FN1

Protein identityUniProt · HPA

UniProt accession

P02751

Gene

FN1

Ensembl

ENSG00000115414

Chromosome

2

Canonical length

2477 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

2477 residues, UniProt reviewed canonical sequence.

>P02751|FN1
     1  MLRGPGPGLL LLAVQCLGTA VPSTGASKSK RQAQQMVQPQ SPVAVSQSKP GCYDNGKHYQ
    61  INQQWERTYL GNALVCTCYG GSRGFNCESK PEAEETCFDK YTGNTYRVGD TYERPKDSMI
   121  WDCTCIGAGR GRISCTIANR CHEGGQSYKI GDTWRRPHET GGYMLECVCL GNGKGEWTCK
   181  PIAEKCFDHA AGTSYVVGET WEKPYQGWMM VDCTCLGEGS GRITCTSRNR CNDQDTRTSY
   241  RIGDTWSKKD NRGNLLQCIC TGNGRGEWKC ERHTSVQTTS SGSGPFTDVR AAVYQPQPHP
   301  QPPPYGHCVT DSGVVYSVGM QWLKTQGNKQ MLCTCLGNGV SCQETAVTQT YGGNSNGEPC
   361  VLPFTYNGRT FYSCTTEGRQ DGHLWCSTTS NYEQDQKYSF CTDHTVLVQT RGGNSNGALC
   421  HFPFLYNNHN YTDCTSEGRR DNMKWCGTTQ NYDADQKFGF CPMAAHEEIC TTNEGVMYRI
   481  GDQWDKQHDM GHMMRCTCVG NGRGEWTCIA YSQLRDQCIV DDITYNVNDT FHKRHEEGHM
   541  LNCTCFGQGR GRWKCDPVDQ CQDSETGTFY QIGDSWEKYV HGVRYQCYCY GRGIGEWHCQ
   601  PLQTYPSSSG PVEVFITETP SQPNSHPIQW NAPQPSHISK YILRWRPKNS VGRWKEATIP
   661  GHLNSYTIKG LKPGVVYEGQ LISIQQYGHQ EVTRFDFTTT STSTPVTSNT VTGETTPFSP
   721  LVATSESVTE ITASSFVVSW VSASDTVSGF RVEYELSEEG DEPQYLDLPS TATSVNIPDL
   781  LPGRKYIVNV YQISEDGEQS LILSTSQTTA PDAPPDTTVD QVDDTSIVVR WSRPQAPITG
   841  YRIVYSPSVE GSSTELNLPE TANSVTLSDL QPGVQYNITI YAVEENQEST PVVIQQETTG
   901  TPRSDTVPSP RDLQFVEVTD VKVTIMWTPP ESAVTGYRVD VIPVNLPGEH GQRLPISRNT
   961  FAEVTGLSPG VTYYFKVFAV SHGRESKPLT AQQTTKLDAP TNLQFVNETD STVLVRWTPP
  1021  RAQITGYRLT VGLTRRGQPR QYNVGPSVSK YPLRNLQPAS EYTVSLVAIK GNQESPKATG
  1081  VFTTLQPGSS IPPYNTEVTE TTIVITWTPA PRIGFKLGVR PSQGGEAPRE VTSDSGSIVV
  1141  SGLTPGVEYV YTIQVLRDGQ ERDAPIVNKV VTPLSPPTNL HLEANPDTGV LTVSWERSTT
  1201  PDITGYRITT TPTNGQQGNS LEEVVHADQS SCTFDNLSPG LEYNVSVYTV KDDKESVPIS
  1261  DTIIPEVPQL TDLSFVDITD SSIGLRWTPL NSSTIIGYRI TVVAAGEGIP IFEDFVDSSV
  1321  GYYTVTGLEP GIDYDISVIT LINGGESAPT TLTQQTAVPP PTDLRFTNIG PDTMRVTWAP
  1381  PPSIDLTNFL VRYSPVKNEE DVAELSISPS DNAVVLTNLL PGTEYVVSVS SVYEQHESTP
  1441  LRGRQKTGLD SPTGIDFSDI TANSFTVHWI APRATITGYR IRHHPEHFSG RPREDRVPHS
  1501  RNSITLTNLT PGTEYVVSIV ALNGREESPL LIGQQSTVSD VPRDLEVVAA TPTSLLISWD
  1561  APAVTVRYYR ITYGETGGNS PVQEFTVPGS KSTATISGLK PGVDYTITVY AVTGRGDSPA
  1621  SSKPISINYR TEIDKPSQMQ VTDVQDNSIS VKWLPSSSPV TGYRVTTTPK NGPGPTKTKT
  1681  AGPDQTEMTI EGLQPTVEYV VSVYAQNPSG ESQPLVQTAV TNIDRPKGLA FTDVDVDSIK
  1741  IAWESPQGQV SRYRVTYSSP EDGIHELFPA PDGEEDTAEL QGLRPGSEYT VSVVALHDDM
  1801  ESQPLIGTQS TAIPAPTDLK FTQVTPTSLS AQWTPPNVQL TGYRVRVTPK EKTGPMKEIN
  1861  LAPDSSSVVV SGLMVATKYE VSVYALKDTL TSRPAQGVVT TLENVSPPRR ARVTDATETT
  1921  ITISWRTKTE TITGFQVDAV PANGQTPIQR TIKPDVRSYT ITGLQPGTDY KIYLYTLNDN
  1981  ARSSPVVIDA STAIDAPSNL RFLATTPNSL LVSWQPPRAR ITGYIIKYEK PGSPPREVVP
  2041  RPRPGVTEAT ITGLEPGTEY TIYVIALKNN QKSEPLIGRK KTDELPQLVT LPHPNLHGPE
  2101  ILDVPSTVQK TPFVTHPGYD TGNGIQLPGT SGQQPSVGQQ MIFEEHGFRR TTPPTTATPI
  2161  RHRPRPYPPN VGEEIQIGHI PREDVDYHLY PHGPGLNPNA STGQEALSQT TISWAPFQDT
  2221  SEYIISCHPV GTDEEPLQFR VPGTSTSATL TGLTRGATYN VIVEALKDQQ RHKVREEVVT
  2281  VGNSVNEGLN QPTDDSCFDP YTVSHYAVGD EWERMSESGF KLLCQCLGFG SGHFRCDSSR
  2341  WCHDNGVNYK IGEKWDRQGE NGQMMSCTCL GNGKGEFKCD PHEATCYDDG KTYHVGEQWQ
  2401  KEYLGAICSC TCFGGQRGWR CDNCRRPGGE PSPEGTTGQS YNQYSQRYHQ RTNTNVNCPI
  2461  ECFMPLDVQA DREDSRE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FN1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

