DegronMD - Q8NEU8(APPL2)

FUNCTION: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:26583432, PubMed:15016378, PubMed:24879834). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses. In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling. In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines. Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting ans insulin signaling pathways and adaptative thermogenesis (PubMed:24879834) (By similarity). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (By similarity). In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (PubMed:24879834). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (By similarity). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (PubMed:19433865) (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor. Required for fibroblast migration through HGF cell signaling (By similarity). {ECO:0000250|UniProtKB:Q8K3G9, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26583432}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.L396F	TCGA-38-4629	LUAD	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.2778
p.E447Q	TCGA-66-2785	LUSC	TCGA	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.6744
p.V404L	TCGA-77-8146	LUSC	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.3056
p.A393V	TCGA-A5-A0G2	UCEC	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1944
p.A393V	TCGA-FS-A1ZY	SKCM	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1944
p.A393V	SIDM00898	Breast Carcinoma	GDSC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1944
p.A393V	AU565	breast	COSMIC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1944
p.A400T	TCGA-AP-A1DV	UCEC	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation altering degron motif	0.7139
p.N397K	TCGA-AR-A24R	BRCA	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.3056
p.P455S	TCGA-B5-A3FA	UCEC	TCGA	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.6752
p.E145Q	TCGA-BT-A20J	BLCA	TCGA	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.6744
p.A136T	TCGA-CM-6171	COAD	TCGA	DLSMAKYSRLP	CBL_PTK	141:151	Mutation rewiring degron network	0.1944
p.A403V	TCGA-CZ-4859	KIRC	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation altering degron motif	0.6936
p.Q398H	TCGA-DK-AA6L	BLCA	TCGA	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation altering degron motif	0.7582
p.D147A	TCGA-DR-A0ZM	CESC	TCGA	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7793
p.D459N	TCGA-EY-A1G8	UCEC	TCGA	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.25
p.Y153C	TCGA-FI-A2D5	UCEC	TCGA	KKENE	DEG_APCC_KENBOX_2	153:157	Mutation altering degron motif	0.7087
p.G163E	DO457	BLCA	ICGC	KKENE	DEG_APCC_KENBOX_2	153:157	Mutation rewiring degron network	0.1667
p.S445Y	DO566	BLCA	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.712
p.A390V	DO229010	COCA	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.A390V	DO229016	COCA	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.A390V	DO229003	COCA	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.A390V	DO229005	COCA	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.A390V	DO229346	LAML	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.M151I	DO15767	HNSC	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7618
p.R454W	DO19893	KIRC	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.8634
p.R454W	DO222339	STAD	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.8634
p.P395H	DO228952	LICA	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.25
p.A144E	DO228952	LICA	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7701
p.T463K	DO229038	LICA	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1389
p.E398Q	DO26520	LUSC	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation altering degron motif	0.6744
p.A144S	DO26590	LUSC	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7588
p.L456W	DO26461	LUSC	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.7015
p.E435Q	DO26790	LUSC	ICGC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.0833
p.M157L	DO45460	LUSC	ICGC	KKENE	DEG_APCC_KENBOX_2	153:157	Mutation altering degron motif	0.711
p.L133F	DO220875	MELA	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation rewiring degron network	0.1111
p.Y138H	DO35442	PACA	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation rewiring degron network	0.25
p.H132R	DO229579	PRAD	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation rewiring degron network	0.0833
p.D410N	DO43578	UCEC	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1389
p.P406S	DO52402	UCEC	ICGC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation substituting flanking lysine	0.3611
p.Q137H	DO42600	UCEC	ICGC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation rewiring degron network	0.2222
p.A464P	SIDM00615	Hepatocellular Carcinoma	GDSC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	SIDM01026	Esophageal Squamous Cell Carcinoma	GDSC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	SIDM01217	Other Blood Cancers	GDSC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	SIDM00173	Head and Neck Carcinoma	GDSC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	SIDM01764	Non-Small Cell Lung Carcinoma	GDSC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	JHH-6	liver	COSMIC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.A464P	KYSE-510	oesophagus	COSMIC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.1111
p.P157H	SIDM00789	Colorectal Carcinoma	GDSC	KKENE	DEG_APCC_KENBOX_2	153:157	Mutation altering degron motif	0.7694
p.E390D	SIDM00741	Small Cell Lung Carcinoma	GDSC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.E390D	NCI-H1694	lung	COSMIC	VTPITS	DEG_SCF_FBW7_1	398:403	Mutation rewiring degron network	0.1111
p.F143I	SIDM01190	Bladder Carcinoma	GDSC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7415
p.F143I	ACH-000720	Bladder Cancer	CCLE	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7415
p.F143I	TCCSUP	urinary tract	COSMIC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7415
p.T448M	ACH-001719	Ovarian Cancer	CCLE	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation altering degron motif	0.6312
p.A458P	KYSE-510	oesophagus	COSMIC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.2778
p.A458P	JHH-6	liver	COSMIC	IAPGTPIQFDIVL	DEG_ODPH_VHL_1	444:456	Mutation rewiring degron network	0.2778
p.A144T	SNU-C2B	large intestine	COSMIC	DLSMAKYSRLP	CBL_PTK	141:151	Mutation altering degron motif	0.7139

Kaplan plot for APPL2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

APPL2

UniProt ID: Q8NEU8

Entrez ID: 55198

Protein name: DCC-interacting protein 13-beta (Dip13-beta) (Adapter protein containing PH domain, PTB domain and leucine zipper motif 2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for APPL2 in