Human Gene FN1 (ENST00000446046.5) from GENCODE V44
Description: Homo sapiens fibronectin 1 (FN1), transcript variant 4, mRNA. (from RefSeq NM_212478) RefSeq Summary (NM_212478): This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]. Gencode Transcript: ENST00000446046.5 Gencode Gene: ENSG00000115414.21 Transcript (Including UTRs) Position: hg38 chr2:215,360,862-215,436,068 Size: 75,207 Total Exon Count: 46 Strand: - Coding Region Position: hg38 chr2:215,361,555-215,435,802 Size: 74,248 Coding Exon Count: 46
ID:FINC_HUMAN DESCRIPTION: RecName: Full=Fibronectin; Short=FN; AltName: Full=Cold-insoluble globulin; Short=CIG; Contains: RecName: Full=Anastellin; Contains: RecName: Full=Ugl-Y1; Contains: RecName: Full=Ugl-Y2; Contains: RecName: Full=Ugl-Y3; Flags: Precursor; FUNCTION: Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. FUNCTION: Anastellin 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. SUBUNIT: Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR, LGALS3BP and COL13A1. Interacts with FBLN7 (By similarity). Interacts with COMP. Interacts with S.aureus fnbA. Interacts with TNR; the interaction inhibits cell adhesion and neurite outgrowth (By similarity). Interacts with FST3. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix. TISSUE SPECIFICITY: Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2 and Ugl-Y3 are found in urine. DEVELOPMENTAL STAGE: Ugl-Y1, Ugl-Y2 and Ugl-Y3 are present in the urine from 0 to 17 years of age. PTM: Sulfated. PTM: It is not known whether both or only one of Thr-2064 and Thr- 2065 are/is glycosylated. PTM: Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers). PTM: Phosphorylation sites are present in the extracellular medium. PTM: Proteolytic processing produces the C-terminal NC1 peptide, anastellin. DISEASE: Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:601894]; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. SIMILARITY: Contains 12 fibronectin type-I domains. SIMILARITY: Contains 2 fibronectin type-II domains. SIMILARITY: Contains 16 fibronectin type-III domains. SEQUENCE CAUTION: Sequence=AAX76513.1; Type=Erroneous gene model prediction; Sequence=BAD93077.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAD91166.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAD97964.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAD97965.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAH18136.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Wikipedia; Note=Fibronectin entry; URL="http://en.wikipedia.org/wiki/Fibronectin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P02751
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04510 - Focal adhesion hsa04512 - ECM-receptor interaction hsa04810 - Regulation of actin cytoskeleton hsa05100 - Bacterial invasion of epithelial cells hsa05200 - Pathways in cancer hsa05222 - Small cell lung cancer
Reactome (by CSHL, EBI, and GO)
Protein P02751 (Reactome details) participates in the following event(s):
R-HSA-349593 Interaction of integrin alphaIIbbeta3 with Fibronectin R-HSA-2327733 FN1 binds Collagen types I-V, VII R-HSA-2545196 FN1 dimerizes R-HSA-202723 Integrin alpha5beta1 binds FN1 dimer R-HSA-354149 Interaction of integrin alphaIIb beta3 with Fibrinogen R-HSA-481007 Exocytosis of platelet alpha granule contents R-HSA-377641 Clustering of Integrin alphaIIb beta3 complexes R-HSA-377643 Dephosphorylation of inactive SRC by PTPB1 R-HSA-377644 Release of CSK from SRC R-HSA-377640 Autophosphorylation of SRC R-HSA-354066 Translocation of FADK1 to Focal complexes R-HSA-429415 SYK binds to integrin alphaIIb beta3 R-HSA-8952289 FAM20C phosphorylates FAM20C substrates R-HSA-354087 Recruitment of GRB2 to p-FADK1 R-HSA-372705 Recruitment of p130Cas to FADK1 R-HSA-354124 Phosphorylation of pFADK1 by SRC R-HSA-354073 Autophosphorylation of FADK1 at Y397 R-HSA-429441 SYK activation by SRC R-HSA-354165 Interaction of SOS with GRB2 bound to FADK1 R-HSA-372697 Crk binding to p130cas R-HSA-372693 Phosphorylation of p130Cas by SRC-FADK1 complex R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802932 Dissociation of BRAF/RAF fusion complex R-HSA-6803227 Dissociation of high activity BRAF complexes R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers R-HSA-216083 Integrin cell surface interactions R-HSA-1474244 Extracellular matrix organization R-HSA-1566977 Fibronectin matrix formation R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-354192 Integrin alphaIIb beta3 signaling R-HSA-114608 Platelet degranulation R-HSA-6785807 Interleukin-4 and 13 signaling R-HSA-109582 Hemostasis R-HSA-76009 Platelet Aggregation (Plug Formation) R-HSA-9006921 Integrin signaling R-HSA-76005 Response to elevated platelet cytosolic Ca2+ R-HSA-449147 Signaling by Interleukins R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275 Post-translational protein phosphorylation R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins R-HSA-372708 p130Cas linkage to MAPK signaling for integrins R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-162582 Signal Transduction R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-392499 Metabolism of proteins R-HSA-597592 Post-translational protein modification R-HSA-168256 Immune System R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6802957 Oncogenic MAPK signaling R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease
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