Fibronectin (FN1)
The protein contains 2386 amino acids for an estimated molecular weight of 262625 Da.
Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape (PubMed:3024962, PubMed:3900070, PubMed:3593230, PubMed:7989369). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). Participates in the regulation of type I collagen deposition by osteoblasts (By similarity).', 'Binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling. (updated: April 7, 2021)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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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Biological Process
Acute-phase response
Angiogenesis
Biological process involved in interaction with symbiont
Blood coagulation
Blood coagulation, fibrin clot formation
Calcium-independent cell-matrix adhesion
Cell adhesion
Cell-matrix adhesion
Cell-substrate adhesion
Cell-substrate junction assembly
Cellular protein metabolic process
Cytokine-mediated signaling pathway
Endodermal cell differentiation
Extracellular matrix disassembly
Extracellular matrix organization
Heart development
Inositol phosphate-mediated signaling
Integrin activation
Integrin-mediated signaling pathway
Interaction with other organism via secreted substance involved in symbiotic interaction
Leukocyte migration
Negative regulation of apoptotic process
Negative regulation of transforming growth factor beta production
Negative regulation of transforming growth factor-beta secretion
Nervous system development
Neural crest cell migration involved in autonomic nervous system development
Peptide cross-linking
Platelet activation
Platelet aggregation
Platelet degranulation
Positive regulation of axon extension
Positive regulation of cell population proliferation
Positive regulation of fibroblast proliferation
Positive regulation of gene expression
Positive regulation of phosphatidylinositol 3-kinase signaling
Positive regulation of substrate-dependent cell migration, cell attachment to substrate
Post-translational protein modification
Regulation of cell shape
Regulation of ERK1 and ERK2 cascade
Regulation of protein phosphorylation
Response to wounding
Substrate adhesion-dependent cell spreading
Wound healing
Cellular Component
Apical plasma membrane
Basal lamina
Basement membrane
Blood microparticle
Collagen-containing extracellular matrix
Endoplasmic reticulum lumen
Endoplasmic reticulum-Golgi intermediate compartment
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Fibrinogen complex
Platelet alpha granule lumen
Proteinaceous extracellular matrix
Molecular Function
Chaperone binding
Collagen binding
Disordered domain specific binding
Enzyme binding
Extracellular matrix structural constituent
Heparin binding
Identical protein binding
Integrin binding
Peptidase activator activity
Protease binding
Protein C-terminus binding
Proteoglycan binding
Signaling receptor binding
The reference OMIM entry for this protein is 135600
Fibronectin 1; fn1
Fn
Large, external, transformation-sensitive protein; lets
DESCRIPTION
Fibronectin-1 belongs to a family of high molecular weight glycoproteins that are present on cell surfaces, in extracellular fluids, connective tissues, and basement membranes. Fibronectins interact with other extracellular matrix proteins and cellular ligands, such as collagen, fibrin, and integrins. Fibronectins are involved in adhesive and migratory processes of cells. Two major forms of fibronectin exist: a plasma soluble form and a cellular form (summary by Muro et al., 2003).CLONING
Kornblihtt et al. (1983) isolated clones corresponding to the human fibronectin gene from a human carcinoma cDNA library. The sequence showed approximately 90% homology to the bovine sequence. Fibronectin mRNA was estimated to be 7.9 kb. The data suggested that fibronectin is coded by a single gene and that the cellular and plasma proteins arise from post-transcriptional events. Kornblihtt et al. (1984) identified 2 different fibronectin cDNA clones and corresponding mRNAs that differed by the presence or absence of a 270-bp internal fragment (termed ED for 'extra domain,' EDA, or EDIIIA) that encodes a 90-residue domain of type III homology found in the bovine protein. This 90-residue fragment is in the C terminus between the cell attachment and heparin-binding domains of the protein. Human liver produced mainly the form without the internal fragment. Kornblihtt et al. (1985) determined that the fibronectin gene encodes a polypeptide of 2,146 to 2,325 residues, depending on which internal splicing has taken place. The primary structure of the protein contains several internal homologous regions, reflecting high complexity. Different motifs showed specific binding domains for fibrin, heparin, collagen, and DNA. Sekiguchi et al. (1986) also found that liver fibronectin cDNAs lacked the ED segment that is present in most cDNAs encoding cellular fibronectin. Furthermore, 2 liver cDNAs differed in sequence at the 'type III connecting segment' (IIICS) region by the presence or absence of 192 bp with flanking regions. Cellular FN1 cDNAs contained the 192-base IIICS region. Thus, cellular fibronectin appears to have extra peptide segments, encoded by the IIICS region and its flanking segments as well as the 270-base ED region, that are mostly absent in liver fibronectin. Gutman and Kornblihtt (1987) described a third region of variability in human fibronectin in addition to the EDA and IIICS regions. This third region resembles the EDA and consists of a 273-nucleotide exon (termed 'EDII,' EDB, or EDIIIB) encoding exactly one 91-amino acid repeat of type III homology located between the DNA- and the cell-binding domains of FN. The 2 corresponding mRNA variants were present in cells known to synthesize the cellular form of FN. Liver cells, which are the source of plasma FN, produced only messengers without the EDB. Gutman and Kornblihtt (1987) concluded that both the EDA and EDB sequences are restricted to cellular FN. Combination of all the possible patterns of splicing in the 3 regions described could theoretically generate as many as 20 distinct FN polypeptides from a single gene.MAPPING
Using human-mouse somatic cell hybrids, Koch et al. (1982) mapped the FN1 gene to chromosome 2, and Prowse et al. (1986) confirmed this assignment with a cDNA probe applied to somatic cell hybrids. Henry et al. (1985) assigned FN1 to 2q23.2-qter with a genomic probe in somatic cell hybrids with rearranged human chromosomes. Wu e ... More on the omim web site
April 10, 2021: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 135600 was added.