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Protein

Agrin

Gene

AGRN

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: 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. 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 homeostasis 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.
Isoform 9: transmembrane agrin (TM-agrin), the predominant 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, isoform 4 and isoform 7: muscle agrin isoforms, which lack the 8-amino acid insert at the 'B' site, but with the insert at the'A' site have no AChr clustering activity nor MUSK activation but bind heparin. Bind alpha-dystroglycan with lower affinity.
Isoform 5: muscle agrin A0B0 lacking inserts at both 'A' and 'B' sites has no heparin-binding nor AChR clustering activity but binds strongly alpha-dystroglycan.
Agrin N-terminal 110 kDa subunit: is involved in modulation of growth factor signaling (By similarity). Involved also in the 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 similarity7 Publications
Agrin C-terminal 22 kDa fragment: this released fragment is important for agrin signaling and to exert a maximal dendritic filopodia-inducing effect. All 'B' splice variants of this fragment also show an increase in the number of filopodia.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1765 – 17651Alternative splice site to produce 'A' isoformBy similarity
Sitei1875 – 18751Critical for cleavage by neurotrypsinBy similarity
Sitei1901 – 19011Alternative splice site to produce 'B' isoformsBy similarity
Sitei1905 – 19051Highly important for the agrin receptor complex activity of the 'B8' insertBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi1953 – 202270Add
BLAST

GO - Molecular functioni

  • acetylcholine receptor regulator activity Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • chondroitin sulfate binding Source: UniProtKB
  • dystroglycan binding Source: UniProtKB
  • heparan sulfate proteoglycan binding Source: UniProtKB
  • heparin binding Source: UniProtKB
  • laminin binding Source: UniProtKB
  • sialic acid binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase activator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Agrin
Cleaved into the following 4 chains:
Gene namesi
Name:AGRN
Synonyms:AGRIN
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
Proteomesi
  • UP000000539 Componenti: Unplaced

Subcellular locationi

Isoform 1 :
Isoform 9 :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Extracellular matrix, Membrane, Secreted, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1902 – 19087HLSNEIP → AAANEIA: No reduction in AGRN-induced MUSK phosphorylation. 1 Publication
Mutagenesisi1905 – 19073NEI → AAA or AES: Large reduction in AGRN-induced MUSK phosphorylation. 1 Publication
Mutagenesisi1905 – 19062NE → AA: Some reduction in AGRN-induced MUSK phosphorylation.
Mutagenesisi1905 – 19051N → A: No effect on AGRN-induced MUSK phosphorylation. 1 Publication
Mutagenesisi1906 – 19061E → A: No effect on AGRN-induced MUSK phosphorylation. 1 Publication
Mutagenesisi1907 – 19071I → A: No effect on AGRN-induced MUSK phosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 20812057AgrinPRO_0000055624Add
BLAST
Chaini25 – 11161092Agrin N-terminal 110 kDa subunitPRO_0000421629Add
BLAST
Chaini1117 – 2081965Agrin C-terminal 110 kDa subunitPRO_0000421630Add
BLAST
Chaini1117 – 1876760Agrin C-terminal 90 kDa fragmentPRO_0000421631Add
BLAST
Chaini1877 – 2081205Agrin C-terminal 22 kDa fragmentPRO_0000421632Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi26 ↔ 98
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence analysis
Disulfide bondi147 ↔ 179Or C-147 with C-185
Disulfide bondi204 ↔ 223Sequence analysis
Disulfide bondi212 ↔ 244Sequence analysis
Disulfide bondi278 ↔ 298Sequence analysis
Disulfide bondi287 ↔ 319Sequence analysis
Disulfide bondi351 ↔ 370Sequence analysis
Disulfide bondi359 ↔ 391Sequence analysis
Disulfide bondi422 ↔ 441Sequence analysis
Disulfide bondi430 ↔ 462Sequence analysis
Disulfide bondi496 ↔ 515Sequence analysis
Disulfide bondi504 ↔ 536Sequence analysis
Glycosylationi508 – 5081N-linked (GlcNAc...)Sequence analysis
Disulfide bondi561 ↔ 580Sequence analysis
Disulfide bondi569 ↔ 601Sequence analysis
Disulfide bondi625 ↔ 645Sequence analysis
Disulfide bondi634 ↔ 666Sequence analysis
Disulfide bondi710 ↔ 730Sequence analysis
Disulfide bondi719 ↔ 751Sequence analysis
Glycosylationi777 – 7771N-linked (GlcNAc...)Sequence analysis
Disulfide bondi793 ↔ 805By similarity
Disulfide bondi795 ↔ 812By similarity
Disulfide bondi814 ↔ 823By similarity
Disulfide bondi826 ↔ 844By similarity
Disulfide bondi847 ↔ 859By similarity
Disulfide bondi849 ↔ 866By similarity
Disulfide bondi868 ↔ 877By similarity
Disulfide bondi880 ↔ 891By similarity
Glycosylationi882 – 8821N-linked (GlcNAc...)Sequence analysis
Disulfide bondi928 ↔ 948Sequence analysis
Glycosylationi932 – 9321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi937 ↔ 969Sequence analysis
Disulfide bondi1351 ↔ 1362By similarity
Disulfide bondi1356 ↔ 1371By similarity
Disulfide bondi1373 ↔ 1382By similarity
Disulfide bondi1568 ↔ 1579By similarity
Disulfide bondi1573 ↔ 1589By similarity
Disulfide bondi1591 ↔ 1600By similarity
Disulfide bondi1607 ↔ 1618By similarity
Disulfide bondi1612 ↔ 1628By similarity
Disulfide bondi1630 ↔ 1639By similarity
Disulfide bondi1836 ↔ 1849By similarity
Disulfide bondi1843 ↔ 1858By similarity
Disulfide bondi1860 ↔ 1869By similarity
Disulfide bondi2052 ↔ 2078

