FN1 (fibronectin 1)

Gene

• Entrez ID: 2335
• Gene name: Fibronectin 1
• Gene symbol: FN1
• Synonyms: CIG, ED-B, FINC, FN, FNZ, GFND, GFND2, LETS, MSF, SMDCF
• Chromosome: 2
• Chromosome location: 2q35
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs113683179	C>G,T	Pathogenic	Splice donor variant
rs137854488	T>C	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs797044906	C>A	Pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs869025199	GAG>-	Pathogenic	Inframe deletion, coding sequence variant, genic downstream transcript variant
rs1064795155	G>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1181638652	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant, synonymous variant
rs1553636502	GTT>-	Uncertain-significance, likely-pathogenic	Inframe deletion, coding sequence variant, genic downstream transcript variant
rs1553658926	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1553658948	C>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1553659131	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1553667072	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1559604072	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1559609410	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1559616744	C>T	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003959	hsa-miR-200c-3p	Microarray	17875710
MIRT003959	hsa-miR-200c-3p	Immunoblot, Luciferase reporter assay, qRT-PCR, Western blot	21501518
MIRT003959	hsa-miR-200c-3p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	28113080
MIRT004009	hsa-miR-200b-3p	Microarray	17875710
MIRT004009	hsa-miR-200b-3p	Luciferase reporter assay, qRT-PCR, Western blot	23408168
MIRT006132	hsa-miR-1-3p	GFP reporter assay, qRT-PCR, Western blot	21924268
MIRT006132	hsa-miR-1-3p	Immunoblot, Immunofluorescence, Immunoprecipitaion, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22210864
MIRT006162	hsa-let-7g-5p	Luciferase reporter assay, Microarray, Western blot	21868760
MIRT029079	hsa-miR-26b-5p	Microarray	19088304
MIRT040254	hsa-miR-615-3p	CLASH	23622248
MIRT440632	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT734107	hsa-miR-140-3p	Luciferase reporter assay	27996039

Transcription factors

Transcription factor	Regulation	Reference
AR	Unknown	21055159
ATF2	Unknown	10471826
CEBPA	Unknown	1320003
EGR1	Activation	15608673;9933644
EGR1	Unknown	10783396
KLF8	Repression	20728449
NFKB1	Activation	10649441;10867646
NFKB1	Unknown	22223884
PARP1	Unknown	22223884
RELA	Activation	10649441;10867646
RELA	Unknown	22223884
SNAI1	Unknown	22223884
SOX17	Repression	24407731
TWIST1	Activation	20646316
TWIST2	Activation	20646316

