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  7. Leucine-rich PPR motif-containing protein, mitochondrial

Tbio Leucine-rich PPR motif-containing protein, mitochondrial

May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters. Binds single-stranded DNA (By similarity).

This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome. [provided by RefSeq, Mar 2012]

 Comments

Property Summary

NCBI Gene PubMed Count 51
PubMed Score 48.17
PubTator Score 41.75

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count Z-score Confidence
cytochrome-c oxidase deficiency disease 19 0.0 5.0
Disease Target Count Z-score Confidence
Leigh disease 81 5.986 3.0
Disease Target Count
Leigh syndrome French-Canadian type 1

Expression

  Differential Expression (18)

Disease log2 FC p
Waldenstrons macroglobulinemia 1.440 1.7e-02
Multiple myeloma 1.409 1.3e-03
astrocytic glioma 1.600 6.0e-03
ependymoma 1.800 1.3e-02
oligodendroglioma 2.000 2.2e-03
osteosarcoma 1.001 3.6e-03
group 3 medulloblastoma 1.300 4.0e-02
atypical teratoid / rhabdoid tumor -1.200 1.2e-05
glioblastoma -1.400 1.0e-04
medulloblastoma, large-cell 1.200 1.4e-03
hereditary spastic paraplegia -1.129 7.8e-03
tuberculosis and treatment for 6 months 1.100 2.2e-04
non-small cell lung cancer 1.009 1.6e-17
intraductal papillary-mucinous carcinoma... 1.100 3.2e-02
intraductal papillary-mucinous neoplasm ... 1.300 2.4e-02
lung cancer 1.600 1.1e-02
Pick disease -1.200 5.5e-04
ovarian cancer 2.100 3.1e-04

Synonym

Accession P42704 A0PJE3 A8K1V1 Q53PC0 Q53QN7 Q6ZUD8 Q7Z7A6 Q96D84
Symbols LSFC
GP130
LRP130
CLONE-23970

Gene

LRPPRC

PANTHER Protein Class (4)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (19)

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 GO Function (6)

 GO Component (12)

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 GO Process (6)

 Compartment GO Term (56)

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 IMPC Phenotype (1)

 OMIM Phenotype (1)

 MGI Phenotype (6)

 GWAS Trait (1)

 HCA RNA Cell Line (56)

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Pathway (11)

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Gene RIF (29)

PMID Text
26510951 study identifies LRPPRC as an important disease-causing gene in an early-onset, multisystem and neurological mitochondrial disease.
26412102 LRPPRC knock-down in mammalian cells leads to an imbalance between mitochondria-encoded and nuclear-encoded subunits of complex IV
25631043 Tetherin binds with the mitochondrion-associated autophagy suppressor LRPPRC and prohibits its association with the autophagy initiation complex.
25379610 Downregulation of LRPPRC expression resulted in the reduced expression of Bcl-2, upregulation of Bax, and cleaved caspase-9 and caspase-3. This induces apoptosis through the mitochondria-mediated pathway in PCa cells.
25214534 LRPPRC levels were reduced in muscle cells and undetectable in liver from French Canadian Leigh Syndrome patients.
25089713 LRPPRC is a transcription factor related to ABCB1 expression and highlight the importance of epigenetic regulation in CML resistance.
24722279 LRPPRC functions as a checkpoint protein that prevents mitochondria from autophagy degradation and impact tumorigenesis.
24375316 LRPPRC overexpression is associated with gastric cancer.
23878239 Data indicate that C14C10.4/MMA-1 Is the Structural and functional homolog of mammalian LRPPRC.
23822101 LRPPRC therefore acts to suppress the initiation of basal levels of autophagy to clean up dysfunctional mitochondria and other cellular debris during the normal cell cycle.
23599432 LRPPRC does not directly regulate mtDNA transcription but rather acts as a post-transcriptional regulator of mammalian mtDNA expression.
23361976 found that the tubulin-binding domain of NF1 is a binding partner of LRPPRC. Our findings provide clues to how loss or mutation of NF1 and LRPPRC may contribute to the manifestations of neurofibromatosis 1 and Leigh Syndrome, French Canadian variant.
23125841 Tandem affinity purification and mass spectrometry analysis identify leucine-rich pentatricopeptide repeat containing (LRPPRC, LRP130), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells
22808186 These data identify LRPPRC as a HIV-1 factor that is involved in HIV-1 replication through more than one mechanism.
22808186 Tandem affinity purification and mass spectrometry analysis identify leucine-rich pentatricopeptide repeat containing (LRPPRC, LRP130), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells
22808186 Knockdown of leucine-rich pentatricopeptide repeat containing (LRPPRC) by shRNA inhibits HIV-1 infection in HeLa T4 beta-gal cells
22661577 The LRPPRC/SLIRP complex suppressed 3' exonucleolytic mRNA degradation mediated by PNPase and SUV3.
22190034 Tandem affinity purification and mass spectrometry analysis identify leucine-rich pentatricopeptide repeat containing (LRPPRC, LRP130), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells
21971050 LRP130 protein remodels mitochondria and stimulates fatty acid oxidation.
21266382 Acute acidotic crises in a child with suspected mitochondrial disease may be suggestive of LRPPRC related COX deficiency.
21109938 LRP130 did not affect the capacity of hepatocarcinoma cells to extrude drugs since LRP130 down-regulation was insufficient to significantly reduce P-glycoprotein.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20633537 LRPPRC protein is imported to the mitochondrial matrix and its mitochondrial targeting sequence is cleaved upon entry.
20220140 Mitochondrial and nuclear genomic responses to loss of LRPPRC expression.
20201926 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
20200222 LRPPRC exists in a high-molecular-weight complex, and it coimmunoprecipitates with SLIRP, a stem-loop RNA-binding protein.
15272088 The LRP130 protein has a role in transcription of the MDR1 and MVP genes.
12529507 using an integrative genomics approach, a single candidate gene, LRPPRC, was identified and shown to be the causative gene underlying Leigh syndrome, French-Canadian type (LSFC)
11827465 regulatory role of LRPPRC in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling, and cytokinesis

