ID FBLN3_HUMAN Reviewed; 493 AA. AC Q12805; A8K3I4; B4DW75; D6W5D2; Q541U7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 09-DEC-2015, entry version 163. DE RecName: Full=EGF-containing fibulin-like extracellular matrix protein 1; DE AltName: Full=Extracellular protein S1-5; DE AltName: Full=Fibrillin-like protein; DE AltName: Full=Fibulin-3; DE Short=FIBL-3; DE Flags: Precursor; GN Name=EFEMP1; Synonyms=FBLN3, FBNL; 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], AND POSSIBLE ALTERNATIVE SPLICING. RC TISSUE=Skin; RX PubMed=7799918; RA Lecka-Czernik B., Lumpkin C.K. Jr., Goldstein S.; RT "An overexpressed gene transcript in senescent and quiescent human RT fibroblasts encoding a novel protein in the epidermal growth factor- RT like repeat family stimulates DNA synthesis."; RL Mol. Cell. Biol. 15:120-128(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8812496; DOI=10.1006/geno.1996.0402; RA Ikegawa S., Toda T., Okui K., Nakamura Y.; RT "Structure and chromosomal assignment of the human S1-5 gene (FBNL) RT that is highly homologous to fibrillin."; RL Genomics 35:590-592(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10601734; DOI=10.1016/S0945-053X(99)00038-4; RA Giltay R., Timpl R., Kostka G.; RT "Sequence, recombinant expression and tissue localization of two novel RT extracellular matrix proteins, fibulin-3 and fibulin-4."; RL Matrix Biol. 18:469-480(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11262647; DOI=10.1076/opge.22.1.27.2239; RA Sauer C.G., White K., Kellner U., Rudolph G., Jurklies B., RA Pauleikhoff D., Weber B.H.; RT "EFEMP1 is not associated with sporadic early onset drusen."; RL Ophthalmic Genet. 22:27-34(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). RC TISSUE=Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). 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.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT DHRD TRP-345. RX PubMed=12242346; DOI=10.1073/pnas.202491599; RA Marmorstein L.Y., Munier F.L., Arsenijevic Y., Schorderet D.F., RA McLaughlin P.J., Chung D., Traboulsi E., Marmorstein A.D.; RT "Aberrant accumulation of EFEMP1 underlies drusen formation in RT Malattia Leventinese and age-related macular degeneration."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13067-13072(2002). RN [10] RP INTERACTION WITH TIMP3. RX PubMed=15123717; DOI=10.1074/jbc.M403026200; RA Klenotic P.A., Munier F.L., Marmorstein L.Y., Anand-Apte B.; RT "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding RT partner of epithelial growth factor-containing fibulin-like RT extracellular matrix protein 1 (EFEMP1). Implications for macular RT degenerations."; RL J. Biol. Chem. 279:30469-30473(2004). RN [11] RP FUNCTION IN EGFR ACTIVATION. RX PubMed=19804359; DOI=10.1515/BC.2009.140; RA Camaj P., Seeliger H., Ischenko I., Krebs S., Blum H., De Toni E.N., RA Faktorova D., Jauch K.W., Bruns C.J.; RT "EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in RT pancreatic carcinoma cells."; RL Biol. Chem. 390:1293-1302(2009). RN [12] RP INTERACTION WITH ECM1. RX PubMed=19275936; DOI=10.1016/j.matbio.2009.02.003; RA Sercu S., Lambeir A.M., Steenackers E., El Ghalbzouri A., RA Geentjens K., Sasaki T., Oyama N., Merregaert J.; RT "ECM1 interacts with fibulin-3 and the beta 3 chain of laminin 332 RT through its serum albumin subdomain-like 2 domain."; RL Matrix Biol. 28:160-169(2009). RN [13] RP FUNCTION. RX PubMed=19887559; DOI=10.1158/1541-7786.MCR-09-0207; RA Hu B., Thirtamara-Rajamani K.K., Sim H., Viapiano M.S.; RT "Fibulin-3 is uniquely upregulated in malignant gliomas and promotes RT tumor cell motility and invasion."; RL Mol. Cancer Res. 7:1756-1770(2009). