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Database: UniProt
Entry: Q9UBX5
LinkDB: Q9UBX5
Original site: Q9UBX5 
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   13-FEB-2019, entry version 181.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Furukawa Y., Kobuke K., Tashiro K., Lu Z., Andon N.L., Schaub R.,
RA   Matsumori A., 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.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics 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-
RT   length human cDNAs encoding secretion or membrane proteins from oligo-
RT   capped cDNA 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.,
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 (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
RT   project: 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.,
RA   Weiss A.S., 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
RT   domain and provide an adaptor function to tropoelastin.";
RL   J. Biol. Chem. 282:8935-8946(2007).
RN   [11]
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.,
RA   Howard M., Wang T., Bishop P.N., Lotery A.J., Kielty C.M., Baldock C.,
RA   Trump D.;
RT   "Fibulin 5 forms a compact dimer in physiological solutions.";
RL   J. Biol. Chem. 284:25938-25943(2009).
RN   [12]
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   [13]
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
RT   a severe form of cutis laxa.";
RL   Hum. Mol. Genet. 11:2113-2118(2002).
RN   [14]
RP   INVOLVEMENT IN ADCL2.
RX   PubMed=12618961; DOI=10.1086/373940;
RA   Markova D., Zou Y., Ringpfeil F., Sasaki T., Kostka G., Timpl R.,
RA   Uitto J., Chu M.-L.;
RT   "Genetic heterogeneity of cutis laxa: a heterozygous tandem
RT   duplication within the fibulin-5 (FBLN5) gene.";
RL   Am. J. Hum. Genet. 72:998-1004(2003).
RN   [15]
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.,
RA   Moore P.A., 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   [16]
RP   VARIANTS ARCL1A ARG-217 AND PRO-227, CHARACTERIZATION OF VARIANTS
RP   ARCL1A ARG-217 AND PRO-227, FUNCTION, INTERACTION WITH ELN,
RP   SUBCELLULAR LOCATION, 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
RT   in recessive cutis laxa.";
RL   Hum. Mol. Genet. 15:3379-3386(2006).
RN   [17]
RP   VARIANTS ARMD3 LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267;
RP   TRP-351; THR-363 AND GLU-412, CHARACTERIZATION OF VARIANTS ARMD3
RP   LEU-60; GLN-71; SER-87; PRO-124; THR-169; SER-267; TRP-351; THR-363
RP   AND GLU-412, VARIANTS ARCL1A ARG-217 AND PRO-227, CHARACTERIZATION OF
RP   VARIANTS ARCL1A ARG-217 AND PRO-227, VARIANTS MET-126 AND ARG-202, AND
RP   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
RT   and cutis laxa.";
RL   Hum. Mutat. 27:568-574(2006).
RN   [18]
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   [19]
RP   VARIANT ARCL1A ARG-217, CHARACTERIZATION OF VARIANT ARCL1A ARG-217,
RP   AND FUNCTION.
RX   PubMed=18185537; DOI=10.1038/sj.jid.5701211;
RA   Claus S., Fischer J., Megarbane H., Megarbane A., Jobard F.,
RA   Debret R., Peyrol S., Saker S., Devillers M., Sommer P., Damour O.;
RT   "A p.C217R mutation in fibulin-5 from cutis laxa patients is
RT   associated with incomplete extracellular matrix formation in a skin
RT   equivalent model.";
RL   J. Invest. Dermatol. 128:1442-1450(2008).
RN   [20]
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.,
RA   de Cid R., Cure S., Saker S., Megarbane A., Fischer J.;
RT   "An autosomal-recessive form of cutis laxa is due to homozygous
RT   elastin mutations, and the phenotype may be modified by a heterozygous
RT   fibulin 5 polymorphism.";
RL   J. Invest. Dermatol. 129:1650-1655(2009).
RN   [21]
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;
RP   TRP-351 AND GLU-412, CHARACTERIZATION OF VARIANTS ARCL1A ARG-217 AND
RP   PRO-227, AND 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
RT   age-related macular degeneration and cutis laxa.";
RL   Invest. Ophthalmol. Vis. Sci. 51:2356-2362(2010).
