ID FBLN5_HUMAN Reviewed; 448 AA. AC Q9UBX5; O75966; Q6IAL4; Q6UWA3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Fibulin-5; DE Short=FIBL-5; DE AltName: Full=Developmental arteries and neural crest EGF-like protein; DE Short=Dance; DE AltName: Full=Urine p50 protein; DE Short=UP50; DE Flags: Precursor; GN Name=FBLN5; Synonyms=DANCE; ORFNames=UNQ184/PRO210; 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]. RC TISSUE=Melanoma; RA Kostka G.; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=10428823; DOI=10.1074/jbc.274.32.22476; RA Nakamura T., Ruiz-Lozano P., Lindner V., Yabe D., Taniwaki M., Furukawa Y., RA Kobuke K., Tashiro K., Lu Z., Andon N.L., Schaub R., Matsumori A., RA Sasayama S., Chien K.R., Honjo T.; RT "DANCE, a novel secreted RGD protein expressed in developing, RT atherosclerotic, and balloon-injured arteries."; RL J. Biol. Chem. 274:22476-22483(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Urine; RA Zemel R., Sholto O., Shaul Y.; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP INTERACTION WITH FBN1 AND ELN, SUBUNIT, AND GLYCOSYLATION. RX PubMed=15790312; DOI=10.1042/bj20050368; RA Freeman L.J., Lomas A., Hodson N., Sherratt M.J., Mellody K.T., Weiss A.S., RA Shuttleworth A., Kielty C.M.; RT "Fibulin-5 interacts with fibrillin-1 molecules and microfibrils."; RL Biochem. J. 388:1-5(2005). RN [10] RP FUNCTION, AND INTERACTION WITH FBN1 AND ELN. RX PubMed=17255108; DOI=10.1074/jbc.m608204200; RA El-Hallous E., Sasaki T., Hubmacher D., Getie M., Tiedemann K., RA Brinckmann J., Baetge B., Davis E.C., Reinhardt D.P.; RT "Fibrillin-1 interactions with fibulins depend on the first hybrid domain RT and provide an adaptor function to tropoelastin."; RL J. Biol. Chem. 282:8935-8946(2007). RN [11] RP INTERACTION WITH ELN; LOX; FBLN5 AND FBN1EFEMP2. RX PubMed=19570982; DOI=10.1074/jbc.m109.019364; RA Choudhury R., McGovern A., Ridley C., Cain S.A., Baldwin A., Wang M.C., RA Guo C., Mironov A. Jr., Drymoussi Z., Trump D., Shuttleworth A., RA Baldock C., Kielty C.M.; RT "Differential regulation of elastic fiber formation by fibulin-4 and -5."; RL J. Biol. Chem. 284:24553-24567(2009). RN [12] RP SUBUNIT, AND GLYCOSYLATION. RX PubMed=19617354; DOI=10.1074/jbc.m109.011627; RA Jones R.P., Wang M.C., Jowitt T.A., Ridley C., Mellody K.T., Howard M., RA Wang T., Bishop P.N., Lotery A.J., Kielty C.M., Baldock C., Trump D.; RT "Fibulin 5 forms a compact dimer in physiological solutions."; RL J. Biol. Chem. 284:25938-25943(2009). RN [13] 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 [14] RP VARIANT ARCL1A PRO-227. RX PubMed=12189163; DOI=10.1093/hmg/11.18.2113; RA Loeys B., van Maldergem L., Mortier G., Coucke P., Gerniers S., RA Naeyaert J.-M., de Paepe A.; RT "Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a RT severe form of cutis laxa."; RL Hum. Mol. Genet. 11:2113-2118(2002). RN [15] RP INVOLVEMENT IN ADCL2. RX PubMed=12618961; DOI=10.1086/373940; RA Markova D., Zou Y., Ringpfeil F., Sasaki T., Kostka G., Timpl R., Uitto J., RA Chu M.-L.; RT "Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication RT within the fibulin-5 (FBLN5) gene."; RL Am. J. Hum. Genet. 72:998-1004(2003). RN [16] RP VARIANTS ARMD3 LEU-60; GLN-71; SER-87; THR-169; TRP-351; THR-363 AND RP GLU-412. RX PubMed=15269314; DOI=10.1056/nejmoa040833; RA Stone E.M., Braun T.A., Russell S.R., Kuehn M.H., Lotery A.J., Moore P.A., RA Eastman C.G., Casavant T.L., Sheffield V.C.; RT "Missense variations in the fibulin 5 gene and age-related macular RT degeneration."; RL N. Engl. J. Med. 351:346-353(2004). RN [17] RP VARIANTS ARCL1A ARG-217 AND PRO-227, CHARACTERIZATION OF VARIANTS ARCL1A RP ARG-217 AND PRO-227, FUNCTION, INTERACTION WITH ELN, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=17035250; DOI=10.1093/hmg/ddl414; RA Hu Q., Loeys B.L., Coucke P.J., De Paepe A., Mecham R.P., Choi J., RA Davis E.C., Urban Z.; RT "Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in RT recessive cutis laxa."; RL Hum. Mol. Genet. 