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Details on Person UniProt:P35555 FBN1
| Class:Id | ReferenceGeneProduct:54676 |
|---|---|
| _chainChangeLog | signal peptide:1-27 added on Sat February 7 2015;chain:28-2871 added on Sat February 7 2015;signal peptide:1-27 removed on Fri August 12 2016;chain:28-2871 removed on Fri August 12 2016;signal peptide:1-24 added on Fri August 12 2016;propeptide:25-44 added on Fri August 12 2016;chain:45-2731 added on Fri August 12 2016;chain:2732-2871 added on Fri August 12 2016 |
| _displayName | UniProt:P35555 FBN1 |
| _timestamp | 2024-11-03 20:14:23 |
| chain | signal peptide:1-24 propeptide:25-44 chain:45-2731 chain:2732-2871 |
| checksum | 501258AF1756B9F7 |
| comment | FUNCTION Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:15062093, PubMed:1860873). Fibrillin-1-containing microfibrils provide long-term force bearing structural support (PubMed:27026396). In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin (PubMed:27026396). In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles (PubMed:27026396). Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell-surface integrins and other extracellular matrix protein and proteoglycan components (PubMed:27026396). Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity). Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11 (PubMed:24039232). This leads to disruption of TNFSF11-induced Ca(2+) signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232). Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1 (PubMed:12807887, PubMed:17158881). Binds heparin and this interaction has an important role in the assembly of microfibrils (PubMed:11461921).FUNCTION Adipokine secreted by white adipose tissue that plays an important regulatory role in the glucose metabolism of liver, muscle and pancreas (PubMed:27087445, PubMed:30853600). Hormone that targets the liver in response to fasting to increase plasma glucose levels (PubMed:27087445). Binds the olfactory receptor OR4M1 at the surface of hepatocytes and promotes hepatocyte glucose release by activating the protein kinase A activity in the liver, resulting in rapid glucose release into the circulation (PubMed:27087445, PubMed:31230984). May act as a regulator of adaptive thermogenesis by inhibiting browning and energy consumption, while increasing lipid deposition in white adipose tissue (By similarity). Also acts as an orexigenic hormone that increases appetite: crosses the blood brain barrier and exerts effects on the hypothalamus (By similarity). In the arcuate nucleus of the hypothalamus, asprosin directly activates orexigenic AgRP neurons and indirectly inhibits anorexigenic POMC neurons, resulting in appetite stimulation (By similarity). Activates orexigenic AgRP neurons via binding to the olfactory receptor OR4M1 (By similarity). May also play a role in sperm motility in testis via interaction with OR4M1 receptor (By similarity).SUBUNIT Interacts with COL16A1 (PubMed:15165854). Interacts with integrin alpha-V/beta-3 (PubMed:15062093). Interacts with ADAMTS10; this interaction promotes microfibril assembly (PubMed:21402694). Interacts with THSD4; this interaction promotes fibril formation (By similarity). Interacts (via N-terminal domain) with FBLN2 and FBLN5 (PubMed:15790312, PubMed:17255108). Interacts with ELN (PubMed:15790312). Forms a ternary complex with ELN and FBLN2 or FBLN5 and a significant interaction with ELN seen only in the presence of FBLN2 or FBLN5 (PubMed:17255108). Interacts (via N-terminal domain) with LTBP2 (via C-terminal domain) in a Ca(+2)-dependent manner (PubMed:17293099). Interacts (via N-terminal domain) with LTBP1 (via C-terminal domain) (PubMed:17293099). Interacts with integrins ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB6 (PubMed:12807887, PubMed:17158881). Interacts (via N-terminal domain) with BMP2, BMP4, BMP7, BMP10 and GDF5 (PubMed:18339631). Interacts (via N-terminal domain) with MFAP2 and MFAP5 (PubMed:15131124). Interacts with ADAMTSL5 (PubMed:23010571). Interacts with MFAP4 (PubMed:26601954). Interacts (via N-terminal domain) with TNFSF11 in a Ca(+2)-dependent manner (PubMed:24039232). Interacts (via N-terminal domain) with EFEMP2; this interaction inhibits EFEMP2 binding to LOX and ELN (PubMed:17255108, PubMed:19349279, PubMed:19570982).INTERACTION Fibrillin-1 and Asprosin chains are still linked together during the secretion from cells, but are subsequently separated by furin (PubMed:24982166).SUBCELLULAR LOCATION Secreted by white adipose tissue and circulates in the plasma.INDUCTION Asprosin levels are elevated in patients with type II diabetes and metabolic syndrome (at protein level).PTM Cleavage of N- and C-terminus by furin is required for incorporation into the extracellular matrix and assembly into microfibrils (PubMed:27026396). The C-terminus, which corresponds to the Asprosin chain, was initially thought to constitute a propeptide (PubMed:24982166). Fibrillin-1 and Asprosin chains are still linked together during the secretion from cells, but are subsequently separated by furin, an essential step for incorporation of Fibrillin-1 into the nascent microfibrils (PubMed:24982166).PTM Forms intermolecular disulfide bonds either with other fibrillin-1 molecules or with other components of the microfibrils.PTM O-glycosylated on serine residues by POGLUT2 and POGLUT3 which is necessary for efficient protein secretion.DISEASE The disease is caused by variants affecting the gene represented in this entry. The majority of the more than a thousand mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.BIOTECHNOLOGY Attractive therapeutic target for type II diabetes and metabolic syndrome.MISCELLANEOUS Was named after the Greek word for white, because of the reduction in subcutaneous white adipose tissue that is displayed by asprosin-deficient patients.SIMILARITY Belongs to the fibrillin family.SEQUENCE CAUTION Extended N-terminus.ONLINE INFORMATION Two birds, one stone - Issue 248 of June 2022 |
| description | recommendedName: fullName evidence="102"Fibrillin-1 component recommendedName: fullName evidence="104"Asprosin /component |
| geneName | FBN1 FBN |
| identifier | P35555 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Aortic aneurysm Calcium Direct protein sequencing Disease variant Disulfide bond Dwarfism EGF-like domain Extracellular matrix Glycoprotein Heparin-binding Hormone Phosphoprotein Proteomics identification Reference proteome Repeat Secreted Signal |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | FBN1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8992448] ENSEMBL:ENSG00000166147 FBN1 [Homo sapiens] |
| secondaryIdentifier | FBN1_HUMAN B2RUU0 D2JYH6 Q15972 Q75N87 |
| sequenceLength | 2871 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:265402] FBN1 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2159838] FBN1(2732-2871) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2159853] FBN1(45-2731) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2514785] FBN1(45-?) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2514817] FBN1(1-2731) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:8956726] FBN1 [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:8956900] p-FBN1 [endoplasmic reticulum lumen] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:8957023] phosphorylated residue at unknown position |
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No pathways have been reviewed or authored by UniProt:P35555 FBN1 (54676)
