FBN1

Protein identityUniProt · HPA

UniProt accession

P35555

Gene

FBN1

Ensembl

ENSG00000166147

Chromosome

15

Canonical length

2871 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus,Plasma membrane

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the fibrillin family of proteins. The encoded preproprotein is proteolytically processed to generate two proteins including the extracellular matrix component fibrillin-1 and the protein hormone asprosin. Fibrillin-1 is an extracellular matrix glycoprotein that serves as a structural component of calcium-binding microfibrils. These microfibrils provide force-bearing structural support in elastic and nonelastic connective tissue throughout the body. Asprosin, secreted by white adipose tissue, has been shown to regulate glucose homeostasis. Mutations in this gene are associated with Marfan syndrome and the related MASS phenotype, as well as ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome. [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

2871 residues, UniProt reviewed canonical sequence.

>P35555|FBN1
     1  MRRGRLLEIA LGFTVLLASY TSHGADANLE AGNVKETRAS RAKRRGGGGH DALKGPNVCG
    61  SRYNAYCCPG WKTLPGGNQC IVPICRHSCG DGFCSRPNMC TCPSGQIAPS CGSRSIQHCN
   121  IRCMNGGSCS DDHCLCQKGY IGTHCGQPVC ESGCLNGGRC VAPNRCACTY GFTGPQCERD
   181  YRTGPCFTVI SNQMCQGQLS GIVCTKTLCC ATVGRAWGHP CEMCPAQPHP CRRGFIPNIR
   241  TGACQDVDEC QAIPGLCQGG NCINTVGSFE CKCPAGHKLN EVSQKCEDID ECSTIPGICE
   301  GGECTNTVSS YFCKCPPGFY TSPDGTRCID VRPGYCYTAL TNGRCSNQLP QSITKMQCCC
   361  DAGRCWSPGV TVAPEMCPIR ATEDFNKLCS VPMVIPGRPE YPPPPLGPIP PVLPVPPGFP
   421  PGPQIPVPRP PVEYLYPSRE PPRVLPVNVT DYCQLVRYLC QNGRCIPTPG SYRCECNKGF
   481  QLDLRGECID VDECEKNPCA GGECINNQGS YTCQCRAGYQ STLTRTECRD IDECLQNGRI
   541  CNNGRCINTD GSFHCVCNAG FHVTRDGKNC EDMDECSIRN MCLNGMCINE DGSFKCICKP
   601  GFQLASDGRY CKDINECETP GICMNGRCVN TDGSYRCECF PGLAVGLDGR VCVDTHMRST
   661  CYGGYKRGQC IKPLFGAVTK SECCCASTEY AFGEPCQPCP AQNSAEYQAL CSSGPGMTSA
   721  GSDINECALD PDICPNGICE NLRGTYKCIC NSGYEVDSTG KNCVDINECV LNSLLCDNGQ
   781  CRNTPGSFVC TCPKGFIYKP DLKTCEDIDE CESSPCINGV CKNSPGSFIC ECSSESTLDP
   841  TKTICIETIK GTCWQTVIDG RCEININGAT LKSQCCSSLG AAWGSPCTLC QVDPICGKGY
   901  SRIKGTQCED IDECEVFPGV CKNGLCVNTR GSFKCQCPSG MTLDATGRIC LDIRLETCFL
   961  RYEDEECTLP IAGRHRMDAC CCSVGAAWGT EECEECPMRN TPEYEELCPR GPGFATKEIT
  1021  NGKPFFKDIN ECKMIPSLCT HGKCRNTIGS FKCRCDSGFA LDSEERNCTD IDECRISPDL
