CPLM-022440

Genbank Nucleotide ID

Insulin-like growth factor 2 mRNA-binding protein 1

Protein Synonyms/Alias

IGF2 mRNA-binding protein 1; IMP-1; Coding region determinant-binding protein; CRD-BP; IGF-II mRNA-binding protein 1; VICKZ family member 1; Zip code-binding protein 1; ZBP-1; Zipcode-binding protein 1

Homo sapiens (Human)

Position	Peptide	Type	References
3	*****MNKLYIGNLN	ubiquitination	[1, 2]
20	VTPADLEKVFAEHKI	ubiquitination	[1, 2, 3]
26	EKVFAEHKISYSGQF	ubiquitination	[1]
138	QTRQAIMKLNGHQLE	ubiquitination	[1]
190	VAAGAPAKQQQVDIP	ubiquitination	[2, 3, 4, 5]
213	YVGAIIGKEGATIRN	ubiquitination	[1, 2, 3, 6, 7, 8]
223	ATIRNITKQTQSKID	ubiquitination	[4]
242	ENAGAAEKAISVHST	ubiquitination	[2]
272	HKEAKDTKTADEVPL	ubiquitination	[2, 3, 4]
280	TADEVPLKILAHNNF	ubiquitination	[2, 3]
330	PERTITVKGAIENCC	ubiquitination	[2, 3]
440	RFASASIKIAPPETP	ubiquitination	[1, 2, 3, 9]
450	PPETPDSKVRMVIIT	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
465	GPPEAQFKAQGRIYG	ubiquitination	[1, 4]
475	GRIYGKLKEENFFGP	ubiquitination	[1, 2, 3]
483	EENFFGPKEEVKLET	ubiquitination	[2, 3]
508	RVIGKGGKTVNELQN	ubiquitination	[2]
561	RDILAQVKQQHQKGQ	ubiquitination	[2]

[1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[6] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[7] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[8] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]

Functional Description

RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD- mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. 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 and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. 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. 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. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung- cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (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).

DOMAIN 2 75 RRM 1.
DOMAIN 81 156 RRM 2.
DOMAIN 195 260 KH 1.
DOMAIN 276 343 KH 2.
DOMAIN 405 470 KH 3.
DOMAIN 487 553 KH 4.
REGION 187 570 Necessary for interaction with ELAVL4 and
REGION 312 323 Sufficient for nuclear export.
REGION 485 495 Sufficient for nuclear export.
MOD_RES 181 181 Phosphoserine.

3D-structure; Alternative splicing; Cell projection; Complete proteome; Cytoplasm; Direct protein sequencing; Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding; Translation regulation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0070937; C:CRD-mediated mRNA stability complex; IDA:UniProtKB.
GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
GO:0005634; C:nucleus; IDA:HPA.
GO:0005886; C:plasma membrane; IDA:HPA.
GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
GO:0048027; F:mRNA 5'-UTR binding; IDA:BHF-UCL.
GO:0000166; F:nucleotide binding; IEA:InterPro.
GO:0045182; F:translation regulator activity; IDA:BHF-UCL.
GO:0070934; P:CRD-mediated mRNA stabilization; IDA:UniProtKB.
GO:0010467; P:gene expression; TAS:Reactome.
GO:0017148; P:negative regulation of translation; IDA:BHF-UCL.
GO:0042035; P:regulation of cytokine biosynthetic process; IC:BHF-UCL.
GO:0010610; P:regulation of mRNA stability involved in response to stress; IMP:UniProtKB.
GO:0006403; P:RNA localization; IEA:Compara.

IPR004087; KH_dom.
IPR004088; KH_dom_type_1.
IPR012677; Nucleotide-bd_a/b_plait.
IPR000504; RRM_dom.

PF00013; KH_1
PF00076; RRM_1

SM00322; KH
SM00360; RRM

PS50084; KH_TYPE_1
PS50102; RRM