O00468 (AGRIN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Agrin

Gene names

Name:	AGRN
Synonyms:	AGRIN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2045 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	Plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Ligand of the MUSK signaling complex that directly binds LRP4 in this complex and induces the phosphorylation of MUSK, the kinase of the complex. 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 By similarity.
Subunit structure	Interacts with LRP4; the interaction is direct and recruits AGRIN to the MUSK signaling complex composed at least of MUSK and LRP4 By similarity. Binds to laminin. Ref.4
Subcellular location	Secreted › extracellular space › extracellular matrix. Note: Synaptic basal lamina at the neuromuscular junction By similarity.
Post-translational modification	Contains heparan sulfate chains as well as N-linked and O-linked oligosaccharides By similarity.
Sequence similarities	Contains 4 EGF-like domains. Contains 9 Kazal-like domains. Contains 2 laminin EGF-like domains. Contains 3 laminin G-like domains. Contains 1 NtA (N-terminal agrin) domain. Contains 1 SEA domain.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Laminin EGF-like domain Repeat Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Heparan sulfate Proteoglycan
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled acetylcholine receptor signaling pathway Traceable author statement. Source: UniProtKB axon guidance Traceable author statement. Source: Reactome clustering of voltage-gated sodium channels Traceable author statement. Source: UniProtKB receptor clustering Inferred from direct assay. Source: UniProtKB
Cellular component	basal lamina Inferred from direct assay. Source: UniProtKB
Molecular function	laminin binding Traceable author statement Ref.1. Source: UniProtKB structural constituent of cytoskeleton Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 2045	2016	Agrin		PRO_0000007471
Regions
	Domain	30 – 157	128	NtA
	Domain	191 – 244	54	Kazal-like 1
	Domain	264 – 319	56	Kazal-like 2
	Domain	337 – 391	55	Kazal-like 3
	Domain	408 – 463	56	Kazal-like 4
	Domain	484 – 536	53	Kazal-like 5
	Domain	540 – 601	62	Kazal-like 6
	Domain	607 – 666	60	Kazal-like 7
	Domain	699 – 752	54	Kazal-like 8
	Domain	793 – 846	54	Laminin EGF-like 1
	Domain	847 – 893	47	Laminin EGF-like 2
	Domain	917 – 971	55	Kazal-like 9
	Domain	1130 – 1252	123	SEA
	Domain	1329 – 1367	39	EGF-like 1
	Domain	1372 – 1548	177	Laminin G-like 1
	Domain	1549 – 1586	38	EGF-like 2
	Domain	1588 – 1625	38	EGF-like 3
	Domain	1635 – 1818	184	Laminin G-like 2
	Domain	1814 – 1853	40	EGF-like 4
	Domain	1864 – 2042	179	Laminin G-like 3
	Compositional bias	974 – 1099	126	Ser/Thr-rich
	Compositional bias	1254 – 1324	71	Ser/Thr-rich
Amino acid modifications
	Glycosylation	135	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	250	1	N-linked (GlcNAc...) Potential
	Glycosylation	777	1	N-linked (GlcNAc...) Potential
	Glycosylation	932	1	N-linked (GlcNAc...) Potential
	Disulfide bond	31 ↔ 103		By similarity
	Disulfide bond	152 ↔ 177		Or C-152 with C-183 By similarity
	Disulfide bond	793 ↔ 805		By similarity
	Disulfide bond	795 ↔ 812		By similarity
	Disulfide bond	814 ↔ 823		By similarity
	Disulfide bond	826 ↔ 844		By similarity
	Disulfide bond	847 ↔ 859		By similarity
	Disulfide bond	849 ↔ 866		By similarity
	Disulfide bond	868 ↔ 877		By similarity
	Disulfide bond	880 ↔ 891		By similarity
	Disulfide bond	1333 ↔ 1344		By similarity
	Disulfide bond	1338 ↔ 1355		By similarity
	Disulfide bond	1357 ↔ 1366		By similarity
	Disulfide bond	1519 ↔ 1548		By similarity
	Disulfide bond	1553 ↔ 1564		By similarity
	Disulfide bond	1558 ↔ 1574		By similarity