15:3379-3386(2006). RN [18] RP VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351; RP THR-363 AND GLU-412, CHARACTERIZATION OF VARIANTS ARMD3 LEU-60; GLN-71; RP SER-87; PRO-124; THR-169; SER-267; TRP-351; THR-363 AND GLU-412, VARIANTS RP ARCL1A ARG-217 AND PRO-227, CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND RP PRO-227, VARIANTS MET-126 AND ARG-202, AND SUBCELLULAR LOCATION. RX PubMed=16652333; DOI=10.1002/humu.20344; RA Lotery A.J., Baas D., Ridley C., Jones R.P., Klaver C.C., Stone E., RA Nakamura T., Luff A., Griffiths H., Wang T., Bergen A.A., Trump D.; RT "Reduced secretion of fibulin 5 in age-related macular degeneration and RT cutis laxa."; RL Hum. Mutat. 27:568-574(2006). RN [19] RP VARIANT ARCL1A PRO-227. RX PubMed=16691202; DOI=10.1038/sj.jid.5700247; RA Elahi E., Kalhor R., Banihosseini S.S., Torabi N., Pour-Jafari H., RA Houshmand M., Amini S.S.H., Ramezani A., Loeys B.; RT "Homozygous missense mutation in fibulin-5 in an Iranian autosomal RT recessive cutis laxa pedigree and associated haplotype."; RL J. Invest. Dermatol. 126:1506-1509(2006). RN [20] RP VARIANT ARCL1A ARG-217, CHARACTERIZATION OF VARIANT ARCL1A ARG-217, AND RP FUNCTION. RX PubMed=18185537; DOI=10.1038/sj.jid.5701211; RA Claus S., Fischer J., Megarbane H., Megarbane A., Jobard F., Debret R., RA Peyrol S., Saker S., Devillers M., Sommer P., Damour O.; RT "A p.C217R mutation in fibulin-5 from cutis laxa patients is associated RT with incomplete extracellular matrix formation in a skin equivalent RT model."; RL J. Invest. Dermatol. 128:1442-1450(2008). RN [21] RP VARIANT MET-301. RX PubMed=19194475; DOI=10.1038/jid.2008.450; RA Megarbane H., Florence J., Sass J.O., Schwonbeck S., Foglio M., de Cid R., RA Cure S., Saker S., Megarbane A., Fischer J.; RT "An autosomal-recessive form of cutis laxa is due to homozygous elastin RT mutations, and the phenotype may be modified by a heterozygous fibulin 5 RT polymorphism."; RL J. Invest. Dermatol. 129:1650-1655(2009). RN [22] RP CHARACTERIZATION OF VARIANTS MET-126 AND ARG-202, CHARACTERIZATION OF RP VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351 RP AND GLU-412, CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND PRO-227, AND RP SUBUNIT. RX PubMed=20007835; DOI=10.1167/iovs.09-4620; RA Jones R.P., Ridley C., Jowitt T.A., Wang M.C., Howard M., Bobola N., RA Wang T., Bishop P.N., Kielty C.M., Baldock C., Lotery A.J., Trump D.; RT "Structural effects of fibulin 5 missense mutations associated with age- RT related macular degeneration and cutis laxa."; RL Invest. Ophthalmol. Vis. Sci. 51:2356-2362(2010). RN [23] RP CHARACTERIZATION OF VARIANTS ARCL1A PRO-227 AND SER-267, CHARACTERIZATION RP OF VARIANT ARMD3 THR-169, CHARACTERIZATION OF VARIANT ARG-202, AND RP SUBCELLULAR LOCATION. RX PubMed=20599547; DOI=10.1016/j.jmb.2010.06.039; RA Schneider R., Jensen S.A., Whiteman P., McCullagh J.S., Redfield C., RA Handford P.A.; RT "Biophysical characterisation of fibulin-5 proteins associated with RT disease."; RL J. Mol. Biol. 401:605-617(2010). RN [24] RP VARIANTS CMT1H ILE-48; SER-90; SER-267 AND CYS-373, AND VARIANT MET-126. RX PubMed=21576112; DOI=10.1093/brain/awr076; RA Auer-Grumbach M., Weger M., Fink-Puches R., Papic L., Froehlich E., RA Auer-Grumbach P., El Shabrawi-Caelen L., Schabhuettl M., Windpassinger C., RA Senderek J., Budka H., Trajanoski S., Janecke A.R., Haas A., Metze D., RA Pieber T.R., Guelly C.; RT "Fibulin-5 mutations link inherited neuropathies, age-related macular RT degeneration and hyperelastic skin."; RL Brain 134:1839-1852(2011). RN [25] RP VARIANT CMT1H CYS-373. RX PubMed=23328402; DOI=10.1093/brain/aws333; RA Safka Brozkova D., Lassuthova P., Neupauerova J., Krutova M., Haberlova J., RA Stejskal D., Seeman P.; RT "Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type RT 1 neuropathy."; RL Brain 136:E232-E232(2013). CC -!