DegronMD - Q6PKG0(LARP1)

FUNCTION: RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:28650797, PubMed:29244122, PubMed:26206669, PubMed:28379136). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28650797, PubMed:29244122, PubMed:28379136). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R879Q	TCGA-AY-5543	COAD	TCGA	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.3056
p.R879Q	DO9748	COAD	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.3056
p.R879Q	SIDM00534	Colorectal Carcinoma	GDSC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.3056
p.R879Q	ACH-000986	Colon/Colorectal Cancer	CCLE	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.3056
p.R879Q	HT-115	large intestine	COSMIC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.3056
p.V222M	TCGA-E6-A1LX	UCEC	TCGA	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.V222M	DO41020	UCEC	ICGC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.V222M	SIDM00487	Colorectal Carcinoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.E526D	TCGA-EY-A1GI	UCEC	TCGA	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation altering degron motif	0.6758
p.E526D	DO41211	UCEC	ICGC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation altering degron motif	0.6758
p.E526Q	TCGA-JW-A852	CESC	TCGA	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation altering degron motif	0.6744
p.E526Q	DO49978	CESC	ICGC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation altering degron motif	0.6744
p.M539T	TCGA-LN-A4A6	ESCA	TCGA	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation blocking ubiquitination signal	0.5278
p.F894L	TCGA-Q1-A73O	CESC	TCGA	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.0556
p.F894L	DO51612	CESC	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.0556
p.V220M	TCGA-VQ-A8P2	STAD	TCGA	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.6389
p.V220M	DO51761	STAD	ICGC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.6389
p.K887N	DO48442	BLCA	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.25
p.S216C	DO222603	BTCA	ICGC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation rewiring degron network	0.0833
p.Y880N	DO234462	ESAD	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation altering degron motif	0.7059
p.E537K	DO48270	ESCA	ICGC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation rewiring degron network	0.1389
p.G884V	DO228948	LICA	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation altering degron motif	0.6421
p.G884V	DO229028	LICA	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation altering degron motif	0.6421
p.Y881C	DO228974	LICA	ICGC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation altering degron motif	0.7087
p.D521Y	DO229038	LICA	ICGC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation blocking phosphorylation signal	0.6667
p.I233T	SIDM00845	Burkitt's Lymphoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation rewiring degron network	0.25
p.P235A	SIDM00845	Burkitt's Lymphoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation rewiring degron network	0.1944
p.P235L	SIDM00845	Burkitt's Lymphoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation rewiring degron network	0.1944
p.Y870F	SIDM01176	B-Lymphoblastic Leukemia	GDSC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.0556
p.Y870F	ACH-000059	Leukemia	CCLE	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.0556
p.Y870F	SUP-B15	haematopoietic and lymphoid tissue	COSMIC	LKENG	DEG_APCC_KENBOX_2	880:884	Mutation rewiring degron network	0.0556
p.A223G	SIDM01113	Other Sarcomas	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.7222
p.V222L	SIDM00703	Non-Small Cell Lung Carcinoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.V222L	ACH-000929	Lung Cancer	CCLE	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.V222L	NCI-H2110	lung	COSMIC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation substituting flanking lysine	0.3611
p.D529Y	SIDM00971	Breast Carcinoma	GDSC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation altering degron motif	0.7325
p.A217V	SIDM00727	Non-Small Cell Lung Carcinoma	GDSC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.5556
p.A217V	ACH-000951	Lung Cancer	CCLE	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.5556
p.A217V	NCI-H2342	lung	COSMIC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation blocking phosphorylation signal	0.5556
p.D533Y	SIDM00017	Squamous Cell Lung Carcinoma	GDSC	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation rewiring degron network	0.25
p.D533Y	ACH-000912	Lung Cancer	CCLE	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation rewiring degron network	0.25
p.Q515E	ACH-001063	Ovarian Cancer	CCLE	VTPVPT	DEG_SCF_FBW7_1	525:530	Mutation blocking phosphorylation signal	0.5
p.T226P	LS-513	large intestine	COSMIC	SDESGE	DEG_Kelch_Keap1_1	225:230	Mutation altering degron motif	0.7031

Kaplan plot for LARP1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

LARP1

UniProt ID: Q6PKG0

Entrez ID: 23367

Protein name: La-related protein 1 (La ribonucleoprotein domain family member 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for LARP1 in