AA Sequence 

MAALLRSARWLLRAGAAPRLPLSLRLLPGGPGRLHAASYLPAARAGPVAGGLLSPARLYAIAAKEKDIQE      1 - 70
ESTFSSRKISNQFDWALMRLDLSVRRTGRIPKKLLQKVFNDTCRSGGLGGSHALLLLRSCGSLLPELKLE     71 - 140
ERTEFAHRIWDTLQKLGAVYDVSHYNALLKVYLQNEYKFSPTDFLAKMEEANIQPNRVTYQRLIASYCNV    141 - 210
GDIEGASKILGFMKTKDLPVTEAVFSALVTGHARAGDMENAENILTVMRDAGIEPGPDTYLALLNAYAEK    211 - 280
GDIDHVKQTLEKVEKSELHLMDRDLLQIIFSFSKAGYPQYVSEILEKVTCERRYIPDAMNLILLLVTEKL    281 - 350
EDVALQILLACPVSKEDGPSVFGSFFLQHCVTMNTPVEKLTDYCKKLKEVQMHSFPLQFTLHCALLANKT    351 - 420
DLAKALMKAVKEEGFPIRPHYFWPLLVGRRKEKNVQGIIEILKGMQELGVHPDQETYTDYVIPCFDSVNS    421 - 490
ARAILQENGCLSDSDMFSQAGLRSEAANGNLDFVLSFLKSNTLPISLQSIRSSLLLGFRRSMNINLWSEI    491 - 560
TELLYKDGRYCQEPRGPTEAVGYFLYNLIDSMSDSEVQAKEEHLRQYFHQLEKMNVKIPENIYRGIRNLL    561 - 630
ESYHVPELIKDAHLLVESKNLDFQKTVQLTSSELESTLETLKAENQPIRDVLKQLILVLCSEENMQKALE    631 - 700
LKAKYESDMVTGGYAALINLCCRHDKVEDALNLKEEFDRLDSSAVLDTGKYVGLVRVLAKHGKLQDAINI    701 - 770
LKEMKEKDVLIKDTTALSFFHMLNGAALRGEIETVKQLHEAIVTLGLAEPSTNISFPLVTVHLEKGDLST    771 - 840
ALEVAIDCYEKYKVLPRIHDVLCKLVEKGETDLIQKAMDFVSQEQGEMVMLYDLFFAFLQTGNYKEAKKI    841 - 910
IETPGIRARSARLQWFCDRCVANNQVETLEKLVELTQKLFECDRDQMYYNLLKLYKINGDWQRADAVWNK    911 - 980
IQEENVIPREKTLRLLAEILREGNQEVPFDVPELWYEDEKHSLNSSSASTTEPDFQKDILIACRLNQKKG    981 - 1050
AYDIFLNAKEQNIVFNAETYSNLIKLLMSEDYFTQAMEVKAFAETHIKGFTLNDAANSRLIITQVRRDYL   1051 - 1120
KEAVTTLKTVLDQQQTPSRLAVTRVIQALAMKGDVENIEVVQKMLNGLEDSIGLSKMVFINNIALAQIKN   1121 - 1190
NNIDAAIENIENMLTSENKVIEPQYFGLAYLFRKVIEEQLEPAVEKISIMAERLANQFAIYKPVTDFFLQ   1191 - 1260
LVDAGKVDDARALLQRCGAIAEQTPILLLFLLRNSRKQGKASTVKSVLELIPELNEKEEAYNSLMKSYVS   1261 - 1330
EKDVTSAKALYEHLTAKNTKLDDLFLKRYASLLKYAGEPVPFIEPPESFEFYAQQLRKLRENSS         1331 - 1394
//

