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UniProtKB - Q9NZI8 (IF2B1_HUMAN)

Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

IGF2BP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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 prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. 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.By similarity15 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionRNA-binding
Biological processmRNA transport, Translation regulation, Transport

Enzyme and pathway databases

ReactomeiR-HSA-428359 Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA
R-HSA-5687128 MAPK6/MAPK4 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor 2 mRNA-binding protein 1
Short name:
IGF2 mRNA-binding protein 1
Short name:
IMP-1
Short name:
IMP1
Alternative name(s):
Coding region determinant-binding protein
Short name:
CRD-BP
IGF-II mRNA-binding protein 1
VICKZ family member 1
Zipcode-binding protein 1
Short name:
ZBP-1
Gene namesi
Name:IGF2BP1
Synonyms:CRDBP, VICKZ1, ZBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000159217.9
HGNCiHGNC:28866 IGF2BP1
MIMi608288 gene
neXtProtiNX_Q9NZI8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi213 – 214KE → EL: 50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 294-E-L-295 and 423-E-L-424. 1 Publication2
Mutagenesisi294 – 295KE → EL: 50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 213-E-L-214 and 423-E-L-424. 1 Publication2
Mutagenesisi423 – 424KK → EL: 50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 213-E-L-214 and 294-E-L-295. 1 Publication2

Organism-specific databases

DisGeNETi10642
OpenTargetsiENSG00000159217
PharmGKBiPA143485501

Polymorphism and mutation databases

BioMutaiIGF2BP1
DMDMi296434536

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002825331 – 577Insulin-like growth factor 2 mRNA-binding protein 1Add BLAST577

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12PhosphoserineCombined sources1
Modified residuei73PhosphoserineCombined sources1
Modified residuei181PhosphoserineCombined sources1
Modified residuei528PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated. Phosphorylation may impair association with ACTB mRNA and hence abolishes translational repression (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NZI8
MaxQBiQ9NZI8
PaxDbiQ9NZI8
PeptideAtlasiQ9NZI8
PRIDEiQ9NZI8
ProteomicsDBi83410
TopDownProteomicsiQ9NZI8-1 [Q9NZI8-1]

PTM databases

iPTMnetiQ9NZI8
PhosphoSitePlusiQ9NZI8
SwissPalmiQ9NZI8

Expressioni

Tissue specificityi

Mainly expressed in the embryo, including in fetal liver, fetal lung, fetal kidney, fetal thymus (at protein level). Also expressed follicles of ovary, as well as in gonocytes of testis, spermatogonia, semen, oocytes and placenta (at protein level). Expressed in various cancers, including testis and lung cancers (at protein level), as well as kidney, prostate and trachea cancers.4 Publications

Inductioni

May be up-regulated in response to CTNNB1/beta-catenin activation.1 Publication

Gene expression databases

BgeeiENSG00000159217 Expressed in 65 organ(s), highest expression level in lung
CleanExiHS_IGF2BP1
HS_ZBP1
GenevisibleiQ9NZI8 HS

Organism-specific databases

HPAiHPA021367
HPA062273

Interactioni

Subunit structurei

Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. During HCV infection, identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon. Interacts (via the KH domains) with HIV-1 GAG (via the second zinc finger motif of NC). Associates (via the RRM domains and KH domains) with HIV-1 particles. Identified in a mRNP complex, composed of at least DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with DHX9, ELAVL2, HNRNPA2B1, HNRNPC, HNRNPH1, HNRNPU, IGF2BP2, ILF2, and YBX1. Interacts with FMR1. Component of a multisubunit autoregulatory RNP complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1/UNR. Directly interacts with PABPC1. Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with ELAVL4 in an RNA-dependent manner. Associates with microtubules and polysomes. Interacts with AGO1 and AGO2.10 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi115886, 160 interactors
ComplexPortaliCPX-1080 CRD-mediated mRNA stability complex
CORUMiQ9NZI8
DIPiDIP-38139N
IntActiQ9NZI8, 67 interactors
MINTiQ9NZI8
STRINGi9606.ENSP00000290341

