ID FBLN1_HUMAN Reviewed; 703 AA. AC P23142; B0QY42; B1AHL4; P23143; P23144; P37888; Q5TIC4; Q8TBH8; Q9HBQ5; AC Q9UC21; Q9UGR4; Q9UH41; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 4. DT 27-NOV-2024, entry version 258. DE RecName: Full=Fibulin-1; DE Short=FIBL-1; DE Flags: Precursor; GN Name=FBLN1; ORFNames=PP213; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), AND VARIANT ARG-141. RX PubMed=2269669; DOI=10.1083/jcb.111.6.3155; RA Argraves W.S., Tran H., Burgess W.H., Dickerson K.; RT "Fibulin is an extracellular matrix and plasma glycoprotein with repeated RT domain structure."; RL J. Cell Biol. 111:3155-3164(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), TISSUE SPECIFICITY, VARIANT RP ARG-141, AND INTERACTION WITH FN1 AND FGB. RX PubMed=9106159; DOI=10.1016/s0945-053x(97)90021-4; RA Tran H., Mattei M.-G., Godyna S., Argraves W.S.; RT "Human fibulin-1D: molecular cloning, expression and similarity with S1-5 RT protein, a new member of the fibulin gene family."; RL Matrix Biol. 15:479-493(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), AND VARIANTS ARG-141 AND ARG-695. RX PubMed=10318851; DOI=10.1074/jbc.274.20.14295; RA Krichevsky A.M., Metzer E., Rosen H.; RT "Translational control of specific genes during differentiation of HL-60 RT cells."; RL J. Biol. Chem. 274:14295-14305(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C), AND VARIANT ARG-141. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C), AND VARIANT ARG-141. RC TISSUE=Brain; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26. RX PubMed=11829738; DOI=10.1042/0264-6021:3620041; RA Castoldi M., Chu M.-L.; RT "Structural and functional characterization of the human and mouse fibulin- RT 1 gene promoters: role of Sp1 and Sp3."; RL Biochem. J. 362:41-50(2002). RN [8] RP PROTEIN SEQUENCE OF 30-44. RX PubMed=2527614; DOI=10.1016/0092-8674(89)90097-4; RA Argraves W.S., Dickerson K., Burgess W.H., Ruoslahti E.; RT "Fibulin, a novel protein that interacts with the fibronectin receptor beta RT subunit cytoplasmic domain."; RL Cell 58:623-629(1989). RN [9] RP SELF-ASSOCIATION, AND INTERACTION WITH FN1. RX PubMed=1400330; DOI=10.1016/s0021-9258(19)88674-x; 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 [10] RP POSSIBLE FUNCTION. RX PubMed=7534784; DOI=10.1177/43.4.7534784; RA Roark E.F., Keene D.R., Haudenschild C.C., Godyna S., Little C.D., RA Argraves W.S.; RT "The association of human fibulin-1 with elastic fibers: an RT immunohistological, ultrastructural, and RNA study."; RL J. Histochem. Cytochem. 43:401-411(1995). RN [11] RP INTERACTION WITH FGB. RX PubMed=7642629; DOI=10.1074/jbc.270.33.19458; RA Tran H., Tanaka A., Litvinovich S.V., Medved L.V., Haudenschild C.C., RA Argraves W.S.; RT "The interaction of fibulin-1 with fibrinogen. A potential role in RT hemostasis and thrombosis."; RL J. Biol. Chem. 270:19458-19464(1995). RN [12] RP DEVELOPMENTAL STAGE. RX PubMed=8737292; DOI=10.1007/bf02331415; RA Miosge N., Gotz W., Sasaki T., Chu M.