Q9WVJ9 · FBLN4_MOUSE
- ProteinEGF-containing fibulin-like extracellular matrix protein 2
- GeneEfemp2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids443 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
In addition, is involved in the control of collagen fibril assembly in tissue throught proteolytic activation of LOX leading to cross- linking of collagen and elastin (PubMed:26178373, PubMed:26220971, PubMed:26690653, PubMed:26711913).
Also promotes ELN coacervation and participates in the deposition of ELN coacervates on to microfibrils but also regulates ELN cross- linking through LOX interaction (PubMed:17324935).
Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling (PubMed:23636094).
Miscellaneous
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 87-88 | Cleavage; by ELANE | ||||
Sequence: VI | ||||||
Site | 90-91 | Cleavage; by MMP2, MMP3, MMP7, MMP9, MMP12 | ||||
Sequence: DL | ||||||
Site | 92-93 | Cleavage | ||||
Sequence: HG |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | basement membrane | |
Cellular Component | collagen-containing extracellular matrix | |
Cellular Component | elastic fiber | |
Cellular Component | extracellular matrix | |
Cellular Component | extracellular space | |
Cellular Component | microfibril | |
Molecular Function | calcium ion binding | |
Molecular Function | heparin binding | |
Molecular Function | protein homodimerization activity | |
Biological Process | aorta development | |
Biological Process | aorta smooth muscle tissue morphogenesis | |
Biological Process | artery development | |
Biological Process | elastic fiber assembly | |
Biological Process | negative regulation of vascular associated smooth muscle cell proliferation | |
Biological Process | positive regulation of aortic smooth muscle cell differentiation | |
Biological Process | positive regulation of collagen fibril organization | |
Biological Process | positive regulation of smooth muscle cell-matrix adhesion | |
Biological Process | regulation of collagen fibril organization | |
Biological Process | vascular associated smooth muscle cell development |
Keywords
- Ligand
Enzyme and pathway databases
Has a role in extracellular matrix assembly, where it is essential for the activity of LOX (Lysyl oxidase enzyme). Required for the transfer of copper ion from copper transporter ATP7A to LOX in the trans-golgi network. This is an important step in the formation of lysine tyrosyl quinone (LTQ), an essential LOX cofactor.
Influences cytoskeletal structure and TGF-beta signaling in vascular smooth muscle cells.
In mutant mice with 4-fold reduction in FBLN-4 protein, altered mitochondrial function and metabolic dysregulation.
Critical to elastogenesis.
Names & Taxonomy
Protein names
- Recommended nameEGF-containing fibulin-like extracellular matrix protein 2
- Alternative names
Gene names
- Community suggested namesFBLN4
- Community suggested namesFBLN4
- Community suggested namesFBLN-4
- Community suggested namesFBLN4
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9WVJ9
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Homozygous mice exhibit severe lung and vascular defects including emphysema, artery tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages (PubMed:16478991, PubMed:19855011, PubMed:26178373, PubMed:28508064).
Mice died perinatally (PubMed:16478991, PubMed:19855011).
Mice with conditional knockout of EFEMP2, in vascular smooth muscle, grow normally, are fertile and exhibit an arterial stiffness (PubMed:19855011).
Mice with conditional knockout of EFEMP2, in endothelial cell (EC) are healthy with an normal aorta (PubMed:20019329).
Mice with conditional knockout of EFEMP2, in smooth muscle cells, die spontaneously at approximately 2 months of age despite absence of embryonic or neonatal lethality. Aortae exhibit large aneurysms exclusively in the ascending aorta. Aneurysms are observed with complete penetrance (PubMed:20019329, PubMed:23636094, PubMed:26220971, PubMed:26486174).
Homozygous mice for the EFEMP2 gene die within 1-2 days after birth. Embryos at 19 dpc show bilateral forelimb contractures (PubMed:26690653, PubMed:26711913).