2,752 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FN1.

Disease | AllUniProt

Conditions FN1 is implicated in, by any mechanism.

• Glomerulopathy with fibronectin deposits 2 (GFND2) MIM:601894
• Spondylometaphyseal dysplasia, corner fracture type (SMDCF) MIM:184255

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 2,034 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spondylometaphyseal dysplasia - Sutcliffe type
• Glomerulopathy with fibronectin deposits 2
• Spondylometaphyseal dysplasia
• FN1-related disorder
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on FN1 was assayed in.

• rheumatoid arthritis B and T cell
• Lyme disease T cell
• Sjogren's syndrome B cell
• multiple sclerosis B cell
• systemic lupus erythematosus B cell
• type 1 diabetes mellitus B cell
• melanoma T cell
• tuberculosis B cell
• mixed connective tissue disease B cell
• colonic benign neoplasm T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against FN1 are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 5
• Arthritis, Rheumatoid 4

ReferencesPubMed · IEDB

Publications for FN1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.34

gnomAD pLI

0

gnomAD missense Z

1.65

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acute-phase response
• angiogenesis
• autophagy
• biological process involved in interaction with symbiont
• blood coagulation, fibrin clot formation
• calcium-independent cell-matrix adhesion
• cell adhesion
• cell-matrix adhesion
• cell-substrate junction assembly
• endodermal cell differentiation
• endothelial cell migration
• enteric nervous system development
• heart development
• integrin activation
• integrin-mediated signaling pathway
• negative regulation of autophagy
• negative regulation of monocyte activation
• negative regulation of transforming growth factor beta production
• nervous system development
• neural crest cell migration
• neural crest cell migration involved in autonomic nervous system development
• 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/protein kinase B signal transduction
• positive regulation of substrate-dependent cell migration, cell attachment to substrate
• regulation of cell shape
• regulation of ERK1 and ERK2 cascade
• regulation of protein phosphorylation
• response to muscle activity
• response to wounding
• substrate adhesion-dependent cell spreading

Molecular functions

• collagen binding
• extracellular matrix structural constituent
• heparin binding
• identical protein binding
• integrin binding
• peptidase activator activity
• protease binding
• proteoglycan binding
• receptor ligand activity
• signaling receptor binding

Cellular components

• apical plasma membrane
• basement membrane
• blood microparticle
• endoplasmic reticulum lumen
• endoplasmic reticulum-Golgi intermediate compartment
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• fibrinogen complex
• plasma membrane
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• Fibronectin, type I
• Fibronectin type II domain
• Fibronectin type III
• Immunoglobulin-like fold
• Kringle-like fold
• Fibronectin type III superfamily
• Fibronectin type II domain superfamily
• Extracellular Matrix Regulatory Proteins
• Fibronectin type I domain
• Fibronectin type II domain
• Fibronectin type III domain

KeywordsUniProt

• Acute phase
• Angiogenesis
• Cell adhesion
• Cell shape
• Disulfide bond
• Dwarfism
• Extracellular matrix
• Glycoprotein
• Heparin-binding
• Isopeptide bond
• Oxidation
• Phosphoprotein
• Pyrrolidone carboxylic acid
• Repeat
• Secreted
• Signal
• Sulfation

InteractionsUniProt · HPA

Protein binding partners of FN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AMBP
• COL13A1
• COMP
• FBLN1
• FBLN7
• FST3
• LGALS3BP
• MYOC
• SVEP1
• TNR
• THBS1
• FSTL3
• ITGA5
• ITGB1
• KPNA2
• LPA
• TGM2
• VHL