Ragulator complex protein LAMTOR5 (LAMTOR5)
The protein contains 91 amino acids for an estimated molecular weight of 9614 Da.
As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. Down-regulates hepatitis B virus (HBV) replication. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cell cycle arrest
Cellular response to amino acid starvation
Cellular response to amino acid stimulus
Negative regulation of apoptotic process
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of gene expression
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of interleukin-8 biosynthetic process
Positive regulation of interleukin-8 production
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of protein localization to nucleus
Positive regulation of RNA polymerase II regulatory region sequence-specific DNA binding
Positive regulation of TOR signaling
Positive regulation of TORC1 signaling
Protein localization to lysosome
Regulation of cell size
Regulation of macroautophagy
Response to virus
Viral genome replication
Molecular Function
The reference OMIM entry for this protein is 608521
Late endosomal/lysosomal adaptor, mitogen-activated protein kinase and mammalian target of rapamycin activator 5; lamtor5
Late endosomal/lysosomal adaptor, mapk and mtor activator 5
Hepatitis b virus x protein-interacting protein; hbxip
Hbx-int
DESCRIPTION
LAMTOR5 is a subunit of the Ragulator/LAMTOR complex (see LAMTOR1, 613510) that resides on the cytosolic face of late endosomes and lysosomes and regulates nutrient availability via RAG small GTPases (see RRAGA, 612194) and mechanistic target of rapamycin complex-1 (mTORC1; see 601231) (Schweitzer et al. (2015)).CLONING
Using hepatitis B virus X protein (HBX) as bait in a yeast 2-hybrid screen of a hepatoma cell line cDNA library, Melegari et al. (1998) cloned HBXIP, which they called XIP. The deduced 91-amino acid protein has a calculated molecular mass of 9.6 kD. It contains a putative leucine zipper motif and may form an amphipathic helix. HBXIP also has 2 putative threonine phosphorylation sites. Northern blot analysis detected a 0.7-kb transcript in all tissues tested, with highest expression in skeletal and cardiac muscle.GENE FUNCTION
By in vitro binding and pull-down assays, Melegari et al. (1998) confirmed that HBXIP interacts with HBX. HBXIP with a mutation in one of its putative threonine phosphorylation sites, thr36 to ala, failed to interact with HBX, while HBXIP with a mutation of the other site, thr12 to ala, still bound HBX. Transient or stable expression of HBXIP in hepatocellular carcinoma cells abolished the transactivation properties of HBX on reporter constructs driven by AP1 (165160) and endogenous HBV enhancer/promoter elements. HBXIP expression in differentiated hepatocellular carcinoma cells reduced wildtype HBV replication to levels observed following infection with an HBX-minus virus. Melegari et al. (1998) hypothesized HBXIP negatively regulates HBX activity and thus alters the replication life cycle of the virus. Marusawa et al. (2003) found that survivin (603352), an antiapoptotic protein that is overexpressed in most human cancers, interacts with HBXIP. Survivin-HBXIP complexes, but neither protein alone, bound procaspase-9 (602234) and prevented its recruitment to APAF1 (602233), thereby selectively suppressing apoptosis initiated via the mitochondria/cytochrome c (123970) pathway. Viral HBX protein also interacted with the survivin-HBXIP complex and suppressed caspase activation in a survivin-dependent manner. Marusawa et al. (2003) concluded that HBXIP functions as a cofactor for survivin and serves as a link between the cellular apoptosis machinery and a viral pathogen involved in hepatocellular carcinogenesis. Using fragments of HBX in protein binding assays, Wen et al. (2008) identified amino acids 137 to 140 (CRHK) of HBX as necessary for binding HBXIP. Mutations in the CRHK motif in HBX abolished HBXIP binding and dysregulated centrosome dynamics, and the mutants failed to localize to centrosomes. Either overexpression of HBX or knockdown of HBXIP, but not overexpression of HBX nonbinding mutants, altered centrosome assembly and induced modification of pericentrin (PCNT1; 170285) and centrin-2 (CETN2; 300006), proteins required for centrosome formation and function. Wen et al. (2008) proposed that HBXIP is a critical target for viral HBX to promote genetic instability through formation of defective spindles and subsequent aberrations in chromosome segregation. The small GTPases RAGA (RRAGA) and RAGB (RRAGB; 300725) dimerize and reside on the cytosolic face of late endosomes and lysosomes via interaction with the Ragulator complex. In response to nutrient availability, the GTP-bound form of RAGA/RAGB recruits mTORC1 to the lysosomal surface and activate ... More on the omim web site
July 5, 2019: Protein entry updated
Automatic update: OMIM entry 608521 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).