RN   [22]
RP   CHARACTERIZATION OF VARIANTS ARCL1A PRO-227 AND SER-267,
RP   CHARACTERIZATION OF VARIANT ARMD3 THR-169, CHARACTERIZATION OF VARIANT
RP   ARG-202, AND 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   [23]
RP   VARIANTS HNARMD ILE-48; SER-90; SER-267 AND CYS-373, AND VARIANT
RP   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.,
RA   Windpassinger C., Senderek J., Budka H., Trajanoski S., Janecke A.R.,
RA   Haas A., Metze D., 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   [24]
RP   VARIANT HNARMD CYS-373.
RX   PubMed=23328402; DOI=10.1093/brain/aws333;
RA   Safka Brozkova D., Lassuthova P., Neupauerova J., Krutova M.,
RA   Haberlova J., Stejskal D., Seeman P.;
RT   "Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth
RT   type 1 neuropathy.";
RL   Brain 136:E232-E232(2013).
CC   -!- FUNCTION: Essential for elastic fiber formation, is involved in
CC       the assembly of continuous elastin (ELN) polymer and promotes the
CC       interaction of microfibrils and ELN (PubMed:18185537). Stabilizes
CC       and organizes elastic fibers in the skin, lung and vasculature (By
CC       similarity). Promotes adhesion of endothelial cells through
CC       interaction of integrins and the RGD motif. Vascular ligand for
CC       integrin receptors which may play a role in vascular development
CC       and remodeling (PubMed:10428823). May act as an adapter that
CC       mediates the interaction between FBN1 and ELN (PubMed:17255108).
CC       {ECO:0000250|UniProtKB:Q9WVH9, ECO:0000269|PubMed:10428823,
CC       ECO:0000269|PubMed:17255108, 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).
CC       Interacts with FBN1 (via N-terminal domain). Forms a ternary
CC       complex with ELN and FBN1 (PubMed:17255108).
CC       {ECO:0000250|UniProtKB:Q9WVH9, ECO:0000269|PubMed:15790312,
CC       ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:17255108,
CC       ECO:0000269|PubMed:19617354, ECO:0000269|PubMed:20007835}.
CC   -!- INTERACTION:
CC       O95967:EFEMP2; NbExp=3; IntAct=EBI-947897, EBI-743414;
CC       P15502:ELN; NbExp=3; IntAct=EBI-947897, EBI-1222108;
CC       P35555:FBN1; NbExp=3; IntAct=EBI-947897, EBI-2505934;
CC       P28300:LOX; NbExp=2; IntAct=EBI-947897, EBI-3893481;
CC       Q14767:LTBP2; NbExp=2; IntAct=EBI-947897, EBI-1546118;
CC       P50222:MEOX2; NbExp=3; IntAct=EBI-947897, EBI-748397;
CC       P32242:OTX1; NbExp=3; IntAct=EBI-947897, EBI-740446;
CC       Q15645:TRIP13; NbExp=3; IntAct=EBI-947897, EBI-358993;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16652333,
CC       ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:20599547}.
CC       Secreted, extracellular space, extracellular matrix
CC       {ECO:0000269|PubMed:17035250}. Note=co-localizes with ELN in
CC       elastic fibers. {ECO:0000269|PubMed:17035250}.
CC   -!- TISSUE SPECIFICITY: Expressed in skin fibroblasts (at protein
CC       level)(PubMed:17035250). Expressed predominantly in heart, ovary,
CC       and colon but also in kidney, pancreas, testis, lung and placenta.
CC       Not detectable in brain, liver, thymus, prostate, or peripheral
CC       blood 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: Neuropathy, hereditary, with or without age-related
CC       macular degeneration (HNARMD) [MIM:608895]: An autosomal dominant
CC       neuropathy of the Charcot-Marie-Tooth disease group, characterized
CC       by distal muscle weakness and atrophy variably affecting the lower
CC       and upper limbs. Distal sensory impairment and decreased nerve
CC       conduction velocities are present in most but not all patients.
CC       Additional variable features are age-related macular degeneration,
CC       joint hypermobility, and hyperelastic skin.
CC       {ECO:0000269|PubMed:21576112, ECO:0000269|PubMed:23328402}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Cutis laxa, autosomal dominant, 2 (ADCL2) [MIM:614434]: A
CC       connective tissue disorder characterized by loose, hyperextensible
CC       skin with decreased resilience and elasticity leading to a
CC       premature aged appearance. Face, hands, feet, joints, and torso
CC       may be differentially affected. Additional variable clinical
CC       features are gastrointestinal diverticula, hernia, and genital
CC       prolapse. Rare manifestations are pulmonary artery stenosis,
CC       aortic aneurysm, bronchiectasis, and emphysema.
CC       {ECO:0000269|PubMed:12618961}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Cutis laxa, autosomal recessive, 1A (ARCL1A)
CC       [MIM:219100]: A connective tissue disorder characterized by loose,
CC       hyperextensible skin with decreased resilience and elasticity
CC       leading to a premature aged appearance. Face, hands, feet, joints,
CC       and torso may be differentially affected. The clinical spectrum of
CC       autosomal recessive cutis laxa is highly heterogeneous with
CC       respect to organ involvement and severity. Type I autosomal
CC       recessive cutis laxa is a specific, life-threatening disorder with
CC       organ involvement, lung atelectasis and emphysema, diverticula of
CC       the gastrointestinal and genitourinary systems, and vascular
CC       anomalies. Associated cranial anomalies, late closure of the
CC       fontanel, joint laxity, hip dislocation, and inguinal hernia have
CC       been 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}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry. Mutations affecting this gene can
CC       modify the phenotype of diseases caused by ELN mutations.
CC       {ECO:0000269|PubMed:19194475}.
CC   -!- DISEASE: Macular degeneration, age-related, 3 (ARMD3)
CC       [MIM:608895]: A form of age-related macular degeneration, a
CC       multifactorial eye disease and the most common cause of
CC       irreversible vision loss in the developed world. In most patients,
CC       the disease is manifest as ophthalmoscopically visible yellowish
CC       accumulations of protein and lipid that lie beneath the retinal
CC       pigment epithelium and within an elastin-containing structure
CC       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
CC       associated with variations affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the fibulin family. {ECO:0000305}.
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   UniGene; Hs.332708; -.
DR   ProteinModelPortal; Q9UBX5; -.
DR   SMR; Q9UBX5; -.
DR   BioGrid; 115771; 19.
DR   CORUM; Q9UBX5; -.
DR   DIP; DIP-44301N; -.
DR   IntAct; Q9UBX5; 26.
DR   MINT; Q9UBX5; -.
DR   STRING; 9606.ENSP00000345008; -.
DR   GlyConnect; 1245; -.
DR   iPTMnet; Q9UBX5; -.
DR   PhosphoSitePlus; Q9UBX5; -.
DR   BioMuta; FBLN5; -.
DR   DMDM; 12643876; -.
DR   REPRODUCTION-2DPAGE; IPI00294615; -.
DR   jPOST; Q9UBX5; -.
DR   PaxDb; Q9UBX5; -.
DR   PeptideAtlas; Q9UBX5; -.
DR   PRIDE; Q9UBX5; -.
DR   ProteomicsDB; 84093; -.
DR   DNASU; 10516; -.
DR   Ensembl; ENST00000342058; ENSP00000345008; ENSG00000140092.
DR   GeneID; 10516; -.
DR   KEGG; hsa:10516; -.
DR   UCSC; uc001xzx.5; human.
DR   CTD; 10516; -.
DR   DisGeNET; 10516; -.
DR   EuPathDB; HostDB:ENSG00000140092.14; -.
DR   GeneCards; FBLN5; -.
DR   GeneReviews; FBLN5; -.
DR   HGNC; HGNC:3602; FBLN5.
DR   HPA; CAB025843; -.