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=20005202; DOI=10.1016/j.bbrc.2009.12.034; RA Wakabayashi T., Matsumine A., Nakazora S., Hasegawa M., Iino T., RA Ota H., Sonoda H., Sudo A., Uchida A.; RT "Fibulin-3 negatively regulates chondrocyte differentiation."; RL Biochem. Biophys. Res. Commun. 391:1116-1121(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., RA Fischer-Posovszky P., Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion RT profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [16] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP VARIANT DHRD TRP-345, AND VARIANT PHE-220. RX PubMed=10369267; DOI=10.1038/9722; RA Stone E.M., Lotery A.J., Munier F.L., Heon E., Piguet B., Guymer R.H., RA Vandenburgh K., Cousin P., Nishimura D., Swiderski R.E., Silvestri G., RA Mackey D.A., Hagerman G.S., Bird A.C., Sheffield V.C., RA Schorderet D.F.; RT "A single EFEMP1 mutation associated with both malattia Leventinese RT and Doyne honeycomb retinal dystrophy."; RL Nat. Genet. 22:199-202(1999). RN [18] RP VARIANT DHRD TRP-345. RX PubMed=11384588; DOI=10.1016/S0002-9394(00)00926-0; RA Matsumoto M., Traboulsi E.I.; RT "Dominant radial drusen and Arg345Trp EFEMP1 mutation."; RL Am. J. Ophthalmol. 131:810-812(2001). RN [19] RP CHARACTERIZATION OF VARIANT DHRD TRP-345. RX PubMed=17666404; DOI=10.1093/hmg/ddm198; RA Fu L., Garland D., Yang Z., Shukla D., Rajendran A., Pearson E., RA Stone E.M., Zhang K., Pierce E.A.; RT "The R345W mutation in EFEMP1 is pathogenic and causes AMD-like RT deposits in mice."; RL Hum. Mol. Genet. 16:2411-2422(2007). CC -!- FUNCTION: Binds EGFR, the EGF receptor, inducing EGFR CC autophosphorylation and the activation of downstream signaling CC pathways. May play a role in cell adhesion and migration. May CC function as a negative regulator of chondrocyte differentiation. CC In the olfactory epithelium, it may regulate glial cell migration, CC differentiation and the ability of glial cells to support neuronal CC neurite outgrowth. {ECO:0000269|PubMed:19804359, CC ECO:0000269|PubMed:19887559, ECO:0000269|PubMed:20005202}. CC -!- SUBUNIT: Interacts with ECM1. Interacts with TIMP3. CC {ECO:0000269|PubMed:15123717, ECO:0000269|PubMed:19275936}. CC -!- INTERACTION: CC Q9WMX2:- (xeno); NbExp=2; IntAct=EBI-536772, EBI-6863748; CC P10398:ARAF; NbExp=3; IntAct=EBI-536772, EBI-365961; CC P54259:ATN1; NbExp=3; IntAct=EBI-536772, EBI-945980; CC P46379:BAG6; NbExp=3; IntAct=EBI-536772, EBI-347552; CC Q9NPQ8-4:RIC8A; NbExp=3; IntAct=EBI-536772, EBI-9091816; CC O43765:SGTA; NbExp=4; IntAct=EBI-536772, EBI-347996; CC Q12933:TRAF2; NbExp=3; IntAct=EBI-536772, EBI-355744; CC Q86UY0:TXNDC5; NbExp=3; IntAct=EBI-536772, EBI-2825190; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}. CC Secreted, extracellular space, extracellular matrix {ECO:0000250}. CC Note=Localizes to the lamina propria underneath the olfactory CC epithelium. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Experimental confirmation may be lacking for some CC isoforms.; CC Name=1; CC IsoId=Q12805-1; Sequence=Displayed; CC Name=2; CC IsoId=Q12805-2; Sequence=VSP_001392; CC Name=3; CC IsoId=Q12805-3; Sequence=VSP_001393; CC Name=4; CC IsoId=Q12805-4; Sequence=VSP_001394; CC Name=5; CC IsoId=Q12805-5; Sequence=VSP_054372, VSP_054373; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: In the eye, associated with photoreceptor CC outer and inner segment regions, the nerve fiber layer, outer CC nuclear layer and inner and outer plexiform layers of the retina. CC {ECO:0000269|PubMed:12242346, ECO:0000269|PubMed:20005202}. CC -!- DISEASE: Doyne honeycomb retinal dystrophy (DHRD) [MIM:126600]: CC Autosomal dominant disease characterized by yellow-white deposits CC known as drusen that accumulate beneath the retinal pigment CC epithelium. {ECO:0000269|PubMed:10369267, CC ECO:0000269|PubMed:11384588}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Up-regulated in malignant gliomas. May increase CC glioma cell adhesiveness and invasive properties. CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}. CC -!