DegronMD - Q9NQC3(RTN4)

FUNCTION: Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:27619977, PubMed:25612671, PubMed:24262037). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:27619977, PubMed:25612671, PubMed:24262037, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable). {ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412, ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289, ECO:0000305}.; FUNCTION: [Isoform A]: Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742}.; FUNCTION: [Isoform B]: Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:11126360, ECO:0000269|PubMed:16965550, ECO:0000305}.; FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:16965550}. View more >>

GO - Biological processes (BP): apoptotic process [GO:0006915]; axonal fasciculation [GO:0007413]; blastocyst formation [GO:0001825]; cardiac epithelial to mesenchymal transition [GO:0060317]; cell adhesion involved in sprouting angiogenesis [GO:0120078]; cell migration involved in vasculogenesis [GO:0035441]; cellular response to hypoxia [GO:0071456]; cellular sphingolipid homeostasis [GO:0090156]; central nervous system vasculogenesis [GO:0022009]; cerebral cortex radial glia-guided migration [GO:0021801]; endoplasmic reticulum organization [GO:0007029]; endoplasmic reticulum tubular network formation [GO:0071787]; endoplasmic reticulum tubular network membrane organization [GO:1990809]; endoplasmic reticulum tubular network organization [GO:0071786]; leukocyte migration involved in inflammatory response [GO:0002523]; negative regulation of amyloid-beta formation [GO:1902430]; negative regulation of axon extension [GO:0030517]; negative regulation of cell growth [GO:0030308]; negative regulation of vasculogenesis [GO:2001213]; nuclear pore complex assembly [GO:0051292]; positive regulation of angiogenesis [GO:0045766]; positive regulation of artery morphogenesis [GO:1905653]; positive regulation of epithelial cell migration [GO:0010634]; positive regulation of ERBB3 signaling pathway [GO:1905580]; positive regulation of hepatocyte proliferation [GO:2000347]; positive regulation of macrophage cytokine production [GO:0060907]; positive regulation of macrophage migration [GO:1905523]; positive regulation of mammary gland epithelial cell proliferation [GO:0033601]; positive regulation of neutrophil migration [GO:1902624]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein localization to endoplasmic reticulum [GO:1905552]; positive regulation of Rac protein signal transduction [GO:0035022]; positive regulation of toll-like receptor 9 signaling pathway [GO:0034165]; protein localization to lysosome [GO:0061462]; protein stabilization [GO:0050821]; regulation of apoptotic process [GO:0042981]; regulation of branching morphogenesis of a nerve [GO:2000172]; regulation of cell migration [GO:0030334] View more >>

GO - Molecular function (MF): View more >>

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

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K668N	TCGA-06-5416	GBM	TCGA	PPPY	ITCH	656:659	Mutation substituting flanking lysine	0.1944
p.P757L	TCGA-42-2590	OV	TCGA	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.1389
p.N655T	TCGA-B5-A3FA	UCEC	TCGA	PPPY	ITCH	656:659	Mutation rewiring degron network	0.3056
p.P740S	TCGA-DU-6407	LGG	TCGA	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.1944
p.E654K	TCGA-E2-A1IN	BRCA	TCGA	PPPY	ITCH	656:659	Mutation rewiring degron network	0.2778
p.S666L	TCGA-G2-A2EF	BLCA	TCGA	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1389
p.E124K	DO51941	BLCA	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation blocking phosphorylation signal	0.5556
p.S751Y	DO3572	BRCA	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.3056
p.D752N	DO8898	COAD	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2778
p.D752N	DO229056	LICA	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2778
p.D752N	DO42033	UCEC	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2778
p.M148V	DO8264	COAD	ICGC	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.7208
p.E126D	DO230313	COCA	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0556
p.E126D	DO41020	UCEC	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0556
p.E126D	DO41458	UCEC	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0556
p.D125V	DO229010	COCA	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0833
p.D125V	DO230659	LAML	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0833
p.D125V	DO231140	LAML	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0833
p.D748V	DO223039	ESCA	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation altering degron motif	0.7785
p.E757D	DO10880	GBM	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.1389
p.I662V	DO15038	HNSC	ICGC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.25
p.T754N	DO229031	LICA	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2222
p.S760R	DO229041	LICA	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.0556
p.H664N	DO229045	LICA	ICGC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1944
p.R104Q	DO50970	LICA	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.1111
p.K120E	DO22990	LIHC	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.2222
p.P147A	DO25867	LUAD	ICGC	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.7503
p.A126P	DO46366	OV	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.0556
p.S760N	DO46657	PAAD	ICGC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.0556
p.D161V	DO51407	PRAD	ICGC	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation rewiring degron network	0.1389
p.K120Q	DO36556	READ	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation rewiring degron network	0.2222
p.S150R	DO229211	THCA	ICGC	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.6316
p.N112H	DO40884	UCEC	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation altering degron motif	0.7423
p.P115S	DO41211	UCEC	ICGC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation altering degron motif	0.6752
p.E647G	SIDM02035	Colorectal Carcinoma	GDSC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.0833
p.P754H	SIDM01007	T-Lymphoblastic Leukemia	GDSC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2222
p.P754H	ACH-002256	Leukemia	CCLE	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2222
p.P754H	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.2222
p.I649V	SIDM01446	Glioblastoma	GDSC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1389
p.I649V	SIDM01448	Head and Neck Carcinoma	GDSC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1389
p.I649V	ACH-000500	Head and Neck Cancer	CCLE	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1389
p.I649V	ACH-000543	Brain Cancer	CCLE	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1389
p.S648C	SIDM01574	Plasma Cell Myeloma	GDSC	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1111
p.S648C	ACH-000588	Myeloma	CCLE	PPPY	ITCH	656:659	Mutation rewiring degron network	0.1111
p.R114K	ACH-000983	Leukemia	CCLE	PVSST	DEG_SPOP_SBC_1	112:116	Mutation altering degron motif	0.7237
p.R114K	KCL-22	haematopoietic and lymphoid tissue	COSMIC	PVSST	DEG_SPOP_SBC_1	112:116	Mutation altering degron motif	0.7237
p.P146S	ACH-000987	Skin Cancer	CCLE	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.5641
p.V151A	ACH-000990	Endometrial/Uterine Cancer	CCLE	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.6936
p.P146H	ACH-000998	Colon/Colorectal Cancer	CCLE	PPPASVSPQ	DEG_SIAH_1	146:154	Mutation altering degron motif	0.6583
p.V756I	ACH-001061	Colon/Colorectal Cancer	CCLE	VDLFSD	LIG_APCC_ABBA_1	745:750	Mutation rewiring degron network	0.1667

Kaplan plot for RTN4 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

RTN4

UniProt ID: Q9NQC3

Entrez ID: 57142

Protein name: Reticulon-4 (Foocen) (Neurite outgrowth inhibitor) (Nogo protein) (Neuroendocrine-specific protein) (NSP) (Neuroendocrine-specific protein C homolog) (RTN-x) (Reticulon-5)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RTN4 in