RBCC Red Blood Cell Collection

FN1 (FN) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Fibronectin; FN (Cold-insoluble globulin; CIG; Anastellin; Ugl-Y1; Ugl-Y2; Ugl-Y3; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00022418
IPI00022418 Splice Isoform 1 Of Fibronectin precursor Splice Isoform 1 Of Fibronectin precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 2 n/a n/a integral membrane protein several different isoforms found at its expected molecular weight found at molecular weight

UniProt P02751
ID FINC_HUMAN Reviewed; 2386 AA.
AC P02751; B7ZLF0; E9PE77; E9PG29; O95609; O95610; Q14312; Q14325;
read moreAC Q14326; Q17RV7; Q564H7; Q585T2; Q59EH1; Q60FE4; Q68DP8; Q68DP9;
AC Q68DT4; Q6LDP6; Q6MZS0; Q6MZU5; Q6N025; Q6N0A6; Q86T27; Q8IVI8;
AC Q96KP7; Q96KP8; Q96KP9; Q9H1B8; Q9HAP3; Q9UMK2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 4.
DT 22-JAN-2014, entry version 192.
DE RecName: Full=Fibronectin;
DE Short=FN;
DE AltName: Full=Cold-insoluble globulin;
DE Short=CIG;
DE Contains:
DE RecName: Full=Anastellin;
DE Contains:
DE RecName: Full=Ugl-Y1;
DE Contains:
DE RecName: Full=Ugl-Y2;
DE Contains:
DE RecName: Full=Ugl-Y3;
DE Flags: Precursor;
GN Name=FN1; Synonyms=FN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS PRO-817 AND
RP ILE-2170.
RX PubMed=11737888; DOI=10.1186/bcr325;
RA Schor S.L., Schor A.M.;
RT "Phenotypic and genetic alterations in mammary stroma: implications
RT for tumour progression.";
RL Breast Cancer Res. 3:373-379(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 16).
RX PubMed=16322219; DOI=10.1158/0008-5472.CAN-05-2038;
RA Kay R.A., Ellis I.R., Jones S.J., Perrier S., Florence M.M.,
RA Schor A.M., Schor S.L.;
RT "The expression of migration stimulating factor, a potent oncofetal
RT cytokine, is uniquely controlled by 3'-untranslated region-dependent
RT nuclear sequestration of its precursor messenger RNA.";
RL Cancer Res. 65:10742-10749(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 14), AND VARIANTS PRO-817 AND
RP ILE-2170.
RC TISSUE=Retinal pigment epithelium;
RX PubMed=16106752; DOI=10.1093/dnares/12.1.53;
RA Kato S., Ohtoko K., Ohtake H., Kimura T.;
RT "Vector-capping: a simple method for preparing a high-quality full-
RT length cDNA library.";
RL DNA Res. 12:53-62(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 14), AND VARIANTS
RP LEU-15; PRO-817 AND ILE-2170.
RC TISSUE=Aortic endothelium;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 7; 8; 9; 10; 13;
RP 14 AND 15), AND VARIANTS LEU-15; PRO-817 AND ILE-2170.
RC TISSUE=Amygdala, Cervix, Endometrial tumor, and Uterine endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10), AND VARIANTS
RP LEU-15; PRO-817 AND ILE-2170.
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-38.
RX PubMed=3770189; DOI=10.1016/0014-5793(86)80029-1;
RA Gutman A., Yamada K.M., Kornblihtt A.R.;
RT "Human fibronectin is synthesized as a pre-propolypeptide.";
RL FEBS Lett. 207:145-148(1986).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, AND VARIANT LEU-15.
RX PubMed=3031656; DOI=10.1073/pnas.84.7.1876;
RA Dean D.C., Bowlus C.L., Bourgeois S.;
RT "Cloning and analysis of the promotor region of the human fibronectin
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:1876-1880(1987).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-2386 (ISOFORM 3), AND VARIANTS
RP PRO-817 AND ILE-2170.
RX PubMed=2992939;
RA Kornblihtt A.R., Umezawa K., Vibe-Pedersen K., Baralle F.E.;
RT "Primary structure of human fibronectin: differential splicing may
RT generate at least 10 polypeptides from a single gene.";
RL EMBO J. 4:1755-1759(1985).
RN [12]
RP PROTEIN SEQUENCE OF 32-290.
RX PubMed=6630202;
RA Garcia-Pardo A., Pearlstein E., Frangione B.;
RT "Primary structure of human plasma fibronectin. The 29,000-dalton NH2-
RT terminal domain.";
RL J. Biol. Chem. 258:12670-12674(1983).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 103-481 (ISOFORMS
RP 1/3/4/5/6/7/8/9/10/11/12/13/14/15), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1116-1422 (ISOFORMS 1/3/4/5/6/8/9/10/14), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 1238-2160 (ISOFORMS 9 AND 12), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1449-1825 (ISOFORMS 8/9/10/13/14), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 1919-2161 (ISOFORMS 3/7/14), AND NUCLEOTIDE SEQUENCE [MRNA] OF
RP 2228-2386 (ISOFORMS 1/3/6/7/8/9/10/11/12/13/14/15).
RC TISSUE=Peripheral blood T-cell, and Umbilical vein endothelial cell;
RA Godfrey H.P., Ebrahim A.A.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PROTEIN SEQUENCE OF 309-608, AND COLLAGEN-BINDING.
RX PubMed=3024962;
RA Owens R.J., Baralle F.E.;
RT "Mapping the collagen-binding site of human fibronectin by expression
RT in Escherichia coli.";
RL EMBO J. 5:2825-2830(1986).
RN [15]
RP PROTEIN SEQUENCE OF 616-705.
RX PubMed=3900070;
RA Calaycay J., Pande H., Lee T., Borsi L., Siri A., Shively J.E.,
RA Zardi L.;
RT "Primary structure of a DNA- and heparin-binding domain (Domain III)
RT in human plasma fibronectin.";
RL J. Biol. Chem. 260:12136-12141(1985).
RN [16]
RP PROTEIN SEQUENCE OF 723-911, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP GLYCOSYLATION AT ASN-877, AND VARIANT PRO-817.
RC TISSUE=Urine;
RX PubMed=17614963; DOI=10.1111/j.1742-4658.2007.05926.x;
RA Iida R., Yasuda T., Kishi K.;
RT "Identification of novel fibronectin fragments detected specifically
RT in juvenile urine.";
RL FEBS J. 274:3939-3947(2007).
RN [17]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 973-2386 (ISOFORM 3), AND VARIANT
RP ILE-2170.
RX PubMed=6462919; DOI=10.1093/nar/12.14.5853;
RA Kornblihtt A.R., Vibe-Pedersen K., Baralle F.E.;
RT "Human fibronectin: cell specific alternative mRNA splicing generates
RT polypeptide chains differing in the number of internal repeats.";
RL Nucleic Acids Res. 12:5853-5868(1984).
RN [18]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1232-1782 (ISOFORMS 7/15).
RX PubMed=3375063; DOI=10.1093/nar/16.8.3545;
RA Paolella G., Henchcliffe C., Sebastio G., Baralle F.E.;
RT "Sequence analysis and in vivo expression show that alternative
RT splicing of ED-B and ED-A regions of the human fibronectin gene are
RT independent events.";
RL Nucleic Acids Res. 16:3545-3557(1988).
RN [19]
RP PROTEIN SEQUENCE OF 1234-1286 (ISOFORM 7).
RX PubMed=2822387;
RA Zardi L., Carnemolla B., Siri A., Petersen T.E., Paolella G.,
RA Sebastio G., Baralle F.E.;
RT "Transformed human cells produce a new fibronectin isoform by
RT preferential alternative splicing of a previously unobserved exon.";
RL EMBO J. 6:2337-2342(1987).
RN [20]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1257-1365 (ISOFORM 11).
RX PubMed=3478690; DOI=10.1073/pnas.84.20.7179;
RA Gutman A., Kornblihtt A.R.;
RT "Identification of a third region of cell-specific alternative
RT splicing in human fibronectin mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7179-7182(1987).
RN [21]
RP PROTEIN SEQUENCE OF 1441-1548.
RX PubMed=7050098;
RA Pierschbacher M.D., Ruoslahti E., Sundelin J., Lind P., Peterson P.A.;
RT "The cell attachment domain of fibronectin. Determination of the
RT primary structure.";
RL J. Biol. Chem. 257:9593-9597(1982).
RN [22]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1448-1540.
RX PubMed=6688418;
RA Oldberg A., Linney E., Ruoslahti E.;
RT "Molecular cloning and nucleotide sequence of a cDNA clone coding for
RT the cell attachment domain in human fibronectin.";
RL J. Biol. Chem. 258:10193-10196(1983).
RN [23]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1448-1540.
RX PubMed=3003095;
RA Oldberg A., Ruoslahti E.;
RT "Evolution of the fibronectin gene. Exon structure of cell attachment
RT domain.";
RL J. Biol. Chem. 261:2113-2116(1986).
RN [24]
RP PROTEIN SEQUENCE OF 1589-2058.
RX PubMed=3593230;
RA Garcia-Pardo A., Rostagno A., Frangione B.;
RT "Primary structure of human plasma fibronectin. Characterization of a
RT 38 kDa domain containing the C-terminal heparin-binding site (Hep III
RT site) and a region of molecular heterogeneity.";
RL Biochem. J. 241:923-928(1987).
RN [25]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1594-2386 (ISOFORMS 1/11/15), AND
RP VARIANT ILE-2170.
RX PubMed=2992573; DOI=10.1021/bi00332a016;
RA Bernard M.P., Kolbe M., Weil D., Chu M.-L.;
RT "Human cellular fibronectin: comparison of the carboxyl-terminal
RT portion with rat identifies primary structural domains separated by
RT hypervariable regions.";
RL Biochemistry 24:2698-2704(1985).
RN [26]
RP PROTEIN SEQUENCE OF 1614-1623; 1730-1748; 1756-1759; 1803-1811;
RP 1860-1923; 1930-1945; 1949-1972; 1982-1989; 1991-2003; 2020-2038;
RP 2060-2131; 2150-2180; 2185-2205 AND 2231-2242, GLYCOSYLATION AT
RP THR-2064 AND THR-2065, LACK OF GLYCOSYLATION AT ASN-2108, MASS
RP SPECTROMETRY, AND VARIANT ILE-2170.
RX PubMed=2012601;
RA Tressel T., McCarthy J.B., Calaycay J., Lee T.D., Legesse K.,
RA Shively J.E., Pande H.;
RT "Human plasma fibronectin. Demonstration of structural differences
RT between the A- and B-chains in the III CS region.";
RL Biochem. J. 274:731-738(1991).
RN [27]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1624-1727 (ISOFORMS 8/9/10/12/13/14).
RX PubMed=6200322;
RA Kornblihtt A.R., Vibe-Pedersen K., Baralle F.E.;
RT "Human fibronectin: molecular cloning evidence for two mRNA species
RT differing by an internal segment coding for a structural domain.";
RL EMBO J. 3:221-226(1984).
RN [28]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1712-1739 (ISOFORMS 1/3/4/5/6/7/11/15).
RX PubMed=3021206; DOI=10.1021/bi00365a032;
RA Sekiguchi K., Klos A.M., Kurachi K., Yoshitake S., Hakomori S.;
RT "Human liver fibronectin complementary DNAs: identification of two
RT different messenger RNAs possibly encoding the alpha and beta subunits
RT of plasma fibronectin.";
RL Biochemistry 25:4936-4941(1986).
RN [29]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1788-2386 (ISOFORMS 4; 5 AND 6), AND
RP VARIANT ILE-2170.
RC TISSUE=Cartilage;
RX PubMed=12127832; DOI=10.1053/joca.2002.0792;
RA Parker A.E., Boutell J., Carr A., Maciewicz R.A.;
RT "Novel cartilage-specific splice variants of fibronectin.";
RL Osteoarthritis Cartilage 10:528-534(2002).
RN [30]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1948-2067 (ISOFORMS 1/8/10/11/15).
RX PubMed=2989004; DOI=10.1016/0014-5793(85)81333-8;
RA Umezawa K., Kornblihtt A.R., Baralle F.E.;
RT "Isolation and characterization of cDNA clones for human liver
RT fibronectin.";
RL FEBS Lett. 186:31-34(1985).
RN [31]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1992-2147.
RX PubMed=3770201; DOI=10.1016/0014-5793(86)81506-X;
RA Vibe-Pedersen K., Magnusson S., Baralle F.E.;
RT "Donor and acceptor splice signals within an exon of the human
RT fibronectin gene: a new type of differential splicing.";
RL FEBS Lett. 207:287-291(1986).
RN [32]
RP PROTEIN SEQUENCE OF 2071-2356 (ISOFORM 3), AND VARIANT ILE-2170.
RX PubMed=4019516;
RA Garcia-Pardo A., Pearlstein E., Frangione B.;
RT "Primary structure of human plasma fibronectin. Characterization of a
