O00425 · IF2B3_HUMAN
- ProteinInsulin-like growth factor 2 mRNA-binding protein 3
- GeneIGF2BP3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids579 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
RNA-binding factor that may recruit 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).
Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152).
Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs
Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152).
Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs
Miscellaneous
Autoantibodies against IGF2BP3 are detected in sera from some patients with a variety of carcinomas.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic stress granule | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Cellular Component | P-body | |
Molecular Function | mRNA 3'-UTR binding | |
Molecular Function | mRNA 5'-UTR binding | |
Molecular Function | N6-methyladenosine-containing RNA reader activity | |
Molecular Function | RNA binding | |
Molecular Function | translation regulator activity | |
Biological Process | anatomical structure morphogenesis | |
Biological Process | CRD-mediated mRNA stabilization | |
Biological Process | mRNA transport | |
Biological Process | negative regulation of translation | |
Biological Process | nervous system development | |
Biological Process | regulation of cytokine production | |
Biological Process | translation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameInsulin-like growth factor 2 mRNA-binding protein 3
- Short namesIGF2 mRNA-binding protein 3; IMP-3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO00425
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Found in lamellipodia of the leading edge, in the perinuclear region, and beneath the plasma membrane. The subcytoplasmic localization is cell specific and regulated by cell contact and growth. Localized at the connecting piece and the tail of the spermatozoa. Colocalized with CD44 mRNA in RNP granules. In response to cellular stress, such as oxidative stress, recruited to stress granules.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 213 | Partial reduction in interaction with m6A-modified mRNA; when associated with E-294. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, modestly impaired binding to ACTB and MYC transcripts and almost no effect on ELAVL1-, DHX9- and HNRNPU-binding, nor on subcellular location; when associated with E-294; 422-E-E-423 and 505-E-E-506. | ||||
Sequence: K → E | ||||||
Mutagenesis | 294 | Partial reduction in interaction with m6A-modified mRNA; when associated with E-213. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, modestly impaired binding to ACTB and MYC transcripts and almost no effect on ELAVL1-, DHX9- and HNRNPU-binding, nor on subcellular location; when associated with E-213; 422-E-E-423 and 505-E-E-506. | ||||
Sequence: K → E | ||||||
Mutagenesis | 423-424 | Loss of interaction with m6A-modified mRNA; when associated with 505-E-E-506. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, modestly impaired binding to ACTB and MYC transcripts and almost no effect on ELAVL1-, DHX9- and HNRNPU-binding, nor on subcellular location; when associated with E-213; E-294 and 505-E-E-506. | ||||
Sequence: KQ → EE | ||||||
Mutagenesis | 505-506 | Loss of interaction with m6A-modified mRNA; when associated with 422-E-E-423. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, modestly impaired binding to ACTB and MYC transcripts and almost no effect on ELAVL1-, DHX9- and HNRNPU-binding, nor on subcellular location; when associated with E-213; E-294 and 422-E-E-423. | ||||
Sequence: KG → EE |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 533 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000282538 | 1-579 | UniProt | Insulin-like growth factor 2 mRNA-binding protein 3 | |||
Sequence: MNKLYIGNLSENAAPSDLESIFKDAKIPVSGPFLVKTGYAFVDCPDESWALKAIEALSGKIELHGKPIEVEHSVPKRQRIRKLQIRNIPPHLQWEVLDSLLVQYGVVESCEQVNTDSETAVVNVTYSSKDQARQALDKLNGFQLENFTLKVAYIPDEMAAQQNPLQQPRGRRGLGQRGSSRQGSPGSVSKQKPCDLPLRLLVPTQFVGAIIGKEGATIRNITKQTQSKIDVHRKENAGAAEKSITILSTPEGTSAACKSILEIMHKEAQDIKFTEEIPLKILAHNNFVGRLIGKEGRNLKKIEQDTDTKITISPLQELTLYNPERTITVKGNVETCAKAEEEIMKKIRESYENDIASMNLQAHLIPGLNLNALGLFPPTSGMPPPTSGPPSAMTPPYPQFEQSETETVHLFIPALSVGAIIGKQGQHIKQLSRFAGASIKIAPAEAPDAKVRMVIITGPPEAQFKAQGRIYGKIKEENFVSPKEEVKLEAHIRVPSFAAGRVIGKGGKTVNELQNLSSAEVVVPRDQTPDENDQVVVKITGHFYACQVAQRKIQEILTQVKQHQQQKALQSGPPQSRRK | |||||||
Modified residue (large scale data) | 179 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 180 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 184 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 184 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 187 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 243 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 249 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 438 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 450 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 475 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 481 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 496 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 528 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 528 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner (PubMed:23640942).
