| Tbio | ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial |
ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP. Targets specific substrates for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:22841477). ATP-dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis. Important for efficient erythropoiesis through upregulation of heme biosynthesis (PubMed:25957689).
The protein encoded by this gene is part of a protease found in mitochondria. This protease is ATP-dependent and targets specific proteins for degradation. The protease consists of two heptameric rings of the CLPP catalytic subunit sandwiched between two hexameric rings of the chaperone subunit encoded by this gene. Targeted proteins are unwound by this protein and then passed on to the CLPP subunit for degradation. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]
The protein encoded by this gene is part of a protease found in mitochondria. This protease is ATP-dependent and targets specific proteins for degradation. The protease consists of two heptameric rings of the CLPP catalytic subunit sandwiched between two hexameric rings of the chaperone subunit encoded by this gene. Targeted proteins are unwound by this protein and then passed on to the CLPP subunit for degradation. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]
Comments
Property Summary
| NCBI Gene PubMed Count | 16 |
| Grant Count | 122 |
| R01 Count | 63 |
| Funding | $21,463,255.42 |
| PubMed Score | 196.10 |
| PubTator Score | 37.60 |
| Disease | log2 FC | p |
|---|---|---|
| hepatocellular carcinoma | 1.100 | 0.000 |
| pancreatic cancer | 1.200 | 0.015 |
| Multiple myeloma | 1.229 | 0.012 |
| osteosarcoma | -1.785 | 0.000 |
| pancreatic ductal adenocarcinoma liver m... | -1.495 | 0.001 |
| tuberculosis and treatment for 6 months | -1.500 | 0.000 |
| lung cancer | 1.400 | 0.001 |
| Breast cancer | 3.100 | 0.024 |
| atypical teratoid/rhabdoid tumor | 1.200 | 0.000 |
| pancreatic carcinoma | 1.200 | 0.015 |
| lung adenocarcinoma | -1.200 | 0.000 |
| ovarian cancer | 1.900 | 0.001 |
| PMID | Text |
|---|---|
| 26142927 | results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells. |
| 25083874 | Optical trapping to assay single-molecule ClpXP unfolding and translocation of substrates consisting of domains with varying stabilities and sequences; find that ClpXP unfolds most domains by a single pathway, with kinetics that depend on the native fold and structural stability. |
| 22841477 | human ClpX, a novel mtDNA regulator, maintains mtDNA nucleoid distribution through TFAM function as a chaperone rather than as a protease and its involvement in mtDNA segregation. |
| 22710082 | Walker B mutation in human CLPX exhibits improved interaction with the model unfolded substrate casein and several putative physiological substrates in vitro. |
| 20877624 | Observational study of gene-disease association. (HuGE Navigator) |
| 18313382 | Results reveal that the ssrA tag interacts with different loops that form the top, middle, and lower portions of the central channel of the ClpX hexamer. |
| 16115876 | hClpX can regulate the appearance of hClpP peptidase activity in mitochondria and might affect the nature of the degradation products released during ATP-dependent proteolytic cycles |
MPSCGACTCGAAAVRLITSSLASAQRGISGGRIHMSVLGRLGTFETQILQRAPLRSFTETPAYFASKDGI 1 - 70 SKDGSGDGNKKSASEGSSKKSGSGNSGKGGNQLRCPKCGDLCTHVETFVSSTRFVKCEKCHHFFVVLSEA 71 - 140 DSKKSIIKEPESAAEAVKLAFQQKPPPPPKKIYNYLDKYVVGQSFAKKVLSVAVYNHYKRIYNNIPANLR 141 - 210 QQAEVEKQTSLTPRELEIRRREDEYRFTKLLQIAGISPHGNALGASMQQQVNQQIPQEKRGGEVLDSSHD 211 - 280 DIKLEKSNILLLGPTGSGKTLLAQTLAKCLDVPFAICDCTTLTQAGYVGEDIESVIAKLLQDANYNVEKA 281 - 350 QQGIVFLDEVDKIGSVPGIHQLRDVGGEGVQQGLLKLLEGTIVNVPEKNSRKLRGETVQVDTTNILFVAS 351 - 420 GAFNGLDRIISRRKNEKYLGFGTPSNLGKGRRAAAAADLANRSGESNTHQDIEEKDRLLRHVEARDLIEF 421 - 490 GMIPEFVGRLPVVVPLHSLDEKTLVQILTEPRNAVIPQYQALFSMDKCELNVTEDALKAIARLALERKTG 491 - 560 ARGLRSIMEKLLLEPMFEVPNSDIVCVEVDKEVVEGKKEPGYIRAPTKESSEEEYDSGVEEEGWPRQADA 561 - 630 ANS 631 - 633 //
| PMID | Year | Title |
|---|---|---|
| 26142927 | 2015 | ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells. |
| 25957689 | 2015 | Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis. |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. |
| 25083874 | 2014 | Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine. |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. |
| 23186163 | 2013 | Toward a comprehensive characterization of a human cancer cell phosphoproteome. |
| 22841477 | 2012 | Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX. |
| 22710082 | 2012 | Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX. |
| 21269460 | 2011 | Initial characterization of the human central proteome. |
| 20877624 | 2010 | Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. |
| More... |