RT 31,000-dalton fragment from the COOH-terminal region containing a free
RT sulfhydryl group and a fibrin-binding site.";
RL J. Biol. Chem. 260:10320-10325(1985).
RN [33]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2291-2386.
RX PubMed=6304699; DOI=10.1073/pnas.80.11.3218;
RA Kornblihtt A.R., Vibe-Pedersen K., Baralle F.E.;
RT "Isolation and characterization of cDNA clones for human and bovine
RT fibronectins.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3218-3222(1983).
RN [34]
RP SULFATION.
RX PubMed=2414772; DOI=10.1073/pnas.82.21.7160;
RA Liu M.C., Yu S., Sy J., Redman C.M., Lipmann F.;
RT "Tyrosine sulfation of proteins from the human hepatoma cell line
RT HepG2.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7160-7164(1985).
RN [35]
RP IDENTIFICATION OF UGL-Y1, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP GLYCOSYLATION.
RX PubMed=3584091;
RA Iida R., Yasuda T., Kishi K.;
RT "Purification of a young age-related glycoprotein (Ugl-Y) from normal
RT human urine.";
RL J. Biochem. 101:357-363(1987).
RN [36]
RP INTERACTION WITH FBLN1.
RX PubMed=1400330;
RA Balbona K., Tran H., Godyna S., Ingham K.C., Strickland D.K.,
RA Argraves W.S.;
RT "Fibulin binds to itself and to the carboxyl-terminal heparin-binding
RT region of fibronectin.";
RL J. Biol. Chem. 267:20120-20125(1992).
RN [37]
RP CHARACTERIZATION OF FIBRIN-BINDING SITE 1.
RX PubMed=7989369;
RA Rostagno A., Williams M.J., Baron M., Campbell I.D., Gold L.I.;
RT "Further characterization of the NH2-terminal fibrin-binding site on
RT fibronectin.";
RL J. Biol. Chem. 269:31938-31945(1994).
RN [38]
RP SUBUNIT, AND FUNCTION OF ANASTELLIN.
RX PubMed=8114919; DOI=10.1038/367193a0;
RA Morla A., Zhang Z., Ruoslahti E.;
RT "Superfibronectin is a functionally distinct form of fibronectin.";
RL Nature 367:193-196(1994).
RN [39]
RP INTERACTION WITH LGALS3BP.
RX PubMed=9501082; DOI=10.1093/emboj/17.6.1606;
RA Sasaki T., Brakebusch C., Engel J., Timpl R.;
RT "Mac-2 binding protein is a cell-adhesive protein of the extracellular
RT matrix which self-assembles into ring-like structures and binds beta1
RT integrins, collagens and fibronectin.";
RL EMBO J. 17:1606-1613(1998).
RN [40]
RP FUNCTION OF ANASTELLIN.
RX PubMed=11209058; DOI=10.1073/pnas.98.2.620;
RA Yi M., Ruoslahti E.;
RT "A fibronectin fragment inhibits tumor growth, angiogenesis, and
RT metastasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:620-624(2001).
RN [41]
RP INTERACTION WITH COL13A1.
RX PubMed=11956183; DOI=10.1074/jbc.M107583200;
RA Tu H., Sasaki T., Snellman A., Gohring W., Pirila P., Timpl R.,
RA Pihlajaniemi T.;
RT "The type XIII collagen ectodomain is a 150-nm rod and capable of
RT binding to fibronectin, nidogen-2, perlecan, and heparin.";
RL J. Biol. Chem. 277:23092-23099(2002).
RN [42]
RP INTERACTION WITH COMP.
RX PubMed=12225811; DOI=10.1016/S0945-053X(02)00015-X;
RA Di Cesare P.E., Chen F.S., Moergelin M., Carlson C.S., Leslie M.P.,
RA Perris R., Fang C.;
RT "Matrix-matrix interaction of cartilage oligomeric matrix protein and
RT fibronectin.";
RL Matrix Biol. 21:461-470(2002).
RN [43]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-528, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [44]
RP FUNCTION OF ANASTELLIN.
RX PubMed=15665290;
RA Ambesi A., Klein R.M., Pumiglia K.M., McKeown-Longo P.J.;
RT "Anastellin, a fragment of the first type III repeat of fibronectin,
RT inhibits extracellular signal-regulated kinase and causes G(1) arrest
RT in human microvessel endothelial cells.";
RL Cancer Res. 65:148-156(2005).
RN [45]
RP GLYCOSYLATION AT THR-279; ASN-430; ASN-528; ASN-542; ASN-877;
RP ASN-1007; ASN-1244 AND ASN-2108.
RX PubMed=16037490; DOI=10.1093/glycob/cwj019;
RA Tajiri M., Yoshida S., Wada Y.;
RT "Differential analysis of site-specific glycans on plasma and cellular
RT fibronectins: application of a hydrophilic affinity method for
RT glycopeptide enrichment.";
RL Glycobiology 15:1332-1340(2005).
RN [46]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-430; ASN-528; ASN-542;
RP ASN-1007 AND ASN-1244, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2384, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [48]
RP INTERACTION WITH FST3.
RX PubMed=16336961; DOI=10.1016/j.yexcr.2005.11.006;
RA Maguer-Satta V., Forissier S., Bartholin L., Martel S., Jeanpierre S.,
RA Bachelard E., Rimokh R.;
RT "A novel role for fibronectin type I domain in the regulation of human
RT hematopoietic cell adhesiveness through binding to follistatin domains
RT of FLRG and follistatin.";
RL Exp. Cell Res. 312:434-442(2006).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2384, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [50]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-528 AND ASN-1007, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [51]
RP GLYCOSYLATION AT ASN-528; ASN-542 AND ASN-1007.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [52]
RP FUNCTION OF ANASTELLIN, AND MUTAGENESIS OF LEU-663 AND TYR-666.
RX PubMed=19379667; DOI=10.1016/j.matbio.2009.01.003;
RA You R., Klein R.M., Zheng M., McKeown-Longo P.J.;
RT "Regulation of p38 MAP kinase by anastellin is independent of
RT anastellin's effect on matrix fibronectin.";
RL Matrix Biol. 28:101-109(2009).
RN [53]
RP STRUCTURE BY NMR OF 1447-1540.
RX PubMed=1311202; DOI=10.1021/bi00122a025;
RA Baron M., Main A.L., Driscoll P.C., Mardon H.J., Boyd J.,
RA Campbell I.D.;
RT "1H NMR assignment and secondary structure of the cell adhesion type
RT III module of fibronectin.";
RL Biochemistry 31:2068-2073(1992).
RN [54]
RP STRUCTURE BY NMR OF 1447-1540.
RX PubMed=1423622; DOI=10.1016/0092-8674(92)90600-H;
RA Main A.L., Harvey T.S., Baron M., Boyd J., Campbell I.D.;
RT "The three-dimensional structure of the tenth type III module of
RT fibronectin: an insight into RGD-mediated interactions.";
RL Cell 71:671-678(1992).
RN [55]
RP STRUCTURE BY NMR OF 183-275, AND DISULFIDE BONDS.
RX PubMed=8308892; DOI=10.1006/jmbi.1994.1083;
RA Williams M.J., Phan I., Harvey T.S., Rostagno A., Gold L.I.,
RA Campbell I.D.;
RT "Solution structure of a pair of fibronectin type 1 modules with
RT fibrin binding activity.";
RL J. Mol. Biol. 235:1302-1311(1994).
RN [56]
RP STRUCTURE BY NMR OF 32-92.
RX PubMed=7583666; DOI=10.1038/nsb1195-946;
RA Potts J.R., Phan I., Williams M.J., Campbell I.D.;
RT "High-resolution structural studies of the factor XIIIa crosslinking
RT site and the first type 1 module of fibronectin.";
RL Nat. Struct. Biol. 2:946-950(1995).
RN [57]
RP STRUCTURE BY NMR OF 406-464.
RX PubMed=9514732; DOI=10.1006/jmbi.1997.1528;
RA Sticht H., Pickford A.R., Potts J.R., Campbell I.D.;
RT "Solution structure of the glycosylated second type 2 module of
RT fibronectin.";
RL J. Mol. Biol. 276:177-187(1998).
RN [58]
RP STRUCTURE BY NMR OF EXTRA ED-B DOMAIN FROM ISOFORM 7.
RX PubMed=10196121; DOI=10.1016/S0969-2126(99)80051-3;
RA Fattorusso R., Pellecchia M., Viti F., Neri P., Neri D., Wuethrich K.;
RT "NMR structure of the human oncofoetal fibronectin ED-B domain, a
RT specific marker for angiogenesis.";
RL Structure 7:381-390(1999).
RN [59]
RP STRUCTURE BY NMR OF 305-405.
RX PubMed=10647176; DOI=10.1016/S0969-2126(00)88336-7;
RA Bocquier A.A., Potts J.R., Pickford A.R., Campbell I.D.;
RT "Solution structure of a pair of modules from the gelatin-binding
RT domain of fibronectin.";
RL Structure 7:1451-1460(1999).
RN [60]
RP STRUCTURE BY NMR OF 305-464, AND GLYCOSYLATION AT ASN-430.
RX PubMed=11285216; DOI=10.1093/emboj/20.7.1519;
RA Pickford A.R., Smith S.P., Staunton D., Boyd J., Campbell I.D.;
RT "The hairpin structure of the (6)F1(1)F2(2)F2 fragment from human
RT fibronectin enhances gelatin binding.";
RL EMBO J. 20:1519-1529(2001).
RN [61]
RP STRUCTURE BY NMR OF 1631-1724.
RX PubMed=11775745; DOI=10.1023/A:1012947209393;
RA Niimi T., Osawa M., Yamaji N., Yasunaga K., Sakashita H., Mase T.,
RA Tanaka A., Fujita S.;
RT "NMR structure of human fibronectin EDA.";
RL J. Biomol. NMR 21:281-284(2001).
RN [62]
RP STRUCTURE BY NMR OF 631-705, AND MUTAGENESIS OF TYR-641; ILE-642;
RP LEU-663; TYR-666; LEU-681; ILE-682; SER-683; ILE-684; GLU-691;
RP VAL-692; ARG-694; PHE-695; ASP-696 AND PHE-697.
RX PubMed=12946358; DOI=10.1016/S0022-2836(03)00890-8;
RA Briknarova K., Aakerman M.E., Hoyt D.W., Ruoslahti E., Ely K.R.;
RT "Anastellin, an FN3 fragment with fibronectin polymerization activity,
RT resembles amyloid fibril precursors.";
RL J. Mol. Biol. 332:205-215(2003).
RN [63]
RP STRUCTURE BY NMR OF 48-140 IN COMPLEX WITH A BACTERIAL
RP FIBRONECTIN-BINDING PROTEIN.
RX PubMed=12736686; DOI=10.1038/nature01589;
RA Schwarz-Linek U., Werner J.M., Pickford A.R., Gurusiddappa S.,
RA Kim J.H., Pilka E.S., Briggs J.A., Gough T.S., Hoeoek M.,
RA Campbell I.D., Potts J.R.;
RT "Pathogenic bacteria attach to human fibronectin through a tandem
RT beta-zipper.";
RL Nature 423:177-181(2003).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1447-1535.
RX PubMed=8120888; DOI=10.1016/0022-2836(94)90013-2;
RA Dickinson C.D., Veerapandian B., Dai X.-P., Hamlin R.C., Xuong N.-H.,
RA Ruoslahti E., Ely K.R.;
RT "Crystal structure of the tenth type III cell adhesion module of human
RT fibronectin.";
RL J. Mol. Biol. 236:1079-1092(1994).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1173-1540.
RX PubMed=8548820; DOI=10.1016/S0092-8674(00)81002-8;
RA Leahy D.J., Aukhil I., Erickson H.P.;
RT "2.0 A crystal structure of a four-domain segment of human fibronectin
RT encompassing the RGD loop and synergy region.";
RL Cell 84:155-164(1996).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1721-1991.
RX PubMed=10075919; DOI=10.1093/emboj/18.6.1468;
RA Sharma A., Askari J.A., Humphries M.J., Jones E.Y., Stuart D.I.;
RT "Crystal structure of a heparin- and integrin-binding segment of human
RT fibronectin.";
RL EMBO J. 18:1468-1479(1999).
RN [67]
RP STRUCTURE BY NMR OF 608-701.
RX PubMed=14657397; DOI=10.1073/pnas.2334390100;
RA Gao M., Craig D., Lequin O., Campbell I.D., Vogel V., Schulten K.;
RT "Structure and functional significance of mechanically unfolded
RT fibronectin type III1 intermediates.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14784-14789(2003).
RN [68]
RP STRUCTURE BY NMR OF 609-809.
RX PubMed=17464288; DOI=10.1038/sj.emboj.7601694;
RA Vakonakis I., Staunton D., Rooney L.M., Campbell I.D.;
RT "Interdomain association in fibronectin: insight into cryptic sites
RT and fibrillogenesis.";
RL EMBO J. 26:2575-2583(2007).
RN [69]
RP STRUCTURE BY NMR OF 93-182, X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF
RP 93-182, AND DISULFIDE BONDS.
RX PubMed=17368672; DOI=10.1016/j.jmb.2007.02.061;
RA Rudino-Pinera E., Ravelli R.B., Sheldrick G.M., Nanao M.H.,
RA Korostelev V.V., Werner J.M., Schwarz-Linek U., Potts J.R.,
RA Garman E.F.;
RT "The solution and crystal structures of a module pair from the
RT Staphylococcus aureus-binding site of human fibronectin -- a tale with
RT a twist.";
RL J. Mol. Biol. 368:833-844(2007).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 93-275 IN COMPLEX WITH