-L., Timpl R., Herken R.; RT "The extracellular matrix proteins fibulin-1 and fibulin-2 in the early RT human embryo."; RL Histochem. J. 28:109-116(1996). RN [13] RP INDUCTION. RX PubMed=8552629; DOI=10.1073/pnas.93.1.316; RA Clinton G.M., Rougeot C., Derancourt J., Roger P., Defrenne A., Godyna S., RA Argraves W.S., Rochefort H.; RT "Estrogens increase the expression of fibulin-1, an extracellular matrix RT protein secreted by human ovarian cancer cells."; RL Proc. Natl. Acad. Sci. U.S.A. 93:316-320(1996). RN [14] RP CALCIUM-BINDING, SELF-ASSOCIATION, AND FN1-BINDING SITES. RX PubMed=9278415; DOI=10.1074/jbc.272.36.22600; RA Tran H., VanDusen W.J., Argraves W.S.; RT "The self-association and fibronectin-binding sites of fibulin-1 map to RT calcium-binding epidermal growth factor-like domains."; RL J. Biol. Chem. 272:22600-22606(1997). RN [15] RP ROLE IN TUMOR FORMATION AND INVASION. RX PubMed=9393974; DOI=10.1038/sj.onc.1201385; RA Qing J., Maher V.M., Tran H., Argraves W.S., Dunstan R.W., McCormick J.J.; RT "Suppression of anchorage-independent growth and matrigel invasion and RT delayed tumor formation by elevated expression of fibulin-1D in human RT fibrosarcoma-derived cell lines."; RL Oncogene 15:2159-2168(1997). RN [16] RP INDUCTION. RX PubMed=9811350; DOI=10.1016/s0002-9440(10)65746-x; RA Roger P., Pujol P., Lucas A., Baldet P., Rochefort H.; RT "Increased immunostaining of fibulin-1, an estrogen-regulated protein in RT the stroma of human ovarian epithelial tumors."; RL Am. J. Pathol. 153:1579-1588(1998). RN [17] RP ROLE IN TUMOR FORMATION AND INVASION. RX PubMed=9466671; RX DOI=10.1002/(sici)1097-0215(19980209)75:4<654::aid-ijc26>3.0.co;2-7; RA Hayashido Y., Lucas A., Rougeot C., Godyna S., Argraves W.S., Rochefort H.; RT "Estradiol and fibulin-1 inhibit motility of human ovarian- and breast- RT cancer cells induced by fibronectin."; RL Int. J. Cancer 75:654-658(1998). RN [18] RP INTERACTION WITH CCN3. RX PubMed=9927660; DOI=10.1073/pnas.96.3.869; RA Perbal B., Martinerie C., Sainson R., Werner M., He B., Roizman B.; RT "The C-terminal domain of the regulatory protein NOVH is sufficient to RT promote interaction with fibulin 1C: a clue for a role of NOVH in cell- RT adhesion signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 96:869-874(1999). RN [19] RP ROLE IN CELL ADHESION AND MOTILITY. RX PubMed=11792823; DOI=10.1242/jcs.114.24.4587; RA Twal W.O., Czirok A., Hegedus B., Knaak C., Chintalapudi M.R., Okagawa H., RA Sugi Y., Argraves W.S.; RT "Fibulin-1 suppression of fibronectin-regulated cell adhesion and RT motility."; RL J. Cell Sci. 114:4587-4598(2001). RN [20] RP INTERACTION WITH APP. RX PubMed=11238726; DOI=10.1046/j.1471-4159.2001.00144.x; RA Ohsawa I., Takamura C., Kohsaka S.; RT "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein RT and modulates its physiological function."; RL J. Neurochem. 76:1411-1420(2001). RN [21] RP INTERACTION WITH HIGH-RISK HUMAN PAPILLOMAVIRUSES E6 PROTEIN (MICROBIAL RP INFECTION), AND INHIBITION OF E6-MEDIATED TRANSFORMATION. RX PubMed=12200142; DOI=10.1016/s0006-291x(02)02041-7; RA Du M., Fan X., Hong E., Chen J.J.; RT "Interaction of oncogenic papillomavirus E6 proteins with fibulin-1."; RL Biochem. Biophys. Res. Commun. 296:962-969(2002). RN [22] RP CHROMOSOMAL TRANSLOCATION WITH RASSF8. RX PubMed=11836357; DOI=10.1136/jmg.39.2.98; RA Debeer P., Schoenmakers E.F.P.M., Twal W.O., Argraves W.S., De Smet L., RA Fryns J.