FBLN5

Protein identityUniProt · HPA

UniProt accession

Q9UBX5

Gene

FBLN5

Ensembl

ENSG00000140092

Chromosome

14

Canonical length

448 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Plasma membrane

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a secreted, extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif and calcium-binding EGF-like domains. It promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. It is prominently expressed in developing arteries but less so in adult vessels. However, its expression is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells. Therefore, the protein encoded by this gene may play a role in vascular development and remodeling. Defects in this gene are a cause of autosomal dominant cutis laxa, autosomal recessive cutis laxa type I (CL type I), and age-related macular degeneration type 3 (ARMD3). [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

448 residues, UniProt reviewed canonical sequence.

>Q9UBX5|FBLN5
     1  MPGIKRILTV TILALCLPSP GNAQAQCTNG FDLDRQSGQC LDIDECRTIP EACRGDMMCV
    61  NQNGGYLCIP RTNPVYRGPY SNPYSTPYSG PYPAAAPPLS APNYPTISRP LICRFGYQMD
   121  ESNQCVDVDE CATDSHQCNP TQICINTEGG YTCSCTDGYW LLEGQCLDID ECRYGYCQQL
   181  CANVPGSYSC TCNPGFTLNE DGRSCQDVNE CATENPCVQT CVNTYGSFIC RCDPGYELEE
   241  DGVHCSDMDE CSFSEFLCQH ECVNQPGTYF CSCPPGYILL DDNRSCQDIN ECEHRNHTCN
   301  LQQTCYNLQG GFKCIDPIRC EEPYLRISDN RCMCPAENPG CRDQPFTILY RDMDVVSGRS
   361  VPADIFQMQA TTRYPGAYYI FQIKSGNEGR EFYMRQTGPI SATLVMTRPI KGPREIQLDL
   421  EMITVNTVIN FRGSSVIRLR IYVSQYPF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FBLN5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

668 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FBLN5.

Disease | AllUniProt

Conditions FBLN5 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, demyelinating, type 1H (CMT1H) MIM:619764
• Cutis laxa, autosomal dominant, 2 (ADCL2) MIM:614434
• Cutis laxa, autosomal recessive, 1A (ARCL1A) MIM:219100
• Macular degeneration, age-related, 3 (ARMD3) MIM:608895

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 688 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Charcot-Marie-Tooth disease, demyelinating, IIA 1H
• Cutis laxa, autosomal recessive, type 1A
• Cutis laxa, autosomal dominant 2
• Hereditary sensorimotor neuropathy with hyperelastic skin
• Macular degeneration, age-related, 3

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.17

gnomAD pLI

1

gnomAD missense Z

1.56

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 1% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell-matrix adhesion
• elastic fiber assembly
• negative regulation of angiogenesis
• negative regulation of transcription by RNA polymerase II
• positive regulation of osteoblast proliferation
• positive regulation of transcription by RNA polymerase II
• protein localization to cell surface
• regulation of removal of superoxide radicals
• secretion
• intramembranous bone growth

Molecular functions

• calcium ion binding
• integrin binding
• protein homodimerization activity

Cellular components

• elastic fiber
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• EGF-like calcium-binding, conserved site
• Complement Clr-like EGF domain
• NOTCH1, EGF-like calcium-binding domain
• Nephronectin domain-containing protein
• Fibulin, C-terminal Ig-like domain
• Calcium-binding EGF domain
• Complement Clr-like EGF-like
• Fibulin C-terminal Ig-like domain

KeywordsUniProt

• Age-related macular degeneration
• Calcium
• Cell adhesion
• Charcot-Marie-Tooth disease
• Disulfide bond
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Neurodegeneration
• Neuropathy
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of FBLN5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ELN
• FBN1
• LOXL1
• ITGB5
• ITGB3
• ITGA9
• NUFIP2