O95967 · FBLN4_HUMAN
- 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
Plays a crucial role in elastic fiber formation in tissue, and in the formation of ultrastructural connections between elastic laminae and smooth muscle cells in the aorta, therefore participates in terminal differentiation and maturation of smooth muscle cell (SMC) and in the mechanical properties and wall integrity maintenance of the aorta (PubMed:27339457).
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 (By similarity).
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:18973305, PubMed:19570982).
Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling (PubMed:23782690).
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 (By similarity).
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:18973305, PubMed:19570982).
Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling (PubMed:23782690).
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
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEGF-containing fibulin-like extracellular matrix protein 2
- Alternative names
Gene names
- Community suggested namesFBLN4
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO95967
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes on the microfibrils surrounding ELN cores.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Cutis laxa, autosomal recessive, 1B (ARCL1B)
- Note
- DescriptionA 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. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.
- See alsoMIM:614437
Natural variants in ARCL1B
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_027019 | 57 | E>K | in ARCL1B; does not affect secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1, highly glycosylated form of LOX and LTBP1; Does not affect interaction with LOX when LOX is non-glycosylated; proteolyzed by PLG; dbSNP:rs119489101 | |
VAR_084029 | 126 | E>K | in ARCL1B; slightly decreased protein abundance in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; strongly decreased secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1 and LTBP1; decreased interaction with LOXL2; new fragments proteolyzed by ELANE; new one fragment proteolyzed by MMP2 | |
VAR_084030 | 126 | E>V | in ARCL1B | |
VAR_084031 | 203 | D>A | in ARCL1B | |
VAR_084032 | 227 | R>C | in ARCL1B | |
VAR_067069 | 267 | C>Y | in ARCL1B; loss of protein expression in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; loss of protein expression; strongly decreased secretion; dbSNP:rs193302866 | |
VAR_067070 | 279 | R>C | in ARCL1B; loss of secretion; dbSNP:rs119489102 | |
VAR_084033 | 397 | A>T | in ARCL1B; increased N-glycosylation; introduced an extra O-glycosylation site; does not affect secretion; decreased elastic fiber assembly; decreased interaction with collagen type IV trimer, FBN1, ELN, LTBP1, LOXL1 and LOXL2; new fragments proteolyzed by ELANE |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_027019 | 57 | in ARCL1B; does not affect secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1, highly glycosylated form of LOX and LTBP1; Does not affect interaction with LOX when LOX is non-glycosylated; proteolyzed by PLG; dbSNP:rs119489101 | |||
Sequence: E → K | ||||||
Natural variant | VAR_084029 | 126 | in ARCL1B; slightly decreased protein abundance in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; strongly decreased secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1 and LTBP1; decreased interaction with LOXL2; new fragments proteolyzed by ELANE; new one fragment proteolyzed by MMP2 | |||
Sequence: E → K | ||||||
Natural variant | VAR_084030 | 126 | in ARCL1B | |||
Sequence: E → V | ||||||
Natural variant | VAR_084031 | 203 | in ARCL1B | |||
Sequence: D → A | ||||||
Natural variant | VAR_084032 | 227 | in ARCL1B | |||
Sequence: R → C | ||||||
Natural variant | VAR_027020 | 259 | in dbSNP:rs601314 | |||