Post-translational modificationi

Contains heparan and chondroitin sulfate chains and alpha-dystroglycan as well as N-linked and O-linked oligosaccharides. Glycosaminoglycans (GAGs), present in the N-terminal 110 kDa fragment, are required for induction of filopodia in hippocampal neurons. The first cluster (Gly/Ser-rich) for GAG attachment contains heparan sulfate (HS)chains and the second cluster (Ser/Thr-rich), contains chondroitin sulfate (CS) chains (By similarity). C-terminal heparin and heparin sulfate binding 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. Inserts at the 'B' site have no effect on sialic acid binding.By similarity1 Publication
At synaptic junctions, cleaved at two conserved sites, alpha and beta, by neurotrypsin. Cleavage at the alpha-site produces the N- and C- terminal 110-kDa subunits. Further cleavage of the C-terminal at the beta site produces C-terminal fragments, C22 and C90, of 90 kDa and 22 kDa respectively (By similarity).By similarity
Proteolytically cleaved in vitro in both the N-terminal and C-terminal by several matrix metaloproteinases (MMPs).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei140 – 1412Cleavage; by MMP1
Sitei153 – 1542Cleavage; by MMP7
Sitei161 – 1622Cleavage; by MMP12
Sitei1116 – 11172Cleavage, alpha site; by neurotrypsinBy similarity
Sitei1821 – 18222Cleavage; by MMP1
Sitei1830 – 18312Cleavage; by MMP7
Sitei1876 – 18772Cleavage, beta site; by neurotrypsinBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Heparan sulfate, Proteoglycan

Proteomic databases

PaxDbiP31696.
PRIDEiP31696.

Expressioni

Tissue specificityi

Detected in embryonic brain, spinal cord, skeletal muscle, vitreous humor and liver (at protein level).1 Publication

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. 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 'B8' insert present in the B8 isoforms. Interacts with DAG1; the interaction is influenced by cell surface glycosaminoglycans and by alternative splicing of AGRN.By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-457650,EBI-2431589From a different organism.
Lamb1P024692EBI-457650,EBI-6662997From a different organism.

GO - Molecular functioni

  • dystroglycan binding Source: UniProtKB
  • heparan sulfate proteoglycan binding Source: UniProtKB
  • laminin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi676782. 1 interaction.
IntActiP31696. 6 interactions.
STRINGi9031.ENSGALP00000039379.