Structurei

Secondary structure

1577
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NZI8
SMRiQ9NZI8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NZI8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 75RRM 1PROSITE-ProRule annotationAdd BLAST74
Domaini81 – 156RRM 2PROSITE-ProRule annotationAdd BLAST76
Domaini195 – 260KH 1PROSITE-ProRule annotationAdd BLAST66
Domaini276 – 343KH 2PROSITE-ProRule annotationAdd BLAST68
Domaini405 – 470KH 3PROSITE-ProRule annotationAdd BLAST66
Domaini487 – 553KH 4PROSITE-ProRule annotationAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni187 – 570Necessary for interaction with ELAVL4 and binding to TAU mRNABy similarityAdd BLAST384
Regioni310 – 324Sufficient for nuclear exportAdd BLAST15
Regioni485 – 495Sufficient for nuclear exportAdd BLAST11

Domaini

Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein. The 4 KH domains are important to suppress HIV-1 infectivity.1 Publication

Sequence similaritiesi

Belongs to the RRM IMP/VICKZ family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2193 Eukaryota
ENOG410ZKB4 LUCA
GeneTreeiENSGT00530000063171
HOGENOMiHOG000000675
HOVERGENiHBG052725
InParanoidiQ9NZI8
KOiK17391
OMAiEKPISIH
OrthoDBiEOG091G17T1
PhylomeDBiQ9NZI8
TreeFamiTF320229

Family and domain databases

CDDicd12625 RRM1_IGF2BP1, 1 hit
cd12628 RRM2_IGF2BP1, 1 hit
Gene3Di3.30.1370.10, 2 hits
3.30.70.330, 2 hits
InterProiView protein in InterPro
IPR034837 IGF2BP1_RRM1
IPR034842 IGF2BP1_RRM2
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF00013 KH_1, 4 hits
PF00076 RRM_1, 2 hits
SMARTiView protein in SMART
SM00322 KH, 4 hits
SM00360 RRM, 2 hits
SUPFAMiSSF54791 SSF54791, 4 hits
SSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50084 KH_TYPE_1, 4 hits
PS50102 RRM, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9NZI8-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA 
        60         70         80         90        100
MKAIETFSGK VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL 
       110        120        130        140        150
LAQYGTVENC EQVNTESETA VVNVTYSNRE QTRQAIMKLN GHQLENHALK 
       160        170        180        190        200
VSYIPDEQIA QGPENGRRGG FGSRGQPRQG SPVAAGAPAK QQQVDIPLRL 
       210        220        230        240        250
LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA EKAISVHSTP 
       260        270        280        290        300
EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK 
       310        320        330        340        350
KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA 
       360        370        380        390        400
YENDVAAMSL QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYSSFM 
       410        420        430        440        450
QAPEQEMVQV FIPAQAVGAI IGKKGQHIKQ LSRFASASIK IAPPETPDSK 
       460        470        480        490        500
VRMVIITGPP EAQFKAQGRI YGKLKEENFF GPKEEVKLET HIRVPASAAG 
       510        520        530        540        550
RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII GHFYASQMAQ 
       560        570 
RKIRDILAQV KQQHQKGQSN QAQARRK
Length:577
Mass (Da):63,481
Last modified:May 18, 2010 - v2
Checksum:i1D036AE5388D05FA
GO
Isoform 2 (identifier: Q9NZI8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-273: Missing.

Show »
Length:438
Mass (Da):48,598
Checksum:i2F615D03F5C00C1E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10Missing AA sequence (PubMed:9891060).Curated1
Sequence conflicti281I → T in AAF37203 (Ref. 1) Curated1
Sequence conflicti320Missing AA sequence (PubMed:9891060).Curated1
Sequence conflicti365I → T in AAF37203 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045366135 – 273Missing in isoform 2. 1 PublicationAdd BLAST139

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF198254 mRNA Translation: AAF37203.1
DQ227344 mRNA Translation: ABB46294.1
AC091133 Genomic DNA No translation available.
AC105030 Genomic DNA No translation available.
CCDSiCCDS11543.1 [Q9NZI8-1]
CCDS54138.1 [Q9NZI8-2]
RefSeqiNP_001153895.1, NM_001160423.1 [Q9NZI8-2]
NP_006537.3, NM_006546.3 [Q9NZI8-1]
UniGeneiHs.144936

Genome annotation databases

EnsembliENST00000290341; ENSP00000290341; ENSG00000159217 [Q9NZI8-1]
ENST00000431824; ENSP00000389135; ENSG00000159217 [Q9NZI8-2]
GeneIDi10642
KEGGihsa:10642
UCSCiuc002iom.4 human [Q9NZI8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF198254 mRNA Translation: AAF37203.1
DQ227344 mRNA Translation: ABB46294.1
AC091133 Genomic DNA No translation available.
AC105030 Genomic DNA No translation available.
CCDSiCCDS11543.1 [Q9NZI8-1]
CCDS54138.1 [Q9NZI8-2]
RefSeqiNP_001153895.1, NM_001160423.1 [Q9NZI8-2]
NP_006537.3, NM_006546.3 [Q9NZI8-1]
UniGeneiHs.144936

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KRMX-ray2.75A/B/C404-566[»]
ProteinModelPortaliQ9NZI8
SMRiQ9NZI8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115886, 160 interactors
ComplexPortaliCPX-1080 CRD-mediated mRNA stability complex
CORUMiQ9NZI8
DIPiDIP-38139N
IntActiQ9NZI8, 67 interactors
MINTiQ9NZI8
STRINGi9606.ENSP00000290341

PTM databases

iPTMnetiQ9NZI8
PhosphoSitePlusiQ9NZI8
SwissPalmiQ9NZI8

Polymorphism and mutation databases

BioMutaiIGF2BP1
DMDMi296434536

Proteomic databases

EPDiQ9NZI8
MaxQBiQ9NZI8
PaxDbiQ9NZI8
PeptideAtlasiQ9NZI8
PRIDEiQ9NZI8
ProteomicsDBi83410
TopDownProteomicsiQ9NZI8-1 [Q9NZI8-1]

Protocols and materials databases

DNASUi10642
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000290341; ENSP00000290341; ENSG00000159217 [Q9NZI8-1]
ENST00000431824; ENSP00000389135; ENSG00000159217 [Q9NZI8-2]
GeneIDi10642
KEGGihsa:10642
UCSCiuc002iom.4 human [Q9NZI8-1]

Organism-specific databases

CTDi10642
DisGeNETi10642
EuPathDBiHostDB:ENSG00000159217.9
GeneCardsiIGF2BP1
H-InvDBiHIX0013955
HGNCiHGNC:28866 IGF2BP1
HPAiHPA021367
HPA062273
MIMi608288 gene
neXtProtiNX_Q9NZI8
OpenTargetsiENSG00000159217
PharmGKBiPA143485501
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2193 Eukaryota
ENOG410ZKB4 LUCA
GeneTreeiENSGT00530000063171
HOGENOMiHOG000000675
HOVERGENiHBG052725
InParanoidiQ9NZI8
KOiK17391
OMAiEKPISIH
OrthoDBiEOG091G17T1
PhylomeDBiQ9NZI8
TreeFamiTF320229

Enzyme and pathway databases

ReactomeiR-HSA-428359 Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA
R-HSA-5687128 MAPK6/MAPK4 signaling

Miscellaneous databases

ChiTaRSiIGF2BP1 human
EvolutionaryTraceiQ9NZI8
GeneWikiiIGF2BP1
GenomeRNAii10642
PROiPR:Q9NZI8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159217 Expressed in 65 organ(s), highest expression level in lung
CleanExiHS_IGF2BP1
HS_ZBP1
GenevisibleiQ9NZI8 HS

Family and domain databases

CDDicd12625 RRM1_IGF2BP1, 1 hit
cd12628 RRM2_IGF2BP1, 1 hit
Gene3Di3.30.1370.10, 2 hits
3.30.70.330, 2 hits
InterProiView protein in InterPro
IPR034837 IGF2BP1_RRM1
IPR034842 IGF2BP1_RRM2
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF00013 KH_1, 4 hits
PF00076 RRM_1, 2 hits
SMARTiView protein in SMART
SM00322 KH, 4 hits
SM00360 RRM, 2 hits
SUPFAMiSSF54791 SSF54791, 4 hits
SSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50084 KH_TYPE_1, 4 hits
PS50102 RRM, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiIF2B1_HUMAN
AccessioniPrimary (citable) accession number: Q9NZI8
Secondary accession number(s): C9JT33
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 162 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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