DR   HPA; HPA000848; -.
DR   HPA; HPA000868; -.
DR   MalaCards; FBLN5; -.
DR   MIM; 219100; phenotype.
DR   MIM; 604580; gene.
DR   MIM; 608895; phenotype.
DR   MIM; 614434; 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   eggNOG; ENOG410IR76; Eukaryota.
DR   eggNOG; ENOG41104WD; LUCA.
DR   GeneTree; ENSGT00940000158774; -.
DR   HOGENOM; HOG000234337; -.
DR   HOVERGEN; HBG051560; -.
DR   InParanoid; Q9UBX5; -.
DR   KO; K17340; -.
DR   OrthoDB; 1174178at2759; -.
DR   PhylomeDB; Q9UBX5; -.
DR   TreeFam; TF317514; -.
DR   Reactome; R-HSA-1566948; Elastic fibre formation.
DR   Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR   SIGNOR; Q9UBX5; -.
DR   GeneWiki; FBLN5; -.
DR   GenomeRNAi; 10516; -.
DR   PRO; PR:Q9UBX5; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   Bgee; ENSG00000140092; Expressed in 199 organ(s), highest expression level in thoracic aorta.
DR   ExpressionAtlas; Q9UBX5; baseline and differential.
DR   Genevisible; Q9UBX5; HS.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR   GO; GO:0071953; C:elastic fiber; IEA:Ensembl.
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:0030023; F:extracellular matrix constituent conferring elasticity; HDA:BHF-UCL.
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:0030198; P:extracellular matrix organization; TAS:Reactome.
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; 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; IPR037288; Fibulin-5.
DR   InterPro; IPR037287; Fibulin_3/4/5.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   PANTHER; PTHR44074; PTHR44074; 1.
DR   PANTHER; PTHR44074:SF4; PTHR44074:SF4; 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; Complete proteome; Disease mutation;
KW   Disulfide bond; EGF-like domain; Extracellular matrix; Glycoprotein;
KW   Neuropathy; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   CHAIN        24    448       Fibulin-5.
FT                                /FTId=PRO_0000007577.
FT   DOMAIN       42     82       EGF-like 1; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      127    167       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      168    206       EGF-like 3; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      207    246       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      247    287       EGF-like 5; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      288    333       EGF-like 6; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   MOTIF        54     56       Cell attachment site. {ECO:0000255}.
FT   CARBOHYD    283    283       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    296    296       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     46     59       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID     53     68       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    131    144       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    138    153       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    155    166       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    172    181       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    177    190       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    192    205       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    211    221       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    217    230       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    232    245       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    251    262       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    258    271       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    273    286       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    292    305       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    299    314       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    320    332       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   VARIANT      48     48       T -> I (in HNARMD; dbSNP:rs141200859).
FT                                {ECO:0000269|PubMed:21576112}.
FT                                /FTId=VAR_076289.
FT   VARIANT      60     60       V -> L (in ARMD3; no effect on secretion;
FT                                no effect on homodimerization;
FT                                dbSNP:rs121434299).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_019814.
FT   VARIANT      71     71       R -> Q (in ARMD3; no effect on secretion;
FT                                no effect on homodimerization;
FT                                dbSNP:rs121434300).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_019815.
FT   VARIANT      87     87       P -> S (in ARMD3; no effect on secretion;
FT                                slightly increases homodimerization in
FT                                absence of Ca(2+); dbSNP:rs121434301).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_019816.
FT   VARIANT      90     90       G -> S (in HNARMD; dbSNP:rs144288844).
FT                                {ECO:0000269|PubMed:21576112}.
FT                                /FTId=VAR_076290.
FT   VARIANT     124    124       Q -> P (in ARMD3; almost abolishes
FT                                secretion; no effect on
FT                                homodimerization).
FT                                {ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_072389.
FT   VARIANT     126    126       V -> M (polymorphism; no effect on
FT                                secretion; slightly increases
FT                                homodimerization in absence of Ca(2+);
FT                                dbSNP:rs61734479).