Structurei

Secondary structure

1
2081
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi31 – 366Combined sources
Beta strandi39 – 5315Combined sources
Turni54 – 574Combined sources
Beta strandi58 – 7013Combined sources
Helixi72 – 787Combined sources
Turni83 – 853Combined sources
Beta strandi86 – 927Combined sources
Beta strandi97 – 993Combined sources
Beta strandi107 – 1148Combined sources
Helixi117 – 1193Combined sources
Turni120 – 1256Combined sources
Beta strandi126 – 1294Combined sources
Helixi138 – 15215Combined sources
Beta strandi1879 – 18813Combined sources
Beta strandi1884 – 18896Combined sources
Beta strandi1892 – 18954Combined sources
Beta strandi1922 – 193514Combined sources
Beta strandi1938 – 19469Combined sources
Beta strandi1954 – 19607Combined sources
Beta strandi1963 – 197210Combined sources
Beta strandi1975 – 19828Combined sources
Beta strandi1985 – 19873Combined sources
Beta strandi1989 – 19968Combined sources
Beta strandi1999 – 20046Combined sources
Beta strandi2010 – 20134Combined sources
Beta strandi2021 – 20233Combined sources
Beta strandi2026 – 20316Combined sources
Turni2037 – 20404Combined sources
Helixi2043 – 20464Combined sources
Beta strandi2050 – 20589Combined sources
Turni2065 – 20673Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JB3X-ray1.60A26-156[»]
1JC7X-ray2.73A26-154[»]
1PXUX-ray2.20A25-155[»]
1PZ7X-ray1.42A/B1870-2081[»]
1PZ8X-ray2.35A/B/C/D1870-2081[»]
1PZ9X-ray2.80A/B1870-2081[»]
1Q56NMR-A1870-2081[»]
3I70X-ray2.30A26-153[»]
ProteinModelPortaliP31696.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31696.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 159135NtAPROSITE-ProRule annotationAdd
BLAST
Domaini193 – 24654Kazal-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini268 – 32154Kazal-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini339 – 39355Kazal-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini409 – 46456Kazal-like 4PROSITE-ProRule annotationAdd
BLAST
Domaini486 – 53853Kazal-like 5PROSITE-ProRule annotationAdd
BLAST
Domaini551 – 60353Kazal-like 6PROSITE-ProRule annotationAdd
BLAST
Domaini616 – 66853Kazal-like 7PROSITE-ProRule annotationAdd
BLAST
Domaini700 – 75354Kazal-like 8PROSITE-ProRule annotationAdd
BLAST
Domaini793 – 84654Laminin EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini847 – 89347Laminin EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini917 – 97155Kazal-like 9PROSITE-ProRule annotationAdd
BLAST
Domaini1144 – 1266123SEAPROSITE-ProRule annotationAdd
BLAST
Domaini1347 – 138337EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini1388 – 1563176Laminin G-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini1564 – 160138EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini1603 – 164038EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini1650 – 1831182Laminin G-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini1832 – 187039EGF-like 4PROSITE-ProRule annotationAdd
BLAST
Domaini1894 – 2078185Laminin G-like 3PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi671 – 6788Gly/Ser-rich
Compositional biasi974 – 1113140Ser/Thr-richAdd
BLAST
Compositional biasi1072 – 109928Gly/Ser-richAdd
BLAST
Compositional biasi1268 – 133770Ser/Thr-richAdd
BLAST

Domaini

The 4 amino acid insert at the 'A' site is required for effecient binding of heparin.
The NtA domain, absent in TM-Agrin, is required for binding laminin and connecting to basal lamina.
Both laminin G-like 2 (G2) and laminin G-like 3 (G3) domains are required for alpha-dystroglycan binding. G3 domain is required for C-terminal heparin, heparan sulfate and sialic acid binding.