-P., Van De Ven W.J.M.; RT "The fibulin-1 gene (FBLN1) is disrupted in a t(12;22) associated with a RT complex type of synpolydactyly."; RL J. Med. Genet. 39:98-104(2002). RN [23] RP INDUCTION. RX PubMed=11850827; DOI=10.1038/sj.onc.1205171; RA Moll F., Katsaros D., Lazennec G., Hellio N., Roger P., Giacalone P.-L., RA Chalbos D., Maudelonde T., Rochefort H., Pujol P.; RT "Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer RT cells."; RL Oncogene 21:1097-1107(2002). RN [24] RP ASSOCIATION WITH BREAST CANCER. RX PubMed=12644824; DOI=10.1038/sj.bjc.6600802; RA Greene L.M., Twal W.O., Duffy M.J., McDermott E.W., Hill A.D., RA O'Higgins N.J., McCann A.H., Dervan P.A., Argraves W.S., Gallagher W.M.; RT "Elevated expression and altered processing of fibulin-1 protein in human RT breast cancer."; RL Br. J. Cancer 88:871-878(2003). RN [25] RP GLYCOSYLATION AT ASN-98. 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., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [27] RP VARIANT PHE-397. RX PubMed=24084572; DOI=10.1038/ejhg.2013.210; RA Bohlega S., Al-Ajlan H., Al-Saif A.; RT "Mutation of fibulin-1 causes a novel syndrome involving the central RT nervous system and connective tissues."; RL Eur. J. Hum. Genet. 22:640-643(2014). CC -!- FUNCTION: Incorporated into fibronectin-containing matrix fibers. May CC play a role in cell adhesion and migration along protein fibers within CC the extracellular matrix (ECM). Could be important for certain CC developmental processes and contribute to the supramolecular CC organization of ECM architecture, in particular to those of basement CC membranes. Has been implicated in a role in cellular transformation and CC tumor invasion, it appears to be a tumor suppressor. May play a role in CC haemostasis and thrombosis owing to its ability to bind fibrinogen and CC incorporate into clots. Could play a significant role in modulating the CC neurotrophic activities of APP, particularly soluble APP. CC {ECO:0000269|PubMed:11792823, ECO:0000269|PubMed:9393974, CC ECO:0000269|PubMed:9466671}. CC -!- SUBUNIT: Homomultimerizes and interacts with various extracellular CC matrix components such as FN1, LAMA1, LAMA2, NID, ACAN, CSPG2 and type CC IV collagen. Interacts also with APP and FGB. Interacts with FBLN7 (By CC similarity). Interacts with CCN3 (PubMed:9927660). {ECO:0000250, CC ECO:0000269|PubMed:9927660}. CC -!- SUBUNIT: (Microbial infection) Interacts with human papillomavirus/HPV CC type 16, 18 and 31 proteins E6. {ECO:0000269|PubMed:12200142}. CC -!- INTERACTION: CC P23142-4; Q9UIJ7: AK3; NbExp=3; IntAct=EBI-11956479, EBI-3916527; CC P23142-4; Q5BKT4: ALG10; NbExp=3; IntAct=EBI-11956479, EBI-13064220; CC P23142-4; P05067: APP; NbExp=3; IntAct=EBI-11956479, EBI-77613; CC P23142-4; P54252: ATXN3; NbExp=3; IntAct=EBI-11956479, EBI-946046; CC P23142-4; Q9UKJ5: CHIC2; NbExp=3; IntAct=EBI-11956479, EBI-741528; CC P23142-4; Q02930-3: CREB5; NbExp=3; IntAct=EBI-11956479, EBI-10192698; CC P23142-4; P42830: CXCL5; NbExp=3; IntAct=EBI-11956479, EBI-12175919; CC P23142-4; P49639: HOXA1; NbExp=3; IntAct=EBI-11956479, EBI-740785; CC P23142-4; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-11956479, EBI-1052037; CC P23142-4; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-11956479, EBI-12196745; CC