Newborn homozygous mice demonstrate normal morphology of the skeleton (PubMed:26690653).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 57 | Knockin mutant mice are viable and survive into adulthood. Mice display abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. In addition to elastic fiber abnormalities in the skin and large arteries, collagen fibrils are irregularly shaped, with many large fibrils in the dermis. Mice have large artery stiffness and systolic hypertension. Reduces protein secretion. | ||||
Sequence: E → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, modified residue, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-27 | |||||
Sequence: MLPFASCLPGSLLLWAFLLLLLGAASP | ||||||
Modified residue | 28 | Pyrrolidone carboxylic acid | ||||
Sequence: Q | ||||||
Chain | PRO_0000007576 | 28-443 | EGF-containing fibulin-like extracellular matrix protein 2 | |||
Sequence: QDPEEPDSYTECTDGYEWDADSQHCRDVNECLTIPEACKGEMKCINHYGGYLCLPRSAAVISDLHGEGPPPPAAHAQQPNPCPQGYEPDEQESCVDVDECTQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECVDIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRSCVDVNECDMGAPCEQRCFNSYGTFLCRCNQGYELHRDGFSCSDIDECGYSSYLCQYRCVNEPGRFSCHCPQGYQLLATRLCQDIDECETGAHQCSEAQTCVNFHGGYRCVDTNRCVEPYVQVSDNRCLCPASNPLCREQPSSIVHRYMSITSERSVPADVFQIQATSVYPGAYNAFQIRSGNTQGDFYIRQINNVSAMLVLARPVTGPREYVLDLEMVTMNSLMSYRASSVLRLTVFVGAYTF | ||||||
Disulfide bond | 58↔121 | |||||
Sequence: CLTIPEACKGEMKCINHYGGYLCLPRSAAVISDLHGEGPPPPAAHAQQPNPCPQGYEPDEQESC | ||||||
Disulfide bond | 65↔80 | |||||
Sequence: CKGEMKCINHYGGYLC | ||||||
Disulfide bond | 71↔109 | |||||
Sequence: CINHYGGYLCLPRSAAVISDLHGEGPPPPAAHAQQPNPC | ||||||
Disulfide bond | 127↔140 | |||||
Sequence: CTQALHDCRPSQDC | ||||||
Disulfide bond | 134↔149 | |||||
Sequence: CRPSQDCHNLPGSYQC | ||||||
Disulfide bond | 151↔162 | |||||
Sequence: CPDGYRKIGPEC | ||||||
Disulfide bond | 168↔177 | |||||
Sequence: CRYRYCQHRC | ||||||
Disulfide bond | 173↔186 | |||||
Sequence: CQHRCVNLPGSFRC | ||||||
Disulfide bond | 188↔201 | |||||
Sequence: CEPGFQLGPNNRSC | ||||||
Glycosylation | 198 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 207↔217 | |||||
Sequence: CDMGAPCEQRC | ||||||
Disulfide bond | 213↔226 | |||||
Sequence: CEQRCFNSYGTFLC | ||||||
Disulfide bond | 228↔241 | |||||
Sequence: CNQGYELHRDGFSC | ||||||
Disulfide bond | 247↔258 | |||||
Sequence: CGYSSYLCQYRC | ||||||
Disulfide bond | 254↔267 | |||||
Sequence: CQYRCVNEPGRFSC | ||||||
Disulfide bond | 269↔281 | |||||
Sequence: CPQGYQLLATRLC | ||||||
Disulfide bond | 287↔300 | |||||
Sequence: CETGAHQCSEAQTC | ||||||
Disulfide bond | 294↔309 | |||||
Sequence: CSEAQTCVNFHGGYRC | ||||||
Disulfide bond | 315↔327 | |||||
Sequence: CVEPYVQVSDNRC | ||||||
Glycosylation | 394 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in tendon around tenocytes (PubMed:26711913).
Prominently expressed in cartilage, bone, perichondrium and ligaments. Also detected in bone marrow stroma (PubMed:26690653).
Expressed in aorta, lung, and esophagus (PubMed:17324935).
