Q9UBX5 (FBLN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibulin-5
Short name=FIBL-5

Alternative name(s):
Developmental arteries and neural crest EGF-like protein
Short name=Dance
Urine p50 protein
Short name=UP50

Gene names

Name:	FBLN5
Synonyms:	DANCE
ORF Names:	UNQ184/PRO210

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	448 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. Could be a vascular ligand for integrin receptors and may play a role in vascular development and remodeling.
Subunit structure	Homodimer. Ref.9
Subcellular location	Secreted.
Tissue specificity	Expressed predominantly in heart, ovary, and colon but also in kidney, pancreas, testis, lung and placenta. Not detectable in brain, liver, thymus, prostate, or peripheral blood leukocytes.
Involvement in disease	Cutis laxa, autosomal dominant, 2 (ADCL2) [MIM:614434]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Cutis laxa, autosomal recessive, 1A (ARCL1A) [MIM:219100]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.13 Age-related macular degeneration 3 (ARMD3) [MIM:608895]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.12
Sequence similarities	Belongs to the fibulin family. Contains 6 EGF-like domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Secreted
Disease	Age-related macular degeneration Disease mutation
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-matrix adhesion Traceable author statement Ref.2. Source: ProtInc elastic fiber assembly Inferred from sequence or structural similarity. Source: BHF-UCL protein localization to cell surface Inferred from sequence or structural similarity. Source: BHF-UCL regulation of cell growth Inferred from electronic annotation. Source: Compara regulation of removal of superoxide radicals Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA elastic fiber Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL proteinaceous extracellular matrix Traceable author statement Ref.2. Source: ProtInc
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro integrin binding Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EFEMP2	O95967	3	EBI-947897,EBI-743414
ELN	P15502	3	EBI-947897,EBI-1222108
FBN1	P35555	3	EBI-947897,EBI-2505934

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 448	425	Fibulin-5		PRO_0000007577
Regions
	Domain	42 – 82	41	EGF-like 1; calcium-binding Potential
	Domain	127 – 167	41	EGF-like 2; calcium-binding Potential
	Domain	168 – 206	39	EGF-like 3; calcium-binding Potential
	Domain	207 – 246	40	EGF-like 4; calcium-binding Potential
	Domain	247 – 287	41	EGF-like 5; calcium-binding Potential
	Domain	288 – 333	46	EGF-like 6; calcium-binding Potential
	Motif	54 – 56	3	Cell attachment site Potential
Amino acid modifications
	Glycosylation	283	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Disulfide bond	46 ↔ 59		By similarity
	Disulfide bond	53 ↔ 68		By similarity
	Disulfide bond	131 ↔ 144		By similarity
	Disulfide bond	138 ↔ 153		By similarity
	Disulfide bond	155 ↔ 166		By similarity
	Disulfide bond	172 ↔ 181		By similarity
	Disulfide bond	177 ↔ 190		By similarity
	Disulfide bond	192 ↔ 205		By similarity
	Disulfide bond	211 ↔ 221		By similarity
	Disulfide bond	217 ↔ 230		By similarity
	Disulfide bond	232 ↔ 245		By similarity
	Disulfide bond	251 ↔ 262		By similarity
	Disulfide bond	258 ↔ 271		By similarity
	Disulfide bond	273 ↔ 286		By similarity
	Disulfide bond	292 ↔ 305		By similarity
	Disulfide bond	299 ↔ 314		By similarity
	Disulfide bond	320 ↔ 332		By similarity
Natural variations
	Natural variant	60	1	V → L in ARMD3. Ref.12 Corresponds to variant rs28939371 [ dbSNP | Ensembl ].		VAR_019814
	Natural variant	71	1	R → Q in ARMD3. Ref.12 Corresponds to variant rs28939372 [ dbSNP | Ensembl ].		VAR_019815
	Natural variant	87	1	P → S in ARMD3. Ref.12 Corresponds to variant rs28939373 [ dbSNP | Ensembl ].		VAR_019816
	Natural variant	169	1	I → T in ARMD3. Ref.12 Corresponds to variant rs28939072 [ dbSNP | Ensembl ].		VAR_019817
	Natural variant	227	1	S → P in ARCL1A. Ref.10 Ref.13 Corresponds to variant rs28939370 [ dbSNP | Ensembl ].		VAR_017153
	Natural variant	351	1	R → W in ARMD3. Ref.12 Corresponds to variant rs28939073 [ dbSNP | Ensembl ].		VAR_019818
	Natural variant	363	1	A → T in ARMD3. Ref.12		VAR_019819
	Natural variant	364	1	D → Y. Corresponds to variant rs1802492 [ dbSNP | Ensembl ].		VAR_026986
	Natural variant	412	1	G → E in ARMD3. Ref.12		VAR_019820
Experimental info
	Sequence conflict	69 – 70	2	IP → HS in AAC62107. Ref.3
	Sequence conflict	147 – 148	2	TE → MK in AAC62107. Ref.3
	Sequence conflict	228	1	F → L in AAQ89257. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9UBX5 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 19FCA51FDA328003	FASTA	448	50,180
	10 20 30 40 50 60 MPGIKRILTV TILALCLPSP GNAQAQCTNG FDLDRQSGQC LDIDECRTIP EACRGDMMCV 70 80 90 100 110 120 NQNGGYLCIP RTNPVYRGPY SNPYSTPYSG PYPAAAPPLS APNYPTISRP LICRFGYQMD 130 140 150 160 170 180 ESNQCVDVDE CATDSHQCNP TQICINTEGG YTCSCTDGYW LLEGQCLDID ECRYGYCQQL 190 200 210 220 230 240 CANVPGSYSC TCNPGFTLNE DGRSCQDVNE CATENPCVQT CVNTYGSFIC RCDPGYELEE 250 260 270 280 290 300 DGVHCSDMDE CSFSEFLCQH ECVNQPGTYF CSCPPGYILL DDNRSCQDIN ECEHRNHTCN 310 320 330 340 350 360 LQQTCYNLQG GFKCIDPIRC EEPYLRISDN RCMCPAENPG CRDQPFTILY RDMDVVSGRS 370 380 390 400 410 420 VPADIFQMQA TTRYPGAYYI FQIKSGNEGR EFYMRQTGPI SATLVMTRPI KGPREIQLDL 430 440 EMITVNTVIN FRGSSVIRLR IYVSQYPF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Kostka G. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Melanoma.
[2]	"DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries." Nakamura T., Ruiz-Lozano P., Lindner V., Yabe D., Taniwaki M., Furukawa Y., Kobuke K., Tashiro K., Lu Z., Andon N.L., Schaub R., Matsumori A., Sasayama S., Chien K.R., Honjo T. J. Biol. Chem. 274:22476-22483(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Zemel R., Sholto O., Shaul Y. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Urine.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[9]	"Fibulin 5 forms a compact dimer in physiological solutions." Jones R.P., Wang M.C., Jowitt T.A., Ridley C., Mellody K.T., Howard M., Wang T., Bishop P.N., Lotery A.J., Kielty C.M., Baldock C., Trump D. J. Biol. Chem. 284:25938-25943(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[10]	"Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa." Loeys B., van Maldergem L., Mortier G., Coucke P., Gerniers S., Naeyaert J.-M., de Paepe A. Hum. Mol. Genet. 11:2113-2118(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCL1A PRO-227.
[11]	"Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene." Markova D., Zou Y., Ringpfeil F., Sasaki T., Kostka G., Timpl R., Uitto J., Chu M.-L. Am. J. Hum. Genet. 72:998-1004(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ADCL2.
[12]	"Missense variations in the fibulin 5 gene and age-related macular degeneration." Stone E.M., Braun T.A., Russell S.R., Kuehn M.H., Lotery A.J., Moore P.A., Eastman C.G., Casavant T.L., Sheffield V.C. N. Engl. J. Med. 351:346-353(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARMD3 LEU-60; GLN-71; SER-87; THR-169; TRP-351; THR-363 AND GLU-412.
[13]	"Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype." Elahi E., Kalhor R., Banihosseini S.S., Torabi N., Pour-Jafari H., Houshmand M., Amini S.S.H., Ramezani A., Loeys B. J. Invest. Dermatol. 126:1506-1509(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCL1A PRO-227.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ133490 mRNA. Translation: CAB38568.1. AF112152 mRNA. Translation: AAD41768.1. AF093118 mRNA. Translation: AAC62107.1. AY358898 mRNA. Translation: AAQ89257.1. CR457140 mRNA. Translation: CAG33421.1. AK075147 mRNA. Translation: BAG52073.1. CH471061 Genomic DNA. Translation: EAW81466.1. BC022280 mRNA. Translation: AAH22280.1.
IPI	IPI00294615.
RefSeq	NP_006320.2. NM_006329.3.
UniGene	Hs.332708.
3D structure databases
ProteinModelPortal	Q9UBX5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBX5. 14 interactions.
MINT	MINT-2868380.
STRING	9606.ENSP00000345008.
Polymorphism databases
DMDM	12643876.
2D gel databases
REPRODUCTION-2DPAGE	IPI00294615.
Proteomic databases
PaxDb	Q9UBX5.
PeptideAtlas	Q9UBX5.
PRIDE	Q9UBX5.
Protocols and materials databases
DNASU	10516.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342058; ENSP00000345008; ENSG00000140092.
GeneID	10516.
KEGG	hsa:10516.
UCSC	uc001xzx.4. human.
Organism-specific databases
CTD	10516.
GeneCards	GC14M092335.
HGNC	HGNC:3602. FBLN5.
HPA	CAB025843. HPA000848. HPA000868.
MIM	219100. phenotype. 604580. gene. 608895. phenotype. 614434. phenotype.
neXtProt	NX_Q9UBX5.
Orphanet	279. Age-related macular degeneration. 90348. Autosomal dominant cutis laxa. 90349. Autosomal recessive cutis laxa type 1. 280598. Hereditary sensorimotor neuropathy with hyperelastic skin.
PharmGKB	PA28015.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG309650.
HOGENOM	HOG000234337.
HOVERGEN	HBG051560.
OrthoDB	EOG4W6NVQ.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q9UBX5.
Bgee	Q9UBX5.
CleanEx	HS_FBLN5.
Genevestigator	Q9UBX5.
GermOnline	ENSG00000140092. Homo sapiens.
Family and domain databases
InterPro	IPR026823. cEGF. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. [Graphical view]
Pfam	PF12662. cEGF. 2 hits. PF07645. EGF_CA. 2 hits. [Graphical view]
SMART	SM00179. EGF_CA. 4 hits. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 4 hits. PS00022. EGF_1. False negative. PS01186. EGF_2. 4 hits. PS50026. EGF_3. 5 hits. PS01187. EGF_CA. 6 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10516.
NextBio	39880.
SOURCE	Search...

Entry information

Entry name

FBLN5_HUMAN

Accession

Primary (citable) accession number: Q9UBX5
Secondary accession number(s): O75966, Q6IAL4, Q6UWA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.