DegronMD - Q8TF40(FNIP1)

FUNCTION: Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases (PubMed:24081491). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (By similarity). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359}. 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.C896F	TCGA-53-A4EZ	LUAD	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.0833
p.I925F	TCGA-77-8148	LUSC	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.S895L	TCGA-98-8021	LUSC	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.0556
p.D836N	TCGA-A5-A2K5	UCEC	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.5821
p.L912F	TCGA-AJ-A3EL	UCEC	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.6981
p.L912F	TCGA-AJ-A3EL	UCEC	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation altering degron motif	0.587
p.D842N	TCGA-AP-A051	UCEC	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1944
p.F270C	TCGA-AX-A0J0	UCEC	TCGA	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.5996
p.F270C	SIDM01123	Prostate Carcinoma	GDSC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.5996
p.F270C	NCI-H660	prostate	COSMIC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.5996
p.S276A	TCGA-BR-8361	STAD	TCGA	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation rewiring degron network	0.2222
p.A926V	TCGA-CK-5916	COAD	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0833
p.E837K	TCGA-D1-A17Q	UCEC	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7022
p.I925N	TCGA-D3-A8GM	SKCM	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.I925N	SIDM00845	Burkitt's Lymphoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.I925N	SIDM00461	Acute Myeloid Leukemia	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.I925N	SIDM01519	Head and Neck Carcinoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.Q113H	TCGA-DF-A2KU	UCEC	TCGA	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1944
p.Q113H	DO223286	UCEC	ICGC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1944
p.K897T	TCGA-DK-A6AW	BLCA	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation substituting flanking lysine	0.2222
p.E845K	TCGA-DK-A6AW	BLCA	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1111
p.E845K	TCGA-FI-A2D4	UCEC	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1111
p.E845K	SIDM00980	Gastric Carcinoma	GDSC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1111
p.E845K	23132-87	stomach	COSMIC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1111
p.L265S	TCGA-EB-A5UM	SKCM	TCGA	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.7667
p.G916W	TCGA-EE-A29E	SKCM	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation altering degron motif	0.6714
p.K923N	TCGA-EO-A22U	UCEC	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation substituting flanking lysine	0.1667
p.K923N	TCGA-EO-A22U	UCEC	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation substituting flanking lysine	0.2778
p.S831N	TCGA-F5-6814	READ	TCGA	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.3056
p.E919D	TCGA-FI-A2D5	UCEC	TCGA	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.1667
p.E919D	TCGA-FI-A2D5	UCEC	TCGA	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.2778
p.V104A	TCGA-FI-A2D5	UCEC	TCGA	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.5825
p.V104A	DO41331	UCEC	ICGC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.5825
p.Q118L	TCGA-UB-A7MB	LIHC	TCGA	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.0556
p.Q118L	DO52318	LIHC	ICGC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.0556
p.Q113R	TCGA-ZQ-A9CR	STAD	TCGA	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1944
p.Q113R	DO50145	STAD	ICGC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1944
p.A254T	DO225346	BRCA	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation altering degron motif	0.7139
p.R263C	DO9490	COAD	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263C	DO9490	COAD	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.R263C	DO36463	READ	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263C	DO36463	READ	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.R263C	DO41235	UCEC	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263C	DO41235	UCEC	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.T847A	DO10276	COAD	ICGC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.0556
p.R263H	DO8842	COAD	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263H	DO8842	COAD	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.R263H	DO8514	COAD	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263H	DO8514	COAD	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.R263H	DO12214	GBM	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.7222
p.R263H	DO12214	GBM	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6667
p.A898V	DO8786	COAD	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.1389
p.R907I	DO8264	COAD	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.8102
p.L915F	DO50330	ESAD	ICGC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation altering degron motif	0.6981
p.N908I	DO234327	ESAD	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.728
p.R251Q	DO223101	ESCA	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.2778
p.D917N	DO13863	GBM	ICGC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation altering degron motif	0.6932
p.L269F	DO16530	KIRC	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.6981
p.R260L	DO20915	KIRP	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation rewiring degron network	0.1944
p.R260L	DO20915	KIRP	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.3056
p.S264R	DO229038	LICA	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.75
p.S264R	DO229038	LICA	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6389
p.N246K	DO229009	LICA	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.1389
p.P275H	DO229008	LICA	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.6944
p.C846S	DO223917	LIHC	ICGC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.0833
