Flotillin-1 (FLOT1)
The protein contains 427 amino acids for an estimated molecular weight of 47355 Da.
May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. (updated: March 4, 2015)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs3180825 |
Biological Process
Axonogenesis
Cellular response to exogenous dsRNA
DsRNA transport
Establishment of protein localization to plasma membrane
Extracellular matrix disassembly
Membrane raft assembly
Plasma membrane raft assembly
Positive regulation of cell adhesion molecule production
Positive regulation of cell junction assembly
Positive regulation of cell-cell adhesion mediated by cadherin
Positive regulation of cytokine production
Positive regulation of endocytosis
Positive regulation of heterotypic cell-cell adhesion
Positive regulation of interferon-beta production
Positive regulation of myoblast fusion
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of protein binding
Positive regulation of protein phosphorylation
Positive regulation of skeletal muscle tissue development
Positive regulation of synaptic transmission, dopaminergic
Positive regulation of toll-like receptor 3 signaling pathway
Protein homooligomerization
Protein kinase C signaling
Protein localization to membrane raft
Protein localization to plasma membrane
Protein stabilization
Regulation of necroptotic process
Regulation of neurotransmitter uptake
Regulation of receptor internalization
Regulation of Rho protein signal transduction
Response to endoplasmic reticulum stress
Cellular Component
Adherens junction
Basolateral plasma membrane
Caveola
Cell-cell adherens junction
Cell-cell contact zone
Cell-cell junction
Centriolar satellite
Cytoplasmic vesicle
Dopaminergic synapse
Early endosome
Endosome
External side of plasma membrane
Extracellular exosome
Flotillin complex
Focal adhesion
GABA-ergic synapse
Glutamatergic synapse
Integral component of membrane
Lamellipodium
Lysosomal membrane
Melanosome
Membrane
Membrane raft
Microtubule organizing center
Plasma membrane
Presynaptic active zone
Sarcolemma
Uropod
The reference OMIM entry for this protein is 606998
Flotillin 1; flot1
CLONING
Bickel et al. (1997) cloned a partial mouse flotillin-1 cDNA from a lung cDNA and a full-length cDNA from a 3T3 L1 mouse adipocyte cDNA library. Flot1 encodes a deduced 428-amino acid protein with a predicted molecular mass of 47 kD. It contains 2 hydrophobic domains and several potential phosphorylation sites. Flot1 shares 47% amino acid identity with both mouse and human FLOT2 (131560). Northern blot analysis of mouse tissues revealed expression in adipose tissue, heart, skeletal muscle, and lung. By Western blot analysis, Flot1 was also found as a 47-kD protein in caveolin-rich membrane domains isolated from human lung and from cultured mouse adipocytes. Zhang et al. (2000) purified human FLOT1 by RT-PCR from CD34+ cord blood and adult bone marrow. By analyzing microarrays, they found weak expression of FLOT1 in 4 of 5 hematopoietic cell lines and no expression in a promyelocytic cell line.GENE FUNCTION
Bickel et al. (1997) found that mouse Flot1 behaves as a resident integral membrane protein of caveolae. It consistently copurified with Flot2 and with caveolin-1 (601047) in the purification of caveolin-rich membranes. Hazarika et al. (1999) found that stable transfection of Flot1, which they called ESA/flotillin-2, in COS-1 cells induced filopodia formation and changed the epithelial morphology to that of neuronal cells. Santamaria et al. (2005) found that prostate tumor overexpressed gene-1 (PTOV1; 610195) interacted with flotillin-1 in detergent-insoluble membrane fractions. Flotillin-1 colocalized with PTOV1 at the plasma membrane and in the nucleus, and it entered the nucleus concomitant with PTOV1 shortly before initiation of S phase. Protein levels of PTOV1 and flotillin-1 oscillated during the cell cycle, with a peak in S phase. Depletion of PTOV1 significantly inhibited nuclear localization of flotillin-1, whereas depletion of flotillin-1 did not affect nuclear localization of PTOV1. Depletion of either protein markedly inhibited cell proliferation under basal conditions. Overexpression of PTOV1 or flotillin-1 strongly induced proliferation, which required their localization to the nucleus and was dependent on the reciprocal protein. Santamaria et al. (2005) concluded that PTOV1 assists flotillin-1 in its translocation to the nucleus and that both proteins are required for cell proliferation. Uptake of cholesterol from intestine and liver is mediated by NPC1L1 (608010), which cycles between the plasma membrane and endocytic recycling compartment in response to cholesterol availability. Using a human liver cell line, rat liver cells expressing human NPC1L1, and transgenic mice, Ge et al. (2011) found that NPC1L1 required FLOT1 and FLOT2 for bulk endocytosis of cholesterol-enriched plasma membrane microdomains. NPC1L1 interacted directly with FLOT1 and FLOT2, which functioned upstream of clathrin (see 118955) in NPC1L1 cholesterol uptake. The flotillins had no effect on recycling NPC1L1 to plasma membranes. In addition, the hypocholesterolemic drug ezetimibe disrupted NPC1L1-flotillin interactions, blocking formation of cholesterol-enriched microdomains.GENE STRUCTURE
Zhang et al. (2000) determined that the FLOT1 gene contains 13 exons.MAPPING
Hartz (2013) mapped the FLOT1 gene to chromosome 6p21.33 based on an alignment of the FLOT1 sequence (GenBank GENBANK AF089750) with the genomic sequence (GRCh37). ... 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. 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 606998 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed