FBLN5_HUMAN
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 03-AUG-2022, entry version 201.
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). {ECO:0000250|UniProtKB:Q9WVH9,
CC ECO:0000269|PubMed:15790312, ECO:0000269|PubMed:17035250,
CC ECO:0000269|PubMed:17255108, ECO:0000269|PubMed:19570982,
CC ECO:0000269|PubMed:19617354, 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}.
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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; 157.
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 GlyGen; Q9UBX5; 5 sites, 5 N-linked glycans (1 site), 2 O-linked glycans (2 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; Q9UBX5; -.
DR PeptideAtlas; Q9UBX5; -.
DR PRIDE; Q9UBX5; -.
DR ProteomicsDB; 84093; -.
DR Antibodypedia; 72; 457 antibodies from 38 providers.
DR DNASU; 10516; -.
DR Ensembl; ENST00000342058.9; ENSP00000345008.4; ENSG00000140092.15.
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 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; ACRGDMV; -.
DR OrthoDB; 1174178at2759; -.
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 1083 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 173 other tissues.
DR ExpressionAtlas; Q9UBX5; baseline and differential.
DR Genevisible; Q9UBX5; HS.
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:0008022; F:protein C-terminus binding; IPI:BHF-UCL.
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:0001558; P:regulation of cell growth; IEA:Ensembl.
DR GO; GO:2000121; P:regulation of removal of superoxide radicals; ISS:BHF-UCL.
DR GO; GO:0046903; P:secretion; IDA:UniProtKB.
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; IPR037288; Fibulin-5.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR PANTHER; PTHR24050:SF21; PTHR24050:SF21; 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; SSF57184; SSF57184; 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.
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 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; unknown
FT pathological 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
