O88477 (IF2B1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor 2 mRNA-binding protein 1
Short name=IGF2 mRNA-binding protein 1
Short name=IMP-1

Alternative name(s):
Coding region determinant-binding protein
Short name=CRD-BP
IGF-II mRNA-binding protein 1
VICKZ family member 1

Gene names

Name:	Igf2bp1
Synonyms:	Vickz1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	577 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC mRNA. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities. Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA. Component of the CRD-mediated complex that promotes MYC mRNA stabilization By similarity. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the CD44 mRNA By similarity. Plays a role in regulating the stability of MYC and CD44 mRNAs By similarity. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations By similarity. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1 By similarity. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling By similarity. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation By similarity. Also involved in growth or survival of lung-cancer cells By similarity. Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' By similarity. Promotes translocation of the beta-actin mRNA to dendrites By similarity. May act as a regulator of mRNA transport to activated synapses in response to synaptic activity By similarity. Ref.14 Ref.17
Subunit structure	Can form homodimers and heterodimers with IGF2BP1 or IGF2BP3 By similarity. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 By similarity. Identification in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 By similarity. Associates with mRNP complex By similarity. Found in a RNP granule complex with FMR1 By similarity. Interacts with FMR1 By similarity. Component of a multi subunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with EIF2C1 and EIF2C2 By similarity. Interacts through the third and fourth KH domains with PABPC1 in a RNA-independent manner By similarity. Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with ELAVL4 in a RNA-dependent manner. Associates with microtubules and polysomes. Ref.9
Subcellular location	Nucleus. Cytoplasm. Note: Found in lamellipodia of the leading edge, in the perinuclear region and beneath the plasma membrane By similarity. The subcytoplasmic localization is cell specific and regulated by cell contact and growth By similarity. Colocalized with H19 RNA at lamellipodia By similarity. Colocalized with CD44 mRNA in RNP granules By similarity. Nuclear export is mediated by XPO1/CRM1 By similarity. In motile cells, is transported towards the leading edge into the cortical region of the lamellipodia where it is connected to microfilaments. Present in the form of granules and into F-actin-rich protrusion of dendrites, spines and subsynaptic sites By similarity. Colocalizes with beta-actin mRNA in dendrites and spines By similarity. Exhibited rapid, bidirectional movements in dendrites and spines By similarity. Neuronal depolarization by KCl induces its rapid efflux from the cell body into dendrites By similarity. Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Targeted to stress granules (SGs), but not processing bodies (PBs), during cellular stress. Colocalizes with G3BP1 and TIAL1 in SGs By similarity. Ref.12 Ref.13
Tissue specificity	Expressed in zygotes and blastocysts (at protein level). Expressed in skeletal muscle, trophoblasts of placenta, oocytes and spermatogonia (at protein level). Expressed in testis and ovary. Ref.10 Ref.16
Developmental stage	Expressed during fetal development at 12.5, 14.5 and 17.5 dpc and declining towards birth (at protein level). Expressed at the basal plasma cell membrane in the basal layer of the epidermis of the skin, lung and intestine from 12.5 to 15.5 dpc (at protein level). Expressed in myoblasts and myotubes at 12.5 dpc (at protein level). Expressed in gonads at 12.5 and 14.5 dpc (at protein level). Expressed in germ cells at 16.5 dpc (at protein level). Expressed during fetal development at 7, 9.5, 10.5, 12.5, 14.5 and 17.5 dpc and declining towards birth. Ref.10 Ref.11 Ref.16
