DegronMD - Q13501(SQSTM1)

FUNCTION: Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (PubMed:16286508, PubMed:20168092, PubMed:24128730, PubMed:28404643, PubMed:22622177). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:24128730, PubMed:20168092). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215). {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:33393215}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S277G	TCGA-05-4384	LUAD	TCGA	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8104
p.S277G	DO23618	LUAD	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8104
p.S266R	TCGA-A5-A1OF	UCEC	TCGA	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7427
p.S266R	DO42568	UCEC	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7427
p.S284A	TCGA-AA-3492	COAD	TCGA	PESSS	DEG_SPOP_SBC_1	273:277	Mutation blocking phosphorylation signal	0.5833
p.S284A	DO8224	COAD	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation blocking phosphorylation signal	0.5833
p.A426V	TCGA-AF-2687	READ	TCGA	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.25
p.K420N	TCGA-AN-A046	BRCA	TCGA	DTIQYSKHP	CBL_PTK	429:437	Mutation blocking ubiquitination signal	0.5278
p.P348L	TCGA-AX-A1CE	UCEC	TCGA	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation altering degron motif	0.6471
p.P348L	TCGA-BH-A0HA	BRCA	TCGA	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation altering degron motif	0.6471
p.V255I	TCGA-CD-A4MG	STAD	TCGA	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.0833
p.V255I	DO48009	STAD	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.0833
p.E345K	TCGA-D3-A2JL	SKCM	TCGA	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2778
p.G425R	TCGA-DA-A3F5	SKCM	TCGA	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2222
p.H340N	TCGA-EE-A3AD	SKCM	TCGA	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.1389
p.N421S	TCGA-HJ-7597	STAD	TCGA	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.1111
p.S276Y	TCGA-IB-7651	PAAD	TCGA	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8231
p.S276Y	DO46657	PAAD	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8231
p.S277I	TCGA-IB-7651	PAAD	TCGA	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8453
p.S277I	DO46657	PAAD	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.8453
p.P438L	TCGA-QS-A5YR	UCEC	TCGA	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.3056
p.P438L	SIDM01062	Breast Carcinoma	GDSC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.3056
p.P438L	ACH-000643	Breast Cancer	CCLE	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.3056
p.P438L	HDQ-P1	breast	COSMIC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.3056
p.R356H	DO720	BLCA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.R356H	DO233855	GACA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.R356H	DO38419	STAD	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.P347L	DO225325	BRCA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation altering degron motif	0.7582
p.P264L	DO1658	BRCA	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7582
p.P264L	DO42280	UCEC	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7582
p.R337I	DO1285	BRCA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.0556
p.L283V	DO48996	CESC	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation rewiring degron network	0.1667
p.S341L	DO51726	COAD	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.1667
p.S341L	DO41572	UCEC	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.1667
p.S341L	DO43955	UCEC	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.1667
p.S284L	DO230311	COCA	ICGC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation blocking phosphorylation signal	0.5833
p.R343Q	DO52438	COCA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6667
p.R343Q	DO234451	ESAD	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6667
p.T266I	DO233764	GACA	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7078
p.W345L	DO229025	LICA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2778
p.A343S	DO229006	LICA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6667
p.C361F	DO229008	LICA	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.5278
p.R343W	DO36902	READ	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6667
p.E261K	DO47278	SKCM	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.25
p.H256N	DO37707	SKCM	ICGC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.1111
p.G341R	DO37435	SKCM	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.1667
p.T338A	DO38195	STAD	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.0833
p.R355C	DO50081	UCEC	ICGC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6944
p.R355C	HDQ-P1	breast	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6944
p.P439L	SIDM00521	Small Cell Lung Carcinoma	GDSC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.P439L	SIDM00457	Plasma Cell Myeloma	GDSC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.P439L	SIDM00294	Small Cell Lung Carcinoma	GDSC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.P439L	COR-L95	lung	COSMIC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.P439L	OPM-2	haematopoietic and lymphoid tissue	COSMIC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.P439L	LU-135	lung	COSMIC	DTIQYSKHP	CBL_PTK	429:437	Mutation rewiring degron network	0.2778
p.V255L	SIDM00390	T-Cell Non-Hodgkin's Lymphoma	GDSC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.0833
p.V255L	SU-DHL-1	haematopoietic and lymphoid tissue	COSMIC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation rewiring degron network	0.0833
p.E274K	SIDM01259	B-Lymphoblastic Leukemia	GDSC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.591
p.E274K	ACH-001669	Leukemia	CCLE	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.591
p.E274K	ACH-002238	Leukemia	CCLE	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.591
p.E274K	GR-ST	haematopoietic and lymphoid tissue	COSMIC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.591
p.L356P	SIDM00333	Endometrial Carcinoma	GDSC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.L356P	ACH-000988	Endometrial/Uterine Cancer	CCLE	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.L356P	MFE-319	endometrium	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.S361F	SIDM00006	Other Solid Cancers	GDSC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.5278
p.S361F	ACH-001552	Skin Cancer	CCLE	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.5278
p.S361F	MCC26	skin	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.5278
p.T269A	ACH-000940	Endometrial/Uterine Cancer	CCLE	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7139
p.T269A	AN3-CA	endometrium	COSMIC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7139
p.K281R	ACH-002027	Endometrial/Uterine Cancer	CCLE	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation blocking ubiquitination signal	0.5278
p.K281R	ACH-002027	Endometrial/Uterine Cancer	CCLE	PESSS	DEG_SPOP_SBC_1	273:277	Mutation blocking ubiquitination signal	0.6667
p.P355L	LU-135	lung	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6944
p.P355L	OPM-2	haematopoietic and lymphoid tissue	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6944
p.P355L	COR-L95	lung	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation blocking phosphorylation signal	0.6944
p.R356C	OPM-2	haematopoietic and lymphoid tissue	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.R356C	LU-135	lung	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.R356C	COR-L95	lung	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2222
p.P354L	HDQ-P1	breast	COSMIC	DPSTGE	DEG_Kelch_Keap1_1	347:352	Mutation rewiring degron network	0.2778
p.S277F	MCC26	skin	COSMIC	PESSS	DEG_SPOP_SBC_1	273:277	Mutation altering degron motif	0.9093
p.L272P	MFE-319	endometrium	COSMIC	KRSRLTPVS	DEG_APCC_DBOX_1	264:272	Mutation altering degron motif	0.7582

Kaplan plot for SQSTM1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

SQSTM1

UniProt ID: Q13501

Entrez ID: 8878

Protein name: Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SQSTM1 in