DegronMD - Q9NZI8(IGF2BP1)

FUNCTION: RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (PubMed:29476152, PubMed:32245947). Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The RNP thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton (By similarity). During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of ACTB (By similarity). May regulate mRNA transport to activated synapses (By similarity). Binds to and stabilizes ABCB1/MDR-1 mRNA (By similarity). During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing (By similarity). Binds to the 3'-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence preventing MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD (PubMed:29476152). Binding to MYC mRNA is enhanced by m6A-modification of the CRD (PubMed:29476152). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to the oncofetal H19 transcript and to the neuron-specific TAU mRNA and regulates their localizations. Binds to and stabilizes BTRC/FBW1A mRNA. Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2. Promotes the directed movement of tumor-derived cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization. Interacts with Hepatitis C virus (HCV) 5'-UTR and 3'-UTR and specifically enhances translation at the HCV IRES, but not 5'-cap-dependent translation, possibly by recruiting eIF3. Interacts with HIV-1 GAG protein and blocks the formation of infectious HIV-1 particles. Reduces HIV-1 assembly by inhibiting viral RNA packaging, as well as assembly and processing of GAG protein on cellular membranes. During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts. {ECO:0000250, ECO:0000269|PubMed:10875929, ECO:0000269|PubMed:16356927, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:16778892, ECO:0000269|PubMed:17101699, ECO:0000269|PubMed:17255263, ECO:0000269|PubMed:17893325, ECO:0000269|PubMed:18385235, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19541769, ECO:0000269|PubMed:19647520, ECO:0000269|PubMed:20080952, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:29476152, ECO:0000269|PubMed:32245947, ECO:0000269|PubMed:8132663, ECO:0000269|PubMed:9891060}. 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.R452C	TCGA-06-5416	GBM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-19-5956	GBM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-AP-A0LM	UCEC	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-B5-A0JY	UCEC	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-EE-A2MR	SKCM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-FR-A7U9	SKCM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	TCGA-WE-A8ZO	SKCM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO13863	GBM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO10880	GBM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO220886	MELA	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO48546	SKCM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO37819	SKCM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO51286	SKCM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO43306	UCEC	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.R452C	DO43041	UCEC	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.719
p.V454F	TCGA-12-1088	GBM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.3056
p.V454F	DO13701	GBM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.3056
p.S449Y	TCGA-17-Z030	LUAD	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.6009
p.L375F	TCGA-34-8456	LUSC	TCGA	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2778
p.L375F	DO219135	LUSC	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2778
p.R452G	TCGA-38-4629	LUAD	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.6457
p.R452G	DO23771	LUAD	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.6457
p.P385Q	TCGA-49-AARQ	LUAD	TCGA	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2222
p.P385Q	DO51189	LUAD	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2222
p.A371S	TCGA-55-7576	LUAD	TCGA	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1667
p.A371S	DO24431	LUAD	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1667
p.S389I	TCGA-66-2787	LUSC	TCGA	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1111
p.S389I	DO26647	LUSC	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1111
p.A237V	TCGA-99-8033	LUAD	TCGA	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.5825
p.A237V	DO23726	LUAD	ICGC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.5825
p.A237T	TCGA-AG-A002	READ	TCGA	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	SIDM00680	Colorectal Carcinoma	GDSC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	SIDM00327	Hodgkin's Lymphoma	GDSC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	ACH-000754	Lymphoma	CCLE	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	ACH-000957	Colon/Colorectal Cancer	CCLE	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	LS-180	large intestine	COSMIC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A237T	L-428	haematopoietic and lymphoid tissue	COSMIC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6028
p.A382T	TCGA-B5-A3FC	UCEC	TCGA	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.3056
p.A382T	DO228903	LICA	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.3056
p.A382T	DO41871	UCEC	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.3056
p.K228E	TCGA-B5-A5OC	UCEC	TCGA	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation blocking ubiquitination signal	0.6389
p.K228E	DO52405	UCEC	ICGC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation blocking ubiquitination signal	0.6389
p.A240T	TCGA-B6-A0I2	BRCA	TCGA	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.25
p.A240T	DO1885	BRCA	ICGC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.25
p.A442V	TCGA-DU-6408	LGG	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.6936
p.A442V	DO22245	LGG	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.6936
p.D230E	TCGA-OR-A5KT	ACC	TCGA	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.25
p.K440N	TCGA-Q1-A5R2	CESC	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation blocking ubiquitination signal	0.75
p.K440N	DO49003	CESC	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation blocking ubiquitination signal	0.75
p.P460S	TCGA-RP-A695	SKCM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1389
p.P460S	DO51270	SKCM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1389
p.E461K	TCGA-VS-A9UP	CESC	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.E461K	DO219737	CESC	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.P459L	TCGA-Z2-AA3S	SKCM	TCGA	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1667
p.P459L	DO51302	SKCM	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1667
p.P384L	DO228927	COCA	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.25
p.A240D	DO227745	COCA	ICGC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.25
p.S388R	DO234220	ESAD	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1389
p.I229K	DO228585	LICA	ICGC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.2222
p.G458V	DO228896	LICA	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1944
p.G458V	DO229019	LICA	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1944
p.R433L	DO228986	LICA	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.R433L	SIDM00216	Colorectal Carcinoma	GDSC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.R433L	ACH-000989	Colon/Colorectal Cancer	CCLE	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.R433L	SNU-175	large intestine	COSMIC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.L370V	DO224544	LUSC	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1389
p.L370V	DO231014	LUSC	ICGC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1389
p.E445K	DO33344	PACA	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.591
p.E445K	ACH-000455	Brain Cancer	CCLE	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.591
p.R433Q	DO229548	PRAD	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.1111
p.A437T	DO41199	UCEC	ICGC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation rewiring degron network	0.2222
p.R233K	SIDM00140	Melanoma	GDSC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6126
p.R233K	ACH-000968	Skin Cancer	CCLE	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6126
p.R233K	COLO-792	skin	COSMIC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation altering degron motif	0.6126
p.P385L	SIDM00167	Head and Neck Carcinoma	GDSC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2222
p.P385L	ACH-000715	Head and Neck Cancer	CCLE	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.2222
p.R452H	SIDM01619	Endometrial Carcinoma	GDSC	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.7133
p.R452H	ACH-000984	Endometrial/Uterine Cancer	CCLE	IAPPETPDSKVRM	DEG_ODPH_VHL_1	441:453	Mutation altering degron motif	0.7133
p.S389T	ACH-001279	Ovarian Cancer	CCLE	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1111
p.H224R	Sarc9371	bone	COSMIC	RKENA	DEG_APCC_KENBOX_2	233:237	Mutation rewiring degron network	0.0833
p.V371M	Sarc9371	bone	COSMIC	PASSS	DEG_SPOP_SBC_1	377:381	Mutation rewiring degron network	0.1667

Kaplan plot for IGF2BP1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

IGF2BP1

UniProt ID: Q9NZI8

Entrez ID: 10642

Protein name: Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2 mRNA-binding protein 1) (IMP-1) (IMP1) (Coding region determinant-binding protein) (CRD-BP) (IGF-II mRNA-binding protein 1) (VICKZ family member 1) (Zipcode-binding protein 1) (ZBP-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IGF2BP1 in