Domain	The third and fourth KH domains encompass the protein dimerization motif and are necessary and sufficient for RNA binding. The KH domains are important for granule formation and localization. Contains two nuclear export signals, situated within the second and fourth KH domains.
Post-translational modification	Phosphorylated. Phosphorylation may influence mRNA translation By similarity.
Sequence similarities	Belongs to the RRM IMP/VICKZ family. Contains 4 KH domains. Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	Translation regulation
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	CRD-mediated mRNA stabilization Inferred from electronic annotation. Source: Compara RNA localization Inferred from electronic annotation. Source: Compara negative regulation of translation Inferred from electronic annotation. Source: Compara regulation of mRNA stability involved in response to stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	CRD-mediated mRNA stability complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	mRNA 3'-UTR binding Inferred from sequence or structural similarity. Source: UniProtKB mRNA 5'-UTR binding Inferred from electronic annotation. Source: Compara nucleotide binding Inferred from electronic annotation. Source: InterPro translation regulator activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 577	577	Insulin-like growth factor 2 mRNA-binding protein 1		PRO_0000282534
Regions
	Domain	2 – 75	74	RRM 1
	Domain	81 – 156	76	RRM 2
	Domain	195 – 260	66	KH 1
	Domain	276 – 343	68	KH 2
	Domain	405 – 470	66	KH 3
	Domain	487 – 553	67	KH 4
	Region	187 – 570	384	Necessary for interaction with IGF2BP1 and binding to TAU mRNA
	Region	312 – 323	12	Sufficient for nuclear export By similarity
	Region	485 – 495	11	Sufficient for nuclear export By similarity
Amino acid modifications
	Modified residue	181	1	Phosphoserine Ref.18
Experimental info
	Sequence conflict	276	1	E → G in AAH51679. Ref.8
	Sequence conflict	406	1	E → G in BAC32119. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	O88477 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: EFBB1AF2FF9F0344	FASTA	577	63,451
	10 20 30 40 50 60 MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA MKAIETFSGK 70 80 90 100 110 120 VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL LAQYGTVENC EQVNTESETA 130 140 150 160 170 180 VVNVTYSNRE QTRQAIMKLN GHQLENHALK VSYIPDEQIT QGPENGRRGG FGSRGQPRQG 190 200 210 220 230 240 SPVAAGAPAK QQPVDIPLRL LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA 250 260 270 280 290 300 EKAISVHSTP EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK 310 320 330 340 350 360 KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA YENDVAAMSL 370 380 390 400 410 420 QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYSSFM QAPEQEMVQV FIPAQAVGAI 430 440 450 460 470 480 IGKKGQHIKQ LSRFASASIK IAPPETPDSK VRMVVITGPP EAQFKAQGRI YGKLKEENFF 490 500 510 520 530 540 GPKEEVKLET HIRVPASAAG RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII 550 560 570 GHFYASQMAQ RKIRDILAQV KQQHQKGQSN LAQARRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant." Bernstein P.L., Herrick D.J., Prokipcak R.D., Ross J. Genes Dev. 6:642-654(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], RNA-BINDING.
[2]	"Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA." Prokipcak R.D., Herrick D.J., Ross J. J. Biol. Chem. 269:9261-9269(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], RNA-BINDING.
[3]	"The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3' untranslated regions and role of ribosome translocation." Herrick D.J., Ross J. Mol. Cell. Biol. 14:2119-2128(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro." Leeds P., Kren B.T., Boylan J.M., Betz N.A., Steer C.J., Gruppuso P.A., Ross J. Oncogene 14:1279-1286(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The c-myc coding region determinant-binding protein: a member of a family of KH domain RNA-binding proteins." Doyle G.A., Betz N.A., Leeds P.F., Fleisig A.J., Prokipcak R.D., Ross J. Nucleic Acids Res. 26:5036-5044(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo and Head.
