Domain

1517 – 1699

183

Laminin G-like 2

Domain

1700 – 1739

40

EGF-like 4

Domain

1775 – 1947

173

Laminin G-like 3

Calcium binding

1811 – 1880

70

By similarity

Calcium binding

1822 – 1891

70

By similarity

Compositional bias

565 – 572

8

Gly/Ser-rich

Compositional bias

900 – 950

51

Ser/Thr-rich

Compositional bias

962 – 968

7

Gly/Ser-rich

Compositional bias

1138 – 1206

69

Ser/Thr-rich

Sites

Site

986 – 987

2

Cleavage, alpha site; by neurotrypsin By similarity

Site

1134

1

Alternative splice site to produce 'x' isoforms

Site

1633

1

Alternative splice site to produce 'y' isoforms

Site

1744

1

Critical for cleavage by neurotrypsin By similarity

Site

1745 – 1746

2

Cleavage, beta site; by neurotrypsin By similarity

Site

1770

1

Alternative splice site to produce 'z' isoforms

Site

1774

1

Highly important for the agrin receptor complex activity of the 'z' insert By similarity

Amino acid modifications

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Glycosylation

672

1

N-linked (GlcNAc...) Potential

Glycosylation

827

1

N-linked (GlcNAc...) Potential

Glycosylation

948

1

N-linked (GlcNAc...) Potential

Disulfide bond

97 ↔ 116

By similarity

Disulfide bond

105 ↔ 137

By similarity

Disulfide bond

171 ↔ 191

By similarity

Disulfide bond

180 ↔ 212

By similarity

Disulfide bond

244 ↔ 263

By similarity

Disulfide bond

252 ↔ 284

By similarity

Disulfide bond

316 ↔ 335

By similarity

Disulfide bond

324 ↔ 356

By similarity

Disulfide bond

389 ↔ 408

By similarity

Disulfide bond

397 ↔ 429

By similarity

Disulfide bond

454 ↔ 473

By similarity

Disulfide bond

462 ↔ 494

By similarity

Disulfide bond

518 ↔ 538

By similarity

Disulfide bond

527 ↔ 559

By similarity

Disulfide bond

604 ↔ 624

By similarity

Disulfide bond

613 ↔ 645

By similarity

Disulfide bond

688 ↔ 700

By similarity

Disulfide bond

690 ↔ 707

By similarity

Disulfide bond

709 ↔ 718

By similarity

Disulfide bond

721 ↔ 739

By similarity

Disulfide bond

742 ↔ 754

By similarity

Disulfide bond

744 ↔ 761

By similarity

Disulfide bond

763 ↔ 772

By similarity

Disulfide bond

775 ↔ 786

By similarity

Disulfide bond

823 ↔ 843

By similarity

Disulfide bond

832 ↔ 864

By similarity

Disulfide bond

1215 ↔ 1226

By similarity

Disulfide bond

1220 ↔ 1237

By similarity

Disulfide bond

1239 ↔ 1248

By similarity

Disulfide bond

1401 ↔ 1430

By similarity

Disulfide bond

1435 ↔ 1446

By similarity

Disulfide bond

1440 ↔ 1456

By similarity

Disulfide bond

1458 ↔ 1467

By similarity

Disulfide bond

1474 ↔ 1485

By similarity

Disulfide bond

1479 ↔ 1495

By similarity

Disulfide bond

1497 ↔ 1506

By similarity

Disulfide bond

1704 ↔ 1718

By similarity

Disulfide bond

1712 ↔ 1727

By similarity

Disulfide bond

1729 ↔ 1738

By similarity

Disulfide bond

1921 ↔ 1947

By similarity

Natural variations

Alternative sequence

1 – 61

61

Missing in isoform 3.

VSP_035995

Alternative sequence

1634 – 1637

4

Missing in isoform 2 and isoform 3.

VSP_035996

Alternative sequence

1771 – 1788

18

Missing in isoform 2 and isoform 3.

VSP_035997

Natural variant

1061

1

F → 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.15

Experimental info

Sequence conflict

1212

1

P → T in AAI50704. Ref.2

Secondary structure

1

.

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1950

Helix Strand Turn

Details...