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0001932	Process	Regulation of protein phosphorylation	IDA	11792823
GO:0002020	Function	Protease binding	IPI	22952693
GO:0002576	Process	Platelet degranulation	TAS
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005102	Function	Signaling receptor binding	IPI	17849409
GO:0005178	Function	Integrin binding	IBA	21873635
GO:0005178	Function	Integrin binding	IDA	19738201
GO:0005178	Function	Integrin binding	IMP	24658351
GO:0005178	Function	Integrin binding	IPI	11792823
GO:0005201	Function	Extracellular matrix structural constituent	HDA	28344315
GO:0005201	Function	Extracellular matrix structural constituent	ISS
GO:0005201	Function	Extracellular matrix structural constituent	RCA	20551380, 23979707, 25037231, 27559042, 28327460, 28675934
GO:0005515	Function	Protein binding	IPI	1400330, 1747115, 2531657, 3141278, 9269765, 9278415, 10627046, 10788510, 11377428, 11773026, 11956183, 12225811, 12421310, 12736686, 15165854, 16336961, 16457822, 18042364, 18160478, 18243143, 18323857, 18411296, 18713862, 19220903, 19542224, 19738201, 20080707, 20541508, 20875085
GO:0005518	Function	Collagen binding	NAS	3024962
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005577	Component	Fibrinogen complex	IDA	3997886
GO:0005604	Component	Basement membrane	IEA
GO:0005615	Component	Extracellular space	HDA	20551380
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	15292204
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005793	Component	Endoplasmic reticulum-Golgi intermediate compartment	IDA	15308636
GO:0006953	Process	Acute-phase response	IEA
GO:0007044	Process	Cell-substrate junction assembly	IBA	21873635
GO:0007155	Process	Cell adhesion	NAS	1423622
GO:0007160	Process	Cell-matrix adhesion	IBA	21873635
GO:0007161	Process	Calcium-independent cell-matrix adhesion	IEA
GO:0007229	Process	Integrin-mediated signaling pathway	IDA	19126672
GO:0007399	Process	Nervous system development	IBA	21873635
GO:0007507	Process	Heart development	IBA	21873635
GO:0008022	Function	Protein C-terminus binding	IPI	16677310
GO:0008201	Function	Heparin binding	NAS	10075919
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	25834989
GO:0008360	Process	Regulation of cell shape	IEA
GO:0009611	Process	Response to wounding	NAS	7989369
GO:0010628	Process	Positive regulation of gene expression	IDA	25834989
GO:0010952	Process	Positive regulation of peptidase activity	IEA
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IDA	19126672
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016504	Function	Peptidase activator activity	IEA
GO:0018149	Process	Peptide cross-linking	IDA	3997886
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019899	Function	Enzyme binding	IPI	12167537, 12421310, 17849409, 19429745
GO:0030198	Process	Extracellular matrix organization	TAS
GO:0031012	Component	Extracellular matrix	IDA	26571399
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0033622	Process	Integrin activation	IMP	24658351
GO:0034446	Process	Substrate adhesion-dependent cell spreading	IDA	16236823, 19126672
GO:0034446	Process	Substrate adhesion-dependent cell spreading	IMP	24658351
GO:0035987	Process	Endodermal cell differentiation	IDA	23154389
GO:0042802	Function	Identical protein binding	IPI	17914904, 18042364, 19826086, 19931242, 20541508
GO:0043394	Function	Proteoglycan binding	IBA	21873635
GO:0043394	Function	Proteoglycan binding	IDA	29030641
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045773	Process	Positive regulation of axon extension	IEA
GO:0048146	Process	Positive regulation of fibroblast proliferation	IDA	25834989
GO:0050900	Process	Leukocyte migration	TAS
GO:0051087	Function	Chaperone binding	IPI	17849409
GO:0051702	Process	Biological process involved in interaction with symbiont	IDA	12167537, 12421310, 19429745
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	23658023, 23979707, 25037231, 27559042, 28327460, 28344315, 28675934
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	20551380
GO:0062023	Component	Collagen-containing extracellular matrix	IBA	21873635
GO:0062023	Component	Collagen-containing extracellular matrix	IDA	1632457, 16157329
GO:0062023	Component	Collagen-containing extracellular matrix	ISS	22261194
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070062	Component	Extracellular exosome	IDA	21276792
GO:0070372	Process	Regulation of ERK1 and ERK2 cascade	IDA	11792823
GO:0070527	Process	Platelet aggregation	IBA	21873635
GO:0071635	Process	Negative regulation of transforming growth factor beta production	IDA	25834989
GO:0072378	Process	Blood coagulation, fibrin clot formation	IBA	21873635
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:0097718	Function	Disordered domain specific binding	IPI	15292204
GO:1901166	Process	Neural crest cell migration involved in autonomic nervous system development	IDA	26571399
GO:1904237	Process	Positive regulation of substrate-dependent cell migration, cell attachment to substrate	IDA	25834989