	Disulfide bond	1576 ↔ 1585		By similarity
	Disulfide bond	1592 ↔ 1603		By similarity
	Disulfide bond	1597 ↔ 1613		By similarity
	Disulfide bond	1615 ↔ 1624		By similarity
	Disulfide bond	1818 ↔ 1832		By similarity
	Disulfide bond	1826 ↔ 1841		By similarity
	Disulfide bond	1843 ↔ 1852		By similarity
	Disulfide bond	2016 ↔ 2042		By similarity
Natural variations
	Natural variant	1666	1	V → I. Corresponds to variant rs17160775 [ dbSNP | Ensembl ].		VAR_048966
Experimental info
	Sequence conflict	343	1	L → R in AAB52917. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O00468 [UniParc]. Last modified September 5, 2006. Version 4. Checksum: 108BDA7146ECB94D	FASTA	2,045	214,846
	10 20 30 40 50 60 MAGRSHPGPL RPLLPLLVVA ACVLPGAGGT CPERALERRE EEANVVLTGT VEEILNVDPV 70 80 90 100 110 120 QHTYSCKVRV WRYLKGKDLV ARESLLDGGN KVVISGFGDP LICDNQVSTG DTRIFFVNPA 130 140 150 160 170 180 PPYLWPAHKN ELMLNSSLMR ITLRNLEEVE FCVEDKPGTH FTPVPPTPPD ACRGMLCGFG 190 200 210 220 230 240 AVCEPNAEGP GRASCVCKKS PCPSVVAPVC GSDASTYSNE CELQRAQCSQ QRRIRLLSRG 250 260 270 280 290 300 PCGSRDPCSN VTCSFGSTCA RSADGLTASC LCPATCRGAP EGTVCGSDGA DYPGECQLLR 310 320 330 340 350 360 RACARQENVF KKFDGPCDPC QGALPDPSRS CRVNPRTRRP EMLLRPESCP ARQAPVCGDD 370 380 390 400 410 420 GVTYENDCVM GRSGAARGLL LQKVRSGQCQ GRDQCPEPCR FNAVCLSRRG RPRCSCDRVT 430 440 450 460 470 480 CDGAYRPVCA QDGRTYDSDC WRQQAECRQQ RAIPSKHQGP CDQAPSPCLG VQCAFGATCA 490 500 510 520 530 540 VKNGQAACEC LQACSSLYDP VCGSDGVTYG SACELEATAC TLGREIQVAR KGPCDRCGQC 550 560 570 580 590 600 RFGALCEAET GRCVCPSECV ALAQPVCGSD GHTYPSECML HVHACTHQIS LHVASAGPCE 610 620 630 640 650 660 TCGDAVCAFG AVCSAGQCVC PRCEHPPPGP VCGSDGVTYG SACELREAAC LQQTQIEEAR 670 680 690 700 710 720 AGPCEQAECG SGGSGSGEDG DCEQELCRQR GGIWDEDSED GPCVCDFSCQ SVPGSPVCGS 730 740 750 760 770 780 DGVTYSTECE LKKARCESQR GLYVAAQGAC RGPTFAPLPP VAPLHCAQTP YGCCQDNITA 790 800 810 820 830 840 ARGVGLAGCP SACQCNPHGS YGGTCDPATG QCSCRPGVGG LRCDRCEPGF WNFRGIVTDG 850 860 870 880 890 900 RSGCTPCSCD PQGAVRDDCE QMTGLCSCKP GVAGPKCGQC PDGRALGPAG CEADASAPAT 910 920 930 940 950 960 CAEMRCEFGA RCVEESGSAH CVCPMLTCPE ANATKVCGSD GVTYGNECQL KTIACRQGLQ 970 980 990 1000 1010 1020 ISIQSLGPCQ EAVAPSTHPT SASVTVTTPG LLLSQALPAP PGALPLAPSS TAHSQTTPPP 1030 1040 1050 1060 1070 1080 SSRPRTTASV PRTTVWPVLT VPPTAPSPAP SLVASAFGES GSTDGSSDEE LSGDQEASGG 1090 1100 1110 1120 1130 1140 GSGGLEPLEG SSVATPGPPV ERASCYNSAL GCCSDGKTPS LDAEGSNCPA TKVFQGVLEL 1150 1160 1170 1180 1190 1200 EGVEGQELFY TPEMADPKSE LFGETARSIE STLDDLFRNS DVKKDFRSVR LRDLGPGKSV 1210 1220 1230 1240 1250 1260 RAIVDVHFDP TTAFRAPDVA RALLRQIQVS RRRSLGVRRP LQEHVRFMDF DWFPAFITGA 1270 1280 1290 1300 1310 1320 TSGAIAAGAT ARATTASRLP SSAVTPRAPH PSHTSQPVAK TTAAPTTRRP PTTAPSRVPG 1330 1340 1350 1360 1370 1380 RRPPAPQQPP KPCDSQPCFH GGTCQDWALG GGFTCSCPAG RGGAVCEKVL GAPVPAFEGR 1390 1400 1410 1420 1430 1440 SFLAFPTLRA YHTLRLALEF RALEPQGLLL YNGNARGKDF LALALLDGRV QLRFDTGSGP 1450 1460 1470 1480 1490 1500 AVLTSAVPVE PGQWHRLELS RHWRRGTLSV DGETPVLGES PSGTDGLNLD TDLFVGGVPE 1510 1520 1530 1540 1550 1560 DQAAVALERT FVGAGLRGCI RLLDVNNQRL ELGIGPGAAT RGSGVGECGD HPCLPNPCHG 1570 1580 1590 1600 1610 1620 GAPCQNLEAG RFHCQCPPGR VGPTCADEKS PCQPNPCHGA APCRVLPEGG AQCECPLGRE 1630 1640 1650 1660 1670 1680 GTFCQTASGQ DGSGPFLADF NGFSHLELRG LHTFARDLGE KMALEVVFLA RGPSGLLLYN 1690 1700 1710 1720 1730 1740 GQKTDGKGDF VSLALRDRRL EFRYDLGKGA AVIRSREPVT LGAWTRVSLE RNGRKGALRV 1750 1760 1770 1780 1790 1800 GDGPRVLGES PVPHTVLNLK EPLYVGGAPD FSKLARAAAV SSGFDGAIQL VSLGGRQLLT 1810 1820 1830 1840 1850 1860 PEHVLRQVDV TSFAGHPCTR ASGHPCLNGA SCVPREAAYV CLCPGGFSGP HCEKGLVEKS 1870 1880 1890 1900 1910 1920 AGDVDTLAFD GRTFVEYLNA VTESEKALQS NHFELSLRTE ATQGLVLWSG KATERADYVA 1930 1940 1950 1960 1970 1980 LAIVDGHLQL SYNLGSQPVV LRSTVPVNTN RWLRVVAHRE QREGSLQVGN EAPVTGSSPL 1990 2000 2010 2020 2030 2040 GATQLDTDGA LWLGGLPELP VGPALPKAYG TGFVGCLRDV VVGRHPLHLL EDAVTKPELR PCPTP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and high expression of human agrin in basement membranes of adult lung and kidney." Groffen A.J.A., Buskens C.A.F., Van Kuppevelt T.H., Veerkamp J.H., Monnens L.A.H., Van den Heuvel L.P.W.J. Eur. J. Biochem. 