Protein: EGF-containing fibulin-like extracellular matrix protein 2 (Fibulin-4) (FIBL-4) (Mutant p53-binding protein 1) (Q9WVJ9)
Organism: Mus musculus (Mouse)
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. 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. Also promotes ELN coacervation and participates in the deposition of ELN coacervates on to microfibrils but also regulates ELN cross- linking through LOX interaction. Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling.
Subcellular location: Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:17324935, ECO:0000269|PubMed:26178373, ECO:0000269|PubMed:26690653}. Secreted, extracellular space, extracellular matrix, basement membrane {ECO:0000269|PubMed:17324935}. Note=Localizes on the microfibrils surrounding ELN cores. {ECO:0000269|PubMed:17324935}.
Sequence: MLPFASCLPGSLLLWAFLLLLLGAASPQDPEEPDSYTECTDGYEWDADSQHCRDVNECLTIPEACKGEMKCINHYGGYLCLPRSAAVISDLHGEGPPPPAAHAQQPNPCPQGYEPDEQESCVDVDECTQALHDCRPSQDCHNLPGSYQCTCPDGYRKIGPECVDIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRSCVDVNECDMGAPCEQRCFNSYGTFLCRCNQGYELHRDGFSCSDIDECGYSSYLCQYRCVNEPGRFSCHCPQGYQLLATRLCQDIDECETGAHQCSEAQTCVNFHGGYRCVDTNRCVEPYVQVSDNRCLCPASNPLCREQPSSIVHRYMSITSERSVPADVFQIQATSVYPGAYNAFQIRSGNTQGDFYIRQINNVSAMLVLARPVTGPREYVLDLEMVTMNSLMSYRASSVLRLTVFVGAYTF
InterPro domains: - IPR052235: Nephronectin domain-containing protein (family) [160-277]
- IPR001881: EGF-like calcium-binding domain (domain) [54-328]
- IPR018097: EGF-like calcium-binding, conserved site (conserved_site) [203-309]
- IPR000152: EGF-type aspartate/asparagine hydroxylation site (ptm) [140-269]
- IPR049883: NOTCH1 EGF-like calcium-binding domain (domain) [54-327]
- IPR013032: EGF-like, conserved site (conserved_site) [257-273]
- IPR000742: EGF-like domain (domain) [123-328]
- IPR009030: Growth factor receptor cysteine-rich domain superfamily (homologous_superfamily) [34-329]
- IPR055088: Fibulin, C-terminal Ig-like domain (domain) [342-439]
- IPR026823: Complement Clr-like EGF domain (domain) [183-246]
Interaction partners: - Elastin
- Fibrillin-1
- Microfibrillar-associated protein 2
- Protein-lysine 6-oxidase
- Lysyl oxidase homolog 1
- Microfibrillar-associated protein 5
- Peptidyl-prolyl cis-trans isomerase FKBP10
- Latent-transforming growth factor beta-binding protein 1
- Collagen alpha-1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005198 (structural molecule activity), GO:0005488 (binding), GO:1901681 (sulfur compound binding), GO:0005201 (extracellular matrix structural constituent), GO:0097367 (carbohydrate derivative binding), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0008201 (heparin binding), GO:0005539 (glycosaminoglycan binding), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0040007 (growth), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048589 (developmental growth), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0035265 (organ growth), GO:0019222 (regulation of metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0033036 (macromolecule localization), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0080134 (regulation of response to stress), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0080135 (regulation of cellular response to stress), GO:0060255 (regulation of macromolecule metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:1901343 (negative regulation of vasculature development), GO:0009891 (positive regulation of biosynthetic process), GO:0098868 (bone growth), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0070727 (cellular macromolecule localization), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0008284 (positive regulation of cell population proliferation), GO:0010556 (regulation of macromolecule biosynthetic process), GO:2000377 (regulation of reactive oxygen species metabolic process), GO:1901342 (regulation of vasculature development), GO:0045229 (external encapsulating structure organization), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:1900407 (regulation of cellular response to oxidative stress), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0060348 (bone development), GO:0043062 (extracellular structure organization), GO:0001501 (skeletal system development), GO:1902882 (regulation of response to oxidative stress), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0033688 (regulation of osteoblast proliferation), GO:0045765 (regulation of angiogenesis), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0008104 (protein localization), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0097435 (supramolecular fiber organization), GO:0031328 (positive regulation of cellular biosynthetic process), GO:2000181 (negative regulation of blood vessel morphogenesis), GO:0016525 (negative regulation of angiogenesis), GO:0090322 (regulation of superoxide metabolic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0085029 (extracellular matrix assembly), GO:1901031 (regulation of response to reactive oxygen species), GO:0006355 (regulation of DNA-templated transcription), GO:0030198 (extracellular matrix organization), GO:1902680 (positive regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0034394 (protein localization to cell surface), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0071944 (cell periphery), GO:0030312 (external encapsulating structure), GO:0031012 (extracellular matrix), GO:0062023 (collagen-containing extracellular matrix), GO:0005604 (basement membrane)