Reviewed,
UniProtKB/Swiss-Prot P42704 (LPPRC_HUMAN)
Last modified
November 25, 2008.
Version 76.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Leucine-rich PPR motif-containing protein, mitochondrial Alternative name(s): 130 kDa leucine-rich protein LRP 130 GP130 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1394 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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. |
| Subunit structure | Interacts with CECR2, HEBP2, MAP1S, RMP/C19orf2 and UXT. Interacts with PPARGC1A. Interacts with FOXO1 By similarity Component of mRNP complexes associated with HNRPA1. |
| Subcellular location | Mitochondrion. Nucleus › nucleoplasm. Nucleus inner membrane. Nucleus outer membrane. Note= Seems to be predominantly mitochondrial. |
| Tissue specificity | Expressed ubiquitously. Expression is highest in heart, skeletal muscle, kidney and liver, intermediate in brain, non-mucosal colon, spleen and placenta, and lowest in small intestine, thymus, lung and peripheral blood leukocytes. |
| Involvement in disease | Defects in LRPPRC are the cause of Leigh syndrome French-Canadian type (LSFC) [MIM:220111]. Leigh syndrome is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. In the Saguenay-Lac Saint Jean region of Quebec province in Canada, a biochemically distinct form of Leigh syndrome with COX deficiency has been described. Patients have been observed to have a developmental delay, hypotonia, mild facial dysmorphism, chronic well-compensated metabolic acidosis, and high mortality due to episodes of severe acidosis and coma. Enzyme activity was close to normal in kidney and heart, 50% of normal in fibroblasts and skeletal muscle, and nearly absent in brain and liver. LSFC patients show reduced (<30%) levels of LRPPRC in both fibroblast and liver mitochondria and a specifically reduced translation of COX subunits MT-CO1/COXI and MT-CO3 (COXIII). |
| Sequence similarities | Contains 20 PPR (pentatricopeptide) repeats. |
| Sequence caution | The sequence AAA67549.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAA67549.1 differs from that shown. Reason: Frameshift at several positions. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ARF6 | P62330 | 1 | EBI-1050853,EBI-638181 | |
| GABARAPL2 | P60520 | 1 | EBI-1050853,EBI-720116 | |
| GSTK1 | Q9Y2Q3 | 1 | EBI-1050853,EBI-1053767 | |
| IKBKE | Q14164 | 1 | EBI-1050853,EBI-307369 | |
| MAGEA6 | P43360 | 1 | EBI-1050853,EBI-1045155 | |
| MAGED1 | Q9Y5V3 | 1 | EBI-1050853,EBI-716006 | |
| NEK6 | Q9HC98 | 1 | EBI-1050853,EBI-740364 | |
| PHLDA3 | Q9Y5J5 | 1 | EBI-1050853,EBI-1055859 | |
| PPARGC1A | Q9UBK2 | 2 | EBI-1050853,EBI-765486 | |
| PTP4A3 | O75365 | 1 | EBI-1050853,EBI-1043866 | |
| TNFRSF10D | Q9UBN6 | 1 | EBI-1050853,EBI-1044859 | |
| WDR8 | Q9P2S5 | 1 | EBI-1050853,EBI-1054904 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 59 | 59 | Mitochondrion Potential | ||||||
| Chain | 60 – 1394 | 1335 | Leucine-rich PPR motif-containing protein, mitochondrial | PRO_0000084467 | |||||
Regions | |||||||||
| Repeat | 126 – 160 | 35 | PPR 1 | ||||||
| Repeat | 161 – 195 | 35 | PPR 2 | ||||||
| Repeat | 196 – 230 | 35 | PPR 3 | ||||||
| Repeat | 231 – 265 | 35 | PPR 4 | ||||||
| Repeat | 266 – 300 | 35 | PPR 5 | ||||||
| Repeat | 301 – 335 | 35 | PPR 6 | ||||||
| Repeat | 403 – 437 | 35 | PPR 7 | ||||||
| Repeat | 438 – 472 | 35 | PPR 8 | ||||||
| Repeat | 678 – 709 | 32 | PPR 9 | ||||||
| Repeat | 710 – 746 | 37 | PPR 10 | ||||||
| Repeat | 747 – 784 | 38 | PPR 11 | ||||||
| Repeat | 785 – 820 | 36 | PPR 12 | ||||||
| Repeat | 821 – 856 | 36 | PPR 13 | ||||||
| Repeat | 954 – 988 | 35 | PPR 14 | ||||||
| Repeat | 1031 – 1065 | 35 | PPR 15 | ||||||
| Repeat | 1066 – 1102 | 37 | PPR 16 | ||||||
| Repeat | 1103 – 1137 | 35 | PPR 17 | ||||||
| Repeat | 1138 – 1175 | 38 | PPR 18 | ||||||
| Repeat | 1176 – 1210 | 35 | PPR 19 | ||||||
| Repeat | 1317 – 1351 | 35 | PPR 20 | ||||||
| Region | 1121 – 1394 | 274 | RNA-binding | ||||||
Natural variations | |||||||||
| Natural variant | 354 | 1 | A → V in LSFC. | VAR_018656 | |||||
Experimental info | |||||||||
| Sequence conflict | 54 | 1 | S → G in BAF82705. Ref.2 | ||||||
| Sequence conflict | 296 | 1 | S → F in AAA67549. Ref.5 | ||||||
| Sequence conflict | 528 – 531 | 4 | LKSN → YFPI in AAH26034. Ref.4 | ||||||
