A map of the genomic organization of the human FRAP1 gene can be found at http://www.ncbi.nlm.nih.gov/projects/sviewer/?id=NC_000001.9&v=11081381..11252951

The FRAP1 gene encompasses approximatively 156 kb and contains 58 exons. The gene resides on the minus strand. Reported location on human chromosome 1 is between 11,089,179-11,245,151 bases in NCBI36 coordinates and 11,089,180-11,245,176 bases in ensemble49 coordinates.

Transcript length is 8,680 bp.

No human pseudogene known.

The amino terminus of FRAP (alias, mTOR) consists of several tandem HEAT ( Huntingtin, EF2, A subunit of PP2A, TOR1) repeats) that are implicated in protein-protein interations (Hay and Sonenberg, 2004; Bhaskar and Hay, 2007). Each HEAT repeat contains two alpha helices of approximatively 40 amino acids.
The carboxy-terminal half contains two FAT (FRAP, ATM, TRAP) domains.
Upstream of the catalytic domain is the FRB (FKBP12-rapamycin binding) domain.
The catalytic domain has sequence similarity to the catalytic domain of phosphatidylinositol kinase (PIK), which is homologous to a family of other protein kinases termed PIKK (PIK-related kinase).
mTOR also contains a putative negative regulatory (NR) domain between the catalytic domain and FATC.
The FATC (FRAP, ATM, TRRAP C-terminal) domain is essential for the kinase activity. The FATC and FAT domains are thought to interact in a way the exposes the catalytic domain.
The protein consists of 2549 amino acids, with a predicted molecular weight of 288,891 Da.
The ternary complex of human FK506-binding protein ( FKBP12), the inhibitor rapamycin, and the FKBP12-rapamycin-binding (FRB) domain of human FRAP has been crystallized at a resolution of 2.7 angstroms (Choi et al., 1996), and then refined at 2.2 angstroms (Liang et al., 1999).
Phosphorylation sites of FRAP (alias, mTOR) are reported in http://www.phosphosite.org .

Expressed is found in numerous tissues, with high levels in testis.

Localization is predominantly cytoplasmic, but the protein is also associated with mitochondrial, endoplasmic reticulum and Golgi membranes (Guertin and Sabatini, 2007). A fraction of protein also may shuttle between the nucleus and cytoplasm.

There are more than 2500 articles specifically referring to FRAP1 or mTOR in PubMed. mTOR is central to several key cellular pathways including insulin signaling, regulation of eIF4e and p70S6 kinase, and hypoxia induced factor 1alpha ( HIF1alpha ) stimulation of vascular endothelial growth factor ( VEGF ). These pathways affect several processes including cell growth (size), protein translation, ribosome biogenesis, regulation of cell cycle progression, response to nutrients and cellular stress, angiogenesis, cell polarity and cytoskeletal reorganization. mTOR also has been shown to play a role in the regulation of autophagy (Pattingre et al., 2008), an adaptive cellular response to nutrient starvation whereby a cytoplasmic vacuole or autophagosome engulfs cellular macromolecules and organelles for degradation.
mTOR protein exists in two functionally distinct complexes named mTOR complex 1 (mTORC1) and complex 2 (mTORC2) (see figure under "Implicated in"). The regulator of mTORC1 signaling and kinase activity is the ras-like small GTPase Rheb (Ras homologue enriched in brain), which binds directly to the mTOR catalytic domain and enables mTORC1 to attain an active configuration (Avruch et al., 2006). Insulin/IGF stimulates the accumulation of Rheb-GTP through activated AKT and subsequent inhibition of the Rheb-GTPase-activating function of the tuberous sclerosis ( TSC1 / TSC2 ) heterodimer. Energy depletion decreases Rheb-GTP through the action of adenosine monophosphate-activated protein kinase (AMPK) to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function and also HIFalpha-mediated transcriptional responses that act upstream of the TSC1/2 complex. Amino-acid depletion inhibits mTORC1 by acting predominantly downstream of the TSC complex, by interfering with the ability of Rheb to bind to mTOR.
As shown below, mTORC1 contains the core components mTOR, Raptor (regulatory associated protein of mTOR), and mLST8/GbetaL (G protein beta-subunit-like protein). It is the mTORC1 complex that is characteristically sensitive to inhibition by rapamycin. mTORC1 is a major regulator of ribosomal biogenesis and protein synthesis, largely through the phosphorylation/inactivation of the 4E-BPs (4E-binding proteins) and the phosphorylation/activation of S6K (ribosomal S6 kinase). The binding of S6K1 and 4E-BP1 to raptor requires a TOR signaling (TOS) motif, which contains an essential phenylalanine followed by four alternating acidic and small hydrophobic amino acids (Schalm and Blenis, 2002). Recently, a TOS motif also has been identified in the N terminus of HIF1alpha, which has been shown to interact with Raptor (Land and Tee, 2007). Furthermore, activation of mTOR by Rheb overexpression enhanced HIF1alpha activity and VEGF-A secretion under hypoxic conditions, whereas the mTOR inhibitor rapamycin blocked the pathway.
PRAS40 (proline-rich AKT substrate 40 kDa) is a novel mTOR binding partner that mediates AKT signals to mTOR independently of TSC1/TSC2 (Vander Haar et al., 2007). Hence, PRAS40 and Rheb are postulated to co-regulate mTORC1 (Guertin and Sabatini, 2007). PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate (Thedieck et al., 2007). Moreover, PRAS40 binds the mTOR kinase domain and its interaction with mTOR is induced under conditions that inhibit mTOR signaling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition (Vander Haar et al., 2007). PRAS40 contains a variant TOS motif and competes with S6K1 and 4E-BP1 by functioning as a direct inhibitor of substrate binding (Oshiro et al., 2007, Wang et al., 2007).
mTORC2 contains mTOR, Rictor (rapamycin-insensitive companion of mTOR), SIN1 (SAPK interacting protein) and mLST8/GbetaL. Proline rich protein 5-like (PRR5) protein also binds specifically to mTORC2, via Rictor and/or SIN1 (Thedieck et al., 2007). mTORC2 has been shown to regulate cell-cycle-dependent polarization of the actin cytoskeleton. Although not as sensitive to rapamycin as mTOR1, mTORC2 may be affected by prolonged rapamycin exposure in some cell types (Sarbassov et al., 2006; Zeng et al., 2007). However, the regulation of mTORC2 is largely unknown and does not function downstream of Rheb (Blaskar and Hay, 2007).
Direct genetic evidence for the importance of various components of the mTORC1 and/or mTORC2 complexes was provided by targeted disruption studies in mice (Guertin et al., 2006). Mice null for mTOR, as well as those lacking Raptor die early in embryonic development. However, mLST8-null embryos survive until e10.5 and resemble embryos missing Rictor. Collectively, mTORC1 function was found to be essential in early development, mLST8 was required only for mTORC2 signaling, and mTORC2 was found to be a necessary component of the AKT-FOXO and PKCalphaalpha pathways.

mouse (Mus musculus): Frap1, 99 % Amino Acid Similarity with Human FRAP1
rat (Rattus norvegicus): Frap1, 99% Amino Acid Similarity with Human FRAP1
dog (Canis familiaris): FRAP1, 99% Amino Acid Similarity with Human FRAP1
worm (Caenorhabditis elegans): B0261.2b, 51% Amino Acid Similarity with Human FRAP1
fruit fly (Drosophila melanogaster): Tor, 64% Amino Acid Similarity with Human FRAP1

No mutations are reported to date.