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 NtA (N-terminal agrin) domain.PROSITE-ProRule annotation
Contains 1 SEA domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410ITSI. Eukaryota.
ENOG410YKSA. LUCA.
HOGENOMiHOG000033860.
HOVERGENiHBG080471.
InParanoidiP31696.

Family and domain databases

Gene3Di2.60.120.200. 3 hits.
3.30.70.960. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR003884. FacI_MAC.
IPR003645. Fol_N.
IPR002350. Kazal_dom.
IPR002049. Laminin_EGF.
IPR001791. Laminin_G.
IPR004850. NtA_dom.
IPR000082. SEA_dom.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00008. EGF. 4 hits.
PF00050. Kazal_1. 2 hits.
PF07648. Kazal_2. 7 hits.
PF00053. Laminin_EGF. 2 hits.
PF00054. Laminin_G_1. 3 hits.
PF03146. NtA. 1 hit.
PF01390. SEA. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 8 hits.
SM00179. EGF_CA. 3 hits.
SM00180. EGF_Lam. 2 hits.
SM00057. FIMAC. 2 hits.
SM00274. FOLN. 6 hits.
SM00280. KAZAL. 9 hits.
SM00282. LamG. 3 hits.
SM00200. SEA. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 3 hits.
SSF50242. SSF50242. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
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.
PS51121. NTA. 1 hit.
PS50024. SEA. 1 hit.
[Graphical view]

Sequences (10)i

Sequence statusi: Complete.

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

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Many isoforms exist including secreted and transmembrane forms, isoforms with different length inserts produced at the 'B' splice site, B0, B8, B11 and B19, with or without the 'A' splice site insert.

