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A2ASQ1

- AGRIN_MOUSE

UniProt

A2ASQ1 - AGRIN_MOUSE

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Protein

Agrin

Gene

Agrn

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.
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.
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).By similarity
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei986 – 9872Cleavage, alpha site; by neurotrypsinBy similarity
Sitei1134 – 11341Alternative splice site to produce 'x' isoforms
Sitei1633 – 16331Alternative splice site to produce 'y' isoforms
Sitei1744 – 17441Critical for cleavage by neurotrypsinBy similarity
Sitei1745 – 17462Cleavage, beta site; by neurotrypsinBy similarity
Sitei1770 – 17701Alternative splice site to produce 'z' isoforms
Sitei1774 – 17741Highly important for the agrin receptor complex activity of the 'z' insertBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi1811 – 188070By similarityAdd
BLAST
Calcium bindingi1822 – 189170By similarityAdd
BLAST

GO - Molecular functioni

  1. acetylcholine receptor regulator activity Source: MGI
  2. calcium ion binding Source: UniProtKB
  3. chondroitin sulfate binding Source: UniProtKB
  4. dystroglycan binding Source: UniProtKB
  5. heparan sulfate proteoglycan binding Source: UniProtKB
  6. sialic acid binding Source: UniProtKB

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. multicellular organismal development Source: UniProtKB-KW
  3. neuromuscular junction development Source: MGI
  4. neurotransmitter receptor metabolic process Source: MGI
  5. plasma membrane organization Source: MGI
  6. positive regulation of filopodium assembly Source: UniProtKB
  7. positive regulation of neuron apoptotic process Source: MGI
  8. positive regulation of protein binding Source: UniProt
  9. positive regulation of protein geranylgeranylation Source: UniProtKB
  10. positive regulation of protein phosphorylation Source: UniProtKB
  11. positive regulation of Rho GTPase activity Source: UniProtKB
  12. positive regulation of synaptic growth at neuromuscular junction Source: UniProtKB
  13. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  14. receptor clustering Source: MGI
  15. regulation of Rac GTPase activity Source: UniProtKB
  16. regulation of receptor activity Source: GOC
  17. regulation of synaptic growth at neuromuscular junction Source: MGI
  18. synaptic transmission Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiREACT_196489. A tetrasaccharide linker sequence is required for GAG synthesis.
REACT_196606. ECM proteoglycans.
REACT_196607. Non-integrin membrane-ECM interactions.
REACT_198569. Retinoid metabolism and transport.
REACT_198654. HS-GAG biosynthesis.
REACT_198967. HS-GAG degradation.
REACT_216309. Integrin cell surface interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Agrin
Cleaved into the following 4 chains:
Gene namesi
Name:Agrn
Synonyms:Agrin
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:87961. Agrn.