FT                                {ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835,
FT                                ECO:0000269|PubMed:21576112}.
FT                                /FTId=VAR_072390.
FT   VARIANT     169    169       I -> T (in ARMD3; decreases secretion;
FT                                slightly increases homodimerization in
FT                                absence of Ca(2+); no effect on protein
FT                                folding; dbSNP:rs28939072).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835,
FT                                ECO:0000269|PubMed:20599547}.
FT                                /FTId=VAR_019817.
FT   VARIANT     202    202       G -> R (polymorphism; slightly increases
FT                                homodimerization in absence of Ca(2+); no
FT                                effect on protein folding; no effect on
FT                                secretion; dbSNP:rs80338765).
FT                                {ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835,
FT                                ECO:0000269|PubMed:20599547}.
FT                                /FTId=VAR_072391.
FT   VARIANT     217    217       C -> R (in ARCL1A; formation of
FT                                extracellular globular aggregates;
FT                                decreases cell growth; reduces
FT                                interaction with ELN; abolishes
FT                                secretion; increases homodimerization;
FT                                dbSNP:rs80338766).
FT                                {ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:17035250,
FT                                ECO:0000269|PubMed:18185537,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_072392.
FT   VARIANT     227    227       S -> P (in ARCL1A; decreases expression;
FT                                produces protein misfolding; abolishes
FT                                secretion; reduces interaction with ELN;
FT                                increases homodimerization; impairs
FT                                elastic fiber development;
FT                                dbSNP:rs28939370).
FT                                {ECO:0000269|PubMed:12189163,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:16691202,
FT                                ECO:0000269|PubMed:17035250,
FT                                ECO:0000269|PubMed:20007835,
FT                                ECO:0000269|PubMed:20599547}.
FT                                /FTId=VAR_017153.
FT   VARIANT     267    267       G -> S (in ARMD3, ARCL1A and HNARMD;
FT                                produces protein misolding; decreases
FT                                secretion; no effect on homodimerization;
FT                                dbSNP:rs149396611).
FT                                {ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835,
FT                                ECO:0000269|PubMed:20599547,
FT                                ECO:0000269|PubMed:21576112}.
FT                                /FTId=VAR_072393.
FT   VARIANT     301    301       L -> M (found in a patient with autosomal
FT                                recessive cutis laxa also carrying a
FT                                mutation in ELN; unknown pathological
FT                                significance; dbSNP:rs377360782).
FT                                {ECO:0000269|PubMed:19194475}.
FT                                /FTId=VAR_072394.
FT   VARIANT     351    351       R -> W (in ARMD3; no effect on secretion;
FT                                slightly increases homodimerization in
FT                                absence of Ca(2+); dbSNP:rs28939073).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_019818.
FT   VARIANT     363    363       A -> T (in ARMD3; no effect on secretion;
FT                                dbSNP:rs121434302).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333}.
FT                                /FTId=VAR_019819.
FT   VARIANT     364    364       D -> Y (in dbSNP:rs1802492).
FT                                /FTId=VAR_026986.
FT   VARIANT     373    373       R -> C (in HNARMD; dbSNP:rs864309526).
FT                                {ECO:0000269|PubMed:21576112,
FT                                ECO:0000269|PubMed:23328402}.
FT                                /FTId=VAR_076291.
FT   VARIANT     412    412       G -> E (in ARMD3; decreases secretion;
FT                                slightly increases homodimerization in
FT                                absence of Ca(2+); dbSNP:rs121434303).
FT                                {ECO:0000269|PubMed:15269314,
FT                                ECO:0000269|PubMed:16652333,
FT                                ECO:0000269|PubMed:20007835}.
FT                                /FTId=VAR_019820.
FT   CONFLICT     69     70       IP -> HS (in Ref. 3; AAC62107).
FT                                {ECO:0000305}.
FT   CONFLICT    147    148       TE -> MK (in Ref. 3; AAC62107).
FT                                {ECO:0000305}.
FT   CONFLICT    228    228       F -> L (in Ref. 4; AAQ89257).
FT                                {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
//
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