Flotillin-2 (FLOT2)

The protein contains 428 amino acids for an estimated molecular weight of 47064 Da.

 

May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. May be involved in epidermal cell adhesion and epidermal structure and function. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 34%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs3736238

The reference OMIM entry for this protein is 131560

Flotillin 2; flot2
Epidermal surface antigen 1; esa1
Membrane component, chromosome 17, surface marker 1; m17s1

CLONING

Human epidermal surface antigen-1 was identified as a 35-kD antigen by means of a mouse monoclonal antibody raised against human keratinocytes. The monoclonal antibody was found to cause keratinocyte dissociation in vitro; hence, the conclusion that the native protein is involved in cell adhesion. Cho et al. (1995) found that mouse Esa cDNA encodes a 379-amino acid protein that is 99.2% identical to the human, differing at only 3 amino acids. Cho et al. (1995) found that both 'nude' and control mice have a second Esa mRNA transcript that conserves amino acid sequence and molecular mass. The mouse and human 5-prime- and 3-prime untranslated sequences are conserved. Similar RNA folding patterns of the 5-prime untranslated region are predicted despite a 91-bp insertion in the mouse.

GENE FUNCTION

Bickel et al. (1997) found that mouse Flot2 consistently copurifies with Flot1 (606998) and with caveolin-1 (601047) in the purification of caveolin-rich membranes. Baumann et al. (2000) screened a yeast 2-hybrid library using the N-terminal region of CAP (605264) and identified the caveolar protein flotillin. Flotillin forms a ternary complex with CAP and the CBL protooncogene product (165360), directing the localization of the CAP-CBL complex to a lipid raft subdomain of the plasma membrane. Localization of the CBL-CAP complex to lipid rafts generates a pathway that is crucial in the regulation of glucose uptake. 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. DHHC5 (ZDHHC5; 614586) belongs to a family of palmitoyl acyltransferases that reversibly modify cysteine residues for the regulation of protein trafficking, stability, and activity. Using a quantitative proteomic analysis of cultured mouse neuronal stem cells, Li et al. (2012) found that palmitoylation and oligomerization of flotillin-2 was abolished in homozygous Dhhc5 mutant neuronal stem cells. The absolute amount of flotillin-2 was not changed in Dhhc5 mutant neurons. In contrast, overexpression of mouse Dhhc5 in COS-7 cells markedly stimulated palmitoylation of human flotillin-2. Human flotillin-2 is myristoylated at gly2 and palmitoylated at cys4, cys19, and cys20. Mutation analysis of human flotillin-2 expressed in COS-7 cells revealed that coexpressed mouse Dhhc5 and endogenous COS-7 cell enzymes palmitoylated flotillin-2 predominantly on cys4 and cys20.

MAPPING

Schroeder et al. (1991) isolated a cDNA for an epidermal surface antigen believed to be involved in epidermal cell adhesion. By analysis of a somatic cell hybrid panel and in situ hybridization using the ESA cDNA, the gene was mapped to 17q11-q12 in the region containing the NF1 gene (613113). Using a RFLP within the ESA1 gene, they showed tight linkage of ESA1 with NF1; ... More on the omim web site

Subscribe to this protein entry history

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 131560 was added.