P23142-4; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-11956479, EBI-11962058; CC P23142-4; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-11956479, EBI-10245913; CC P23142-4; Q5T751: LCE1C; NbExp=3; IntAct=EBI-11956479, EBI-12224199; CC P23142-4; Q5T754: LCE1F; NbExp=3; IntAct=EBI-11956479, EBI-11958008; CC P23142-4; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-11956479, EBI-9394625; CC P23142-4; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-11956479, EBI-11955689; CC P23142-4; Q96FE5: LINGO1; NbExp=3; IntAct=EBI-11956479, EBI-719955; CC P23142-4; Q8IXW0: LMNTD2; NbExp=3; IntAct=EBI-11956479, EBI-12028858; CC P23142-4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11956479, EBI-16439278; CC P23142-4; P52815: MRPL12; NbExp=3; IntAct=EBI-11956479, EBI-358272; CC P23142-4; Q02548: PAX5; NbExp=3; IntAct=EBI-11956479, EBI-296331; CC P23142-4; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-11956479, EBI-3907610; CC P23142-4; O43609: SPRY1; NbExp=3; IntAct=EBI-11956479, EBI-3866665; CC P23142-4; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-11956479, EBI-5235829; CC P23142-4; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-11956479, EBI-12817837; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=D; CC IsoId=P23142-1; Sequence=Displayed; CC Name=A; CC IsoId=P23142-2; Sequence=VSP_001383; CC Name=B; CC IsoId=P23142-3; Sequence=VSP_001384; CC Name=C; CC IsoId=P23142-4; Sequence=VSP_001385; CC -!- TISSUE SPECIFICITY: Isoform A and isoform B are only expressed in CC placenta. Isoform C and isoform D are expressed in a variety of tissues CC and cultured cells. {ECO:0000269|PubMed:9106159}. CC -!- DEVELOPMENTAL STAGE: Widely expressed during embryonic development. CC Prominent in the matrix of the leptomeningeal anlage, in basement CC membranes of the neuroepithelium and the perineurium of peripheral CC nerves. In embryos of gestational week (gw) 4, staining was observed in CC the early mesenchymal bone anlagen. In gw 6.5 and 8, all perichondrial CC structures showed expression but the chondrocytes themselves showed no CC staining. In gw 10, expression is prominent in the interterritorial CC matrix surrounding the hypertrophic chondrocytes. CC {ECO:0000269|PubMed:8737292}. CC -!- INDUCTION: Expression increased by estrogen in ovarian cancer cells. CC {ECO:0000269|PubMed:11850827, ECO:0000269|PubMed:8552629, CC ECO:0000269|PubMed:9811350}. CC -!- DISEASE: Note=A chromosomal aberration involving FBLN1 is found in a CC complex type of synpolydactyly referred to as 3/3-prime/4 CC synpolydactyly associated with metacarpal and metatarsal synostoses. CC Reciprocal translocation t(12;22)(p11.2;q13.3) with RASSF8. Fibroblasts CC derived from a patient with synpolydactyly displayed alterations in the CC level of isoform D splice variant incorporated into the ECM and CC secreted into the conditioned culture medium. By contrast, the CC expression of isoform C was not perturbed in the patients fibroblasts. CC Furthermore, no aberrant polypeptides were detected in extracts of CC cultured patients fibroblasts. The translocation t(12;22) may result in CC haploinsufficiency of the isoform D splice variant, which could lead to CC the observed limb malformation. {ECO:0000269|PubMed:11836357}. CC -!