Sequence: I → V | ||||||
Natural variant | VAR_067069 | 267 | in ARCL1B; loss of protein expression in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; loss of protein expression; strongly decreased secretion; dbSNP:rs193302866 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_067070 | 279 | in ARCL1B; loss of secretion; dbSNP:rs119489102 | |||
Sequence: R → C | ||||||
Natural variant | VAR_084033 | 397 | in ARCL1B; increased N-glycosylation; introduced an extra O-glycosylation site; does not affect secretion; decreased elastic fiber assembly; decreased interaction with collagen type IV trimer, FBN1, ELN, LTBP1, LOXL1 and LOXL2; new fragments proteolyzed by ELANE | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 513 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-23 | |||||
Sequence: MLPCASCLPGSLLLWALLLLLLG | ||||||
Chain | PRO_0000007575 | 24-443 | EGF-containing fibulin-like extracellular matrix protein 2 | |||
Sequence: SASPQDSEEPDSYTECTDGYEWDPDSQHCRDVNECLTIPEACKGEMKCINHYGGYLCLPRSAAVINDLHGEGPPPPVPPAQHPNPCPPGYEPDDQDSCVDVDECAQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECVDIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRSCVDVNECDMGAPCEQRCFNSYGTFLCRCHQGYELHRDGFSCSDIDECSYSSYLCQYRCINEPGRFSCHCPQGYQLLATRLCQDIDECESGAHQCSEAQTCVNFHGGYRCVDTNRCVEPYIQVSENRCLCPASNPLCREQPSSIVHRYMTITSERSVPADVFQIQATSVYPGAYNAFQIRAGNSQGDFYIRQINNVSAMLVLARPVTGPREYVLDLEMVTMNSLMSYRASSVLRLTVFVGAYTF | ||||||
Disulfide bond | 58↔121 | |||||
Sequence: CLTIPEACKGEMKCINHYGGYLCLPRSAAVINDLHGEGPPPPVPPAQHPNPCPPGYEPDDQDSC | ||||||
Disulfide bond | 65↔80 | |||||
Sequence: CKGEMKCINHYGGYLC | ||||||
Disulfide bond | 71↔109 | |||||
Sequence: CINHYGGYLCLPRSAAVINDLHGEGPPPPVPPAQHPNPC | ||||||
Disulfide bond | 127↔140 | |||||
Sequence: CAQALHDCRPSQDC | ||||||
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: CHQGYELHRDGFSC | ||||||
Disulfide bond | 247↔258 | |||||
Sequence: CSYSSYLCQYRC | ||||||
Disulfide bond | 254↔267 | |||||
Sequence: CQYRCINEPGRFSC | ||||||
Disulfide bond | 269↔281 | |||||
Sequence: CPQGYQLLATRLC | ||||||
Disulfide bond | 287↔300 | |||||
Sequence: CESGAHQCSEAQTC | ||||||
Disulfide bond | 294↔309 | |||||
Sequence: CSEAQTCVNFHGGYRC | ||||||
Disulfide bond | 315↔327 | |||||
Sequence: CVEPYIQVSENRC | ||||||
Glycosylation | 394 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated; contains mostly complex-type glycans (PubMed:23782690, PubMed:27339457).
Not O-glycosylated (PubMed:27339457).
Not O-glycosylated (PubMed:27339457).
Cleaved by ELANE; produces a 50-55 kDa fragment (PubMed:27339457).
Cleaved by MMP2 and MMP9; produces several fragments (PubMed:27339457).
Cleaved by MMP2 and MMP9; produces several fragments (PubMed:27339457).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer; disulfide-linked (PubMed:19570982, PubMed:23782690).
Multimer; allows heparin binding (PubMed:23782690).
Monomer (By similarity).
Interacts with FBN1 (via N-terminal domain); this interaction inhibits EFEMP2 binding to LOX and ELN (PubMed:17255108, PubMed:19349279, PubMed:19570982).
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 (PubMed:19570982, PubMed:19855011, PubMed:27339457).
Interacts with PITX2 (PubMed:22919265).
Interacts with ELN with moderate affinity; this interaction regulates ELN self-assembly maturation stage (PubMed:19570982).
Interacts with FBLN5 with moderate affinity (PubMed:19570982).
Interacts with LOXL1 (via propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3 (PubMed:27339457).
Interacts with PCOLCE (By similarity).
Interacts with collagen type IV trimer (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived endostatin (By similarity).
Interacts with EMILIN1; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix (By similarity).
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:27339457).
Multimer; allows heparin binding (PubMed:23782690).
Monomer (By similarity).
