DegronMD - O00468(AGRN)

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. 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. This secreted isoform forms a bridge, after release from motor neurons, to basal lamina through binding laminin via the NtA domain.; FUNCTION: [Isoform 2]: Transmembrane form that is 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.; FUNCTION: Isoform 1, isoform 4 and isoform 5: neuron-specific (z+) isoforms that contain C-terminal insertions of 8-19 AA are potent activators of AChR clustering. Isoform 5, agrin (z+8), containing the 8-AA insert, forms a receptor complex in myotubules containing the neuronal AGRN, the muscle-specific kinase MUSK and LRP4, a member of the LDL receptor family. The splicing factors, NOVA1 and NOVA2, regulate AGRN splicing and production of the 'z' isoforms.; FUNCTION: Isoform 3 and isoform 6: lack any 'z' insert, are muscle-specific and may be involved in endothelial cell differentiation.; FUNCTION: [Agrin N-terminal 110 kDa subunit]: Is 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). {ECO:0000250, ECO:0000269|PubMed:19631309, ECO:0000269|PubMed:21969364}.; FUNCTION: [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. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P1019S	TCGA-35-4122	LUAD	TCGA	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.P1019S	DO23782	LUAD	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.R1898H	TCGA-A6-5665	COAD	TCGA	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.25
p.R1898H	DO9756	COAD	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.25
p.T1902M	TCGA-AX-A1CE	UCEC	TCGA	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation altering degron motif	0.7423
p.T1902M	DO42280	UCEC	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation altering degron motif	0.7423
p.P1019Q	TCGA-BJ-A28R	THCA	TCGA	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.P1019Q	DO39026	THCA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.R1915L	TCGA-DA-A1I1	SKCM	TCGA	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1111
p.R1915L	DO37966	SKCM	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1111
p.P1019L	TCGA-DF-A2KU	UCEC	TCGA	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.P1019L	DO223286	UCEC	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1111
p.R1898C	TCGA-IB-7651	PAAD	TCGA	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.25
p.R1898C	DO46657	PAAD	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.25
p.A1916V	TCGA-IB-7651	PAAD	TCGA	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.0833
p.A1916V	DO46657	PAAD	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.0833
p.A1012T	DO217788	BRCA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.3056
p.S1896R	DO222548	COCA	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1944
p.S1896R	DO46386	OV	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1944
p.A1912V	DO233280	GACA	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1944
p.A1912V	SIDM00473	Oral Cavity Carcinoma	GDSC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1944
p.L1907F	DO233885	GACA	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation altering degron motif	0.6981
p.Q1015P	DO232852	NACA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.2222
p.T1016N	DO232761	PBCA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1944
p.S1009N	DO229221	THCA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation altering degron motif	0.7069
p.G1002R	DO229232	THCA	ICGC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1944
p.G1002R	ACH-001345	Colon/Colorectal Cancer	CCLE	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1944
p.T1913M	DO41199	UCEC	ICGC	DSGALHS	DEG_SCF_TRCP1_1	1901:1907	Mutation rewiring degron network	0.1667
p.P1008L	SIDM00007	Other Solid Cancers	GDSC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation altering degron motif	0.6471
p.P1008L	ACH-001550	Skin Cancer	CCLE	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation altering degron motif	0.6471
p.P1008L	MCC13	skin	COSMIC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation altering degron motif	0.6471
p.P998L	SIDM00349	Esophageal Squamous Cell Carcinoma	GDSC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.0833
p.P998L	TE-15	oesophagus	COSMIC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.0833
p.P998L	TE-10	oesophagus	COSMIC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.0833
p.H1013Q	ACH-002278	Neuroblastoma	CCLE	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.2778
p.M1016V	C-4-I	cervix	COSMIC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.1944
p.T1013M	SNU-1040	large intestine	COSMIC	APSST	DEG_SPOP_SBC_1	1007:1011	Mutation rewiring degron network	0.2778

Kaplan plot for AGRN in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

AGRN

UniProt ID: O00468

Entrez ID: 375790

Protein name: Agrin [Cleaved into: Agrin N-terminal 110 kDa subunit; Agrin C-terminal 110 kDa subunit; Agrin C-terminal 90 kDa fragment (C90); Agrin C-terminal 22 kDa fragment (C22)]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for AGRN in