- SIMILARITY: Contains 6 EGF-like domains. {ECO:0000255|PROSITE- CC ProRule:PRU00076}. CC -!- WEB RESOURCE: Name=Mutations of the EFEMP1 gene; Note=Retina CC International's Scientific Newsletter; CC URL="http://www.retina-international.org/files/sci-news/efempmut.htm"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/EFEMP1ID49818ch2p16.html"; 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; U03877; AAA65590.1; -; mRNA. DR EMBL; AY004330; AAK11491.1; -; Genomic_DNA. DR EMBL; AY004321; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004322; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004325; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004324; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004323; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004326; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004328; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004329; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AY004327; AAK11491.1; JOINED; Genomic_DNA. DR EMBL; AK290599; BAF83288.1; -; mRNA. DR EMBL; AK301402; BAG62937.1; -; mRNA. DR EMBL; AC010895; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096549; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471053; EAX00080.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00081.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00082.1; -; Genomic_DNA. DR EMBL; BC014410; AAH14410.1; -; mRNA. DR EMBL; BC098561; AAH98561.1; -; mRNA. DR CCDS; CCDS1857.1; -. [Q12805-1] DR PIR; I38449; I38449. DR RefSeq; NP_001034437.1; NM_001039348.2. [Q12805-1] DR RefSeq; NP_001034438.1; NM_001039349.2. [Q12805-1] DR UniGene; Hs.732348; -. DR UniGene; Hs.76224; -. DR ProteinModelPortal; Q12805; -. DR SMR; Q12805; 44-78, 172-409. DR BioGrid; 108496; 52. DR IntAct; Q12805; 28. DR MINT; MINT-1466511; -. DR STRING; 9606.ENSP00000347596; -. DR PhosphoSite; Q12805; -. DR BioMuta; EFEMP1; -. DR DMDM; 9973182; -. DR MaxQB; Q12805; -. DR PaxDb; Q12805; -. DR PRIDE; Q12805; -. DR DNASU; 2202; -. DR Ensembl; ENST00000355426; ENSP00000347596; ENSG00000115380. [Q12805-1] DR Ensembl; ENST00000394555; ENSP00000378058; ENSG00000115380. [Q12805-1] DR GeneID; 2202; -. DR KEGG; hsa:2202; -. DR UCSC; uc002rzi.3; human. [Q12805-1] DR UCSC; uc010ypc.2; human. DR CTD; 2202; -. DR GeneCards; EFEMP1; -. DR HGNC; HGNC:3218; EFEMP1. DR HPA; CAB016368; -. DR MalaCards; EFEMP1; -. DR MIM; 126600; phenotype. DR MIM; 601548; gene. DR neXtProt; NX_Q12805; -. DR Orphanet; 75376; Familial drusen. DR PharmGKB; PA27652; -. DR eggNOG; ENOG410IR77; Eukaryota. DR eggNOG; ENOG410YCRW; LUCA. DR GeneTree; ENSGT00760000118806; -. DR HOGENOM; HOG000234337; -. DR HOVERGEN; HBG051560; -. DR InParanoid; Q12805; -. DR KO; K18262; -. DR OMA; VQTGRNN; -. DR OrthoDB; EOG7W9RTF; -. DR PhylomeDB; Q12805; -. DR TreeFam; TF317514; -. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR ChiTaRS; EFEMP1; human. DR GeneWiki; EFEMP1; -. DR GenomeRNAi; 2202; -. DR NextBio; 35475649; -. DR PRO; PR:Q12805; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; Q12805; -. DR CleanEx; HS_EFEMP1; -. DR ExpressionAtlas; Q12805; baseline and differential. DR Genevisible; Q12805; HS. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005578; C:proteinaceous extracellular matrix; TAS:ProtInc. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB. DR GO; GO:0005006; F:epidermal growth factor-activated receptor activity; IDA:UniProtKB. DR GO; GO:0043010; P:camera-type eye development; IEP:UniProtKB. DR GO; GO:0048048; P:embryonic eye morphogenesis; IEP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome. DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0048050; P:post-embryonic eye morphogenesis; IEP:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR InterPro; IPR026823; cEGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_N_dom. DR Pfam; PF12662; cEGF; 2. DR Pfam; PF07645; EGF_CA; 3. DR SMART; SM00179; EGF_CA; 4. DR SUPFAM; SSF57184; SSF57184; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 4. DR PROSITE; PS01186; EGF_2; 4. DR PROSITE; PS50026; EGF_3; 4. DR PROSITE; PS01187; EGF_CA; 6. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Complete proteome; Disease mutation; KW Disulfide bond; EGF-like domain; Extracellular matrix; Glycoprotein; KW Growth factor; Polymorphism; Reference proteome; Repeat; Secreted; KW Signal. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 493 EGF-containing fibulin-like extracellular FT matrix protein 1. FT /FTId=PRO_0000007570. FT DOMAIN 26 71 EGF-like 1; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 173 213 EGF-like 2; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 214 253 EGF-like 3; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 254 293 EGF-like 4; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 294 333 EGF-like 5; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 334 378 EGF-like 6; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT REGION 259 493 Mediates interaction with TIMP3. FT CARBOHYD 249 249 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 177 190 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 184 199 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 201 212 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 218 228 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 224 237 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 239 252 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 258 268 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 264 277 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 279 292 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 298 309 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 305 318 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 320 332 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 338 350 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 344 359 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 365 377 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT VAR_SEQ 1 58 Missing (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054372. FT VAR_SEQ 1 8 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_001392. FT VAR_SEQ 58 58 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_001393. FT VAR_SEQ 106 106 Missing (in isoform 4). {ECO:0000305}. FT /FTId=VSP_001394. FT VAR_SEQ 214 293 Missing (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054373. FT VARIANT 220 220 I -> F. {ECO:0000269|PubMed:10369267}. FT /FTId=VAR_009512. FT VARIANT 345 345 R -> W (in DHRD; misfolded, accumulates FT in cells due to inefficient secretion; FT induces the formation of deposits between FT Bruch's membrane and the retinal pigment FT epithelium where it accumulates). FT {ECO:0000269|PubMed:10369267, FT ECO:0000269|PubMed:11384588, FT ECO:0000269|PubMed:12242346, FT ECO:0000269|PubMed:17666404}. FT /FTId=VAR_009513. SQ SEQUENCE 493 AA; 54641 MW; 128CA5ED140DF414 CRC64; MLKALFLTML TLALVKSQDT EETITYTQCT DGYEWDPVRQ QCKDIDECDI VPDACKGGMK CVNHYGGYLC LPKTAQIIVN NEQPQQETQP AEGTSGATTG VVAASSMATS GVLPGGGFVA SAAAVAGPEM QTGRNNFVIR RNPADPQRIP SNPSHRIQCA AGYEQSEHNV CQDIDECTAG THNCRADQVC INLRGSFACQ CPPGYQKRGE QCVDIDECTI PPYCHQRCVN TPGSFYCQCS PGFQLAANNY TCVDINECDA SNQCAQQCYN ILGSFICQCN QGYELSSDRL NCEDIDECRT SSYLCQYQCV NEPGKFSCMC PQGYQVVRSR TCQDINECET TNECREDEMC WNYHGGFRCY PRNPCQDPYI LTPENRCVCP VSNAMCRELP QSIVYKYMSI RSDRSVPSDI FQIQATTIYA NTINTFRIKS GNENGEFYLR QTSPVSAMLV LVKSLSGPRE HIVDLEMLTV SSIGTFRTSS VLRLTIIVGP FSF //