[7]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: 129/Sv X 129SvCp. Tissue: Embryonic stem cell.
[9]	"The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells." Atlas R., Behar L., Elliott E., Ginzburg I. J. Neurochem. 89:613-626(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-20; 27-52; 302-325; 509-525 AND 555-561, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A MRNP COMPLEX WITH ELAVL4 AND G3BP, INTERACTION WITH ELAVL4, ASSOCIATION WITH POLYSOMES.
[10]	"A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development." Nielsen J., Christiansen J., Lykke-Andersen J., Johnsen A.H., Wewer U.M., Nielsen F.C. Mol. Cell. Biol. 19:1262-1270(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]	"H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein." Runge S., Nielsen F.C., Nielsen J., Lykke-Andersen J., Wewer U.M., Christiansen J. J. Biol. Chem. 275:29562-29569(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[12]	"Cytoplasmic trafficking of IGF-II mRNA-binding protein by conserved KH domains." Nielsen F.C., Nielsen J., Kristensen M.A., Koch G., Christiansen J. J. Cell Sci. 115:2087-2097(2002) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH MICROTUBULES, RNA-BINDING, SUBCELLULAR LOCATION.
[13]	"Nuclear transit of human zipcode-binding protein IMP1." Nielsen J., Adolph S.K., Rajpert-De Meyts E., Lykke-Andersen J., Koch G., Christiansen J., Nielsen F.C. Biochem. J. 376:383-391(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Targeted knockdown of the RNA-binding protein CRD-BP promotes cell proliferation via an insulin-like growth factor II-dependent pathway in human K562 leukemia cells." Liao B., Patel M., Hu Y., Charles S., Herrick D.J., Brewer G. J. Biol. Chem. 279:48716-48724(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins." Yisraeli J.K. Biol. Cell 97:87-96(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[16]	"Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer." Hammer N.A., Hansen T.O., Byskov A.G., Rajpert-De Meyts E., Groendahl M.L., Bredkjaer H.E., Wewer U.M., Christiansen J., Nielsen F.C. Reproduction 130:203-212(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[17]	"CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease." Sparanese D., Lee C.H. Nucleic Acids Res. 35:1209-1221(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, RNA-BINDING.
[18]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF061569 mRNA. Translation: AAC72743.1. AK044850 mRNA. Translation: BAC32119.1. AK013940 mRNA. Translation: BAB29071.1. AL603682 Genomic DNA. Translation: CAM18266.1. AL606704 Genomic DNA. Translation: CAM22496.1. BC051679 mRNA. Translation: AAH51679.1.
IPI	IPI00131056.
RefSeq	NP_034081.1. NM_009951.4.
UniGene	Mm.294769. Mm.490105.
3D structure databases
HSSP	HSSP built from PDB template 2CQH based on UniProtKB Q9Y6M1.
ProteinModelPortal	O88477.
SMR	O88477. Positions 1-161, 198-349, 405-562.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48578N.
PTM databases
PhosphoSite	O88477.
Proteomic databases
PaxDb	O88477.
PRIDE	O88477.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000013559; ENSMUSP00000013559; ENSMUSG00000013415.
GeneID	140486.
KEGG	mmu:140486.
UCSC	uc007lay.2. mouse.
Organism-specific databases
CTD	10642.
MGI	MGI:1890357. Igf2bp1.
Phylogenomic databases
eggNOG	NOG249985.
GeneTree	ENSGT00530000063171.
HOGENOM	HOG000000675.
HOVERGEN	HBG052725.
InParanoid	O88477.
OMA	EQETVHV.
OrthoDB	EOG405S0T.
Gene expression databases
Bgee	O88477.
Genevestigator	O88477.
Family and domain databases
Gene3D	3.30.70.330. 2 hits.
InterPro	IPR004087. KH_dom. IPR004088. KH_dom_type_1. IPR012677. Nucleotide-bd_a/b_plait. IPR000504. RRM_dom. [Graphical view]
Pfam	PF00013. KH_1. 4 hits. PF00076. RRM_1. 1 hit. [Graphical view]
SMART	SM00322. KH. 4 hits. SM00360. RRM. 2 hits. [Graphical view]
PROSITE	PS50084. KH_TYPE_1. 4 hits. PS50102. RRM. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	369796.
SOURCE	Search...

Entry information

Entry name

IF2B1_MOUSE

Accession

Primary (citable) accession number: O88477
Secondary accession number(s): Q80US9, Q8BRH1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program