| Sequence conflict | 556 | 1 | L → V in AAA67549. Ref.5 | ||||||
| Sequence conflict | 583 | 1 | Y → N in AAA67549. Ref.5 | ||||||
| Sequence conflict | 648 | 1 | S → R in AAA67549. Ref.5 | ||||||
| Sequence conflict | 676 | 1 | Q → R in BAC86287. Ref.2 | ||||||
| Sequence conflict | 702 | 1 | K → R in BAC86287. Ref.2 | ||||||
| Sequence conflict | 750 – 752 | 3 | KYV → NYL in AAA67549. Ref.5 | ||||||
| Sequence conflict | 769 | 1 | N → K in AAA67549. Ref.5 | ||||||
| Sequence conflict | 1192 | 1 | N → D in BAC86287. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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." Xu F., Morin C., Mitchell G., Ackerley C., Robinson B.H. Biochem. J. 382:331-336(2004) [PubMed: 15139850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN COX ASSEMBLY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION. |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus and Testis. |
| [3] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Muscle, Placenta and Testis. |
| [5] | "Molecular cloning and expression of the gene for a major leucine-rich protein from human hepatoblastoma cells (HepG2)." Hou J., Wang F., McKeehan W.L. In Vitro Cell. Dev. Biol. Anim. 30A:111-114(1994) [PubMed: 8012652] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 108-1394. Tissue: Liver. |
| [6] | Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 156-170; 260-280; 304-314; 454-463; 530-541; 656-672; 740-750; 764-772; 1050-1059; 1091-1098; 1177-1189 AND 1339-1347, MASS SPECTROMETRY. Tissue: B-cell lymphoma and Colon carcinoma. |
| [7] | "Distinct RNP complexes of shuttling hnRNP proteins with pre-mRNA and mRNA: candidate intermediates in formation and export of mRNA." Mili S., Shu H.J., Zhao Y., Pinol-Roma S. Mol. Cell. Biol. 21:7307-7319(2001) [PubMed: 11585913] [Abstract] Cited for: FUNCTION IN MRNA EXPORT, IDENTIFICATION IN NMRNP COMPLEXES, MASS SPECTROMETRY. |
| [8] | "Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity." Liu L., McKeehan W.L. Genomics 79:124-136(2002) [PubMed: 11827465] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH CECR2; HEBP2; MAP1S; RMP AND UXT. |
| [9] | "LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding domain, is bound in vivo to mitochondrial and nuclear RNAs." Mili S., Pinol-Roma S. Mol. Cell. Biol. 23:4972-4982(2003) [PubMed: 12832482] [Abstract] Cited for: RNA-BINDING, FUNCTION IN MRNA EXPORT, SUBCELLULAR LOCATION. |
| [10] | "LRP130, a single-stranded DNA/RNA-binding protein, localizes at the outer nuclear and endoplasmic reticulum membrane, and interacts with mRNA in vivo." Tsuchiya N., Fukuda H., Nakashima K., Nagao M., Sugimura T., Nakagama H. Biochem. Biophys. Res. Commun. 317:736-743(2004) [PubMed: 15081402] [Abstract] Cited for: FUNCTION IN MRNA EXPORT, SUBCELLULAR LOCATION. |
| [11] | "New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein." Labialle S., Dayan G., Gayet L., Rigal D., Gambrelle J., Baggetto L.G. Nucleic Acids Res. 32:3864-3876(2004) [PubMed: 15272088] [Abstract] Cited for: FUNCTION IN TRANSCRIPTION REGULATION, MASS SPECTROMETRY, SUBCELLULAR LOCATION. |
| [12] | "Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein." Liu L., Vo A., Liu G., McKeehan W.L. Biochem. Biophys. Res. Commun. 332:670-676(2005) [PubMed: 15907802] [Abstract] Cited for: INTERACTION WITH MAP1S. |
| [13] | "Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex." Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H., Tempst P., Spiegelman B.M. Genes Dev. 20:2996-3009(2006) [PubMed: 17050673] [Abstract] Cited for: FUNCTION IN TRANSCRIPTION REGULATION, INTERACTION WITH PPARGC1A. |
| [14] | "Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics." Mootha V.K., Lepage P., Miller K., Bunkenborg J., Reich M., Hjerrild M., Delmonte T., Villeneuve A., Sladek R., Xu F., Mitchell G.A., Morin C., Mann M., Hudson T.J., Robinson B., Rioux J.D., Lander E.S. Proc. Natl. Acad. Sci. U.S.A. 100:605-610(2003) [PubMed: 12529507] [Abstract] Cited for: VARIANT LSFC VAL-354. |
Cross-references
Sequence databases | |
|---|---|
| AY289212 mRNA. Translation: AAP41922.1. AK125781 mRNA. Translation: BAC86287.1. AK290016 mRNA. Translation: BAF82705.1. AC108476 Genomic DNA. Translation: AAY24012.1. AC127379 Genomic DNA. Translation: AAY24043.1. BC010282 mRNA. Translation: AAH10282.1. BC026034 | |

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