  1081  CGRGQCVNTP GDFECKCDEG YESGFMMMKN CMDIDECQRD PLLCRGGVCH NTEGSYRCEC
  1141  PPGHQLSPNI SACIDINECE LSAHLCPNGR CVNLIGKYQC ACNPGYHSTP DRLFCVDIDE
  1201  CSIMNGGCET FCTNSEGSYE CSCQPGFALM PDQRSCTDID ECEDNPNICD GGQCTNIPGE
  1261  YRCLCYDGFM ASEDMKTCVD VNECDLNPNI CLSGTCENTK GSFICHCDMG YSGKKGKTGC
  1321  TDINECEIGA HNCGKHAVCT NTAGSFKCSC SPGWIGDGIK CTDLDECSNG THMCSQHADC
  1381  KNTMGSYRCL CKEGYTGDGF TCTDLDECSE NLNLCGNGQC LNAPGGYRCE CDMGFVPSAD
  1441  GKACEDIDEC SLPNICVFGT CHNLPGLFRC ECEIGYELDR SGGNCTDVNE CLDPTTCISG
  1501  NCVNTPGSYI CDCPPDFELN PTRVGCVDTR SGNCYLDIRP RGDNGDTACS NEIGVGVSKA
  1561  SCCCSLGKAW GTPCEMCPAV NTSEYKILCP GGEGFRPNPI TVILEDIDEC QELPGLCQGG
  1621  KCINTFGSFQ CRCPTGYYLN EDTRVCDDVN ECETPGICGP GTCYNTVGNY TCICPPDYMQ
  1681  VNGGNNCMDM RRSLCYRNYY ADNQTCDGEL LFNMTKKMCC CSYNIGRAWN KPCEQCPIPS
  1741  TDEFATLCGS QRPGFVIDIY TGLPVDIDEC REIPGVCENG VCINMVGSFR CECPVGFFYN
  1801  DKLLVCEDID ECQNGPVCQR NAECINTAGS YRCDCKPGYR FTSTGQCNDR NECQEIPNIC
  1861  SHGQCIDTVG SFYCLCHTGF KTNDDQTMCL DINECERDAC GNGTCRNTIG SFNCRCNHGF
  1921  ILSHNNDCID VDECASGNGN LCRNGQCINT VGSFQCQCNE GYEVAPDGRT CVDINECLLE
  1981  PRKCAPGTCQ NLDGSYRCIC PPGYSLQNEK CEDIDECVEE PEICALGTCS NTEGSFKCLC
  2041  PEGFSLSSSG RRCQDLRMSY CYAKFEGGKC SSPKSRNHSK QECCCALKGE GWGDPCELCP
  2101  TEPDEAFRQI CPYGSGIIVG PDDSAVDMDE CKEPDVCKHG QCINTDGSYR CECPFGYILA
  2161  GNECVDTDEC SVGNPCGNGT CKNVIGGFEC TCEEGFEPGP MMTCEDINEC AQNPLLCAFR
  2221  CVNTYGSYEC KCPVGYVLRE DRRMCKDEDE CEEGKHDCTE KQMECKNLIG TYMCICGPGY
  2281  QRRPDGEGCV DENECQTKPG ICENGRCLNT RGSYTCECND GFTASPNQDE CLDNREGYCF
  2341  TEVLQNMCQI GSSNRNPVTK SECCCDGGRG WGPHCEICPF QGTVAFKKLC PHGRGFMTNG
  2401  ADIDECKVIH DVCRNGECVN DRGSYHCICK TGYTPDITGT SCVDLNECNQ APKPCNFICK
  2461  NTEGSYQCSC PKGYILQEDG RSCKDLDECA TKQHNCQFLC VNTIGGFTCK CPPGFTQHHT
  2521  SCIDNNECTS DINLCGSKGI CQNTPGSFTC ECQRGFSLDQ TGSSCEDVDE CEGNHRCQHG
  2581  CQNIIGGYRC SCPQGYLQHY QWNQCVDENE CLSAHICGGA SCHNTLGSYK CMCPAGFQYE
  2641  QFSGGCQDIN ECGSAQAPCS YGCSNTEGGY LCGCPPGYFR IGQGHCVSGM GMGRGNPEPP
  2701  VSGEMDDNSL SPEACYECKI NGYPKRGRKR RSTNETDASN IEDQSETEAN VSLASWDVEK
  2761  TAIFAFNISH VSNKVRILEL LPALTTLTNH NRYLIESGNE DGFFKINQKE GISYLHFTKK
  2821  KPVAGTYSLQ ISSTPLYKKK ELNQLEDKYD KDYLSGELGD NLKMKIQVLL H

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FBN1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

62 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FBN1.