Other IDs

• MIM: 135600
• HGNC: 3778
• e!Ensembl: ENSG00000115414

Protein

• UniProt ID: P02751
• Protein name: Fibronectin (FN) (Cold-insoluble globulin) (CIG) [Cleaved into: Anastellin; Ugl-Y1; Ugl-Y2; Ugl-Y3]
• Protein function: 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). ; [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.
• PDB: 1E88, 1E8B, 1FBR, 1FNA, 1FNF, 1FNH, 1J8K, 1O9A, 1OWW, 1Q38, 1QGB, 1QO6, 1TTF, 1TTG, 2CG6, 2CG7, 2CK2, 2CKU, 2EC3, 2FN2, 2FNB, 2GEE, 2H41, 2H45, 2HA1, 2MNU, 2N1K, 2OCF, 2RKY, 2RKZ, 2RL0, 3CAL, 3EJH, 3GXE, 3M7P, 3MQL, 3R8Q, 3T1W, 3ZRZ, 4GH7, 4JE4, 4JEG, 4LXO, 4MMX, 4MMY, 4MMZ, 4PZ5, 5DC0, 5DC4, 5DC9, 5DFT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00039	fn1	52 → 87	Fibronectin type I domain	Domain
  PF00039	fn1	97 → 135	Fibronectin type I domain	Domain
  PF00039	fn1	141 → 179	Fibronectin type I domain	Domain
  PF00039	fn1	186 → 225	Fibronectin type I domain	Domain
  PF00039	fn1	231 → 270	Fibronectin type I domain	Domain
  PF00039	fn1	308 → 342	Fibronectin type I domain	Domain
  PF00040	fn2	360 → 401	Fibronectin type II domain	Domain
  PF00040	fn2	420 → 461	Fibronectin type II domain	Domain
  PF00039	fn1	470 → 508	Fibronectin type I domain	Domain
  PF00039	fn1	518 → 555	Fibronectin type I domain	Domain
  PF00039	fn1	561 → 599	Fibronectin type I domain	Domain
  PF00041	fn3	609 → 692	Fibronectin type III domain	Domain
  PF00041	fn3	723 → 801	Fibronectin type III domain	Domain
  PF00041	fn3	812 → 891	Fibronectin type III domain	Domain
  PF00041	fn3	908 → 988	Fibronectin type III domain	Domain
  PF00041	fn3	998 → 1078	Fibronectin type III domain	Domain
  PF00041	fn3	1093 → 1163	Fibronectin type III domain	Domain
  PF00041	fn3	1175 → 1258	Fibronectin type III domain	Domain
  PF00041	fn3	1268 → 1349	Fibronectin type III domain	Domain
  PF00041	fn3	1359 → 1439	Fibronectin type III domain	Domain
  PF00041	fn3	1449 → 1530	Fibronectin type III domain	Domain
  PF00041	fn3	1543 → 1623	Fibronectin type III domain	Domain
  PF00041	fn3	1633 → 1713	Fibronectin type III domain	Domain
  PF00041	fn3	1723 → 1803	Fibronectin type III domain	Domain
  PF00041	fn3	1815 → 1894	Fibronectin type III domain	Domain
  PF00041	fn3	1904 → 1984	Fibronectin type III domain	Domain
  PF00041	fn3	2110 → 2182	Fibronectin type III domain	Domain
  PF00039	fn1	2206 → 2245	Fibronectin type I domain	Domain
  PF00039	fn1	2251 → 2288	Fibronectin type I domain	Domain
  PF00039	fn1	2295 → 2330	Fibronectin type I domain	Domain

• Sequence:

  MLRGPGPGLLLLAVQCLGTAVPSTGASKSKRQAQQMVQPQSPVAVSQSKPGCYDNGKHYQ
  INQQWERTYLGNALVCTCYGGSRGFNCESKPEAEETCFDKYTGNTYRVGDTYERPKDSMI
  WDCTCIGAGRGRISCTIANRCHEGGQSYKIGDTWRRPHETGGYMLECVCLGNGKGEWTCK
  PIAEKCFDHAAGTSYVVGETWEKPYQGWMMVDCTCLGEGSGRITCTSRNRCNDQDTRTSY
  RIGDTWSKKDNRGNLLQCICTGNGRGEWKCERHTSVQTTSSGSGPFTDVRAAVYQPQPHP
  QPPPYGHCVTDSGVVYSVGMQWLKTQGNKQMLCTCLGNGVSCQETAVTQTYGGNSNGEPC
  VLPFTYNGRTFYSCTTEGRQDGHLWCSTTSNYEQDQKYSFCTDHTVLVQTRGGNSNGALC
  HFPFLYNNHNYTDCTSEGRRDNMKWCGTTQNYDADQKFGFCPMAAHEEICTTNEGVMYRI
  GDQWDKQHDMGHMMRCTCVGNGRGEWTCIAYSQLRDQCIVDDITYNVNDTFHKRHEEGHM
  LNCTCFGQGRGRWKCDPVDQCQDSETGTFYQIGDSWEKYVHGVRYQCYCYGRGIGEWHCQ
  PLQTYPSSSGPVEVFITETPSQPNSHPIQWNAPQPSHISKYILRWRPKNSVGRWKEATIP
  GHLNSYTIKGLKPGVVYEGQLISIQQYGHQEVTRFDFTTTSTSTPVTSNTVTGETTPFSP
  LVATSESVTEITASSFVVSWVSASDTVSGFRVEYELSEEGDEPQYLDLPSTATSVNIPDL
  LPGRKYIVNVYQISEDGEQSLILSTSQTTAPDAPPDTTVDQVDDTSIVVRWSRPQAPITG
  YRIVYSPSVEGSSTELNLPETANSVTLSDLQPGVQYNITIYAVEENQESTPVVIQQETTG
  TPRSDTVPSPRDLQFVEVTDVKVTIMWTPPESAVTGYRVDVIPVNLPGEHGQRLPISRNT
  FAEVTGLSPGVTYYFKVFAVSHGRESKPLTAQQTTKLDAPTNLQFVNETDSTVLVRWTPP
  RAQITGYRLTVGLTRRGQPRQYNVGPSVSKYPLRNLQPASEYTVSLVAIKGNQESPKATG
  VFTTLQPGSSIPPYNTEVTETTIVITWTPAPRIGFKLGVRPSQGGEAPREVTSDSGSIVV
  SGLTPGVEYVYTIQVLRDGQERDAPIVNKVVTPLSPPTNLHLEANPDTGVLTVSWERSTT
  PDITGYRITTTPTNGQQGNSLEEVVHADQSSCTFDNLSPGLEYNVSVYTVKDDKESVPIS
  DTIIPEVPQLTDLSFVDITDSSIGLRWTPLNSSTIIGYRITVVAAGEGIPIFEDFVDSSV
  GYYTVTGLEPGIDYDISVITLINGGESAPTTLTQQTAVPPPTDLRFTNIGPDTMRVTWAP
  PPSIDLTNFLVRYSPVKNEEDVAELSISPSDNAVVLTNLLPGTEYVVSVSSVYEQHESTP
  LRGRQKTGLDSPTGIDFSDITANSFTVHWIAPRATITGYRIRHHPEHFSGRPREDRVPHS
  RNSITLTNLTPGTEYVVSIVALNGREESPLLIGQQSTVSDVPRDLEVVAATPTSLLISWD
  APAVTVRYYRITYGETGGNSPVQEFTVPGSKSTATISGLKPGVDYTITVYAVTGRGDSPA
  SSKPISINYRTEIDKPSQMQVTDVQDNSISVKWLPSSSPVTGYRVTTTPKNGPGPTKTKT
  AGPDQTEMTIEGLQPTVEYVVSVYAQNPSGESQPLVQTAVTNIDRPKGLAFTDVDVDSIK
  IAWESPQGQVSRYRVTYSSPEDGIHELFPAPDGEEDTAELQGLRPGSEYTVSVVALHDDM
  ESQPLIGTQSTAIPAPTDLKFTQVTPTSLSAQWTPPNVQLTGYRVRVTPKEKTGPMKEIN
  LAPDSSSVVVSGLMVATKYEVSVYALKDTLTSRPAQGVVTTLENVSPPRRARVTDATETT
  ITISWRTKTETITGFQVDAVPANGQTPIQRTIKPDVRSYTITGLQPGTDYKIYLYTLNDN
  ARSSPVVIDASTAIDAPSNLRFLATTPNSLLVSWQPPRARITGYIIKYEKPGSPPREVVP
  RPRPGVTEATITGLEPGTEYTIYVIALKNNQKSEPLIGRKKTDELPQLVTLPHPNLHGPE
  ILDVPSTVQKTPFVTHPGYDTGNGIQLPGTSGQQPSVGQQMIFEEHGFRRTTPPTTATPI
  RHRPRPYPPNVGEEIQIGHIPREDVDYHLYPHGPGLNPNASTGQEALSQTTISWAPFQDT
  SEYIISCHPVGTDEEPLQFRVPGTSTSATLTGLTRGATYNVIVEALKDQQRHKVREEVVT
  VGNSVNEGLNQPTDDSCFDPYTVSHYAVGDEWERMSESGFKLLCQCLGFGSGHFRCDSSR
  WCHDNGVNYKIGEKWDRQGENGQMMSCTCLGNGKGEFKCDPHEATCYDDGKTYHVGEQWQ
  KEYLGAICSCTCFGGQRGWRCDNCRRPGGEPSPEGTTGQSYNQYSQRYHQRTNTNVNCPI
  ECFMPLDVQADREDSRE

• Sequence length: 2477