Subcellular locationi

GO - Cellular componenti

  1. basal lamina Source: MGI
  2. basement membrane Source: MGI
  3. cell junction Source: UniProtKB-KW
  4. cell surface Source: MGI
  5. extracellular region Source: Reactome
  6. extracellular space Source: MGI
  7. Golgi lumen Source: Reactome
  8. integral component of membrane Source: UniProtKB-KW
  9. plasma membrane Source: UniProtKB-KW
  10. synapse Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 19501950AgrinPRO_0000356178Add
BLAST
Chaini48 – 986939Agrin N-terminal 110 kDa subunitPRO_0000421617Add
BLAST
Chaini987 – 1950964Agrin C-terminal 110 kDa subunitPRO_0000421618Add
BLAST
Chaini987 – 1745759Agrin C-terminal 90 kDa fragmentPRO_0000421619Add
BLAST
Chaini1746 – 1950205Agrin C-terminal 22 kDa fragmentPRO_0000421620Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi97 ↔ 116By similarity
Disulfide bondi105 ↔ 137By similarity
Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi171 ↔ 191By similarity
Disulfide bondi180 ↔ 212By similarity
Disulfide bondi244 ↔ 263By similarity
Disulfide bondi252 ↔ 284By similarity
Disulfide bondi316 ↔ 335By similarity
Disulfide bondi324 ↔ 356By similarity
Disulfide bondi389 ↔ 408By similarity
Disulfide bondi397 ↔ 429By similarity
Disulfide bondi454 ↔ 473By similarity
Disulfide bondi462 ↔ 494By similarity
Disulfide bondi518 ↔ 538By similarity
Disulfide bondi527 ↔ 559By similarity
Disulfide bondi604 ↔ 624By similarity
Disulfide bondi613 ↔ 645By similarity
Glycosylationi672 – 6721N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi688 ↔ 700By similarity
Disulfide bondi690 ↔ 707By similarity
Disulfide bondi709 ↔ 718By similarity
Disulfide bondi721 ↔ 739By similarity
Disulfide bondi742 ↔ 754By similarity
Disulfide bondi744 ↔ 761By similarity
Disulfide bondi763 ↔ 772By similarity
Disulfide bondi775 ↔ 786By similarity
Disulfide bondi823 ↔ 843By similarity
Glycosylationi827 – 8271N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi832 ↔ 864By similarity
Glycosylationi948 – 9481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi1215 ↔ 1226By similarity
Disulfide bondi1220 ↔ 1237By similarity
Disulfide bondi1239 ↔ 1248By similarity
Disulfide bondi1401 ↔ 1430By similarity
Disulfide bondi1435 ↔ 1446By similarity
Disulfide bondi1440 ↔ 1456By similarity
Disulfide bondi1458 ↔ 1467By similarity
Disulfide bondi1474 ↔ 1485By similarity
Disulfide bondi1479 ↔ 1495By similarity
Disulfide bondi1497 ↔ 1506By similarity
Disulfide bondi1704 ↔ 1718By similarity
Disulfide bondi1712 ↔ 1727By similarity
Disulfide bondi1729 ↔ 1738By similarity
Disulfide bondi1921 ↔ 1947By similarity

Post-translational modificationi

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.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). Cleavage is developmentally regulated. In developing brain, neurotrypsin-mediated cleavage occurs mainly during late fetal days and in the first postnatal week.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Heparan sulfate, Proteoglycan

Proteomic databases

MaxQBiA2ASQ1.
PaxDbiA2ASQ1.
PRIDEiA2ASQ1.

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

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

Gene expression databases

BgeeiA2ASQ1.
ExpressionAtlasiA2ASQ1. baseline and differential.
GenevestigatoriA2ASQ1.