Isoform 1 (identifier: P31696-1) [UniParc]FASTAAdd to basket

Also known as: LN-agrin, agrin A4B19

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
MGGSGAAATL ALGLALGLAL GGWANCPERE LQRREEEANV VLTGTVEEIM
60 70 80 90 100
NVDPVHHTYS CKVRVWRYLK GKDIVTHEIL LDGGNKVVIG GFGDPLICDN
110 120 130 140 150
QVSTGDTRIF FVNPAPQYMW PAHRNELMLN SSLMRITLRN LEEVEHCVEE
160 170 180 190 200
HRKLLADKPN SYFTQTPPTP RDACRGMLCG FGAVCERSPT DPSQASCVCK
210 220 230 240 250
KTACPVVVAP VCGSDYSTYS NECELEKAQC NQQRRIKVIS KGPCGSKDPC
260 270 280 290 300
AEVTCSFGST CVRSADGQTA GCVCPASCSG VAESIVCGSD GKDYRSECDL
310 320 330 340 350
NKHACDKQEN VFKKFDGACD PCKGILNDMN RVCRVNPRTR RVELLSRPEN
360 370 380 390 400
CPSKREPVCG DDGVTYASEC VMGRTGAIRG LEIQKVRSGQ CQHQDKCKDE
410 420 430 440 450
CKFNAVCLKR WHARCSCDRI TCDGTYRPVC ARDSRTYSND CERQKAECHQ
460 470 480 490 500
KAAIPVKHSG PCDLGTPSPC LSVECTFGAT CVVKNREPVC ECQQVCQGRY
510 520 530 540 550
DPVCGSDNRT YGNPCELNAM ACVLKREIRV KHKGPCDRCG KCQFGAICEA
560 570 580 590 600
ETGRCVCPTE CVPSSQPVCG TDGNTYGSEC ELHVRACTQQ KNILVAAQGD
610 620 630 640 650
CKSCGTTVCS FGSTCVGGQC VCPRCEQQPL AQVCGTDGLT YDNRCELRAA
660 670 680 690 700
SCQQQKSIEV AKMGPCEDEC GSGGSGSGDG SECEQDRCRH YGGWWDEDAE
710 720 730 740 750
DDRCVCDFTC LAVPRSPVCG SDDVTYANEC ELKKTRCEKR QNLYVTSQGA
760 770 780 790 800
CRALTTTPPP LPVVHCSQTI YGCCPDNMTL ALGVGAAGCP STCQCNPYGS
810 820 830 840 850
YGGTCDPATG QCSCKPGVGG LKCDRCEPGF WNFRGIVTDS KSGCTPCNCD
860 870 880 890 900
PVGSVRDDCE QMTGLCSCKT GITGMKCNQC PNGSKMGMAG CEKDPSAPKS
910 920 930 940 950
CEEMSCEFGA TCVEVNGFAH CECPSPLCSE ANMTKVCGSD GVTYGDQCQL
960 970 980 990 1000
KTIACRQGQL ITVKHVGQCH ESITHTSHTM PPTPLPTLPL DKLIVPPPLQ
1010 1020 1030 1040 1050
LTTQAPEPTE LATTSLLMEA SPTTRSHPTT RRVTTTRPVT TPWMTHGVLK
1060 1070 1080 1090 1100
TTVRPLSTSP VVLATTQPPY AESGSAEGSG DQEMSISGDQ ESSGAGSAGE
1110 1120 1130 1140 1150
EEVEESQVTP TPAIERATCY NTPLGCCSDG KTAAADAEGS NCPATKVFQG
1160 1170 1180 1190 1200
VLILEEVEGQ ELFYTPEMAD PKSELFGETA RSIESALDEL FRNSDVKNDF
1210 1220 1230 1240 1250
KSIRVRDLGQ SSAVRVIVES HFDPATSYTA ADVQAASLKQ IRASKKRTIL
1260 1270 1280 1290 1300
VKKPQQEHVK FMDFDWIPRI FTTTITTTTA TTMAPATTRR HTTASAATTA
1310 1320 1330 1340 1350
HILRQDTVGH PSAKLAAPAS TRRPTSTLPT TARRKPTRQP PSTTKKPSRP
1360 1370 1380 1390 1400
CDSHPCLHGG TCEDDGREFT CRCPAGKGGA VCEKPIRYFI PSFGGKSYLA
1410 1420 1430 1440 1450
FKMMKAYHTV RIAMEFRATE LSGLLLYNGQ NRGKDFISLA LVGGFVELRF
1460 1470 1480 1490 1500
NTGSGTGVIT SKVRVEPGKW HQLVVNRNRR SGMLAVDGEH VSGESPTGTD
1510 1520 1530 1540 1550
GLNLDTDLFV GGAPEDQMAV VAERTAATVG LKGSIRLLDV NNQMYDLREK
1560 1570 1580 1590 1600
GSDVLYGSGV GECGNDPCHP NPCHHGASCH VKEAEMFHCE CLHSYTGPTC
1610 1620 1630 1640 1650
ADERNPCDPT PCHISATCLV LPEGGAMCAC PMGREGEFCE RVTEQDHTMP
1660 1670 1680 1690 1700
FLPEFNGFSY LELNGLQTLF LTCRQMSMEV VFLAKSPSGM IFYNGQKTDG
1710 1720 1730 1740 1750
KGDFVSLALH DGYLEYRYDL GKGAAVLRSK EPVPLNTWIS VLLERSGRKG
1760 1770 1780 1790 1800
VMRINNGERV MGESPKSRKV PHAFLNLKEP FYVGGAPDFS KLARAAAIST
1810 1820 1830 1840 1850
SFYGAVQRIS IKGVPLLKEQ HIRSAVEIST FRAHPCTQKP NPCQNGGTCS
1860 1870 1880 1890 1900
PRLESYECAC QRGFSGAHCE KVIIEKAAGD AEAIAFDGRT YMEYHNAVTK
1910 1920 1930 1940 1950
SHLSNEIPAP DALDYPAEPS EKALQSNHFE LSIKTEATQG LILWSGKGLE
1960 1970 1980 1990 2000
RSDYIALAIV DGFVQMMYDL GSKPVVLRST VPINTNHWTH IKAYRVQREG
2010 2020 2030 2040 2050
SLQVGNEAPI TGSSPLGATQ LDTDGALWLG GMERLSVAHK LPKAYSTGFI
2060 2070 2080
GCIRDVIVDR QELHLVEDAL NNPTILHCSA K
Length:2,081
Mass (Da):224,980
Last modified:March 6, 2013 - v3
Checksum:i87FEFE1A11664F0E
GO
Isoform 2 (identifier: P31696-2) [UniParc]FASTAAdd to basket

Also known as: Agrin-related protein 1, agrin A4B0

The sequence of this isoform differs from the canonical sequence as follows:
     1902-1920: Missing.

