DegronMD - P98164(LRP2)

FUNCTION: Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (By similarity). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal uptake of metallothionein-bound heavy metals (PubMed:15126248). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (By similarity). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (By similarity). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (By similarity). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (By similarity). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (By similarity). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (By similarity). During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells (By similarity). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (By similarity). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (By similarity). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (By similarity). Required for normal hearing, possibly through interaction with estrogen in the inner ear (By similarity). {ECO:0000250|UniProtKB:A2ARV4, ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158, ECO:0000269|PubMed:15126248, ECO:0000269|PubMed:23825075}. View more >>

GO - Biological processes (BP): 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.P4614S	TCGA-38-4632	LUAD	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5641
p.P4614S	DO23858	LUAD	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5641
p.A4646T	TCGA-66-2755	LUSC	TCGA	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation rewiring degron network	0.0556
p.A4646T	DO27365	LUSC	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation rewiring degron network	0.0556
p.R4629T	TCGA-85-8048	LUSC	TCGA	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation rewiring degron network	0.2778
p.R4629T	DO27389	LUSC	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation rewiring degron network	0.2778
p.A4611V	TCGA-AP-A056	UCEC	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.A4611V	TCGA-B5-A3FA	UCEC	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.A4611V	TCGA-BS-A0UF	UCEC	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.A4611V	DO52402	UCEC	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.A4611V	DO41488	UCEC	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.A4611V	DO43971	UCEC	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation altering degron motif	0.5825
p.E4604G	TCGA-B8-A54D	KIRC	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.1944
p.E4604G	DO49730	KIRC	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.1944
p.K4291N	TCGA-CM-5861	COAD	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.K4291N	TCGA-ER-A19F	SKCM	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.K4291N	DO7918	COAD	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.K4291N	DO37679	SKCM	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.W4286C	TCGA-E6-A1LX	UCEC	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.2222
p.W4286C	DO41020	UCEC	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.2222
p.S4618L	TCGA-EB-A41A	SKCM	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2778
p.S4618L	DO221128	MALY	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2778
p.S4618L	DO222527	MELA	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2778
p.S4618L	DO37429	SKCM	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2778
p.S4618L	ACH-001656	Leukemia	CCLE	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2778
p.L4284S	TCGA-EE-A3JD	SKCM	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.2778
p.L4284S	DO50299	SKCM	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.2778
p.S4627L	TCGA-EO-A22X	UCEC	TCGA	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6667
p.S4627L	TCGA-FR-A726	SKCM	TCGA	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6667
p.S4627L	TCGA-VR-A8EO	ESCA	TCGA	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6667
p.S4627L	DO48665	SKCM	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6667
p.S4627L	DO43907	UCEC	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6667
p.K4289N	TCGA-ER-A19T	SKCM	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.25
p.K4289N	DO51251	SKCM	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.25
p.G4292E	TCGA-ER-A42L	SKCM	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.0556
p.G4292E	DO223910	SKCM	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.0556
p.E4290K	TCGA-FS-A1ZN	SKCM	TCGA	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1111
p.E4290K	DO38165	SKCM	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1111
p.P4620S	TCGA-FW-A3R5	SKCM	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2222
p.P4620S	DO37406	SKCM	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2222
p.E4604K	TCGA-WS-AB45	COAD	TCGA	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.1944
p.E4604K	DO51734	COAD	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.1944
p.E4281Q	DO48414	BLCA	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation altering degron motif	0.5633
p.E4602V	DO230311	COCA	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.1389
p.Q4283K	DO234425	ESAD	ICGC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.3056
p.P4625L	DO220886	MELA	ICGC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.0833
p.P4625L	DO220886	MELA	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation rewiring degron network	0.1667
p.P4633L	DO27943	ORCA	ICGC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation altering degron motif	0.7582
p.E4270K	SIDM01237	Hepatocellular Carcinoma	GDSC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1389
p.E4270K	ACH-000739	Liver Cancer	CCLE	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1389
p.E4270K	ACH-001021	Liver Cancer	CCLE	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1389
p.E4270K	C3A	liver	COSMIC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation rewiring degron network	0.1389
p.A4599V	SIDM00193	Colorectal Carcinoma	GDSC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.0556
p.A4599V	ACH-000991	Colon/Colorectal Cancer	CCLE	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.0556
p.A4599V	SNU-81	large intestine	COSMIC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.0556
p.K4291R	SIDM01045	Endometrial Carcinoma	GDSC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.K4291R	ACH-000978	Endometrial/Uterine Cancer	CCLE	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.K4291R	EN	endometrium	COSMIC	LDIFED	LIG_APCC_ABBA_1	4277:4282	Mutation substituting flanking lysine	0.1944
p.P4620L	SIDM00511	Small Cell Lung Carcinoma	GDSC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2222
p.P4620L	ACH-000257	Lung Cancer	CCLE	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2222
p.P4620L	COR-L279	lung	COSMIC	VAATPPPS	DEG_SCF_FBW7_1	4609:4616	Mutation rewiring degron network	0.2222
p.T4641S	SIDM00048	Non-Small Cell Lung Carcinoma	GDSC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6389
p.T4641S	SIDM00954	Breast Carcinoma	GDSC	PTPTYS	DEG_SCF_FBW7_1	4631:4636	Mutation blocking phosphorylation signal	0.6389

Kaplan plot for LRP2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

LRP2

UniProt ID: P98164

Entrez ID: 4036

Protein name: Low-density lipoprotein receptor-related protein 2 (LRP-2) (Glycoprotein 330) (gp330) (Megalin)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for LRP2 in