Beta strand

1520 – 1525

6

Beta strand

1527 – 1530

4

Helix

1533 – 1535

3

Beta strand

1545 – 1555

11

Beta strand

1557 – 1564

8

Beta strand

1572 – 1578

7

Beta strand

1581 – 1590

10

Beta strand

1592 – 1596

5

Beta strand

1605 – 1614

10

Beta strand

1617 – 1622

6

Beta strand

1628 – 1631

4

Beta strand

1649 – 1652

4

Helix

1657 – 1659

3

Helix

1662 – 1664

3

Beta strand

1671 – 1679

9

Helix

1687 – 1689

3

Beta strand

1690 – 1695

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Transmembrane agrin) (TM-agrin) [UniParc]. Last modified February 20, 2007. Version 1. Checksum: 0679A3F6D8BD1286	FASTA	1,950	207,539
	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
	Isoform 2 [UniParc]. Checksum: 8D720587D8FCA978	FASTA	1,928	205,041
	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 ESPVPHTMLN LKEPLYVGGA PDFSKLARGA AVASGFDGAI QLVSLRGHQL 1690 1700 1710 1720 1730 1740 LTQEHVLRAV DVAPFAGHPC TQAVDNPCLN GGSCIPREAT YECLCPGGFS GLHCEKGIVE 1750 1760 1770 1780 1790 1800 KSVGDLETLA FDGRTYIEYL NAVTESSEKA LQSNHFELSL RTEATQGLVL WIGKVGERAD 1810 1820 1830 1840 1850 1860 YMALAIVDGH LQLSYDLGSQ PVVLRSTVKV NTNRWLRVRA HREHREGSLQ VGNEAPVTGS 1870 1880 1890 1900 1910 1920 SPLGATQLDT DGALWLGGLQ KLPVGQALPK AYGTGFVGCL RDVVVGHRQL HLLEDAVTKP ELRPCPTL
	Isoform 3 [UniParc]. Checksum: D3CCD34419F1FE14	FASTA	1,867	198,336
	10 20 30 40 50 60 MPPDVCRGML CGFGAVCEPS VEDPGRASCV CKKNVCPAMV APVCGSDAST YSNECELQRA 70 80 90 100 110 120 QCNQQRRIRL LRQGPCGSRD PCANVTCSFG STCVPSADGQ TASCLCPTTC FGAPDGTVCG 130 140 150 160 170 180 SDGVDYPSEC QLLRHACANQ EHIFKKFDGP CDPCQGSMSD LNHICRVNPR TRHPEMLLRP 190 200 210 220 230 240 ENCPAQHTPI CGDDGVTYEN DCVMSRIGAA RGLLLQKVRS GQCQTRDQCP ETCQFNSVCL 250 260 270 280 290 300 SRRGRPHCSC DRVTCDGAYR PVCAQDGHTY DNDCWRQQAE CRQQQTIPPK HQGPCDQTPS 310 320 330 340 350 360 PCRGAQCAFG ATCTVKNGKA VCECQRVCSG GYDPVCGSDG VTYGSVCELE SMACTLGREI 370 380 390 400 410 420 RVARRGPCDR CGQCRFGSLC EVETGRCVCP SECVESAQPV CGSDGHTYAS ECELHVHACT 430 440 450 460 470 480 HQISLYVASA GHCQTCGETV CTFGAVCSAG QCVCPRCEHP PPGPVCGSDG VTYLSACELR 490 500 510 520 530 540 EAACQQQVQI EEARAGPCEP AECGSGGSGS GEDNACEQEL CRQHGGVWDE DSEDGPCVCD 550 560 570 580 590 600 FSCQSVLKSP VCGSDGVTYS TECHLKKARC EARQELYVAA QGACRGPTLA PLLPMASPHC 610 620 630 640 650 660 AQTPYGCCQD NVTAAQGVGL AGCPSTCHCN PHGSYSGTCD PVTGQCSCRP GVGGLRCDRC 670 680 690 700 710 720 EPGFWNFRGI VTDGHSGCTP CSCDPRGAVR DDCEQMTGLC SCRPGVAGPK CGQCPDGQAL 730 740 750 760 770 780 GHLGCEADPT TPVTCVEMHC EFGASCVEEA GFAQCVCPTL TCPEANSTKV CGSDGVTYGN 790 800 810 820 830 840 ECQLKTIACR QRLDISIQSL GPCRESVAPG VSPTSASMTT PRHILSRTLA SPHSSLPLSP 850 860 870 880 890 900 STTAHDWPTP LPTSPQTVVG TPRSTAATPS DVASLATAIF RESGSTNGSG DEELSGDEEA 910 920 930 940 950 960 SGGGSGGLEP PVGSVVVTHG PPIERASCYN SPLGCCSDGK TPSLDSEGSN CPATKAFQGV 970 980 990 1000 1010 1020 LELEGVEGQE LFYTPEMADP KSELFGETAR SIESTLDDLF RNSDVKKDFW SIRLRELGPG 1030 1040 1050 1060 1070 1080 KLVRAIVDVH FDPTTAFQAP DVGQALLQQI QVSRPWALAV RRPLREHVRF LDFDWFPTFF 1090 1100 1110 1120 1130 1140 TGAATGTTAA VATARATTVS RLSASSVTPR VYPSYTSRPV GRTTAPLTTR RPPTTTASID 1150 1160 1170 1180 1190 1200 RPRTPGPQRP PKSCDSQPCL HGGTCQDLDS GKGFSCSCTA GRAGTVCEKV QLPSVPAFKG 1210 1220 1230 1240 1250 1260 HSFLAFPTLR AYHTLRLALE FRALETEGLL LYNGNARGKD FLALALLDGH VQFRFDTGSG 1270 1280 1290 1300 1310 1320 PAVLTSLVPV EPGRWHRLEL SRHWRQGTLS VDGEAPVVGE SPSGTDGLNL DTKLYVGGLP 1330 1340 1350 1360 1370 1380 EEQVATVLDR TSVGIGLKGC IRMLDINNQQ LELSDWQRAV VQSSGVGECG DHPCSPNPCH 1390 1400 1410 1420 1430 1440 GGALCQALEA GVFLCQCPPG RFGPTCADEK NPCQPNPCHG SAPCHVLSRG GAKCACPLGR 1450 1460 1470 1480 1490 1500 SGSFCETVLE NAGSRPFLAD FNGFSYLELK GLHTFERDLG EKMALEMVFL ARGPSGLLLY 1510 1520 1530 1540 1550 1560 NGQKTDGKGD FVSLALHNRH LEFRYDLGKG AAIIRSKEPI ALGTWVRVFL ERNGRKGALQ 1570 1580 1590 1600 1610 1620 VGDGPRVLGE SPVPHTMLNL KEPLYVGGAP DFSKLARGAA VASGFDGAIQ LVSLRGHQLL 1630 1640 1650 1660 1670 1680 TQEHVLRAVD VAPFAGHPCT QAVDNPCLNG GSCIPREATY ECLCPGGFSG LHCEKGIVEK 1690 1700 1710 1720 1730 1740 SVGDLETLAF DGRTYIEYLN AVTESSEKAL QSNHFELSLR TEATQGLVLW IGKVGERADY 1750 1760 1770 1780 1790 1800 MALAIVDGHL QLSYDLGSQP VVLRSTVKVN TNRWLRVRAH REHREGSLQV GNEAPVTGSS 1810 1820 1830 1840 1850 1860 PLGATQLDTD GALWLGGLQK LPVGQALPKA YGTGFVGCLR DVVVGHRQLH LLEDAVTKPE LRPCPTL

