Atlas of Genetics and Cytogenetics in Oncology and Haematology
FNIP1 (folliculin interacting protein 1)
| Identity |
| Other names | KIAA1961 |
| MGC 667 | |
| Hugo | FNIP1 |
| Location | 5q23.3 |
| DNA/RNA |
 | |
| 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). |
| Protein |
| 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, 5'AMP-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 | 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 |
| External links |
| Bibliography |
| Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. |
| Nagase T, Kikuno R, Ohara O |
| DNA research : an international journal for rapid publication of reports on genes and genomes. 2001 ; 8 (6) : 319-327. |
| PMID 11853319 |
| Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. |
| Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, Zbar B |
| Proceedings of the National Academy of Sciences of the United States of America. 2006 ; 103 (42) : 15552-15557. |
| PMID 17028174 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 07-2007 | Laura S. Schmidt |
| National Cancer Institute-Frederick, Frederick, MD 21702, USA |
| Citation |
| This paper should be referenced as such : |
| Schmidt LS . FNIP1 (folliculin interacting protein 1). Atlas Genet Cytogenet Oncol Haematol. July 2007 . URL : http://AtlasGeneticsOncology.org/Genes/FNIP1ID44003ch5q23.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:23:40 2008 |
For comments and suggestions or contributions, please contact us