Disease | AllUniProt

Conditions FBN1 is implicated in, by any mechanism.

• Marfan syndrome (MFS) MIM:154700
• Ectopia lentis 1, isolated, autosomal dominant (ECTOL1) MIM:129600
• Weill-Marchesani syndrome 2 (WMS2) MIM:608328
• Overlap connective tissue disease (OCTD) MIM:604308
• Stiff skin syndrome (SSKS) MIM:184900
• Geleophysic dysplasia 2 (GPHYSD2) MIM:614185
• Acromicric dysplasia (ACMICD) MIM:102370

Disease | GeneticClinVar

3,604 pathogenic / likely-pathogenic of 9,302 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Marfan syndrome
• Familial thoracic aortic aneurysm and aortic dissection
• Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections
• Cardiovascular phenotype
• Isolated thoracic aortic aneurysm

Disease | AutoantibodyPubMed

Conditions in which antibodies against FBN1 are reported. Each links to that disease's full target list.

• Scleroderma, Systemic 9

ReferencesPubMed · IEDB

Publications for FBN1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.05

gnomAD pLI

1

gnomAD missense Z

5.06

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• camera-type eye development
• cell adhesion mediated by integrin
• cellular response to insulin-like growth factor stimulus
• cellular response to transforming growth factor beta stimulus
• embryonic eye morphogenesis
• gene expression
• glucose homeostasis
• glucose metabolic process
• heart development
• lung alveolus development
• metanephros development
• negative regulation of osteoclast development
• negative regulation of osteoclast differentiation
• post-embryonic eye morphogenesis
• sequestering of BMP in extracellular matrix
• sequestering of TGFbeta in extracellular matrix
• skeletal system development

Molecular functions

• calcium ion binding
• extracellular matrix constituent conferring elasticity
• extracellular matrix structural constituent
• heparin binding
• hormone activity
• identical protein binding
• integrin binding
• protein-containing complex binding

Cellular components

• basement membrane
• endoplasmic reticulum lumen
• extracellular matrix
• extracellular region
• extracellular space
• microfibril

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• EGF-like, conserved site
• TB domain
• EGF-like calcium-binding, conserved site
• NELL2-like, EGF domain
• Complement Clr-like EGF domain
• TGF-beta binding (TB) domain superfamily
• Fibrillin 1, unique N-terminal domain
• Fibrillin, first EGF domain
• NOTCH1, EGF-like calcium-binding domain
• von Willebrand factor C/EGF & Fibrillin
• TB domain
• Calcium-binding EGF domain
• Human growth factor-like EGF
• Complement Clr-like EGF-like
• EGF domain
• Coagulation Factor Xa inhibitory site
• Fibrillin 1 unique N-terminal domain
• Fibrillin, first EGF domain

KeywordsUniProt

• Aortic aneurysm
• Calcium
• Disulfide bond
• Dwarfism
• EGF-like domain
• Extracellular matrix
• Glycoprotein
• Heparin-binding
• Hormone
• Phosphoprotein
• Repeat
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of FBN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ADAMTS10
• ADAMTSL5
• COL16A1
• ELN
• MFAP4
• THSD4
• ITGA5
• BMP2
• BMP7
• EFEMP2
• FBLN2
• ITGB1
• MFAP2
• BMP4
• ITGB3
• TNFSF11
• ITGB6
• BMP10
• GDF5
• MFAP5
• FBLN5
• ADAMTSL4