RP STAPHYLOCOCCUS AUREUS FNBA.
RX PubMed=18713862; DOI=10.1073/pnas.0803556105;
RA Bingham R.J., Rudino-Pinera E., Meenan N.A.G., Schwarz-Linek U.,
RA Turkenburg J.P., Hoeoek M., Garman E.F., Potts J.R.;
RT "Crystal structures of fibronectin-binding sites from Staphylococcus
RT aureus FnBPA in complex with fibronectin domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12254-12258(2008).
RN [71]
RP STRUCTURE BY NMR OF 2239-2299.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the 11th FN1 domain from human fibronectin 1.";
RL Submitted (MAR-2008) to the PDB data bank.
RN [72]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 516-608 IN COMPLEX WITH TYPE
RP I COLLAGEN.
RX PubMed=19251642; DOI=10.1073/pnas.0812516106;
RA Erat M.C., Slatter D.A., Lowe E.D., Millard C.J., Farndale R.W.,
RA Campbell I.D., Vakonakis I.;
RT "Identification and structural analysis of type I collagen sites in
RT complex with fibronectin fragments.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4195-4200(2009).
RN [73]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-940; PRO-1120 AND ASN-2380.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [74]
RP VARIANTS GFND2 CYS-973; ARG-1834 AND ARG-1883, VARIANTS LEU-15 AND
RP VAL-1960, AND CHARACTERIZATION OF VARIANTS GFND2 ARG-1834 AND
RP ARG-1883.
RX PubMed=18268355; DOI=10.1073/pnas.0707730105;
RA Castelletti F., Donadelli R., Banterla F., Hildebrandt F.,
RA Zipfel P.F., Bresin E., Otto E., Skerka C., Renieri A., Todeschini M.,
RA Caprioli J., Caruso R.M., Artuso R., Remuzzi G., Noris M.;
RT "Mutations in FN1 cause glomerulopathy with fibronectin deposits.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:2538-2543(2008).
RN [75]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-2170, AND MASS SPECTROMETRY.
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Fibronectins bind cell surfaces and various compounds
CC including collagen, fibrin, heparin, DNA, and actin. Fibronectins
CC are involved in cell adhesion, cell motility, opsonization, wound
CC healing, and maintenance of cell shape. Involved in osteoblast
CC compaction through the fibronectin fibrillogenesis cell-mediated
CC matrix assembly process, essential for osteoblast mineralization.
CC Participates in the regulation of type I collagen deposition by
CC osteoblasts.
CC -!- FUNCTION: Anastellin binds fibronectin and induces fibril
CC formation. This fibronectin polymer, named superfibronectin,
CC exhibits enhanced adhesive properties. Both anastellin and
CC superfibronectin inhibit tumor growth, angiogenesis and
CC metastasis. Anastellin activates p38 MAPK and inhibits
CC lysophospholipid signaling.
CC -!- SUBUNIT: Mostly heterodimers or multimers of alternatively spliced
CC variants, connected by 2 disulfide bonds near the carboxyl ends;
CC to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR,
CC LGALS3BP and COL13A1. Interacts with FBLN7 (By similarity).
CC Interacts with COMP. Interacts with S.aureus fnbA. Interacts with
CC TNR; the interaction inhibits cell adhesion and neurite outgrowth
CC (By similarity). Interacts with FST3.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=3; IntAct=EBI-1220319, EBI-6927928;
CC P29279:CTGF; NbExp=5; IntAct=EBI-1220319, EBI-2835375;
CC P14738:fnbA (xeno); NbExp=18; IntAct=EBI-1220319, EBI-8398157;
CC Q53682:fnbB (xeno); NbExp=19; IntAct=EBI-1220319, EBI-8398005;
CC P06241:FYN; NbExp=2; IntAct=EBI-7133890, EBI-515315;
CC P11684:SCGB1A1; NbExp=3; IntAct=EBI-1220319, EBI-7797649;
CC P21980:TGM2; NbExp=3; IntAct=EBI-1220319, EBI-727668;
CC P40337:VHL; NbExp=2; IntAct=EBI-1220319, EBI-301246;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=17;
CC Comment=Additional isoforms seem to exist;
CC Name=1;
CC IsoId=P02751-1; Sequence=Displayed;
CC Name=2; Synonyms=MSF-FN70, Migration stimulation factor FN70;
CC IsoId=P02751-2; Sequence=VSP_003255, VSP_003256, VSP_003257;
CC Name=3; Synonyms=V89;
CC IsoId=P02751-3; Sequence=VSP_008110;
CC Name=4; Synonyms=Fibronectin III-15X;
CC IsoId=P02751-4; Sequence=VSP_008107, VSP_008111, VSP_008112;
CC Name=5; Synonyms=Fibronectin (V+I-10)-;
CC IsoId=P02751-5; Sequence=VSP_008107, VSP_008113;
CC Name=6; Synonyms=Fibronectin (V+III-15)-;
CC IsoId=P02751-6; Sequence=VSP_008109;
CC Name=7; Synonyms=Fibronectin containing extra ED-B domain;
CC IsoId=P02751-7; Sequence=VSP_008104, VSP_008110;
CC Name=8; Synonyms=Fibronectin not containing EIIIA domain;
CC IsoId=P02751-8; Sequence=VSP_008106;
CC Name=9; Synonyms=Fibronectin not containing EIIIA and EIIIB and
CC uses V64 variant of IIICS region;
CC IsoId=P02751-9; Sequence=VSP_008106, VSP_008108, VSP_008110;
CC Name=10;
CC IsoId=P02751-10; Sequence=VSP_008106, VSP_008107;
CC Name=11; Synonyms=Fibronectin containing extra type III repeat
CC (EDII), exon x+2;
CC IsoId=P02751-11; Sequence=VSP_008105;
CC Name=12;
CC IsoId=P02751-12; Sequence=VSP_013681, VSP_008106, VSP_008108,
CC VSP_008110;
CC Name=13;
CC IsoId=P02751-13; Sequence=VSP_008104, VSP_008106, VSP_008107;
CC Note=No experimental confirmation available;
CC Name=14;
CC IsoId=P02751-14; Sequence=VSP_008106, VSP_008110;
CC Name=15;
CC IsoId=P02751-15; Sequence=VSP_008104;
CC Note=No experimental confirmation available;
CC Name=16; Synonyms=Migration stimulation factor, MSF;
CC IsoId=P02751-16; Sequence=VSP_003257;
CC Note=Expressed by fetal and tumor-associated cells;
CC Name=17;
CC IsoId=P02751-17; Sequence=VSP_047310, VSP_047311;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Plasma FN (soluble dimeric form) is secreted
CC by hepatocytes. Cellular FN (dimeric or cross-linked multimeric
CC forms), made by fibroblasts, epithelial and other cell types, is
CC deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2
CC and Ugl-Y3 are found in urine.
CC -!- DEVELOPMENTAL STAGE: Ugl-Y1, Ugl-Y2 and Ugl-Y3 are present in the
CC urine from 0 to 17 years of age.
CC -!- PTM: Sulfated.
CC -!- PTM: It is not known whether both or only one of Thr-2064 and Thr-
CC 2065 are/is glycosylated.
CC -!- PTM: Forms covalent cross-links mediated by a transglutaminase,
CC such as F13A or TGM2, between a glutamine and the epsilon-amino
CC group of a lysine residue, forming homopolymers and heteropolymers
CC (e.g. fibrinogen-fibronectin, collagen-fibronectin
CC heteropolymers).
CC -!- PTM: Phosphorylation sites are present in the extracellular
CC medium.
CC -!- PTM: Proteolytic processing produces the C-terminal NC1 peptide,
CC anastellin.
CC -!- DISEASE: Glomerulopathy with fibronectin deposits 2 (GFND2)
CC [MIM:601894]: Genetically heterogeneous autosomal dominant
CC disorder characterized clinically by proteinuria, microscopic
CC hematuria, and hypertension that leads to end-stage renal failure
CC in the second to fifth decade of life. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 12 fibronectin type-I domains.
CC -!- SIMILARITY: Contains 2 fibronectin type-II domains.
CC -!- SIMILARITY: Contains 16 fibronectin type-III domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX76513.1; Type=Erroneous gene model prediction;
CC Sequence=BAD93077.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAD91166.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAD97964.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAD97965.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=CAH18136.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Fibronectin entry;
CC URL="http://en.wikipedia.org/wiki/Fibronectin";
CC -----------------------------------------------------------------------
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DR EMBL; AJ276395; CAC20427.1; -; mRNA.
DR EMBL; AJ535086; CAD59389.1; -; mRNA.
DR EMBL; AJ849445; CAH60958.1; -; mRNA.
DR EMBL; AB191261; BAD52437.1; -; mRNA.
DR EMBL; AB209840; BAD93077.1; ALT_INIT; mRNA.
DR EMBL; AL832202; CAD91166.1; ALT_INIT; mRNA.
DR EMBL; BX537590; CAD97791.1; -; mRNA.
DR EMBL; BX538017; CAD97964.1; ALT_INIT; mRNA.
DR EMBL; BX538018; CAD97965.1; ALT_INIT; mRNA.
DR EMBL; BX640608; CAE45714.1; -; mRNA.
DR EMBL; BX640731; CAE45847.1; -; mRNA.
DR EMBL; BX640875; CAE45932.1; -; mRNA.
DR EMBL; BX640920; CAE45958.1; -; mRNA.
DR EMBL; CR749281; CAH18136.1; ALT_INIT; mRNA.
DR EMBL; CR749316; CAH18171.1; -; mRNA.
DR EMBL; CR749317; CAH18172.1; -; mRNA.
DR EMBL; AC012462; AAX76513.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC073284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW70536.1; -; Genomic_DNA.
DR EMBL; BC117176; AAI17177.1; -; mRNA.
DR EMBL; BC143763; AAI43764.1; -; mRNA.
DR EMBL; M15801; AAA53376.1; -; Genomic_DNA.
DR EMBL; AF312399; AAG30571.1; -; mRNA.
DR EMBL; X02761; CAA26536.1; -; mRNA.
DR EMBL; U41850; AAD00014.1; -; mRNA.
DR EMBL; U42404; AAD00015.1; -; mRNA.
DR EMBL; U42592; AAD00017.1; -; mRNA.
DR EMBL; U42593; AAD00018.1; -; mRNA.
DR EMBL; U42594; AAD00019.1; -; mRNA.
DR EMBL; U42455; AAD09448.1; -; mRNA.
DR EMBL; U42456; AAD09449.1; -; mRNA.
DR EMBL; U42458; AAD09450.1; -; mRNA.
DR EMBL; U42457; AAD04751.1; -; mRNA.
DR EMBL; X07718; CAB52436.1; ALT_TERM; Genomic_DNA.
DR EMBL; X07717; CAB52437.1; -; Genomic_DNA.
DR EMBL; M18179; AAA52461.1; -; Genomic_DNA.
DR EMBL; M18177; AAA52461.1; JOINED; Genomic_DNA.
DR EMBL; M18178; AAA52461.1; JOINED; Genomic_DNA.
DR EMBL; M12549; AAA58483.1; -; Genomic_DNA.
DR EMBL; M10905; AAA52462.1; -; mRNA.
DR EMBL; M14059; AAA52463.1; -; mRNA.
DR EMBL; AJ320525; CAC86914.1; -; mRNA.
DR EMBL; AJ320526; CAC86915.1; -; mRNA.
DR EMBL; AJ320527; CAC86916.1; -; mRNA.
DR EMBL; M27589; AAA52465.1; -; mRNA.
DR EMBL; X04530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A26460; FNHU.
DR PIR; I52394; I52394.
DR PIR; S00848; S00848.
DR RefSeq; NP_002017.1; NM_002026.2.
DR RefSeq; NP_473375.2; NM_054034.2.
DR RefSeq; NP_997639.1; NM_212474.1.
DR RefSeq; NP_997641.1; NM_212476.1.
DR RefSeq; NP_997643.1; NM_212478.1.
DR RefSeq; NP_997647.1; NM_212482.1.
DR RefSeq; XP_005246457.1; XM_005246400.1.
DR RefSeq; XP_005246463.1; XM_005246406.1.
DR RefSeq; XP_005246470.1; XM_005246413.1.
DR RefSeq; XP_005246472.1; XM_005246415.1.
DR RefSeq; XP_005246474.1; XM_005246417.1.
DR UniGene; Hs.203717; -.
DR PDB; 1E88; NMR; -; A=305-464.
DR PDB; 1E8B; NMR; -; A=305-464.
DR PDB; 1FBR; NMR; -; A=183-275.
DR PDB; 1FNA; X-ray; 1.80 A; A=1452-1542.
DR PDB; 1FNF; X-ray; 2.00 A; A=1173-1540.
DR PDB; 1FNH; X-ray; 2.80 A; A=1721-1991.
DR PDB; 1J8K; NMR; -; A=1631-1724.
DR PDB; 1O9A; NMR; -; A=48-140.
DR PDB; 1OWW; NMR; -; A=608-701.
DR PDB; 1Q38; NMR; -; A=631-705.
DR PDB; 1QGB; NMR; -; A=48-140.
DR PDB; 1QO6; NMR; -; A=305-405.
DR PDB; 1TTF; NMR; -; A=1447-1540.
DR PDB; 1TTG; NMR; -; A=1447-1540.
DR PDB; 2CG6; X-ray; 1.55 A; A=93-182.
DR PDB; 2CG7; X-ray; 1.20 A; A=93-182.
DR PDB; 2CK2; X-ray; 2.00 A; A/B=1447-1542.
DR PDB; 2CKU; NMR; -; A=93-182.
DR PDB; 2EC3; NMR; -; A=2239-2299.
DR PDB; 2FN2; NMR; -; A=406-464.
DR PDB; 2FNB; NMR; -; A=1961-1966.
DR PDB; 2GEE; X-ray; 2.01 A; A=1266-1356.
DR PDB; 2H41; NMR; -; A=721-809.
DR PDB; 2H45; NMR; -; A=721-809.
DR PDB; 2HA1; NMR; -; A=609-809.
