Cytoplasmic FMR1-interacting protein 1 (CYFIP1)
The protein contains 1253 amino acids for an estimated molecular weight of 145182 Da.
Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). May act as an invasion suppressor in cancers. (updated: Nov. 22, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs34683919 | |
| dbSNP:rs17137190 | |
| dbSNP:rs7170637 |
Biological Process
Axon extension
Axon guidance
Cell morphogenesis
Cell projection assembly
Cellular response to insulin stimulus
Cognition
Dendrite extension
Fc-gamma receptor signaling pathway involved in phagocytosis
Lamellipodium assembly
Modification of synaptic structure
Negative regulation of synaptic vesicle recycling
Neutrophil degranulation
Positive regulation of Arp2/3 complex-mediated actin nucleation
Positive regulation of axon extension
Positive regulation of dendrite development
Positive regulation of lamellipodium assembly
Positive regulation of neurotrophin TRK receptor signaling pathway
Positive regulation of ruffle assembly
Rac protein signal transduction
Regulation of cell shape
Regulation of modification of postsynaptic actin cytoskeleton
Regulation of myelination
Regulation of translation
Regulation of translation at postsynapse, modulating synaptic transmission
Response to electrical stimulus
Ruffle organization
Vascular endothelial growth factor receptor signaling pathway
Cellular Component
Axonal growth cone
Central region of growth cone
Cytosol
Dendritic growth cone
Dendritic spine
Excitatory synapse
Extracellular exosome
Extracellular region
Filopodium tip
Focal adhesion
Lamellipodium
MRNA cap binding complex
Neuron projection
Neuronal cell body
Perinuclear region of cytoplasm
Peripheral region of growth cone
Ruffle
SCAR complex
Secretory granule lumen
Specific granule lumen
Synapse
Terminal bouton
Tertiary granule lumen
The reference OMIM entry for this protein is 606322
Cytoplasmic fmrp-interacting protein 1; cyfip1
Specifically rac1-associated protein 1; sra1
Kiaa0068
CLONING
By sequencing clones obtained from an immature myeloid cell line (KG-1) cDNA library, Nomura et al. (1994) cloned CYFIP1, which they designated KIAA0068. The deduced protein contains 1,271 amino acids. Northern blot analysis detected CYFIP1 expression in all human tissues and cell lines examined. Highest expression was in lung, kidney, spleen, prostate, and ovary, as well as in HeLa cells and KG-1 cells. To identify novel proteins that interact with the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene (309550), Schenck et al. (2001) used yeast 2-hybrid screening with the FMRP N terminus as bait. They identified 2 proteins as FMRP interactors, CYFIP1 and CYFIP2 (606323). CYFIP1 contains 1,253 amino acids and shares 88% sequence identity with CYFIP2. CYFIP1 and CYFIP2 are members of a highly conserved protein family and share approximately 99% sequence identity with their mouse orthologs. By genomic sequence analysis to identify novel genes adjacent to the imprinted domain in the Prader-Willi syndrome (PWS; 176270)/Angelman (AS; 105830) syndrome deletion region of chromosome 15, Chai et al. (2003) identified CYFIP1. Northern blot analysis detected a 4.4-kb transcript in all human and mouse tissues examined, with highest expression in placenta.GENE FUNCTION
Schenck et al. (2001) found that CYFIP1 interacts exclusively with FMRP, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P (600819) and FXR2P (605339). The interaction of FMRP and CYFIP involves the domain of FMRP that also mediates homo- and heteromerization, suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. Schenck et al. (2001) determined that CYFIP1 and CYFIP2 are distributed in an identical pattern in the cytoplasm, showing colocalization with FMRP and ribosomes. CYFIP1 has been shown to interact with the small GTPase RAC1 (602048), which is implicated in development and maintenance of neuronal structures (Kobayashi et al., 1998). Consistent with FMRP and RAC1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts. RAC1 stimulates actin remodeling at the cell periphery, leading to lamellipodia formation. Steffen et al. (2004) found that Sra1 and Nap1 (NCKAP1; 604891) interacted with Wave2 (WASF2; 605875) and Abi1 (SSH3BP1; 603050) in resting mouse melanoma cells or following Rac1 activation. Microinjection of constitutively active RAC1 resulted in translocation of Sra1, Nap1, Wave2, and Abi1 to the tips of membrane protrusions. Moreover, removal of SRA1 or NAP1 by RNA interference in human or mouse cells abrogated formation of RAC1-dependent lamellipodia. Microinjection of active RAC1 failed to restore lamellipodia protrusion in cells lacking either SRA1 or NAP1. Steffen et al. (2004) concluded that SRA1 and NAP1 are essential components of a WAVE2- and ABI1-containing complex linking RAC1 to site-directed actin assembly.GENE STRUCTURE
Chai et al. (2003) determined that the CYFIP1 gene contains 31 exons and spans 111.4 kb. The 5-prime end is associated with a strong CpG island. The mouse Cyfip1 gene has a similar 31-exon structure.MAPPING
By analysis of a panel of human-rodent hybrid cell lines, Nomura et al. (1994) mapped the CYFIP1 gene to chromosome 15. By genomic sequence analysis, Chai et al. (2003) mapped the CYFIP1 gene to chromosome 15q11.2, within a region deleted in some cases of PWS and AS. CYFIP1 lie ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CYFIP1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606322 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed