FNIP1 (folliculin interacting protein 1)

2007-07-01   Laura S. Schmidt  

National Cancer Institute-Frederick, Frederick, MD 21702, USA

Identity

HGNC
LOCATION
5q31.1
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Atlas Image

Description

The FNIP1 gene consists of a 6655 nt mRNA (using NM 133372 derived from AC005593.1, DQ145719.1, AC008695.9 and AL832008.1, the coding sequence extends from nt143 to nt3643) and contains 18 coding exons. The initiation codon is located within exon 1.

Transcription

Northern blot analysis revealed an about 7 kb FNIP1 mRNA transcript that was expressed in most major adult tissues, with strongest expression in heart, liver and placenta, and expression in kidney and lung, tissues involved in the Birt-Hogg-Dube syndrome phenotype (see below). Several alternate transcripts lacking one or more exons have been reported. Transcript 1 is the full-length isoform. Transcript 2 lacks exon 7 (NM 001008738).

Proteins

Description

The FNIP1 protein contains 1166 amino acids and has an estimated molecular weight of 130 kDa.

Localisation

Epitope-tagged FNIP1 expressed in HeLa cells localized exclusively in the cytoplasm.

Function

Coimmunoprecipitation studies to elucidate the function of folliculin (FLCN) (encoded by the tumor suppressor gene, BHD/FLCN, which is mutated in the Birt-Hogg-Dube syndrome) identified a novel folliculin-interacting protein, FNIP1, which interacts through the C-terminus of FLCN. FNIP1 overexpression enhanced phosphorylation of FLCN and phospho-FLCN preferentially bound to FNIP1.
FNIP1 is a novel protein with no domains to suggest function. By coimmunoprecipitation studies FNIP1 was also found to interact with the heterotrimer, 5AMP-activated protein kinase (AMPK), a key molecule for energy sensing and a negative regulator of mTOR (mammalian target of rapamycin). AMPK, which bound to FNIP1, was preferentially in its phosphorylated (active) form and FNIP1 could act as a substrate for AMPK phosphorylation both in vitro and in vivo. Inhibition of AMPK kinase activity resulted in reduced FNIP1 protein expression in HEK293 cells suggesting that phosphorylation of FNIP1 by AMPK may enhance protein stability. These data suggest that FNIP1 and its interacting partner, FLCN, may be involved in energy and nutrient-sensing through the AMPK and mTOR signaling pathways.
FNIP1 was also shown to interact with HSP90 by coimmunoprecipitation in HEK293 cells.

Homology

A comparison of FNIP1 proteins across species identified 5 blocks of conserved sequence with at least 35% similarity. FNIP1 homologs have been identified in Mus musculus, Gallus gallus, Xenopus tropicalis, Danio rerio, Drosophila melanogaster and Caenorhabditis elegans.

Implicated in

Entity name
Birt-Hogg-Dube(BHD) syndrome
Note
FNIP1 interacts with FLCN, encoded by a novel tumor suppressor gene, BHD/FLCN, which is mutated in the germline of patients with BHD syndrome.
Disease
Genodermatosis characterized by the triad of benign tumors of the hair follicle, spontaneous pneumothorax and kidney tumors

Article Bibliography

Pubmed IDLast YearTitleAuthors
170281742006Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.Baba M et al
118533192001Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.Nagase T et al

Other Information

Locus ID:

NCBI: 96459
MIM: 610594
HGNC: 29418
Ensembl: ENSG00000217128

Variants:

dbSNP: 96459
ClinVar: 96459
TCGA: ENSG00000217128
COSMIC: FNIP1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000217128ENST00000307954J3KNG8
ENSG00000217128ENST00000307968Q8TF40
ENSG00000217128ENST00000510461Q8TF40
ENSG00000217128ENST00000511848Q8TF40
ENSG00000217128ENST00000615660A0A087WX11

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
mTOR signaling pathwayKEGGko04150
mTOR signaling pathwayKEGGhsa04150

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
377727722024Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.0
388381342024Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse.0
377727722024Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.0
388381342024Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse.0
365999542023Familial multiple discoid fibromas is linked to a locus on chromosome 5 including the FNIP1 gene.1
370796662023Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1.20
365999542023Familial multiple discoid fibromas is linked to a locus on chromosome 5 including the FNIP1 gene.1
370796662023Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1.20
329055802021Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency.14
334595962021Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells.11
329055802021Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency.14
334595962021Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells.11
321815002020Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and pre-excitation syndrome.11
329418022020A Cellular Mechanism to Detect and Alleviate Reductive Stress.63
321815002020Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and pre-excitation syndrome.11

Citation

Laura S. Schmidt

FNIP1 (folliculin interacting protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-07-01

Online version: http://atlasgeneticsoncology.org/gene/44003/img/css/lib/welcome