DR PDB; 2OCF; X-ray; 2.95 A; D=1447-1540.
DR PDB; 2RKY; X-ray; 1.80 A; A/C=183-275.
DR PDB; 2RKZ; X-ray; 2.00 A; A/B/C/D/E/F=93-182.
DR PDB; 2RL0; X-ray; 2.00 A; A/B/D/F/I/K=184-272.
DR PDB; 3CAL; X-ray; 1.70 A; A/C=93-182.
DR PDB; 3EJH; X-ray; 2.10 A; A/B=516-608.
DR PDB; 3GXE; X-ray; 2.60 A; A/B=516-608.
DR PDB; 3M7P; X-ray; 2.50 A; A=297-604.
DR PDB; 3MQL; X-ray; 3.00 A; A=305-515.
DR PDB; 3R8Q; X-ray; 2.40 A; A=1721-1991.
DR PDB; 3T1W; X-ray; 2.40 A; A=1173-1448.
DR PDB; 3ZRZ; X-ray; 1.70 A; A/B=93-182.
DR PDB; 4GH7; X-ray; 2.60 A; B/D=1173-1357.
DR PDB; 4JE4; X-ray; 2.31 A; B=1450-1486.
DR PDB; 4JEG; X-ray; 2.30 A; B=1450-1486.
DR PDBsum; 1E88; -.
DR PDBsum; 1E8B; -.
DR PDBsum; 1FBR; -.
DR PDBsum; 1FNA; -.
DR PDBsum; 1FNF; -.
DR PDBsum; 1FNH; -.
DR PDBsum; 1J8K; -.
DR PDBsum; 1O9A; -.
DR PDBsum; 1OWW; -.
DR PDBsum; 1Q38; -.
DR PDBsum; 1QGB; -.
DR PDBsum; 1QO6; -.
DR PDBsum; 1TTF; -.
DR PDBsum; 1TTG; -.
DR PDBsum; 2CG6; -.
DR PDBsum; 2CG7; -.
DR PDBsum; 2CK2; -.
DR PDBsum; 2CKU; -.
DR PDBsum; 2EC3; -.
DR PDBsum; 2FN2; -.
DR PDBsum; 2FNB; -.
DR PDBsum; 2GEE; -.
DR PDBsum; 2H41; -.
DR PDBsum; 2H45; -.
DR PDBsum; 2HA1; -.
DR PDBsum; 2OCF; -.
DR PDBsum; 2RKY; -.
DR PDBsum; 2RKZ; -.
DR PDBsum; 2RL0; -.
DR PDBsum; 3CAL; -.
DR PDBsum; 3EJH; -.
DR PDBsum; 3GXE; -.
DR PDBsum; 3M7P; -.
DR PDBsum; 3MQL; -.
DR PDBsum; 3R8Q; -.
DR PDBsum; 3T1W; -.
DR PDBsum; 3ZRZ; -.
DR PDBsum; 4GH7; -.
DR PDBsum; 4JE4; -.
DR PDBsum; 4JEG; -.
DR ProteinModelPortal; P02751; -.
DR SMR; P02751; 48-274, 297-606, 609-809, 1173-1540, 1631-1991, 2242-2299.
DR DIP; DIP-29547N; -.
DR IntAct; P02751; 442.
DR MINT; MINT-1779779; -.
DR BindingDB; P02751; -.
DR ChEMBL; CHEMBL3810; -.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB00015; Reteplase.
DR DrugBank; DB00031; Tenecteplase.
DR PhosphoSite; P02751; -.
DR UniCarbKB; P02751; -.
DR DMDM; 300669710; -.
DR DOSAC-COBS-2DPAGE; P02751; -.
DR PaxDb; P02751; -.
DR PRIDE; P02751; -.
DR DNASU; 2335; -.
DR Ensembl; ENST00000323926; ENSP00000323534; ENSG00000115414.
DR Ensembl; ENST00000336916; ENSP00000338200; ENSG00000115414.
DR Ensembl; ENST00000345488; ENSP00000273049; ENSG00000115414.
DR Ensembl; ENST00000354785; ENSP00000346839; ENSG00000115414.
DR Ensembl; ENST00000356005; ENSP00000348285; ENSG00000115414.
DR Ensembl; ENST00000357009; ENSP00000349509; ENSG00000115414.
DR Ensembl; ENST00000357867; ENSP00000350534; ENSG00000115414.
DR Ensembl; ENST00000359671; ENSP00000352696; ENSG00000115414.
DR Ensembl; ENST00000421182; ENSP00000394423; ENSG00000115414.
DR Ensembl; ENST00000432072; ENSP00000399538; ENSG00000115414.
DR Ensembl; ENST00000443816; ENSP00000415018; ENSG00000115414.
DR Ensembl; ENST00000446046; ENSP00000410422; ENSG00000115414.
DR GeneID; 2335; -.
DR KEGG; hsa:2335; -.
DR UCSC; uc002vfh.3; human.
DR CTD; 2335; -.
DR GeneCards; GC02M216225; -.
DR HGNC; HGNC:3778; FN1.
DR HPA; CAB000126; -.
DR HPA; HPA027066; -.
DR MIM; 135600; gene.
DR MIM; 601894; phenotype.
DR neXtProt; NX_P02751; -.
DR Orphanet; 84090; Fibronectin glomerulopathy.
DR PharmGKB; PA28194; -.
DR eggNOG; NOG12793; -.
DR HOVERGEN; HBG005731; -.
DR KO; K05717; -.
DR OMA; IPGHLNS; -.
DR OrthoDB; EOG7X9G60; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; FN1; human.
DR EvolutionaryTrace; P02751; -.
DR GeneWiki; Fibronectin; -.
DR GenomeRNAi; 2335; -.
DR NextBio; 35481280; -.
DR PRO; PR:P02751; -.
DR ArrayExpress; P02751; -.
DR Bgee; P02751; -.
DR Genevestigator; P02751; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0005577; C:fibrinogen complex; IDA:BHF-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0005578; C:proteinaceous extracellular matrix; NAS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; NAS:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; NAS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; NAS:UniProtKB.
DR GO; GO:0016504; F:peptidase activator activity; IEA:Ensembl.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007161; P:calcium-independent cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0007044; P:cell-substrate junction assembly; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0018149; P:peptide cross-linking; IDA:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:BHF-UCL.
DR Gene3D; 2.10.10.10; -; 2.
DR Gene3D; 2.60.40.10; -; 16.
DR InterPro; IPR000083; Fibronectin_type1.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR000562; FN_type2_col-bd.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013806; Kringle-like.
DR Pfam; PF00039; fn1; 12.
DR Pfam; PF00040; fn2; 2.
DR Pfam; PF00041; fn3; 16.
DR SMART; SM00058; FN1; 12.
DR SMART; SM00059; FN2; 2.
DR SMART; SM00060; FN3; 16.
DR SUPFAM; SSF49265; SSF49265; 10.
DR SUPFAM; SSF57440; SSF57440; 2.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01253; FN1_1; 12.
DR PROSITE; PS51091; FN1_2; 12.
DR PROSITE; PS00023; FN2_1; 2.
DR PROSITE; PS51092; FN2_2; 2.
DR PROSITE; PS50853; FN3; 16.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Alternative splicing; Angiogenesis;
KW Cell adhesion; Cell shape; Complete proteome;
KW Direct protein sequencing; Disease mutation; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Heparin-binding; Isopeptide bond;
KW Phosphoprotein; Polymorphism; Pyrrolidone carboxylic acid;
KW Reference proteome; Repeat; Secreted; Signal; Sulfation.
FT SIGNAL 1 31
FT CHAIN 32 2386 Fibronectin.
FT /FTId=PRO_0000019235.
FT CHAIN 627 702 Anastellin.
FT /FTId=PRO_0000390479.
FT CHAIN 723 911 Ugl-Y1.
FT /FTId=PRO_0000300249.
FT CHAIN 723 903 Ugl-Y2.
FT /FTId=PRO_0000300250.
FT CHAIN 723 ? Ugl-Y3.
FT /FTId=PRO_0000300251.
FT DOMAIN 50 90 Fibronectin type-I 1.
FT DOMAIN 95 138 Fibronectin type-I 2.
FT DOMAIN 139 182 Fibronectin type-I 3.
FT DOMAIN 184 228 Fibronectin type-I 4.
FT DOMAIN 229 273 Fibronectin type-I 5.
FT DOMAIN 306 345 Fibronectin type-I 6.
FT DOMAIN 355 403 Fibronectin type-II 1.
FT DOMAIN 415 463 Fibronectin type-II 2.
FT DOMAIN 468 511 Fibronectin type-I 7.
FT DOMAIN 516 558 Fibronectin type-I 8.
FT DOMAIN 559 602 Fibronectin type-I 9.
FT DOMAIN 610 702 Fibronectin type-III 1.
FT DOMAIN 722 812 Fibronectin type-III 2.
FT DOMAIN 813 904 Fibronectin type-III 3.
FT DOMAIN 909 998 Fibronectin type-III 4.
FT DOMAIN 999 1088 Fibronectin type-III 5.
FT DOMAIN 1089 1175 Fibronectin type-III 6.
FT DOMAIN 1176 1266 Fibronectin type-III 7.
FT DOMAIN 1269 1361 Fibronectin type-III 8.
FT DOMAIN 1362 1449 Fibronectin type-III 9.
FT DOMAIN 1450 1543 Fibronectin type-III 10.
FT DOMAIN 1544 1635 Fibronectin type-III 11.
FT DOMAIN 1636 1723 Fibronectin type-III 12; extra domain.
FT DOMAIN 1724 1817 Fibronectin type-III 13.
FT DOMAIN 1818 1904 Fibronectin type-III 14.
FT DOMAIN 1905 1995 Fibronectin type-III 15.
FT DOMAIN 2103 2197 Fibronectin type-III 16.
FT DOMAIN 2204 2248 Fibronectin type-I 10.
FT DOMAIN 2249 2291 Fibronectin type-I 11.
FT DOMAIN 2293 2336 Fibronectin type-I 12.
FT DNA_BIND 907 1172
FT REGION 52 272 Fibrin- and heparin-binding 1.
FT REGION 308 608 Collagen-binding.
FT REGION 464 477 Critical for collagen binding.
FT REGION 1267 1540 Cell-attachment.
FT REGION 1721 1991 Heparin-binding 2.
FT REGION 1813 1991 Binds to FBLN1.
FT REGION 1992 2102 Connecting strand 3 (CS-3) (V region).
FT REGION 2206 2337 Fibrin-binding 2.
FT MOTIF 1524 1526 Cell attachment site.
FT SITE 663 663 Important for superfibronectin formation.
FT SITE 666 666 Important for superfibronectin formation.
FT SITE 2108 2108 Not glycosylated.
FT MOD_RES 32 32 Pyrrolidone carboxylic acid.
FT MOD_RES 876 876 Sulfotyrosine (Potential).
FT MOD_RES 881 881 Sulfotyrosine (Potential).
FT MOD_RES 2384 2384 Phosphoserine.
FT CARBOHYD 279 279 O-linked (GalNAc...).
FT CARBOHYD 430 430 N-linked (GlcNAc...).
FT CARBOHYD 528 528 N-linked (GlcNAc...) (complex).
FT CARBOHYD 542 542 N-linked (GlcNAc...) (complex).
FT CARBOHYD 877 877 N-linked (GlcNAc...).
FT CARBOHYD 1007 1007 N-linked (GlcNAc...) (complex).
FT CARBOHYD 1244 1244 N-linked (GlcNAc...).
FT CARBOHYD 2064 2064 O-linked (GalNAc...).
FT CARBOHYD 2065 2065 O-linked (GalNAc...).
FT CARBOHYD 2108 2108 N-linked (GlcNAc...).
FT DISULFID 52 78
FT DISULFID 76 87
FT DISULFID 97 125
FT DISULFID 123 135
FT DISULFID 141 169
FT DISULFID 167 179
FT DISULFID 186 215
FT DISULFID 213 225
FT DISULFID 231 260
FT DISULFID 258 270
FT DISULFID 308 335
FT DISULFID 333 342
FT DISULFID 360 386
FT DISULFID 374 401
FT DISULFID 420 446
FT DISULFID 434 461
FT DISULFID 470 498 By similarity.
FT DISULFID 496 508 By similarity.
FT DISULFID 518 545 By similarity.
FT DISULFID 543 555 By similarity.
FT DISULFID 561 589 By similarity.
FT DISULFID 587 599 By similarity.
FT DISULFID 2206 2235 By similarity.
FT DISULFID 2233 2245 By similarity.
FT DISULFID 2251 2278 By similarity.
FT DISULFID 2276 2288 By similarity.
FT DISULFID 2295 2319 By similarity.
FT DISULFID 2317 2333 By similarity.
FT DISULFID 2367 2367 Interchain (with C-2371).
FT DISULFID 2371 2371 Interchain (with C-2367).
FT CROSSLNK 34 34 Isoglutamyl lysine isopeptide (Gln-Lys)
FT (interchain with K-?) (By similarity).
FT CROSSLNK 35 35 Isoglutamyl lysine isopeptide (Gln-Lys)
FT (interchain with K-?) (By similarity).
FT CROSSLNK 47 47 Isoglutamyl lysine isopeptide (Gln-Lys)
FT (interchain with K-?) (By similarity).
FT VAR_SEQ 368 388 GRTFYSCTTEGRQDGHLWCST -> DRTDST (in
FT isoform 2).
FT /FTId=VSP_003255.
FT VAR_SEQ 648 657 KNSVGRWKEA -> VSIPPRNLGY (in isoform 2).
FT /FTId=VSP_003256.
FT VAR_SEQ 658 2386 Missing (in isoform 2 and isoform 16).
FT /FTId=VSP_003257.
FT VAR_SEQ 1256 1487 Missing (in isoform 12).
FT /FTId=VSP_013681.
FT VAR_SEQ 1265 1265 P -> PEVPQLTDLSFVDITDSSIGLRWTPLNSSTIIGYRI
FT TVVAAGEGIPIFEDFVDSSVGYYTVTGLEPGIDYDISVITL
FT INGGESAPTTLTQQT (in isoform 7, isoform 13
FT and isoform 15).
FT /FTId=VSP_008104.
FT VAR_SEQ 1266 1365 AVPPPTDLRFTNIGPDTMRVTWAPPPSIDLTNFLVRYSPVK
FT NEEDVAELSISPSDNAVVLTNLLPGTEYVVSVSSVYEQHES
FT TPLRGRQKTGLDSPTGID -> EVPQLTDLSFVDITDSSIG
FT LRWTPLNSSTIIGYRITVVAAGEGIPIFEDFVDSSVGYYTV
FT TGLEPGIDYDISVITLINGGESAPTTLTQQTAVPPPTDLR
FT (in isoform 11).
FT /FTId=VSP_008105.
FT VAR_SEQ 1631 1721 NIDRPKGLAFTDVDVDSIKIAWESPQGQVSRYRVTYSSPED
FT GIHELFPAPDGEEDTAELQGLRPGSEYTVSVVALHDDMESQ
FT PLIGTQSTA -> T (in isoform 8, isoform 9,
FT isoform 10, isoform 12, isoform 13 and
FT isoform 14).
FT /FTId=VSP_008106.
FT VAR_SEQ 1991 2110 Missing (in isoform 4, isoform 5, isoform
FT 10 and isoform 13).
FT /FTId=VSP_008107.
FT VAR_SEQ 1991 2015 Missing (in isoform 9 and isoform 12).
FT /FTId=VSP_008108.
FT VAR_SEQ 1992 2193 Missing (in isoform 6).
FT /FTId=VSP_008109.
FT VAR_SEQ 1992 2016 Missing (in isoform 17).
FT /FTId=VSP_047310.
FT VAR_SEQ 2081 2111 Missing (in isoform 3, isoform 7, isoform
FT 9, isoform 12 and isoform 14).
FT /FTId=VSP_008110.
FT VAR_SEQ 2082 2112 Missing (in isoform 17).
FT /FTId=VSP_047311.
FT VAR_SEQ 2148 2151 FRVP -> STKA (in isoform 4).
FT /FTId=VSP_008111.
FT VAR_SEQ 2152 2386 Missing (in isoform 4).
FT /FTId=VSP_008112.
FT VAR_SEQ 2193 2247 Missing (in isoform 5).
FT /FTId=VSP_008113.
FT VARIANT 15 15 Q -> L (in dbSNP:rs1250259).