- FUNCTION: Essential for elastic fiber formation, is involved in the CC assembly of continuous elastin (ELN) polymer and promotes the CC interaction of microfibrils and ELN (PubMed:18185537). Stabilizes and CC organizes elastic fibers in the skin, lung and vasculature (By CC similarity). Promotes adhesion of endothelial cells through interaction CC of integrins and the RGD motif. Vascular ligand for integrin receptors CC which may play a role in vascular development and remodeling CC (PubMed:10428823). May act as an adapter that mediates the interaction CC between FBN1 and ELN (PubMed:17255108). {ECO:0000250|UniProtKB:Q9WVH9, CC ECO:0000269|PubMed:10428823, ECO:0000269|PubMed:17255108, CC ECO:0000269|PubMed:18185537}. CC -!- SUBUNIT: Homodimer (PubMed:20007835). Monomer (PubMed:15790312, CC PubMed:19617354), homodimerizes in presence of Ca(2+) CC (PubMed:19617354). Interacts with ELN (PubMed:17035250, CC PubMed:15790312). Interacts (via N-terminus) with the integrins CC ITGAV/ITGB3, ITGAV/ITGB5 and ITGA9/ITGB1 (By similarity). Interacts CC with FBN1 (via N-terminal domain). Forms a ternary complex with ELN and CC FBN1 (PubMed:17255108). Interacts with EFEMP2 with moderate affinity CC (PubMed:19570982). Interacts with LOXL1 (By similarity). CC {ECO:0000250|UniProtKB:Q9WVH9, ECO:0000269|PubMed:15790312, CC ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:17255108, CC ECO:0000269|PubMed:19570982, ECO:0000269|PubMed:19617354, CC ECO:0000269|PubMed:20007835}. CC -!- INTERACTION: CC Q9UBX5; O95967: EFEMP2; NbExp=3; IntAct=EBI-947897, EBI-743414; CC Q9UBX5; P15502: ELN; NbExp=3; IntAct=EBI-947897, EBI-1222108; CC Q9UBX5; P35555: FBN1; NbExp=3; IntAct=EBI-947897, EBI-2505934; CC Q9UBX5; P22607: FGFR3; NbExp=3; IntAct=EBI-947897, EBI-348399; CC Q9UBX5; P28799: GRN; NbExp=3; IntAct=EBI-947897, EBI-747754; CC Q9UBX5; P28300: LOX; NbExp=2; IntAct=EBI-947897, EBI-3893481; CC Q9UBX5; Q14767: LTBP2; NbExp=2; IntAct=EBI-947897, EBI-1546118; CC Q9UBX5; P50222: MEOX2; NbExp=3; IntAct=EBI-947897, EBI-748397; CC Q9UBX5; Q7Z417: NUFIP2; NbExp=4; IntAct=EBI-947897, EBI-1210753; CC Q9UBX5; P32242: OTX1; NbExp=3; IntAct=EBI-947897, EBI-740446; CC Q9UBX5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-947897, EBI-5235340; CC Q9UBX5; Q15645: TRIP13; NbExp=3; IntAct=EBI-947897, EBI-358993; CC Q9UBX5; O76024: WFS1; NbExp=3; IntAct=EBI-947897, EBI-720609; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16652333, CC ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:20599547}. Secreted, CC extracellular space, extracellular matrix CC {ECO:0000269|PubMed:17035250}. Note=co-localizes with ELN in elastic CC fibers. {ECO:0000269|PubMed:17035250}. CC -!- TISSUE SPECIFICITY: Expressed in skin fibroblasts (at protein CC level)(PubMed:17035250). Expressed predominantly in heart, ovary, and CC colon but also in kidney, pancreas, testis, lung and placenta. Not CC detectable in brain, liver, thymus, prostate, or peripheral blood CC leukocytes (PubMed:10428823). {ECO:0000269|PubMed:10428823, CC ECO:0000269|PubMed:17035250}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15790312, CC ECO:0000269|PubMed:19617354}. CC -!