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.

IPI

IPI00378698.
IPI00648938.
IPI00874558.

UniGene

Mm.273098.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PVE	X-ray	1.40	A/B	1510-1701	[»]

ProteinModelPortal

A2ASQ1.

SMR

A2ASQ1. Positions 67-646, 688-774, 1213-1949.

ModBase

Search...

Proteomic databases

PaxDb

A2ASQ1.

PRIDE

A2ASQ1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000071248; ENSMUSP00000071229; ENSMUSG00000041936.
ENSMUST00000105574; ENSMUSP00000101199; ENSMUSG00000041936.
ENSMUST00000105575; ENSMUSP00000101200; ENSMUSG00000041936.

UCSC

uc008wgf.1. mouse.

Organism-specific databases

MGI

MGI:87961. Agrn.

Phylogenomic databases

eggNOG

NOG312635.

GeneTree

ENSGT00530000063501.

HOGENOM

HOG000033860.

HOVERGEN

HBG080471.

InParanoid

A2ASQ1.

OMA

TNRWLRV.

Enzyme and pathway databases

Reactome

REACT_112621. Metabolism.
REACT_115433. Developmental Biology.
REACT_118324. Disease.

Gene expression databases

ArrayExpress

A2ASQ1.

Bgee

A2ASQ1.

Genevestigator

A2ASQ1.

Family and domain databases

Gene3D

2.60.120.200. 4 hits.

InterPro

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.
[Graphical view]

Pfam

PF00008. 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]

SMART

SM00181. 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]

SUPFAM

SSF49899. ConA_like_lec_gl. 3 hits.

PROSITE

PS00022. 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]

ProtoNet

Search...

Other

ChiTaRS

AGRN. mouse.

EvolutionaryTrace

A2ASQ1.

SOURCE

Search...

Entry information

Entry name

AGRIN_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 59 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program