FT /FTId=VAR_043917.
FT VARIANT 817 817 T -> P (in dbSNP:rs2577301).
FT /FTId=VAR_059529.
FT VARIANT 940 940 D -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036018.
FT VARIANT 973 973 Y -> C (in GFND2).
FT /FTId=VAR_043918.
FT VARIANT 1120 1120 R -> P (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036019.
FT VARIANT 1467 1467 S -> R (in dbSNP:rs11687611).
FT /FTId=VAR_056576.
FT VARIANT 1834 1834 W -> R (in GFND2; reduced binding to
FT heparin, endothelial cells and podocytes;
FT impaired capability to induce stress-
FT fiber formation).
FT /FTId=VAR_043919.
FT VARIANT 1883 1883 L -> R (in GFND2; reduced binding to
FT heparin, endothelial cells and podocytes;
FT impaired capability to induce stress-
FT fiber formation).
FT /FTId=VAR_043920.
FT VARIANT 1960 1960 I -> V (in dbSNP:rs1250209).
FT /FTId=VAR_043921.
FT VARIANT 2121 2121 I -> V (in dbSNP:rs17449032).
FT /FTId=VAR_056577.
FT VARIANT 2170 2170 V -> I (in dbSNP:rs1250209).
FT /FTId=VAR_061486.
FT VARIANT 2380 2380 D -> N (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036020.
FT MUTAGEN 641 641 Y->A: Severely compromised ability to
FT form fibronectin aggregates; when
FT associated with A-681 and A-683.
FT MUTAGEN 642 642 I->A: Little effect on ability to form
FT fibronectin aggregates; when associated
FT with A-682; A-684 and A-692.
FT MUTAGEN 663 663 L->A: No effect on secondary structure
FT nor on fibronectin binding nor on
FT activation of p38 K but abolishes
FT polymerization activity; when associated
FT with A-666.
FT MUTAGEN 666 666 Y->A: No effect on secondary structure
FT nor on fibronectin binding nor on
FT activation of p38 kinase but abolishes
FT polymerization activity; when associated
FT with A-663.
FT MUTAGEN 681 681 L->A: Severely compromised ability to
FT form fibronectin aggregates; when
FT associated with A-641 and A-683.
FT MUTAGEN 682 682 I->A: Little effect on ability to form
FT fibronectin aggregates; when associated
FT with A-642; A-684 and A-692.
FT MUTAGEN 683 683 S->A: Severely compromised ability to
FT form fibronectin aggregates; when
FT associated with A-641 and A-681.
FT MUTAGEN 684 684 I->A: Little effect on ability to form
FT fibronectin aggregates; when associated
FT with A-642; A-682 and A-692.
FT MUTAGEN 691 691 E->A: Slightly enhanced ability to form
FT fibronectin aggregates; when associated
FT with A-694 and A-696.
FT MUTAGEN 692 692 V->A: Little effect on ability to form
FT fibronectin aggregates; when associated
FT with A-642; A-682 and A-684.
FT MUTAGEN 694 694 R->A: Slightly enhanced ability to form
FT fibronectin aggregates; when associated
FT with A-691 and A-696.
FT MUTAGEN 695 695 F->A: Loss of ability to form fibronectin
FT aggregates; when associated with A-697.
FT MUTAGEN 696 696 D->A: Slightly enhanced ability to form
FT fibronectin aggregates; when associated
FT with A-691 and A-694.
FT MUTAGEN 697 697 F->A: Loss of ability to form fibronectin
FT aggregates; when associated with A-695.
FT CONFLICT 32 32 Q -> R (in Ref. 5; CAH18171).
FT CONFLICT 69 69 Y -> N (in Ref. 5; CAH18172).
FT CONFLICT 73 73 A -> V (in Ref. 11; CAA26536).
FT CONFLICT 126 126 I -> V (in Ref. 5; CAH18136).
FT CONFLICT 199 199 E -> G (in Ref. 5; CAD91166).
FT CONFLICT 247 247 S -> R (in Ref. 1; CAD59389 and 2;
FT CAH60958).
FT CONFLICT 260 260 C -> R (in Ref. 5; CAH18172).
FT CONFLICT 289 289 V -> A (in Ref. 5; CAE45847).
FT CONFLICT 355 355 S -> L (in Ref. 13; AAD00015).
FT CONFLICT 375 375 T -> A (in Ref. 5; CAH18136).
FT CONFLICT 411 411 R -> Q (in Ref. 13; AAD00015).
FT CONFLICT 518 518 C -> R (in Ref. 5; CAD97791).
FT CONFLICT 552 552 R -> K (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 580 580 V -> A (in Ref. 5; CAH18172).
FT CONFLICT 678 678 E -> Q (in Ref. 15; AA sequence).
FT CONFLICT 704 705 TP -> PT (in Ref. 15; AA sequence).
FT CONFLICT 980 980 V -> L (in Ref. 5; CAD97791).
FT CONFLICT 1030 1030 T -> A (in Ref. 5; CAH18136).
FT CONFLICT 1048 1048 V -> D (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 1134 1134 D -> G (in Ref. 5; CAH18136).
FT CONFLICT 1137 1137 S -> N (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 1152 1152 T -> I (in Ref. 5; CAH18136).
FT CONFLICT 1222 1222 E -> G (in Ref. 5; CAD97791).
FT CONFLICT 1226 1226 H -> Q (in Ref. 5; CAE45932).
FT CONFLICT 1555 1555 D -> G (in Ref. 5; CAE45714).
FT CONFLICT 1601 1601 G -> S (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 1622 1622 Q -> E (in Ref. 26; AA sequence).
FT CONFLICT 1715 1721 IGTQSTA -> VQTAVTT (in Ref. 28;
FT AAA52463).
FT CONFLICT 1726 1726 T -> A (in Ref. 5; CAE45847).
FT CONFLICT 1755 1755 R -> W (in Ref. 5; CAH18136).
FT CONFLICT 1768 1768 I -> V (in Ref. 18; CAB52436).
FT CONFLICT 1783 1783 M -> T (in Ref. 5; CAE45932).
FT CONFLICT 1927 1927 R -> C (in Ref. 13; AAD00014).
FT CONFLICT 1934 1934 I -> V (in Ref. 5; CAH18172).
FT CONFLICT 1992 1992 D -> G (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 2023 2023 V -> A (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 2027 2027 G -> R (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 2251 2251 C -> R (in Ref. 5; CAH18172).
FT CONFLICT 2312 2312 Y -> N (in Ref. 5; CAD97965/CAD97964).
FT CONFLICT 2341 2341 S -> T (in Ref. 5; CAE45714/CAH18171/
FT CAH18172/CAE45958).
FT CONFLICT 2367 2367 C -> Y (in Ref. 5; CAE45932).
FT STRAND 52 54
FT STRAND 57 59
FT STRAND 64 69
FT STRAND 72 78
FT TURN 81 83
FT STRAND 85 89
FT STRAND 96 98
FT TURN 100 102
FT STRAND 105 107
FT STRAND 111 116
FT STRAND 119 127
FT TURN 128 131
FT STRAND 132 136
FT STRAND 140 143
FT STRAND 146 149
FT STRAND 153 157
FT STRAND 161 171
FT TURN 172 175
FT STRAND 176 181
FT STRAND 185 188
FT TURN 189 192
FT STRAND 193 196
FT STRAND 200 205
FT TURN 206 208
FT STRAND 209 217
FT TURN 218 221
FT STRAND 222 226
FT STRAND 230 233
FT TURN 234 237
FT STRAND 238 241
FT STRAND 245 249
FT STRAND 251 253
FT STRAND 255 262
FT TURN 263 266
FT STRAND 267 271
FT STRAND 302 304
FT STRAND 307 309
FT TURN 311 313
FT STRAND 315 317
FT STRAND 321 326
FT STRAND 329 336
FT STRAND 339 344
FT TURN 353 356
FT STRAND 360 366
FT STRAND 369 373
FT STRAND 381 383
FT STRAND 385 391
FT HELIX 392 395
FT STRAND 398 401
FT HELIX 403 405
FT TURN 413 417
FT STRAND 422 426
FT STRAND 429 433
FT STRAND 440 442
FT STRAND 445 451
FT HELIX 452 455
FT STRAND 458 460
FT HELIX 465 467
FT STRAND 469 471
FT STRAND 477 479
FT STRAND 483 485
FT STRAND 490 492
FT STRAND 495 500
FT TURN 501 504
FT STRAND 505 513
FT STRAND 517 520
FT STRAND 523 526
FT STRAND 529 534
FT STRAND 540 547
FT TURN 548 551
FT STRAND 552 557
FT STRAND 559 562
FT TURN 564 566
FT STRAND 569 571
FT STRAND 575 578
FT STRAND 585 591
FT TURN 592 595
FT STRAND 596 601
FT STRAND 613 615
FT STRAND 626 631
FT STRAND 634 636
FT STRAND 638 647
FT TURN 648 651
FT STRAND 655 659
FT STRAND 661 664
FT STRAND 665 668
FT STRAND 673 688
FT STRAND 690 699
FT HELIX 732 734
FT STRAND 736 739
FT STRAND 747 756
FT TURN 757 759
FT STRAND 764 769
FT STRAND 774 777
FT STRAND 785 794
FT STRAND 799 808
FT STRAND 1178 1184
FT STRAND 1186 1189
FT STRAND 1191 1196
FT STRAND 1205 1212
FT TURN 1213 1215
FT STRAND 1221 1225
FT STRAND 1231 1233
FT STRAND 1243 1251
FT STRAND 1259 1263
FT STRAND 1271 1277
FT STRAND 1283 1288
FT STRAND 1296 1304
FT HELIX 1308 1310
FT STRAND 1312 1316
FT STRAND 1322 1325
FT STRAND 1333 1342
FT STRAND 1350 1355
FT STRAND 1362 1368
FT STRAND 1371 1379
FT STRAND 1386 1393
FT STRAND 1402 1407
FT STRAND 1412 1417
FT STRAND 1423 1432
FT STRAND 1440 1445
FT STRAND 1455 1459
FT STRAND 1464 1467
FT STRAND 1476 1484
FT TURN 1485 1490
FT STRAND 1492 1497
FT STRAND 1502 1505
FT STRAND 1513 1521
FT STRAND 1525 1527
FT STRAND 1534 1539
FT STRAND 1639 1644
FT STRAND 1647 1651
FT STRAND 1662 1668
FT TURN 1669 1671
FT STRAND 1672 1676
FT STRAND 1686 1689
FT STRAND 1696 1704
FT STRAND 1706 1708
FT STRAND 1714 1719
FT STRAND 1726 1733
FT STRAND 1738 1743
FT STRAND 1751 1763
FT STRAND 1766 1770
FT STRAND 1776 1779
FT STRAND 1787 1796
FT STRAND 1804 1809
FT STRAND 1818 1825
FT STRAND 1830 1835
FT STRAND 1843 1853
FT STRAND 1857 1861
FT STRAND 1866 1870
FT STRAND 1878 1887
FT STRAND 1895 1900
FT STRAND 1907 1915
FT STRAND 1918 1924
FT STRAND 1932 1938
FT STRAND 1957 1960
FT STRAND 1968 1977
FT STRAND 1985 1990
FT STRAND 2253 2255
FT STRAND 2263 2267
FT STRAND 2269 2280
FT TURN 2281 2284
FT STRAND 2285 2290
SQ SEQUENCE 2386 AA; 262625 MW; 5F7EDB9700335098 CRC64;
MLRGPGPGLL LLAVQCLGTA VPSTGASKSK RQAQQMVQPQ SPVAVSQSKP GCYDNGKHYQ
INQQWERTYL GNALVCTCYG GSRGFNCESK PEAEETCFDK YTGNTYRVGD TYERPKDSMI
WDCTCIGAGR GRISCTIANR CHEGGQSYKI GDTWRRPHET GGYMLECVCL GNGKGEWTCK
PIAEKCFDHA AGTSYVVGET WEKPYQGWMM VDCTCLGEGS GRITCTSRNR CNDQDTRTSY
RIGDTWSKKD NRGNLLQCIC TGNGRGEWKC ERHTSVQTTS SGSGPFTDVR AAVYQPQPHP
QPPPYGHCVT DSGVVYSVGM QWLKTQGNKQ MLCTCLGNGV SCQETAVTQT YGGNSNGEPC
VLPFTYNGRT FYSCTTEGRQ DGHLWCSTTS NYEQDQKYSF CTDHTVLVQT RGGNSNGALC
HFPFLYNNHN YTDCTSEGRR DNMKWCGTTQ NYDADQKFGF CPMAAHEEIC TTNEGVMYRI
GDQWDKQHDM GHMMRCTCVG NGRGEWTCIA YSQLRDQCIV DDITYNVNDT FHKRHEEGHM
LNCTCFGQGR GRWKCDPVDQ CQDSETGTFY QIGDSWEKYV HGVRYQCYCY GRGIGEWHCQ
PLQTYPSSSG PVEVFITETP SQPNSHPIQW NAPQPSHISK YILRWRPKNS VGRWKEATIP
GHLNSYTIKG LKPGVVYEGQ LISIQQYGHQ EVTRFDFTTT STSTPVTSNT VTGETTPFSP
LVATSESVTE ITASSFVVSW VSASDTVSGF RVEYELSEEG DEPQYLDLPS TATSVNIPDL
LPGRKYIVNV YQISEDGEQS LILSTSQTTA PDAPPDTTVD QVDDTSIVVR WSRPQAPITG
YRIVYSPSVE GSSTELNLPE TANSVTLSDL QPGVQYNITI YAVEENQEST PVVIQQETTG
TPRSDTVPSP RDLQFVEVTD VKVTIMWTPP ESAVTGYRVD VIPVNLPGEH GQRLPISRNT
FAEVTGLSPG VTYYFKVFAV SHGRESKPLT AQQTTKLDAP TNLQFVNETD STVLVRWTPP
RAQITGYRLT VGLTRRGQPR QYNVGPSVSK YPLRNLQPAS EYTVSLVAIK GNQESPKATG
VFTTLQPGSS IPPYNTEVTE TTIVITWTPA PRIGFKLGVR PSQGGEAPRE VTSDSGSIVV
SGLTPGVEYV YTIQVLRDGQ ERDAPIVNKV VTPLSPPTNL HLEANPDTGV LTVSWERSTT
PDITGYRITT TPTNGQQGNS LEEVVHADQS SCTFDNLSPG LEYNVSVYTV KDDKESVPIS
DTIIPAVPPP TDLRFTNIGP DTMRVTWAPP PSIDLTNFLV RYSPVKNEED VAELSISPSD
NAVVLTNLLP GTEYVVSVSS VYEQHESTPL RGRQKTGLDS PTGIDFSDIT ANSFTVHWIA
PRATITGYRI RHHPEHFSGR PREDRVPHSR NSITLTNLTP GTEYVVSIVA LNGREESPLL
IGQQSTVSDV PRDLEVVAAT PTSLLISWDA PAVTVRYYRI TYGETGGNSP VQEFTVPGSK
STATISGLKP GVDYTITVYA VTGRGDSPAS SKPISINYRT EIDKPSQMQV TDVQDNSISV
KWLPSSSPVT GYRVTTTPKN GPGPTKTKTA GPDQTEMTIE GLQPTVEYVV SVYAQNPSGE
SQPLVQTAVT NIDRPKGLAF TDVDVDSIKI AWESPQGQVS RYRVTYSSPE DGIHELFPAP
DGEEDTAELQ GLRPGSEYTV SVVALHDDME SQPLIGTQST AIPAPTDLKF TQVTPTSLSA
QWTPPNVQLT GYRVRVTPKE KTGPMKEINL APDSSSVVVS GLMVATKYEV SVYALKDTLT
SRPAQGVVTT LENVSPPRRA RVTDATETTI TISWRTKTET ITGFQVDAVP ANGQTPIQRT
IKPDVRSYTI TGLQPGTDYK IYLYTLNDNA RSSPVVIDAS TAIDAPSNLR FLATTPNSLL
VSWQPPRARI TGYIIKYEKP GSPPREVVPR PRPGVTEATI TGLEPGTEYT IYVIALKNNQ
KSEPLIGRKK TDELPQLVTL PHPNLHGPEI LDVPSTVQKT PFVTHPGYDT GNGIQLPGTS
GQQPSVGQQM IFEEHGFRRT TPPTTATPIR HRPRPYPPNV GEEIQIGHIP REDVDYHLYP
HGPGLNPNAS TGQEALSQTT ISWAPFQDTS EYIISCHPVG TDEEPLQFRV PGTSTSATLT
GLTRGATYNV IVEALKDQQR HKVREEVVTV GNSVNEGLNQ PTDDSCFDPY TVSHYAVGDE
WERMSESGFK LLCQCLGFGS GHFRCDSSRW CHDNGVNYKI GEKWDRQGEN GQMMSCTCLG
NGKGEFKCDP HEATCYDDGK TYHVGEQWQK EYLGAICSCT CFGGQRGWRC DNCRRPGGEP
SPEGTTGQSY NQYSQRYHQR TNTNVNCPIE CFMPLDVQAD REDSRE
//