- DISEASE: Charcot-Marie-Tooth disease, demyelinating, 1H (CMT1H) CC [MIM:619764]: An autosomal dominant demyelinating form of Charcot- CC Marie-Tooth disease, a disorder of the peripheral nervous system, CC characterized by progressive weakness and atrophy, initially of the CC peroneal muscles and later of the distal muscles of the arms. Charcot- CC Marie-Tooth disease is classified in two main groups on the basis of CC electrophysiologic properties and histopathology: primary peripheral CC demyelinating neuropathies (designated CMT1 when they are dominantly CC inherited) and primary peripheral axonal neuropathies (CMT2). CC Demyelinating neuropathies are characterized by severely reduced nerve CC conduction velocities (less than 38 m/sec), segmental demyelination and CC remyelination with onion bulb formations on nerve biopsy, slowly CC progressive distal muscle atrophy and weakness, absent deep tendon CC reflexes, and hollow feet. CMT1H is characterized by peripheral CC sensorimotor neuropathy with onset usually in adulthood. Affected CC individuals present with foot deformities, upper or lower limb sensory CC disturbances, and motor deficits, mainly impaired gait. Rare patients CC may have hyperelastic skin or develop age-related macular degeneration. CC {ECO:0000269|PubMed:21576112, ECO:0000269|PubMed:23328402}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cutis laxa, autosomal dominant, 2 (ADCL2) [MIM:614434]: A CC connective tissue disorder characterized by loose, hyperextensible skin CC with decreased resilience and elasticity leading to a premature aged CC appearance. Face, hands, feet, joints, and torso may be differentially CC affected. Additional variable clinical features are gastrointestinal CC diverticula, hernia, and genital prolapse. Rare manifestations are CC pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and CC emphysema. {ECO:0000269|PubMed:12618961}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Cutis laxa, autosomal recessive, 1A (ARCL1A) [MIM:219100]: A CC connective tissue disorder characterized by loose, hyperextensible skin CC with decreased resilience and elasticity leading to a premature aged CC appearance. Face, hands, feet, joints, and torso may be differentially CC affected. The clinical spectrum of autosomal recessive cutis laxa is CC highly heterogeneous with respect to organ involvement and severity. CC Type I autosomal recessive cutis laxa is a specific, life-threatening CC disorder with organ involvement, lung atelectasis and emphysema, CC diverticula of the gastrointestinal and genitourinary systems, and CC vascular anomalies. Associated cranial anomalies, late closure of the CC fontanel, joint laxity, hip dislocation, and inguinal hernia have been CC observed but are uncommon. {ECO:0000269|PubMed:12189163, CC ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:16691202, CC ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:18185537, CC ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Mutations affecting this gene can modify the phenotype of CC diseases caused by ELN mutations. {ECO:0000269|PubMed:19194475}. CC -!- DISEASE: Macular degeneration, age-related, 3 (ARMD3) [MIM:608895]: A CC form of age-related macular degeneration, a multifactorial eye disease CC and the most common cause of irreversible vision loss in the developed CC world. In most patients, the disease is manifest as ophthalmoscopically CC visible yellowish accumulations of protein and lipid that lie beneath CC the retinal pigment epithelium and within an elastin-containing CC structure known as Bruch membrane. {ECO:0000269|PubMed:15269314, CC ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835, CC ECO:0000269|PubMed:20599547}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}. 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; AJ133490; CAB38568.1; -; mRNA. DR EMBL; AF112152; AAD41768.1; -; mRNA. DR EMBL; AF093118; AAC62107.1; -; mRNA. DR EMBL; AY358898; AAQ89257.1; -; mRNA. DR EMBL; CR457140; CAG33421.1; -; mRNA. DR EMBL; AK075147; BAG52073.1; -; mRNA. DR EMBL; CH471061; EAW81466.1; -; Genomic_DNA. DR EMBL; BC022280; AAH22280.1; -; mRNA. DR CCDS; CCDS9898.1; -. DR RefSeq; NP_006320.2; NM_006329.3. DR AlphaFoldDB; Q9UBX5; -. DR BioGRID; 115771; 158. DR CORUM; Q9UBX5; -. DR DIP; DIP-44301N; -. DR IntAct; Q9UBX5; 39. DR MINT; Q9UBX5; -. DR STRING; 9606.ENSP00000345008; -. DR GlyConnect; 1245; 6 N-Linked glycans (1 site). DR GlyCosmos; Q9UBX5; 4 sites, 7 glycans. DR GlyGen; Q9UBX5; 7 sites, 5 N-linked glycans (1 site), 4 O-linked glycans (4 sites). DR iPTMnet; Q9UBX5; -. DR PhosphoSitePlus; Q9UBX5; -. DR BioMuta; FBLN5; -. DR DMDM; 12643876; -. DR REPRODUCTION-2DPAGE; IPI00294615; -. DR CPTAC; CPTAC-2212; -. DR jPOST; Q9UBX5; -. DR MassIVE; Q9UBX5; -. DR PaxDb; 9606-ENSP00000345008; -. DR PeptideAtlas; Q9UBX5; -. DR ProteomicsDB; 84093; -. DR Pumba; Q9UBX5; -. DR Antibodypedia; 72; 516 antibodies from 38 providers. DR DNASU; 10516; -. DR Ensembl; ENST00000342058.9; ENSP00000345008.4; ENSG00000140092.16. DR GeneID; 10516; -. DR KEGG; hsa:10516; -. DR MANE-Select; ENST00000342058.9; ENSP00000345008.4; NM_006329.4; NP_006320.2. DR UCSC; uc001xzx.5; human. DR AGR; HGNC:3602; -. DR CTD; 10516; -. DR DisGeNET; 10516; -. DR GeneCards; FBLN5; -. DR GeneReviews; FBLN5; -. DR HGNC; HGNC:3602; FBLN5. DR HPA; ENSG00000140092; Low tissue specificity. DR MalaCards; FBLN5; -. DR MIM; 219100; phenotype. DR MIM; 604580; gene. DR MIM; 608895; phenotype. DR MIM; 614434; phenotype. DR MIM; 619764; phenotype. DR neXtProt; NX_Q9UBX5; -. DR OpenTargets; ENSG00000140092; -. DR Orphanet; 90348; Autosomal dominant cutis laxa. DR Orphanet; 90349; Autosomal recessive cutis laxa type 1. DR Orphanet; 280598; Hereditary sensorimotor neuropathy with hyperelastic skin. DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration. DR PharmGKB; PA28015; -. DR VEuPathDB; HostDB:ENSG00000140092; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000158774; -. DR HOGENOM; CLU_004826_0_1_1; -. DR InParanoid; Q9UBX5; -. DR OMA; LICRFGF; -. DR OrthoDB; 19806at2759; -. DR PhylomeDB; Q9UBX5; -. DR TreeFam; TF317514; -. DR PathwayCommons; Q9UBX5; -. DR Reactome; R-HSA-1566948; Elastic fibre formation. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR SignaLink; Q9UBX5; -. DR SIGNOR; Q9UBX5; -. DR BioGRID-ORCS; 10516; 11 hits in 1161 CRISPR screens. DR ChiTaRS; FBLN5; human. DR GeneWiki; FBLN5; -. DR GenomeRNAi; 10516; -. DR Pharos; Q9UBX5; Tbio. DR PRO; PR:Q9UBX5; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9UBX5; Protein. DR Bgee; ENSG00000140092; Expressed in thoracic aorta and 175 other cell types or tissues. DR ExpressionAtlas; Q9UBX5; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0007160; P:cell-matrix adhesion; TAS:ProtInc. DR GO; GO:0048251; P:elastic fiber assembly; IMP:UniProtKB. DR GO; GO:0034394; P:protein localization to cell surface; ISS:BHF-UCL. DR GO; GO:2000121; P:regulation of removal of superoxide radicals; ISS:BHF-UCL. DR GO; GO:0046903; P:secretion; IDA:UniProtKB. DR CDD; cd00054; EGF_CA; 1. DR Gene3D; 2.10.25.10; Laminin; 7. 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; IPR009030; Growth_fac_rcpt_cys_sf. DR PANTHER; PTHR24034; EGF-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24034:SF107; FIBULIN-5; 1. DR Pfam; PF12662; cEGF; 3. DR Pfam; PF07645; EGF_CA; 2. DR SMART; SM00181; EGF; 5. DR SMART; SM00179; EGF_CA; 6. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 2. DR PROSITE; PS00010; ASX_HYDROXYL; 4. DR PROSITE; PS01186; EGF_2; 4. DR PROSITE; PS50026; EGF_3; 5. DR PROSITE; PS01187; EGF_CA; 6. DR Genevisible; Q9UBX5; HS. PE 1: Evidence at protein level; KW Age-related macular degeneration; Calcium; Cell adhesion; KW Charcot-Marie-Tooth disease; Disease variant; Disulfide bond; KW EGF-like domain; Extracellular matrix; Glycoprotein; Neurodegeneration; KW Neuropathy; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..448 FT /note="Fibulin-5" FT /id="PRO_0000007577" FT DOMAIN 42..82 FT /note="EGF-like 1; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 127..167 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 168..206 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 207..246 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 247..287 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 288..333 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 245..448 FT /note="Interaction with LOXL1" FT /evidence="ECO:0000250|UniProtKB:Q9WVH9" FT MOTIF 54..56 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT CARBOHYD 283 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 46..59 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 53..68 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 131..144 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 138..153 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 155..166 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 172..181 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 177..190 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 192..205 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 211..221 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 217..230 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 232..245 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 251..262 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 258..271 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 273..286 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 292..305 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 299..314 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 320..332 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT VARIANT 48 FT /note="T -> I (in CMT1H; dbSNP:rs141200859)" FT /evidence="ECO:0000269|PubMed:21576112" FT /id="VAR_076289" FT VARIANT 60 FT /note="V -> L (in ARMD3; no effect on secretion; no effect FT on homodimerization; dbSNP:rs121434299)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835" FT /id="VAR_019814" FT VARIANT 71 FT /note="R -> Q (in ARMD3; no effect on secretion; no effect FT on homodimerization; dbSNP:rs121434300)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835" FT /id="VAR_019815" FT VARIANT 87 FT /note="P -> S (in ARMD3; no effect on secretion; slightly FT increases homodimerization in absence of Ca(2+); FT dbSNP:rs121434301)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835" FT /id="VAR_019816" FT VARIANT 90 FT /note="G -> S (in CMT1H; dbSNP:rs144288844)" FT /evidence="ECO:0000269|PubMed:21576112" FT /id="VAR_076290" FT VARIANT 124 FT /note="Q -> P (in ARMD3; almost abolishes secretion; no FT effect on homodimerization)" FT /evidence="ECO:0000269|PubMed:16652333, FT ECO:0000269|PubMed:20007835" FT /id="VAR_072389" FT VARIANT 126 FT /note="V -> M (no effect on secretion; slightly increases FT homodimerization in absence of Ca(2+); dbSNP:rs61734479)" FT /evidence="ECO:0000269|PubMed:16652333, FT ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:21576112" FT /id="VAR_072390" FT VARIANT 169 