Interactioni

Subunit structurei

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.By similarity1 Publication

Structurei

Secondary structure

1
1950
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1520 – 15256Combined sources
Beta strandi1527 – 15304Combined sources
Helixi1533 – 15353Combined sources
Beta strandi1545 – 155511Combined sources
Beta strandi1557 – 15648Combined sources
Beta strandi1572 – 15787Combined sources
Beta strandi1581 – 159010Combined sources
Beta strandi1592 – 15965Combined sources
Beta strandi1605 – 161410Combined sources
Beta strandi1617 – 16226Combined sources
Beta strandi1628 – 16314Combined sources
Beta strandi1649 – 16524Combined sources
Helixi1657 – 16593Combined sources
Helixi1662 – 16643Combined sources
Beta strandi1671 – 16799Combined sources
Helixi1687 – 16893Combined sources
Beta strandi1690 – 16956Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3PVEX-ray1.40A/B1510-1701[»]
ProteinModelPortaliA2ASQ1.
SMRiA2ASQ1. Positions 67-828, 1212-1949.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiA2ASQ1.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2626CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini48 – 19501903ExtracellularSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei27 – 4721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini86 – 13954Kazal-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini159 – 21456Kazal-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini232 – 28655Kazal-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini303 – 35856Kazal-like 4PROSITE-ProRule annotationAdd
BLAST
Domaini379 – 43153Kazal-like 5PROSITE-ProRule annotationAdd
BLAST
Domaini442 – 49655Kazal-like 6PROSITE-ProRule annotationAdd
BLAST
Domaini502 – 56160Kazal-like 7PROSITE-ProRule annotationAdd
BLAST
Domaini594 – 64754Kazal-like 8PROSITE-ProRule annotationAdd
BLAST
Domaini688 – 74154Laminin EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini742 – 78847Laminin EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini812 – 86655Kazal-like 9PROSITE-ProRule annotationAdd
BLAST
Domaini1014 – 1136123SEAPROSITE-ProRule annotationAdd
BLAST
Domaini1211 – 124939EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini1254 – 1430177Laminin G-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini1431 – 146838EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini1470 – 150738EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini1517 – 1699183Laminin G-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini1700 – 173940EGF-like 4PROSITE-ProRule annotationAdd
BLAST
Domaini1775 – 1947173Laminin G-like 3PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi565 – 5728Gly/Ser-rich
Compositional biasi900 – 95051Ser/Thr-richAdd
BLAST
Compositional biasi962 – 9687Gly/Ser-rich
Compositional biasi1138 – 120669Ser/Thr-richAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Contains 4 EGF-like domains.PROSITE-ProRule annotation
Contains 9 Kazal-like domains.PROSITE-ProRule annotation
Contains 2 laminin EGF-like domains.PROSITE-ProRule annotation
Contains 3 laminin G-like domains.PROSITE-ProRule annotation
Contains 1 SEA domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Laminin EGF-like domain, Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG312635.
GeneTreeiENSGT00530000063501.
HOGENOMiHOG000033860.
HOVERGENiHBG080471.
InParanoidiA2ASQ1.
OrthoDBiEOG7BGHJZ.
PhylomeDBiA2ASQ1.
TreeFamiTF326548.

Family and domain databases

Gene3Di2.60.120.200. 4 hits.
3.30.70.960. 1 hit.
InterProiIPR013320. ConA-like_dom.
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]
PfamiPF00008. 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]
SMARTiSM00181. 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]
SUPFAMiSSF49899. SSF49899. 3 hits.
SSF82671. SSF82671. 1 hit.
PROSITEiPS00022. 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]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