MIM 135600
*RECORD*
*FIELD* NO
135600
*FIELD* TI
*135600 FIBRONECTIN 1; FN1
;;FN;;
LARGE, EXTERNAL, TRANSFORMATION-SENSITIVE PROTEIN; LETS
read more*FIELD* TX

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 et al. (1993) mapped
FN1 to 2q34 by fluorescence in situ hybridization.

Skow et al. (1987) mapped the mouse Fn1 gene to the midregion of
chromosome 1, about 4 cM distal to the Cryg locus (123660). The mapping
was done by study of recombinant inbred strains of mice and a RFLP
identified with a cDNA for human fibronectin. Zneimer and Womack (1988)
mapped fibronectin to mouse chromosome 1 by in situ hybridization.

- Pseudogene

In meiotic chromosomes, Jhanwar et al. (1986) observed 2 sites of FN
hybridization on chromosome 2, 2p16-p14 and 2q34-q36, and 1 on
chromosome 11, 11q12.1-q13.5. Only the chromosome 2 sites showed
hybridization in somatic cells. The authors suggested that 1 of the 2
sites on chromosome 2 might represent a pseudogene.

BIOCHEMICAL FEATURES

By NMR spectroscopy, Schwarz-Linek et al. (2003) determined the
structure of a streptococcal (S. dysgalactiae) fibronectin-binding
protein peptide (B3) in complex with the module pair (1)F1(2)F1 of human
fibronectin. This identified the (1)F1- and (2)F1-binding motifs in B3
that form additional antiparallel beta-strands on sequential F1
modules--the first example of a tandem beta-zipper. Sequence analyses of
larger regions of the fibronectin-binding proteins from S. pyogenes and
S. aureus revealed a repeating pattern of F1-binding motifs that match
the pattern of F1 modules in the N-terminal bacterium-binding site of
fibronectin. Schwarz-Linek et al. (2003) concluded that in the process
of fibronectin-mediated invasion of host cells, the bacterial proteins
seem to exploit the modular structure of fibronectin by forming extended
tandem beta-zippers.

GENE FUNCTION

A major function of the fibronectins is in the adhesion of cells to
extracellular materials such as solid substrata and matrices. Bing et
al. (1982) showed that fibronectin binds to C1q (see 120550) in the same
manner that it binds collagen. Because fibronectin stimulates
endocytosis and promotes the clearance of particulate material from the
circulation, Bing et al. (1982) suggested that fibronectin functions in
the clearance of C1q-coated material such as immune complexes or
cellular debris.

Matsuura et al. (1988) found that a single glycosylation at a defined
threonine residue of the IIICS region of fibronectin defines an
antigenic epitope recognized by monoclonal antibody FDC-6, which
specifically recognizes fibronectin isolated from fetal and malignant
cells and tissues.

Commenting on the use of high-density DNA microarrays in gene expression
profiling, Ridley (2000) pointed out that the results of Clark et al.
(2000) and Bittner et al. (2000) indicated that fibronectin is required
for the metastasis of melanoma cells.

Alternatively spliced FN1 EDA and EDB are prominently expressed during
wound healing, lung, liver and kidney fibrosis, vascular intimal
proliferation, and cardiac transplantation. Liao et al. (2002) found
that the EDA segment of cellular FN1 binds integrins ITGA9
(603963)-ITGB1 (135630) and ITGA3 (605025)-ITGB1 on cells. The findings
established a mechanism by which cell adhesion to fibronectin can be
regulated by alternative splicing.

Sakai et al. (2003) demonstrated that fibronectin is essential for cleft
formation during the initiation of epithelial branching in the formation
of salivary glands. Fibronectin mRNA and fibrils appeared transiently
and focally in forming cleft regions of submandibular salivary gland
epithelia, accompanied by an adjacent loss of E cadherin (192090)
localization. Decreasing fibronectin blocked cleft formation and
branching, whereas exogenous fibronectin accelerated it. Similar effects
of fibronectin suppression and augmentation were observed in developing
lung and kidney. Mechanistic studies revealed that fibrillar fibronectin
could induce cell-matrix adhesions on cultured human salivary epithelial
cells with a local loss of cadherins at cell-cell junctions. The
findings indicated that fibronectin expression is required for branching
morphogenesis associated with the conversion of cell-cell adhesions to
cell-matrix adhesions.

Jiang et al. (2003) observed that the soluble trimeric, but not
monomeric, fibronectin domain FNIII7-10 bound specifically to integrin
ITGAV (193210)-ITGB3 (173470) on the leading edge of migratory cells.
Studies using force breakage indicated that the actin-binding protein
talin-1 (TLN1; 186745) initially forms a molecular bond between closely
packed fibronectin-integrin complexes and the actin cytoskeleton before
the recruitment of other proteins. These mechanical forces on
matrix-integrin-cytoskeleton linkages are crucial for cell viability,
morphology, and organ function.

Matsunaga et al. (2003) found that VLA4 (see 192975)-positive leukemic
cells acquired resistance to anoikis (loss of anchorage) or drug-induced
apoptosis through the phosphatidylinositol-3-kinase (see 601232)/AKT
(164730)/BCL2 (151430) signaling pathway, which is activated by the
interaction of VLA4 and fibronectin. This resistance was negated by
VLA4-specific antibodies. In a mouse model of minimal residual disease,
Matsunaga et al. (2003) achieved a 100% survival rate by combining
VLA4-specific antibodies and cytosine arabinoside, whereas cytosine
arabinoside alone prolonged survival only slightly. In addition, overall
survival at 5 years was 100% for 10 VLA4-negative patients and 44.4% for
15 VLA4-positive patients. Matsunaga et al. (2003) concluded that the
interaction between VLA4 on leukemic cells and fibronectin on stromal
cells may be crucial in bone marrow minimal residual disease and
prognosis in acute myelogenous leukemia.

