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FBLN1_HUMAN
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   03-AUG-2022, entry version 245.
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="http://atlasgeneticsoncology.org/Genes/FBLN1ID44462ch22q13.html";
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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; 125.
DR   IntAct; P23142; 83.
DR   MINT; P23142; -.
DR   STRING; 9606.ENSP00000331544; -.
DR   GlyConnect; 1244; 8 N-Linked glycans (2 sites).
DR   GlyGen; P23142; 4 sites, 10 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; P23142; -.
DR   PhosphoSitePlus; P23142; -.
DR   BioMuta; FBLN1; -.
DR   DMDM; 215274249; -.
DR   CPTAC; non-CPTAC-1123; -.
DR   EPD; P23142; -.
DR   jPOST; P23142; -.
DR   MassIVE; P23142; -.
DR   MaxQB; P23142; -.
DR   PaxDb; P23142; -.
DR   PeptideAtlas; P23142; -.
DR   PRIDE; 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   Antibodypedia; 886; 329 antibodies from 34 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   CTD; 2192; -.
DR   DisGeNET; 2192; -.
DR   GeneCards; FBLN1; -.
DR   HGNC; HGNC:3600; FBLN1.
DR   HPA; ENSG00000077942; Low tissue specificity.
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; LRITHYH; -.
DR   OrthoDB; 1174178at2759; -.
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 1069 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 190 other tissues.
DR   ExpressionAtlas; P23142; baseline and differential.
DR   Genevisible; P23142; HS.
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:0008022; F:protein C-terminus binding; IPI:UniProtKB.
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   InterPro; IPR000020; Anaphylatoxin/fibulin.
DR   InterPro; IPR026823; cEGF.
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; IPR009030; Growth_fac_rcpt_cys_sf.
DR   Pfam; PF12662; cEGF; 3.
DR   Pfam; PF07645; EGF_CA; 4.
DR   PIRSF; PIRSF036313; Fibulin-1; 1.
DR   SMART; SM00104; ANATO; 3.
DR   SMART; SM00181; EGF; 9.
DR   SMART; SM00179; EGF_CA; 8.
DR   SUPFAM; SSF57184; SSF57184; 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   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; unknown pathological
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
 
 
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