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) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MPPLPLEHRP RQQPGASVLV RYFMIPCNIC LILLATSTLG FAVLLFLSNY
60 70 80 90 100
KPGIHFTAAP SMPPDVCRGM LCGFGAVCEP SVEDPGRASC VCKKNVCPAM
110 120 130 140 150
VAPVCGSDAS TYSNECELQR AQCNQQRRIR LLRQGPCGSR DPCANVTCSF
160 170 180 190 200
GSTCVPSADG QTASCLCPTT CFGAPDGTVC GSDGVDYPSE CQLLRHACAN
210 220 230 240 250
QEHIFKKFDG PCDPCQGSMS DLNHICRVNP RTRHPEMLLR PENCPAQHTP
260 270 280 290 300
ICGDDGVTYE NDCVMSRIGA ARGLLLQKVR SGQCQTRDQC PETCQFNSVC
310 320 330 340 350
LSRRGRPHCS CDRVTCDGAY RPVCAQDGHT YDNDCWRQQA ECRQQQTIPP
360 370 380 390 400
KHQGPCDQTP SPCRGAQCAF GATCTVKNGK AVCECQRVCS GGYDPVCGSD
410 420 430 440 450
GVTYGSVCEL ESMACTLGRE IRVARRGPCD RCGQCRFGSL CEVETGRCVC
460 470 480 490 500
PSECVESAQP VCGSDGHTYA SECELHVHAC THQISLYVAS AGHCQTCGET
510 520 530 540 550
VCTFGAVCSA GQCVCPRCEH PPPGPVCGSD GVTYLSACEL REAACQQQVQ
560 570 580 590 600
IEEARAGPCE PAECGSGGSG SGEDNACEQE LCRQHGGVWD EDSEDGPCVC
610 620 630 640 650
DFSCQSVLKS PVCGSDGVTY STECHLKKAR CEARQELYVA AQGACRGPTL
660 670 680 690 700
APLLPMASPH CAQTPYGCCQ DNVTAAQGVG LAGCPSTCHC NPHGSYSGTC
710 720 730 740 750
DPVTGQCSCR PGVGGLRCDR CEPGFWNFRG IVTDGHSGCT PCSCDPRGAV
760 770 780 790 800
RDDCEQMTGL CSCRPGVAGP KCGQCPDGQA LGHLGCEADP TTPVTCVEMH
810 820 830 840 850
CEFGASCVEE AGFAQCVCPT LTCPEANSTK VCGSDGVTYG NECQLKTIAC
860 870 880 890 900
RQRLDISIQS LGPCRESVAP GVSPTSASMT TPRHILSRTL ASPHSSLPLS
910 920 930 940 950
PSTTAHDWPT PLPTSPQTVV GTPRSTAATP SDVASLATAI FRESGSTNGS
960 970 980 990 1000
GDEELSGDEE ASGGGSGGLE PPVGSVVVTH GPPIERASCY NSPLGCCSDG
1010 1020 1030 1040 1050
KTPSLDSEGS NCPATKAFQG VLELEGVEGQ ELFYTPEMAD PKSELFGETA
1060 1070 1080 1090 1100
RSIESTLDDL FRNSDVKKDF WSIRLRELGP GKLVRAIVDV HFDPTTAFQA
1110 1120 1130 1140 1150
PDVGQALLQQ IQVSRPWALA VRRPLREHVR FLDFDWFPTF FTGAATGTTA
1160 1170 1180 1190 1200
AVATARATTV SRLSASSVTP RVYPSYTSRP VGRTTAPLTT RRPPTTTASI
1210 1220 1230 1240 1250
DRPRTPGPQR PPKSCDSQPC LHGGTCQDLD SGKGFSCSCT AGRAGTVCEK
1260 1270 1280 1290 1300
VQLPSVPAFK GHSFLAFPTL RAYHTLRLAL EFRALETEGL LLYNGNARGK
1310 1320 1330 1340 1350
DFLALALLDG HVQFRFDTGS GPAVLTSLVP VEPGRWHRLE LSRHWRQGTL
1360 1370 1380 1390 1400
SVDGEAPVVG ESPSGTDGLN LDTKLYVGGL PEEQVATVLD RTSVGIGLKG
1410 1420 1430 1440 1450
CIRMLDINNQ QLELSDWQRA VVQSSGVGEC GDHPCSPNPC HGGALCQALE
1460 1470 1480 1490 1500
AGVFLCQCPP GRFGPTCADE KNPCQPNPCH GSAPCHVLSR GGAKCACPLG
1510 1520 1530 1540 1550
RSGSFCETVL ENAGSRPFLA DFNGFSYLEL KGLHTFERDL GEKMALEMVF
1560 1570 1580 1590 1600
LARGPSGLLL YNGQKTDGKG DFVSLALHNR HLEFRYDLGK GAAIIRSKEP
1610 1620 1630 1640 1650
IALGTWVRVF LERNGRKGAL QVGDGPRVLG ESPKSRKVPH TMLNLKEPLY
1660 1670 1680 1690 1700
VGGAPDFSKL ARGAAVASGF DGAIQLVSLR GHQLLTQEHV LRAVDVAPFA
1710 1720 1730 1740 1750
GHPCTQAVDN PCLNGGSCIP REATYECLCP GGFSGLHCEK GIVEKSVGDL
1760 1770 1780 1790 1800
ETLAFDGRTY IEYLNAVTES ELTNEIPAPE TLDSRALFSE KALQSNHFEL
1810 1820 1830 1840 1850
SLRTEATQGL VLWIGKVGER ADYMALAIVD GHLQLSYDLG SQPVVLRSTV
1860 1870 1880 1890 1900
KVNTNRWLRV RAHREHREGS LQVGNEAPVT GSSPLGATQL DTDGALWLGG
1910 1920 1930 1940 1950
LQKLPVGQAL PKAYGTGFVG CLRDVVVGHR QLHLLEDAVT KPELRPCPTL
Length:1,950
Mass (Da):207,539
Last modified:February 20, 2007 - v1
Checksum:i0679A3F6D8BD1286
GO
Isoform 2 (identifier: A2ASQ1-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:1,928
Mass (Da):205,041
Checksum:i8D720587D8FCA978
GO
Isoform 3 (identifier: A2ASQ1-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:1,867
Mass (Da):198,336
Checksum:iD3CCD34419F1FE14
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1212 – 12121P → T in AAI50704. (PubMed:15489334)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1061 – 10611F → 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. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6161Missing in isoform 3. 1 PublicationVSP_035995Add
BLAST
Alternative sequencei1634 – 16374Missing in isoform 2 and isoform 3. 1 PublicationVSP_035996
Alternative sequencei1771 – 178818Missing in isoform 2 and isoform 3. 1 PublicationVSP_035997Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
UniGeneiMm.273098.