Text Mined References (61)

PMID Year Title
26510951 2015 LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
26412102 2015 The loss of LRPPRC function induces the mitochondrial unfolded protein response.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25631043 2015 The viral restriction factor tetherin prevents leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) from association with beclin 1 and B-cell CLL/lymphoma 2 (Bcl-2) and enhances autophagy and mitophagy.
25379610 2014 Downregulation of LRPPRC induces apoptosis in prostate cancer cells through the mitochondria-mediated pathway.
25214534 2015 Tissue-specific responses to the LRPPRC founder mutation in French Canadian Leigh Syndrome.
25089713 2014 ABCB1 regulation through LRPPRC is influenced by the methylation status of the GC -100 box in its promoter.
24722279 2014 Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin.
24375316 2014 The significance of LRPPRC overexpression in gastric cancer.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23878239 2013 Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.
23822101 2013 Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability.
23599432 2013 The leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) does not activate transcription in mammalian mitochondria.
23361976 2013 A novel neurofibromin (NF1) interaction with the leucine-rich pentatricopeptide repeat motif-containing protein links neurofibromatosis type 1 and the French Canadian variant of Leigh's syndrome in a common molecular complex.
23358156 2014 Childhood intelligence is heritable, highly polygenic and associated with FNBP1L.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22808186 2012 Knockdown of the cellular protein LRPPRC attenuates HIV-1 infection.
22681889 2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
22661577 2012 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria.
22658674 2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
22045337 2012 LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs.
21971050 2011 LRP130 protein remodels mitochondria and stimulates fatty acid oxidation.
21525035 2011 PEX14 is required for microtubule-based peroxisome motility in human cells.
21269460 2011 Initial characterization of the human central proteome.
21266382 2011 LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.
21150319 2010 Proteomic profiling of Myc-associated proteins.
21109938 2011 Leucine-rich protein 130 contributes to apoptosis resistance of human hepatocarcinoma cells.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20843780 2011 Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.
20633537 2010 LRPPRC is a mitochondrial matrix protein that is conserved in metazoans.
20220140 2010 Mitochondrial and nuclear genomic responses to loss of LRPPRC expression.
20201926 2010 Human variation in alcohol response is influenced by variation in neuronal signaling genes.
20200222 2010 LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria.
19946888 2010 Defining the membrane proteome of NK cells.
19725078 2009 Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19262567 2009 Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP.
18063578 2008 The layered structure of human mitochondrial DNA nucleoids.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17314511 2007 Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.
17050673 2006 Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex.
15907802 2005 Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15272088 2004 New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein.
15139850 2004 The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette) gene in cytochrome oxidase assembly: mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNA.
15081402 2004 LRP130, a single-stranded DNA/RNA-binding protein, localizes at the outer nuclear and endoplasmic reticulum membrane, and interacts with mRNA in vivo.
14743216 2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12832482 2003 LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding domain, is bound in vivo to mitochondrial and nuclear RNAs.
12762840 Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells.
12529507 2003 Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11827465 2002 Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity.
11585913 2001 Distinct RNP complexes of shuttling hnRNP proteins with pre-mRNA and mRNA: candidate intermediates in formation and export of mRNA.
11464862 2001 Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.
9110174 1997 Large-scale concatenation cDNA sequencing.
8619474 1996 A "double adaptor" method for improved shotgun library construction.
8012652 1994 Molecular cloning and expression of the gene for a major leucine-rich protein from human hepatoblastoma cells (HepG2).