Show »
Length:2,062
Mass (Da):222,962
Checksum:i76AE3422BAD30EB3
GO
Isoform 3 (identifier: P31696-3) [UniParc]FASTAAdd to basket

Also known as: Agrin-related protein 2, agrin A4B8

The sequence of this isoform differs from the canonical sequence as follows:
     1910-1920: Missing.

Show »
Length:2,070
Mass (Da):223,824
Checksum:iF3B5C882943686E2
GO
Isoform 4 (identifier: P31696-4) [UniParc]FASTAAdd to basket

Also known as: Agrin A4B11

The sequence of this isoform differs from the canonical sequence as follows:
     1902-1909: Missing.

Show »
Length:2,073
Mass (Da):224,118
Checksum:i6E67129075A4E130
GO
Isoform 5 (identifier: P31696-5) [UniParc]FASTAAdd to basket

Also known as: Muscle agrin, agrin A0B0

The sequence of this isoform differs from the canonical sequence as follows:
     1766-1769: Missing.
     1902-1920: Missing.

Show »
Length:2,058
Mass (Da):222,462
Checksum:i7716B82777335B3A
GO
Isoform 6 (identifier: P31696-6) [UniParc]FASTAAdd to basket

Also known as: Agrin A0B8

The sequence of this isoform differs from the canonical sequence as follows:
     1766-1769: Missing.
     1910-1920: Missing.

Show »
Length:2,066
Mass (Da):223,324
Checksum:iDFFD9BC55A44F646
GO
Isoform 7 (identifier: P31696-7) [UniParc]FASTAAdd to basket

Also known as: Muscle agrin, agrin A0B11

The sequence of this isoform differs from the canonical sequence as follows:
     1766-1769: Missing.
     1902-1909: Missing.

Show »
Length:2,069
Mass (Da):223,619
Checksum:i2C46FA7C3DF7A6FE
GO
Isoform 8 (identifier: P31696-8) [UniParc]FASTAAdd to basket

Also known as: Agrin A0B19

The sequence of this isoform differs from the canonical sequence as follows:
     1766-1769: Missing.

Show »
Length:2,077
Mass (Da):224,480
Checksum:iDEA9C1133093F7A2
GO
Isoform 9 (identifier: P31696-9) [UniParc]FASTAAdd to basket

Also known as: TM-agrin, SN-agrin

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MGGSGAAATL...NVDPVHHTYS → MTACQYPMAP...FAVLLFLNNY
     61-157: Missing.

Note: Transmembrane isoform produced by usage of an alternative first exon.
Show »
Length:1,981
Mass (Da):214,057
Checksum:i1976A4A4FF374688
GO
Isoform 10 (identifier: P31696-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-156: Missing.