254:123-128(1998) [PubMed: 9652404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Kato S. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retinal pigment epithelium.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Agrin binds to the nerve-muscle basal lamina via laminin." Denzer A.J., Brandenberger R., Gesemann M., Chiquet M., Ruegg M.A. J. Cell Biol. 137:671-683(1997) [PubMed: 9151673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-172, INTERACTION WITH LAMIN.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1558-2045. Tissue: Brain, Colon and Kidney.
[6]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U84406 mRNA. Translation: AAB52917.1. AB191264 mRNA. Translation: BAD52440.1. AL645608 Genomic DNA. Translation: CAI15575.2. AF016903 mRNA. Translation: AAC39776.1. BC004220 mRNA. Translation: AAH04220.2. BC007649 mRNA. Translation: AAH07649.1. BC034009 mRNA. Translation: AAH34009.1. BC063620 mRNA. Translation: AAH63620.1.
IPI	IPI00374563.
RefSeq	NP_940978.2. NM_198576.3.
UniGene	Hs.273330.
3D structure databases
ProteinModelPortal	O00468.
SMR	O00468. Positions 36-146, 159-752, 802-888, 900-973, 1332-1535, 1556-1625, 1633-1810, 1821-1853, 1862-2042.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00468. 3 interactions.
MINT	MINT-4053526.
STRING	O00468.
PTM databases
PhosphoSite	O00468.
Proteomic databases
PRIDE	O00468.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379370; ENSP00000368678; ENSG00000188157.
GeneID	375790.
KEGG	hsa:375790.
UCSC	uc001ack.1. human.
Organism-specific databases
CTD	375790.
GeneCards	GC01P000946.
H-InvDB	HIX0000012.
HGNC	HGNC:329. AGRN.
HPA	HPA040090.
MIM	103320. gene.
neXtProt	NX_O00468.
Orphanet	98913. Postsynaptic congenital myasthenic syndromes.
PharmGKB	PA162375938. PA24626.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14843.
HOVERGEN	HBG080471.
InParanoid	O00468.
OMA	CEQAECG.
OrthoDB	EOG4HQDHD.
PhylomeDB	O00468.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	O00468.
Bgee	O00468.
CleanEx	HS_AGRN.
Genevestigator	O00468.
GermOnline	ENSG00000188157. Homo sapiens.
Family and domain databases
InterPro	IPR004850. Agrin_NtA. IPR008985. ConA-like_lec_gl. IPR013320. ConA-like_subgrp. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR002049. EGF_laminin. IPR003645. Fol_N. IPR001791. Laminin_G. IPR012679. Laminin_G_1. IPR002350. Prot_inh_Kazal. IPR011497. Prot_Inh_Kazal_2. IPR000082. SEA. IPR008993. TIMP-like_OB-fold. [Graphical view]
Gene3D	G3DSA:2.60.120.200. ConA_like_subgrp. 3 hits.
KO	K06254.
Pfam	PF00008. EGF. 3 hits. PF00050. Kazal_1. 3 hits. PF07648. Kazal_2. 6 hits. PF00053. Laminin_EGF. 2 hits. PF00054. Laminin_G_1. 3 hits. PF03146. NtA. 1 hit. PF01390. SEA. 1 hit. [Graphical view]
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. SSF50242. TIMP_like. 1 hit.
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. PS51121. NTA. 1 hit. PS50024. SEA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	100617.
SOURCE	Search...

Entry information

Entry name

AGRIN_HUMAN

Accession

Primary (citable) accession number: O00468
Secondary accession number(s): Q5SVA2 , Q60FE1, Q7KYS8, Q8N4J5, Q96IC1, Q9BTD4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2004
Last sequence update:	September 5, 2006
Last modified:	January 25, 2012
This is version 109 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.