MOLECULAR GENETICS

In affected members of 6 unrelated families with glomerulopathy with
fibronectin deposits (GFND2; 601894), Castelletti et al. (2008)
identified 3 heterozygous mutations in the FN1 gene
(135600.0001-135600.0003). Studies of the mutant proteins suggested that
GFND-associated mutations in FN1 impair the control of the assembly of
FN1 into fibrils and the balance between soluble and insoluble
fibronectin. Six (40%) of 15 affected families were found to have FN1
mutations.

HISTORY

- Early Mapping Studies

In clones derived from human-mouse hybrids, Owerbach et al. (1978) found
that LETS segregated with chromosome 8 and with glutathione reductase
(GSR; 138300), which is also located on 8p. Smith et al. (1979)
concluded that chromosomes 3 and 11 are essential to expression of
fibronectin. Eun and Klinger (1980) also found synteny of fibronectin
production and chromosome 11. Kurkinen et al. (1980) postulated that the
inconsistencies may reflect the synthesis of different polypeptide
chains. Using a specific immunoassay for fibronectin in mouse-human cell
hybrids, Rennard et al. (1981) found 100% concordance between expression
of human fibronectin and glutathione reductase. The authors suggested
that a gene on chromosome 8 may control the presence or absence of FN on
the cell surface, whereas another gene mapped to chromosome 11 may
involve the fibrillar morphology of cellular FN. Smith et al. (1982)
also concluded that the production of soluble fibronectin was associated
with chromosome 11. Clones that contained human chromosome 3 in the
absence of chromosome 11 did not produce fibronectin, and 2 clones that
did not produce fibronectin were positive for glutathione reductase.
They concluded that the structural gene for FN was on chromosome 11.

ANIMAL MODEL

To investigate the role of plasma fibronectin in vivo, Sakai et al.
(2001) generated plasma fibronectin-deficient adult mice using Cre-loxP
conditional gene-knockout technology. Sakai et al. (2001) demonstrated
that plasma fibronectin-deficient mice show increased neuronal apoptosis
and larger infarction areas following transient focal cerebral ischemia.
Surprisingly, plasma fibronectin was not essential for skin wound
healing or hemostasis.

Muro et al. (2003) generated mice with constitutive inclusion or
complete exclusion of the EDA exon in the Fn1 gene. Both types of
homozygous mice developed normally and were viable. However, those
without the EDA exon showed abnormal skin wound healing. Adult mice with
constitutive expression of the EDA exon showed a major decrease of Fn1
in all tissues. Both mutant mice had significantly shorter life spans
compared to wildtype mice. The findings indicated that EDA splicing
regulation is necessary for long-term maintenance of biologic functions.

*FIELD* AV
.0001
GLOMERULOPATHY WITH FIBRONECTIN DEPOSITS 2
FN1, TRP1925ARG

In affected members of an Italian family with glomerulopathy with
fibronectin deposits (601894), Castelletti et al. (2008) identified a
heterozygous 5773T-A transversion in exon 36 of the FN1 gene, resulting
in a trp1925-to-arg (W1925R) substitution in the III-13 repeat of the
HepII heparin-binding domain. The family was first described by Strom et
al. (1995). Clinical features included proteinuria, hypertension,
microhematuria, slowly decreasing renal function, and the presence of
enlarged glomeruli with fibronectin-positive subendothelial and
mesangial deposits on renal biopsy. The deposited fibronectin was mainly
plasma-derived. In vitro functional expression studies showed that the
mutant protein had decreased binding to heparin and to endothelial
cells. Castelletti et al. (2008) hypothesized that abnormal fibronectin
could disturb cell spreading and the cytoskeleton in glomerular
endothelial cells and podocytes, which would alter glomerular properties
and induce abnormal protein trafficking. In addition, mutations in the
FN1 gene could alter the balance between soluble and insoluble
fibronectin.

.0002
GLOMERULOPATHY WITH FIBRONECTIN DEPOSITS 2
FN1, LEU1974ARG

In affected members of a family from New Zealand with glomerulopathy
with fibronectin deposits (601894), Castelletti et al. (2008) identified
a heterozygous 5921T-G transversion in exon 37 of the FN1 gene,
resulting in a leu1974-to-arg (L1974R) substitution in the III-13 repeat
of the HepII heparin-binding domain. In vitro functional expression
studies showed that the mutant protein had decreased binding to heparin
and to endothelial cells.

.0003
GLOMERULOPATHY WITH FIBRONECTIN DEPOSITS 2
FN1, TYR983CYS

In affected members of 4 unrelated families with glomerulopathy with
fibronectin deposits (601894), Castelletti et al. (2008) identified a
heterozygous 2918A-G transition in the FN1 gene, resulting in a
tyr973-to-cys (Y983C) substitution in the III-4 repeat in the HepIII
heparin-binding domain. Three of the families had previously been
reported by Mazzucco et al. (1992), Assmann et al. (1995), and Niimi et
al. (2002). The 4 families were of different ethnic origin and did not
share a disease haplotype, thus excluding a founder effect.

*FIELD* SA
Clemmensen (1981); Hirano et al. (1983); McDonagh (1981); Mosesson
and Amrani (1980); Odermatt et al. (1985); Zardi et al. (1982); Zardi
et al. (1979)
*FIELD* RF
1. Assmann, K. J. M.; Koene, R. A. P.; Wetzels, J. F. M.: Familial
glomerulonephritis characterized by massive deposits of fibronectin. Am.
J. Kidney Dis. 25: 781-791, 1995.

2. Bing, D. H.; Almeda, S.; Isliker, H.; Lahav, J.; Hynes, R. O.:
Fibronectin binds to the C1q component of complement. Proc. Nat.
Acad. Sci. 79: 4198-4201, 1982.

3. Bittner, M.; Meltzer, P.; Chen, Y.; Jiang, Y.; Seftor, E.; Hendrix,
M.; Radmacher, M.; Simon, R.; Yakhini, Z.; Ben-Dor, A.; Sampas, N.;
Dougherty, E.; and 16 others: Molecular classification of cutaneous
malignant melanoma by gene expression profiling. Nature 406: 536-540,
2000.

4. Castelletti, F.; Donadelli, R.; Banterla, F.; Hildebrandt, F.;
Zipfel, P. F.; Bresin, E.; Otto, E.; Skerka, C.; Renieri, A.; Todeschini,
M.; Caprioli, J.; Caruso, M. R.; Artuso, R.; Remuzzi, G.; Noris, M.
: Mutations in FN1 cause glomerulopathy with fibronectin deposits. Proc.
Nat. Acad. Sci. 105: 2538-2543, 2008.

5. Clark, E. A.; Golub, T. R.; Lander, E. S.; Hynes, R. O.: Genomic
analysis of metastasis reveals an essential role for RhoC. Nature 406:
532-535, 2000. Note: Erratum: Nature 411: 974 only, 2001.

6. Clemmensen, I.: Fibronectin and its role in connective tissue
diseases. (Editorial) Europ. J. Clin. Invest. 11: 145-146, 1981.

7. Eun, C. K.; Klinger, H. P.: Human chromosome 11 affects the expression
of fibronectin fibers in human-times-mouse cell hybrids. Cytogenet.
Cell Genet. 27: 57-65, 1980.

8. Gutman, A.; Kornblihtt, A. R.: Identification of a third region
of cell-specific alternative splicing in human fibronectin mRNA. Proc.
Nat. Acad. Sci. 84: 7179-7182, 1987.

9. Henry, I.; Jeanpierre, M.; Weil, D.; Grzeschik, K. H.; Ramirez,
F.; Junien, C.: The structural gene for fibronectin (FN) maps to
2q323-qter. (Abstract) Cytogenet. Cell Genet. 40: 650 only, 1985.

10. Hirano, H.; Yamada, Y.; Sullivan, M.; de Crombrugghe, B.; Pastan,
I.; Yamada, K. M.: Isolation of genomic DNA clones spanning the entire
fibronectin gene. Proc. Nat. Acad. Sci. 80: 46-50, 1983.

11. Jhanwar, S. C.; Jensen, J. T.; Kaelbling, M.; Chaganti, R. S.
K.; Klinger, H. P.: In situ localization of human fibronectin (FN)
genes to chromosome regions 2p14-p16, 2q34-q36, and 11q12.1-q13.5
in germ line cells, but to chromosome 2 sites only in somatic cells. Cytogenet.
Cell Genet. 41: 47-53, 1986.

12. Jiang, G.; Giannone, G.; Critchley, D. R.; Fukumoto, E.; Sheetz,
M. P.: Two-piconewton slip bond between fibronectin and the cytoskeleton
depends on talin. Nature 424: 334-337, 2003.

13. Koch, G. A.; Schoen, R. C.; Klebe, R. J.; Shows, T. B.: Assignment
of a fibronectin gene to human chromosome 2 using monoclonal antibodies. Exp.
Cell Res. 141: 293-302, 1982.

14. Kornblihtt, A. R.; Umezawa, K.; Vibe-Pedersen, K.; Baralle, F.
E.: Primary structure of human fibronectin: differential splicing
may generate at least 10 polypeptides from a single gene. EMBO J. 4:
1755-1759, 1985.

15. Kornblihtt, A. R.; Vibe-Pedersen, K.; Baralle, F. E.: Human fibronectin:
molecular cloning evidence for two mRNA species differing by an internal
segment coding for a structural domain. EMBO J. 3: 221-226, 1984.

16. Kornblihtt, A. R.; Vibe-Pedersen, K.; Baralle, F. E.: Isolation
and characterization of cDNA clones for human and bovine fibronectins. Proc.
Nat. Acad. Sci. 80: 3218-3222, 1983.

17. Kurkinen, M.; Vartio, T.; Vaheri, A.: Polypeptides of human plasma
fibronectin are similar but not identical. Biochim. Biophys. Acta 624:
490-498, 1980.

18. Liao, Y.-F.; Gotwals, P. J.; Koteliansky, V. E.; Sheppard, D.;
Van De Water, L.: The EIIIA segment of fibronectin is a ligand for
integrins alpha-9-beta-1 and alpha-4-beta-1 providing a novel mechanism
for regulating cell adhesion by alternative splicing. J. Biol. Chem. 277:
14467-14474, 2002.

19. Matsunaga, T.; Takemoto, N.; Sato, T.; Takimoto, R.; Tanaka, I.;
Fujimi, A.; Akiyama, T.; Kuroda, H.; Kawano, Y.; Kobune, M.; Kato,
J.; Hirayama, Y.; Sakamaki, S.; Kohda, K.; Miyake, K.; Niitsu, Y.
: Interaction between leukemic-cell VLA-4 and stromal fibronectin
is a decisive factor for minimal residual disease of acute myelogenous
leukemia. Nature Med. 9: 1158-1165, 2003. Note: Erratum: Nature
Med. 11: 578 only, 2005.

20. Matsuura, H.; Takio, K.; Titani, K.; Greene, T.; Levery, S. B.;
Salyan, M. E. K.; Hakomori, S.: The oncofetal structure of human
fibronectin defined by monoclonal antibody FDC-6. J. Biol. Chem. 263:
3314-3322, 1988.

21. Mazzucco, G.; Maran, E.; Rollino, C.; Monga, G.: Glomerulonephritis
with organized deposits: a mesangiopathic, not immuno complex-mediated
disease? Hum. Path. 23: 63-68, 1992.

22. McDonagh, J.: Fibronectin: a molecular glue. Arch. Path. Lab.
Med. 105: 393-396, 1981.

23. Mosesson, M. W.; Amrani, D. L.: The structure and biologic activities
of plasma fibronectin. Blood 56: 145-158, 1980.

24. Muro, A. F.; Chauhan, A. K.; Gajovic, S.; Iaconcig, A.; Porro,
F.; Stanta, G.; Baralle, F. E.: Regulated splicing of the fibronectin
EDA exon is essential for proper skin wound healing and normal lifespan. J.
Cell. Biol. 162: 149-160, 2003.

25. Niimi, K.; Tsuru, N.; Uesugi, N.; Takebayashi, S.: Fibronectin
glomerulopathy with nephrotic syndrome in a 3-year-old male. Pediat.
Nephrol. 17: 363-366, 2002.

26. Odermatt, E.; Tamkun, J. W.; Hynes, R. O.: Repeating modular
structure of the fibronectin gene: relationship to protein structure
and subunit variation. Proc. Nat. Acad. Sci. 82: 6571-6575, 1985.

27. Owerbach, D.; Doyle, D.; Shows, T. B.: Genetics of the large,
external, transformation-sensitive (LETS) protein: assignment of a
gene coding for expression of LETS to human chromosome 8. Proc. Nat.
Acad. Sci. 75: 5640-5644, 1978.

28. Prowse, K. R.; Tricoli, J. V.; Klebe, R. J.; Shows, T. B.: Assignment
of the human fibronectin structural gene to chromosome 2. Cytogenet.
Cell Genet. 41: 42-46, 1986.