Show »
Length:2,074
Mass (Da):224,132
Checksum:i976F97F9A1E6EDF7
GO

Sequence cautioni

The sequence AAA48585.1 differs from that shown. Reason: Frameshift at position 110. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1247 – 12493RTI → SIL in AAA48586 (PubMed:1314620).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6060MGGSG…HHTYS → MTACQYPMAPGALERDRLYQ HKVSLVVRYFMIPCNICLIL LATSTLGFAVLLFLNNY in isoform 9. 1 PublicationVSP_045770Add
BLAST
Alternative sequencei61 – 15797Missing in isoform 9. 1 PublicationVSP_045771Add
BLAST
Alternative sequencei150 – 1567Missing in isoform 10. CuratedVSP_045772
Alternative sequencei1766 – 17694Missing in isoform 5, isoform 6, isoform 7 and isoform 8. 1 PublicationVSP_045773
Alternative sequencei1902 – 192019Missing in isoform 2 and isoform 5. 1 PublicationVSP_045774Add
BLAST
Alternative sequencei1902 – 19098Missing in isoform 4 and isoform 7. 1 PublicationVSP_045775
Alternative sequencei1910 – 192011Missing in isoform 3 and isoform 6. 1 PublicationVSP_045776Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U35613 mRNA. Translation: AAC59740.1.
M94271 mRNA. Translation: AAA48585.1. Frameshift.
M97371 mRNA. Translation: AAA48586.1.
M97372 mRNA. No translation available.
U07271 mRNA. Translation: AAA16788.1.
PIRiJH0591. AGCH.
UniGeneiGga.4448.
Gga.48948.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U35613 mRNA. Translation: AAC59740.1.
M94271 mRNA. Translation: AAA48585.1. Frameshift.
M97371 mRNA. Translation: AAA48586.1.
M97372 mRNA. No translation available.
U07271 mRNA. Translation: AAA16788.1.
PIRiJH0591. AGCH.
UniGeneiGga.4448.
Gga.48948.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JB3X-ray1.60A26-156[»]
1JC7X-ray2.73A26-154[»]
1PXUX-ray2.20A25-155[»]
1PZ7X-ray1.42A/B1870-2081[»]
1PZ8X-ray2.35A/B/C/D1870-2081[»]
1PZ9X-ray2.80A/B1870-2081[»]
1Q56NMR-A1870-2081[»]
3I70X-ray2.30A26-153[»]
ProteinModelPortaliP31696.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi676782. 1 interaction.
IntActiP31696. 6 interactions.
STRINGi9031.ENSGALP00000039379.

Proteomic databases

PaxDbiP31696.
PRIDEiP31696.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410ITSI. Eukaryota.
ENOG410YKSA. LUCA.
HOGENOMiHOG000033860.
HOVERGENiHBG080471.
InParanoidiP31696.

Miscellaneous databases

EvolutionaryTraceiP31696.
NextBioi20816574.