- DISEASE: Note=Elevated expression and altered processing of FBLN1 CC protein is associated with human breast cancer. CC {ECO:0000269|PubMed:12644824}. CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG17241.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44462/FBLN1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X53741; CAA37770.1; -; mRNA. DR EMBL; X53742; CAA37771.1; -; mRNA. DR EMBL; X53743; CAA37772.1; -; mRNA. DR EMBL; U01244; AAB17099.1; -; mRNA. DR EMBL; AF126110; AAK37822.1; -; mRNA. DR EMBL; AF217999; AAG17241.1; ALT_FRAME; mRNA. DR EMBL; AL021391; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z95331; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z98047; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022497; AAH22497.1; -; mRNA. DR EMBL; AY040589; AAK82945.1; -; Genomic_DNA. DR CCDS; CCDS14067.1; -. [P23142-1] DR CCDS; CCDS14068.1; -. [P23142-3] DR CCDS; CCDS14069.1; -. [P23142-4] DR CCDS; CCDS43028.1; -. [P23142-2] DR PIR; C36346; C36346. DR RefSeq; NP_001987.2; NM_001996.3. [P23142-4] DR RefSeq; NP_006476.2; NM_006485.3. [P23142-3] DR RefSeq; NP_006477.2; NM_006486.2. [P23142-1] DR RefSeq; NP_006478.2; NM_006487.2. [P23142-2] DR AlphaFoldDB; P23142; -. DR BioGRID; 108486; 133. DR IntAct; P23142; 106. DR MINT; P23142; -. DR STRING; 9606.ENSP00000331544; -. DR GlyConnect; 1244; 8 N-Linked glycans (2 sites). DR GlyCosmos; P23142; 4 sites, 9 glycans. DR GlyGen; P23142; 9 sites, 50 N-linked glycans (2 sites), 3 O-linked glycans (6 sites). DR iPTMnet; P23142; -. DR PhosphoSitePlus; P23142; -. DR BioMuta; FBLN1; -. DR DMDM; 215274249; -. DR CPTAC; non-CPTAC-1123; -. DR jPOST; P23142; -. DR MassIVE; P23142; -. DR PaxDb; 9606-ENSP00000331544; -. DR PeptideAtlas; P23142; -. DR ProteomicsDB; 2960; -. DR ProteomicsDB; 54057; -. [P23142-1] DR ProteomicsDB; 54058; -. [P23142-2] DR ProteomicsDB; 54059; -. [P23142-3] DR ProteomicsDB; 54060; -. [P23142-4] DR Pumba; P23142; -. DR Antibodypedia; 886; 325 antibodies from 33 providers. DR DNASU; 2192; -. DR Ensembl; ENST00000262722.11; ENSP00000262722.7; ENSG00000077942.19. [P23142-4] DR Ensembl; ENST00000327858.11; ENSP00000331544.6; ENSG00000077942.19. [P23142-1] DR Ensembl; ENST00000340923.9; ENSP00000342212.5; ENSG00000077942.19. [P23142-2] DR Ensembl; ENST00000442170.6; ENSP00000393812.2; ENSG00000077942.19. [P23142-3] DR GeneID; 2192; -. DR KEGG; hsa:2192; -. DR MANE-Select; ENST00000327858.11; ENSP00000331544.6; NM_006486.3; NP_006477.3. DR UCSC; uc003bgg.2; human. [P23142-1] DR AGR; HGNC:3600; -. DR CTD; 2192; -. DR DisGeNET; 2192; -. DR GeneCards; FBLN1; -. DR HGNC; HGNC:3600; FBLN1. DR HPA; ENSG00000077942; Tissue enhanced (choroid). DR MalaCards; FBLN1; -. DR MIM; 135820; gene. DR MIM; 608180; phenotype. DR neXtProt; NX_P23142; -. DR OpenTargets; ENSG00000077942; -. DR Orphanet; 404451; FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome. DR Orphanet; 295197; Synpolydactyly type 2. DR PharmGKB; PA28013; -. DR VEuPathDB; HostDB:ENSG00000077942; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000156642; -. DR HOGENOM; CLU_004826_1_1_1; -. DR InParanoid; P23142; -. DR OMA; KCAEGEL; -. DR OrthoDB; 19806at2759; -. DR PhylomeDB; P23142; -. DR TreeFam; TF317514; -. DR PathwayCommons; P23142; -. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR SignaLink; P23142; -. DR BioGRID-ORCS; 2192; 10 hits in 1147 CRISPR screens. DR ChiTaRS; FBLN1; human. DR GeneWiki; FBLN1; -. DR GenomeRNAi; 2192; -. DR Pharos; P23142; Tbio. DR PRO; PR:P23142; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P23142; protein. DR Bgee; ENSG00000077942; Expressed in endocervix and 192 other cell types or tissues. DR ExpressionAtlas; P23142; baseline and differential. DR GO; GO:0005604; C:basement membrane; IEA:Ensembl. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0071953; C:elastic fiber; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005201; F:extracellular matrix structural constituent; IDA:UniProtKB. DR GO; GO:0070051; F:fibrinogen binding; IPI:UniProtKB. DR GO; GO:0001968; F:fibronectin binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0016504; F:peptidase activator activity; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB. DR GO; GO:0072378; P:blood coagulation, fibrin clot formation; IDA:UniProtKB. DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:2000146; P:negative regulation of cell motility; IDA:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IDA:UniProtKB. DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB. DR GO; GO:1904188; P:negative regulation of transformation of host cell by virus; IMP:UniProtKB. DR GO; GO:0071635; P:negative regulation of transforming growth factor beta production; IDA:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:1904237; P:positive regulation of substrate-dependent cell migration, cell attachment to substrate; IDA:UniProtKB. DR CDD; cd00017; ANATO; 2. DR CDD; cd00054; EGF_CA; 4. DR FunFam; 2.10.25.10:FF:000341; Fibulin 2; 1. DR FunFam; 2.10.25.10:FF:000078; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000104; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000108; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000139; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000150; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000241; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000257; Fibulin-1; 1. DR FunFam; 2.10.25.10:FF:000010; Pro-epidermal growth factor; 1. DR Gene3D; 2.10.25.10; Laminin; 9. DR InterPro; IPR000020; Anaphylatoxin/fibulin. DR InterPro; IPR026823; cEGF. DR InterPro; IPR050751; ECM_structural_protein. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR017048; Fibulin-1. DR InterPro; IPR055088; Fibulin_C. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR049883; NOTCH1_EGF-like. DR PANTHER; PTHR24034; EGF-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24034:SF166; VACUOLAR-SORTING RECEPTOR 1; 1. DR Pfam; PF01821; ANATO; 2. DR Pfam; PF12662; cEGF; 3. DR Pfam; PF07645; EGF_CA; 4. DR Pfam; PF22914; Fibulin_C; 1. DR PIRSF; PIRSF036313; Fibulin-1; 1. DR SMART; SM00104; ANATO; 3. DR SMART; SM00181; EGF; 9. DR SMART; SM00179; EGF_CA; 8. DR SUPFAM; SSF57196; EGF/Laminin; 3. DR SUPFAM; SSF57184; Growth factor receptor domain; 2. DR PROSITE; PS01177; ANAPHYLATOXIN_1; 3. DR PROSITE; PS01178; ANAPHYLATOXIN_2; 3. DR PROSITE; PS00010; ASX_HYDROXYL; 4. DR PROSITE; PS01186; EGF_2; 3. DR PROSITE; PS50026; EGF_3; 5. DR PROSITE; PS01187; EGF_CA; 8. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Chromosomal rearrangement; KW Direct protein sequencing; Disulfide bond; EGF-like domain; KW Extracellular matrix; Glycoprotein; Host-virus interaction; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..29 FT /evidence="ECO:0000269|PubMed:2527614" FT CHAIN 30..703 FT /note="Fibulin-1" FT /id="PRO_0000007563" FT DOMAIN 36..76 FT /note="Anaphylatoxin-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022" FT DOMAIN 77..111 FT /note="Anaphylatoxin-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022" FT DOMAIN 112..144 FT /note="Anaphylatoxin-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022" FT DOMAIN 176..215 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 216..261 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 262..307 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 308..355 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 356..398 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 399..440 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 441..480 FT /note="EGF-like 7; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 481..524 FT /note="EGF-like 8; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 525..578 FT /note="EGF-like 9; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 356..440 FT /note="Self-association and FN1-binding; calcium is FT necessary for homotypic binding, but not for heterotypic FT binding" FT CARBOHYD 98 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:19139490" FT CARBOHYD 535 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 539 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 36..61 FT /evidence="ECO:0000250" FT DISULFID 37..68 FT /evidence="ECO:0000250" FT DISULFID 50..69 FT /evidence="ECO:0000250" FT DISULFID 78..109 FT /evidence="ECO:0000250" FT DISULFID 91..110 FT /evidence="ECO:0000250" FT DISULFID 112..136 FT /evidence="ECO:0000250" FT DISULFID 113..143 FT /evidence="ECO:0000250" FT DISULFID 126..144 FT /evidence="ECO:0000250" FT DISULFID 180..190 FT /evidence="ECO:0000250" FT DISULFID 186..199 FT /evidence="ECO:0000250" FT DISULFID 201..214 FT /evidence="ECO:0000250" FT DISULFID 220..233 FT /evidence="ECO:0000250" FT DISULFID 227..242 FT /evidence="ECO:0000250" FT DISULFID 248..260 FT /evidence="ECO:0000250" FT DISULFID 266..279 FT /evidence="ECO:0000250" FT DISULFID 273..288 FT /evidence="ECO:0000250" FT DISULFID 294..306 FT /evidence="ECO:0000250" FT DISULFID 312..325 FT /evidence="ECO:0000250" FT DISULFID 319..334 FT /evidence="ECO:0000250" FT DISULFID 341..354 FT /evidence="ECO:0000250" FT DISULFID 360..373 FT /evidence="ECO:0000250" FT DISULFID 367..382 FT /evidence="ECO:0000250" FT DISULFID 384..397 FT /evidence="ECO:0000250" FT DISULFID 403..415 FT /evidence="ECO:0000250" FT DISULFID 411..424 FT /evidence="ECO:0000250" FT DISULFID 426..439 FT /evidence="ECO:0000250" FT DISULFID 445..454 FT /evidence="ECO:0000250" FT DISULFID 450..463 FT /evidence="ECO:0000250" FT DISULFID 465..479 FT /evidence="ECO:0000250" FT DISULFID 485..498 FT /evidence="ECO:0000250" FT DISULFID 494..507 FT /evidence="ECO:0000250" FT DISULFID 509..523 FT /evidence="ECO:0000250" FT DISULFID 529..542 FT /evidence="ECO:0000250" FT DISULFID 536..551 FT /evidence="ECO:0000250" FT DISULFID 556..577 FT /evidence="ECO:0000250" FT VAR_SEQ 567..703 FT /note="Missing (in isoform A)" FT /evidence="ECO:0000303|PubMed:2269669" FT /id="VSP_001383" FT VAR_SEQ 567..703 FT /note="LQQEKTDTVRCIKSCRPNDVTCVFDPVHTISHTVISLPTFREFTRPEEIIFL FT RAITPPHPASQANIIFDITEGNLRDSFDIIKRYMDGMTVGVVRQVRPIVGPFHAVLKLE FT MNYVVGGVVSHRNVVNVHIFVSEYWF -> QKSKKGRQNTPAGSSKEDCRVLPWKQGLE FT DTHLDA (in isoform B)" FT /evidence="ECO:0000303|PubMed:2269669" FT /id="VSP_001384" FT VAR_SEQ 567..703 FT /note="LQQEKTDTVRCIKSCRPNDVTCVFDPVHTISHTVISLPTFREFTRPEEIIFL FT RAITPPHPASQANIIFDITEGNLRDSFDIIKRYMDGMTVGVVRQVRPIVGPFHAVLKLE FT MNYVVGGVVSHRNVVNVHIFVSEYWF -> RCERLPCHENRECSKLPLRITYYHLSFPT FT NIQAPAVVFRMGPSSAVPGDSMQLAITGGNEEGFFTTRKVSPHSGVVALTKPVPEPRDL FT LLTVKMDLSRHGTVSSFVAKLFIFVSAEL (in isoform C)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15498874, ECO:0000303|PubMed:2269669" FT /id="VSP_001385" FT VARIANT 141 FT /note="Q -> R (in dbSNP:rs136730)" FT /evidence="ECO:0000269|PubMed:10318851, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15498874, FT ECO:0000269|PubMed:2269669, ECO:0000269|PubMed:9106159" FT /id="VAR_015650" FT VARIANT 397 FT /note="C -> F (found in a family with syndactyly, FT undescended testes, delayed motor milestones, intellectual FT disability and signs of brain atrophy; uncertain FT significance; dbSNP:rs397509432)" FT /evidence="ECO:0000269|PubMed:24084572" FT /id="VAR_072739" FT VARIANT 509 FT /note="C -> S (in dbSNP:rs1802787)" FT /id="VAR_055720" FT VARIANT 695 FT /note="H -> R (in dbSNP:rs13268)" FT /evidence="ECO:0000269|PubMed:10318851" FT /id="VAR_055721" FT CONFLICT 13 FT /note="P -> Q (in Ref. 6; AAH22497)" FT /evidence="ECO:0000305" FT CONFLICT 36 FT /note="C -> S (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 41..42 FT /note="HR -> SH (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 521 FT /note="R -> S (in Ref. 6; AAH22497)" FT /evidence="ECO:0000305" FT CONFLICT 548 FT /note="G -> A (in Ref. 1; CAA37770/CAA37771/CAA37772, 2; FT AAB17099 and 3; AAK37822)" FT /evidence="ECO:0000305" FT CONFLICT P23142-4:650 FT /note="E -> K (in Ref. 4; AAG17241)" FT /evidence="ECO:0000305" FT CONFLICT P23142-4:662 FT /note="L -> F (in Ref. 4; AAG17241)" FT /evidence="ECO:0000305" FT CONFLICT P23142-4:680..682 FT /note="SAE -> FAK (in Ref. 4; AAG17241)" FT /evidence="ECO:0000305" SQ SEQUENCE 703 AA; 77214 MW; 302F7ED2DF34CA71 CRC64; MERAAPSRRV PLPLLLLGGL ALLAAGVDAD VLLEACCADG HRMATHQKDC SLPYATESKE CRMVQEQCCH SQLEELHCAT GISLANEQDR CATPHGDNAS LEATFVKRCC HCCLLGRAAQ AQGQSCEYSL MVGYQCGQVF QACCVKSQET GDLDVGGLQE TDKIIEVEEE QEDPYLNDRC RGGGPCKQQC RDTGDEVVCS CFVGYQLLSD GVSCEDVNEC ITGSHSCRLG ESCINTVGSF RCQRDSSCGT GYELTEDNSC KDIDECESGI HNCLPDFICQ NTLGSFRCRP KLQCKSGFIQ DALGNCIDIN ECLSISAPCP IGHTCINTEG SYTCQKNVPN CGRGYHLNEE GTRCVDVDEC APPAEPCGKG HRCVNSPGSF RCECKTGYYF DGISRMCVDV NECQRYPGRL CGHKCENTLG SYLCSCSVGF RLSVDGRSCE DINECSSSPC SQECANVYGS YQCYCRRGYQ LSDVDGVTCE DIDECALPTG GHICSYRCIN IPGSFQCSCP SSGYRLAPNG RNCQDIDECV TGIHNCSINE TCFNIQGGFR CLAFECPENY RRSAATLQQE KTDTVRCIKS CRPNDVTCVF DPVHTISHTV ISLPTFREFT RPEEIIFLRA ITPPHPASQA NIIFDITEGN LRDSFDIIKR YMDGMTVGVV RQVRPIVGPF HAVLKLEMNY VVGGVVSHRN VVNVHIFVSE YWF //