Interacts with IGF2BP1 (PubMed:17289661).
Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1 (PubMed:23640942, PubMed:29476152).
Interacts with IGF2BP1 (PubMed:17289661).
Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1 (PubMed:23640942, PubMed:29476152).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O00425 | DYRK1A Q13627 | 3 | EBI-1058566, EBI-1053596 | |
BINARY | O00425 | PCBP1 Q15365 | 3 | EBI-1058566, EBI-946095 | |
BINARY | O00425 | TARDBP Q13148 | 6 | EBI-1058566, EBI-372899 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-75 | RRM 1 | ||||
Sequence: NKLYIGNLSENAAPSDLESIFKDAKIPVSGPFLVKTGYAFVDCPDESWALKAIEALSGKIELHGKPIEVEHSVP | ||||||
Domain | 81-156 | RRM 2 | ||||
Sequence: RKLQIRNIPPHLQWEVLDSLLVQYGVVESCEQVNTDSETAVVNVTYSSKDQARQALDKLNGFQLENFTLKVAYIPD | ||||||
Region | 160-192 | Disordered | ||||
Sequence: AQQNPLQQPRGRRGLGQRGSSRQGSPGSVSKQK | ||||||
Domain | 195-260 | KH 1 | ||||
Sequence: DLPLRLLVPTQFVGAIIGKEGATIRNITKQTQSKIDVHRKENAGAAEKSITILSTPEGTSAACKSI | ||||||
Domain | 276-343 | KH 2 | ||||
Sequence: EIPLKILAHNNFVGRLIGKEGRNLKKIEQDTDTKITISPLQELTLYNPERTITVKGNVETCAKAEEEI | ||||||
Domain | 405-470 | KH 3 | ||||
Sequence: TETVHLFIPALSVGAIIGKQGQHIKQLSRFAGASIKIAPAEAPDAKVRMVIITGPPEAQFKAQGRI | ||||||
Domain | 487-553 | KH 4 | ||||
Sequence: KLEAHIRVPSFAAGRVIGKGGKTVNELQNLSSAEVVVPRDQTPDENDQVVVKITGHFYACQVAQRKI |
Domain
All KH domains contribute to binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute (PubMed:29476152).
The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules
The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules
Sequence similarities
Belongs to the RRM IMP/VICKZ family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O00425-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length579
- Mass (Da)63,705
- Last updated2009-07-28 v2
- Checksum78884F56A9D98CDE
O00425-2
- Name2
- Differences from canonical
- 1-381: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8WD15 | F8WD15_HUMAN | IGF2BP3 | 81 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_024172 | 1-381 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 410 | in Ref. 1; AAD09223/AAC35208 | ||||
Sequence: L → Q | ||||||
Sequence conflict | 494 | in Ref. 2; CAH56186 | ||||
Sequence: V → A |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U76705 EMBL· GenBank· DDBJ | AAD09223.1 EMBL· GenBank· DDBJ | mRNA | ||
U97188 EMBL· GenBank· DDBJ | AAC35208.1 EMBL· GenBank· DDBJ | mRNA | ||
BX640800 EMBL· GenBank· DDBJ | CAE45883.1 EMBL· GenBank· DDBJ | mRNA | ||
BX648488 EMBL· GenBank· DDBJ | CAH56186.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005082 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC021876 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC079780 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC065269 EMBL· GenBank· DDBJ | AAH65269.1 EMBL· GenBank· DDBJ | mRNA |