Family and domain databases

Gene3Di2.60.120.200. 3 hits.
3.30.70.960. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR003884. FacI_MAC.
IPR003645. Fol_N.
IPR002350. Kazal_dom.
IPR002049. Laminin_EGF.
IPR001791. Laminin_G.
IPR004850. NtA_dom.
IPR000082. SEA_dom.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PfamiPF00008. EGF. 4 hits.
PF00050. Kazal_1. 2 hits.
PF07648. Kazal_2. 7 hits.
PF00053. Laminin_EGF. 2 hits.
PF00054. Laminin_G_1. 3 hits.
PF03146. NtA. 1 hit.
PF01390. SEA. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 8 hits.
SM00179. EGF_CA. 3 hits.
SM00180. EGF_Lam. 2 hits.
SM00057. FIMAC. 2 hits.
SM00274. FOLN. 6 hits.
SM00280. KAZAL. 9 hits.
SM00282. LamG. 3 hits.
SM00200. SEA. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 3 hits.
SSF50242. SSF50242. 1 hit.
SSF82671. SSF82671. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
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.
PS51121. NTA. 1 hit.
PS50024. SEA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site."
    Gesemann M., Denzer A.J., Ruegg M.A.
    J. Cell Biol. 128:625-636(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), FUNCTION.
  2. "An amino-terminal extension is required for the secretion of chick agrin and its binding to extracellular matrix."
    Denzer A.J., Gesemann M., Schumacher B., Rueegg M.A.
    J. Cell Biol. 131:1547-1560(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-221 (ISOFORMS 1 AND 9), GLYCOSYLATION, INTERACTION WITH LAMININ, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Spinal cord.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-2073 (ISOFORM 1).
    Tissue: Brain.
  4. "Developmental expression and alternative splicing of chick agrin RNA."
    Thomas W.S., O'Dowd D.K., Smith M.A.
    Dev. Biol. 158:523-535(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1901-1921 (ISOFORM 1).
    Strain: White leghorn.
  5. "The agrin gene codes for a family of basal lamina proteins that differ in function and distribution."
    Rueegg M.A., Tsim K.W.K., Horton S.E., Kroeger S., Escher G., Gensch E.M., McMahan U.J.
    Neuron 8:691-699(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING.
  6. "Alternative splicing of agrin alters its binding to heparin, dystroglycan, and the putative agrin receptor."
    Gesemann M., Cavalli V., Denzer A.J., Brancaccio A., Schumacher B., Ruegg M.A.
    Neuron 16:755-767(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING, INTERACTION WITH DAG1, HEPARIN BINDING.
  7. "Agrin binds to the nerve-muscle basal lamina via laminin."
    Denzer A.J., Brandenberger R., Gesemann M., Chiquet M., Ruegg M.A.
    J. Cell Biol. 137:671-683(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: LAMININ BINDING.
  8. "Effects of purified recombinant neural and muscle agrin on skeletal muscle fibers in vivo."
    Bezakova G., Helm J.P., Francolini M., Lomo T.
    J. Cell Biol. 153:1441-1452(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "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 (ISOFORMS 1 AND 9), SUBCELLULAR LOCATION.
  10. "Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters."
    Winzen U., Cole G.J., Halfter W.
    J. Biol. Chem. 278:30106-30114(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEPARAN SULFATE BINDING, CHONDROITIN SULFATE BINDING.
  11. "Glycosaminoglycan-dependent and -independent inhibition of neurite outgrowth by agrin."
    Baerwald-de la Torre K., Winzen U., Halfter W., Bixby J.L.
    J. Neurochem. 90:50-61(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEPARAN SULFATE BINDING, CHONDROITIN SULFATE BINDING, FUNCTION.
  12. "Activation of muscle-specific receptor tyrosine kinase and binding to dystroglycan are regulated by alternative mRNA splicing of agrin."
    Scotton P., Bleckmann D., Stebler M., Sciandra F., Brancaccio A., Meier T., Stetefeld J., Ruegg M.A.
    J. Biol. Chem. 281:36835-36845(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ALTERNATIVE SPLICING, INTERACTION WITH DAG1, HEPARIN BINDING, MUTAGENESIS OF ASN-1905; GLU-1906; ILE-1907; 1905-ASN--ILE-1907 AND 1902-HIS--PRO-1908.
  13. "Thermodynamic and structural studies of carbohydrate binding by the agrin-G3 domain."
    Sallum C.O., Kammerer R.A., Alexandrescu A.T.
    Biochemistry 46:9541-9550(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DAG1, STRUCTURE OF CARBOHYDRATES, FUNCTION.
  14. "An interdomain disulfide bridge links the NtA and first FS domain in agrin."
    McFarlane A.A., Stetefeld J.
    Protein Sci. 18:2421-2428(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERDOMAIN DISULFIDE BOND.
  15. "The process-inducing activity of transmembrane agrin requires follistatin-like domains."
    Porten E., Seliger B., Schneider V.A., Woll S., Stangel D., Ramseger R., Kroger S.
    J. Biol. Chem. 285:3114-3125(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF ISOFORM 9.
  16. "Site specific cleavage mediated by MMPs regulates function of agrin."
    Patel T.R., Butler G., McFarlane A., Xie I., Overall C.M., Stetefeld J.
    PLoS ONE 7:E43669-E43669(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING BY MMPS, FUNCTION.
  17. Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-156 IN COMPLEX WITH LAMININ, DISULFIDE BOND.
  18. Cited for: STRUCTURE BY NMR OF 1870-2081 IN COMPLEX WITH CALCIUM IONS, X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 1870-2081 IN COMPLEX WITH CALCIUM IONS, DISULFIDE BOND.
  19. "Structure and laminin-binding specificity of the NtA domain expressed in eukaryotic cells."
    Mascarenhas J.B., Rueegg M.A., Sasaki T., Eble J.A., Engel J., Stetefeld J.
    Matrix Biol. 23:507-513(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 26-156, INTERACTION WITH LAMININ, DISULFIDE BOND.

Entry informationi

Entry nameiAGRIN_CHICK
AccessioniPrimary (citable) accession number: P31696
Secondary accession number(s): Q90609, Q90685
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: March 6, 2013
Last modified: May 11, 2016
This is version 163 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.