p.T923I	DO45223	LIRI	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation substituting flanking lysine	0.1667
p.T923I	DO45223	LIRI	ICGC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation substituting flanking lysine	0.2778
p.R260C	DO48682	LIRI	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation rewiring degron network	0.1944
p.R260C	DO48682	LIRI	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.3056
p.V273L	DO51192	LUAD	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation rewiring degron network	0.3056
p.I897F	DO26458	LUSC	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation substituting flanking lysine	0.2222
p.E270G	DO52655	MALY	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation altering degron motif	0.7199
p.S913N	DO220876	MELA	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.7069
p.S913N	DO220876	MELA	ICGC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation altering degron motif	0.7069
p.V273A	DO51474	PACA	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation rewiring degron network	0.3056
p.I897N	DO50288	SKCM	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation substituting flanking lysine	0.2222
p.P825L	DO219491	SKCM	ICGC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1389
p.S248A	DO48032	STAD	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.1944
p.S264N	DO229259	THCA	ICGC	LLITPFPS	DEG_SCF_FBW7_1	265:272	Mutation blocking phosphorylation signal	0.75
p.S264N	DO229259	THCA	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation blocking phosphorylation signal	0.6389
p.S255N	DO42977	UCEC	ICGC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation altering degron motif	0.7069
p.D831N	DO42568	UCEC	ICGC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.3056
p.K895N	DO43755	UCEC	ICGC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.0556
p.R258Q	SIDM00216	Colorectal Carcinoma	GDSC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation altering degron motif	0.6218
p.R258Q	SNU-175	large intestine	COSMIC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation altering degron motif	0.6218
p.S103F	SIDM01169	Ovarian Carcinoma	GDSC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.3056
p.S103F	ACH-000885	Ovarian Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.3056
p.S103F	TOV-21G	ovary	COSMIC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.3056
p.V927I	SIDM00608	Plasma Cell Myeloma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.V927I	SIDM00157	Neuroblastoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.V927I	SIDM00556	Neuroblastoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.V927I	SIDM00240	Cervical Carcinoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.V927I	SIDM00306	Non-Small Cell Lung Carcinoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.V927I	SIDM01472	Hepatocellular Carcinoma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.S108F	SIDM00796	Head and Neck Carcinoma	GDSC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7982
p.S108F	ACH-000740	Head and Neck Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7982
p.S108F	A253	salivary gland	COSMIC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7982
p.D904E	SIDM00391	Plasma Cell Myeloma	GDSC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.3056
p.D904E	SIDM00391	Plasma Cell Myeloma	GDSC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.1111
p.P901H	SIDM00112	Kidney Carcinoma	GDSC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.2222
p.P901H	U031	kidney	COSMIC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation rewiring degron network	0.2222
p.L115I	SIDM00217	Colorectal Carcinoma	GDSC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1389
p.L115I	ACH-000999	Colon/Colorectal Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1389
p.L115I	SNU-1040	large intestine	COSMIC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.1389
p.S106L	SIDM00839	Colorectal Carcinoma	GDSC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7667
p.S106L	ACH-000950	Colon/Colorectal Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7667
p.S106L	LoVo	large intestine	COSMIC	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation altering degron motif	0.7667
p.D907N	SIDM00859	B-Cell Non-Hodgkin's Lymphoma	GDSC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.5821
p.D907N	Farage	haematopoietic and lymphoid tissue	COSMIC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.5821
p.N832S	ACH-000472	Head and Neck Cancer	CCLE	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7069
p.N832S	HSC-2	upper aerodigestive tract	COSMIC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7069
p.D842H	ACH-000635	Ovarian Cancer	CCLE	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.1944
p.K102R	ACH-000831	Endometrial/Uterine Cancer	CCLE	VTSSS	DEG_SPOP_SBC_1	104:108	Mutation rewiring degron network	0.2778
p.M910I	ACH-001384	Thyroid Cancer	CCLE	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.7618
p.M910I	RO82-W-1	thyroid	COSMIC	QRDTLSILV	DEG_APCC_DBOX_1	905:913	Mutation altering degron motif	0.7618
p.N837S	ACH-002256	Leukemia	CCLE	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7069
p.N837S	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7069
p.N823T	SNU-81	large intestine	COSMIC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation rewiring degron network	0.0833
p.S249G	ESO51	oesophagus	COSMIC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.2222
p.M927I	RO82-W-1	thyroid	COSMIC	LVPHGD	LIG_APCC_ABBA_1	912:917	Mutation rewiring degron network	0.0556
p.D251G	Daudi	haematopoietic and lymphoid tissue	COSMIC	DSGIARS	DEG_SCF_TRCP1_1	253:259	Mutation rewiring degron network	0.2778
p.S836F	23132-87	stomach	COSMIC	MSLFDE	LIG_APCC_ABBA_1	832:837	Mutation altering degron motif	0.7982

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

FNIP1

UniProt ID: Q8TF40

Entrez ID: 96459

Protein name: Folliculin-interacting protein 1

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FNIP1 in