FT /note="I -> T (in ARMD3; decreases secretion; slightly FT increases homodimerization in absence of Ca(2+); no effect FT on protein folding; dbSNP:rs28939072)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835, FT ECO:0000269|PubMed:20599547" FT /id="VAR_019817" FT VARIANT 202 FT /note="G -> R (slightly increases homodimerization in FT absence of Ca(2+); no effect on protein folding; no effect FT on secretion; dbSNP:rs80338765)" FT /evidence="ECO:0000269|PubMed:16652333, FT ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547" FT /id="VAR_072391" FT VARIANT 217 FT /note="C -> R (in ARCL1A; formation of extracellular FT globular aggregates; decreases cell growth; reduces FT interaction with ELN; abolishes secretion; increases FT homodimerization; dbSNP:rs80338766)" FT /evidence="ECO:0000269|PubMed:16652333, FT ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:18185537, FT ECO:0000269|PubMed:20007835" FT /id="VAR_072392" FT VARIANT 227 FT /note="S -> P (in ARCL1A; decreases expression; produces FT protein misfolding; abolishes secretion; reduces FT interaction with ELN; increases homodimerization; impairs FT elastic fiber development; dbSNP:rs28939370)" FT /evidence="ECO:0000269|PubMed:12189163, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:16691202, FT ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:20007835, FT ECO:0000269|PubMed:20599547" FT /id="VAR_017153" FT VARIANT 267 FT /note="G -> S (in ARMD3, ARCL1A and CMT1H; produces protein FT misolding; decreases secretion; no effect on FT homodimerization; dbSNP:rs149396611)" FT /evidence="ECO:0000269|PubMed:16652333, FT ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547, FT ECO:0000269|PubMed:21576112" FT /id="VAR_072393" FT VARIANT 301 FT /note="L -> M (found in a patient with autosomal recessive FT cutis laxa also carrying a mutation in ELN; uncertain FT significance; dbSNP:rs377360782)" FT /evidence="ECO:0000269|PubMed:19194475" FT /id="VAR_072394" FT VARIANT 351 FT /note="R -> W (in ARMD3; no effect on secretion; slightly FT increases homodimerization in absence of Ca(2+); FT dbSNP:rs28939073)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835" FT /id="VAR_019818" FT VARIANT 363 FT /note="A -> T (in ARMD3; no effect on secretion; FT dbSNP:rs121434302)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333" FT /id="VAR_019819" FT VARIANT 364 FT /note="D -> Y (in dbSNP:rs1802492)" FT /id="VAR_026986" FT VARIANT 373 FT /note="R -> C (in CMT1H; dbSNP:rs864309526)" FT /evidence="ECO:0000269|PubMed:21576112, FT ECO:0000269|PubMed:23328402" FT /id="VAR_076291" FT VARIANT 412 FT /note="G -> E (in ARMD3; decreases secretion; slightly FT increases homodimerization in absence of Ca(2+); FT dbSNP:rs121434303)" FT /evidence="ECO:0000269|PubMed:15269314, FT ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835" FT /id="VAR_019820" FT CONFLICT 69..70 FT /note="IP -> HS (in Ref. 3; AAC62107)" FT /evidence="ECO:0000305" FT CONFLICT 147..148 FT /note="TE -> MK (in Ref. 3; AAC62107)" FT /evidence="ECO:0000305" FT CONFLICT 228 FT /note="F -> L (in Ref. 4; AAQ89257)" FT /evidence="ECO:0000305" SQ SEQUENCE 448 AA; 50180 MW; 19FCA51FDA328003 CRC64; MPGIKRILTV TILALCLPSP GNAQAQCTNG FDLDRQSGQC LDIDECRTIP EACRGDMMCV NQNGGYLCIP RTNPVYRGPY SNPYSTPYSG PYPAAAPPLS APNYPTISRP LICRFGYQMD ESNQCVDVDE CATDSHQCNP TQICINTEGG YTCSCTDGYW LLEGQCLDID ECRYGYCQQL CANVPGSYSC TCNPGFTLNE DGRSCQDVNE CATENPCVQT CVNTYGSFIC RCDPGYELEE DGVHCSDMDE CSFSEFLCQH ECVNQPGTYF CSCPPGYILL DDNRSCQDIN ECEHRNHTCN LQQTCYNLQG GFKCIDPIRC EEPYLRISDN RCMCPAENPG CRDQPFTILY RDMDVVSGRS VPADIFQMQA TTRYPGAYYI FQIKSGNEGR EFYMRQTGPI SATLVMTRPI KGPREIQLDL EMITVNTVIN FRGSSVIRLR IYVSQYPF //