Developmental stage
Gene expression databases
Interaction
Subunit
Multimer; allows heparin binding (By similarity).
Monomer (PubMed:17324935).
Binds preferentially to p53 mutants (PubMed:10380882).
Interacts with FBN1 (via N-terminal domain); this interaction inhibits EFEMP2 binding to LOX and ELN (By similarity).
Interacts with ELN with moderate affinity; this interaction regulates ELN self-assembly maturation stage (PubMed:16478991, PubMed:17324935).
Interacts with PCOLCE (PubMed:26220971).
Interacts with collagen type IV trimer (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived endostatin (PubMed:17324935).
Interacts with EMILIN1; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix (PubMed:28717224).
Interacts with LTBP4; the LTBP4 long form (LTBP4L) has a stronger binding affinity than the LTBP4 short form and the LTBP4 long form promotes fibrillar deposition of EFEMP2 (PubMed:25713297).
Interacts with LOX (via propeptide); this interaction is strong and facilitates formation of ternary complexes with ELN during elastic fiber assembly; this interaction limits interaction of EFEMP2 with FBLN5 (By similarity).
Interacts with PITX2 (By similarity).
Interacts with FBLN5 with moderate affinity (By similarity).
Interacts with LOXL1 (via propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 36-81 | EGF-like 1; atypical | ||||
Sequence: YTECTDGYEWDADSQHCRDVNECLTIPEACKGEMKCINHYGGYLCL | ||||||
Region | 91-117 | Disordered | ||||
Sequence: LHGEGPPPPAAHAQQPNPCPQGYEPDE | ||||||
Domain | 123-163 | EGF-like 2; calcium-binding | ||||
Sequence: DVDECTQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECV | ||||||
Domain | 164-202 | EGF-like 3; calcium-binding | ||||
Sequence: DIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRSCV | ||||||
Domain | 203-242 | EGF-like 4; calcium-binding | ||||
Sequence: DVNECDMGAPCEQRCFNSYGTFLCRCNQGYELHRDGFSCS | ||||||
Domain | 243-282 | EGF-like 5; calcium-binding | ||||
Sequence: DIDECGYSSYLCQYRCVNEPGRFSCHCPQGYQLLATRLCQ | ||||||
Domain | 283-328 | EGF-like 6; calcium-binding | ||||
Sequence: DIDECETGAHQCSEAQTCVNFHGGYRCVDTNRCVEPYVQVSDNRCL |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length443
- Mass (Da)49,425
- Last updated1999-11-01 v1
- Checksum4969C0328A23DD88
Computationally mapped potential isoform sequences
There are 12 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PYW6 | E9PYW6_MOUSE | Efemp2 | 82 | ||
E9Q3N9 | E9Q3N9_MOUSE | Efemp2 | 402 | ||
E9Q3F3 | E9Q3F3_MOUSE | Efemp2 | 280 | ||
E9Q1U0 | E9Q1U0_MOUSE | Efemp2 | 128 | ||
E9Q2A0 | E9Q2A0_MOUSE | Efemp2 | 153 | ||
E9Q2T8 | E9Q2T8_MOUSE | Efemp2 | 191 | ||
F6R0V7 | F6R0V7_MOUSE | Efemp2 | 70 | ||
F7AYH6 | F7AYH6_MOUSE | Efemp2 | 120 | ||
G5E8D6 | G5E8D6_MOUSE | Efemp2 | 462 | ||
F6Z1C2 | F6Z1C2_MOUSE | Efemp2 | 157 | ||
A0A494BAR1 | A0A494BAR1_MOUSE | Efemp2 | 404 | ||
A0A494BBF0 | A0A494BBF0_MOUSE | Efemp2 | 455 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 30 | in Ref. 3; AA sequence | ||||
Sequence: P → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF104223 EMBL· GenBank· DDBJ | AAD45219.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012269 EMBL· GenBank· DDBJ | AAH12269.1 EMBL· GenBank· DDBJ | mRNA |