DegronMD - P35555(FBN1)

FUNCTION: [Fibrillin-1]: 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:1860873, PubMed:15062093). 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). {ECO:0000250|UniProtKB:Q61554, ECO:0000269|PubMed:11461921, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15062093, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:1860873, ECO:0000269|PubMed:24039232, ECO:0000303|PubMed:27026396}.; FUNCTION: [Asprosin]: 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). {ECO:0000250|UniProtKB:Q61554, ECO:0000269|PubMed:27087445, ECO:0000269|PubMed:30853600, ECO:0000269|PubMed:31230984}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A10T	TCGA-BR-4184	STAD	TCGA	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.6028
p.A10T	DO38328	STAD	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.6028
p.R5C	TCGA-BR-8591	STAD	TCGA	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.719
p.R5C	DO47973	STAD	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.719
p.R5H	TCGA-CK-5913	COAD	TCGA	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.7133
p.R5H	DO8826	COAD	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.7133
p.R2C	TCGA-HU-A4GQ	STAD	TCGA	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.719
p.R2C	DO47767	STAD	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation altering degron motif	0.719
p.S19F	TCGA-QK-A8Z8	HNSC	TCGA	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation rewiring degron network	0.0833
p.S19F	DO52097	HNSC	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation rewiring degron network	0.0833
p.L16I	DO229006	LICA	ICGC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation rewiring degron network	0.1667
p.Y20C	SIDM01132	Other Solid Cancers	GDSC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation rewiring degron network	0.0556
p.Y20C	PFSK-1	central nervous system	COSMIC	RRGRLLEIA	DEG_APCC_DBOX_1	2:10	Mutation rewiring degron network	0.0556

DegronMD: protein-targeted degradation, mutation and drug response to degrons

FBN1

UniProt ID: P35555

Entrez ID: 2200

Protein name: Fibrillin-1 [Cleaved into: Asprosin]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for FBN1 in