Genome annotation databases

EnsembliENSMUST00000105575; ENSMUSP00000101200; ENSMUSG00000041936. [A2ASQ1-1]
UCSCiuc008wgf.2. mouse. [A2ASQ1-2]
uc008wgg.1. mouse. [A2ASQ1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
UniGenei Mm.273098.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3PVE X-ray 1.40 A/B 1510-1701 [» ]
ProteinModelPortali A2ASQ1.
SMRi A2ASQ1. Positions 67-828, 1212-1949.
ModBasei Search...
MobiDBi Search...

Proteomic databases

MaxQBi A2ASQ1.
PaxDbi A2ASQ1.
PRIDEi A2ASQ1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000105575 ; ENSMUSP00000101200 ; ENSMUSG00000041936 . [A2ASQ1-1 ]
UCSCi uc008wgf.2. mouse. [A2ASQ1-2 ]
uc008wgg.1. mouse. [A2ASQ1-1 ]

Organism-specific databases

MGIi MGI:87961. Agrn.

Phylogenomic databases

eggNOGi NOG312635.
GeneTreei ENSGT00530000063501.
HOGENOMi HOG000033860.
HOVERGENi HBG080471.
InParanoidi A2ASQ1.
OrthoDBi EOG7BGHJZ.
PhylomeDBi A2ASQ1.
TreeFami TF326548.

Enzyme and pathway databases

Reactomei REACT_196489. A tetrasaccharide linker sequence is required for GAG synthesis.
REACT_196606. ECM proteoglycans.
REACT_196607. Non-integrin membrane-ECM interactions.
REACT_198569. Retinoid metabolism and transport.
REACT_198654. HS-GAG biosynthesis.
REACT_198967. HS-GAG degradation.
REACT_216309. Integrin cell surface interactions.

Miscellaneous databases

ChiTaRSi AGRN. mouse.
EvolutionaryTracei A2ASQ1.
PROi A2ASQ1.
SOURCEi Search...

Gene expression databases

Bgeei A2ASQ1.
ExpressionAtlasi A2ASQ1. baseline and differential.
Genevestigatori A2ASQ1.

Family and domain databases

Gene3Di 2.60.120.200. 4 hits.
3.30.70.960. 1 hit.
InterProi IPR013320. ConA-like_dom.
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 ]
Pfami 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 ]
SMARTi 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 ]
SUPFAMi SSF49899. SSF49899. 3 hits.
SSF82671. SSF82671. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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. 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.

Entry informationi

Entry nameiAGRIN_MOUSE
AccessioniPrimary (citable) accession number: A2ASQ1
Secondary accession number(s): A2ASP9, A2ASQ0, B2RWU1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 16, 2008
Last sequence update: February 20, 2007
Last modified: October 29, 2014
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3