29. Rennard, S. I.; Church, R. L.; Rohrbach, D. H.; Shupp, D. E.;
Abe, S.; Hewitt, A. T.; Murray, J. C.; Martin, G. R.: Localization
of the human fibronectin (FN) gene on chromosome 8 by a specific enzyme
immunoassay. Biochem. Genet. 19: 551-566, 1981.

30. Ridley, A.: Molecular switches in metastasis. Nature 406: 466-467,
2000.

31. Sakai, T.; Johnson, K. J.; Murozono, M.; Sakai, K.; Magnuson,
M. A.; Wieloch, T.; Cronberg, T.; Isshiki, A.; Erickson, H. P.; Fassler,
R.: Plasma fibronectin supports neuronal survival and reduces brain
injury following transient focal cerebral ischemia but is not essential
for skin-wound healing and hemostasis. Nature Med. 7: 324-330, 2001.

32. Sakai, T.; Larsen, M.; Yamada, K. M.: Fibronectin requirement
in branching morphogenesis. Nature 423: 876-881, 2003.

33. Schwarz-Linek, U.; Werner, J. M.; Pickford, A. R.; Gurusiddappa,
S.; Kim, J. H.; Pilka, E. S.; Briggs, J. A. G.; Gough, T. S.; Hook,
M.; Campbell, I. D.; Potts, J. R.: Pathogenic bacteria attach to
human fibronectin through a tandem beta-zipper. Nature 423: 177-181,
2003.

34. Sekiguchi, K.; Klos, A. M.; Kurachi, K.; Yoshitake, S.; Hakomori,
S.: Human liver fibronectin complementary DNAs: identification of
two different messenger RNAs possibly encoding the alpha and beta
subunits of plasma fibronectin. Biochemistry 25: 4936-4941, 1986.

35. Skow, L. C.; Adkison, L.; Womack, J. E.; Beamer, W. G.; Taylor,
B. A.: Mapping of the mouse fibronectin gene (Fn-1) to chromosome
1: conservation of the Idh-1--Cryg--Fn-1 synteny group in mammals. Genomics 1:
283-286, 1987.

36. Smith, M.; Gold, L. I.; Pearlstein, E.; Krinsky, A.: Expression
of mouse and human fibronectin in hybrid cells. (Abstract) Cytogenet.
Cell Genet. 25: 205 only, 1979.

37. Smith, M.; Krinsky, A. M.; Arredondo-Vega, F. X.; Pearlstein,
E.: Production of soluble fibronectin by RAG x human fibroblast hybrids.
(Abstract) Cytogenet. Cell Genet. 32: 318 only, 1982.

38. Strom, E. H.; Fanfi, G.; Krapf, R.; Abt, A. B.; Mazzucco, G.;
Monga, G.; Gloor, F.; Neuweiler, J.; Riess, R.; Stosiek, P.; Hebert,
L. A.; Sedmak, D. D.; Gudat, F.; Mihatsch, M. J.: Glomerulopathy
associated with predominant fibronectin deposits: a newly recognized
hereditary disease. Kidney Intern. 48: 163-170, 1995.

39. Wu, B.-L.; Milunsky, A.; Wyandt, H.; Hoth, C.; Baldwin, C.; Skare,
J.: In situ hybridization applied to Waardenburg syndrome. Cytogenet.
Cell Genet. 63: 29-32, 1993.

40. Zardi, L.; Cianfriglia, M.; Balza, E.; Carnemolla, B.; Siri, A.;
Croce, C. M.: Species-specific monoclonal antibodies in the assignment
of the gene for human fibronectin to chromosome 2. EMBO J. 1: 929-933,
1982.

41. Zardi, L.; Siri, A.; Carnemolla, B.; Santi, L.; Gardner, W. D.;
Hoch, S. O.: Fibronectin: a chromatin-associated protein? Cell 18:
649-657, 1979.

42. Zneimer, S. M.; Womack, J. E.: Regional localization of the fibronectin
and gamma crystallin genes to mouse chromosome 1 by in situ hybridization. Cytogenet.
Cell Genet. 48: 238-241, 1988.

*FIELD* CN
Cassandra L. Kniffin - reorganized: 3/18/2008
Cassandra L. Kniffin - updated: 3/12/2008
Victor A. McKusick - updated: 5/20/2004
Ada Hamosh - updated: 8/26/2003
Ada Hamosh - updated: 7/25/2003
Ada Hamosh - updated: 7/8/2003
Ada Hamosh - updated: 5/9/2003
Ada Hamosh - updated: 4/4/2001
Ada Hamosh - updated: 8/2/2000

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
carol: 01/04/2013
terry: 8/8/2012
carol: 11/22/2011
carol: 7/19/2011
terry: 4/29/2009
carol: 3/18/2008
ckniffin: 3/12/2008
mgross: 5/17/2005
joanna: 2/4/2005
tkritzer: 5/20/2004
alopez: 9/2/2003
alopez: 8/26/2003
terry: 8/26/2003
tkritzer: 7/25/2003
alopez: 7/9/2003
terry: 7/8/2003
alopez: 5/9/2003
terry: 5/9/2003
carol: 1/8/2002
alopez: 4/5/2001
terry: 4/4/2001
alopez: 8/2/2000
terry: 4/30/1999
terry: 6/5/1998
mark: 3/18/1997
warfield: 4/8/1994
pfoster: 4/1/1994
carol: 5/26/1993
supermim: 3/16/1992
carol: 3/4/1992
carol: 8/15/1990

MIM 601894
*RECORD*
*FIELD* NO
601894
*FIELD* TI
#601894 GLOMERULOPATHY WITH FIBRONECTIN DEPOSITS 2; GFND2
;;GLOMERULAR NEPHRITIS, FAMILIAL, WITH FIBRONECTIN DEPOSITS;;
read moreFIBRONECTIN GLOMERULOPATHY
*FIELD* TX
A number sign (#) is used with this entry because glomerulopathy with
fibronectin deposits can be caused by heterozygous mutation in the gene
encoding fibronectin-1 (FN1; 135600).

DESCRIPTION

Glomerulopathy with fibronectin deposits 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. Pathologic examination
shows enlarged glomeruli with mesangial and subendothelial fibrillary
deposits that show strong immunoreactivity to fibronectin (Castelletti
et al., 2008).

For a discussion of genetic heterogeneity of GFND, see 137950.

CLINICAL FEATURES

Mazzucco et al. (1992) described an Italian mother and daughter with
slowly progressive nephrotic syndrome. Proteinuria was first detected at
ages 25 and 11 years, respectively. Renal biopsy from both patients
showed similar glomerular changes, including marked widening of the
mesangial stalk, irregular thickening of the basement membrane, and
presence of mesangial and subendothelial deposits. Electron microscopy
disclosed huge glomerular electron-dense deposits containing 12-nm
fibrils. Immunohistochemical studies showed strong fibronectin staining
in the mesangium and along glomerular basement membranes. Most
glomerular fibronectin was plasma-derived, as shown by specific
monoclonal antibodies. The mother showed a slow decrease of glomerular
function, and a second biopsy performed 8 years after the first
investigation showed scarcely modified glomerular changes, consistent
with an indolent evolution. In a review of the histologic findings of
the mother and daughter reported by Mazzucco et al. (1992), Strom et al.
(1995) stated that the deposits were granular in nature with a few 12-nm
fibrils in the mesangial and subendothelial spaces. In a follow-up of
this family, Castelletti et al. (2008) noted that the 53-year-old mother
had moderately reduced renal function and the 25-year-old daughter had
normal renal function. A paternal aunt of the mother died at 37 years of
nephropathy.

Assmann et al. (1995) reported an affected father and son from the
Netherlands. Low-grade proteinuria and hypertension were discovered in
the father at age 30 years, and proteinuria in the son at age 18. Renal
biopsies from both patients disclosed a distinct form of fibrillary
glomerulonephritis that was characterized by massive deposits of a
homogeneous eosinophilic material in the mesangial and subendothelial
areas. Staining for amyloid was negative, and staining for
immunoglobulins was faint. However, the material stained strongly for
plasma-derived fibronectin. Electron microscopy showed that the
mesangial and subendothelial deposits were composed of irregularly
arranged fibrils or microtubules 10 to 12 nm in diameter. In both
patients, the disorder showed indolent course with hardly any
deterioration of renal function. Assmann et al. (1995) concluded that
fibrillary glomerulonephritis with massive deposits of fibronectin
represents a rare form of familial glomerulonephritis.

Niimi et al. (2002) reported a 3-year-old Japanese boy with proteinuria,
microscopic hematuria, and hypertension. Renal function was intact, but
renal biopsy showed enlarged glomeruli with granular fibronectin
deposits in the peripheral loop and mesangium. There were no immune
deposits and no evidence of systemic disease. Twelve other family
members were subsequently found to have mild hematuria or proteinuria,
but none were biopsied. Renal function in the proband was preserved
during 7 years of follow-up.

INHERITANCE

Autosomal dominant inheritance was supported in 6 affected families
reviewed by Strom et al. (1995). There were affected individuals in 2
generations in 4 of the families, including a father and 4 sons in 1.

MAPPING

By linkage analysis of a large Italian family with GFND2 first reported
by Strom et al. (1995), Castelletti et al. (2008) found linkage to the
FN1 gene on chromosome 2q34 (2-point Z-max = 3.084 for markers D2S128
and D2S2361). Linkage was excluded from the GFND1 locus on 1q32.

MOLECULAR GENETICS

In affected individuals from 6 unrelated families with GFND2,
Castelletti et al. (2008) identified heterozygous mutations in the FN1
gene (135600.0001-135600.0003). Four of the families had previously been
reported by Mazzucco et al. (1992), Strom et al. (1995), Assmann et al.
(1995), and Niimi et al. (2002). Although 3 families shared the same
mutation, there was no evidence for a founder effect. Six (40%) of 15
affected families were found to have FN1 mutations, suggesting genetic
heterogeneity.

*FIELD* RF
1. Assmann, K. J. M.; Koene, R. A. P.; Wetzels, J. F. M.: Familial
glomerulonephritis characterized by massive deposits of fibronectin. Am.
J. Kidney Dis. 25: 781-791, 1995.

2. Castelletti, F.; Donadelli, R.; Banterla, F.; Hildebrandt, F.;
Zipfel, P. F.; Bresin, E.; Otto, E.; Skerka, C.; Renieri, A.; Todeschini,
M.; Caprioli, J.; Caruso, M. R.; Artuso, R.; Remuzzi, G.; Noris, M.
: Mutations in FN1 cause glomerulopathy with fibronectin deposits. Proc.
Nat. Acad. Sci. 105: 2538-2543, 2008.

3. Mazzucco, G.; Maran, E.; Rollino, C.; Monga, G.: Glomerulonephritis
with organized deposits: a mesangiopathic, not immuno complex-mediated
disease? Hum. Path. 23: 63-68, 1992.

4. Niimi, K.; Tsuru, N.; Uesugi, N.; Takebayashi, S.: Fibronectin
glomerulopathy with nephrotic syndrome in a 3-year-old male. Pediat.
Nephrol. 17: 363-366, 2002.

5. Strom, E. H.; Fanfi, G.; Krapf, R.; Abt, A. B.; Mazzucco, G.; Monga,
G.; Gloor, F.; Neuweiler, J.; Riess, R.; Stosiek, P.; Hebert, L. A.;
Sedmak, D. D.; Gudat, F.; Mihatsch, M. J.: Glomerulopathy associated
with predominant fibronectin deposits: a newly recognized hereditary
disease. Kidney Int. 48: 163-170, 1995.

*FIELD* CS
INHERITANCE:
Autosomal dominant

CARDIOVASCULAR:
[Vascular];
Hypertension due to renal disease

GENITOURINARY:
[Kidneys];
Proteinuria;
Microscopic hematuria;
Nephrotic syndrome;
Renal failure;
End-stage renal disease;
Enlarged glomeruli;
Mesangial and subendothelial granular or fibrillar deposits which
show immunoreactivity to fibronectin

MISCELLANEOUS:
Onset of proteinuria in the second to fourth decades;
Onset of end-stage renal disease 15 to 20 years after onset;
Slow progression

MOLECULAR BASIS:
Caused by mutation in the fibronectin 1 gene (FN1, 135600.0001)

*FIELD* CN
Cassandra L. Kniffin - revised: 3/12/2008

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 07/20/2012
joanna: 7/20/2012
ckniffin: 3/12/2008

*FIELD* CN
Cassandra L. Kniffin - reorganized: 3/18/2008
Cassandra L. Kniffin - updated: 3/12/2008
Victor A. McKusick - updated: 9/28/2000
Victor A. McKusick - updated: 1/26/1999
Victor A. McKusick - updated: 1/11/1999

*FIELD* CD
Victor A. McKusick: 6/23/1997

*FIELD* ED
terry: 07/25/2011
carol: 7/19/2011
carol: 3/18/2008
ckniffin: 3/12/2008
joanna: 3/18/2004
carol: 11/25/2001
mcapotos: 10/17/2000
mcapotos: 10/13/2000
terry: 9/28/2000
carol: 1/29/1999
terry: 1/26/1999
carol: 1/18/1999
terry: 1/11/1999
jenny: 6/27/1997
alopez: 6/26/1997
jenny: 6/23/1997