Interacts with FBN1 (via N-terminal domain); this interaction inhibits EFEMP2 binding to LOX and ELN (PubMed:17255108, PubMed:19349279, PubMed:19570982).
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 (PubMed:19570982, PubMed:19855011, PubMed:27339457).
Interacts with PITX2 (PubMed:22919265).
Interacts with ELN with moderate affinity; this interaction regulates ELN self-assembly maturation stage (PubMed:19570982).
Interacts with FBLN5 with moderate affinity (PubMed:19570982).
Interacts with LOXL1 (via propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3 (PubMed:27339457).
Interacts with PCOLCE (By similarity).
Interacts with collagen type IV trimer (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived endostatin (By similarity).
Interacts with EMILIN1; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix (By similarity).
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:27339457).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 36-81 | EGF-like 1; atypical | ||||
Sequence: YTECTDGYEWDPDSQHCRDVNECLTIPEACKGEMKCINHYGGYLCL | ||||||
Domain | 123-163 | EGF-like 2; calcium-binding | ||||
Sequence: DVDECAQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECV | ||||||
Domain | 164-202 | EGF-like 3; calcium-binding | ||||
Sequence: DIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRSCV | ||||||
Domain | 203-242 | EGF-like 4; calcium-binding | ||||
Sequence: DVNECDMGAPCEQRCFNSYGTFLCRCHQGYELHRDGFSCS | ||||||
Domain | 243-282 | EGF-like 5; calcium-binding | ||||
Sequence: DIDECSYSSYLCQYRCINEPGRFSCHCPQGYQLLATRLCQ | ||||||
Domain | 283-328 | EGF-like 6; calcium-binding | ||||
Sequence: DIDECESGAHQCSEAQTCVNFHGGYRCVDTNRCVEPYIQVSENRCL |
Sequence similarities
Belongs to the fibulin family.
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)49,405
- Last updated2007-03-20 v3
- Checksum9315CFBBAA0FD3A7
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 5 | in Ref. 1; CAA10791 | ||||
Sequence: A → T | ||||||
Sequence conflict | 24-27 | in Ref. 9; AA sequence | ||||
Sequence: SASP → APLA | ||||||
Sequence conflict | 44-51 | in Ref. 2; AAC62108 | ||||
Sequence: EWDPDSQH → TQTAN | ||||||
Sequence conflict | 46 | in Ref. 4; BAF84768 | ||||
Sequence: D → G | ||||||
Sequence conflict | 96 | in Ref. 4; BAG50843 | ||||
Sequence: P → L | ||||||
Sequence conflict | 103-111 | in Ref. 2; AAC62108 | ||||
Sequence: AQHPNPCPP → VNTQPLPT | ||||||
Sequence conflict | 294 | in Ref. 2; AAC62108 | ||||
Sequence: C → W | ||||||
Sequence conflict | 354-356 | in Ref. 2; AAC62108 | ||||
Sequence: RSV → AER | ||||||
Sequence conflict | 355 | in Ref. 3; AAF65188 | ||||
Sequence: S → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ132819 EMBL· GenBank· DDBJ | CAA10791.2 EMBL· GenBank· DDBJ | mRNA | ||
AF093119 EMBL· GenBank· DDBJ | AAC62108.1 EMBL· GenBank· DDBJ | mRNA | ||
AF109121 EMBL· GenBank· DDBJ | AAF65188.1 EMBL· GenBank· DDBJ | mRNA | ||
AK000980 EMBL· GenBank· DDBJ | BAG50843.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292079 EMBL· GenBank· DDBJ | BAF84768.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358899 EMBL· GenBank· DDBJ | AAQ89258.1 EMBL· GenBank· DDBJ | mRNA | ||
AK075453 EMBL· GenBank· DDBJ | BAG52143.1 EMBL· GenBank· DDBJ | mRNA | ||
AP001201 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC010456 EMBL· GenBank· DDBJ | AAH10456.1 EMBL· GenBank· DDBJ | mRNA |